Testing for thiopurine methyltransferase status for safe and effective thiopurine administration: a systematic review of clinical guidance documents.

A common pharmacogenomic test is for thiopurine S-methyltransferase (TPMT) status prior to treatment with thiopurine drugs, used to treat auto-immune conditions and pediatric cancer. Guidelines assist practitioners with decisions regarding testing and treatment. The objectives were to conduct a systematic review and critical appraisal of guidance documents with statements regarding TPMT testing and thiopurine dosing. Guidelines, clinical protocols and care pathways from all disciplines were eligible. A quality appraisal was carried out by three appraisers using the Appraisal of Guidelines for Research and Evaluation II. Of the 20 documents found, 5 recommended genotyping while 4 recommended phenotyping. Thirteen documents provided dosing recommendations based on TPMT status. The quality appraisal revealed wide variation across documents. The National Institute for Health and Clinical Excellence and Cincinnati Children's Hospital guidelines demonstrated the highest overall quality with scores of 79 and 76, respectively. Low-scoring documents failed to use systematic methods to develop recommendations or to provide evidence to support recommendations. Guidance documents that included dosing recommendations demonstrated higher quality.

Hypocalcemia after thyroidectomy: mechanisms and management.

Hypocalcemia persists as a problem after thyroidectomy. We reviewed our experience with 245 thyroidectomies to define the spectrum of hypocalcemia, elucidate the mechanisms of hypocalcemia, and formulate a rational basis for its management. Postoperative hypocalcemia occurred in 8.6% of all patients undergoing thyroid surgery with incidence the highest in patients with total thyroidectomy for cancer (28%) and those with subtotal thyroidectomy for thyrotoxicosis (23%). Incidence was low in patients having subtotal thyroidectomy for other diseases (1.5%) and lobectomy (0%). The high incidence of hypocalcemia following subtotal thyroidectomy for thyrotoxicosis but not for other diseases suggests that a mechanism other than removal or damage of the parathyroids is responsible for the hypocalcemia. This may well be thyrotoxic osteodystrophy. This hypocalcemia usually occurs early, is of moderate degree, and is transient. Management includes calcium gluconate for acute symptoms and calcium lactate with vitamin D2 for chronic symptoms.

Parathyroid autotransplantation.

Autotransplantation of the parathyroid to the forearm has been performed in eight patients following total or subtotal parathyroidectomy. The mass of gland implanted was approximately one half that used in other series. Bilateral simultaneous parathormone levels drawn at three months after autografting several higher levels in the autografted arm in every patient examined. Replacement calcium and vitamin D therapy were withdrawn from two patients within eight months after transplant, and it is anticipated that all patients will be off maintenance at 12 months. Electron and light microscopy of grafted tissue has revealed viable glands with intracellular secretory granules, many mitochondria, and little fat. Indications for autotransplantation include patients with refractory renal osteodystrophy, reoperations for primary hyperparathyroidism, and extensive extirpative cancer surgery of the head and neck.

Treatment of corrosive burns of the esophagus.

Forty patients with caustic ingestion have been treated between 1955 and 1975. Strong alkali was the corrosive in 95%, and 80% were under 10 years old. Early esophageal stricture developed in 18 patients four weeks after lye ingestion. Among these, esophageal bougienge restored an adequate lumen in two patients with short, soft annular strictures, and right colon interposition was used for esophageal subsitution in ten who had long, dense strictures. We recommend early diagnostic esophagoscopy, to the uppermost level of burn injury only, to determine the presence and severity of the esophageal injury. If esophagoscopy reveals esophageal burn injury, corticosteroid and antibiotic therapy are continued. If no burn injury is visualized, the patient is spared unnecessary treatment. Long, dense strictures unresponsive to bougienage place the patient at risk from instrumental perforation, and these patients should undergo colon interposition through a substernal extrapleural tunnel.

Retrograde venous cardiac perfusion for myocardial revascularization: an experimental evaluation.

This study evaluates cardiac function in dogs during retrograde perfusion through the coronary sinus. Five hearts perfused retrograde in an ex vivo apparatus demonstrated rapid and marked increases in weight and perfusion pressure, became hemorrhagic, and contracted poorly within one hour. Five similarly perfused hearts treated with phenoxybenzamine experienced no increase in weight or perfusion pressure and maintained good color and contractions for up to one hour. Five additional hearts treated with phenoxybenzamine did not develop hemorrhage, edema, increased weight, or increased perfusion pressure but could maintain the systemic circulation for only brief periods after 15 minutes of intermittent cardiopulmonary bypass support. We conclude that cardiac viability can be maintained with retrograde perfusion enhanced with alpha blocking agents. However, hearts so perfused cannot maintain adequate systemic pressure. The data suggests that extensive myocardial revascularization through the retrograde venous route would be ineffective.

Peripheral arterial injuries: a reassessment.

Ninety-four patients with peripheral arterial injuries were subjected to acute repair, negative exploration, or late repair of the complications of the arterial injury (false aneurysm, A-V fistula, and/or limb ischemia). The causes of failure after acute injury include extensive local soft tissue and bony damage, severe concomitant head, chest or abdominal wounding, stubborn reliance on negative arteriograms in patients with probable arterial injury, failure to repair simultaneous venous injuries, or harvesting of a vein graft from a severely damaged extremity. There is a positive correlation between non-operative expectant treatment and the incidence of late vascular complications requiring late arterial repair. Delayed complications of arterial injuries occurred most frequently in wounds below the elbow and knee.