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Biomedical subjects

L Kaiser

Publications and source records attributed to L Kaiser.

At least 19 recordsLinked to original sources
PubMed1995

Early and prolonged decrease of viremia in HIV-1-infected patients treated with didanosine.

Fourteen patients previously treated with zidovudine were monitored for laboratory parameters and clinical events during 1 year after introduction of didanosine (ddI) monotherapy. Proviral human immunodeficiency virus type 1 (HIV-1) copy numbers (cell-associated DNA) and concentration of free virions (viremia) were determined using a semiquantitative polymerase chain reaction (PCR). High levels of circulating virus were detected in all patients (range, 17 to 5,934 x 10(3)/ml of serum). Within 4 weeks of therapy, a decrease of viremia (60 to 98%) was observed in nine patients. After 1 year of treatment, eight of these nine patients still had decreased viremia when proviral HIV DNA was decreased or stable, and CD4+ lymphocytes were stable or higher in seven of these eight patients. Antiviral effect was more pronounced in the six patients with CD4+ > 100/mm3 at entry, five of them belonging to the subgroup of the seven responding patients as compared to two of eight patients with CD4+ < 100/mm3. Clinical events in this small group were not statistically correlated with virologic parameters; however, responding patients had a tendency to stabilize or gain weight. This study suggests that measurement of viremia deserves further study as a marker of antiviral efficacy and might predict, even at 4 weeks, the beneficial potential of ddI.

AIDS-Related Opportunistic Infections↗
PubMed1995

[Uveitis associated with rifabutin treatment. Apropos of 3 patients].

Disseminated Mycobacterium-avium complex (MAC) infection develops in most patients with AIDS. We report three cases of anterior uveitis with vitritis in AIDS patients treated by the combination of rifabutin, clarithromycin and ethambutol for MAC bacteremia. Uveitis secondary to the introduction of rifabutin treatment is suggested.

AIDS-Related Opportunistic Infections↗
PubMed1995

Foscarnet decreases human immunodeficiency virus RNA.

Foscarnet inhibits human immunodeficiency virus (HIV) replication in vitro and decreases p24 antigenemia in patients with cytomegalovirus (CMV) retinitis. To evaluate the effect of foscarnet on HIV replication, HIV RNA was quantitated in 17 patients before and during foscarnet therapy. Fifteen patients had CMV retinitis, 1 had CMV encephalitis, and 1 had intractable zoster. A decrease in HIV RNA was observed in 16 of 17 patients. Before the introduction of foscarnet, mean HIV RNA was 5.82 +/- 0.24 log RNA/mL and, after a median of 13 days of therapy, mean HIV RNA was 5.30 +/- 0.27 log RNA/mL (P < .001). Among patients with detectable p24 antigen at baseline, a significant decrease was observed (P = .017). This decrease in HIV RNA demonstrates that foscarnet is a potent antiretroviral drug.

AIDS-Related Opportunistic Infections↗
PubMed1995

Response of HIV RNA to didanosine as a predictive marker of survival.

OBJECTIVE: To evaluate whether early changes in viraemia in response to didanosine (ddI) predict death and occurrence of new AIDS-defining events. METHODS: Forty-three patients were followed during ddI treatment with sequential determinations of serum viraemia, mutations associated with drug resistance, CD4 counts and clinical evaluation. Patients were stratified into two groups of equal size, responders and nonresponders, using the median of individual changes in viraemia 1 month after initiation of ddI therapy. RESULTS: After 1 month of ddI, mean viraemia decreased by 0.35 log RNA copies/ml of serum (P < 0.001) in the population. A significant difference in survival (median, 14 and 35 months in nonresponders and responders, respectively; log rank, P = 0.004) and in the delay to the occurrence of new AIDS-defining events (median, 8 and 33 months in nonresponders and responders, respectively; log rank, P = 0.018) was observed. After stratification for presence of AIDS before starting ddI, viraemia response at 1 month remained predictive of both overall and AIDS-defining event-free survival (log rank, P = 0.0006 and P = 0.01). After a similar stratification for initial CD4, viraemia response still predicted overall survival (log rank, P = 0.009), but its predictive value for AIDS-defining event-free survival did not reach statistical significance (P = 0.12). High initial levels of HIV RNA, presence of mutation 215 or previous duration of zidovudine therapy were not predictive of survival. CONCLUSIONS: In patients treated with ddI, changes in viraemia at 1 month predict survival independently of initial AIDS diagnosis and initial CD4 counts.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Cyclooxygenase inhibitors depress norepinephrine constriction of rat abdominal, but not thoracic, aorta.

Experiments were done on aortic rings (thoracic and abdominal) from young and retired breeder Lewis and Sprague-Dawley male rats. Constriction responses to norepinephrine, 5-hydroxytryptamine (5-HT), and prostaglandin F2 alpha, were done +/- the cyclooxygenase blockers, indomethacin or mefenamic acid. Indomethacin significantly depressed norepinephrine constriction in abdominal (but not thoracic) aorta of all groups. In additional studies of abdominal aorta from Lewis retired breeders, indomethacin and mefenamic acid depressed norepinephrine (but not 5-HT or prostaglandin F2 alpha) construction. Furthermore, indomethacin depressed norepinephrine constriction in vessels denuded of endothelial cells. The thromboxane receptor antagonist SQ 29548 did not alter norepinephrine constriction. Thus, in rat abdominal aorta, norepinephrine constriction is mediated by a constrictor prostanoid of vascular smooth muscle origin that is not thromboxane A2.

Adrenergic alpha-Antagonists↗
PubMed1994

Dirofilaria immitis: heartworm products contract rat trachea in vitro.

Subtle decreases in racing performance have been noted in asymptomatic greyhounds with heartworm burdens insufficient to obstruct pulmonary outflow, suggesting that alternative mechanisms may be involved in the pathogenesis of canine heartworm disease. Endothelium-dependent relaxation is depressed in the in vivo femoral artery of heartworm-infected dogs, in the in vitro pulmonary artery from heartworm-infected dogs, and in the in vitro rat aorta exposed to heartworms, heartworm-conditioned medium, and serum from heartworm-infected dogs. These findings suggest that circulating filarial factors may play a role in the pathogenesis of heartworm infection. We examined the effect of Dirofilaria immitis, the canine heartworm, on acetylcholine-induced contraction of rat tracheal rings. In epithelium-intact rings, both heartworms and heartworm-conditioned medium increased acetylcholine-induced contraction. Pretreatment of the parasites with aspirin prevented the filarial-induced increase in acetylcholine-induced contraction, suggesting that parasite cyclooxygenase products are responsible for the effect. In addition, heartworms caused contraction in both epithelium-intact and denuded rings and this effect was markedly decreased by pretreatment of the worms with aspirin. Filarial cyclooxygenase metabolites may cause airway hyperreactivity and parasite-derived factors could play a role in the subtle changes in exercise performance seen in asymptomatic greyhounds with low worm burdens. Comparable mechanisms may be operating in other filarial diseases, including those that affect humans in tropical countries.

Acetylcholine↗
PubMed1994

Dirofilaria immitis: depression of endothelium-dependent relaxation of canine femoral artery seen in vivo does not persist in vitro.

In heartworm-infected dogs, circulating filarial factors appear to be responsible for the seasonal depression of endothelium-dependent responses seen in the in vivo femoral artery. The effect of heartworm infection on vascular responses of the femoral artery in vitro, when the vessel is not constantly exposed to circulating factors, is unknown. Experiments were designed to test the hypothesis that in vivo exposure to circulating filarial factors leads to changes in the magnitude and mechanism of endothelium-dependent relaxation that are demonstrable in vitro. Rings of femoral artery from heartworm-infected and noninfected control dogs were suspended in muscle baths, and dose-response relationships to endothelium-dependent (methacholine) and -independent (sodium nitroprusside) vasodilators were done. To determine the mechanism of relaxation, dose-response relationships were also done in the presence of an inhibitor of nitric oxide synthase (L-NAME), an inhibitor of guanylate cyclase (methylene blue), or an inhibitor of cyclooxygenase (mefenamic acid). Heartworm infection did not depress endothelium-dependent relaxation of the femoral artery in vitro. Furthermore, the mechanism of relaxation in heartworm and control femoral artery is identical. These data suggest that the effect of circulating filarial factors that alter the magnitude and mechanism of relaxation in systemic vessels in heartworm-infected dogs rapidly disappears in their absence. This results has important bearing on the dynamics of heartworm-induced pathophysiological changes during infection and could influence the nature and chronology of responses to therapy.

Animals↗
PubMed1994

Comparative pharmacokinetics and safety of ciprofloxacin 400 mg i.v. thrice daily versus 750 mg po twice daily.

Comparative pharmacokinetics of i.v. and oral ciprofloxacin was studied in 24 healthy male subjects given 400 mg i.v. tds or 750 mg po bd in a randomized, double-blind, placebo controlled, crossover fashion with at least a 10 day washout period. Blood and urine samples were obtained following the first (single dose) and last (steady state) dose in each treatment period. After single dosing and under steady state conditions, the calculated 24 h area under the serum concentration versus time curve, (AUC0-24) after 400 mg i.v. tds (AUC0-8 x 3) was equivalent to the AUC0-24 after 750 mg po bd (AUC0-12 x 2). Peak serum concentrations produced by the i.v. regimen were very similar to those observed after the 750 mg oral dose. The extent of accumulation was similar following either dosing regimen and was approximately 35%. Overall, the incidence of adverse effects (none of which was serious) was higher with the i.v. regimen than with the oral regimen, mainly due to injection site reaction, which was the most commonly reported adverse event.

Administration, Oral↗
PubMed1994

Critical care nurse practitioners: evolution of the advanced practice nursing role.

This literature review was done to explore the use of master's-prepared nurse practitioners to manage critically ill patients. Data-based, anecdotal, clinical, analytic, and position papers published over the past 10 years in the medical and nursing literature were reviewed. This article synthesizes findings on the use of nurse practitioners in clinical settings including primary and specialty care settings, describes favorable outcomes of advanced practice nurses, and identifies factors that must be addressed as these roles increase in use in critical care settings. Nurse practitioners' movement into critical care settings should be undertaken. Additional federal support to ensure the preparation of these practitioners in adequate numbers is needed. Attention to issues of direct reimbursement, salaries, impact of changing role boundaries, malpractice coverage, and prescription privileges must be addressed. Research programs to examine the effect of nurse practitioners in specialized care should continue.

Critical Care↗
PubMed1993

Adult bacterial nasopharyngitis: a clinical entity?

OBJECTIVE: To investigate bacterial nasopharyngitis as a cause of adult upper respiratory infection. DESIGN: Prospective case series. SETTING: Walk-in medical clinic of a university hospital. PATIENTS: 507 patients with cold or flu symptoms, sore throat, or recent cough; 21 control subjects without symptoms of upper respiratory infection. MEASUREMENTS AND MAIN RESULTS: After thorough history and physical examination, the patients underwent nasopharyngeal aspiration and throat culture. Nasopharyngeal specimens were cultured for both bacteria and viruses; antigens for influenza, parainfluenza, and respiratory syncytial virus were sought by enzyme-linked immunosorbent assay (ELISA); serum antibodies to viral respiratory pathogens were determined. Group A beta-hemolytic streptococci grew from the throat specimens of 39 of the 507 patients (8%) or 38 of 334 patients (11%) who had clinical diagnoses of pharyngitis. Thirty-three cases of influenza A, 20 cases of influenza B, and seven cases of parainfluenza infections were diagnosed. Bacteria were cultured from the nasopharyngeal secretions of 284 patients (56%). In contrast to pharyngeal culture, commensal mixed flora were rarely found in nasopharyngeal culture. Nasopharyngeal culture of bacteria usually considered to be respiratory pathogens was significantly associated with the presence of leukocytes. Streptococcus pneumoniae (odds ratio 6.0, 95% confidence interval 2.6-14.2), Moraxella catarrhalis (odds ratio 12.9, 95% confidence interval 3.1-79.5), and Hemophilus influenzae (odds ratio 3.0, 95% confidence interval 1.2-7.4) were all associated with the presence of leukocytes. In contrast, nasopharyngeal culture of coagulase-negative staphylococci, mixed flora, and the documentation of a viral infection were not associated with the presence of leukocytes. For none of 21 control subjects were "pathogenic" bacteria found. CONCLUSIONS: These data suggest that potentially pathogenic bacteria may have a causal role in adult nasopharyngitis, although further data are needed to confirm this hypothesis.

Adolescent↗
PubMed1993

Effect of serum from dogs infected with Dirofilaria immitis on endothelium-dependent relaxation of rat aorta in vitro.

Endothelium-dependent relaxation of canine femoral artery in vivo is depressed in dogs infected with Dirofilaria immitis (heartworms). In vitro, endothelium-dependent relaxation of aorta from rat is depressed in the presence of adult heartworms or heartworm-conditioned media. The depression of relaxation is attributable, in part, to a low molecular weight, biologically active product that is released by the adult parasites. Because heartworms reside in the right heart and pulmonary arteries, biologically active factors produced by the parasites could circulate and alter endothelial cell function. The hypothesis that filarial factors in serum from heartworm-infected dogs depress endothelium-dependent relaxation was tested. Rings of thoracic aorta from rats were constricted by use of norepinephrine, and cumulative dose-response relationships to methacholine and nitroglycerin were evaluated in the presence of serum from heartworm-infected dogs or serum from noninfected (control) dogs. Nitroglycerin relaxation was not different; however, methacholine relaxation was significantly depressed in rings exposed to serum from heartworm-infected dogs when compared with that of controls. These results supported the hypothesis suggested that circulating filarial factors have the potential to influence the behavior of any endothelial cell surface.

Acetylcholine↗
PubMed1992

Dirofilaria immitis: do filarial cyclooxygenase products depress endothelium-dependent relaxation in the in vitro rat aorta?

Endothelial cells modulate the function of their underlying smooth muscle. Thus, altered endothelial behavior could be important in the pathogenesis of vascular and lymphatic diseases, including human and animal filariasis. Endothelium-dependent relaxation is depressed in both in vivo canine femoral artery of dogs infected with Dirofilaria immitis and in vitro rat aorta exposed to adult D. immitis. The experiments reported here were designed to determine if filarial cyclooxygenase products could depress endothelium-dependent relaxation in vitro. Pretreatment of the parasites, but not the vascular ring, with either indomethacin or aspirin, prevented filarial-induced depression of relaxation. Analysis of heartworm-conditioned medium by gas chromatography--mass spectrometry revealed two peaks in the biologically active medium that were not present in the control. One peak had a retention time and chromatographic profile characteristic of derivatized PGD2 standard, and the other was not identified. Incubation of the vascular ring with PGD2 mimicked filarial-induced depression of endothelium-dependent relaxation at low, but not high, concentrations of acetylcholine. Thus, filarial PGD2 may be involved in altered endothelium-dependent relaxation seen in heartworm-infected dogs.

Acetylcholine↗
PubMed1992

Pharmacokinetic profiles of ciprofloxacin after single intravenous and oral doses.

Ciprofloxacin was administered to 12 healthy male volunteers at doses of 300 and 400 mg intravenously (i.v.) and 500 and 750 mg orally in a randomized, double-blind, single-dose, four-period crossover study. On each treatment day, each subject received both oral and i.v. formulations, one of which was a placebo. Blood and urine samples were obtained through 24 h postdose. By each dosing route, the pharmacokinetic profiles were dose proportional. The 400-mg i.v. dose was equivalent to the 500-mg oral dose with respect to the area under the concentration-time curve and was equivalent to the 750-mg oral dose with respect to the maximum concentration of ciprofloxacin in serum. The oral bioavailability was 78.0%. The steady-state volume of distribution averaged 178 liters, and the terminal half-life in serum after i.v. dosing was approximately 4.3 h. Renal clearance accounted for approximately 60% of total body clearance. No significant adverse events were associated with either route of administration.

Administration, Oral↗
PubMed1992

Injury in nonischemic lung after unilateral pulmonary ischemia with reperfusion.

We developed an in vivo intact canine model to study pulmonary ischemia-reperfusion (IR) injury. The surgical approach simulates that of unilateral lung transplantation but is free of technical difficulties and other factors related to lung preservation. Serial measurements of regional pulmonary blood flow (rPBF), extravascular density (EVD), and transcapillary protein flux were made with the quantitative imaging technique of positron emission tomography. Eleven experimental and six control animals were studied. After 2 h of warm ischemia followed by reperfusion, no significant change occurred in rPBF despite significantly increased EVD, which was greater on the ischemic than on the nonischemic side. Protein flux, measured as a rate constant, was also greater on the ischemic than on the nonischemic side (median 181 x 10(-4)/min, range 104-619, vs. median 90, range 33-132) immediately after reperfusion. Both sides were also significantly different from control values (median 37, range 21-57). On both sides, protein flux decreased over time and at 5 h after reperfusion was not different from that of controls. Data from the control animals showed that these findings in the experimental animals were not due to surgical technique, deterioration in the surgical preparation, or hyperperfusion of the nonischemic lung. Thus IR injury of one lung can lead to similar, but less severe, injury in the contralateral lung. Because injury in the nonischemic lung develops only after reperfusion of the ischemic lung, injury to the nonischemic lung is probably humorally mediated. The model is a useful and relevant method for studying the physiological consequences of pulmonary IR injury.

Animals↗
PubMed1992

Inflammation and oxygen free radical formation during pulmonary ischemia-reperfusion injury.

In a companion study, we showed that 2 h of warm unilateral lung ischemia followed by reperfusion resulted in bilateral tissue injury, indicated by increases in extravascular density (EVD) and permeability, measured as the pulmonary transcapillary escape rate (PTCER) for radiolabeled transferrin. EVD and PTCER measurements were obtained with the quantitative imaging technique of positron emission tomography (PET). In the current study, we evaluated this increase in EVD histologically and correlated EVD and PTCER with measurements of oxidant-reactive sulfhydryls (RSH) in plasma as a marker of oxygen free radical (OFR) formation. Histologically edema, leukocyte infiltration, and hemorrhage were all present on the ischemic side, but only after reperfusion, whereas only neutrophil infiltration was observed on the nonischemic side. Histology scores correlated with EVD (r = 0.81) and PTCER (r = 0.75), but permeability was abnormal at times even in the absence of neutrophil infiltration. Plasma RSH concentration from the ischemic lung decreased significantly (P less than 0.05) during pulmonary ischemia (i.e., before reperfusion) and returned to baseline on reperfusion. The degree of RSH oxidation did not correlate with the severity of injury as measured by PET or histology. Thus pulmonary ischemia-reperfusion injury is characterized by inflammation, hemorrhage, edema, and OFR formation. Injury occurred after reperfusion, not after ischemia alone. In addition, injury to the contralateral nonischemic lung suggests a neutrophil-independent circulating mediator of injury.

Animals↗
PubMed1992

Effects of increasing age on vascular responses of the in vivo femoral artery of adult beagles.

One of the problems associated with using random-source dogs to study in vivo vascular responses is their unknown background. Since aging is known to influence vascular responses, unknown variations in age could influence experimental results. The vast majority of aging studies examine arteries in vitro. This study was undertaken to determine if increasing age of adult beagles influences in vivo femoral artery responses to acetylcholine, norepinephrine, and nitroglycerin. Experiments were performed on three groups: young (3.2 years), middle aged (6 years), and old age (8.7 years). Femoral artery responses (change in diameter, mm) to topical application of increasing concentrations of vasoactive drugs were measured by sonomicrometry. Dose-response relationships to acetylcholine were not different between groups, except at the lowest concentration (-8 log M) where young dogs had enhanced relaxation responses. Constriction to norepinephrine and relaxation to nitroglycerin were not altered by age. Thus, in the in vivo canine femoral artery of adult beagle dogs, vascular responses are essentially unaffected by increasing age.

Acetylcholine↗