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Biomedical subjects

D Greenberg

Publications and source records attributed to D Greenberg.

At least 73 records · Page 4Linked to original sources

Decreased adrenal sex steroid levels in the absence of glucocorticoid suppression in postmenopausal asthmatic women.

BACKGROUND AND AIM: Reduction of serum sex steroid levels has been reported to occur after the administration of beta-adrenergic medication. In that beta-adrenergic blockade is a central pathophysiologic feature of asthma, this study was done to explore the possibility of hormonal alteration in asthma. METHODS: Sex steroids obtained from 22 postmenopausal asthmatic and 22 age-matched, postmenopausal, nonasthmatic women were assayed. No subject had received estrogens, progestins, or oral corticosteroids for 120 days before the study. RESULTS: Mean dehydroepiandrosterone sulfate (DHEAS; p < 0.002), dehydroepiandrosterone (DHEA; p < 0.03), estradiol (p < 0.02), and estrone (p < 0.02) levels were lower in asthmatic patients compared with nonasthmatic subjects. Results could not be accounted for by current medication. Patients with asthma demonstrated no decrease in 17-hydroxyprogesterone or cortisol compared with nonasthmatic subjects, limiting findings to the delta 5, and not the delta 4, steroidogenic pathway. In a second phase of the study, DHEAS was measured before and after 3 days of oral beta-agonist stimulation in eight postmenopausal asthmatic women. Serum DHEAS concentration increased in eight of eight subjects, from a mean of 28.6 +/- 19.9 micrograms/dl (mean +/- SD) to 40.7 +/- 24.8 micrograms/dl (p = 0.002). Serum cortisol concentration was unchanged. CONCLUSION: The results indicate that postmenopausal asthmatic women have lower serum levels of adrenally derived sex steroids than their nonasthmatic peers and that this anomaly may be ameliorated by adrenergic stimulation.

Adrenergic beta-Agonists↗

Intergroup comparisons of carpal tunnel dimensions.

Although it is a common disease entity worldwide, idiopathic carpal tunnel syndrome is rarely seen in black South Africans. This study compares anatomic dimensions of the carpal canal in black and white population groups, using computed tomography. No significant anatomic differences were found between the groups tested; thus, other explanations need to be sought to explain the difference in occurrence of carpal tunnel syndrome in these groups. A parameter, the carpal canal index, was defined and may prove useful in future investigations of this region.

Adult↗

Reduction of nasopharyngeal carriage of pneumococci during the second year of life by a heptavalent conjugate pneumococcal vaccine.

Children 12-18 months old were randomized to receive one dose of a conjugate heptavalent pneumococcal vaccine, two doses of the same vaccine, or one dose of a 23-valent native polysaccharide vaccine. Before immunization, pneumococci included in the conjugate vaccine were isolated from 24% of the children, and an antibiotic-resistant pneumococcus was isolated from 22% of the children. The vaccines had no effect on carriage of non-vaccine-type pneumococci. In contrast, there was a significant reduction in carriage of vaccine-type pneumococci 3 months after one dose and 1 month after a second dose of conjugate vaccine (from 25% to 9% and 7%, respectively; P < .001). No effect was seen after vaccination with the nonconjugate vaccine. One year after immunization, carriage of antibiotic-resistant vaccine-type pneumococci in children receiving conjugate vaccine was lower than that in children receiving the nonconjugate vaccine (4% vs. 14%, P = .042). Conjugate pneumococcal vaccines may reduce spread of pneumococci in the community.

Antibodies, Bacterial↗

Impaired bacteriologic response to oral cephalosporins in acute otitis media caused by pneumococci with intermediate resistance to penicillin.

BACKGROUND: Penicillin resistance of Streptococcus pneumoniae, one of the most common causes of acute otitis media, has recently increased and is now highly prevalent in many regions. However, its contribution to clinical failure still must be proved. Because the role of antibiotics in acute otitis media is to eradicate the pathogens present in the middle ear fluid, we conducted a randomized controlled study to determine bacterial eradication of pathogens in acute otitis media by two commonly used oral cephalosporins, cefuroxime axetil (30 mg/kg/day) and cefaclor (40 mg/kg/day). METHODS: Patients 6 to 36 months old with pneumococcal otitis media seen in the Pediatrics Emergency Room were studied. An initial middle ear fluid culture was obtained at enrollment, and a second culture was obtained on Day 4 or 5 during treatment. Follow-up was done also on Days 10, 17 and 42 after initiation of treatment. In cases of clinical relapse a third culture was obtained. RESULTS: In total 78 patients were enrolled, 41 in the cefuroxime axetil group and 37 in the cefaclor group. Of the 78 S. pneumoniae isolates 31 (40%) were intermediately penicillin-resistant (MIC 0.125 to 1.0 microgram/ml). Of the 47 patients with penicillin-susceptible organisms 3 (6%) had bacteriologic failure vs. 4 of 19 (21%) and 7 of 11 (64%) of those with MIC of 0.125 to 0.25 microgram/ml and 0.38 to 1.0 microgram/ml, respectively (P < 0.001). For intermediately resistant pneumococci, in 7 of 12 (58%) of those receiving cefaclor the isolate was not eradicated vs. only 4 of 19 (21%) of those receiving cefuroxime axetil (P = 0.084). MIC to the administered cephalosporin of > 0.5 microgram/ml was associated with bacteriologic failure. Clinical failure was observed in 9 of 14 (64%) patients with bacteriologic failure vs. 10 of 52 (19%) patients with bacteriologic eradication (P = 0.003). CONCLUSION: Intermediately penicillin-resistant S. pneumoniae is associated with an impaired bacteriologic and clinical response of acute otitis media to cefaclor and cefuroxime axetil. This effect was more pronounced with cefaclor than with cefuroxime axetil.

Acute Disease↗

Intestinal fat differentially suppresses sham feeding of different gustatory stimuli.

To determine the intestinal contribution to short-term satiety for solutions of varying palatability, 10 ml of either 0.15 M NaCl or lipid (Intralipid: 0.125, 0.25, 0.5, and 1.0 kcal/ml) was infused at a rate of 0.5 ml/min into the duodenum of rats that were sham feeding either a liquid diet (0.5 kcal/ml), 0.3 M sucrose (0.4 kcal/ml), or a 0.1 M solution of glucose polymers (Polycose 0.4 kcal/ml). Differences in palatability were estimated by the total consumption of each solution over 90 min in a one-bottle test. The intake of solutions maximally ingested during the saline infusions (Polycose > Sucrose > liquid diet) was the most sensitive to the lipid infusions. All four lipid concentrations suppressed intake of Polycose, the solution consumed the most; the three highest concentrations suppressed intake of sucrose (intermediate consumption), and only the two highest concentrations suppressed intake of the complete diet, the solution consumed the least. Nevertheless, the duration of suppression was shorter for the solutions the rats drank the most. For the solution the rats drank the least (liquid diet), the two high concentrations of lipid that suppressed intake did so for the entire experimental period, whereas for Polycose, al lipid infusions suppressed intake, but it recovered to control levels for all but the highest concentration. Other studies have reported that increasing diet palatability shortens the duration of satiety. The current results suggest that this effect may reflect the duration of intake suppression elicited by nutrients in the intestine.

Animals↗

Next-generation informatics. A new picture of quality medicine.

It's up to the physician executive to make an informed choice when selecting a "next-generation" information system. Look for systems that truly integrate (not merely interface) managed care components, clinical capabilities, and other features in a model that mimics the workflow of an actual practice. Take the time to learn about the technology. Consider how a vendor's product will work at every point within your organization. Seven critical features that physician executives should consider in their decision-making are described.

Decision Making↗

Liver-specific expression of the human factor VII gene.

Promoter and silencer elements of the immediate 5' flanking region of the gene coding for human factor VII were identified and characterized. The major transcription start site, designated as +1, was determined by RACE (rapid amplification of cDNA ends) analysis of human liver cDNA and was found to be located 50 bp upstream from the translation start site. Two minor transcription start sites were found at bp +32 bp and +37. Progressive deletions of the 5' flanking region were fused to the chloramphenicol acetyltransferase reporter gene and transient expression in HepG2 and HeLa cells was measured. Two promoter elements that were essential for hepatocyte-specific transcription were identified. The first site, FVIIP1, located at bp -19 to +1, functioned independently of orientation or position and contributed about one-third of the promoter activity of the factor VII gene. Electrophoretic mobility-shift, competition, and anti-hepatocyte nuclear factor 4 (HNF4) antibody supershift experiments demonstrated that this site contained an HNF-4 binding element homologous to the promoters in the genes coding for factor IX and factor X. The second site, FVIIP2, located at bp -50 to -26, also functioned independent of orientation or position and contributed about two thirds of the promoter activity in the gene for factor VII. Functional assays with mutant sequences demonstrated that a 10-bp G + C-rich core sequence which shares 90% sequence identity with the prothrombin gene enhancer was essential for the function of the second site. Mobility-shift and competition assays suggested that this site also binds hepatic-specific factors as well as the transcription factor Sp1. Two silencer elements located upstream of the promoter region spanning bp -130 to -103 (FVIIS1 site) and bp -202 to -130 (FVIIS2) were also identified by reporter gene assays.

Antibodies↗

Identification and characterization of a cell envelope protein of Haemophilus influenzae contributing to phase variation in colony opacity and nasopharyngeal colonization.

Haemophilus influenzae undergoes spontaneous phase variation in colony morphology. Organisms from transparent colonies efficiently colonize the nasopharynx in an infant rat model of H. influenzae carriage, whereas organisms from more opaque colonies are deficient at colonization. A genetic approach relying on the transformability of H. influenzae was used to identify a locus contributing to opacity variation. By screening a library of chomosomal DNA from an opaque variant of strain Rd, it was possible to isolate a single clone capable of transforming a transparent Rd host to a more opaque phenotype. A region containing two genes, designated oapA and oapB, was identified. The deduced amino acid sequence of oapB has similarity to a consensus sequence for bacterial lipoproteins. Genetically defined mutations in oapA were transformed into the transparent Rd to confirm that this gene is required for expression of the transparent colony phenotype. Although oapA lacks a signal sequence, gene fusions to phoA show that OapA is secreted in H. influenzae and undergoes phase variation in expression. Mutagenesis of oapA in strain Rd, and type b strain Eagan, resulted in loss of the ability to colonize the nasopharynx of infant rats. The type b mutant, however, was as virulent as its parent strain when inoculated intraperitoneally. This suggests that the contribution of OapA to pathogenesis is limited to events associated with colonization of the mucosal surface.

Animals↗

Fetal pseudohypoaldosteronism: another cause of hydramnios.

Pseudohypoaldosteronism (PHA) is a rare hereditary salt-wasting syndrome which is caused by decreased renal tubular responsiveness to aldosterone. The syndrome consists of hyponatremia, hyperkalemia, dehydration, failure to thrive and increased urinary salt loss. A case of PHA was previously described where fetal polyuria was the probable cause of hydramnios. We present four new cases of PHA, from two families, who were born after pregnancies complicated by severe hydramnios and premature labor. We suggest that PHA should be included in the differential diagnosis of hydramnios, since appropriate investigations might lead to the early diagnosis and treatment of a life-threatening disease.

Adult↗

Time course for entry of intestinally infused lipids into blood of rats.

The early time course of the absorption of duodenally infused 14C-labeled Intralipid into either the hepatic portal circulation or systemic circulation was measured. Plasma radioactivity did not increase significantly at either site until 30 min after the intestinal infusion began and was maximal between 60 and 120 min. In studies on the effects of intestinal lipid infusions on sham feeding in rats we find significant suppressions of sham feeding after only 10 min. Thus the time course for lipid absorption is different from that of the satiating effects of duodenally infused fats. These results are consistent with the hypothesis that the satiating effect of fats infused into the small intestine occurs before entry of absorbed fats into the blood and is not dependent on recently absorbed circulating fat.

Animals↗

Modification of the fungi-fluor and the genetic systems fluorescent antibody methods for detection of Pneumocystis carinii in bronchoalveolar lavage specimens.

Four hundred forty-five bronchoalveolar lavage specimens from patients with the human immunodeficiency virus were preserved in Saccomano's fixative and stained for Pneumocystis carinii cysts by a modified method with Fungi-Fluor Solution A (Polysciences, Warrington, Pa) and the Genetic Systems Pneumocystis carinii Immunofluorescence Antibody (Genetic Systems Corp, Seattle, Wash). The majority of patients had been treated for suspected P carinii pneumonia for a few days prior to collection of bronchoalveolar lavage specimens. P carinii cysts were detected in 194 (43.6%) specimens. Both stains identified P carinii in 166 (37.3%) specimens and were negative in 251 (56.4%), yielding a concordance rate of 93.7%. P carinii cysts were detected in 25 (5.6%) specimens by the Genetic Systems stain only, and in 3 (0.7%) specimens by the Fungi-Fluor stain only. The sensitivity for detecting cysts of P carinii was significantly greater with the Genetic Systems stain (P < .01).

Bronchoalveolar Lavage Fluid↗

Two-year trial of maintenance neuroleptic dose reduction in schizophrenic out-patients: predictors of relapse.

Low dose maintenance therapy has been proposed as a pharmacological strategy for reducing exposure to neuroleptic drugs in schizophrenia. However, reliable predictors of post-dose reduction relapse, which could guide clinicians in selecting patients suitable for this type of treatment, have not yet been determined. In this study, 41 schizophrenic out-patients were assigned, on the basis of their previously clinically determined dosages, to one of two reduced maintenance fluphenazine decanoate regimes (35 mg/4 wks. or 10 mg/4 wks.) and were assessed, subsequently, for a 2-year period. Demographic, clinical and treatment characteristics of relapsers (22 patients) and non-relapsers (18 patients) were compared using univariate and multivariate tests. Four parameters: age, course of illness, duration of illness and duration since last psychiatric hospitalization, suggested, in univariate tests, significant discrimination between relapsers and non-relapsers. Stepwise discriminant function analyses defined a highly significant function (p < .01) which included only 3 predictors of relapse. In order of importance, these predictors were: (1) a history of chronic psychosis (2) male sex, and (3) an illness of short duration. Parameters such as age, baseline rating scales scores, magnitude of dose reduction and baseline maintenance dose failed to improve the ability to discriminate between relapsers and non-relapsers. Implications of these findings for clinical practice are discussed.

Adult↗

Devazepide alters meal patterns in lean, but not obese, male Zucker rats.

Meal patterns were recorded for 10.5 h in six lean and eight obese adult male Zucker rats after treatment with the cholecystokinin type A (CCKA) receptor antagonist, devazepide (750 micrograms/kg, IP, at 1330 h) or vehicle. In lean rats, devazepide significantly increased total food intake by 11%, average meal size by 35%, and meal duration by 49%. Devazepide also significantly decreased the average number of meals by 18%, although this was a smaller effect. Devazepide had none of these effects in obese rats. Devazepide treatment altered the meal pattern of lean rats so that it was similar to that of obese rats. These results demonstrate that endogenous CCK has a satiating effect in lean, but not in obese, male Zucker rats, which is the first demonstration of a loss of a physiological satiety signal in the obese Zucker rat. This defect could be due to: 1) a decrease in the release of endogenous CCK, 2) a decrease in the rate of CCK synthesis, or 3) the production of an abnormal form of CCK.

Animals↗

The chimeric mapping problem: algorithmic strategies and performance evaluation on synthetic genomic data.

The Human Genome Project requires better software for the creation of physical maps of chromosomes. Current mapping techniques involve breaking large segments of DNA into smaller, more-manageable pieces, gathering information on all the small pieces, and then constructing a map of the original large piece from the information about the small pieces. Unfortunately, in the process of breaking up the DNA some information is lost and noise of various types is introduced; in particular, the order of the pieces is not preserved. Thus, the map maker must solve a combinatorial problem in order to reconstruct the map. Good software is indispensable for quick, accurate reconstruction. The reconstruction is complicated by various experimental errors. A major source of difficulty--which seems to be inherent to the recombination technology--is the presence of chimeric DNA clones. It is fairly common for two disjoint DNA pieces to form a chimera, i.e., a fusion of two pieces which appears as a single piece. Attempts to order chimera will fail unless they are algorithmically divided into their constituent pieces. Despite consensus within the genomic mapping community of the critical importance of correcting chimerism, algorithms for solving the chimeric clone problem have received only passing attention in the literature. Based on a model proposed by Lander (1992a, b) this paper presents the first algorithms for analyzing chimerism. We construct physical maps in the presence of chimerism by creating optimization functions which have minimizations which correlate with map quality. Despite the fact that these optimization functions are invariably NP-complete our algorithms are guaranteed to produce solutions which are close to the optimum. The practical import of using these algorithms depends on the strength of the correlation of the function to the map quality as well as on the accuracy of the approximations. We employ two fundamentally different optimization functions as a means of avoiding biases likely to decorrelate the solutions from the desired map. Experiments on simulated data show that both our algorithm which minimizes the number of chimeric fragments in a solution and our algorithm which minimizes the maximum number of fragments per clone in a solution do, in fact, correlate to high quality solutions. Furthermore, tests on simulated data using parameters set to mimic real experiments show that that the algorithms have the potential to find high quality solutions with real data. We plan to test our software against real data from the Whitehead Institute and from Los Alamos Genomic Research Center in the near future.

Algorithms↗