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Biomedical subjects

R Lüthy

Publications and source records attributed to R Lüthy.

At least 37 records · Page 2Linked to original sources
PubMed1997

[Cervical lymphadenitis in an immunocompetent patient: Mycobacterium gordonae as the cause?].

HISTORY AND FINDINGS: A 76-year-old man went to an ENT outpatient clinic because of stabbing pain in the left throat and difficult swallowing. He was found to have tonsillitis on the left and cervical lymphadenitis. The symptoms regressed on treatment with amoxycillin and clavulanic acid, but the cervical lymphadenitis persisted. Fine-needle biopsy of the cervical swelling was not diagnostic. Computed tomography of the neck showed an encapsulated liquid space-occupying lesion with infiltration of surrounding soft tissues. TREATMENT AND COURSE: The cervical lymph-node mass was excised and histologically found to contain epithelioid granulomas with a few giant cells and scattered centrally caseous necroses. Tuberculostatic treatment was started; drainage fluid from the wound grew acid-fast bacilli, identified by gene probe as Mycobacterium gordonae. CONCLUSIONS: Mycobacterium gordonae is ubiquitous in the environment and is being identified ever more frequently in microbiological laboratories, usually as contaminant. It rarely causes infections of soft tissues and the lungs or systemically.

Aged↗
PubMed1997

Preparation for emergency relief after biological warfare.

Upon invitation by the World Health Organization during the Gulf War, a task force "Scorpio" independent from the nations involved in the armed conflict was formed whose task was to determine whether, which and to what extent biological warfare agents had been used. risk assessment concluded that anthrax and Clostridium botulinum toxin were the major risks. The 21 civilian experts had rapidly to decide on the doctrine of operation, to assemble material which could be used and to be immunized or protected otherwise against the potential risks. Biological warfare agents may be used anywhere any time, be it by terrorists or during open or clandestine hostilities. The general population cannot rely on the military to take care of civilian relief, thus international and national organizations may wish to establish similar task forces basing on the "Scorpio" model on a national or regional basis.

Anthrax↗
PubMed1997

The diversity of antigen-specific TCR repertoires reflects the relative complexity of epitopes recognized.

Antigen-selected T cell receptor (TCR) repertoires vary in complexity from very limited to extremely diverse. We have previously characterized two different CD8 T cell responses, which are restricted by the same mouse major histocompatibility complex (MHC) class I molecule, H-2 Kd. The TCR repertoire in the response against a determinant from Plasmodium berghei circumsporozoite protein (PbCS; region 252-260) is very diverse, whereas TCRs expressed by clones specific for a determinant in region 170-179 of HLA-CW3 (human) MHC class I molecule show relatively limited structural diversity. We had already demonstrated that cytolytic T lymphocyte (CTL) clones specific for the PbCS peptide display diverse patterns of antigen recognition when tested with a series of single Ala-substituted PbCS peptides or mutant. H-2 Kd molecules. We now show that CW3-specific CTL clones display much less diverse patterns of recognition. Our earlier functional studies with synthetic peptide variants suggested that the optimal peptides recognized were 9 (or 8) residues long for PbCS and 10 residues long for CW3. We now present more direct evidence that the natural CW3 ligand is indeed a 10-mer. Our functional data together with molecular modeling suggest that the limited TCR repertoire selected during the CW3 response is not due to a paucity of available epitopes displayed at the surface of the CW3 peptide/Kd complex. We discuss other factors, such as the expression of similar self MHC peptide sequences, that might be involved in trimming this TCR repertoire.

Animals↗
PubMed1997

Exchange blood transfusion in severe falciparum malaria: retrospective evaluation of 61 patients treated with, compared to 63 patients treated without, exchange transfusion.

The rationale for exchange blood transfusion (ET) in severe falciparum malaria is threefold: reduction of parasitaemia, reduction of presumptive 'toxic' factors, and improvement of the rheological quality of the blood. We evaluated the records of 61 patients treated with ET to describe the present status of malaria treatment in Germany, Austria and Switzerland and to assess the efficacy of ET. Clinical data of 61 patients treated with ET were compared to data of 63 patients treated in 2 hospitals where ETs were generally not performed. We found that exchange transfusion is applied according to the clinician's subjective impression rather than strict guidelines. Logistic regression analysis adjusting for the differences in clinical parameters between patients treated with or without ET did not identify treatment as a prognostic indicator (odds ratio for relative risk of death with ET: 1.3; 95% CI: 0.4-4.9). Exchange transfusion did not significantly improve the unfavourable prognosis in cases of severe falciparum malaria. However, failure to reach statistical significance may be due to the retrospective design of the study and therefore non-systematic approach.

Adult↗
PubMed1997

Simple monitoring of antiretroviral therapy with a signal-amplification-boosted HIV-1 p24 antigen assay with heat-denatured plasma.

OBJECTIVE: Virus load determination has become indispensable for the management of HIV patients, but depends on expensive assays of a low throughput. We evaluated whether a highly improved HIV-1 p24 antigen detection procedure which involves heat-mediated immune complex dissociation and signal-amplification-boosted enzyme-linked immunosorbent assay (ELISA) was suitable for antiretroviral treatment monitoring. DESIGN AND METHODS: Virus load in plasma was determined for 127 plasma samples taken at 0, 2, 6, 12, 18, 24, 30 and 36 weeks from 23 patients with CD4+ T cells < 50 x 10(6)/l who received indinavir 800 mg three times daily in addition to prior antiretroviral treatment. Tests included polymerase chain reaction (PCR) for viral RNA, measured prospectively with the Roche Amplicor kit, and retrospective batch testing of heat-denatured samples for p24 antigen by the DuPont HIV-1 p24 Core Profile ELISA linked with a tyramide signal amplification step. Particle-associated reverse transcriptase (RT) by the product-enhanced RT (PERT) assay was determined as an independent third-opinion viral load marker. RESULTS: p24 antigen was detected as sensitively as viral RNA. Overall detection during a median observation time of 25 weeks (range, 0-39) amounted to 75.6% for antigen and 73.6% for RNA. The antigen detection limit was 0.2 pg/ml. Antigen was detectable in all 23 baseline samples, whereas RNA was undetectable in one. Antigen and RNA levels in 79 samples positive for both markers correlated with r = 0.714 (P < 0.0001). Average changes in levels of p24 antigen and RNA at eight timepoints correlated with r = 0.982 (P < 0.0001). In individual patients, the two parameters behaved similarly, and in certain cases virtually identically. RT activity was measurable in all samples. CONCLUSIONS: The performance of this antigen detection procedure is comparable to RNA PCR, thus providing a simple, high throughput alternative in monitoring the efficacy of antiretroviral treatment.

Adult↗
PubMed1997

Are immunological markers, social and personal resources, or a complaint-free state predictors of progression among HIV-infected patients?

Predictors of disease progression were studied in 89 asymptomatic HIV-infected patients who were prospectively evaluated for psychosocial variables and the development of clinical symptoms over a period of 2 years. The subjects were assessed for symptoms, laboratory measures, demographic variables, social and personal resources, mental status, alcohol, nicotine and drug use, sexual activity and risk behaviour, and sexually transmitted diseases. After 1 year, 17% of the patients had developed HIV-associated symptoms (symptomatic disease or AIDS), and after 2 years, 32% had developed symptoms or had died. In the multivariate analyses, the baseline CD4 count was the only significant predictor of disease progression during both observation periods. Psychosocial measures did not predict the progression of HIV infection.

Adaptation, Psychological↗
PubMed1997

HIV-associated primary pulmonary hypertension. A case control study. Swiss HIV Cohort Study.

To assess the clinical and echocardiographic time course, prognosis, and possible etiology of HIV-associated primary pulmonary hypertension (PPH), we prospectively followed all 19 patients in whom PPH was diagnosed in our centers. Women (12 cases) and injecting drug use (16 cases) predominated; the median CD4 lymphocytes count was 83/microliter (range, 1 to 740). Matched control subjects without PPH were identified within the Swiss HIV Cohort Study. Frozen serum samples of both groups were then reanalyzed for autoimmune parameters, neopterin, beta-2-microglobulin, and thyroid-stimulating hormone. The median follow up of the patients was 1.3 yr. Follow-up Doppler echocardiography was available in 13 patients. The RVSP-RAP pressure gradient decreased by 3.2 mm Hg for those six patients who received antiretroviral treatment but increased by 19.0 mm Hg for untreated patients (p = 0.026). PPH was the cause of eight of 17 deaths. The probability of surviving was significantly decreased in patients with PPH in comparison with the control subjects; the median survival was 1.3 versus 2.6 yr (p < 0.05). Patients with PPH had significantly higher anticardiolipin IgM, anti SS-B, and neopterin, but all other laboratory values did not differ between cases and control subjects. In conclusion, HIV-associated PPH contributed significantly to mortality. Antiretroviral treatment may exert a beneficial effect on the pressure gradient. A possible role of an autoimmune phenomenon in the pathogenesis could not be substantiated.

Adult↗
PubMed1996

[Mycobacterium haemophilum infection in a patient with AIDS].

HISTORY AND FINDINGS: A 35-year-old HIV-infected man with a CD4 cell count of 100/microliter who had returned from a holiday in Spain presented with fever, chronic diarrhoea, cough, oral ulcers, subcutaneous nodules of about 1 cm in diameter and crusted skin ulcers of about 2 cm in diameter at his right arm, both wrists and buttocks. INVESTIGATIONS: Microscopic examination and culture of smears of a skin ulcer revealed acid-fast bacteria. Mycobacterial cultures of blood, sputum, urine and stool remained sterile. TREATMENT AND COURSE: Before the microorganisms were identified culturally, atypical mycobacteriosis was assumed and treatment with rifampicin, ethambutol, isoniazid and clarithromycin was started. Mycobacterium haemophilum was identified by using molecular biological techniques. Within 3 weeks the patient became afebrile and the skin ulcers healed completely. After a 7-week course, the treatment had to be stopped, and one month later painful subcutaneous nodules developed again at his arms and legs. A relapse of Mycobacterium haemophilum infection was confirmed by culture of a fine needle aspirate of a nodule. The same treatment was restarted and the nodules disappeared. CONCLUSIONS: Mycobacterium haemophilum, first identified in 1978, is an emerging pathogen in immunocompromised patients. Clinical manifestations usually are skin ulcers, subcutaneous nodules and subcutaneous abscesses, and less frequently, systemic infection. Treatment options of this life threatening disease have yet to be defined but therapeutic response to tuberculostatic combination therapy has been observed. Since Mycobacterium haemophilum is a fastidious organism, special laboratory methods are required for cultivation as well as for identification.

AIDS-Related Opportunistic Infections↗
PubMed1996

[Intestinal cryptosporidiosis in HIV infection: clinical features, course and therapy].

OBJECTIVE: To determine retrospectively the clinical features and course of HIV-associated intestinal Cryptosporidium infection and its response to paromomycin. PATIENTS AND METHODS: Case notes of all patients treated for cryptosporidiosis over a two-year period at an HIV out-patient clinic were analysed (26 men, four women; median CD4-lymphocyte count: 20/microliter). Median follow-up time was 6(1-22) months. RESULTS: 15 patients had persistent diarrhoea, two remained asymptomatic, seven had a remission and in five the disease took a fulminant course with severe diarrhoea ending in death within 4 months. 15 of the patients died during the period of observation, eight of them of cryptosporidiosis-associated cachexia. Mean survival time was about one year. Eight patients had multiple intestinal infections at the time the diagnosis was made and seven developed them later, which correlated with the poorer survival chances. Four patients had proven and 13 probably cryptosporidiosis-associated involvement of the biliary tract, but this did not affect the survival chances. 21 of 28 patients with diarrhoea were treated with paromomycin. In 13 of them there was for a time complete or partial response to treatment, but no response in eight. Those who responded well or partially to paromomycin had a significantly better survival chance than those without response. There was no correlation between the severity of immunosuppression and the severity of the cryptosporidiosis-associated diarrhoea, the response to paromomycin and the worse survival chance in the presence of multiple intestinal infections. CONCLUSIONS: The reasons for the different courses taken by HIV-associated cryptosporidiosis and the different therapeutic responses remain unclear. There is no known causal treatment, but 60% of patients improved temporarily on paromomycin.

Adult↗
PubMed1996

Epidemiology of AIDS-related Kaposi's sarcoma in Europe over 10 years. AIDS in Europe Study Group.

OBJECTIVES: To determine the incidence and risk factors associated with Kaposi's sarcoma (KS) occurrence as an AIDS-defining condition or after the diagnosis of AIDS. DESIGN: Multicentre retrospective cohort study of AIDS in Europe database from 52 clinical centres in 17 European countries. METHODS: Patients' charts (n = 6546) were reviewed and collected in the database of the AIDS in Europe Study Group from 1979 to 1989. At the time of AIDS diagnosis 1394 patients had KS, whereas an additional 525 others developed KS after AIDS diagnosis. Univariate analysis and development of multivariate models determined factors associated with KS occurrence. RESULTS: Frequency of KS as an AIDS-defining condition significantly declined over time (P < 0.0001). In our cohort of patients, homo-/bisexual men from central Europe with CD4 cell counts > 150 x 10(6)/l were statistically more likely to develop KS at the time of AIDS diagnosis (P < 0.0001). For patients with an AIDS diagnosis other than KS, the probability of developing KS during the follow-up was 10 and 24% after 12 and 36 months, respectively. Variables significantly associated with a further KS development were transmission group, central European residence, previous herpes simplex infection other than ulcers, and low CD4 cells (< 150 x 10(6)/l). Previous zidovudine therapy had no influence on KS appearance. For patients who developed KS subsequent to AIDS diagnosis, there was no significant decline of the incidence over the 10-year time period. CONCLUSIONS: This large cohort study clearly shows that demographic data such as sex, transmission group and region of Europe have a major influence on KS development. It also suggests that KS as an AIDS-defining disease occurs earlier in the course of the chronic HIV infection than other opportunistic diseases. Reasons for geographical variations and its declining frequency as an initial AIDS diagnosis remain undetermined.

AIDS-Related Opportunistic Infections↗
PubMed1996

Heat-mediated immune complex dissociation and enzyme-linked immunosorbent assay signal amplification render p24 antigen detection in plasma as sensitive as HIV-1 RNA detection by polymerase chain reaction.

OBJECTIVE: To compare heat denaturation and acidification as immune complex dissociation (ICD) methods in adult HIV-1 infection and to increase the sensitivity by a signal-amplification-boosted HIV-1 p24 antigen enzyme-linked immunosorbent assay (ELISA). DESIGN: Prospective and retrospective blinded study of paired serum and plasma samples from 245 patients (112 of class A, 66 of B, 67 of C of the Centers for Disease Control and Prevention 1993 classification). METHODS: Plasma and sera were prospectively tested for antigen by ELISA using native, acidified, or heat-denatured material. Retrospective tests included batch analysis of heat-denatured samples for antigen by the signal-amplification-boosted ELISA and for viral RNA. RESULTS: With serum, native antigen was reactive in 26.5%. Acidification increased the rate to 53.1% (P < or = 0.0001), but was inefficient at a CD4+ count > or = 500 x 10(6)/l. Heat denaturation further elevated the rate to 67.8% (P < or = 0.0007) and the use of plasma to 78.0% (P < or = 0.008). The boosted ELISA, performed with plasma samples diluted 1 :6, which eliminated the problem of heat-induced sample coagulation, was confirmed positive in 89.5% of serum and 97.8% of plasma samples. RNA was detected in 95.7%. CONCLUSION: Heat-mediated ICD combined with a signal-amplification-boosted ELISA detects HIV-1 expression as sensitively as a polymerase chain reaction kit for viral RNA, but at only a fraction of the cost. The procedure uses a 50 microliters plasma sample and should be fully automatable.

Adult↗
PubMed1995

[Intensive care aspects in severe tropical malaria: clinical aspects, therapy and prognostic factors].

In a retrospective study we analyzed the clinical and blood chemical data of 12 patients with severe tropical malaria in the intensive care units of the University Hospital Zurich and the Stadtspital Triemli, Zurich, between 1991 and 1994. None of the 12 patients had been exposed to malaria before or had taken drugs for chemoprophylaxis. 7 patients survived, 5 died from complications of malaria. According to the criteria of severe tropical malaria defined by the WHO, the following pathological clinical and blood chemical parameters were noted on admission: cerebral coma (2/12); blood hemoglobin < 5 g/dl (0/12), < 8 g/dl (2/12); serum creatinine > 265 mumol/l (3/12); blood glucose < 2.2 mmol/l (0.12); circulatory collapse/shock (0/12); bleeding/signs of disseminated intravascular coagulation in laboratory tests (4/12); acidosis with pH < 7.25 (1/12). Further signs of severe tropical malaria were: hyperparasitemia > 5% (9/12); qualitative and quantitative disturbances of consciousness (6/12); thrombocytopenia < 30 x 10(9)/l (9/12); hyponatremia 125-135 mmol/l (9/12), < 125 mmol/l (2/12); rhabdomyolysis with creatine kinase > 1000 U/l (4/12). The basic treatment consisted of parenteral quinine hydrochloride in all patients; doxycycline was added in 8 cases, clindamycin in 3. Adjuvant therapy with desferrioxamin was given in 3 cases. 6 patients had exchange transfusions. Parasitemia cleared in all patients within 5 to 6 days. Later in the course, 5 patients developed acute respiratory distress syndrome, 6 required hemofiltration due to oliguria, and one became comatose.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Nephrotoxicity, high frequency ototoxicity, efficacy and serum kinetics of once versus thrice daily dosing of netilmicin in patients with serious infections.

The effect of dosing regimen on nephrotoxicity, high frequency ototoxicity, efficacy and serum kinetics was studied in a prospective, randomised clinical study. Therapy was started with total daily doses of 6 mg/kg given once (od) or thrice (tid) daily to 56 and 57 patients, respectively. Subsequent doses were adjusted according to serum levels. No major differences in toxicity or efficacy were noticed between od and tid regimens: clinical failures occurred in two and two patients, four and five patients suffered from a decrease of > or = 20 dB at least unilaterally at one frequency between 8 and 18 kHz, six and seven patients had a > 25 mumol/L or > 25% increase in serum creatinine, respectively. Serum creatinine or creatinine clearance did not change significantly during either therapy. Major differences between the two study groups were limited to pharmacokinetic parameters. Od dosing resulted in higher peak (mean of 21.6 vs 7.2 mg/L) and lower trough levels (0.5 vs 1.4 mg/L). Half-lives of netilmicin determined between 1 and 8 h increased significantly during therapy with tid (from a mean of 2.75 to a mean of 3.33 h, P < 0.01) but not significantly with od (rise from 2.8 to 3.03 h). Much longer half-lives were determined between 8 and 24 h in the od group (mean of 5.7 h, P < 0.01). In conclusion, only minimal differences in toxicity and efficacy were observed. Their clinical relevance appears to be minimal.

Adolescent↗
PubMed1995

Monitoring of co-trimoxazole concentrations in serum during treatment of pneumocystis carinii pneumonia.

The purpose of this prospective randomized open trial was to investigate the impact of monitoring concentrations in serum on the efficacy and side effects of high-dose co-trimoxazole therapy. Forty consecutive patients with microscopically confirmed Pneumocystis carinii pneumonia were enrolled. Therapy was started with 5 and 25 mg of trimethoprim and sulfamethoxazole, respectively, per kg of body weight given every 6 h for 2 days and continued every 8 h either with (group A) or without (group B) monitoring and dose adjustments according to sulfamethoxazole levels in serum (target, 150 to 200 micrograms/ml) for a total of 21 days. Only 7 of 19 patients (83%). Patients who were treated for the full period and patients for whom co-trimoxazole was prematurely stopped had similar concentrations of sulfamethoxazole (157 +/- 52 versus 155 +/- 47 micrograms/ml) and trimethoprim (5.0 +/- 1.4 versus 5.6 +/- 1.0 microgram/ml). Concentrations of sulfamethoxazole and trimethoprim in group A (158 +/- 39 and 5.6 +/- 1.8 micrograms/ml, respectively) did not differ from those in group B (153 +/- 57 and 5.1 +/- 1.6 micrograms/ml, respectively), and the average daily maintenance doses for groups A (75.4 mg/kg plus 15.1 mg/kg) and B (76.4 mg/kg plus 15.3 mg/kg) were nearly identical. Although the average sulfamethoxazole concentrations were maintained within the target zone in the monitoring group (day 5, 160 +/- 44 micrograms/ml; day 10, 160 +/- 41 micrograms/ml; day 15, 168 +/- micrograms/ml; and day 21, 157 +/- 95 micrograms/ml), only 28% of the individual sulfamethoxazole levels were within the target range of 150 to 200 micrograms/ml after the dose adjustments (32% in group B without intervention). Response rates were similar in both groups. Complete response or improvement was observed in 18 of 19 (group A) and 19 of 21 (group B) patients. The method used for monitoring sulfamethoxazole levels with subsequent dose adjustment did not allow us to reliably achieve the target concentrations and did not significantly alter the incidence of side effects or the efficacy of the therapy.

AIDS-Related Complex↗