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Biomedical subjects

D Citron

Publications and source records attributed to D Citron.

11 recordsLinked to original sources

p27-p16 Chimera: a superior antiproliferative for the prevention of neointimal hyperplasia.

Cyclin-dependent kinase inhibitors (CDKi's) may be useful to treat hyperproliferative vascular disorders, such as restenosis induced following angioplasty or vein engraftment. We have shown that a novel fusion protein of the CDKi's p27 and p16, named W9, significantly reduces proliferation of human coronary smooth muscle cells in vitro, by blocking cell proliferation without inducing apoptosis. We have now evaluated the efficacy of adenovirus-mediated gene transfer of W9 (AV-W9) in a balloon-injury model, in the carotid arteries of cholesterol-fed rabbits. We observed that intravascular delivery of 2 x 10(11) viral particles of AV-W9 3 days following balloon injury inhibited intimal hyperplasia by 60% compared to a control virus (P > 0.001). PCNA expression in the AV-W9-treated vessels, a marker of injury-induced cell proliferation, was also reduced compared to the control virus-treated vessels. Direct comparison of the efficacy of AV-W9 and AV-p16 and AV-p27 in this model indicated that delivery of either of the parental genes was significantly less effective in inhibiting intimal thickening compared to the AV-W9 treatment. We conclude that combining the activities of multiple cell cycle regulatory proteins greatly increases the potency of cytostatic gene therapy in the treatment of balloon injury-induced intimal hyperplasia and represents a promising potential approach to preventing postangioplasty restenosis.

Adenoviridae↗

Alterations in human fecal flora, including ingrowth of Clostridium difficile, related to cefoxitin therapy.

To evaluate the effects of parenteral cefoxitin therapy on human fecal flora, we cultured fecal specimens obtained from six patients before, during, and after therapy and used standard methods to identify and quantify all microorganisms. The major changes (observed in at least three patients) included the acquisition or proliferation of group D Streptococcus species, coagulase-negative Staphylococcus species, cefoxitin-resistant members of the family Enterobacteriaceae, Pseudomonas species, and various species of the Bacteroides fragilis group. The most striking finding was ingrowth of Clostridium difficile, noted in five of the six patients. There was concomitant eradication or decrease of cefoxitin-susceptible Enterobacteriaceae family members, Bacteroides species other than the B. fragilis group, Clostridium species other than C. difficile, and Lactobacillus species. These marked alterations of fecal flora may have important clinical consequences.

Adult↗

[Amineptine-induced cholestatic hepatitis. 5 cases (author's transl)].

The authors have observed 5 cases of cholestatic jaundice with cytolysis during treatment with amineptine, a new tricyclic compound recently made available. The responsibility of the drug was virtually certain for the following reasons: (a) there was no other cause of jaundice, such as viral infection, gallstones, toxic agents or association with other hepatotoxic drugs; (b) clinical and biochemical findings were similar in all patients; (c) in 2 patients, reintroduction of the drug after temporary withdrawal resulted in rapid recurrence of the condition, with the same symptoms and course. The shorter delay (2 and 8 days instead of 11 and 18 days) between absorption of amineptine and reappearance of the symptoms in these two patients is suggestive of an immunoallergic mechanism.

Adult↗

Detection, identification, and comparison of Capnocytophaga, Bacteroides ochraceus, and DF-1.

Working independently, three laboratories had recognized considerable similarity among certain strains of dysgonic, fermentative, capnophilic, surface translocating, gram-negative bacilli referred to as Capnocytophaga, Bacteroides ochraceus, and Center for Disease Control biogroup DF-1. To determine the relationship among these groups, 21 strains were exchanged and independently characterized by the three laboratories. Additionally, a fourth laboratory examined the deoxyribonucleic acid homologies of the same strains. Using methods common to dental microbiology, eight of the strains had been isolated from the gingival sulcus and periodontal lesions and identified as Capnocytophaga. Three strains isolated from blood and transtracheal aspirate had been characterized by conventional anaerobic methods and recorded as B. ochraceus. Ten strains isolated from sputum, blood, throat, spinal fluid, and tracheal aspirate had been identified as DF-1 with the methods of E. O. King and a buffered single-substrate technique. All strains were similar in respect to colonial and microscopic morphology, surface translocation, biochemical features, gas-liquid chromatograms of metabolic end products, and deoxyribonucleic acid composition. We conclude that these biogroups should be termed Capnocytophaga species.

Bacterial Infections↗

Selective and differential medium for isolation of Clostridium difficile.

Clostridium difficile is a recognized cause of pseudomembranous (antimicrobial agent-associated) colitis and may be one of the causes of antimicrobial agent-induced diarrhea. A selective and differential agar medium that contains cycloserine, cefoxitin, fructose, and egg yolk (CCFA) was developed to facilitate the isolation of C. difficile from fecal specimens. Quantitative cultures of 16 stock strains of C. difficile on this medium (and on a medium containing cycloserine, fructose, and egg yolk) yielded counts equivalent to those obtained on blood agar; other media selective for clostridia, including Clostrisel agar, reinforced clostridial agar plus 0.2% para-cresol, and egg yolk-neomycin agar (the latter was inoculated with cultures subjected to prior heat shocking), were also tested and found to be inhibitory to the growth of C. difficile. Of 28 fecal or colostomy effluent specimens cultured on the above media, 14 yielded C. difficile. CCFA was found to be the most sensitive and selective of these media for the recovery of C. difficile. Colonies of C. difficile growing on CCFA had distinctive morphological and fluorescent properties which were sufficient for presumptive identification. CCFA should provide a rapid method for the screening of fecal specimens from patients with antimicrobial agent-associated diarrhea or colitis for C. difficile.

Animals↗

Acoustic reflex and loudness discomfort in acute facial paralysis.

An extensive research protocol was used to evaluate the conditions of 48 consecutive patients with acute facial paralysis. The results indicated that after nerve excitability testing, the acoustic reflex was the most efficient indicator of impending nerve degeneration and predictor of recovery. The presence of increased sensitivity to intense acoustic stimuli (loudness discomfort level) indicated poor prognosis. The data demonstrate that dysacusis (hyperacusis) is not related to stapedial muscle paralysis and also question the validity of "topographic diagnosis" in determination of the site of the lesion in facial paralysis.

Adolescent↗

Electrodermal response, delayed auditory feedback, and lengthened off-time procedures. Comparison of use for medical-legal audiological assessment.

Results of conventional audiological procedures, lengthened off-time Békésy, and electrodermal response audiometry are compared with pure-tone delayed auditory feedback procedures for 100 subjects referred for medical-legal audiological evaluation. Specific attention is given to a new economical prototype unit for pure-tone delayed auditory feedback, to the comparison of results of special test procedures, and to the nonorganic hearing loss population.

Adult↗

Suppression of gastric acid secretion in patients with gastroesophageal reflux disease results in gastric bacterial overgrowth and deconjugation of bile acids.

The aim of this study was to test the hypothesis that gastric bacterial overgrowth is a side effect of acid suppression therapy in patients with gastroesophageal reflux disease (GERD) and that the bacteria-contaminated gastric milieu is responsible for an increased amount of deconjugated bile acids. Thirty patients with GERD who were treated with 40 mg of omeprazole for at least 3 months and 10 patients with GERD who were off medication for at least 2 weeks were studied. At the time of upper endoscopy, 10 ml of gastric fluid was aspirated and analyzed for bacterial growth and bile acids. Bacterial overgrowth was defined by the presence of more than 1000 bacteria/ml. Bile acids were quantified via high-performance liquid chromatography. Eleven of the 30 patients taking omeprazole had bacterial overgrowth compared to one of the 10 control patients. The median pH in the bacteria-positive patients was 5.3 compared to 2.6 in those who were free of bacteria and 3.5 in the control patients who were off medication. Bacterial overgrowth only occurred when the pH was >3.8. The ratio of conjugated to unconjugated bile acids changed from 4:1 in the patients without bacterial overgrowth to 1:3 in those with bacterial growth greater than 1000/ml. Proton pump inhibitor therapy in patients with GERD results in a high prevalence of gastric bacterial overgrowth. The presence of bacterial overgrowth markedly increases the concentration of unconjugated bile acids. These findings may have implications in the pathophysiology of gastroesophageal mucosal injury.

Anti-Ulcer Agents↗

Delayed feedback audiometry: reliability of repeated measures.

The test-retest reliability of hearing thresholds at 1000 Hz measured by a delayed auditory feedback procedure was compared with the reliability of thresholds obtained with voluntary responses to the same signal in 10 adults with normal hearing sensitivity. Thresholds for each procedure were obtained three times on each of 5 different days. Although the delayed feedback procedure yielded estimates of threshold which averaged 4.6 dB greater than those estimated by voluntary responses (p less than 0.05), there was no evidence that experience over time resulted in a change for the poorer in the precision of the test.

Adult↗

Implementation of recommended health maintenance activities in geriatric care.

To determine the extent to which health screening and preventive measures are actually documented in family practice, a random sample of 216 charts of established patients over 65 in seven practices was audited. Overall, a high rate of documentation (greater than 95%) was observed for blood pressure measurement. Intermediate rates of documentation (35% to 75%) were observed for oral cavity examination, smoking history, and skin examination. Low rates (less than 30%) were present for tetanus immunization, influenza immunization, stool occult blood testing, visual screening, hearing screening, mental status testing, social support description, and discussion of care preferences (living will). Several diagnoses for which screening was infrequently documented were recorded at rates approaching expected community prevalence figures, a finding that suggests widespread performance of informal or undocumented health screening in these practices. Recommended measures to increase the performance and documentation of preventive care include changes in the medical record, alterations in reimbursement, and delegation to nonphysician office staff.

Aged↗