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Biomedical subjects

S M Smith

Publications and source records attributed to S M Smith.

At least 307 records · Page 17Linked to original sources

Pathologic findings in mesangiopathic glomerulonephritis in Navajo Indians.

Immune complex-associated mesangiopathic glomerulonephritis was found in 64% of renal biopsies performed on Navajos over a 16-year period. It is characterized by mild mesangial expansion and predominant immunoglobulin (Ig) A and/or IgM deposits. Statistical analysis shows that glomerular deposits of IgG and C3, glomerular sclerosis, interstitial fibrosis, interstitial inflammation, and tubular atrophy are associated with renal insufficiency at the time of biopsy, and can be integrated into a pathologic index that has a high correlative value. Mesangiopathic glomerulonephritis is probably responsible for the high rates of non-diabetic end-stage renal disease seen in Navajo Indians.

Adolescent↗

Seizure propensity with imipenem.

Five patients with seizures related to imipenem administration are described. The potential of imipenem therapy to cause seizure was further studied in a mouse model and compared with the potential for seizure with penicillin and cefotaxime therapy. Penicillin caused ataxia and seizure at a mean mouse serum level of 5800 microns/mL, cefotaxime at 3400 microns/mL, and imipenem at a much lower serum concentration of 1900 microns/mL. The potent activity of imipenem therapy against bacteria, allowing for a clinical dose of only 2 g/d, is unfortunately offset by its higher propensity to induce neurologic symptoms in humans and mice at much smaller doses than would therapy with penicillin G or the cephalosporins, such as cefotaxime.

Aged↗

Low incidence of glomerulosclerosis in normal kidneys.

Forty normal kidneys were selected from a series of 146 renal samples obtained at forensic autopsies of American Indians and whites. Glomeruli were counted and the percentage of globally sclerosed, obsolescent glomeruli was calculated for each case. The mean for sclerotic glomeruli was less than 3% in any age group younger than 56 years. This finding is in agreement with the results of similar studies, but substantially lower than the figures quoted in textbooks. Analysis of the combination of our data with studies performed by other authors shows that the 90th percentile of glomerular sclerosis can be calculated for any age by subtracting 10 from half the patient's age. No ethnic- or sex-related differences were seen in any age group.

Adolescent↗

Frequent association of mesangial glomerulonephritis and alcohol abuse: a study of 3 ethnic groups.

Renal and hepatic samples were obtained from 121 forensic autopsies. In 64% of 107 individuals with evidence of alcohol abuse (AA), mesangial changes of mild cellular increase, deposits of IgA and IgM, and electron-dense deposits were found, with significantly higher incidence than seen in 14 controls. This mesangial glomerulonephritis (mesGN) was not limited to subjects with cirrhosis but was also observed in individuals with noncirrhotic alcoholic liver disease. Therefore, AA could be relevant in a larger number of mesGN patients than formerly suspected. When cases were separated by ethnicity, the incidence and severity of alcoholic liver disease were found to be essentially the same in American Indians, Hispanics, and Anglos. At the same time, mesGN in individuals with evidence of AA was more frequent in American Indians (87%) than in Caucasians (47%) (P less than 0.0001), with no statistically significant differences between Hispanics and Anglos. The possibility of ethnic influences on the predisposition to alcohol abuse-related mesGN is raised, although the importance of different patterns of alcohol ingestion cannot be ruled out.

Adult↗

A pharmacological analysis of the 5-HT receptor mediating inhibition of 5-HT release in the guinea-pig frontal cortex.

The release of [3H]5-HT from guinea-pig frontal cortex slices was elicited by continuous exposure to Krebs solution containing elevated K+ ions (30 mM) and 10 microM fluvoxamine. K+-stimulated release was inhibited by 5-carboxamidotryptamine (pIC25 8.1), 5-HT (7.4), RU 24969 (6.5) and GR 43175 (6.4). 8-OH-DPAT was without effect on K+-evoked release of [3H]5-HT at concentrations up to 1 microM. The inhibitory effects of 5-HT were antagonised by metitepine (pA2 8.2), metergoline (7.0), methysergide (6.5), cyanopindolol (6.5), yohimbine (6.5) and mesulergine (6.2) but not by the 5-HT3 antagonist, ICS 205-930 (1 microM). The results are discussed in the context of the known pharmacology of 5-HT receptor subtypes. It is concluded that the 5-HT receptor modulating 5-HT release in the guinea-pig frontal cortex does not correspond to any of the 5-HT1-subtype recognition sites or to 5-HT2 or 5-HT3 receptors.

Animals↗

5-Aminosalicylic acid protects against ischemia/reperfusion-induced gastric bleeding in the rat.

The aim of the present study was to determine whether the split products of sulfasalazine, sulfapyridine, and 5-aminosalicylic acid can ameliorate ischemia/reperfusion-induced injury to the gastric mucosa. Gastric mucosal damage was assessed by measuring (a) 51Cr-labeled red blood cell leakage into the gastric lumen, (b) the area of gross mucosal lesions, and (c) the extent of histologically demonstrable mucosal damage. In rats treated with 5-aminosalicylic acid, but not in those treated with sulfapyridine, the leakage of 51Cr-labeled red blood cells and the area of gross mucosal lesions after ischemia/reperfusion were significantly reduced as compared with untreated (control) rats. Inasmuch as 5-aminosalicylic acid (the therapeutic moiety of sulfasalazine) has been reported to be a hydroxyl radical scavenger, we also assessed the effects of dimethylsulfoxide (another hydroxyl radical scavenger) on ischemia/reperfusion-induced gastric mucosal injury. In rats treated with dimethylsulfoxide, leakage of 51Cr-labeled red blood cells and the area of gross mucosal lesions after ischemia/reperfusion were significantly reduced as compared with control rats. The results of this study support the contention that ischemia/reperfusion-induced gastric bleeding involves the hydroxyl radical and indicate that 5-aminosalicylic acid significantly attenuates this vascular injury.

Aminosalicylic Acids↗

Interaction of ciprofloxacin with ampicillin and vancomycin for Streptococcus faecalis.

Streptococcus faecalis is known to be resistant to killing by many of the commonly used antimicrobial agents. Ciprofloxacin, a member of the quinolone class of compounds, was studied for its ability to inhibit and to kill S. faecalis. The rate of killing by ciprofloxacin was slow and was comparable to that of ampicillin or vancomycin. The antimicrobial effect of combining ciprofloxacin with ampicillin or with vancomycin was also studied using checkerboard double-dilution and killing kinetics. There was no synergy or antagonism between ciprofloxacin and either cell wall active agent. Unlike the aminoglycosides, the addition of ciprofloxacin did not produce additional killing over that of ampicillin or of vancomycin alone.

Ampicillin↗

Hemin increases aerobic capacity of cultured regenerating skeletal myotubes.

Regeneration of damaged, mature muscle occurs by differentiation of satellite cells. In culture, satellite cell myoblasts proliferate, align, and fuse to form cross-striated, contracting myotubes. The biochemical changes and the factors that regulate differentiation in satellite cells have not been investigated previously. We report here that no significant differences in glucose uptake rate or glucose oxidation rate were observed between regenerating myoblasts and myotubes, whereas the aerobic oxidation of palmitic acid increased 7.3-fold between these differentiation states. Specific activities of enzymes of critical importance in aerobic metabolism or in production of ATP were increased 2- to 3.5-fold during fusion. Addition of 20 microM hemin to regenerating muscle cultures potentiated the aerobic capacity as evidenced by a 23.6% increase in palmitate oxidation rate. Hemin also increased the specific activities of all nonheme enzymes investigated with the exception of phosphofructokinase. This augmentation of aerobic metabolism together with the time frame of active muscle differentiation suggests a complex role for hemin in myogenesis.

Aerobiosis↗

Norepinephrine turnover in iron deficiency at three environmental temperatures.

Iron-deficient anemic rats had a significant elevation in urinary norepinephrine (NE) after 7 days at 30 and 24 degrees C, but not at 10 degrees C, compared with control animals. NE turnover studies were performed to examine sympathetic nervous system activity in a tissue-specific fashion. NE content in myocardium decreased by nearly 50% in hypertrophied iron-deficient hearts at all three temperatures, whereas fractional turnover rates were compensatorily increased. In contrast, interscapular brown adipose tissue NE turnover was significantly reduced to 30% of normal in iron-deficient animals at both 30 and 10 degrees C. Serum triiodothyronine concentrations were similar to controls at 30 degrees C but were decreased at lower temperatures. Serum tetraiodothyronine concentrations were lower in iron-deficient animals at all three environmental temperatures. We conclude that increased sympathetic nervous system activity compensatory to temperatures below thermoneutrality is less well controlled in iron-deficient animals than in controls, and at a low environmental temperature this may possibly explain the poor thermoregulatory capacity of iron-deficient animals. A generalized hypernoradrenergic state is not supported by our NE turnover study and does not explain the elevated urine NE concentrations.

Adipose Tissue↗

Amdinocillin: interaction with other beta-lactam antibiotics for gram-negative bacteria.

Amdinocillin was studied alone and in combination with three other beta-lactam antibiotics (aztreonam, cefoperazone, and ceftriaxone) for activity against gram-negative bacilli. These antibiotic combinations failed to show synergy by the checker-board double-dilution test or by killing kinetic studies. However, amdinocillin did show additive killing action when combined with the other beta-lactam antibiotics studied. Amdinocillin failed to induce or inhibit beta-lactamase production in species of Enterobacteriaceae, but with Pseudomonas aeruginosa, beta-lactamase production was induced. It is concluded that the activity of amdinocillin alone or in combination with another beta-lactam antibiotic should not be more effective in the treatment of infections by gram-negative bacilli than just using the beta-lactam antibiotic alone at a higher dose.

Amdinocillin↗

Conditions affecting the results of susceptibility testing for the quinolone compounds.

The quinolone class of compounds was studied for conditions which might affect susceptibility results. These compounds included amifloxacin, ciprofloxacin, difloxacin, enoxacin, norfloxacin, ofloxacin, and RO 23-6240. Ciprofloxacin, a representative quinolone, was found to have rapid bactericidal activity, equivalent to that of gentamicin, in contrast to the slower activity of a cephalosporin, cefotaxime. Test conditions that might affect susceptibility test results included divalent magnesium and calcium cation concentrations and pH. For strains of Staphylococcus aureus, Enterobacteriaceae, and enterococcus, the effects were not large. A pH of 5.0 in general increased the minimum inhibitory concentrations (MICs) for the organisms against most carboxyquinolones, up to 8-fold, as compared to that at pH 7.4. In comparison, a similar lowering of pH caused an increased in MIC of 32-fold for gentamicin and no change for cefotaxime. Increasing the concentrations of divalent cations increased the MICs on the average of only 4-fold. Of the quinolones, difloxacin was the least affected by change in concentration of divalent cations and by pH. Such changes are not expected to greatly affect the efficacy of therapy of those members of Enterobacteriaceae which have MICs much less than 0.1 micrograms/ml, but might diminish therapeutic efficacy for those organisms such as Streptococcus aureus with MICs of 1.0 microgram/ml or higher.

Bacteria↗

Activity of cefixime (FK 027) for resistant gram-negative bacilli.

Cefixime is an orally absorbable cephalosporin with an extended spectrum of in vitro activity for gram-negative bacteria especially members of the Enterobacteriaceae. Gram-negative rod isolates collected over a three month period were tested against cefixime. Greater than 99% of Escherichia coli isolates was susceptible to cefixime including those resistant to ampicillin. Similarly isolates of Klebsiella, Proteus and Providencia were also exquisitely susceptible to cefixime as were 91% of Enterobacter cloacae and 71% of Enterobacter aerogenes. Killing kinetics of cefixime did not differ from that of the intravenously administered third-generation cephalosporin, cefotaxime. The addition of magnesium and calcium divalent cations or the lowering of the pH to 5.0 did not affect the action of this antibiotic. The extended spectrum of this oral antibiotic may be useful in treatment of urinary tract and skin and soft tissue infections caused by the more resistant gram-negative rods.

Ampicillin Resistance↗

Occurrence of bacteremia during and after hemorrhagic shock.

In recent research, hemorrhagic shock and septic shock have been studied as two separate entities. We have developed a treated model of hemorrhagic shock in which unrestrained and unanesthetized rats are bled to a mean arterial pressure of 30 torr until 80% of the maximum shed volume must be returned. Rats are maintained preshock and treated post shock with a 20% glucose-electrolyte solution. Survival of these animals is 62% at 24 hours post shock and all animals are dead at 72 hours post shock. Blood cultures obtained during shock become positive at 2 hours into the shock period and are significant compared to controls at 3 to 5 hours of shock (p less than 0.0001). Blood cultures obtained after the period of shock are significantly positive at 24 and 48 hours post shock (p less than 0.05) compared to controls. Intrashock cultures are monomicrobial; the majority of post-shock cultures are polymicrobial. All cultured organisms are normal rat enteric flora. Histologic changes of renal failure are also demonstrated post shock. We suggest that bacterial invasion, possibly from the gut, plays a role in the sepsis seen in patients following severe hemorrhagic shock. Sepsis may precede rather than follow the immune incompetence which accompanies shock.

Animals↗