Diabetic Foot Care

Firstly, Risk Assessment:
- peripheral neuropathy
- peripheral vascular disease
- previous ulceration
- foot deformity
- poor glycaemic control
- absence of footcare education
- low SES

If low risk foot

- General foot care and advice
- Annual review (use monofilament)

If “At risk” foot i.e. neuropathy, absent pulses, or other risk factor

Conservative:
Education about the risk of foot problems,
Advise patient about daily inspection
Foot protection - avoidance of walking on bare foot, wearing of well fitting footware and loose cotton socks

If there is Ulcer -As above with :

Conservative:
Education about the risk of foot problems,
Advise patient about daily inspection
Foot protection - avoidance of walking on bare foot, wearing of well fitting footware and loose cotton socks

Medical: IV antibiotics

Surgical:
Wound debridement
Evaluate patient for PVD with ABI
Evaluate bone involvement if bone seen or easily detected by probing or if ulcer depth is more than 3mm and ESR more than 40
X ray
Bone scan
MRI ( 98 % sensitivity and 81 % specificity )

Testing Endocrine Function

Prolactin - check prolactin level.

Growth hormone

• Basal growth hormone level does not determine GH deficiency because 50% of a person's GH levels are undetectable in a 24-hour period. At the same time there are pulses of growth hormone secretion which are almost impossible to distinguish from acromegaly.

• Basal IGF - 1 level - useful for deficiency as well as excess of growth hormone secretion. Some clinicians advocate that stimulation testing may not be required in patients with other anterior pituitary hormone deficiencies and a low IGF-1 level.

• Insulin tolerance test - the gold standard test for the diagnosis of GH deficiency.

• GH-releasing hormone-arginine test is as accurate as ITT and it is less dangerous.

• Oral glucose tolerance test showing an elevated IGF-1 value and an elevated GH value with failure to suppress after oral glucose administration is suggestive of acromegaly.

Hypothalmo-pituitary-adrenal axis

Mineralocorticoid deficiency

• Undetectable serum cortisol is diagnostic of adrenal insufficiency. A cortisol > 580 nmol/L precludes the diagnosis of adrenal insufficiency.

• Short synacthen test can be used to confirm the adrenal insufficiency.

Mineralocorticoid excess

• Aldosterone renin ratio is the best screening test for hyperaldosteronism. The ratio is unaffected by most antihypertensive except spironolactone.

• 24 hr urinary aldosterone collection can be confirmatory for hyperaldosteronism.

• Intravenous saline loading test to assess suppression of aldosteronecan also be used to confirm the diagnosis.

Chronic Myeloid Leukaemia

50 % of patients are asymptomatic but splenomegaly present in > 50 % of cases of CML in the initial chronic phase.

• Diagnosis is based on blood counts and proof of diagnosis is attained by demonstration of philadelphia chromosome, t ( 9;22 ).

The typical clinical course is triphasic:

• Chronic phase

• Accelerated phase ( 15 - 29 % of blast in blood or BM, more than 20 % basophils in blood, thrombocytosis or thrombocytopenia unrelated to therapy or clonal cytogenetic evolution.
  

• Blast phase/ blast crisis ( 30 % or more of the blasts in blood and bone marrow ).

The current standard therapy is Imatinib.

BRCA in breast cancer

Family susceptibility to breast cancer accounts for approximately 25 % of all breast cancer cases. However, in familial cancer, mutations in the BRCA 1/2, CHEK 2, TP53 and PTEN genes account for 5 -10 % of breast and ovarian cancer.

In unselected cases, BRCA 1 and BRCA 2 accounts for only 3 - 5 % of breast and ovarian cancer but higher prevalence is noted in those with a family history which are going to discuss later.

Women with BRCA 1 carries a life time risk of 80 % of developing breast cancer and 60 % of ovarian cancer, and with BRCA 2 have a life time risk of 80 % for breast cancer and 20 % for ovarian cancer.

Genetic testing criteria may differ between countries but widely accepted criteria for referral includes:

• three or more cases of breast cancer and / or ovarian cancer cases, at least one being diagnosed less than 50 years

• two breast cancer cases aged less than 40 years old

• male breast cancer

• bilateral breast cancer

Management:

Surveillance - self examinations and clinical examination twice a year together with yearly mammogram / MRI starting from age 25 - 30 years.

Chemoprevention - adjuvant tamoxifen reduces the risk of contralateral breast cancer in affected BRCA mutation carriers, while the benefit of tamoxifen for primary prevention has not been demonstrated.

Prophylactic bilateral mastectomy - most women find this strategy unacceptable for primary prevention. Contralateral prophylactic mastectomy is an option to consider in those carrier with early breast cancer.

Prophylactic bilateral salpingo-oophorectomy - it is associated with a risk reduction of breast cancer in premenopausal BRCA mutation carriers and risk reduction of ovarian cancer. It is recommended after age 35 and when child bearing decisons are complete.

Fertility Preservation in Cancer Patients

Gonadal toxicity can be resulted from ionising radiation and chemotherapeutic agents especially alkylating agents such as chlorambucil, cyclophosphamide and melphalan.

All patients at risk for infertility who have not completed childbearing should discuss germ cell storage options with the medical team.

Male - Semen cryopreservation of at least three samples with 48-h abstinence intervals is recommended. For azoospermic men, testicular sperm extraction may be an option for fertility preservation. Prepubertal males may participate in clinical research of testicular tissue/spermatogonial stem cell storage.

Female - Embryo cryopreservation and ovary transposition are the only established fertility preservation options for female patients. Experimental fertility preservation options are oocyte cryopreservation for women without a partner and ovarian tissue storage for those who cannot undergo ovarian stimulation or are prepubertal.

Opportunistic Infections

Toxoplasma gondii infection

• Disease occurs almost exclusively because of reactivation of latent tissue cysts. Primary infection occurs after eating undercooked meat containing tissue cysts or ingestion of oocysts that have been shed in cat feces.

• Clinical disease is rare among patients with CD4+ T lymphocyte counts >200 cells/μL. The greatest risk is among patients with a CD4+ T lymphocyte count less than 50.
  

• The most common clinical presentation of T. gondii infection among patients with AIDS is of a focal encephalitis.

• Patients with TE are almost uniformly seropositive for anti-toxoplasma IgG antibodies. The absence of IgG antibody makes a diagnosis of toxoplasmosis unlikely but not impossible. Anti-toxoplasma IgM antibodies are usually absent.

• CT/MRI scan can demonstrate mass lesion.

• CT guided brain biopsy can demonstrate Toxoplasma Gondi. Detection of T. gondii by PCR in cerebrospinal fluid has produced disappointing results.
  

• Differentials includes CNS lymphoma, mycobacterial infection (especially TB), fungal infection (e.g. cryptococcosis), Chagas disease, bacterial abscess, and rarely PML, which can be distinguished on the basis of imaging studies (PML lesions typically involve white matter rather than gray matter, are noncontrast enhancing, and indicate no mass effect).

• The initial therapy of choice consists of the combination of pyrimethamine plus sulfadiazine plus leucovorin. Acute therapy should be continued for at least 6 weeks, if there is clinical and radiologic improvement. Longer courses might be appropriate if clinical or radiologic disease is extensive or response is incomplete at 6 weeks.

Cryptosporidiosis

• Those at greatest risk for disease are patients with advanced immunosuppression (i.e., CD4+ T lymphocyte counts generally less than 100.
  

• Feces from infected animals, including humans, can contaminate water supplies and recreational water with viable oocysts despite standard chlorination.

• The most common presentation of cryptosporidiosis is the acute or subacute onset of profuse, nonbloody watery diarrhea. Cholangitis and pancreatitis occur among patients with prolonged disease.

• Diagnosis of cryptosporidiosis is primarily based on microscopic identification of the oocysts in stool or tissue. Cryptosporidial enteritis can be diagnosed on small intestinal biopsy.

• ART with immune restoration is associated with complete resolution and all patient should be offered ART. Chemotherapeutic and Immunotherapeutic agent does not have consistent success.

Microsporidiosis

• They are ubiquitous organisms and are likely zoonotic and/or waterborne in origin.

• The most common manifestation of microsporidiosis is diarrhea but encephalitis, ocular infection, sinusitis, myositis, and disseminated infection are also described.

• In gastrointestinal disease, examination of three stools with chromotrope and chemofluorescent stains is often sufficient for diagnosis. If stool examination is negative and microsporidiosis is suspected, a small bowel biopsy should be performed.

• ART with immune restoration is associated with complete resolution and all patient should be offered ART. Albendazole is also recommended for initial therapy.

Progressive Multifocal Leukoencephalopathy Caused by JC Virus

• PML is the only known disease caused by the JC virus. This disease has an insidious onset and characterized by cognitive dysfunction, dementia, seizures, ataxia, aphasia, cranial nerve deficits, hemiparesis or quadriparesis, and eventually coma.

• Typical computed tomographic abnormalities include single or multiple hypodense, nonenhancing cerebral white matter lesions, although cerebellum and brain stem are occasionally involved.

• Brain biopsy can demonstrate characteristic pathologic foci of demyelination and oligodendrocytes with enlarged nuclei and basophilic-staining intranuclear material. PCR detection of JC virus DNA in CSF provides supportive diagnostic information.

• No effective therapy for JC virus exists.

Adrenal Incidentaloma

During the evaluation of adrenal incidentaloma, two questions need to be asked:
1) is the the lesion hormonally active?
2) does it have radiologic characteristics suggestive of a malignant lesion?

Is the lesion hormonally active?

• The patient should be tested for hypercortisolism, hyperaldosteronism ( if hypertensive ) and phaeochromocytoma.

• Hypercortisolism - the simplest screening test is a 1 mg overnight dexamethasone suppression test. If clinical suspicion is high, such as in patients with hypertension, obesity, diabetes mellitus or osteoporosis, 3 tests ( salivary cortisol, dexamethasone suppression test and 24 hr urinary free cortisol ) can be used.

• Phaeochromocytoma - should undergo measurement of plasma fractionated metanephrines and normetanephrines or 24 hr total urinary metanephrines and fractionated catecholamines.

• Aldosteronism - an aldosterone-to-renin ratio should be performed and if > 20, further confimation by demonstrating lack of aldosterone suppression with salt loading.

Does it have radiologic characteristics suggestive of a malignant lesion?

• Although size should not be used as the only parameter to guide treatment, a 4-cm cutoff had a 93 percent sensitivity of detecting adrenocortical carcinoma, even though specificity was limited (76 percent of masses larger than 4 cm in diameter were benign). As a result, surgical removal of masses larger than 4 cm, particularly in younger patients is recommended.

• A homogeneous adrenal mass <4>50 percent at 10 minutes) is very likely to be a benign cortical adenoma.

• The imaging characteristics that suggest adrenal carcinoma or metastases include: irregular shape, inhomogeneous density, high unenhanced CT attenuation values (>20 HU), delayed contrast medium washout (eg, <50>4 cm, and tumor calcification.

Thryroid Nodule

Thyroid nodules are very common clinical finding with an estimated prevalence of 3 - 7 %.

Investigation:

Laboratory Evaluation

• Measurement of TSH concentration is the single most useful laboratory test in the initial evaluation of thyroid nodules.

• Thyroid peroxidase antibody should be measured in patient with high TSH level. Patients with raised TPO Ab and a firm, diffusely enlarged thyroid are very suggestive of autoimmune or Hashimoto's thyroiditis.

• Calcitonin level should be measured as it is a useful marker of medullary thyroid carcinoma, especially in patient with family history of MTC or MEN 2.

Diagnostic Imaging Studies

• High resolution USS is the most sensitive test available to detect thyroid lesions. Nodules with malignant potential should be identified and FNA biopsy should be suggested to the patients.

• Thyroid Scintigraphy is useful in hyperthyroid patient to differentiate cold and hot nodule.

Cytological Studies

• Fine needle aspiration cytology/ biopsy has been established as a safe and reliable. FNAC/B results can be

Diagonostic ( satisfactory specimen )

• Benign
• Malignant
• Suspicious

Non-diagnostic ( unsatisfactory speciment )

• Foam cells
• Cyst fluid
• Blood

Interpretation

Hyperthyroidism ( Low TSH ) - need scintigraphy

• Hot nodule - can be MNG or solitary thyroid nodule. MNG need further USS study to exclude for suspicious lesion and if required FNAC/B.

• Cold nodule - need further work up with FNAC/B.

Euthyroid - need further work up depending on the size and risk factors for malignant lesions.

• Risk factors includes:

History of head and neck irradiation
Family history of MTC or MEN 2
Age less than 20 or more than 70
Male sex
Growing nodule
Firm or hard consistency
Fixed nodule
Cervical adenopathy
Persistent hoarseness, dysphonia, dysphagia or dyspnoea

• More than 10 mm or risk factors - need FNAC/B.

• Less than 10 mm and no risk factors - USS first to look for suspicious lesion and if suggestive, FNAC/B.

Hypothroidism ( high TSH ) - need USS scan.

• If suspicious for malignancy on USS - then FNAC/B is warranted.

• If not suscpicious - then TPO Ab is suggested to confirm for Hashimoto's thyroiditis and autoimmune thyroiditis.

Hypogonadism

When hypogonadism develops before the age of puberty, the manifestations are those of impaired puberty:

• Small testes, phallus, and prostate
• Scant pubic and axillary hair
• Disproportionately long arms and legs (from delayed
• epiphyseal closure)
• Reduced male musculature
• Gynecomastia
• Persistently high-pitched voice

Postpubertal loss of testicular function results in slowly evolving subtle clinical symptoms and signs. In aging men, these symptoms and signs may be difficult to appreciate because they are often attributed to “getting older.” The growth of body hair usually slows, but the voice and the size of the phallus usually remain unchanged. Prostate size may decrease in hypogonadal men, but the amount of change is related to the severity of testosterone deficiency. Typical temporal hair recession and balding usually do not occur, and if they did, these manifestations would not be expected to prompt a patient to seek medical attention. Patients with hypogonadism may have the following findings:

• Progressive decrease in muscle mass
• Loss of libido
• Impotence
• Oligospermia or azoospermia
• Occasionally, menopausal-type hot flushes (with acute onset of hypogonadism)
• Poor ability to concentrate

The major objectives of the initial assessment of a patient with possible hypogonadism are to distinguish primary gonadal failure (hypergonadotropic hypogonadism with low testosterone and increased FSH and LH levels) from hypothalamic-pituitary disorders (hypogonadotropic hypogonadism with low testosterone and low to normal FSH and LH levels) and to make a specific diagnosis.

• Men with hypogonadotropic disorders may achieve fertility with gonadal stimulation.

• Men with hypergonadotropic disorders are treated with testosterone to achieve virilization and are usually, but not invariably, incapable of achieving fertility.

Investigation:

• Level of testosterone determination is the threshold test in the evaluation of suspected male hypogonadism.

• If the clinical findings indicate that hypogonadism is present and the total testosterone levels are normal or borderline low, the level of SHBG or free testosterone should be determined.

• Gonadotrophins ( FSH and LH ) is used to determine whether the hypogonadism is related to a primary testicular disorder or to pituitary disease. FSH has a longer half-life than does LH and is more likely to provide adequate results on a single blood sample.

• GnRH Stimulation Test

• In men with acquired hypogonadotropic hypogonadism, who usually have a reduced libido and impotence, a prolactin level should be determined to evaluate for the presence of a prolactinoma or other cause of hyperprolactinemia. High prolactin levels can reduce GnRH and testosterone levels.

• Pituitary Imaging

• Bone Mineral densitometry

Acromegaly

Acromegaly is often a chronic debilitating condition that, if left uncontrolled, is associated with increased morbidity and mortality.

GH stimulates hepatic production of insulin-like growth factor-I (IGF-I). GH produces some of its somatic effects directly; others are mediated by IGF-I.

Investigation:

Once acromegaly is suspected, measurement of serum IGF-I should be the next step. Acromegaly in the absence of high IGF-I levels is extremely rare.

Measuring GH during an OGTT has been a standard technique for diagnosis of acromegaly for almost 40 years. If the GH level does not decline to below 1 ng/mL during the test, the patient has acromegaly.

Although random GH levels are not generally useful in diagnosing acromegaly, patients with diabetes mellitus have
GH levels that respond to glucose; however, performance of an OGTT in patients with very high levels of glucose is not always advisable.

Low, but nonsuppressible, levels of GH after oral administration of glucose (GH >1 ng/mL) are frequently noted in patients who have undergone surgical treatment and who have normal IGF-I concentrations. In such patients, the acromegaly is considered controlled but not cured. If the patient is asymptomatic, close follow-up without therapy is reasonable. Currently, prophylactic irradiation is not considered warranted in this context. If symptoms such as heat intolerance or glucose intolerance emerge, or if the IGF-I level becomes high, further therapy is warranted.

Management:

Measurement of GHRH can be helpful in detecting an ectopic source of the acromegaly. A GHRH test should be done when a patient has no obvious pituitary tumor, but there is proven acromegaly.

• Surgical treatment should be considered the first therapeutic option in every patient with acromegaly. Those patients who present with severe mass effect manifested as visual loss or double vision are appropriate candidates for urgent surgical treatment.

• Medical therapy may be offered as first-line treatment but only after the surgical option has been discussed with the patient.

1. Somatostatin analogue such as octreotide.
2. GH receptor antagonists such as pegvisomant.
3. Dopamine agonist such as carbargoline.

• Pituitary irradiation is most commonly used as adjunctive therapy after surgical resection. In young adults who desire fertility, the patients (men and women) must be informed that any type of pituitary irradiation may impair gonadotropin function.

• Treatment of associated condition such as cardiovascular or respiratory condition. Colonoscopy should be done at the time of diagnosis of acromegaly and then follow guidelines (colonoscopy every 5 years if no cancer or polyps are detected, with more frequent follow-up if any lesions are detected ).

Heparin Induced Thrombocytopenia

Heparin may be used for both prevention and the treatment of thrombosis. In HIT, the platelet count in the blood falls below the normal range, a condition called thrombocytopenia. However, it is generally not low enough to lead to an increased risk of bleeding.

Usual scenario:
Relative fall in platelet count >/50 % with absolute count of not less than 20 associated with

• arterial or venous thrombosis
• skin necrosis
• anaphylatoid reaction

There is no alternative explanation for thrombocytopenia.

A clinical probability score ( 4 Ts ):


Management:


Bilateral lower extremity compression USS should be performed in all patients with HIT, whether or not there is clinical evidence of lower limb DVT as it will influence the duration of anticoagulation.

For patients with HIT associated thrombosis, anticoagulate for a defined course typically 3 - 6 months as with other provoked thromboses.

For patients with HIT without thrombosis, the optimal duration of anticoagulation is unknown but anticoagulation for at least 0ne months is usual.

Non-heparin anticoagulants such as danaparoid, lepirudin and Fondaparinux is recommended.

HIT patients are at risk of venous limb gangrene during initiation of warfarin and warfarin should not be introduced until the platelet count is more than 150.

Renal Artery Stenosis

Renovascular hypertension is the systemic hypertension due to narrowing of the renal arteries. From a haemodynaemic point of view, a proximal stenosis is significant when there is a pressure gradient across the stenosis.

RAS has two main aetiologies: atherosclerosis and fibromuscular dysplasia.

Caring for Australasians with Renovascular Diesease ( CARI ) guidelines, the following classification has been devised based ont he likelihood of progression:

• Less than 50 % stenosis - insignificant
• 50 - 70 % stenosis - moderate
• more than 70 % stenosis - severe

Indication for screening RAS:

• Refractory hypertension ( > 160/100 mmHg and resistant to more than 4 antihypertensives )
• A greater than 40 % rise in serum creatinine level after the commencement of ACE inhibitor / ARB therapy.
• Progressive and rapid decline in renal function with other causes excluded.
• Proven episodes of pulmonary oedema and normal baseline left ventricular function.

Which Imaging tools to be used?

• Duplex ultrasonography - least invasive but subsequent tests are required due to high rate of false positive and negative results.
• Intra-arterial digital substraction angiography - definitive tool to diagnose the presence RAS.
• CT angiography - it is an accurate, minimally invasive screening test especially suited to the diagnosis of RAS due to fibromuscular dysplasia.
• Gadolinium enhanced MR angiography - highly sensitive in detecting atherosclerotic RAS and has significantly higher accuracy than any other modality in excluding the disease. However, the use of gadolinium is contraindicated in patients with GFR less than 30ml/min due to risk of nephrogenic systemic sclerosis.

Management:

Medical Therapy - In unilateral RAS, angiotensin converting enzyme inhibitors and angiotensin receptor blockers are useful for their ability to improve blood pressure and their overall cardiovascular benefit. a small initial rise in serum creatinine ( less than 30 % ) is transient and acceptable.

In bilateral RAS, ARB and ACEI are considered contraindicated. Acute renal failure occurs in about 30 % of patients but is usually reversible. In some patients, ACEI/ARB has high benefits, such as congestive cardiac failure patient, ACEI and ARB should be initiated in hospital setting.

Endovascular Treatment - There has been no difference in either blood pressure reduction and renal decline after 12 months when medical therapy has been compared with endovascular therapy.
Disappointly, the adverse event rate in those undergoing angioplasty has ranged from 10 - 25 %.

It seems reasonable to restrict renovascularisation to those patients with high grade stenosis ( > 70 % ) and with specific clinical problems:

• Refractory hypertension ( > 160 mmHg ) and resistant to more than four antihypertensive agents
• > 30 % rise in creatinine level on commencement of ACEI
• Progressive vascular renal decline
• Recurrent, unexplained pulmonary oedema with normal left ventricular function on echocardiography

Post Transplant Lymphoproliferative Disorder ( PTLD )

In the first year after organ transplantation, recipients are at the greatest risk of developing lymphoproliferative diseases (PTLDs), which are induced most often by Epstein-Barr virus (EBV) infection, and patients should therefore be screened prior to or at the time of transplantation for EBV antibodies.

In the rare cases (<5%) where the recipient is EBV seronegative, he or she has a 95% likelihood of receiving an organ from an EBV-seropositive donor, which translates into a high risk of primary EBV infection with seroconversion soon after transplantation. In such cases, the recipient should receive a prophylactic antiviral treatment with acyclovir, valacyclovir or ganciclovir, starting at the time of transplant and lasting for at least 3 months.

The treatment of PTLD should be based on accurate pathology with extensive cell markers and phenotyping.

The treatment modalities are as follows.

• Reduction of basal immunosuppression in all cases (either maintain only steroids, or decrease by at least 50% the anti-calcineurin drugs and stop other immunosuppressive drugs).

• In the case of EBV-positive B-cell lymphoma, antiviral treatment with acyclovir, valacyclovir or ganciclovir may be initiated for at least 1 month or according to the blood level of EBV replication when available.

• In the case of rare lymphomas from the mucosal-associated lymphoid tissue (MALT) with positive Helicobacter pylori, full eradication of H. pylori should be carried out. Subsequent H. pylori prophylaxis should be implemented to avoid relapse.

• In the case of CD20-positive lymphomas, treatment with rituximab, a chimeric monoclonal antibody directed against CD20, should be carried out with one i.v. injection per week for 4 weeks.

• In the case of diffuse lymphomas or improper response to previous treatment, CHOP chemotherapy should be used alone or in combination with rituximab. The CHOP regimen is cyclophosphamide, doxorubicine, vincristine and prednisone.

• Complete cessation of immunosuppression with or without graft nephrectomy should also be considered.

PCP prophylaxis post renal transplant

Approximately 5% of patients develop Pneumocystis carinii pneumonia (PCP) after renal transplantation if they do not receive prophylaxis.

PCP is a severe disease, with a very high fatality rate. Therefore, all renal transplant recipients should receive PCP prophylaxis.

The treatment of choice is trimethoprim-sulfamethoxazole (TMP-SMX), at a dose of 80/400 mg/day or 160/800 mg every other day, for at least 4 months.

Patients who are treated for rejection should receive TMP-SMX prophylaxis for 3-4 months.

In the case of TMP-SMX intolerance, aerosolized pentamidine (300 mg once or twice per month) is an alternative for prophylaxis.

The first-line treatment of PCP is high-dose TMP-SMX. Patients with a PaO2 of <70 mmHg initially should be treated parenterally, and the administration of additional steroids should be considered.

Pregnancy and Transplantion

Women with end stage kidney disease have hypothalmic gonadal dysfunction and infertility. Infertility also occurs with end-stage disease of other organs such as heart, liver and lung.

However, there is still a risk of unwanted pregnancy and so all women with end-stage organ disease who are of child bearing age need effective contraception.

Within the first months after transplantation, gondal dysfunction rapidly reverses, and female fertility returns, conferring a substantial possibility of conception.

Most transplantation centres have advised that conception is safe after the second post-transplantation year, on the assumption that the graft function well. A consensus conference held by the Women's Health Committee of American Society of Transplantation in 2003 concluded that pregnancy is usually safe after the first year, provided that allograft function is stable and that no rejection episodes have occurred in the year before conception.

Pregnancy after transplantation should be considered a high-risk pregnancy and should be monitored by both an obstetrician and the transplant physician.

Pregnancy should be diagnosed as early as possible.

The principal risks are infection, proteinuria, anaemia, arterial hypertension and acute rejection for the mother, and prematurity and low birth weight for the foetus.

Pregnant women and transplanted patients are at increased risk of infections, especially bacterial urinary tract infections and acute pyelonephritis of the graft.

Urine cultures should be performed monthly and all asymptomatic infections should be treated. Monitoring of viral infections is also recommended.

Acute rejection episodes are uncommon but may occur after delivery. Therefore, immunosuppression should be re-adjusted immediately after delivery.

Because pre-eclampsia develops in 30% of pregnant patients, especially those with prior arterial transplant hypertension, blood pressure, renal function, proteinuria and weight should be monitored every 2-4 weeks, with more attention during the third trimester. Anti-hypertensive agents should be changed to those tolerated during pregnancy. ACE inhibitors and angiotensin II receptor antagonists are absolutely contra-indicated.

Immunosuppressive therapy based on cyclosporine or tacrolimus with or without steroids and azathioprine may be continued in renal transplant women during pregnancy. Other drugs, such as mycophenolate mofetil and sirolimus, are not recommended.

Vaginal delivery is recommended, but caesarean section is required in at least 50% of cases. Delivery should occur in a specialized centre.

In the puerperium, renal function, proteinuria, blood pressure, cyclosporine/tacrolimus blood levels and fluid balance should be closely monitored.

Because of drug transfer into maternal milk, breastfeeding is not recommended.

Differential Diagnosis of chronic Renal Graft Dysfunction

Any significant deterioration in graft function should be investigated using the appropriate diagnostic tools and, if possible, therapeutic interventions should be initiated. The usual causes of a decline in glomerular filtration rate after the first year include:

Causes related to allograft includes:

• Chronic allograft rejection
• Acute rejection
• Transplant renal artery stenosis
• Ureteric obstruction
• Recurrent and De novo glomerlonephritis
• BK virus nephropathy
• Calcineurin induced nephropathy
  

Causes not related to allograft includes:

• Pre-renal
• Renal
• Post-renal

The Solitary Pulmonary Nodule

A solitary pulmonary nodule or coin lesion is an approximately round lesion that is less than 3 cm in diameter and that is completely surrounded by pulmonary parenchyma without other abnormalities.

Lesions larger than 3 cm are called masses and are often malignant.

Pulmonary nodules are usually discovered incidentally on CXR but CT scan is considered the required standard.

Radiographic features distinguishing benign and malignant:

Margins - two pattern of margin are relatively specific for cancer.

• Corona radiata/ spiculated appearance - very fine linear strands extending 4 - 5 mm outward from the nodule.

• Scalloped border - associated with intermediate probability of cancer.

Calcification - suggest it is a benign lesion.

• laminated or central pattern is typical of granuloma.

• popcorn pattern is seen in harmartomas.

Growth rate - the volume-dobuling time for malignant bronchogenic tumours is rarely less than a month or more than a year.

If the lesion is spherical, a 30 percent increase in diameter represents a doubling of volume.

Gynaecomastia

The pathophysiological process of gynaecomastia involves an imbalance between free estrogen and free androgen action in the breast tissue.

Evaluation

Once the diagnosis of gynaecomastia is established, it is important to review all medications, including over the counter drugs such as herbal products.

• Spironolactone
• Cimetidine
• Alcohol
• Marijuana
• Estrogen/anti-testosterone

Other causes that need to be considered and the investigations:

• hcG - increased in testicular tumour.

• Increased LH with decreased Testosterone - primary hypogonadism.

• Normal or decreased LH with decreased testosterone - prolactin secreting tumour or secondary hypogonadism ( check prolactin level )

• Increased LH and testosterone - Hyperthyroidism/androgen resistance ( check TFT )

• Normal or decreased LH and increased estridiol - Sertoli-Leydig's cell neoplasm or adrenal neoplasm

• Normal hcG, testosterone, estridiol and LH - idiopathic gynaecomastia

Adenomatous Polyps of the Colon

Colonic adenomas are the precursor lesions of almost all colorectal cancers but 90 % of adenoma do not progress to cancer.

Consensus guidelines for colonoscopic surveillance after polypectomy:

• 1 - 2 low risk adenomas - 5 to 10 years
• 3 - 10 low risk adenomas or any high risk adenoma - 3 years
• More than 10 adenomas - less than 3 years
• Inadequately removed adenomas - 2 to 6 months
• Small, rectal, hyperplastic polyps - 10 yr or other average risk screening option.

More intensive surveillance is indicated when the patient's family history is suggestive of hereditary nonpolyposis colorectal cancer, an adenomatous syndrome, or a hyperplastic polyposis syndrome.

High risk adenomas are adenoma larger than 1 cm or histologically advanced adenomas ( tubulovillous or villous and those with high grade dysplasia.

Approach to immunocompromised patients

Causes:

• Congenital

• Acquired

Age

Immunosuppressive medication

Malignancy

• Hodgkin's disease
• Chronic lymphocytic leukemia
• Multiple myeloma
• Solid tumors
  

Microbial infection

• HIV, AIDS
• Measles
  

Disorder of biochemical haemostasis

• Diabetes mellitus
• Renal insufficiency/dialysis
• Hepatic insufficiency/cirrhosis
• Malnutrition

Other

• Stress
• Asplenia/hyposplenism

General Recommendation for the care of the transplant recipient:

Immunization and prophylaxis

• Yearly influenza and pneumovax vaccine every 5 years
• PCP prophylaxis if necessary

Cancer Surveillance

• Male - Prostrate cancer screening
• Female - Mammogram, Pap smear yearly
• Both - Colonoscopy in patients over 50 years and annual dermatology screening

Cardiovascular

• Aggressive risk factors modification
• Aspirin unless contraindicated

Bone disease

• Calcium and vitamin D supplementation
• DEXA scan within 6 mths of transplantation and then yearly

Pregnancy and Heart disease

Cardiac disease is now the leading cause of maternal mortality in the United Kingdom.

Haemodynamic changes in pregnancy

• Plasma volume increases by 30 - 50 % during pregnancy.

• Systemic vascular resistance reduces by 30 %.

• Oxygen consumption increases throughout the pregnancy.

• Haemodynamic changes persist for 2 - 3 weeks post delivery but may not completely resolve for upto 12 weeks.

• During labour and delivery cardiac output is further increased, especially after delivery of placenta, due to increased venous return from uterine contraction.

Pre-pregnancy counselling and assessment

• It should be done by a cardiologist or obstetrician with an interest in heart disease in pregnancy.

• Counselling should include the effects of pregnancy on the mother and fetus as well.

Maternal Risks - It is important to be realistic with the prospective parents and if pregnancy is deemed high risk, alternatives such as adoption or surrogacy should be discussed and appropriate advice about contraception given.

• Predictors of adverse maternal events

NYHA class >II
Cyanosis ( SaO2 less than 90%
Prior Cardiovascular event
Systemic ventricular ejection fraction less than 40%
Left Heart Obstruction

Estimated risk of adverse event is 5 %, 27 % and 75 % with 0, 1 or > 1 of these risk factors respectively.

• There are some conditions that should be considered prohibitively high risk with a > 10 % risk of maternal death, and includes:

Pulmonary hypertension
Marfan syndrome with dilated aortic root ( risk reduced with surgical repair )
Severe left heart obstructive lesions ( risk reduced with repair ).
Systemic ventricular dysfunction

Fetal Risk

• In general, drugs known to be teratogenic should be stopped preconception or once pregnancy is confirmed.

ACEI
Angiotensin II receptor antagonists
Amiodarone
Warfarin
Spironolactone

MS, which is the most frequent VHD encountered during pregnancy, is often poorly tolerated when valve area is ,1.5 cm2, even in previously asymptomatic patients. Dyspnoea worsens between the third and fifth months, which corresponds to the increase in cardiac output. The persistence of dyspnoea or pulmonary hypertension is associated with a high risk of complications at delivery, thereby threatening the life of both the mother and foetus.

Severe AS is less frequently encountered during pregnancy. Complications occur mainly in patients who were symptomatic before pregnancy.225 The risk of heart failure during pregnancy or at delivery is low when mean aortic gradient is ,50 mmHg.

Foetal prognosis is also impaired in the case of stenotic heart valve disease, due to growth retardation, preterm delivery, and low birth weight. For these reasons, patients with severe MS or AS should be treated before pregnancy if possible, even in asymptomatic patients.

Chronic AR and MR are well tolerated during pregnancy, even when severe, provided LV systolic function is preserved.However, the risk of complications is high when LVEF is ,40%, the prognosis being close to that of cardiomyopathy. Conversely, acute regurgitation is poorly tolerated.

In patients with Marfan’s syndrome, the risk of aortic-related complications including dissection during pregnancy increases markedly when AR is more than mild or when maximum aortic diameter is .40 mm. In these cases, pregnancy should be preceded by replacement of the ascending aorta, in particular, when the native aortic valve can be preserved. Aortic complications should be considered in any patient presenting with chest pain or pain in the posterior thorax.

When the first visit occurs during pregnancy, early termination may be considered in the following situations:

• Severe LV dysfunction (EF ,40%).
• Marfan’s syndrome with aneurysm of ascending aorta 40 mm.
• Severe symptomatic stenotic valve disease, which cannot be treated using percutaneous procedures.

Immunosuppressant

Immunosuppressive agents are used to:

• Prevent the rejection of transplanted organs and tissues
• Treat autoimmune diseases or diseases that are most likely of autoimmune origin

Because the majority of them act non-selectively, the immune system is less able to resist infections and the spread of malignant cells.

Immunosuppressive drugs can be classified into five groups:

• Glucocorticoids
• Calcineurin inhibitors such as cyclosporin and tacrolimus
• Sirolimus derivatives such as everolimus, sirolimus
• Mycophenolate mofetil
  
• Antibodies
• Cytotoxics
  

Glucocorticoids:

• suppress cellular and humoral immune system
• anti-inflammatory effects

Calcineurin inhibitor - cyclosporin and tacrolimus

• Cyclosporin and tacrolimus block the action of calcineurin in activated T cells. This prevents production of interleukin-2 and other cytokines which normally stimulate T cell proliferation and differentiation.

• Common side effects include gingival hyperplasia, hirsutism and nephrotoxicity.

Sirolimus Derivatives:

• Bind to the same intracellular protein (FKBP-12 ), then blocks the activity of mammalian target of rapamycin (mTOR) kinase preventing cell cycle progression and cytokine-induced T and B cell proliferation.

• Common side effects include rash, neutropenia, proteinuria and interstitial lung disease.

Mycophenolate mofetil

• selectively suppresses lymphocyte proliferation and antibody formation by inhibiting inosine monophosphate dehydrogenase.

• Common side effects include GI symptoms.

Antibodies:

Antibodies are sometimes used as a quick and potent immunosuppressive therapy to prevent the acute rejection.

Includes:

• Polyclonal antibodies which inhibit T cell and cause lysis.
  
• Monoclonal antibodies which are directed towards exactly defined antigens.

Cytotoxics:

In immunotherapy, they are used in smaller doses than in the treatment of malignant diseases. They affect the proliferation of both T cells and B cells.

includes:
Alkylating agents - such as cyclophosphamide, which is probably the most potent immunosuppressive compound.
Anti-metabolites

• Folic acid analog - such as methotrexate
• Purine analogs - azathioprine and mercaptopurine

Azathioprine can cause irreversible bone marrow failure for those with a particular polymorphism of the TPMT gene.

Drug interactions with allopurinol.

Gastroparesis

Gastroparesis, also called delayed gastric emptying, is a disorder in which the stomach takes too long to empty its contents.

The vagus nerve controls the movement of food through the digestive tract. If the vagus nerve is damaged, the muscles of the stomach and intestines do not work normally, and the movement of food is slowed or stopped.

Major Causes of Gastroparesis

• diabetes
• surgery on the stomach or vagus nerve
• postviral syndromes
  
• anorexia nervosa
• medications, particularly anticholinergics and narcotics (drugs that slow contractions in the intestine)
  
• nervous system diseases, including abdominal migraine and Parkinson's disease
• smooth muscle disorders such as amyloidosis and scleroderma
• metabolic disorders, including hypothyroidism

Diagnosis

The diagnosis of gastroparesis is confirmed through one or more of the following tests.

• Gastric manometry
  
• Radioisotope gastric-emptying scan
• Upper GI endoscopy to exclude other causes of nausea
• USS to exclude the cholecystitis and pancreatitis.

Treatment

It is important to note that in most cases treatment does not cure gastroparesis—it is usually a chronic condition. Treatment helps the patients to manage the condition so that they can be as healthy and comfortable as possible.

Removal of causes of gastroparesis is important such as better glucose control.

Dietary approach

• six small meals a day instead of three large ones.
• Low fibre diet

Prokinetic Agents

• Metocloparamide
• Domperidone
• Ondansetron
• Erythromycin

Feeding tube or parenteral therapy

Newer therapy include gastric pacemaker

Work up for Transplant

Cardiovascular Investigation - vessels and heart ar the Achilles heel in the transplanted patient

Evaluation of iliac and lower extremity vessels prior to transplantation

• Approapirate procedure a stenotic lesions in these areas are doppler/duplex sonography or angiography. These examinations are particularly indicated in patients with signs of peripheral vascular occulsive disease.

Evaluation of cardiac performance

• Mainly two diseases must be excluded which are common in dialysis patients: 1) coronary artery stenosis ( present in 40 % of patients at the start of dialysis ), 2) Aortic valve calcification and stenosis.
• Stress echocardiogram are useful.
• If the stress echocardiogram reveals signs indicating previous MI, coronary angiogram is strongly recommended.
• Coronary angioplasty or bypass procedure are necessary, if required, before putting patient on the waiting list.
  

Evaluation of carotid arteries

• Carotid duplex/doppler is useful as coronary artery disease is an indicator of coronary artery disease.
• In polycystic kidney disease, cerebral aneurysm should be excluded by MRI.

Respiratory examination

• CXR
• Respiratory Function Test

Oncology

• Skin cancer - need dermatological review
  
• for women - need mammogram and pap smear
• for men over 50 yrs - need PSA and PRDE of prostrate gld
• for analgesic nephropathy patient - urothelial cancer need to be checked.
• There is a consensus that a waiting period of 5 yrs should be respected before the patient is put on the waiting list.
  

Exculsion of chronic bacterial or viral infection

Chronic Bacterial Infection:

• Tuberculosis
• Dental Check up for dental root abscess
• Cholecystolithiasis and diverticulosis need to be treated before transplantation

Chronic Viral Infection:

• Hepatitis B and C
• HIV
• CMV carrier status is important as well

Immunological Investigation

• HLA types
• Blood groups

Multiple Sclerosis

Multiple sclerosis is the chronic inflammatory demyelinating disease of the central nervous system.

Clinical course:

• Relapsing and remitting
• Primary progressive
• Secondary progressive

Management:

Symptomatic Treatment

• Anti-spasmodic agent
• Mild relapse - nil treatment.
• Moderate to severe relapse - high dose methylprednisolone.
• Recent accelerated deterioration of PP/SP MS - high dose methylprednisolone.

Disease modifying agent

• Interferon beta reduces the frequency of relapses in RR - MS by about a third and its severity.
• Glatiramer is useful in case of tolerance to Glatiramer.
• Natlizumab - if interferon beta and Glatiramer are ineffective.
• Mitoxantrone

Causes of Nephritis and Nephrotic syndrome

Nephritis Syndrome

Nephritic syndrome is characterized by proteinuria, hematuria, azotemia, red blood cell casts, oliguria and hypertension.

The main features are hypertension and RBC casts.

The proteinuria in nephritic syndrome is not severe, if it is severe the patient likely has a mix of nephritic syndrome and nephrotic syndrome.

Causes:

• IgA Nephropathy and Henoch Schonlein purpura
• Mesangiocapillary GN
• Idiopathic crescentic GN
• Lupus nephritis
• Post-infectious GN
• Anti-GBM disease
• ANCA positive small vessel vasculitis

Nephrotic Syndrome

It is a clinical syndrome defined as proteinuria of more than 3.5 g per day, hypoalbuminaemia, generalised oedema and hyperlipidaemia.

Causes:

• Minimal change nephropathy
• Membranous nephropathy
• Focal segmental glomerulosclerosis
• Mesangiocapillary glomerulonephritis
• Lupus Nephritis
• Diabetes glomerulosclerosis
• Renal amyloidosis

Acute Renal Failure

Differentiating acute and chronic renal failure

The only two consistently useful indicators are:

1) Previous measurement of renal function

2) USS - long standing renal disease leads to loss of renal parenchyma and reduce renal size. A small less than ( 9 - 10 cm ) echobright and often cystic kidneys are characteristic of chronic kidney disease.

Exception is Diabetic nephropathy which tend to have relatively normal size kidney!

3) Laboratory are rarely helpful:

• Normal Hb argue against CKD but anaemia can be found in both CKD and ARF.
• Low calcium and high phosphate are secondary to impaired synthesis of vitamin D as found in patient with CKD.

Classification of ARF

Acute renal failure can be divided into pre-renal, renal and post-renal.

Intrinsic renal ARF - encompass all causes of ARF in which renal parenchyma has been damaged.

Large Blood Vessels

• Renal artery stenosis
• Cholesterol emboli
• Renal Vein thrombosis

Small Blood Vessels and Glomeruli

• Glomerulonephritis
• Vasculitis
• Scleroderma renal crisis
• Thrombotic microangiopathies
• Malignant hypertension
  

Tubulointerstitium

• Acute Interstitial Nephritis
• Cast nephropathy ( complicating myeloma )
• Contrast nephrotoxicity
  
• Tumour lysis
• Urate nephropathy
  

Acute Tubular Necrosis

• Ischaemic
• Nephrotoxic - aminoglycosides, myoglobin

The Nephritic and myeloma screen are necessary if an intrinsic renal cause of ARF ( but not ATN ) is suspected.

• Infection - 2 sets of blood cultures & ASO titre, HIV and Hepatitis serology with cryoglobulin level.
  
• Myeloma screen - plasma protein electrophoresis and immunoglobulin levels
  
• Anti-nuclear antibody ( ANA )
• Rheumatoid factor ( RF )
• Anti-neutrophil cytoplasmic antibody ( ANCA )
• Anti-glomerular basement membrane antibody ( anti-GBM )

Hepatomegaly

Causes:

Fluid

• Infection/Inflammation

Acute/Chronic Viral Hepatitis
Autoimmune Hepatitis
Cholangiohepatitis
Liver abscess

• Right sided heart failure

• Budd Chiari Syndrome

Fibrous tissue - early cirrhosis

Cells

• Myeloproliferative disorder
• Leukaemia
• Lymphoma
• Thalassaemia
• HCC
• Metastatic tumor
  

Protein/Glycogen/Fat

• Fatty liver
• Amyloidosis
• Glycogen storage disease

Miscellaneous

• Cysts
• Reidel's lobe
• Low lying diaphragm - COPD

Diagnosis:

Sometimes the diagnosis of underlying aetiology for hepatomegaly is challenging.

Often history provides many clues to the diagnosis. Look for:

• Risk factors for viral hepatitis
• History of autoimmune hepatitis
• Foreign travels
• Thrombophilia for Budd Chiari syndrome
• History of alcohol intake
• Fever, night sweat and weight loss for haematological malignancy

Peripheral Neuropathy

There are several patterns of peripheral nerve disease:

• Mononeuropathy
• Multiple mononeuropathy
• Symmetrical polyneuropathy
• Plexopathy
• Radiculopathy
• Polyradiculopathy

The time course may be:

• Acute - reaching its nadir in <4 weeks
  
• Subacute - reaching its nadir in 4 - 8 weeks
• Chronic - taking 8 weeks to develop.

The deficit may be:

• Motor - proximal/distal & symmetrical/asymmetrical
• Sensory - the key features to look for here is pain and ataxia
• Autonomic

The underlying pathology may be:

• Axonal
• Demyelinating
• Mixed

Pure Motor:

Differential diagnosis includes - myopathy & disease of neuromuscular junction.

• Motor Neurone Disease
• Multifocal Motor Neuropathy

Prominent Motor symptoms together with sensory symptoms include:

• AIDP/CIDP
• Acute Intermittent Porphyria
• Lead Intoxication
• Charcot's Marie Tooth Disease

Pain:

Small Nerve Fibres involvement: has normal muscle power, reflexes and vibratory/proprioceptive senses as these are carried by large fibres. There will be reduced pinprick and thermal sensation in the affected area. Vibratory sensation can be mildly reduced at the toes.

The causes are extensive

• Mostly idiopathic
  
• Impaired glucose tolerance and Diabetes Mellitus and
  
• Sjogren's syndrome
• Hypothyroidism
• HIV infection/ Hepatitis C infection
• Vitamin B12 deficiency
  
• Neurotoxic Drug Exposure

Large Nerve Fibres involvement:

Sensory Ataxia: The best recognised causes are

• A paraneoplastic syndrome associated with anti-Hu antibodies, often due to small cell lung cancer
• Sjögren’s syndrome
  
• Cisplatin toxic neuropathy
  
• Pyridoxine toxicity
• many cases remain ‘idiopathic’ despite extensive workup and careful follow-up

Autonomic Features:

• Acute: AIDP
• Chronic: Diabetes and Amyloidosis

This blog emphasied about the symmetrical generalised neuropathy.

The differential diagnosis of more or less symmetrical generalised neuropathy is much more extensive and complicated than that of mononeuropathies.

Initial Investigations for symmetrical polyneuropathy include:

• Blood Test - FBC, eLFT, Ca, TFT, ESR, HbA1c, B12/Folate, serum protein electrophoresis
• Immunology - ANA
• Radiology - CXR
• Neurophysiology - Nerve conduction study
  

Chronic Axonal neuropathy:

Causes:

• Hereditary
• Infection - leprosy and HIV
• Diabetes
• Alcohol
• Amyloidosis
• Endocrinology - myxoedema and acromegaly
• Drugs
• Toxins
• Uraemia
• Cirrhosis
• Paraneoplastic

Chronic demyelinating neuropathy

Causes:

• Chronic inflammatory demyelinating polyradiculoneuropathy
• Multifocal motor neuropathy
• Para-protein associated demyelinating neuropathy
• Charcot-Marie-Tooth disease type 1 and type X.

Chronic Inflammatory demyelinating polyradiculoneuropathy - CIDP

It is important to distinguish CIDP from chronic axonal neuropathy because it responds well to treatement with immunotherapy.

Clues are:

• A relapsing course
• Proximal as well as distal weakness
• Increased CSF protein and normal cell count ( in at least 80 % )

Management:
Corticosteroids, intravenous immunoglobulin and plasma exchange are all beneficial but prolong treatment is necessary. In pure motor CIDP, which may be worsened by corticosteroids, IV Ig should be the first choice.

Multifocal motor neuropathy:

Clinically, it may resemble amyotrophic lateral sclerosis (ALS) with predominant lower motor neuron involvement, but muscle atrophy and more rapid progression are lacking.

Sometimes it can be confused with a pure motor form of CIDP as well.

The diagnosis depends on finding multifocal motor but not sensory conduction block at sites not subject to compression.

Management:
About 80 % of patients respond to IV Ig which has to be repeated every month.

Hereditary neuropathy:
The commonest cause is Charcot-Marie-Tooth disease. Other causes include:

• Hereditary sensory and autonomic neuropathy
• Distal hereditary motor neuropathy
• Familial amyloid polyneuropathy
• neuropathy associated with multisystem hereditary disorders such as metachromatic leukodystrophy, mitochondrial disorders and Refsum's disease.

Usually, the initial symptom of CMT is foot drop early in the course of the disease. This can also cause hammer toe, where the toes are always curled. Wasting of muscle tissue of the lower parts of the legs may give rise to "stork leg" or "inverted bottle" appearance. Weakness in the hands and forearms occurs in many people later in life as the disease progresses.

A definitive diagnosis for a specific type of CMT is established via genetic testing for most types.

Acute Neuropathy
Acute neuromuscular paralysis has a wide differential diagnosis but GBS is the commonest cause.

Differential diagnosis of acute neuromuscular paralysis include:
Cortical lesion- such as CVA, encephalitis
Cord lesion - compression from abscess, haematoma, tranverse myelitis
Peripheral neuropathy:

• Gullain - Barre syndrome
• Poliomyelitis
• Rabies
• Acute intermittent porphyria
• Drug induced
• Diphtheria
• Thiamine deficiency
• Critical illness neuropathy

Neuromuscular transmission:

• Tick bite paralysis
• Myasthenia gravis
• Lambert Eaton myasthenic syndrome

Disorder of muscle:

• Hypokalaemia
• Hypophosphataemia
• Inflammatory myopathy
• Periodic paralysis
• Acute rhabdomyolysis

Involuntary Treatment

Statutory Health Attorney

A statutory health attorney is someone with automatic authority to make health care decisions on your behalf if you are an adult whose ability to make decisions is permanently or temporarily impaired.

They can consent to most health care issues, including withdrawing life-sustaining measures.

You do not need to fill out forms or formally appoint a statutory health attorney. A person automatically acts in this role when the need arises because of their relationship to you. They do not need any special expertise to perform the role but must be over 18 and capable of making decisions about health care.

Those who can act as a statutory health attorney are (in order of preference, and provided they are readily available and culturally appropriate):

• the patient’s spouse or de facto partner (if the relationship is close and continuing)
• the patient’s primary carer, but not a paid carer (although you may receive a carer’s pension)
• a close adult friend or relative
• the Adult Guardian as a last resort.

Enduring Power of Attorney ( cannot be used in abortion, transplant and tissue donation.

Firstly, there are two types of power of attorney:

• general power of attorney
• enduring power of attorney.

A general power of attorney is given to someone to make financial decisions on your behalf when you are absent, for example, if you are overseas and need someone else to sell your house or pay your bills.

An enduring power of attorney is put in place in the event something happens to you (usually illness or accident) that makes you unable to make your own decisions.

Both types involve a formal agreement giving someone else the power to make decisions on your behalf. It works like this:

1. You sign a form giving power of attorney to the person of your choice.
2. You specify the types of decisions that the person you choose can make.
3. The person agrees to the appointment by signing the acceptance section of the form. This makes them your attorney.
4. As your attorney, they can then act on your behalf if necessary.

Adult Gardianship

The role of the Adult Guardian is to protect the rights and interests of adults who are unable to make decisions for themselves. This lack of decision-making ability, known as impaired capacity, may be caused by intellectual or psychiatric disability, acquired brain injury, dementia or temporary illness such as delirium.

As an independent statutory officer, the Adult Guardian operates free from inteference from government and non-government organisations.

Both the Adult Guardian and Public Advocate are concerned with protecting these people’s rights and interests. However, the Public Advocate does not deal with individual cases, but looks at widespread deficiencies in institutions and systems that affect a large number of people.

For example, while the Adult Guardian might obtain a warrant to remove a person with impaired capacity who is being exploited by a carer, the Public Advocate looks at how the system has failed this person, and could be failing others in similar situations.

Advance Health directive

If you become seriously ill, unconscious or are unable to communicate your health care wishes, critical decisions may need to be made. You can make an advance health directive to make your wishes known in case you are in this situation.

You can make a directive if you are over 18 and have the capacity to do so. This means that you:

• understand the nature and consequences of your health care decisions
• understand the nature and effect of the directive
• freely and voluntarily make these decisions
• communicate decisions in some way.

Motor Neurone Disease

Epidemiology
The incidence is approximately 2 in 100 000 population per year and the average age of onset is roughly 65 years.

Types:
Amyotrophic lateral sclerosis ( ALS )

• Fundamental to the diagnosis is progressive weakness with mixed upper and lower motor neuron signs. Brisk reflexes in the presence of local wasting is a strong clue to the diagnosis.
• Visible fasciculations are usually prominent but tend to fade as the illness progresses.
• Differential diagnosis includes cervical spondylotic myeloradiculopathy and paraneoplastic neuromuscular syndrome.

Progressive muscular atrophy:

• True lower motor neuron MND is rare because many patients develop upper motor neuron signs at some point in the disease and are probably best classified as lower motor neuron predominant ALS.
• Differential diagnosis includes conduction block neuropathy, paraneoplastic neuropathy, X linked spinobulbar muscular atrophy ( Kennedy's syndrome ) and adult onset spinal muscular atrophy.

Primary lateral sclerosis:

• rare and accounts for 1 - 2% of MND.
• It is characterised by an ascending spastic tetraparesis with involvement of speech in the majority by 3 years.
• Urinary urgency is common.

Flail arm variant:

• Bilateral weakness and wasting of the proximal upper limb which may not spread to other regions for a number of years is sometimes associated with a dropped head.
• Despite proximity of the affected segments to the respiratory neurons, vital capacity may be unaffected until late in the disease.

Lower limb onset:

• It may remain confine to lower limb and present with with gradual ascending distal weakness.

Progressive bulbar palsy:

• The speech and swallowing involvement is the early features of a condition which rapidly generalises to the limbs and respiratory msucles and has a poor prognosis.

Investigations:
Essential

• Blood test - FBC, eLFT, Ca/PO4, ESR, CK and plasma protein electrophoresis.
• Nerve conduction study and EMG
• MRI spine / brain as indicated by clinical signs

In selective cases

• Blood test - B12, antineuronal antibodies, HIV serology, lyme serology and antiacetylcholine receptor antibodies
• Lumbar puncture
• Muscle biopsy

Treatment:
Aim for supportive treatement.
Riluzole is currently the only drug licensed for the treatment of MND.

• The probability of survival at 1 year after starting the drug is 9 % greater than the placebo ( 2 -3 months greater life expetancy ).
• There is no evidence of any effect on quality of life or improvement in specific symptoms.

Wrist Drop

Wrist drop is due to weakness of extensor carpi radialis longus ( supplied by C5/6 and the radial nerve ) and the extensor carpi ulnaris ( supplied by C7/8 and the posterior interosseous branch of the radial nerve ).

Anatomy of radial nerve:
It originates from the posterior cord of the brachial plexus with roots from C5, C6, C7, C8 & T1.

Branches

• Above spiral groove - nerve to triceps
• Below the spiral groove and above the elbow - brachioradialis
• Below the elbow - nerve to extensor carpi radialis longus and posterior interosseus nerve

Posterior interosseus nerve supply the extensor carpi ulnaris and extensor digitorum.

Radial nerve has sensory supply to posterior arm, forearm and dorsum of hand.

Causes of wrist drop:

• Radial nerve lesion
• Radiculopathy ( C7,8 ), if there is involvement of the finger flexors as well.
• Cortical lesion

Management:

• Nerve Conduction Study should be done.
• Spontaneous recovery is the rule and splinting helps hand function.
• If the palsy last more than 12 weeks then surgical decompression is an another option.

Pulmonary Hypertension

Pulmonary Hypertension is a mean pulmonary artery pressure more than 25 mmHg, with a pulmonary capillary or left atrial pressure less than 15 mmHg.

Causes:

Pulmonary arterial hypertension

• Sporadic
• Familial
• Related to:
• Collagen vascular disease
• HIV infection
• Drugs and toxins - fenfluramine
• Systemic to pulmonary shunts - ASD, PDA, Portal Hypertension

Pulmonary Venous Hypertension

• Left sided heart disease such as MS, LVF, AS

Pulmonary Hypertension associated with hypoxaemia

• Sleep disordered breathing
• Long term exposure to high altitude
• COPD
• Interstitial lung disease

Pulmonary Hypertension due to chronic thrombotic disease

• Pulmonary embolism

Miscellaneous

• Sarcoidosis
• Compression of pulmonary vessels such as tumour

Treatment:
General:

• Anticoagulation - all patients with pulmonary hypertension are at risk of venous thromboembolism and intrapulmonary thrombus because of sluggish pulmonary blood blow, dilated heart chambers and venous stasis.
• Long term oxygen therapy
• Immunization with annual influenza and pneumococcal vaccine.

Vasodilator therapy

• Calcium channel blocker - nifedipine and amlodipine
• Prostaglandin analogues - ilioprost
• Endothelin receptor antagonists - bosenten
• Phosphodiesterase inhibitors - sildenafil

Smoking Cessation

Currently, 16.6 % of australians aged 14 years or older smoke daily. This represents 2.9 millions people in australia, one in two of whom will die prematurely from a smoking related disease if they continue to smoke.

Counseling about cessation of smoking behaviour involves six stages:

• Pre-contemplation
• Contemplation
• Determination
• Action
• Maintenance
• Relapse

The role of a doctor to find out which stages the patients are at and to give information and support to achieve the smoking cessation.

Once the patients are determined to stop smoking, pharmacotherapy should be offered to the nicotine dependent smokers.

Method: The most popular method used is the cold turkey method - quitting abruptly with no medication or assistance.

Only 3 - 5 % of smokers who try to quit without treatment remain abstinent six to 12 months later.

Cut down then stop method is a new strategy for smokers who are not currently willing or able to stop smoking but are prepared to cut down. Smoker gradually cut down their cigarette use and stop smoking completely by six months and then nicotine replacement therapy is ceased by 12 months.

Australian and international guidelines now advise using medication to assist quitting in all smokers who are nicotine
dependent, except where indicated.

To assess the nicotine dependence the patients should be asked:

• Do you usually smoke within 30 minutes of waking?
• Do you smoke between 10 and 15 or more cigarettes per day?
• Have you had cravings or withdrawl symptoms during previous quit attempts?

Nicotine dependence is likely if there is a positive answer to any of these questions.

Nicotine Replacement therapy

• Pre-quit treatment with nicotine patches two weeks before quit day.
• Nicotine patches are then continued for the full course of 10 to 14 weeks after quit day.
• Quick acting forms of NRT such as lozenges and chewing gum are suitable for prompt relief of withdrawl symptoms or cravings as they arise.

Varenicline: reduces cravings and withdrawl symptoms as other treatment do but also reduces satisfaction gained from smoking a cigarette.
Varenicline is taken as a 12 weeks course of 1 mg twice a day after an initial one week titration phase. The patient should quit smoking between seven and 10 days after the first dose.
Side effects include nausea, depression and suicidal ideation.

Bupropion: is an effective first line therapy. There is a one in 1000 risk of seizures in patients taking it and it is contraindicated in patients with predisposing risk factors for seizures.

Obesity

Not all obese people eat more than the average person, but all obviously eat more than they need!

Obesity is a leading preventable cause of death worldwide, with increasing prevalence in adults and children, and it is viewed as one of the most serious public health problems of the 21st century. Obesity is stigmatized in the modern western world, though it has been perceived as a symbol of wealth and fertility at other times in history, and still is in many parts of Africa.

WHO Classification:
Overweight - BMI 25 - 30.
Obese
Class I / moderate - BMI 30 - 35
Class II / severe - BMI 35 - 40
Class III/ very severe - BMI more than 40

Aetiology:

• Genetics
• Endocrine - hypothyroidism, Cushing's syndrome and growth hormone deficiency
• Obstructive sleep apnoea
  
• Life style - sedentary habit, increased calorie intake

Morbidity and Mortality associated with obesity:

• Psychological
• CVA
• Cardiovascular: Hypertension, IHD, PVD and heart failure
• Respiratory: OSA/OHS
• Gatroenterology: hiatus hernia, fatty liver, gall stones
• Endocrine: diabetes, hyperlipidaemia
• Musculoskeletal: back pain, osteoarthritis, varicose vein and recurrent cellulitis.

Treatment of Obesity:

It should be divided into initial weight loss phase and long term maintenance phase.
Initial weight loss phase:

Increasing energy expenditure:

• Unfortunately increased physical activity alone with no change in food intake is associated with only moderate weight reduction.
• Many patients simply compensate for increased activity by increasing their food intake.
• Commercial weight loss program are available.

Reducing energy intake:
Life Style changes:

• Food chart
• Dietician advices about reducing portion of food intake and change in energy density of food
• Psychological method such as distraction away from food

Pharmacological methods:

Sibutramine is a noradrenaline and serotonin reuptake inhibito that acts centrally to increase satiety while increasing energy expenditure. It is available as 10 mg or 15 mg dose.
It side effects include insomnia, agitation and constipation as well as slight increase in blood pressure.

Orlistat is a lipase inhibitor acting in the intestine to decrease the absorption of fat by approximately 30 %. Its side effects include flatulence, bloating or other gastrointestinal effects.

Sertraline and fluoxetine are not licensed for the management of obesity but they can be of particular benefit in patients with mild depression or with obsessive thoughts regarding food intake. For many patients these drugs can limit the sense of deprivation associated with dieting.

Non-pharmacological methods:

Although patients with simple obesity ( BMI between 30 - 40 ) can lose weight using many different techniques, those with morbid obesity has many limitations including poor mobility.

Patients with extreme morbid obesity ( BMI > 50 ) have great difficulty walking more than 2000 steps a day.

Three non-pharmacological methods are currently used:

Very low calorie diets - optifast

• Optifast three meals per day replacement take in fewer than 800 calories per dya yet do not feel hunger because they produce ketones. It is also used in Australia to reduce liver size prior to a laproscopic gastric band procedure.

Intragastric balloon is beneficial for in obese patients with lower BMI ( 30 - 35 ) who do not fit the criteria for a laproscopic gastric banding procedure.

Bariatric surgery - either restrictive or malabsorptive or both.

• Indications: BMI > 40 or BMI > 35 with complications such as DM, IHD, Hypertension or sleep apnoea.

Maintenance phase:

A new concept of weight maintenance is the idea of a trigger weight.

Patient try to maintain their weight by reducing energy intake and increasing their energy expenditure. Once they hit above the trigger weight, they come back for the initial successful methods of weight loss.

Erectile Dysfunction

Erectile dysfunction is the most common sexual problem in men.

Erectile dysfunction is the inability to achieve and maintain an erection of sufficient rigidity for satisfactory sexual intercourse.

Causes:

• Endocrine: hypogonadism, thyroid disease
  
• Vascular such as smoker, IHD, PVD and CVA patients
• Neurogenic: autonomic neuropathy such as diabetes
• Drugs such as beta blocker
• Psychogenic: such as depression and anxiety

Management:
History

• Presence of nocturnal emission and frequent satisfactory morning erections makes endocrine disease unlikely.
• Review past medical history and drug chart.
• Five - Item Version of the International Index of Erectile Function Questionnaire

http://www.medal.org/OnlineCalculators/ch16/ch16.09/ch16.09.07.php

Physical examination

• External genitalia examination
• Check for peripheral pulses.

Investigations

• Blood test: FBC, UE, LFT, PSA, morning total testosterone, gonadotrophins and prolactin level and thyroid function test.

Treatment:
Non-pharmacological - such as removal of offending drugs, cessation of smoking and Vaccum device.
Pharmacological -
Modify the reversible causes such as replacement of testosterone, treatment of thyroid disorder.
Drugs
First line - Phosphodiesterase inhibitor such as sildenafil, tadalafil and vardanefil. However, they are contraindicated in patients who use the nitrate therapy.
Second line - intracorporal injection of vasodilator such as alprostadil.

Polycythemia

Polycythemia vera is a myeloproliferative disorder that need to be distinguished from other causes of increased haemoglobin level such as:

• Smoker's polycythemia
• Relative polycythemia - dehydration
• Secondary polycythemia - such as hypoxia, renal cell cancer which produces erythropoietin

In 2005, the JAK2-V617F mutation was described in the JAK2 gene. This mutation occurs in about 95% of patients with polycythemia vera. This mutation can also occurs in other myleproliferative disorders such as primary myelofibrosis or essential thrombocythemia, although they do not occur in the general population.

As a result, Current WHO diagnostic criteria was adjusted for the diagnosis of polycythemia vera as follows:

The presence of both major criteria and at least one minor criteria or the first major criteria and at least two minor criteria is required for a diagnosis of polycythemia vera.

The major criteria are:

1. Raised Haemoglobin lvel, haematocrit or red cell count
2. the presence of JAK2 gene

The minor criteria are:

• typical bone marrow histology
• low serum erythropoietin level
• formation of endogenous erythroid colonies on marrow culture

Diagnositic Algorithm:

If high haemoglobin level is found, repeat the haemoglobin test to determine if the raised level is borderline or transient.

If haemotocrit is less than or equal to 0.54 in men or 0.47 in women:
Consider causes other than polycythemia vera.

If haemotocrit is more than 0.54 in men or 0.47 in women:

• Firstly check oxygen satuation level, if less than 92% then it is likely due to secondary cause.
• If it is more than 92%, check for JAK2 gene mutation, erythropoietin level and/or bone marrow biopsy.
  

Diagnosis and Treatment of hepatocellular carcinoma ( HCC )

Risk factors:

HCC is unusual among human cancers in that the etiological agent responsible is usually readily identifiable. The prevalence of HCC worldwide parallels that of viral hepatitis. Alcohol, genetic haemochromatosis and rarely primary biliary cirrhosis are associated.
The risk of HCC development is much greater in men for the majority of aetiologies.
Cirrhosis is present in the vast majority of patients with HCC in the UK and europe: estimates varies between 90 % and 95 %. It is unclear if cirrhosis per se is biologically important in the tumorigenic pathway, or if tumour development and fibrogenesis take place concurrently but with fibrosis taking a shorter time period.
Non-cirrhotic HCC occur in the young patients ( fibrolamellar variant ) and in the elderly ( apparent de novo HCC )

Natural History of HCC:

• The estimated doubling time is one to 19 months with a median of 6 months.
• 50 - 90 % of patients with Child Pugh A cirrhosis will survive a year untreated with only 20 % of Child Pugh C patients.
• Smaller HCC at presentation have realtively long tumor doubling time and overall survival with tumour size less than 5 cm was 81 -100 % at one year and 17 - 21% at three year with no therapy.

Screening:

As per British Gastroenterology guidelines, surveillance for hepatocellular carcinoma should be considered in the following high risk groups:

1. Male and Female with established cirrhosis due to hepatitis B virus, particularly those with ongoing viral replication.
2. Male and Female with established cirrhosis due to HCV.
3. Male and Female with established cirrhosis due to genetic haemochromatosis.
4. Male with alcohol related cirrhosis who are abstinent from alcohol or likely to comply with treatment
5. Male with cirrhosis due to primary biliary cirrhosis.

The risk of HCC development in cirrhosis due to autoimmune hepatitis, primary sclerosing cholangitis in both sexes, and alcoholic and primary biliary cirrhosis in women is generally low.

If the surveillance is offered, it should be six monthly abdominal ultrasound assessments in combination with serum alpha feto protein estimation.

AFP, a normal serum protein synthesised by fetal liver cells and yolk sac cells, is the most widely used screening test for HCC. The normal range for AFP is 10 - 20 ng/ml and a level > 400 ng/ml is usually regarded as diagnostic. Two thirds of HCC less than 4 cm however has AFP levels less than 200 ng/ml and up to 20 % of HCC do not produce AFP, even when very large. A rising AFT over time, even if the levels does not reach 400 ng/ml is virtually diagnostic of HCC.

Diagnosis of HCC:

When a patient presents with a liver mass, irrespective of screening, there is a requirement to make a diagnosis and to stage the disease.

If the patient known to have pre-existing cirrhosis:

A mass greater than 2 cm has 95 % chance of being HCC.
- If the AFP is raised, this confirms the diagnosis and further investigation is only required to establish the most appropriate therapy.
- If the AFP is normal, further imaging ( CT/MRI or lipoidol angiography with follow up CT) will usually allow a confident diagnosis to be made.
- In a very few cases where there is real diagnosis in doubt, biopsy may be indicated.

A mass less than 2 cm on ultrasound, probably 75 % of such nodules turn out to be HCC. Again radiological diagnosis CT/MRI and AFP may establish a definitive diagnosis. If not either a repeat examination to show enlargement of the lesion, percutaneous fine needle aspiration, or biopsy may be indicated.

The risk of seedling of tumor in the needle tract occurs in 1 - 3 %. Biopsy of potentially operable lesions should be avoided where possible.

Treatment of HCC:

Surgical Methods:
The only proven potentially curative therapy for HCC remains surgical, either hepatic resection or liver transplatation, and patients with single small HCC ( less than 5 cm ) or up to three lesions less than 3 cm should be referred for assessments of these treatment modalities.

• Liver transplantation should be considered in any patient with cirrhosis.
• Hepatic resection should be considered as primary therapy in any patient with HCC and a non-cirrhotic liver.
• Hepatic resection can be carried out in highly selective patients with hepatic cirrhosis and well preserved hepatic function ( Child-Pugh A) who are unsuitable for liver transplantation.
• Patients with replicating HBV had a worse outlook due to HBV recurrence and were previously not considered candidates for transplantation. Effective antiviral therapy is now available and patients with small HCC, as defined above should be assessed for transplantation.

Non-surgical methods:

Non-surgical methods should only be used where surgical therapy is not possible.

• Percutaneous Ethanol injection ( PEI ) has been shown to produce necrosis of small HCC. It is best suited to peripheral lesions, less than 3 cm in diameter.
• Chemoembolisation
• Systemic chemotherapy with standard agents has a poor response rate.
• Hormonal therapy with tamoxifen has shown no survival beneift.

What a pain!

Pain management ( of Non-malignant cause )is still a very much more of an art than a science and those who like black and white solution to clinical problem will be disappointed.

Acute Pain
Acute pain, associated with trauma or surgery, is generally easier to manage than chronic pain. This is because the type of pain is usually related to form of tissue damage resulting in excitation of nociceptor nerve endings. Few would deny that the use of potent opioid drugs in these circumstances is worthwhile.

Chronic Pain
Chronic pain is defined as pain lasting more than three months which is the upper limit of normal time for wound healing. Patients experiencing pain do not present with objective signs or symptoms as they would with high blood pressure or a raised blood glucose level.

There are three types of pain behaviour:

• Nociceptive pain due to excitation of mechanical, thermal or chemical nociceptors
• Neuropathic pain, defined as pain related to disease or injury of the peripheral or central nervous system
• Pain disorders that exist when it is not possible to explain the patient's symptoms on a physical basis. Pain disorder can be subconscious ( conversion disorder ) or conscious ( malingering ).

Management:
Non-pharmacological treatment plays an essential role in the management of chronic or persistent pain.
Firstly, it is important to reassure the patient that there is no serious underlying pathology, giving a simple but understandable explanation of the causes of pain.

It is recognised that because of a patient pressure a request for an X-ray or CT scan will usually be made. A careful explanation of these findings are needed because patients may interpret relatively benign reports in an alarmist way, further reinforcing abnormal beliefs about the cause of their pain.

Secondly, patient expectation need to be addressed to ensure that they are realistic. For many patients, whether they have nonspecific pain issues or specific but not otherwise treatable conditions, resolution of all pain symptoms is often impossible and patient's expectations need to reflect this. However, it is important to emphasie that despite pain, an improvement in function and quality of life is still possible.

Thirdly, Unlike acute pain management, physiotherapy is important to rehabilitate the patient and bed rest must be discouraged. The major aim of the whole management program is to improve activity and functional status of patients with the hoping returning back to usual employment.

Excessive reliance on passive coping strategies such as medication should be discouraged. Often patients with chronic pain are deconditioned and has high BMI due to psychological problem, unhealthy life style and lack of movement due to pain.

Fourthly, It is important to address the patient's psychosocial problems.

Due to persistent pain, many of these patients are unemployed, on disability pension adding to financial burden. They are therefore prone to suffer anxiety, depression and low self esteem.
Moreover, they are more likely to be socially isolated and has unhealthy life style such as smoking and drinking leading to cardiopulmonary diseases.

Psychologist referral should be made for cognitive behaviour therapy for the patient to be able to cope with the pain and related psychological problem. If low mood is detected, then use of antidepressant such as SSRI should be considered.

Despite the best efforts, some patients seem to rely soley on mediations and fail to engage in an appropriate rehabilitation program. These patients are sometimes referred to as ''chemical copers''. Management of these patients should involve clearly set boundaries, especially with regard to request for extra medication. Care should be taken to avoid unnecessary investigations, referrals and treatements. Significant support is required from the treating doctors, as well as allied health professionals, family and community services.

Pharmacological treatment:
Recent meta-analysis demonstrate a modest reduction in pain with dosages of upto 100 mg per day of morphine equivalent but this is not always accompanied by improved function. There is some agreement that in patients already receiving regular opioid medication for persistent pain, a ceiling for the total daily dose should be considered. Some authorities have suggested a ceiling of 100 mg per day morphine equivalents.

Surgery is no panacea and it may provide some temporary relief from pain such as facet joint injection in chronic back pain.

For neuropathic pain, first line medication is tricyclic antidepressant and if they are unable to tolerate it then pregabalin or gabapentin are recommended. Second line agents include anticonvulsant such as valporate or carbamazepine and serotonin noradrenaline reuptake inhibitor.