Penetrance and clinical consequences of a gross SDHB deletion in a large family.

Mutations in the gene encoding subunit B of the mitochondrial enzyme succinate dehydrogenase (SDHB) are inherited in an autosomal dominant manner and are associated with hereditary paraganglioma (PGL) and pheochromocytoma. The phenotype of patients with SDHB point mutations has been previously described. However, the phenotype and penetrance of gross SDHB deletions have not been well characterized as they are rarely described. The objective was to describe the phenotype and estimate the penetrance of an exon 1 large SDHB deletion in one kindred. A retrospective and prospective study of 41 relatives across five generations was carried out. The main outcome measures were genetic testing, clinical presentations, plasma catecholamines and their O-methylated metabolites. Of the 41 mutation carriers identified, 11 were diagnosed with PGL, 12 were found to be healthy carriers after evaluation, and 18 were reportedly healthy based on family history accounts. The penetrance of PGL related to the exon 1 large SDHB deletion in this family was estimated to be 35% by age 40. Variable expressivity of the phenotype associated with a large exon 1 SDHB deletion was observed, including low penetrance, diverse primary PGL tumor locations, and malignant potential.

Radionuclide left ventricular dV/dt for the assessment of cardiac function in patients with coronary disease.

To investigate potential uses of left-ventricular (LV) systolic ejection rate (LV dV/dt) in the evaluation of LV function, we examined the effect of exercise, angiotensin, and leg raising on LV ejection fraction and LV dV/dt in patients with coronary-artery disease. The following observations were made: a) LV ejection fraction and dV/dt changed proportionately, but in opposite directions, during supine exercise; b) LV ejection fraction and dV/dt decreased to a similar extent during angiotensin infusions; and c) LV ejection fraction and dV/dt were unchanged by leg raising. The changes in peak and mean LV dV/dt were similar. Regardless of the physiologic state, peak LV dV/dt occurred during the first third of systole. These data imply that in this population there were no specific advantages of LV dV/dt over LV ejection fraction in the evaluation of LV performance.

Comparison of gated radionuclide scans and chest radiographs. Assessment of left ventricular impairment in patients with coronary disease.

Diagnostic efficacy of gated cardiac blood pool imaging was studied in 41 consecutive patients with LV ejection fractions (LVEF) less than or equal to 0.50. Eighty percent of patients were receiving therapy for LV failure at the time of the study. All patients had documented coronary-artery disease (CAD). Chest x-ray films were interpreted blindly by a senior radiologist. Cardiothoracic ratio of less than or equal to 0.50 was recorded as normal. Radionuclide assessment of LV function contributes importantly to the diagnostic and screening value of chest x-ray films. Patients with coronary disease and clinical evidence of heart failure should have radioisotopic studies even if chest x-ray film findings are normal. In patients with coronary artery disease and enlarged LV on chest films, radionuclide study of left ventricular performance aids in defining LV impairment, and in the prognostication of subsequent clinical course.

Angiotensin infusion effects on left ventricular function. Assessment in normal subjects and in patients with coronary disease.

Radionuclide multigating of the cardiac cycle was employed to assess effects of angiotensin infusion on left ventricular function. In six normal subjects, angiotensin infusion decreased heart rate (HR) from 72 +/- SEM 2 to 57 +/- 2 beats/min (P less than 0.001); while systolic blood pressure (BP) increased from 119 +/- 2 to 178 +/- 1 mm Hg (P less than 0.001), and ejection fraction (EF) declined from 58 +/- 1 to 47 +/- 2 percent (P less than 0.05). In contrast, in 11 normal subjects, supine exercise increased HR and systolic BP by 55 and 49 percent, whereas EF increased from 64 +/- 1 to 71 +/- 1 (P less than 0.001). In ten patients with CAD, angiotensin infusion produced no change in HR, increased systolic BP by 34 percent, and decreased EF by 11 percent. Angiotensin infusion induced left ventricular depression in normal subjects and in patients with CAD. It cannot substitute for exercise in intervention radionuclide ventriculography.

Preduodenal portal vein: its surgical significance.

Preduodenal portal vein is a rare anatomical variant which may be one of many anomalies in the neonate with duodenal "atresia." Preduodenal portal vein also may be an occasional finding in an adult undergoing biliary, gastric, or pancreatic surgery. Awareness and recognition of the anomaly are essential for the avoidance of injury during such operations. We report here a symptomless patient whose preduodenal portal vein was discovered at cholecystectomy.

Successful chemotherapy of hepatic metastases in a case of succinate dehydrogenase subunit B-related paraganglioma.

Compared to other familial pheochromocytoma/paragangliomas (PHEO/PGLs), the succinate dehydrogenase subunit B (SDHB)-related PHEO/PGLs often present with aggressive and rapidly growing metastatic lesions. Currently, there is no proven effective treatment for malignant PHEO/PGLs. Here, we present a 35-year-old white man with primary malignant abdominal extra-adrenal 11 cm paraganglioma underwent surgical successful resection. But 6 months later, he developed extensive bone, liver, and lymph nodes metastasis, which were demonstrated by computed tomography scan and the (18)F-fluorodeoxyglucose positron emission tomography. However, his (123)I-metaiodobenzylguanidine scintigraphy was negative; therefore, the cyclophosphamide, vincristine, and dacarbazine (CVD) combination chemotherapy was initiated. The combination chemotherapy was very effective showing 80% overall reduction in the liver lesions and 75% overall reduction in the retroperitoneal mass and adenopathy, and normalization of plasma catecholamine and metanephrine levels. However, plasma levels of dopamine (DA) and methoxytyramine (MTY) were only partially affected and remained consistently elevated throughout the remaining period of follow-up evaluation. Genetic testing revealed an SDHB gene mutation. Here, we present an SDHB-related PHEO/PGL patient with extensive tumor burden, numerous organ lesions, and rapidly growing tumors, which responded extremely well to CVD therapy. We conclude patients with SDHB-related PHEO/PGLs can be particularly sensitive to CVD chemotherapy and may have an excellent outcome if this therapy is used and continued on periodic basis. The data in this patient also illustrate the importance of measuring plasma levels of DA and MTY to provide a more complete and accurate assessment of the biochemical response to therapy than provided by measurements restricted to other catecholamines and O-methylated metabolites.

Results of proximal gastric vagotomy over 1-5 years in a district general hospital.

One hundred and seventy-three underwent proximal gastric vagotomy for duodenal ulceration over a 6-year period. One hundred and fifteen of these have been followed up for 1-5 years. The operative mortality was nil and the result was satisfactory in 91 per cent. The incidence of side effects was small, notably that of dumping being 2.4 per cent and of diarrhoea, 3.6 per cent. Incidence of postoperative heartburn was reduced from 13 per cent to 4 per cent by the introduction of hepatic interposition. The incidence of recurrent ulceration was 5.1 per cent after an average interval of 2 years and that of new gastric ulceration 2.6 per cent after an average of 4 years. There were no recurrent ulcers in those who had peroperative Burge tests, although secretory studies showed no difference between those tested and those not tested. Most recurrences occurred in the earliest cases operated on before Burge testing was introduced and when only 2 cm of the lower oesophagus were exposed.