Limitations to exercise- and maximal insulin-stimulated muscle glucose uptake

The hypothesis of this investigation was that insulin and muscle contraction, by increasing the rate of skeletal muscle glucose transport, would bias control so that glucose delivery to the sarcolemma (and t tubule) and phosphorylation of glucose intracellularly would exert more influence over glucose uptake. Because of the substantial increases in blood flow (and hence glucose delivery) that accompany exercise, we predicted that glucose phosphorylation would become more rate determining during exercise. The transsarcolemmal glucose gradient (TSGG; the glucose concentration difference across the membrane) is inversely related to the degree to which glucose transport determines the rate of glucose uptake. The TSGG was determined by using isotopic methods in conscious rats during euglycemic hyperinsulinemia [Ins; 20 mU/(kg. min); n = 7], during treadmill exercise (Ex, n = 6), and in sedentary, saline-infused rats (Bas, n = 13). Rats received primed, constant intravenous infusions of trace 3-O-[3H]methyl-D-glucose and [U-14C]mannitol. Then 2-deoxy-[3H]glucose was infused for the calculation of a glucose metabolic index (Rg). At the end of experiments, rats were anesthetized, and soleus muscles were excised. Total soleus glucose concentration and the steady-state ratio of intracellular to extracellular 3-O-[3H]methyl-D-glucose (which distributes on the basis of the TSGG) were used to calculate ranges of possible glucose concentrations ([G]) at the inner and outer sarcolemmal surfaces ([G]im and [G]om, respectively). Soleus Rg was increased in Ins and further increased in Ex. In Ins, total soleus glucose, [G]om, and the TSGG were decreased compared with Bas, while [G]im remained near 0. In Ex, total soleus glucose and [G]im were increased compared with Bas, and there was not a decrease in [G]om as was observed in Ins. In addition, accumulation of intracellular free 2-deoxy-[3H]glucose occurred in soleus in both Ex and Ins. Taken together, these data indicate that, in Ex, glucose phosphorylation becomes an important limitation to soleus glucose uptake. In Ins, both glucose delivery and glucose phosphorylation influence the rate of soleus glucose uptake more than under basal conditions.     

Macrophage-derived cytokines in the follicular fluids of women with infertility due to immunological causes. Elevated levels of interleukin 6 and low levels of granulocyte-macrophage colony-stimulating factor

Myoclonus of the middle ear is a rare condition characterized by abnormal repetitive muscle contractions of the tympanic cavity. In this paper we describe what we believe is the first reported case of continuous high-frequency objective tinnitus caused by middle ear myoclonus. During exploratory tympanomastoidectomy it was hypothesized that a small dural arteriovenous malformation not identified on previous tests was the cause of the tinnitus. However, complete disappearance of the tinnitus during administration of curare for anesthesia led us to believe that the tinnitus might have been caused by myoclonus of the middle ear. Sectioning of the stapedius and tensor tympani tendons rendered the patient asymptomatic and confirmed the diagnosis of middle ear myoclonus. At follow-up of one year, the patient's quality of life had improved substantially; the tinnitus did not recur and she no longer had vertigo.     

Mechanism of irreversible inactivation of phosphomannose isomerases by silver ions and flamazine

Silver ions and silver-containing compounds have been used as topical antimicrobial agents in a variety of clinical situations. We have previously shown that the enzyme phosphomannose isomerase (PMI) is essential for the biosynthesis of Candida albicans cell walls. In this study, we find that PMI can be inhibited by silver ions. This process is shown to be irreversible, and is a two-step process, involving an intermediate complex with a dissociation constant, Ki, of 59 +/- 8 microM, and a maximum rate of inactivation of 0.25 +/- 0.04 min-1 in 50 mM Hepes buffer, pH 8.0 at 37 degrees C. The enzyme can be protected against this inactivation by the substrate mannose 6-phosphate, with a dissociation constant of 0.31 +/- 0.04 mM, close to its Km value. Flamazine (silver sulfadiazine) is a silver-containing antibiotic which is used clinically as a topical antimicrobial and antifungal agent. We compared the ability of silver sulfadiazine and two other silver-containing compounds to irreversibly inactivate C. albicans PMI. The addition of the organic moiety increased the affinity of the compounds, with silver sulfadiazine showing a Ki of 190 +/- 30 nM. In all cases, the maximum inhibition rate was similar, implying a similar rate-determining step. Silver sulfadiazine does not inhibit Escherichia coli PMI, and this suggests a role of the only free cysteine, Cys-150, in the inactivation process. To confirm this, we mutated this residue to alanine in C. albicans PMI. The resultant Cys150 --> Ala mutant protein showed similar Vm and Km values to the wild-type enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)     

Treating achalasia: from whalebone to laparoscope

Reports of bile duct injuries are from tertiary care institutions and, therefore, may not report the spectrum of management that these patients receive in the care of these injuries. From June 14,1990 (the first operation) to June 30, 1995, 2654 laparoscopic cholecystectomies (LCs) were reviewed at this community hospital medical center to determine risk factors contributing to the etiology of these injuries, time and symptoms at presentation, duration of illness, and management of these injuries. None of the 13 general surgeons practicing during this time period had laparoscopic training in a general surgical residency. There were six major bile duct injuries (0.25%), of which five were available for further review. All occurred in women with cholelithiasis and chronic cholecystitis. Two operations were routine and two were associated with biliary tract anomalies. In two patients, the injuries were detected at LCs and definitive biliary-enteric anastomoses were performed immediately. Three patients presented at 2, 15, and 42 days after LC. In two patients, one or more operative procedures were performed before definitive repair and these patients were referred to tertiary care centers. One patient was managed with sequential CT-guided drainage catheters after attempted closure of the defect. The length of illness for these five patients was 8, 69, 348, 402, and 435 days with a follow-up of 245, 345, 531, 575, and 1088 days. Laparoscopic experience before injury by the operating surgeon was 3, 26, 35, 77, and 333 operations. Major biliary tract injuries occurred during routine cholecystectomy, length of illness was substantial for most patients, and biliary-enteric anastomosis was definitive for four of the five patients. The operating surgeons' "learning curve" did not seem as important as in other studies.     

Extension of a typology of alcohol dependence based on relative genetic and environmental loading

Mild, severe, and dyssocial subtypes of alcohol dependence, previously identified among Caucasian men from the Epidemiologic Catchment Area study, were also identified among Caucasian men and women with DSM-IV alcohol dependence from the National Longitudinal Alcohol Epidemiologic Survey (n = 2,703; 1,746 respectively). These subtypes were not identified among African American and Hispanic American men or women with DSM-IV alcohol dependence. Among Caucasians with alcohol dependence, the subtypes were characterized by differential loading on three dimensions: genetic, general environmental, and dyssocial environmental symptom scales developed in a prior twin study. The mild subtype (60% of men and 66% of women) was distinguished by low mean scores on all three scales; the dyssocial subtype (24% of men and 20% of women) by low mean genetic and general environmental scores but high mean dyssocial environmental scores; and the severe subtype (16% of men and 14% of women) by high scores on the genetic and general environmental scales. These subtypes also showed the expected distinctions in clinical characteristics. The severe subtype showed greater comorbid drug dependence and major depression, more treatment seeking, and a higher prevalence of parental alcoholism. The severe subtype also showed significantly greater genetic influence adjusted for overall severity of alcohol dependence (genetic ratio). Only the severe subtype showed a pattern of scale scores and clinical characteristics suggestive of substantial genetic influence. The present study indicates a robustness of the typology originally developed among DSM-III alcohol-dependent Caucasian men by empirical extension of the subtypes to a different sample of Caucasian men and, separately, Caucasian women. The use of this typology may aid in distinguishing between Caucasian alcohol-dependent individuals on the basis of relative genetic influence, enabling genetic, behavioral, and epidemiological investigations to reduce genetic or environmental "noise" and better focus on specific aspects of alcohol dependence.     

Ischemic proctosigmoiditis

Rectal ischemia is rare because of excellent collateral supply. Although rectosigmoid ischemia is usually accompanied by more proximal colonic involvement, it may occur alone. METHODS: A retrospective review of all patients diagnosed as having colonic ischemia at the Mayo Clinic from 1976 to 1991 was performed. Clinical, endoscopic, radiological, and pathological data were obtained from patient charts. Patients with involvement of the rectosigmoid colon extending to no more than 30 cm above the dentate line on endoscopy were included in the study. A single radiologist reviewed CT scans and aortograms, and a single pathologist reviewed tissue specimens. RESULTS: Ten of 328 patients with ischemic colitis had isolated ischemic proctosigmoiditis. Six patients had acute ischemia (i.e., symptom duration of less than 4 wk), and four had chronic ischemia (symptoms for 4 wk or longer). Ischemic proctosigmoiditis affects elderly patients with atherosclerosis. An identifiable precipitating factor, such as a major illness or hemodynamic disturbance, was identified in four of six patients with acute ischemic proctosigmoiditis and in one of four patients with chronic ischemic proctosigmoiditis. CT revealed rectal wall thickening and/or perirectal stranding. Angiography may demonstrate atheromatous disease of the aortoiliac vessels. Acute and "chronic" presentations had similar histopathological changes. CONCLUSIONS: Ischemic proctosigmoiditis is rare. In contrast to generalized colonic ischemia, patients with acute rectal ischemia often have clearly identifiable precipitating factors. Conservative management is appropriate for uncomplicated acute ischemic proctosigmoiditis. Patients with chronic ischemic proctosigmoiditis. Patients with chronic ischemic proctosigmoiditis may develop bowel perforation necessitating a proctectomy or colonic diversion. Recognition of this entity and differentiation from idiopathic inflammatory bowel disease is important to determine appropriate therapy.     

Spinal neurilemmomas and neurofibromas: central dot sign in postgadolinium MRI

The MR studies of three histologically proven spinal neurilemmomas and neurofibromas were reviewed retrospectively. There were two benign neurilemmomas (schwannomas) and one neurofibroma. The common characteristic of these cases was a central low intensity focus ("dot") seen on postcontrast T1-weighted imaging. The low intensity foci corresponded histologically to a congeries of changes including edema, microcysts, foam cells, hyalinization of blood vessels, old hemorrhage, and dystrophic calcification.     

"Indianism" and MMPI scores of men alcoholics

Mean MMPI profiles of 40 Indian and 40 White veterans were similar, but "Indianism," as measured by the Indian Culturalization Test, was significantly related to scores on Hs, Hy, Pt and Sc scales. Caution is advised in using the MMPI in the diagnosis of Indians' psychiatric problems.     

The Influence of Adherend Topography on the Fracture Toughness of Aluminium-Epoxy Adhesive Joints in Humid Environments

The adherend surface topography has a dramatic effect on the durability of structural bonds formed between aluminium and an epoxy adhesive. Systematic changes in the micro-roughness of an aluminium adherend were achieved using an ultra-milling technique to prepare surfaces with topographies ranging from ultra-flat to a sawtooth profile with a base angle of approximately 60° and a peak-to-valley depth of 10 μm. The fracture toughness of double-cantilever beam specimens, stressed in the Mode 1 direction and exposed to a humid environment was found to change by a factor of approximately one hundred as the sawtooth profile angle was increased. These changes in fracture toughness may be accounted for through complex interrelationships between moisture diffusion and interphase mechanical properties, each with a strong dependence on the surface micro-topography.     

Electrophoretic deposition of carbon nanotubes onto carbon-fiber fabric for production of carbon/epoxy composites with improved mechanical properties

Carbon nanotubes (CNTs) have been deposited onto carbon-fiber fabric using electrophoretic deposition (EPD) prior to the infusion of epoxy resin for the production of carbon/epoxy composites. The carbon-fiber fabric employed for EPD was used in the as-received condition, in which the proprietary epoxy sizing-agent was present. CNTs were functionalized prior to EPD using ozone treatment for oxidation, followed by chemical reaction with polyethyleneimine. The CNT oxidation used a novel recirculating system which enabled ozonolysis to be conducted on large-volume solutions of CNTs in the presence of high-powered sonication, facilitating preparation of stable dispersions suitable for EPD. Significant increases in the shear strength and fracture toughness of the carbon/epoxy composites with the CNT treatment have been measured relative to composites without the CNT treatment. Analysis of fracture surfaces revealed interlaminar regions with high levels of CNTs and evidence of good adhesion between the carbon nanotubes and sized carbon-fiber, which is believed to have contributed to the measured improvement in mechanical properties.