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Biomedical subjects

F Suter

Publications and source records attributed to F Suter.

At least 37 records · Page 2Linked to original sources

Elevated concentrations of plasma alpha-melanocyte stimulating hormone are associated with reduced disease progression in HIV-infected patients.

To determine whether concentrations of the anti-inflammatory peptide alpha-melanocyte stimulating hormone (alpha-MSH) are associated with accelerated or reduced disease progression in patients with HIV infection, plasma concentrations of alpha-MSH and two other anticytokine molecules, interleukin-1 receptor antagonist (IL-1 ra) and soluble tumor necrosis factor receptor (s TNF r), were taken repeatedly from HIV-positive patients over a 1-year period. Samples from 87 patients were collected by using special precautions to ensure accurate measurement of the peptide. Alpha-MSH concentrations were determined by radioimmunoassay; IL-1 ra and s TNF r concentrations were measured by using enzyme-linked immunosorbent assays. Clinical and immunologic variables were recorded to determine whether there is an association between cytokine antagonist concentrations and disease progression. Elevated concentrations of circulating alpha-MSH were associated with reduced progression of the disease. Circulating alpha-MSH was greater in non-progressors than in progressors; the association between elevated alpha-MSH and reduced disease progression was even more pronounced in patients with baseline CD4+ T cell counts less than 200/microL. No such association was observed for the other two anticytokine molecules, and there was no significant correlation between the plasma concentration of either cytokine antagonist and alpha-MSH. The present evidence and previous findings indicate that elevated concentrations of alpha-MSH are associated with reduced disease progression in HIV-infected patients.

Adult↗

Comprehensive investigation of the presence of JC virus in AIDS patients with and without progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML), a viral-induced demyelinating disease, is becoming relatively common, while many diagnostic and pathogenetic aspects remain to be clarified. A study was therefore undertaken in 64 AIDS patients suffering from various neurological disorders, including PML (12 subjects), with the specific objective of searching for JC virus (JCV) DNA by nested PCR (n-PCR) in cerebrospinal fluid (CSF), peripheral blood mononuclear cells (PBMCs), and urine collected from all patients. CSF examination, CD4 and CD8 counts, neurological examinations, and neuroradiological investigations were undertaken. JCV DNA was detected in 92% of CSF specimens in 75% of the PBMCs and urine samples from the PML patients, whereas among the non-PML patients JCV DNA was not detected in any CSF samples, but was found in 10% of PBMCs and in 39% of the urine specimens. BKV and JCV DNA viruria was observed simultaneously in 6% of the AIDS patients without PML. The routine CSF tests including IgG oligoclonal bands, the Link, and Tourtellotte IgG indexes, did not show a typical pattern in PML cases. The data obtained clearly indicate that the detection of JCV DNA in CSF constitutes an efficient marker for PML diagnosis. The simultaneous presence of JCV DNA in the CSF, PBMCs, and urine samples from the PML patients, who did not differ from controls with regard to their immunosuppressive status, suggests that JCV could be carried into the central nervous system (CNS) by infected PBMCs.

AIDS-Related Opportunistic Infections↗

Comparison of pharmacokinetics and dynamics of two dosage regimens of foscarnet in AIDS patients with Cytomegalovirus retinitis.

OBJECTIVE: To compare the pharmacokinetics of foscarnet administered as an infusion twice daily (BID) or thrice daily (TID), and to compare the effects on the electrolyte balance, cardiac and renal functions over a 3-week induction treatment of Cytomegalovirus (CMV) retinitis. METHODS: Pharmacokinetics/dynamics of foscarnet were investigated on treatment days 1, 14 and 21. Twelve AIDS patients with CMV retinitis completed the investigation period. Concentrations of foscarnet and electrolytes were assayed by high-performance liquid chromatography (HPLC) and by an ion-selective analyser, respectively. RESULTS: The pharmacokinetics of the two regimens were essentially similar. Foscarnet plasma and creatinine clearances were 2.0 and 1.6 ml.min-1.kg-1, respectively, in the BID group at steady state (day 21). In the TID group the corresponding values were 1.8 and 1.7 ml.min-1.kg-1, respectively. In both regimens the elimination half-life of foscarnet was 2-3 h. Ionized calcium concentrations were transiently decreased and strongly inversely correlated to foscarnet plasma concentrations in both regimens with no significant differences between groups. A trend towards prolongation of the QTc interval was seen when data from both treatments were analysed together. CONCLUSION: Our data suggest comparable pharmacokinetics of foscarnet after intermittent administration BID or TID during a 3-week induction period.

AIDS-Related Opportunistic Infections↗

Early ganciclovir therapy effectively controls viremia and avoids the need for cytomegalovirus (CMV) prophylaxis in renal transplant patients with cytomegalovirus antigenemia.

Cytomegalovirus (CMV) infection is still a problem for organ transplant recipients despite studies that long-term prophylaxis with high dose of acyclovir or ganciclovir given to all organ recipients may limit the consequences of infection and disease. In the present report of 160 consecutive renal transplant patients, we used a diagnostic assay for CMV antigenemia (detection of CMV antigen in peripheral blood leukocytes) and treated with ganciclovir only those patients who had a positive test. No patient in this series had routine prophylaxis. Out of 160 patients, 71 had clinical and/or laboratory signs of infection, and were tested for early antigen in peripheral leukocytes. The test was positive in 35, all of whom received a course of 3 wk ganciclovir treatment which effectively cured CMV in 34 count of 35. One patient was ganciclovir-resistant, but responded to foscarnet. None of the 36 patients who had no early antigenemia and did not receive treatment developed the disease. The treatment was extremely well tolerated in all our patients with no adverse events. Thus, even though this was not a controlled study, our present results may be taken to indicate that long-term acyclovir or ganciclovir for all organ transplant recipients might be no longer totally justified. We conclude that detecting viral antigen in circulating leukocytes identifies patients who are indeed at risk of developing severe CMV disease. When these patients are treated early enough, CMV is eliminated with a relatively short course of ganciclovir, which has virtually no side effects.

Adolescent↗

Adjuvant therapy with essential fatty acids (EFAs) for primary liver tumors: some hypotheses.

Hepatocarcinoma is responsible for approximately 1 million deaths annually. It is usually discovered at an advanced stage and, if inoperable, has a poor prognosis. New therapies combining chemotherapy, hyperthermia, radiotherapy and immunomodulators have been recently attempted with various levels of success. Once the tumor is detected at an early stage, some possibilities of cure seem to emerge either by intratumoral percutaneous injection (PEI) of alcohol or by chemoembolization and interstitial hyperthermia. When the tumor volume is more than 5 cm, these therapies are less successful and radiotherapy can be used. All the techniques described have some limits; PEI, for instance, does not achieve a complete eradication of lesions > 3 cm and a non-homogenous alcohol distribution within the tumor leads to areas of necrosis. Radiotherapy, even if effective, is limited by dose-related radiation hepatitis. Another important limiting factor is the incomplete response to therapy and tumor recurrence. Essential fatty acids, especially gamma linolenic acid (GLA) and eicosapentaenoic acid (EPA) are discussed here for their ability to control primary tumor proliferation and increase response to chemotherapy, radiotherapy and hyperthermic treatment, thanks to their effects on cellular membranes (increased lipoperoxidation and modification of tumor stroma).

Animals↗

Mycobacterium conspicuum sp. nov., a new species isolated from patients with disseminated infections.

A new type of slowly growing, nonphotochromogenic mycobacterium was recovered from two patients with disseminated disease. The growth characteristics, acid fastness, acids were consistent with those for Mycobacterium species. The results of biochemical investigations, lipid analyses, and comparative 16S rRNA sequencing showed that these isolates represent a new slowly growing Mycobacterium species which is named Mycobacterium conspicuum.

Adult↗

Structural and spectral characterisation of the antenna complexes of Rhodocyclus gelatinosus. Indications of a hairpin-like-arranged antenna apoprotein with an unusually high alanine content.

The core antenna/reaction-centre complex RC-B875 and the peripheral antenna complex B800-850 of the two strains DSM 149 and DSM 151 of the purple non-sulphur bacterium Rhodocyclus gelatinosus have been isolated from photosynthetic membranes by means of lauryl-N,N-dimethyl-amineoxide as a detergent and subsequent sucrose-gradient centrifugation. The two complexes were characterised spectroscopically by absorption and circular dichroism (CD) spectroscopy at room temperature. CD measurements revealed very weak signals for the core antenna B875 whereas for the peripheral antenna B800-850, a strong biphasic CD signal was observed, attributable to the B850 pigments. There is apparently no CD signal present for the B800 pigments. The core and the peripheral antenna complex are built up by a distinct alpha/beta-polypeptide pair. The pigment/protein ratio in the peripheral antenna complex is 3 bacteriochlorophyll/(alpha/beta)-polypeptide pair. The amino acid sequences of the alpha and beta polypeptides of both complexes from the two strains of Rc. gelatinosus were established by automated Edman degradation, chemical and enzymic digestion, amino acid composition analyses and carboxypeptidase digestion. In the case of the beta polypeptides, the amino acid sequence determination was confirmed by ion-spray MS of the isolated antenna apoproteins. The inter-strain (DSM 149 and 151) positional identity between the equivalent apoproteins is extremely large and varies in the range 90-100%. The B875-beta polypeptide from Rc. gelatinosus exhibits shortened C-termini, as detected for the analogous antenna apoproteins of Rhodobacter sphaeroides and Rhodobacter capsulatus, which can be correlated with weak core antenna near-infrared CD signals. However, the B800-850-alpha polypeptide of Rc. gelatinosus, with 71 amino acids, exhibits an extended C-terminal portion indicative of the formation of a second transmembrane domain, which so far has not been observed for bacterial antenna apoproteins. This part of the molecule is extremely rich in alanine and proline residues. All the sequenced antenna apoproteins of Rc. gelatinosus exhibit a characteristic membrane-buried histidine which is thought to ligate the B875 or the B850 pigments. In the B800-850-beta apoprotein, a second, so far beta-antenna-apoprotein-specific histidine, is replaced by a glutamine residue. A careful inspection of the determined antenna structures of Rc. gelatinosus revealed some remarkable structural similarities within presumed cofactor-binding sites of Fe-S-type-reaction-centre apoproteins, indicating possible basic structural motifs for complexing bacteriochlorophyll molecules.

Alanine↗

Teicoplanin versus cefamandole in the prevention of infection in total hip replacement.

In a prospective, controlled, single-blind study the efficacy of teicoplanin versus cefamandole in preventing infections in total hip replacement was investigated in 496 consecutive patients. A single intravenous dose of teicoplanin (400 mg) was as effective as two intravenous doses of cefamandole (2 g before and 1 g after surgery). No major complications were observed in either group. Infective wound complications were observed only in the cefamandole group. These infections, although not dangerous for the patients, required supplementary antibiotic treatment in all cases. Teicoplanin is a reasonable choice as a prophylactic agent in orthopaedic surgery when a high risk of infection due to staphylococci is present.

Aged↗

Pharmacodynamic effects of subinhibitory concentrations of imipenem on Pseudomonas aeruginosa in an in vitro dynamic model.

The postantibiotic effect (PAE), sub-MIC effect (SME), and postantibiotic sub-MIC effect (PASME) of imipenem on Pseudomonas aeruginosa were investigated with an in vitro dynamic model reproducing in vivo elimination kinetics of the antibiotic. The PASMEs were constantly longer than the corresponding SMEs, but differences between them were not statistically significant. Both PASMEs and SMEs were initially bactericidal and were significantly longer than PAEs. The mean values of both PASMEs and SMEs were over 12 h. SMEs appear to be more relevant for the bacterial growth kinetics than PAEs.

Humans↗

Bactericidal activity of two different dosage regimens of imipenem in an in-vitro dynamic model.

The antimicrobial activity of imipenem was tested in an in-vitro model mimicking human serum pharmacokinetics after either 1000 mg im once daily or 500 mg im twice daily. Six recent clinical isolates of Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae and Salmonella group B were used as test strains. Our results suggest that a single daily dose of imipenem 1000 mg im exerts an antibacterial action comparable to that obtained with two divided doses of 500 mg.

Dose-Response Relationship, Drug↗

The primary structure of the antenna polypeptides of Ectothiorhodospira halochloris and Ectothiorhodospira halophila. Four core-type antenna polypeptides in E. halochloris and E. halophila.

Antenna polypeptides from two species of the family Ectothiorhodospiraceae have been investigated. By means of gel filtration and subsequent high-performance liquid chromatography, at least five polypeptides were isolated from each of Ectothiorhodospira halochloris and Ectothiorhodospira halophila. The majority of their primary structures was identified by Edman degradation. Comparison of these polypeptide sequences with the known primary structures of antenna polypeptides from various purple non-sulfur bacteria revealed interesting new aspects with regard to the structure of the core-peripheral antenna system. E. halochloris and E. halophila contain two pairs of alpha- and beta-polypeptides each with typical primary structure elements of core complexes, indicating a modified antenna complex organization.

Alkylation↗

Zidovudine prophylaxis after accidental exposure to HIV: the Italian experience. The Italian Study Group on Occupational Risk of HIV Infection.

OBJECTIVES: To evaluate the use of zidovudine prophylaxis in HIV-exposed health-care workers (HCW) in Italy and to determine its short-term toxicity. DESIGN: Longitudinal, open study with retrospective and prospective collection of data. SETTING: All Italian clinical centres that care for HIV-infected patients and are licensed by the Ministry of Health to dispense zidovudine and 30 hospitals participating in the Italian Multicentre Study on Occupational Risk of HIV Infection. STUDY POPULATION: HCW and other individuals who accepted zidovudine prophylaxis after accidental exposure to HIV. RESULTS: Data were collected for 224 HIV-exposed individuals until 30 June 1991. An increase in zidovudine prophylaxis was observed. All but 10 subjects received 1000-1250 mg zidovudine per day. Anaemia (five cases), neutropenia (one case) and an increase in serum alanine aminotransferase levels (two cases) were the only haematochemical side-effects observed; none of the subjects ceased prophylaxis because of side-effects. More than 50% of subjects had constitutional reactions; as a result, prophylaxis was stopped by 29 patients. These adverse effects began within 10 days of prophylaxis; all resolved after prophylaxis was stopped. No HIV-antibody seroconversions were observed after a mean follow-up of 8 months. CONCLUSIONS: Zidovudine prophylaxis has become a feature of the management of occupational exposures to HIV in health-care settings; short-term toxicity is mild, dose-related and reversible. Further studies are needed to assess the risk of long-term sequelae.

Administration, Oral↗

The effect of ciprofloxacin on oral contraceptive steroid treatments.

The effect of ciprofloxacin, a new broad-spectrum quinolone derivative, on concomitant oral contraceptive steroids has been studied in a double-blind cross-over placebo-controlled randomized trial. Ten healthy women using long-term oral contraceptive steroids received either ciprofloxacin 500 mg BID or placebo during two consecutive cycles. Therapy was continued for seven days from the first day of contraceptive treatment. FSH, LH and oestradiol blood levels were repeatedly determined to monitor contraceptive steroid efficacy. A seven-day treatment with ciprofloxacin did not affect steroid treatment outcome and appears to be safe in women using this contraceptive method.

Adult↗

European experience with itraconazole in systemic mycoses.

Since January 1985 more than 100 patients with deep fungal infections have been treated with itraconazole (200 to 400 mg/day) in Northern Italy. Evaluation of the drug efficacy and tolerance was possible in one patient with sporotrichosis, in 34 with aspergillosis, and in 36 with cryptococcosis (mainly patients positive for human immunodeficiency virus). Response to itraconazole alone was obtained in the case of sporotrichosis and in 24 of 34 patients with different forms of aspergillosis (of the 18 patients with invasive pulmonary aspergillosis, 15 were cured). Patients with cryptococcosis received itraconazole for active infection and/or for prevention of relapse. Active infection was treated successfully with itraconazole alone in 9 of 12 patients and with itraconazole plus flucytosine in 8 of 10 patients. Of the 31 patients who received itraconazole maintenance therapy for up to 27 months, 4 (13%) had relapses; 14 (45%) did not have relapses, and decline of serum antigen was detected in 12 of them; and 13 (42%) were completely cured (serum antigen titer dropped to zero). With the exception of hypokalemia in one patient, itraconazole was well tolerated even in patients who received the drug for several months or years.

Antifungal Agents↗

Treatment of bone and soft tissue infections with teicoplanin.

The use of teicoplanin was evaluated in a group of 33 patients, which included 18 prosthetic infections, seven with osteomyelitis, five skin and soft tissue infections, and three cases of septic arthritis. The bacterial pathogens isolated were 27 isolates of Staphylococcus aureus (methicillin sensitive 18; methicillin resistant 9), Staph. hominis (2), Staph. epidermidis (1), Staph. haemolyticus (2), Enterococcus faecalis (1), Streptococcus pyogenes (1), Peptococcus spp. (1). Eleven patients had polymicrobial infections (Gram-positive plus Gram-negative and/or anaerobic bacteria). In ten cases (nine polymicrobial infections) teicoplanin was used in combination with other antibiotics. Teicoplanin was administered intravenously 400 mg every 24 h in 26 cases, 200 mg every 24 h in six cases and 600 mg every 24 h in one case. The duration of the treatment ranged from 9 to 73 days with a mean of 27.3. Efficacy was evaluable in 30 patients, because in three patients treatment was stopped because of adverse reactions. Cure or improvement was noted in 28 patients (93%). Bacteriological cure occurred in 25 patients (83.3%).

Adolescent↗

The complete amino-acid sequence and the phylogenetic origin of phycocyanin-645 from the cryptophytan alga Chroomonas sp.

The first complete amino-acid sequence of the cryptomonad phycobiliprotein phycocyanin-645 from Chroomonas sp. is presented. The alpha 1-subunit contains 70 amino-acid residues and the alpha 2-subunit 80 residues. In each of the alpha-subunits a green, 697-nm absorbing chromophore is covalently bound to Cys18. Both alpha-subunits contain a high number of charged residues. The phycocyanin-645 beta-subunit consists of 177 amino-acid residues. Two phycocyanobilin chromophores are singly bound to Cys beta 82 and Cys beta 158. A purple cryptoviolin-like chromophore is doubly bound to Cys beta 50 and Cys beta 61. Sequence comparisons revealed that the phycocyanin-645 beta-subunit is closely related to red algal phycoerythrin (73% identical amino-acid residues) and not so close to C-phycocyanin (55% identical amino-acid residues). The phycocyanin-645 alpha-subunits represent a special type of phycobiliprotein and a direct relationship to other phycobiliproteins or any light-harvesting polypeptide-pigment complexes could not be derived by sequence comparisons.

Amino Acid Sequence↗