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R Lüthy

Publications and source records attributed to R Lüthy.

At least 37 records · Page 2Linked to original sources
PubMed1991

Secondary structure-based profiles: use of structure-conserving scoring tables in searching protein sequence databases for structural similarities.

The profile method, for detecting distantly related proteins by sequence comparison, has been extended to incorporate secondary structure information from known X-ray structures. The sequence of a known structure is aligned to sequences of other members of a given folding class. From the known structure, the secondary structure (alpha-helix, beta-strand or "other") is assigned to each position of the aligned sequences. As in the standard profile method, a position-dependent scoring table, termed a profile, is calculated from the aligned sequences. However, rather than using the standard Dayhoff mutation table in calculating the profile, we use distinct amino acid mutation tables for residues in alpha-helices, beta-strands or other secondary structures to calculate the profile. In addition, we also distinguish between internal and external residues. With this new secondary structure-based profile method, we created a profile for eight-stranded, antiparallel beta barrels of the insecticyanin folding class. It is based on the sequences of retinol-binding protein, insecticyanin and beta-lactoglobulin. Scanning the sequence database with this profile, it was possible to detect the sequence of avidin. The structure of streptavidin is known, and it appears to be distantly related to the antiparallel beta barrels. Also detected is the sequence of complement component C8, which we therefore predict to be a member of this folding class.

Amino Acid Sequence↗
PubMed1991

A method for the quantification of intracellular zidovudine nucleotides.

An assay to quantify the phosphorylation products of zidovudine (AZT) in peripheral blood mononuclear cells (PBMC) was developed. Extracts of PBMC were separated by high-performance liquid chromatography. Eluted AZT mono- (MP), di- (DP), and triphosphate (TP) were collected in separate portions. Treatment with alkaline phosphatase yielded equimolar amounts of AZT, which after solid-phase enrichment were assayed by radioimmunoassay. Detection limit was 0.1 pmol/10(6) PBMC for each nucleotide. Recoveries of 102%-118% were observed. AZT nucleotides were measured in samples from three patients receiving 250 mg of AZT every 12 h. Intracellular concentrations of AZT-MP after 1-2 h ranged from 0.9 to 1.4 pmol/10(6) PBMC and then declined to 0.3-1.1 pmol/10(6) PBMC after 4 h. AZT-DP and AZT-TP reached concentrations of 0.3-0.5 pmol/10(6) PBMC after 1-2 h and could not be detected after 4 h in any of the three patients. Duplicate determinations deviated by less than 20%.

Alkaline Phosphatase↗
PubMed1991

The efficacy and safety of zidovudine with or without acyclovir in the treatment of patients with AIDS-related complex. The European-Australian Collaborative Group.

Our objective was to evaluate the efficacy and safety of zidovudine (250 mg every 6 h) alone or in combination with acyclovir (800 mg every 6 h) as treatment for AIDS-related complex (ARC). A double-blind, controlled clinical trial of 6 months therapy was conducted at teaching hospital ambulatory clinics in eight European countries and Australia; 199 patients were studied. Time to development of AIDS-defining opportunistic infections (OI) and AIDS-associated neoplasms, survival, performance status, body weight and CD4+ cell counts were measured. During the study six (9%) zidovudine recipients, five (7%) combination recipients and 12 (18%) placebo recipients developed AIDS-defining OI; the probability of developing an OI was 0.23, 0.09 and 0.08 for the placebo, zidovudine and combination recipients, respectively. Four patients in the placebo group, three in the zidovudine group and one in the combination group died during the study. Patients receiving zidovudine with or without acyclovir had moderate increases in CD4+ cell counts compared with placebo recipients and serum HIV p24 antigen level decreased significantly in all those receiving zidovudine. Fourteen (21%) patients in the zidovudine group and 16 (24%) in the combination group experienced bone-marrow suppression compared with three (5%) placebo recipients. Red-cell transfusions were administered to 6, 19 and 13% of placebo, zidovudine and combination recipients, respectively. These data confirm the efficacy of zidovudine therapy after 4 weeks' treatment in the reduction of development of OI in patients with ARC and support the use of a maintenance dose of 250 mg zidovudine 6-hourly. Given the increased development of OI in the treated groups compared with placebo during the first 4 weeks of therapy, we cannot exclude an initial adverse effect of zidovudine and recommend caution in the use of a loading dose of zidovudine. At 6 months there was no apparent difference in efficacy between the combination of zidovudine and acyclovir compared with zidovudine alone. Moreover, the addition of high-dose acyclovir resulted in a minimal increase in the risk of toxicity.

AIDS-Related Complex↗
PubMed1991

Poor antibody response after tetanus and pneumococcal vaccination in immunocompromised, HIV-infected patients.

Ten patients with symptomatic HIV infection (six with ARC, four with AIDS) received tetanus and 23-valent pneumococcal vaccination. Anti-tetanus IgG and IgM, and anti-pneumococcal IgG against all 23 capsular types of the vaccine were measured on days 0, 11, 17, 30, and 90. Anti-pneumococcal IgG were simultaneously determined in two plasma pools of 100 healthy unimmunized blood donors and of 112 healthy adults who had previously received a 14-valent pneumococcal vaccination. Peak IgG responses to both vaccines were observed on day 17; thereafter, the antibody levels gradually fell again. Anti-tetanus IgG rose from 0.6 U/ml (geometric mean) to 2.0 U/ml on day 17. Anti-tetanus IgM remained unchanged. Anti-pneumococcal IgG increased only by 1.14-fold compared with pre-vaccination levels (geometric mean of IgG rises against all 23 polysaccharides in 10 patients), and exceeded the upper 95% limit of unvaccinated blood donors in only 30 out of 230 specimens. Pre-vaccination levels for pneumococcal type-specific IgG were significantly higher in HIV-infected patients compared with the pool of unimmunized healthy controls, possibly indicating a higher rate of previous pneumococcal infections in HIV-seropositive subjects. However, post-pneumococcal vaccination levels were significantly lower in HIV-infected patients than in the pool of healthy controls. The increase in anti-tetanus IgG significantly correlated with the level of CD4 lymphocytes and with in vitro lymphocyte proliferation by pokeweed mitogen (5 micrograms/ml) and phytohaemagglutinin (2.5 micrograms/ml), confirming a particularly low vaccination response in patients who were severely immunocompromised.

AIDS-Related Complex↗
PubMed1991

Interface-area-to-volume ratio of interstitial fluid in humans determined by pharmacokinetic analysis of netilmicin in small and large skin blisters.

Human pharmacokinetics of netilmicin during multiple dosing were studied in serum and in the fluid of skin blisters with two different ratios of interface area to fluid volume. The kinetics in the blisters followed the serum concentration-time curve with a delay but with a similar elimination half-life of 2.4 h. The kinetics in the 40-microliters blisters followed closely the theoretically calculated concentrations of the peripheral compartment of a two-compartment model. In contrast, the concentrations in the 120-microliter blisters increased less rapidly, lower peaks were achieved, and concentrations decreased with a significantly longer delay. A very similar area-specific flow or clearance rate of 1.6 microliters.h-1.mm-2 was calculated for the interface area between the serum compartment and either the small or large blisters. The observed rapid mass transfer between serum and blister fluid suggests similar oscillations of concentrations in serum and in small interstitial fluid compartments.

Adult↗
PubMed1991

Exploring the doctor-patient relationship reduces staff stress and enhances empathy when caring for AIDS patients.

At our AIDS outpatient clinic we presently care for more than 1,200 HIV-infected patients. All physicians in this unit have participated for 1 year in a case work group supervised by a liaison psychiatrist. The doctor-patient relationship, the assessment in the case work group and the ensuing influence on perception and behavior are demonstrated by 3 cases. Different issues challenge the doctor-patient relationship: the serious prognosis of predominantly young AIDS patients; isolation and stigmatization of patients; fear of contagion, and questions of confidentiality regarding contact tracing. Reflection upon the doctor-patient relationship improves communication skills and increases empathy towards AIDS patients.

Acquired Immunodeficiency Syndrome↗
PubMed1991

[Secondary prevention in HIV infection].

In HIV seropositive persons, secondary prophylaxis should prevent HIV-associated diseases, including opportunistic and other complications, and delay progression of HIV infection. Efforts to control transmission of secondary infections are of limited value, since these complications are mainly caused by endogenous opportunistic microorganisms. Vaccines are currently available for only a few of the pathogens that are potentially important in this clinical setting; they include influenza, Streptococcus pneumoniae and hepatitis B. However, antibody responses to these vaccines may be unsatisfactory in immunocompromised persons. Chemoprophylactic regimens have been devised primarily for prevention of Pneumocystis carinii pneumonia and tuberculosis. Recently, antiretroviral therapy with zidovudine has shown promise in delaying progression of AIDS in asymptomatic HIV seropositive individuals with impaired cellular immunity.

Communicable Disease Control↗
PubMed1990

Progression of HIV infection in misusers of injected drugs who stop injecting or follow a programme of maintenance treatment with methadone.

OBJECTIVE: To see whether misusers of injected drugs who stop injecting or switch to a programme of maintenance treatment with methadone have a reduced risk of progression of HIV infection when compared with a group of persistent misusers. DESIGN: Observational cohort study in HIV seropositive subjects with a current or past history of misusing injected drugs. SETTING: HIV outpatient clinic at the University Hospital of Zurich, Switzerland. PATIENTS: 297 Current and former parenteral drug misusers (median age 27) with asymptomatic HIV infection. During the observation period 80 subjects adhered to a programme of maintenance treatment with methadone, 124 continued with parenteral drug misuse, and 93 former misusers remained free of illicit drugs. No antiretroviral treatment was given during the study. MAIN OUTCOME MEASURES: Probability of progression of HIV infection from asymptomatic to symptomatic (Centers for Disease Control stage IV) as calculated by life table analysis and compared in the three groups of patients by means of a log rank test, and predictors of disease progression as analysed with a Cox proportional hazards regression model. RESULTS: The 297 patients were followed up for a median of 16 months. The median duration of injecting drug misuse before enrollment was 7.1 years. There were no significant differences among the three groups with respect to CD4+ counts at the beginning of the study (median 0.44 x 10(9)/l). Life table analysis showed a significantly lower probability of progression of HIV disease in both the methadone treated group and former drug misusers than in persistent injecting drug misusers. Multivariate regression analysis showed a relative risk of progression of the disease of 1.78 (95% confidence interval 1.20 to 2.67; p less than 0.01) in persistent injecting drug misusers, 0.48 (0.29 to 0.77; p less than 0.01) in the methadone treated group, and 0.66 (0.41 to 1.06; p = 0.085) in former drug misusers. CONCLUSIONS: Stopping the misuse of injected drugs slows the progression of HIV disease in infected subjects. Drug treatment programmes are effective in secondary prevention of HIV associated morbidity.

Adult↗
PubMed1990

[Extraintestinal strongyloidiasis in the acquired immunodeficiency syndrome].

A 41-year old man of Brazilian origin, suffering from AIDS for one year, fell ill with pyrexia of over 39 degrees C, dyspnoea, chest pain and deterioration in his general condition. At the same time he noted a discrete skin eruption, mainly on the upper limbs. Diarrhoea began later. A chest radiograph revealed bilateral infiltrates. The blood showed leucocytosis (11,000/microliters) with pronounced increase of eosinophil granulocytes (47.5%). Alkaline phosphatase was raised to 170 U/l. Suspicion of strongyloidiasis was confirmed by the discovery of numerous Strongyloides stercoralis larvae in the faeces. A few days after starting treatment with mebendazole, 400 mg daily, he felt better and the diarrhoea stopped. However, as the lung infiltrates remained unchanged and hilar lymph node enlargement now appeared, the dose of mebendazole was raised to 2500 mg daily. The abnormal findings then cleared up: Strongyloides stercoralis larvae ceased to be demonstrable and the patient gained 10 kg in weight.

Acquired Immunodeficiency Syndrome↗
PubMed1990

[Disseminated histoplasmosis as the first manifestation of HIV infection].

A 29-year-old man who had been abroad for several years (mainly Mexico) fell ill with fever (up to 39.8 degrees C), night sweats, weight loss of 10 kg in 6 months (height 181 cm, weight 50.5 kg) and abdominal pain. Computed tomography of the abdomen revealed many enlarged abdominal lymph nodes. Serological tests were positive for HIV antibodies. Fine-needle biopsy of one of the enlarged lymph nodes revealed numerous macrophages with round inclusions, typical for Histoplasma capsulatum. Disseminated histoplasmosis was confirmed by direct antigen demonstration in serum and urine. The patient's serious clinical condition clearly improved and lymph node enlargement regressed after starting specific i.v. treatment with amphotericin B (initially 20 mg/dl, then 50 mg/dl). Although complete cure of the histoplasmosis in connection with the HIV infection is not to be expected, the patient has remained without symptoms for four months on 50 mg weekly of amphotericin B i.v., later changed to imidazole derivatives (400 mg ketoconazole or 200 mg itraconazole, respectively.

Adult↗
PubMed1990

Compliance and laboratory data predict relapse rate of Pneumocystis carinii pneumonia during prophylaxis with aerosol pentamidine.

We evaluated 43 AIDS patients on prophylaxis with aerosol pentamidine (60 mg biweekly) after Pneumocystis carinii pneumonia (PCP). The effects of patients' inhalation compliance and of laboratory data during the initial PCP on subsequent PCP relapses were assessed. After a median of 8 months (range, 2-21.5 months) on pentamidine prophylaxis, 13 patients suffered a PCP relapse. Six of them had missed at least one inhalation within the last month before the relapse. Two of these six relapses were fatal. The relapse occurrence was significantly associated with the percentage of missed inhalations. Additional significant associations were found between relapses, low levels of T4 lymphocytes, and elevated serum lactate dehydrogenase during the initial PCP episode (29 patients). Mean levels of T4 lymphocytes were 27/mm3 and 47/mm3 in patients with and without subsequent relapses, mean levels of lactate dehydrogenase were 692 U/L and 605 U/L, respectively. Multivariate Cox regression did not reveal further differences between patients with and without relapses. The increased relapse risk associated with poor inhalation compliance stresses the need for appropriate guidance and motivation of the patients.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Profile analysis.

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Amino Acid Sequence↗
PubMed1990

Prognostic score for Pneumocystis carinii pneumonia.

Sixty episodes of Pneumocystis carinii pneumonia in 59 patients were evaluated for risk factors predicting fatal outcome within 14 days after bronchoscopy. We found significantly higher values for serum lactate dehydrogenase (p less than 0.001), alveolar-arterial oxygen difference (p less than 0.001) and percentage of bronchoalveolar lavage neutrophils (p less than 0.001) in patients dying within 14 days, but there was considerable overlap of these variables between the two groups. Using a score system combining the three parameters allowed however an excellent discrimination between the two groups.

Acquired Immunodeficiency Syndrome↗
PubMed1990

[HIV infections].

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Antiviral Agents↗