Effect of profound hearing loss on a central auditory nucleus

The present study was designed to investigate the type and extent of degeneration occurring in the human central auditory system subsequent to profound hearing loss. The authors have examined the size of one population of neurons in the ventral cochlear nucleus in seven subjects with profound hearing loss (audiometric responses poorer than 90-100 dB HL). Six normal subjects, ages 35-78, were used as controls. Cell size in the hearing-impaired subjects ranged from normal to reduced by more than 50 percent. Two factors appear to contribute to the variability in cell size reduction. The correlation coefficient (Spearman rs) of cell size with duration of profound deafness was -0.48, indicating a moderate tendency for neurons to become smaller with longer periods of deafness. The correlation coefficient of cell size with number of surviving cochlear ganglion cells was 0.73, indicating a stronger tendency for neurons to be larger with greater eighth nerve innervation of the cochlear nucleus. Two cases of Scheibe degeneration showed the most severe degenerative change in the central auditory system.     

Comparability of self-report of familial alcoholism among male and female college students

There is a general impression in the literature that women are more accurate reporters of familial psychiatric history. In this regard, this study presents data from a large cohort of young men (n = 427) and women (n = 607) who in answering a questionnaire self-reported alcohol abuse symptoms for various biological relatives. No significant gender differences emerged for any of the family history comparisons including reports for father, mother, either parent, any first- or second-degree relatives, or men or women relatives. The findings are discussed in the context of the existing literature.     

Hand-assisted laparoscopic live donor nephrectomy

Selenium is essential for humans because it protects the heart against cardiomyopathy. It may also reduce ischaemic heart disease owing to its antioxidant activity. It is known that Indian migrants in a number of countries have high incidences of ischaemic heart disease. In this study, fasting plasma selenium concentrations of Sikh migrants in Sydney (Australia) were measured to investigate whether selenium concentration is reduced in this community. The mean concentration of selenium in plasma (91.8 +/- 15.0 ng ml-1, n = 196) was within the normal range. A significantly higher plasma selenium concentration was demonstrated in males than in females (p < 0.01). This was mainly due to the difference in mean selenium concentrations between genders in vegetarians because no significant difference was observed in non-vegetarian males versus females. The mean concentration of selenium in teetotal males was similar to those who consumed alcohol. Despite significant variations with gender and diet, the selenium concentrations were within the normal range. The results suggest that selenium status is adequate in the Sikh community even though vegetarian diet is common and alcohol use is condones in males.     

Physiological regulation of early and late stages of megakaryocytopoiesis by thrombopoietin

Thrombopoietin (TPO) has recently been cloned and shown to regulate megakaryocyte and platelet production by activating the cytokine receptor c-mpl. To determine whether TPO is the only ligand for c-mpl and the major regulator of megakaryocytopoiesis, TPO deficient mice were generated by gene targeting. TPO-/- mice have a >80% decrease in their platelets and megakaryocytes but have normal levels of all the other hematopoietic cell types. A gene dosage effect observed in heterozygous mice suggests that the TPO gene is constitutively expressed and that the circulating TPO level is directly regulated by the platelet mass. Bone marrow from TPO-/- mice have decreased numbers of megakaryocyte-committed progenitors as well as lower ploidy in the megakaryocytes that are present. These results demonstrate that TPO alone is the major physiological regulator of both proliferation and differentiation of hematopoietic progenitor cells into mature megakaryocytes but that TPO is not critical to the final step of platelet production.     

Hepatic toxicity associated with fluorouracil plus levamisole adjuvant therapy

PURPOSE: To determine the frequency and nature of hepatic toxicity associated with fluorouracil (5-FU) plus levamisole adjuvant therapy. PATIENTS AND METHODS: All patients had resection of stage II or stage III colon cancer and were randomized to receive observation only, levamisole alone, or 5-FU plus levamisole. Serial liver function studies were documented in 1,025 patients who did not develop recurrence during the year of therapy. RESULTS: One hundred forty-nine (39.6%) of 376 patients treated with 5-FU plus levamisole showed laboratory abnormalities consistent with hepatic toxicity, compared with 16.3% of 251 patients treated with levamisole alone and 16.1% of 398 untreated controls. Most common was elevation of alkaline phosphatase, frequently accompanied by elevations of transaminase or serum bilirubin. Characteristically, these changes were mild, not associated with symptoms, and resolved when therapy was stopped. In some instances, they were associated with elevated carcinoembryonic antigen (CEA) tests or with fatty liver seen on computed tomographic (CT) scan or liver biopsy. CONCLUSION: Mild and reversible hepatotoxicity is a common consequence of 5-FU plus levamisole adjuvant therapy, but this is only rarely symptomatic. However, the oncologist should be alert to this phenomenon, since the associated laboratory and imaging findings may simulate those associated with hepatic metastasis.     

Reversible parotid enlargement and pseudo-Sj?gren's syndrome secondary to hypertriglyceridemia

We describe 2 patients with a Sj?gren-like syndrome apparently secondary to hypertriglyceridemia. Both had bilateral parotitis in addition to musculoskeletal and sicca symptoms. Parotid gland histology revealed fatty infiltration with no inflammation. Therapy with dietary modification and triglyceride lowering drugs resulted in resolution of symptoms and parotid swelling in one patient. In the 2nd patient, hypertriglyceridemia was resistant to triglyceride lowering drugs, and parotid symptoms and swelling continued unabated. Our findings suggest aggressive treatment of hyperlipidemia in pseudo-Sj?gren's syndrome may result in amelioration of musculoskeletal and parotid symptoms.     

N-acetylcysteine does not influence the activity of endothelium-derived relaxing factor in vivo

Nitric oxide forms complexes with an array of biomolecular carriers that retain biological activity. This reactivity of nitric oxide in physiological systems has led to some dispute as to whether endothelium-derived relaxing factors nitric oxide or a closely related adduct thereof, such as a nitrosothiol. In vitro bioassays used to address this question are limited by the exclusion of biological thiols that are requisite for nitrosothiol formation. Thus, the purpose of this study was to obtain insight into the identity of endothelium-derived relaxing factor in vivo. We reasoned that if endothelium-derived relaxing factor in nitric oxide, infusion of physiological concentrations of thiol would potentiate its bioactivity by analogy with effects seen in vitro, whereas nitrosothiol would be resistant to such modulation. We used venous-occlusion plethysmography to study forearm blood flow in normal subjects. Methacholine (0.3 to 10 micrograms/min) and nitroglycerin (1 to 30 micrograms/min) were infused via the brachial artery to elicit endothelium-dependent and endothelium-independent vasodilation, respectively. Dose-response determinations were made for each drug before and after an intra-arterial infusion of the reduced thiol, N-acetylcysteine, at rates estimated to achieve a physiological concentration of 1 mmol/L. Methacholine increased forearm blood flow in a dose-dependent manner. Infusion of N-acetylcysteine did not change the sensitivity (ED50, 1.7 versus 1.7 micrograms/min, P = NS) or maximal response to methacholine. In contrast, thiol increased the sensitivity to nitroglycerin (ED50, 4.7 versus 2.8 micrograms/min, P < .01). Thus, conflicting with reports in vitro, thiol does not modulate endothelium-derived relaxing factor responses in vivo. These data indicate that sulfhydryl groups are not a limiting factor for endothelium-derived relaxing factor responses in forearm resistance vessels in normal humans and are in keeping with reports that nitrosothiol contributes to endothelium-derived relaxing factor bioactivity in plasma and vascular smooth muscle. Potentiation of the effects of nitroglycerin by N-acetylcysteine can be attributed to its enhanced biotransformation to an endothelium-derived relaxing factor equivalent, such as nitrosothiol. These observations support the notion of an equilibrium between nitric oxide and nitrosothiol in biological systems that may be influenced by redox state.     

Transluminal balloon angioplasty, stents, and atherectomy

Arterial bypass grafting for occlusive disease is still considered the gold standard in the treatment of arterial occlusive disease. However, less invasive methods are available for select patients. Percutaneous balloon angioplasty has been shown to be effective in focal iliac artery stenosis, with patency rates of 50% to 90% at 5 years. Patency rates for femoropopliteal lesions are generally less than 50% at 2 years. Complications seen with balloon angioplasty often can be treated with arterial stents. Stents can be categorized into balloon-expandable, which provide a rigid scaffold to support the artery, self-expanding, which exert radial force to resist external compression, and thermal expanding stents, which allow for the use of a smaller introducer sheath. Another treatment option is atherectomy, in which the offending lesion is removed instead of fracturing and dilating the lumen. Although overall initial results of atherectomy have not been favorable, short lesions with eccentric atheroma or intimal hyperplasia, such as those seen in dialysis access fistulas or vein graft stenoses, may respond well.