Electrophysiological Characterization of a Novel Conotoxin That Blocks Molluscan Sodium Channels

A novel peptide toxin, PnIVB, isolated from the venom of Conus pennaceus blocks voltage-gated sodium current in Aplysia neurons. Complete blockade is obtained at a PnIVB concentration of 80±2.2 nM and 50% blockade at 16±0.86 nM. The potency of PnIVB in blocking Aplysia sodium current is four orders of magnitude larger than that of tetrodotoxin. The toxin has no paralytic activity when injected into fish. The rapid blockade of sodium current by PnIVB is not associated with a change in the activation or inactivation kinetics of the current, or with the reversal potential. Sodium current blockade is reversible after a 30 min wash with 50 times the bath volume. The novel conotoxin PnlVB can be used as a powerful tool for mollusc neurobiological research and as a molecular probe to explore the structure-function relations of voltage-gated sodium channel subtypes.     

Bacteremia and fungemia in patients with acquired immune deficiency syndrome

Patients with acquired immune deficiency syndrome (AIDS) are known to have identifiable host defense deficiencies, especially deficiencies in cell-mediated immunity. They are at increased risk for developing infections of the bloodstream caused by Cryptococcus neoformans and Salmonella species. However, bacteremias caused by other enteric gram-negative rods and Pseudomonas aeruginosa are found less frequently in patients with AIDS than in patients without AIDS (P less than 0.001 and P less than 0.01, respectively). The findings of specific organisms in blood is consistent with the known types of host defense deficiencies in these patients.     

Receptor-mediated toxicity of pahutoxin, a marine trunkfish surfactant.

Pahutoxin (PHN, choline chloride ester of 3-acetoxypalmitic acid) is a natural fish-killing (ichthyotoxic) agent derived from the defensive secretions of trunkfish. In spite of its obvious structural resemblance to synthetic cationic long-chain quaternary ammonium detergents, we show that PHN's action does not rely on its surfactant properties and is in fact, receptor-mediated. The above conclusion is supported by the following data: 1. Ichthyotoxicity is not related to its detergency or surfactivity, as indicated by the fact that the lethal concentration is about 1.5 orders of magnitude below its critical micelle concentration value (69 microM) and its liposomal/seawater partition coefficient is low (62-85); 2. The trunkfish is tolerant to its own pahutoxin; 3. Ichthyotoxicity occurs only upon application to the surrounding water, suggesting the existence of externally located receptors; 4. The receptor hypothesis was supported by the aid of equilibrium saturation binding assays revealing the presence of specific binding sites to PHN on the fish gill membranes; 5. The PHN tolerant trunkfish was shown to be devoid of PHN-binding sites. Some chemo-ecological, and environmental implications are discussed.     

Initial experience of videocapsule endoscopy for diagnosing small-bowel tumors in patients with GI polyposis syndromes

BACKGROUND: Small-bowel tumors frequently occur in familial adenomatous polyposis and other GI polyposis syndromes. These tumors are difficult to detect with conventional techniques. Our aim was to assess the utility of videocapsule endoscopy in the detection of small-bowel tumors in this setting. METHODS: We examined 19 familial adenomatous polyposis patients and 3 patients with either Peutz-Jeghers syndrome, hyperplastic polyposis, or Cowden disease. OBSERVATIONS: Prevalence of small-bowel polyps on videocapsule endoscopy was 59% in all patients, 52.6% in familial adenomatous polyposis patients, and 75% in a subgroup of familial adenomatous polyposis patients with exon 15 mutations. Videocapsule endoscopy was safe and well tolerated in all patients. CONCLUSIONS: Videocapsule endoscopy has a high yield in detecting small-bowel tumors in patients with GI polyposis syndromes. It may be especially indicated in familial adenomatous polyposis patients with the aggressive phenotype of the disease, e.g., mutations in exon 15.     

Effect of improved diagnosis of renal cell carcinoma on the course of the disease

The impact of the improved diagnosis of renal cell carcinoma (RCC) on the course of the disease was evaluated in 188 patients who were diagnosed and treated at a single medical center. Sixty-seven patients (group A) who had undergone nephrectomy between 1979 and 1983 for RCC initially diagnosed by intravenous pyelography (IVP) were compared with 121 patients (group B) who had undergone nephrectomy between 1983 and 1989, diagnosed by ultrasound and/or computed tomography (CT) scan. Incidental asymptomatic tumors were found in 18 of 67 (26.9%) group A patients and in 57 of 121 (47.1%) group B patients (P < 0.001). The incidence of small tumors of <5 cm in diameter was significantly lower in group A compared to group B (25.4% vs. 47.9%, respectively, P < 0.01). The disease-free 5-year survival rate for group A was 40% compared to 80% for group B. It is concluded that the introduction of modern imaging techniques has improved the survival of patients with RCC and decreased the progression rate of the disease. © 1994 Wiley-Liss, inc.     

Raised intracranial pressure

Opinion statement Raised intracranial pressure is a relatively common problem facing the clinician treating neurocritically ill patients. It is a leading cause of death in patients with intracranial pathology. There is a lack of controlled clinical trials evaluating most of the therapies currently available for raised intracranial pressure. The basic pathophysiologic and clinical principles of raised intracranial pressure are discussed and the major treatment options are presented. Patients with raised intracranial pressure should be evaluated immediately with particular attention to airway and hemodynamic status. Controlled hyperventilation and hyperosmolality (using mannitol or hypertonic saline solutions) frequently are administered simultaneously. In patients with refractory elevation of intracranial pressure other therapies such as barbiturate coma and surgical interventions are available.     

A subunit vaccine against hemorrhagic enteritis adenovirus

Hemorrhagic enteritis virus (HEV) is an adenovirus that infects turkeys and causes immunosuppression and mortality. The virus used for the inactivated vaccine is extracted from spleens of infected turkeys, since its propagation in tissue cultures or embryonated eggs is unsuitable for mass production. The aim of this study was to develop a subunit vaccine based on a capsid protein of the virus. The knob protein, together with an adjacent part of the shaft domain pertaining to the fiber protein of HEV, was expressed in Escherichia coli and tested as a vaccine. Vaccination with this recombinant protein conferred protection against challenge in controlled and in floor-pen experiments. This finding suggests that the knob protein may be used as safe and efficient vaccine against hemorrhagic enteritis of turkeys. The possibility that the knob proteins of other adenoviruses may be protective and serve as vaccine is also discussed.     

Nasopharyngeal carcinoma in the pediatric age group: the northern Israel (Rambam) medical center experience, 1989-2004

Nasopharyngeal carcinoma (NPC) is rare in children, accounting for less than 1% of all malignancies. Radiation therapy has been the mainstay of treatment of many years, but to improve survival, the use of chemotherapy has been advocated. This is a retrospective analysis of 13 patients less than 20 years of age treated for NPC the Rambam Medical Center during 1989 to 2004. Eight boys and five girls with a median age of 14.5 years (range 10-19) were included. Median follow up (including patients who died) was 6.15 years (range 1-15 years). Duration of symptoms was 1 to 24 months (median 5 months). Of the 13 patients, one patient had stage I, 6 had stage III, 5 had stage IV-A, and 1 had stage IV-B disease. Ten patients (77%) had undifferentiated carcinoma (WHO type III) and three patients (23%) had nonkeratinizing carcinoma (WHO type II). Most of the children received two or three courses of neoadjuvant multiagent chemotherapy consisting of cisplatin and 5-FU, followed by radiotherapy with doses in excess of 60 Gy. One child received concomitant chemoradiation. Ten of the 13 patients (77%) are alive without disease 6 years after diagnosis (range 1-15 years). One patient developed local and distant metastases 1 year after diagnosis and is currently receiving combined radiochemotherapy. Two patients died. Overall survival was 84%; event-free survival was 77%. Nine patients (69%) developed moderate to severe long-term complications. Pediatric NPC is curable by combined radiation and chemotherapy, with doses of radiation in excess of 60 Gy. Long-term follow-up is important for early detection of second malignancies as well as for radiation-induced endocrinologic deficiencies and other normal tissue complications.     

Cumulative AIDS incidence and altered pneumonia mortality.

We grouped New Jersey residents according to age, sex, race, and residence-specific cumulative incidence of AIDS since the onset of the AIDS epidemic: less than 15, 15-99, 100-499, and greater than or equal to 500 cases per 100,000 people, respectively. We determined mortality from bacterial and viral pneumonias (International Classification of Diseases [ICD] 480.0-486.9) from underlying cause of death files. Between 1980 and 1986, pneumonia mortality increased from 15.1 deaths per 100,000 per year (95% confidence interval [CI] 10.4, 19.7) to 25.0 deaths per 100,000 per year (95% CI 19.2, 30.8), an increase of 10.0 deaths per 100,000 per year (95% CI 2.6, 17.3), among those 25-44 years of age in the highest cumulative incidence group for AIDS. Increases in other population subgroups were approximately proportional to each subgroup's AIDS cumulative incidence. In particular, pneumonia mortality did not increase among those 25-44 years of age in groups with low cumulative incidence of AIDS. Deficiency of cell-mediated immunity, a diagnosis commonly applied in AIDS cases, was listed as a secondary diagnosis in 14% of the pneumonia deaths of persons 25-44 years of age in 1986 and in none of those in 1980.