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Biomedical subjects

R Nuesch

Publications and source records attributed to R Nuesch.

10 recordsLinked to original sources

Effect of highly active antiretroviral therapy on hospitalization characteristics of HIV-infected patients.

In order to determine the impact that highly active antiretroviral therapy (HAART) has on inpatients with HIV infection, HIV-infected patients hospitalized from 1994 to 1999 at the Department of Internal Medicine, University of Basel, Switzerland, were investigated. During the observation period, 578 HIV-related hospitalizations occurred, and 502 charts from 262 different patients were available for evaluation. Analyses showed significant reductions in hospital mortality (from 13.2% to 6.5%) and length of stay for HIV-related admissions (from 16 to 11 days) in the post-HAART period, and the percentage of AIDS-related admissions decreased from 54.5% to 47.6%. However, the admission of HIV-infected patients to the intensive care unit increased from 6.3% to 11.8%, which could indicate that treating physicians have greater confidence in the outcome of HIV-infected patients due to better therapeutic options. Since the advent of HAART, the yearly number of admissions related to HIV dropped by 49% and HAART was administered often during hospital stay. By the end of the study period, death due to multiple HIV-associated diseases and wasting had disappeared.

Antiretroviral Therapy, Highly Active↗

Clustering of bloodstream infections during maggot debridement therapy using contaminated larvae of Protophormia terraenovae.

BACKGROUND: The treatment of human wounds with fly larvae is an ancient procedure recently reintroduced into medical practice under the term of biosurgery. The crucial technical problem of biosurgery is asepsis of the larvae. PATIENTS AND METHODS: Since February 1999, we conducted a prospective observational study on the use of maggot debridement therapy in the management of ulcers refractory to standard treatment. RESULTS: During the first 5 months we observed five bloodstream infections (four with Providencia stuartii and one with Candida albicans) in 24 patients (21%) treated with maggots. The blood isolates could be traced back to contaminated maggots. Accordingly, the disinfecting procedure of the maggots was optimized and the fly species was changed from Protophormia terraenovae to Phaenicia (Lucilia) sericata. With the new procedure, no case of sepsis occurred in 45 patients treated between January 2000 and December 2001 (p < 0.005). CONCLUSION: Despite promising benefits, maggot debridement therapy can be threatened by serious infectious complications. With an appropriate disinfecting procedure, maggots free of pathogens can be obtained. Provided the maggots have been effectively disinfected, their application on chronic ulcers seems to be safe.

Aged↗

Relation between insufficient response to antihypertensive treatment and poor compliance with treatment: a prospective case-control study.

OBJECTIVES: To prospectively compare compliance with treatment in patients with hypertension responsive to treatment versus patients with treatment resistant hypertension. DESIGN: Prospective case-control study. SETTING: Outpatient department in a large city hospital in Switzerland, providing primary, secondary, and tertiary care. PARTICIPANTS: 110 consecutive medical outpatients with hypertension and taking stable treatment with at least two antihypertensive drugs for at least four weeks. MAIN OUTCOME MEASURES: Treatment compliance assessed with MEMS devices; blood pressure determined by 12 hour daytime ambulatory monitoring (pressure <135/85 mm Hg in patients aged </=60 years and <155/90 mm Hg in patients aged >60 indicated hypertension responsive to treatment). RESULTS: Complete data were available for 103 patients, of whom 86 took >/=80% of their prescribed doses ("compliant") and 17 took <80% ("non-compliant"). Of the 49 patients with treatment resistant hypertension, 40 (82%) were compliant, while 46 (85%) of the 54 patients responsive to treatment were compliant. CONCLUSION: Non-compliance with treatment was not more prevalent in patients with treatment resistant hypertension than in treatment responsive patients.

Aged↗

Simultaneous occurrence of 2 HIV-related immunereconstitution diseases after initiation of highly active antiretroviral therapy.

The case of a 44-y-old woman with HIV infection and cytomegalovirus retinitis in whom antiretroviral therapy (HAART) revealed pulmonary cryptococcosis is presented. Pulmonary cryptococcosis occurred simultaneously with immune recovery uveitis after starting HAART, showing that complex clinical pictures may arise from immunreconstitution diseases.

AIDS-Related Opportunistic Infections↗

Nutritional supplements combined with dietary counselling diminish whole body protein catabolism in HIV-infected patients.

BACKGROUND: Weight loss and protein malnutrition are frequent complications in HIV-infected patients. The effect of an oral nutritional supplement combined with nutritional counselling on whole body protein metabolism was assessed. MATERIALS AND METHODS: HIV-infected individuals with a body mass index < 21 kg m-2 or CD4-T cells < 500 micro L-1 in stable clinical condition were randomly allocated to [1] receive either oral nutritional supplements (containing 2510 kJ, complete macro- and micronutrients) and dietary counselling (n = 8), or [2] identical monitoring but no supplements or specific nutritional advice (controls, n = 7). Whole body leucine kinetics and leucine oxidation rate were determined by [1-13C]-leucine infusions and lean and fat mass were measured before and 12 weeks after intervention. RESULTS: Leucine oxidation (protein catabolism) decreased in the group receiving nutritional intervention from 0.33 +/- 0.02 to 0.26 +/- 0.02 micromol kg-1 min-1 after 12 weeks (P < 0.05; P < 0.05 vs. control group) but remained unchanged in the control group. Whole body leucine flux showed a tendency to decrease in the intervention group from 1.92 +/- 0.19 to 1.73 +/- 0.14 micromol kg-1 min-1 (P = 0.07) and remained unchanged in the control group (2.21 +/- 0.16 and 2.27 +/- 0.14 micromol kg-1 min-1, respectively). Lean body mass determined by bioelectrical impedance analysis increased in the nutritional intervention group from 84 +/- 2 to 86 +/- 2 per cent (P < 0.05) and fat mass decreased from 17 +/- 2 to 14 +/- 2 per cent (P < 0.05) of total body weight whereas neither mass changed in the control group. Nutritional intervention had no significant effect on lymphocyte CD4 counts, on plasma TNFR 55, TNFR 75 and ILR 2 concentrations and on quality of life. CONCLUSIONS: The data demonstrate an anticatabolic effect of nutritional supplements combined with dietary counselling in HIV-infected subjects. They suggest that diminished whole body protein catabolism resulted in a change of body composition (increased lean mass, decreased fat mass).

Body Composition↗

A comparison of efficacy and specificity of three NK depleting antibodies.

This study compares in vivo efficacy and specificity of the three NK cell depleting antibodies anti-asialo GM1, anti-NK 1.1 and the recently described TM beta 1, which is directed against the interleukin-2 receptor beta chain. All three antibodies are equally efficacious as assessed by abolishing NK mediated cytolytic activity induced by a high dose virus infection or Poly IC against YAC-1 targets. Similarly, the generation of virus-specific cytotoxic T cells (CTL) was unimpaired after NK depletion in two different virus infections. However, if mice are treated with the antibodies several days after virus infection, when strong CTL responses have already been generated, anti-asialo GM1 and-to a lesser extent-also TM beta 1 have a significant effect on CTL activity. Only after treatment with anti-NK 1.1 antibody, CTL activity was not significantly impaired. We conclude, that of the NK depleting antibodies currently available, anti-NK 1.1 allows the best differentiation of activated CTL and NK cells in vivo.

Animals↗

Effects of cilazapril on vascular structure and function in essential hypertension.

Hypertension is associated with an altered design of resistance vessels and decreased endothelium-dependent vasodilator response to acetylcholine. A role of angiotensin II in both defects is suggested by animal experiments in which angiotensin-converting enzyme inhibition reverted structural and functional changes. We investigated the effects of 20 weeks of therapy with the angiotensin-converting enzyme inhibitor cilazapril (5 mg twice daily) on the endothelium-dependent response to brachial artery infusions of acetylcholine and the endothelium-independent vascular relaxation after sodium nitroprusside in 22 subjects with mild to moderate essential hypertension. In addition, we measured minimal forearm vascular resistance (ratio of mean arterial pressure and forearm blood flow after heating, ischemia, and ischemic exercise) as an indirect estimate of vascular structure. Cilazapril decreased blood pressure (151 +/- 14/99 +/- 7 mm Hg during placebo to 138 +/- 17/89 +/- 8 mm Hg after cilazapril treatment, P<.01) and baseline (42.2 +/- 12.6 to 37.1 +/- 10.6 U, P<.05) and minimal (3.0 +/- 1.1 to 2.4 +/- 0.7 U, 15.9 +/- 20.2%; P<.05) forearm vascular resistances. The change in minimal forearm vascular resistance was unrelated to age, duration of hypertension, or changes in blood pressure. Sodium nitroprusside increased forearm blood flow from 2.6 +/- 1.0 to 11.4 +/- 5.9 mL/min per 100 mL and acetylcholine to 21.5 +/- 17.8. Both responses did not change after cilazapril. The data provide indirect evidence that cilazapril therapy may improve vascular structure in human hypertension. The lack of relationship between vascular and blood pressure changes would be compatible with experimental evidence supporting a role for angiotensin II in the development and regression of vascular changes, but this needs further study. Therapy with cilazapril for 20 weeks, like other antihypertensive therapy, does not seem to influence endothelial vasodilator function in humans to a significant degree.

Adult↗

The Fas receptor in HIV infection: expression on peripheral blood lymphocytes and role in the depletion of T cells.

OBJECTIVE: To analyse the role of the apoptosis-inducing Fas receptor in the depletion of CD4+ and CD8+ T cells in HIV-infected individuals. METHODS: Peripheral blood lymphocytes (PBL) obtained from HIV-infected subjects of all 1993 Centers for Disease Control and Prevention (CDC) stages and from non-infected controls were examined. A two-colour cytofluorometry was employed using monoclonal antibodies against Fas receptor (CD95) in combination with the surface markers CD4, CD8, CD28, CD26 and CD45RO. CD4+ and CD8+ T-cell-enriched PBL were used as target cells to assess their susceptibility to lysis by CD4+ cytotoxic T lymphocytes (CTL) which kill via the Fas pathway. RESULTS: Fas+PBL are more elevated in HIV-infected individuals than in HIV-negative controls and increase significantly from CDC stages A to C. Whereas Fas+CD4+ and Fas-CD4+ T-cell populations decline in parallel with the progression of HIV infection, the Fas+CD8+, but not of the Fas-CD8+ fraction, significantly increases. The Fas+CD8+ lymphocytes are susceptible to Fas-mediated lysis as they are efficiently killed by Fas-ligand+CD4+CTL. CONCLUSION: The Fas receptor may contribute, but not as a unique cause, to the decline of CD4+ T cells in HIV-infected individuals. This and the significant increase of the number of Fas+ CD8+ T cells indicates that Fas-mediated immune regulation is disturbed.

Animals↗

Effects of angiotensin converting enzyme inhibition on endothelial vasodilator function in primary human hypertension.

Hypertension in animal models and in humans is associated with a decreased vasodilator response to acetylcholine which causes vascular relaxation by release of endothelium-derived relaxing factor from the endothelium. Since lowering of blood pressure, particularly with angiotensin converting enzyme inhibitors, improved the response to acetylcholine we investigated the effects of brachial artery infusions of ascending dosages of acetylcholine on forearm blood flow before and after 5 months of therapy with the angiotensin converting enzyme inhibitor, cilazapril, in 10 patients with mild to moderate primary hypertension. Cilazapril decreased blood pressure from 150.8 +/- 14.4/98.9 +/- 4.3 mmHg during placebo to 138.8 +/- 15.6/88.6 +/- 8.9 mmHg (P < 0.01). Brachial artery acetylcholine infusions increased forearm blood flow from 2.95 +/- 1.5 to a maximum of 22.8 +/- 11.5 ml.min-1.100 ml-1 forearm tissue and decreased forearm vascular resistance from 48.1 +/- 34.1 to 6.9 +/- 6.9 units before cilazapril. This response did not change after cilazapril therapy. Our findings in patients with primary hypertension, therefore, do not support the concept that angiotensin converting enzyme inhibition influences endothelium-dependent vascular relaxation to acetylcholine to a significant degree. Whether this lack of effect on endothelial vasodilator function is specific for the vascular bed chosen for study or whether it represents a fundamental difference between animal models and human hypertension remains an important issue to be clarified.

Acetylcholine↗