Disseminated histoplasmosis in an immunocompetent host.
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Adrenal Glands↗
Biomedical subjects
F Siddiqui
Publications and source records attributed to F Siddiqui.
Prevalence of hepatitis A virus and hepatitis B virus immunity in patients with polymerase chain reaction-confirmed hepatitis C: implications for vaccination strategy.
OBJECTIVES: Administration of vaccine for hepatitis A virus (HAV) and hepatitis B virus (HBV) is recommended for patients with chronic hepatitis C (CHC) because of the potential for increased severity of acute hepatitis superimposed on existing liver disease. The aim of this study is to determine the prevalence of antibodies directed against HAV and HBV in patients with CHC, analyze demographic and risk factors associated with this prevalence, and develop a cost-effective vaccination strategy. METHODS: We reviewed records from 1092 CHC patients. Demographics and information regarding risk factors were obtained by history and questionnaire administered to all patients. The costs of vaccination and antibody testing were determined, based on standard laboratory and clinic charges at our institution. HAV and HBV markers were correlated to race, age, and risk factors. RESULTS: Of the total population studied (n = 1092), 72% were African-Americans, 27% white, and 1% others. Of 671 CHC patients tested for anti-HAV IgG, 252 (38%) were positive. Of 743 CHC patients tested for HBV antibodies (anti-hepatitis B core IgG or anti-hepatitis B surface), 494 (67%) were positive. African-Americans are more likely to have antibodies to HAV and HBV (67% and 75%, respectively) compared to whites (27% and 20%). The prevalence of anti-HAV was 76% in patients >60 yr, 34% in the 40- to 60-yr-old age group, and 21% in patients <40 yr. The highest prevalence of HBV antibodies was found in patients between the ages of 40-60 yr. No HCV risk factors were associated with increased HAV risk. In CHC patients with HBV antibodies, however, illicit injection drug use was the predominant risk factor. CONCLUSIONS: The prevalence of anti-HAV in patients with CHC was found to be similar to that of the general population in the United States (33% according to recent Centers for Disease Control data), consistent with the hypothesis that the two infections do not share risk factors. Because the prevalence of HAV immunity is low in CHC patients <40 yr, empiric HAV vaccination is cost effective. If two doses of vaccine are to be given, however, antibody testing of all HCV patients is indicated. In the subset of patients >60 yr of age or who are African-American, where the prevalence of HAV exposure is considerably higher, it would be cost effective to check the antibody ($36.00), before vaccination ($97.00). The prevalence of HBV antibodies, however, is significantly increased in patients with CHC compared with the general population (5.3% per the Centers for Disease Control), likely as a result of exposure to similar parenteral risk factors. HBV antibody testing ($26.00 per test) should, therefore, be undertaken in all CHC patients who are hepatitis B surface antigen negative, as this approach is cost-effective compared to empiric HBV vaccination ($438.00 for a three injection course).
Adult↗
Resistance to linezolid: characterization of mutations in rRNA and comparison of their occurrences in vancomycin-resistant enterococci.
To assess the potential for emergence of resistance during the use of linezolid, we tested 10 clinical isolates of vancomycin-resistant enterococci (VRE) (four Enterococcus faecalis, five Enterococcus faecium, and one Enterococcus gallinarum) as well as a vancomycin-susceptible control (ATCC 29212) strain of E. faecalis. The enterococci were exposed to doubling dilutions of linezolid for 12 passes. After the final passage, the linezolid plate growing VRE contained a higher drug concentration with E. faecalis than with E. faecium. DNA sequencing of the 23S rRNA genes revealed that linezolid resistance in three E. faecalis isolates was associated with a guanine to uracil transversion at bp 2576, while the one E. faecium isolate for which the MIC was 16 microg/ml contained a guanine to adenine transition at bp 2505.
Acetamides↗
Fluoroquinolone resistance is a poor surrogate marker for type II topoisomerase mutations in clinical isolates of Streptococcus pneumoniae.
The association between fluoroquinolone susceptibility and DNA mutations coding for amino acid substitutions in the quinolone resistance-determining region was assessed with 44 clinical isolates of Streptococcus pneumoniae. Twenty-three strains bore at least one amino acid substitution. Only seven strains with mutations were suggested by diminished susceptibility to ciprofloxacin (MIC, > or =2 microg/ml).
Amino Acid Substitution↗
Peritubular dentin formation: crystal organization and the macromolecular constituents in human teeth.
Peritubular dentin (PTD) is a relatively dense mineralized tissue that surrounds the tubules of coronal tooth dentin. It is composed mainly of crystals of carbonated apatite together with a small amount of collagen. Its mode of formation has been investigated by studying the relatively dense particles isolated from a powdered preparation. Electron microscopic examination of the PTD particles, including 3-dimensional image reconstruction and electron diffraction, shows that the organization of the crystals of PTD is very similar to that of the adjacent intertubular dentin (ITD). The latter contains relatively large amounts of collagen and the carbonated apatite crystals are closely associated with the collagen matrix. The proteins present in the PTD particles are soluble after decalcification and stain with Stains All. The principal protein has higher molecular weight and a quite different amino acid composition than the phosphophoryns of the intertubular dentin. The interface between the PTD and the ITD shows structural continuity. These data show how two distinct carbonated apatite-based mineralized tissues can be organized and formed contiguously within the same organ by utilizing different sets of matrix proteins.
Adult↗
Assembly of the type 1 procollagen molecule: selectivity of the interactions between the alpha 1(I)- and alpha 2(I)-carboxyl propeptides.
Assembly of the heterotrimeric procollagen I molecule is initiated by interactions between the carboxyl propeptide domains of the completed nascent pro alpha chains. The [pro alpha 1(I)]2[pro alpha 2(I)] heterotrimer is the predominant molecule, with much smaller amounts of stable [pro alpha 1(I)]3 homotrimer also being formed. However, the [pro alpha 2(1)]3 homotrimer has not been detected, raising questions as to the mechanism of chain assembly and why [pro alpha2(1)]3 homotrimers are not formed. These questions have been examined here by expressing the intact and amino- or carboxyl-terminal truncated C-propeptides of the pro alpha chains recombinantly in bacteria and in a coupled transcription/translation reticulocyte lysate system. Their interactions were studied in vitro by binding analyses and in vivo by using the yeast two-hybrid system. The C-pro alpha 1(I) interacted with itself, and with C-pro alpha 2(I), as expected. Surprisingly, the C-pro alpha 2(I) also interacted with itself, both in vitro and in vivo. While the interaction of C-pro alpha 2(I) with itself and C-pro alpha 1(I) in vitro was strong, these interactions were weaker in vivo. Deletion of 36 amino acids from the C-terminal domain of C-pro alpha 1 had no effect on its binding to intact self or intact C-pro alpha 2, but the same deletion in C-pro alpha 2 completely abolished its binding to intact C-pro alpha 2 and to C-pro alpha 1. Comparable N-terminal deletions in C-pro alpha 1 or C-pro alpha 2 diminished, but did not abolish, their binding to intact C-pro alpha 1 and C-pro alpha 2. In the yeast two-hybrid system, C-pro alpha 2 interacted with itself more weakly than with C-pro alpha 1. Molecular modeling and circular dichroism analyses showed that C-pro alpha 1 and C-pro alpha 2 have different folded structures and stability. Studies with antibodies specific to the C-pro alpha1 and alpha2 peptides showed them to precipitate different, specific, and distinct cell proteins from fibroblast lysates. The C-pro alpha 2(I) antibody complexed with more cell proteins. We hypothesize that the lack of pro alpha 2(I) homotrimers is not due to the inability of the C-pro alpha 2(I) to interact with itself, but rather to the competing presence of other cell proteins. The specificity of these interactions may reside in conformational differences in N- and C-terminal sequences of the two propeptides or in their different folding patterns.
Amino Acid Sequence↗
Alterations in cardiac membrane beta-adrenoceptors and adenylyl cyclase due to hypochlorous acid.
Although neutrophils and eosinophils are known to produce hypochlorous acid (HOCI) at the site of cardiac injury, the exact role of this toxic oxidant on the signal transduction mechanism in the heart is not clear. In this study, the effects of HOCI on beta-adrenoceptors, G-proteins and adenylyl cyclase activity were assessed by incubating rat heart membranes with HOCl. The basal as well as forskolin-, NaF-, 5-guanylylimidodiphosphate-, and isoproterenol-stimulated adenylyl cyclase activities were depressed by incubating cardiac membranes with HOCl. While both the density and affinity of the beta1-adrenoceptors were decreased by treatment of cardiac membranes with HOCl, the characteristics of the beta2-adrenoceptors were not modified significantly. Although cholera toxin-stimulated adenylyl cyclase activity, cholera toxin-catalyzed ADP-ribosylation and stimulatory guanine nucleotide binding protein immunoreactivity were depressed by HOCl, the pertussis toxin-stimulated adenylyl cyclase activity, pertussis toxin-catalyzed ADP ribosylation and inhibitory guanine nucleotide binding protein immunoreactivity were unaltered by HOCl. The presence of L-methionine in the incubation medium prevented the HOCl-induced alterations in adenylyl cyclase activities and characteristics of beta1-adrenoceptors. These results suggest that HOCl may be one of the factors attenuating the beta-adrenoceptor linked signal transduction mechanism in conditions such as ischemic heart disease.
Adenosine Diphosphate↗
Soluble fibrin augments platelet/tumor cell adherence in vitro and in vivo, and enhances experimental metastasis.
There is considerable evidence for a relationship between hemostasis and malignancy. Since platelet adhesion to tumor cells has been implicated in the metastatic process and plasma levels of fibrinogen (Fg) and soluble fibrin (sFn) monomer are increased in cancer, we hypothesized that these molecules might enhance tumor-platelet interaction. We therefore studied binding of sFn monomer to tumor cells in a static microplate adhesion assay and determined the effect of pre-treating tumor cells with sFn on tumor cell-induced thrombocytopenia and experimental metastasis. Soluble fibrin (produced by adding thrombin to FXIII- and plasminogen-free Fg in the presence of Gly-Pro-Arg-Pro-amide (GPRP-NH2) significantly increased platelet adherence to tumor cells. This effect was primarily mediated by the integrins alphaIIb beta3 on the platelet and CD 54 (ICAM-1) on the tumor cells. Platelets adhered to untreated A375 cells (28 +/- 8 platelets/tumor cell) and this was not significantly affected by pre-treatment of the tumor cells with fibrinogen or GPRP-NH2. Although thrombin treatment increased adherence, pre-incubation of the tumor cells with sFn resulted in a further increase in platelet binding to tumor cells. In contrast to untreated tumor cells, intravenous injection of sFn-treated A 375 cells reduced the platelet count in anticoagulated mice, supporting the in vitro finding that sFn enhanced tumor cell-platelet adherence. In a more aggressive model of experimental metastasis, treating tumor cells with sFn enhanced lung seeding by 65% compared to untreated cells. Extrapolation of our data to the clinical situation suggests that coagulation activation, and subsequent increase in circulating Fn monomer, may enhance platelet adhesion to circulating tumor cells and thereby facilitate metastatic spread.
Animals↗
Racial background is a determinant of average warfarin dose required to maintain the INR between 2.0 and 3.0.
Warfarin is a commonly used prophylactic agent for the prevention of thromboembolic disease. We hypothesized that racial background influenced warfarin dosage, and tested this by recording the international normalized ratio (INR) in 867 patients aged 40-90 routinely passing through our Anticoagulation Service whose target INR was 2-3. Mean (95% confidence interval) dose was 4.1 (4.0-4.2) mg/d in 737 Caucasians, 5.5 (4.9-6.1) mg/d in 72 Asians, and 6.7 (5. 8-7.6) mg/d in 58 Afro-Caribbeans (P < 0.05) between each group). In a subgroup of 302 (41 Asians, 22 Afro-Caribbeans, 239 Caucasians), body mass index did not influence warfarin use. Despite small numbers, we conclude that racial background, but not body mass index, is a determinant of warfarin dosage. The reasons for this could be genetic, cultural (diet related), or both.
Anticoagulants↗
Successful treatment of persistent vancomycin-resistant Enterococcus faecium bacteremia with linezolid and gentamicin.
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Acetamides↗
In vitro activities of linezolid against important gram-positive bacterial pathogens including vancomycin-resistant enterococci.
The emergence of resistance in gram-positive bacteria has necessitated a search for new antimicrobial agents. Linezolid is an oxazolidinone, a new class of antibacterial agents with enhanced activity against pathogens. We compared the activity of linezolid to those of other antimicrobial agents against 3,945 clinical isolates. Linezolid demonstrated potent activity against all isolates tested. For all vancomycin-susceptible enterococci, staphylococci, and streptococci, the activity of linezolid was comparable to that of vancomycin. Against oxacillin-resistant staphylococci and vancomycin-resistant enterococci, linezolid was the most active agent tested. In summary, linezolid appears to be a promising new antimicrobial agent for the treatment of gram-positive infections.
Acetamides↗
Laparoscopic versus open appendectomy: a metaanalysis.
BACKGROUND: There have been numerous retrospective and uncontrolled series of laparoscopic appendectomy (LA), as well as 16 prospective randomized studies published to date. Although most of these have concluded that the laparoscopic technique is as least as good as open appendectomy (OA), there has been considerable controversy as to whether LA is superior. To help clarify this issue, we performed a metaanalysis of the randomized prospective studies. STUDY DESIGN: A metaanalysis of all formally randomized prospective trials of LA versus OA in adults. RESULTS: A total of 1,682 patients were analyzed. When compared with OA, LA results in significantly less postoperative pain, earlier resumption of solid foods, a shorter hospital stay, and a faster return to normal activities. The wound infection rate in the LA patients is less than one half the rate in patients undergoing OA. LA, however, requires longer operating times and the incidence of intraabdominal abscess is higher, but this failed to reach statistical significance. There were no differences in complications or hospital charges. CONCLUSIONS: LA offers considerable advantages over OA, primarily because of its ability to reduce the incidence of wound infections and shorten recovery times. Its widespread acceptance should be considered. The trend toward increased intraabdominal abscess formation is worrisome, however, and demands further investigation.
Abdominal Abscess↗
Cross-contamination of specimens with Mycobacterium tuberculosis: clinical significance, causes, and prevention.
At the Veterans Affairs Lakeside Medical Center, two episodes of specimen cross-contamination with Mycobacterium tuberculosis were detected during a 54-month period by molecular strain typing using DNA restriction fragment length polymorphism for 3 patients without clinical or radiologic signs of tuberculosis (TB). A cross-contaminated specimen was the only culture-positive specimen for each of the 3 patients. Laboratory features of cross-contamination included acid-fast smear negativity, growth only in broth or solid medium, and growth in solid medium with 5 or fewer colonies. Retrospective analysis demonstrated identical features for occasional culture-positive specimens from 54 patients with TB during the same period. However, productive cough, pleural pain, weight loss, night sweats, chest radiograph results suggestive of TB, positive tuberculin skin testing, and/or multiple culture-positive specimens were invariably present in patients with TB with such specimens. Most patients with TB (50/54; 93%) had multiple specimens positive in culture for M. tuberculosis, and the few patients with TB with single culture-positive specimens were symptomatic. These results indicate that correlation with clinical manifestations is necessary to determine the significance of isolated, acid-fast smear negative, and/or low-yield culture-positive specimens. Although the prevalence of specimen cross-contamination is low (0.1%), possible sources (especially the use of single-reagent delivery systems for multiple specimens) should be eliminated by mycobacteriology laboratories.
Adult↗
Aspirin enhances the benefits of late reperfusion on infarct shape. A possible mechanism of the beneficial effects of aspirin on survival after acute myocardial infarction.
BACKGROUND: The time window of the benefits of late reperfusion on infarct shape is limited. In rats, these benefits diminish in a wave front over time, with minimal benefits when reperfusion follows 16 hours of coronary occlusion. The mechanism of the benefits of aspirin on survival after acute myocardial infarction is unknown. The purpose of this study was to test the ability of aspirin to enhance the benefits of late coronary artery reperfusion on infarct shape and to examine the mechanism of the benefits of aspirin on infarct shape. METHODS AND RESULTS: Rats were entered into two different protocols, the morphometric and the histological protocols. In the morphometric protocol, rats were randomized into two groups: the aspirin group, in which rats underwent left coronary artery occlusion followed by treatment with aspirin (12 mg/kg i.v.), and the control group, in which rats underwent left coronary artery occlusion followed by treatment with placebo. Rats in both groups were reperfused 8 hours after coronary occlusion. Rats in the aspirin group received aspirin in the drinking water (12 +/- 2 mg/kg daily). Morphometric analysis was performed 2 weeks after acute myocardial infarction. In the histological protocol, rats underwent the same randomization, coronary occlusion, and reperfusion protocols. Hearts were removed 24 hours after coronary occlusion, and microvessels were assessed for patency. Infarct size expressed as a percent of circumference was similar in the aspirin and placebo treatment groups (28 +/- 2% versus 33 +/- 3%, P = NS). Septal thickness was also similar in both groups (1.8 +/- 0.1 versus 2.1 +/- 0.1 mm, P = NS for aspirin versus placebo). The aspirin-treated group had thicker infarcts compared with the placebo-treated group (0.8 +/- 0.1 versus 0.5 +/- 0.1 mm, P < .05) and less expanded infarcts (expansion index, 1.2 +/- 0.1 versus 2.0 +/- 0.2, P < .05). Aspirin was associated with increased patency of the microvessels in the infarcted area compared with the placebo group (96% versus 64% of microvessels patent, P < .001). CONCLUSIONS: Aspirin enhances the benefit of late coronary artery reperfusion on infarct shape after 8 hours of coronary occlusion. The benefits of aspirin on infarct shape after late reperfusion are related to increased patency of the microvessels in the infarcted area.
Animals↗
Regulation of N-methyl-D-aspartate receptor-mediated calcium transport and norepinephrine release in rat hippocampus synaptosomes by polyamines.
The role of polyamines (PA) synthesis in NMDA receptor-mediated 45Ca2+ fluxes and norepinephrine release was studied in rat hippocampal synaptosomes. NMDA (50 microM) caused a sharp (> 2-fold) transient increase in PA synthesis regulating enzyme, ornithine decarboxylase (ODC) activity with concomitant elevation in PA levels in the order putrescine > spermidine > spermine. ODC inhibitor, alpha-difluoromethylornithine (DFMO), and NMDA antagonist, 2-amino-5-phosphonovaleric acid (D-AP5), both blocked increases in ODC activity and PA levels. Activation of NMDA receptors induced a sharp (3 to 4-fold) and quick (15 seconds) increase in 45Ca2+ uptake by synaptosomes within 15 seconds of exposure at 37 degrees C. The efflux of 45Ca2+ and 3H-norepinephrine (NE) release at 22 degrees C from pre-loaded synaptosomes was also significantly (2 to 4-fold) enhanced by NMDA within 15 seconds. These NMDA receptor-mediated effects on calcium fluxes and NE release were blocked by NMDA receptor-antagonists (DAP-5 and MK-801) and PA synthesis inhibitor, DFMO and the DFMO inhibition nullified by exogenous putrescine. These observations establish that ODC/PA cascade play an important role in transduction of excitatory amino acid mediated signals at NMDA receptors.
2-Amino-5-phosphonovalerate↗
Effects of Late Coronary Artery Reperfusion on Left Ventricular Remodeling Persist for 10 Weeks After Experimental Rat Myocardial Infarction and Are Associated with Improved Survival.
Objective: To test the hypothesis that coronary artery reperfusion performed too late to reduce infarct size improves survival by altering left ventricular remodeling and preventing progressive left ventricular dilation. Background: Several clinical trials have suggested that late coronary artery reperfusion without infaret size reduction is associated with a survival benefit. Although the mechanism is not known, survival benefits could be related to decreased infarct expansion associated with late coronary artery reperfusion. Decreased infarct expansion results in decreased left ventricular volume, and the resulting decreased wall stress could prevent or attenuate progressive left ventricular dilation and improve survival. Methods: Rats (n = 84) were randomized to undergo sham operation, permanent left coronary artery ligation, or 2 hours of left coronary artery ligation followed by reperfusion. Ten weeks later, hemodynandic measurements were made before and after volume loading. The rats were killed, the hearts were removed, and passive pressure-volume curves were obtained. The hearts were fixed at a constant pressure and analyzed morphometrically. Results: When examined 10 weeks after experimental myocardial infarction late eperfusion's effects on left ventricular remodeling resulted in reduced left ventricular volume when compared to hearts with infarcts supplied by a permanently occluded coronary artery (1.9 +/- 0.1 ml/kg vs. 2.1 +/- 0.2 ml/kg; p < 0.01). Although there was a trend toward less thinning along (0.95 +/- 0.13 mm vs. 1.00 +/- 0.10 mm; p = NS) and less expansion (2.3 +/- 0.4 vs. 2.8 +/- 0.9; p = NS) in reperfused hearts compared to hearts with a permanently occluded coronary artery, changes in infarct shape 10 weeks after infarction were not significantly different. Reperfusion's beneficial effects on remodeling of noninfarcted myocardiurn were associated with improved survival. Mortality was higher in the permanently occluded rats than in the reperfused rats (35% vs. 12%; p < 0.05). Conclusion: Late coronary artery reperfusion has a beneficial effect on remodeling of noninfarcted myocardum that results in reduced left ventricular volume in rat hearts examined 10 weeks after infarction. These beneficial effects on left ventricular remodeling are associated with improved survival.
Journal Article↗
N-methyl-D-aspartate receptor excitotoxicity involves activation of polyamine synthesis: protection by alpha-difluoromethylornithine.
We investigated the role of polyamines and their regulatory enzyme ornithine decarboxylase in N-methyl-D-aspartate-induced excitotoxicity in embryonic chick retina. N-Methyl-D-aspartate (200 microM) produced an early increase in ornithine decarboxylase activity, putrescine concentration, and Ca2+ entry, leading to selective neuronal death by 30 min. This response was attenuated by the ornithine decarboxylase inhibitor alpha-difluoromethylornithine and the N-methyl-D-aspartate receptor antagonist 5-aminophosphonovaleric acid. Exogenous putrescine increased intracellular putrescine and spermine levels and reversed neuroprotection by alpha-difluoromethylornithine, but not by 5-aminophosphonovaleric acid. N-Methyl-D-aspartate-receptor stimulation of putrescine/polyamine synthesis mediates abnormal Ca2+ entry and acute excitotoxic neuronal death. Postreceptor inhibition of the ornithine decarboxylase/polyamine cascade by alpha-difluoromethylornithine may provide neuroprotection against N-methyl-D-aspartate-induced excitotoxicity.
Animals↗
Localization of inhaled trimellitic anhydride to lung with a respiratory lymph node antibody secreting cell response.
Male Sprague-Dawley rats were exposed to trimellitic anhydride (TMA) by inhalation (500 micrograms/m3), 4 hours a day, for 1 to 10 days. TMA was localized to lung cells by immunoelectron microscopy. Enzyme-linked immunosorbent assay (ELISA) and Western blot analysis were used in an attempt to localize TMA to lung lavage proteins. The lung-associated lymph node (LALN) B-lymphocyte response was measured by quantitation of immunoglobulin (Ig)G, IgA, and IgM antibody secreting cells specific for TMA rat serum albumin (TM-RSA) by use of the enzyme-linked immunospot assay (ELISPOT) method. The IgG, IgM, and IgA antibody response to TM-RSA in serum and lavage fluid was quantitated by ELISA. Lung injury was assessed by the number of external lung hemorrhagic foci and lung weight. Immunoelectron microscopy localized TMA to alveolar and bronchial cells on all exposure days. ELISA detected trace amounts of TMA haptenized lavage proteins that could not be detected by Western blot analysis. A marked increase occurred in lung injury from day 7 to 10. The LALN IgG, IgA, and IgM antibody secreting cell response to TM-RSA paralleled measures of lung injury. IgG, IgM, and IgA serum and lavage antibody to TM-RSA were correlated with lung injury measures. Lavage and serum IgG antibody levels had the highest correlation with lung injury.
Administration, Inhalation↗