Amino acid sequence of the plasma membrane ATPase of Neurospora crassa: deduction from genomic and cDNA sequences.

The plasma membrane of Neurospora crassa contains an electrogenic H+-ATPase (EC 3.6.1.35), for which we have isolated and sequenced both genomic and cDNA clones. The ATPase gene is interrupted by four small introns (58-124 base pairs). It encodes a protein of 920 amino acids (Mr, 99,886) possessing as many as eight transmembrane segments. The Neurospora ATPase shows significant amino acid sequence homology with the Na+,K+- and Ca2+-transporting ATPases of animal cells, particularly in regions that appear to be involved in ATP binding and hydrolysis.     

Surgical options in the patient with chronic pancreatitis

There are a number of indications for surgical intervention in chronic pancreatitis, but the most common is intractable pain. Many surgical procedures can be applied in the patient with chronic pain, and the variety of procedures reflects the fact that no single procedure is ideal for all patients. Duct drainage procedures are safe and have a significant response rate, but only about one third of patients experience long-lasting complete relief of pain. Procedures that combine resection and duct drainage are generally more effective, with long-term success rates in the 80% range. The development of the Frey and Beger procedures, two methods for pancreatic head resection that preserve the anatomy of the stomach, duodenum, and bile duct, represents an advance in surgical therapy of chronic pancreatitis. Total pancreatectomy with islet autotransplantation is a procedure that may be appropriate in certain subsets of patients. Thoracoscopic splanchnicectomy is a new, minimally invasive procedure, still in evaluation, which may become a very valuable method when the sole indication for surgery is intractable pain.     

Sodium channel mutations in paramyotonia congenita exhibit similar biophysical phenotypes in vitro.

Mutations in the skeletal muscle voltage-gated Na+ channel alpha-subunit have been found in patients with two distinct hereditary disorders of sarcolemmal excitation: hyperkalemic periodic paralysis (HYPP) and paramyotonia congenita (PC). Six of these mutations have been functionally expressed in a heterologous cell line (tsA201 cells) using the recombinant human skeletal muscle Na+ channel alpha-subunit cDNA hSkM1. PC mutants from diverse locations in this subunit (T1313M, L1433R, R1448H, R1448C, A1156T) all exhibit a similar disturbance in channel inactivation characterized by reduced macroscopic rate, accelerated recovery, and altered voltage dependence. PC mutants had no significant abnormality in activation. In contrast, one HYPP mutation studied (T704M) has a normal inactivation rate but exhibits shifts in the midpoints of steady-state activation and inactivation along the voltage axis. These findings help to explain the phenotypic differences between HYPP and PC at the molecular and biophysical level and contribute to our understanding of Na+ channel structure and function.     

Use of brachytherapy in management of locally recurrent rectal cancer

PURPOSE: Locally recurrent rectal cancer is associated with poor quality of life and has justified aggressive surgical and adjuvant approaches to control the disease. This study was designed to evaluate if the use of brachytherapy in association with wide surgical excision (debulking operation) can offer reasonable palliation for patients with locally recurrent rectal cancer. MATERIALS AND METHODS: Patients with biopsy-proven locally recurrent rectal cancer who were not candidates for intraoperative radiation therapy and who were previously considered as having unresectable tumors were included in the study and were followed-up from May 1981 to November 1990. All of them had undergone laparotomy and had either radical or debulking surgical resection performed. At the same time, brachytherapy was used with temporary or permanent implant of seeds of iridium-192 or iodine-125. RESULTS: Thirty patients were included. Patients ranged in age from 28 to 74 years, and 16 patients were female. No mortality was observed, and morbidity was low (small-bowel obstruction (1 patient), intestinal fistula (1 patient), and urinary fistula (1 patient). Histologic examination of the specimen showed gross residual disease in 67 percent of patients and microscopic disease in 25 percent of patients. Long-term follow-up was possible in 28 patients. Mean follow-up and local control were, respectively, 26.5 months and 37.5 percent for gross residual disease and 34 months and 66 percent for microscopic residual disease. Eighteen patients (64 percent) had locally recurrent rectal cancer under control at the time of the last follow-up, with seven patients (25 percent) having no evidence of local or distant recurrence. CONCLUSION: This is the first report of brachytherapy for locally recurrent rectal cancer. This appears to offer a therapeutic alternative to patients who are not candidates for intraoperative radiation therapy. Surgical morbidity and mortality are acceptable. Local control in 18 patients (64 percent) is comparable with intraoperative radiation therapy or more morbid surgical alternatives. Cancer-related deaths are most often related to disseminated disease, which suggests the need for systemic therapy in addition to brachytherapy.     

Exercise radionuclide ventriculography in children: normal values for exercise variables and right and left ventricular function.

Thirty two children (aged 5-19 years) with no clinical evidence of significant cardiovascular disease undertook continuous staged supine exercise on a bicycle ergometer. Multigated radionuclide ventriculography was performed at rest and during each exercise stage. Exercise duration and total workload both increased with age. Aerobic work correlated better with age than did total work. In most children the ejection fraction for both ventricles increased by at least 5% with exercise. Right ventricular ejection fraction did not decrease with exercise in any subject but left ventricular ejection fraction decreased by 2% and 9% in two. The response of end diastolic volume to exercise was variable, but there was a consistent decrease in mean (SD) end systolic volume of the left (29(22)%) and right (30(19)%) ventricles. Cardiac index (mean (SD)) increased by 234(65)% with exercise. The left ventricular:right ventricular end diastolic volume ratio (mean (SD)) at rest was 1.26(0.26). It is concluded that exercise radionuclide ventriculography is an excellent technique for a combined assessment of exercise capacity and an evaluation of ventricular size and performance in children. These values for supine bicycle exercise in children without significant cardiovascular disease will be useful for future comparisons with other groups.     

Pulmonary arterial compression syndrome caused by false aneurysm of left ventricular outflow tract

A 29 year old man experienced exertional dyspnea and coughing 3 1/2 years after insertion of a Braunwald-Cutter aortic valve prosthesis. Clinical examination suggested pulmonary arterial hypertension, and cardiac catheterization revealed a saccular lesion apparently arising from the left ventricular outflow tract and producing compression of the right pulmonary artery. Origin from the left ventricular outflow tract just under the aortic ring was confirmed at operation. The lesion apparently arose from an anular excavation related to previous endocarditis with abscess formation. Reported cases of similar aneurysmal lesions are briefly reviewed, and other known causes of the pulmonary arterial compression syndrome are discussed.     

Transperineal ultrasonography

PURPOSE: The aim of this preliminary study was to present an alternative method to assess the anal sphincters by ultrasonography using a conventional ultrasound surface probe by transperineal approach. METHODS: Transperineal ultrasonography was performed in 20 asymptomatic volunteers to assess the anal sphincters. Ultrasonographic findings were compared with conventional anal endosonography pictures available in the literature. RESULTS: Images of the anal sphincters obtained by transperineal ultrasound were found to be similar to those produced by conventional anal endosonography. Internal and external anal sphincters were easily demonstrated in addition to mucosal and submucosal layers. CONCLUSIONS: Transperineal ultrasonography is a new technique that enables imaging of anal sphincters and anal canal structures with potential application in functional and inflammatory anorectal disorders.Dr. Kleinübing was supported by grant from National Agency CAPES Brazil.Presented at 1° Encontro Catarinense de Colo-Proctologia, Joinville—SC—Brazil, December 12, 1997.     

Mutation analysis in families with discordant phenotypes of phenylalanine hydroxylase deficiency. Inheritance and expression of the hyperphenylalaninaemias

Summary Neonatal hyperphenylalaninaemia caused by mutations in the gene encoding phenylalanine hydroxylase (PAH) represents a wide spectrum of metabolic phenotypes, ranging from classical phenylketonuria (PKU) to mild hyperphenylalaninaemia (MHP). The marked interindividual heterogeneity is due to the expression of multiple PAH mutations in genetic compounds. We have investigated four unusual families in which both PKU and MHP were present. In each family three different mutations in the PAH gene were identified, including two associated with PKU and one associated with MHP. The unexpected outcome of discordant phenotypes within the families described is explained by previously unrecognized parental MHP. By mutation analysis we have also predicted the phenotypical outcome in a hyperphenylalaninaemic infant born to a mother who before pregnancy had been diagnosed as having MHP. Our results demonstrate the utility of nucleic acid analysis in follow-up in PKU screening programmes.     

Toxic dilatation of the colon complicating pseudomembranous enterocolitis

Summary A case of toxic dilatation of the colon complicating antibiotic-induced pseudomembranous enterocolitis, believed to be the first to be reported, has been presented. This disease must be differentiated from toxic dilatation of the colon complicating ulcerative colitis, since treatment for the two conditions differs. Rapid, but carefully controlled, fluid and electrolyte repletion with use of a centrovenous pressure monitor may make the difference between survival and death.