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Biomedical subjects

D Kaye

Publications and source records attributed to D Kaye.

At least 73 records · Page 4Linked to original sources

Cyclosporine therapy after cardiac transplantation causes hypertension and renal vasoconstriction without sympathetic activation.

BACKGROUND: Hypertension frequently complicates the use of cyclosporine A (CyA) therapy, and it has been suggested that sympathoexcitation may be the underlying mechanism in this form of hypertension. METHODS AND RESULTS: To further investigate the possibility of a neurogenic mechanism for this hypertensive effect, we studied the effects of CyA on renal blood flow (n = 11), forearm blood flow (n = 8), and sympathetic nervous system activity, assessed by renal and whole-body radiolabeled norepinephrine plasma kinetics and muscle sympathetic nerve firing (using microneurography) in cardiac transplant recipients receiving CyA and a reference group of healthy age-matched control subjects (n = 17). In 11 cardiac transplant patients (2 hours after cyclosporine dose), renal blood flow was significantly lower than that in 8 control subjects (680 +/- 88 vs 1285 +/- 58 mL/min, P < .001). In 5 of these transplant patients, renal blood flow was measured before and for 2 hours after oral cyclosporine and fell progressively over this period, by 37% (P < .01). Total body and renal norepinephrine spillover rates in transplant patients were similar to those in control subjects (3070 +/- 538 vs 2618 +/- 313 pmol/min and 579 +/- 124 vs 573 +/- 95 pmol/min, respectively), and there was no progressive effect in the 2 hours after cyclosporine dosing. Forearm blood flow was increased 2 hours after CyA administration (1.74 +/- 0.31 to 3.12 +/- 0.50 mL x 100 mL-1 x min-1, P < .001), whereas mean arterial blood pressure and noninvasively determined cardiac output (indirect Fick method) were unchanged. Muscle sympathetic nerve discharge rates recorded in 6 of these transplant patients were not different from those in 9 healthy control subjects (37.9 +/- 10.1 vs 41.3 +/- 2.3 bursts per 100 beats per minute). During 90 to 120 minutes of recording after cyclosporine dosing, nerve firing rates remained unchanged. CONCLUSIONS: CyA therapy causes acute renal vasoconstriction without accompanying systemic hemodynamic effects. These renal effects are nonneural, not being attributable to sympathoexcitation.

Cyclosporine↗

Neurologic complications of infective endocarditis.

The average overall incidence of neurologic complications in patients with infective endocarditis is 30%, with the vast majority of these complications in patients with left-sided valvular disease. The incidence of central nervous system manifestations, particularly of embolic events, tends to be higher in cases of endocarditis caused by more virulent organisms, such as S. aureus and the Enterobacteriaceae. The clinical presentation is dependent on the area of the central nervous system involved. CT and MRI scanning are useful radiologic imaging techniques for the diagnosis of central nervous system complications in patients with infective endocarditis; cerebral angiography should be used in patients with suspected intracranial mycotic aneurysm. The cornerstone of management is appropriate antimicrobial therapy. Neurosurgical intervention may be required for certain patients with intracranial mycotic aneurysms that do not disappear after antimicrobial therapy or for aneurysms that enlarge or bleed. Anticoagulants should be continued in patients with prosthetic valve endocarditis who do not have evidence of intracranial hemorrhage. Anticoagulants should be avoided (unless thromboembolic events are from a site other than the vegetation) in patients with native valve endocarditis owing to the risk of hemorrhagic central nervous system complications. Case fatality rates tend to be higher in patients with neurologic complications of infective endocarditis. Earlier diagnostic and therapeutic interventions for patients with central nervous system complications of infective endocarditis will, it is hoped, improve the outcome in patients with this disorder.

Anti-Bacterial Agents↗

Hospital-acquired infection with vancomycin-resistant Enterococcus faecium transmitted by electronic thermometers.

OBJECTIVES: To describe an epidemic of vancomycin-resistant Enterococcus faecium causing bacteremia and bacteriuria, to identify the source of infection, to delineate risk factors associated with acquisition of the organism, and to determine antibiotic sensitivities for the organism. DESIGN: Investigation of an epidemic, including a case-control study. SETTING: Medical-surgical intensive care unit and ward in a university medical center. PATIENTS: Nine patients infected or colonized with vancomycin-resistant Enterococcus faecium and 20 noninfected controls. MEASUREMENTS: Clinical data, environmental surveillance cultures, and in-vitro microbiologic studies. RESULTS: Colonization or infection by vancomycin-resistant E. faecium was associated with an increased duration of treatment with ceftazidime, 13.2 compared with 4.6 days, and a greater number of nonisolated days of hospitalization in the intensive care unit, 19.9 compared with 6.4 days for infected and noninfected patients, respectively (P less than 0.05). Environmental surveillance cultures recovered the organism repeatedly from the rectal probe handles of three electronic thermometers used exclusively on nonisolated patients in the intensive care unit. Restriction endonuclease analysis of plasmid DNA showed that all clinical and environmental isolates were identical. Infection control measures, including isolation of colonized or infected patients and removal of the rectal thermometer probes suspected to be responsible for transmission, resulted in termination of the outbreak. In-vitro, time-kill studies showed that the combination of ciprofloxacin, rifampin, and gentamicin resulted in bactericidal activity against the organism. CONCLUSIONS: This nosocomial outbreak of infection due to a highly vancomycin-resistant strain of Enterococcus is the first epidemic in which an electronic thermometer has been implicated as the vehicle of transmission for an infectious agent.

Adolescent↗

Evaluation of new anti-infective drugs for the treatment of infective endocarditis. Infectious Diseases Society of America and the Food and Drug Administration.

These guidelines describe the design and implementation of clinical trials to assess the safety and efficacy of anti-infective drugs for the treatment of infective endocarditis. Identification and enrollment of patients in clinical trials is based on a modification of traditional criteria. To accrue a sufficient number of patients, only those with streptococcal or staphylococcal endocarditis should be included in studies. Results of treatment with approved drugs allow for projection of expected bacteriologic cure rates and survival rates. Prospective randomized, double-blind studies are recommended. These guidelines are based on the premise that future protocols may include shorter courses of therapy, combinations of drugs, or progression from parenteral to oral therapy. Clinical response is judged as cure, failure, or indeterminate; there is no "improved" category. Microbiologic response is categorized as eradication, persistence, or relapse. When a patient has shown no clinical evidence of active disease for a protracted period, there may be no need to perform a posttreatment blood culture; for such patients, the microbiologic response is termed presumptive eradication. Several months of follow-up may be necessary to detect late relapses.

Anti-Infective Agents↗

Heterogeneous effects of exogenous lymphokines on lymphoproliferation of elderly subjects.

Although the ability of peripheral blood mononuclear cells of a population of elderly subjects (mean age 85.3) to proliferate in response to the T cell mitogens phytohemagglutinin (PHA) and concanavalin A (Con A) is significantly reduced compared to young subjects (mean age 24.7), the response of the elderly subjects is heterogeneous. While 47% of the elderly subjects responded at about half the level of young controls, 15% responded at less than 20% the level and the remaining 38% responded comparably to young controls. Similar heterogeneity was observed in lymphokine production. However, there was no significant correlation between the level of proliferative response and production of either interleukin 2 (IL-2) or interferon gamma (IFN-g). In an effort to further explore the role of lymphokines in the decreased proliferative response of elderly subjects, various concentrations of exogenous IL-2 and/or IFN-gamma were added at the initiation of the mitogen stimulated cultures. Similar increases in both the level of response and the number of subjects demonstrating an increase was observed for both young and elderly subjects upon addition of either IL-2 or IFN-gamma. However, addition of a combination of IL-2 and IFN produced more pronounced effects in the elderly subjects. Approximately 1/3 of the elderly subjects who demonstrated decreased PHA-induced proliferation doubled their PHA induced proliferative response upon addition of a combination of lymphokines. The amounts of IL-2 and IFN-gamma required for this increase varied for each individual.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Heterogeneity of changes in lymphoproliferative ability with increasing age.

Although mean mitogen-induced lymphoproliferation decreases with increased age, the response of individual subjects demonstrates great heterogeneity. Results of this study clearly illustrate that individual variation is apparent not only in the level of proliferation, but also in the amount of interleukin-2 (IL-2) detectable after mitogen stimulation. Further, addition of exogenous IL-2 significantly increases proliferation in only about one third of elderly subjects. Data from inbred strains of rats housed under identical environmental conditions indicate that although genetic factors greatly influence both the level of proliferation and the rate of decline with age, variation occurs even within one inbred strain of rat.

Adult↗

Urinary excretion of Tamm-Horsfall protein in elderly women.

The incidence of urinary tract infection is higher in the geriatric population than in younger adults despite the exclusion of patients with known risk factors. Tamm-Horsfall protein, a renal glycoprotein excreted in urine, may constitute a natural defense mechanism against ascending urinary tract infection by binding mannose-sensitive fimbriated microorganisms. We hypothesized that the quantity of Tamm-Horsfall protein excreted is decreased in the elderly. Native aggregated Tamm-Horsfall protein was measured in urine samples from 24 young women (group 1, mean age 33 years) and 47 female nursing home patients (group 2, mean age 84 years) using enzyme-linked immunosorbent assay techniques. Another 16 elderly women (group 3, mean age 85 years) had active urinary tract infection. The aggregated Tamm-Horsfall protein was then disaggregated by dilution and quantified. Significant differences in mean urinary disaggregated Tamm-Horsfall protein concentrations were found between groups 1 (64.22 mg./l.) and 2 (35.07 mg./l.), and between groups 1 and 3 (34.71 mg./l.), respectively. In contrast, mean aggregated Tamm-Horsfall protein levels were significantly higher in group 2 (1.56 mg./l.) than in group 1 (0.92 mg./l.) or group 3 (0.97 mg./l.). Our studies show that urinary disaggregated Tamm-Horsfall protein concentration is decreased in the elderly, and that aggregated Tamm-Horsfall protein is increased compared to younger adults. The aggregated Tamm-Horsfall protein concentration is decreased in the elderly during episodes of urinary tract infection.

Adolescent↗

Special problems of urinary tract infection in the elderly.

Bacteriuria is much more common among elderly than among younger populations, and is most often asymptomatic. Asymptomatic bacteriuria in the elderly is a benign condition in the vast majority of cases and does not require therapy. When symptomatic lower UTI occurs, short-course (3-day) therapy with any of several agents is indicated, and is usually effective. Women with frequently recurrent symptomatic UTI may benefit from estrogen therapy. Fourteen days of therapy is indicated in patients with upper UTI. The typical signs and symptoms of pyelonephritis may be altered or absent in elderly patients.

Aged↗

Epidemiology of asymptomatic bacteriuria in elderly women.

We studied asymptomatic bacteriuria in elderly ambulatory women residents without indwelling catheters in self-contained apartment houses at the Philadelphia Geriatric Center (PGC), in the nursing home at PGC, and in several life-care communities (LCC). Subjects were studied every 6 months from January 1983 through January 1989, and since enrollment was continuous some participated in more surveys than others. PGC residents were middle class and lived either in a self care apartment house (CL) or nursing home (NH); LCC residents were middle or upper class. Antimicrobial therapy for asymptomatic bacteriuria was not given by the study team. The ages of the 865 women studied averaged 80.3, 82.8, and 83.3 years in LCC, CL, and NH, respectively. On each survey about 11% at LCC, 18% at CL, and 25% at NH sites had positive cultures. Turnover was high. The conversion rate from a negative to a positive culture was 5% at LCC, 11% at CL, and 8% at NH. The reversion rate from a positive to a negative culture was 33% at LCC, 34% at CL and 31% at NH (P greater than 0.05). Persistent infection with the same organism was uncommon. Infection risk was associated with residence, which was partially explained by a factor evaluating mobility, but was unrelated to age or scores evaluating activities of daily living or mental status. Besides mobility, other more complex factors play a role in the acquisition of infection.

Activities of Daily Living↗

Attitudes of elderly people about clinical research on aging.

This study determined the factors influencing participation of elderly people in research. It involved subjects who signed consent for a study and those who refused consent. Consenters had significantly more positive feelings about being used as a subject; giving urine; giving blood; having a physical examination; being interviewed; taking an IQ test; answering questions; being a subject to help others; finding out about problems and as a way to pass time; and telling an interviewer the truth. Reasons given for partaking in research were the personality of the interviewer, interest in the project, and benefits to subject or others.

Aged↗

Oral temafloxacin versus vancomycin for therapy of experimental endocarditis caused by methicillin-resistant Staphylococcus aureus.

We compared oral temafloxacin, a new fluoroquinolone agent, with vancomycin, each with and without rifampin, in the therapy of rats with aortic valve endocarditis caused by a clinical isolate of methicillin-resistant Staphylococcus aureus. The temafloxacin, vancomycin, and rifampin MICs and MBCs were 0.78 and 1.56, 1.56 and 3.13, and less than 0.024 and 0.78 microgram/ml, respectively. The animals were classified into the following six treatment groups: vancomycin (60 mg/kg) +/- rifampin (6 mg/kg) each intramuscularly every 12 h for 5 days; temafloxacin (100 mg/kg) orally +/- rifampin (6 mg/kg) intramuscularly every 12 h for 5 days; rifampin (6 mg/kg) intramuscularly every 12 h for 5 days; and untreated controls. All regimens with either vancomycin or temafloxacin resulted in improved survival over controls, but only temafloxacin regimens resulted in a significant reduction in bacterial counts in vegetations. These data support further investigation of the efficacy of temafloxacin in treating serious infections caused by methicillin-resistant S. aureus.

4-Quinolones↗

The role of T cell phenotypes in decreased lymphoproliferation of the elderly.

A possible mechanism of the decreased mitogen-induced lymphoproliferation of the elderly is a shift in the relative numbers of T lymphocyte subpopulations. Results from studies examining such changes have been conflicting. In an effort to resolve this conflict, alterations in T cell subsets in the peripheral blood of a large number of relatively healthy, elderly subjects (149; mean age 84.6) were evaluated. Although there were several differences in percentages of subpopulations between elderly and young subjects, no significant differences in the absolute numbers of lymphocytes, monocytes, or T cell subsets between the groups were observed. In addition, there was no correlation between mitogen-induced lymphoproliferation and T cell subsets. Since the decreased mitogen response could reflect a difference in the ability of one T cell subset to proliferate, the phenotype of the T cells after stimulation with PHA was determined. Although the elderly demonstrated a decreased number of all T cell subsets after PHA stimulation compared to young subjects, the most pronounced decrease was in CD8+ cells. Further, young individuals demonstrated a significant increase in the percentage of CD8+ cells (p less than 0.001) after 72 hr of culture with PHA; elderly subjects showed no change in the percentage of T cell subsets. Although both groups had an increase in interleukin 2 receptor (IL2R), transferrin receptor (TfR), and MHC class II Ag (HLA-DR) positive cells after PHA stimulation, the mean percentage of TfR+ cells was significantly greater in the young than in the elderly (p less than 0.05). This decreased expression of TfR+ cells in the elderly was reflected by a decreased percentage of CD8+ cells expressing TfR. In addition, the percentages of CD8+ cells, CD8+ cells expressing TfR, and CD8+ cells expressing IL2R after activation correlated with PHA-induced proliferation. These results suggest that the impaired lymphoproliferative ability of elderly cells is not related to the proportions of T cell subsets present in peripheral blood. Rather, there appears to be some defect in the ability of all T cells, but especially of the T suppressor/cytotoxic cells, of the elderly to respond to PHA manifested by a decreased expression of transferrin receptors.

Adult↗

DNA polymorphisms among Escherichia coli isolated from bacteriuric women.

Restriction fragment length polymorphism (RFLP) patterns, plasmid profiles, and antimicrobial susceptibility patterns of paired sequential Escherichia coli isolates from antibiotic-treated and untreated elderly women were analyzed. Isolates from 26 of 27 subjects who were treated successfully with antibiotics but became reinfected differed by RFLP analysis, whereas 10 of 12 subjects who failed treatment and 11 of 14 untreated subjects had paired isolates with identical RFLP banding patterns. Only 40 of the 53 pairs of isolates could be analyzed by plasmid profiles; 36 of these 40 were concordant with RFLP analysis. Antimicrobial susceptibility patterns showed poor concordance with RFLP analysis. This study demonstrates the utility of RFLP analysis and indicates that isolation of E. coli from elderly women after sterilization of the urinary tract usually results from introduction of a new strain; elderly women who fail antibiotic therapy or receive no therapy may remain persistently infected with the same E. coli strain.

Aged↗

The effect of stimulation of left atrial receptors on coronary blood flow in anaesthetized dogs.

1. To determine whether stimulation of atrial receptors reflexly affects coronary blood flow, experiments were performed in seven dogs anaesthetized with alpha-chloralose. The left upper and middle pulmonary vein-atrial junctions and atrial appendage were stretched by distension of small balloons. Coronary blood flow was measured using an electromagnetic flowmeter positioned around the origin of the left anterior descending or circumflex coronary artery. 2. Following prevention of the reflex increase in heart rate by atrial pacing or propranolol, distension of the small balloons was shown to result in a decrease in mean coronary blood flow. 3. Cooling of the cervical vagosympathetic nerve trunks to 9 degrees C abolished the response of a decrease in mean coronary blood flow to distension of the balloons. 4. The response of a decrease in mean coronary blood flow was abolished by bretylium tosylate. 5. It was shown that a decrease in mean coronary blood flow occurred in response to stimulation of left atrial receptors, and that this decrease was reflex in nature. This reflex response is likely to involve atrial receptors discharging into afferent myelinated vagal fibres, and the efferent limb involves cardiac sympathetic pathways.

Animals↗