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K Schliefer

Publications and source records attributed to K Schliefer.

8 recordsLinked to original sources

Enteric dysfunction in patients with asymptomatic HIV-infection versus patients with hypoproteinemia/hypalbuminemia and advanced HIV-infection.

BACKGROUND: It is unclear whether enteric dysfunction and protein losses contribute to hypoproteinemia, which heralds poor survival in HIV infection. METHODS: We investigated alpha-1-antitrypsin-clearance (AAT-CL), D-xylose resorption and total gut transition time in 14 HIV+ patients with hypoproteinemia (serum protein < 6 g/dl, albumin < 3 g/dl, median CD4-cell count 58/microl; (group I)), in 10 asymptomatic HIV+ patients (median CD4-cell count 290/microl, (group II)) and in 15 healthy volunteers (group III). RESULTS: AAT-CL in group I (16.5 (2.9 278.2) ml/d; median (range)) was higher than in groups II (9.5 (1.7 23.1) ml/d) and III (10.6 (0.8 19.5) ml/d; p = 0.0114). Likewise, D-xylose recovery was on average threefold lower in group I than in groups II (p = 0.0009) and III ( p < 0.0001), whereas total gut transition time was significantly shorter in both HIV-infected groups (group I: 49.8 h (23.5-72.7), p=0.0431; group II: 32.6 h (23-54.6), p=0.0104) than in the healthy controls (group III 61.6 h (39.1-87.7)). CONCLUSIONS: Thus, impaired intestinal resorption and enteral protein losses may contribute to hypoproteinemia in advanced HIV infection, whereas accelerated intestinal motility may be present already in asymptomatic stages of HIV infection.

Adult↗

Decrease of elevated N,N-dimethylglycine and N-methylglycine in human immunodeficiency virus infection during short-term highly active antiretroviral therapy.

This study investigates fasting serum levels of methionine and related metabolites, vitamin B6, and folate during highly active antiretroviral therapy in therapy-naive human immunodeficiency virus (HIV)-1-infected outpatients. The research design consisted of before and during therapy measurements with a median treatment period of 100 days (range, 50 to 188) in frozen samples. The subjects included 17 consecutive HIV-1-infected outpatients (15 men and 2 women; 25 to 65-years-old). Controls were 42 healthy individuals (28 men and 14 women; 24- to 82-years-old) without serologic evidence of HIV and/or hepatitis C infection and normal clinical chemistry. Subjects received treatment with the reverse transcriptase inhibitors, azidothymidine (AZT) or stavudine (D4T) plus lamivudine (3TC) and either the protease inhibitors, indinavir (IND), nelfinavir (NELF), ritonavir (RITV), or saquinavir (SAQ) at the standard dosage. Serum concentrations of methionine, total homocysteine (tHcy), cystathionine (CYSTA), N,N-dimethylglycine (DMG), N-methylglycine (MG), methylmalonic acid (MMA), and total cysteine, as well as vitamin B6, folate, and soluble tumor necrosis factor receptor p75 were taken at baseline and during highly active antiretroviral therapy. Baseline, serum tHcy, MMA, CYSTA, vitamin B6 concentrations were not significantly different from healthy controls. There was, however, a trend towards lower folate serum concentrations at baseline in HIV-infected patients as compared with healthy controls (P =.06). There were no significant correlations between tHcy and vitamin B6, folate, or MMA. Elevated baseline levels of DMG and MG decreased significantly during antiretroviral therapy (P =.0019 and.04, respectively), whereas no significant changes in serum concentrations of CYSTA, MMA, or methionine were detected. tHcy increased in 12 of 17 patients (P =.09). HIV-infected patients displayed significant alterations (elevated DMG and MG serum concentrations) in metabolite levels of the betaine pathway in methionine metabolism, which might be positively influenced by newly initiated antiretroviral combination therapy.

Adult↗

Painful multifocal arthritis: therapy with rhenium 186 hydroxyethylidenediphosphonate ((186)Re HEDP) after failed treatment with medication--initial results of a prospective study.

Eight patients (77 joints) with polyarthritis were treated systemically with 570 MBq (15.4 mCi) of rhenium 186 ((186)Re) hydroxyethylidenediphosphonate (HEDP). Pain and disease activity were assessed monthly. In six (75%) of eight patients, a single injection of (186)Re HEDP led to an improvement in disease activity. Systemic low-dose treatment with (186)Re HEDP can reduce pain and disease activity in patients with polyarthritis.

Arthritis, Rheumatoid↗

[Orthotopic liver transplantation in a 33-year-old patient with fulminant hepatitis B and HIV infection].

HISTORY AND CLINICAL FINDINGS: A 33-year-old man with fulminant hepatitis B infection was to have an orthotopic liver transplantation (OLTX) because of the otherwise poor prognosis. During preparations for it he was found also to have an HIV-infection. INVESTIGATIONS: Preoperatively the Quick value was 9%, and he had a grade 2 encephalopathy. His immune status was impaired: 477 CD4-T-helper cells/microliter. Virus load, measured with a quantitative HIV-RNA test, was < 80 copies/ml (i.e. below demonstrable level). DIAGNOSIS, TREATMENT AND COURSE: After the first transplantation had ended in organ failure, a second one two days later was successful. But there were several complications postoperatively: ischaemic-toxic tubular renal failure requiring haemodialysis, underperfusion of the right lobe of the liver due to arterial stenosis, pleural effusion, cytomegalovirus infection and cyclosporin-induced hypertension. But all these were successfully managed. At the time of this report, 27 months later, the patient felt well and his immune state was stable. During these 2 years he had a practically normal T-helper count and HIV-RNA measured below 80 copies/ml with good liver function. There has been no indication for antiviral treatment and there have been no complications relating to immunosuppression. CONCLUSION: The low life expectancy before effective antiviral drugs are available explains the reluctance to perform OLTX in HIV-infected patients. The favourable course in this case, using highly efficacious combined antiretroviral treatment now being available, indicates that after careful consideration, OLTX can be performed in selected patients with HIV.

Adult↗

T(H)1 to T(H)2 shift of cytokines in peripheral blood of HIV-infected patients is detectable by reverse transcriptase polymerase chain reaction but not by enzyme-linked immunosorbent assay under nonstimulated conditions.

BACKGROUND: Dysregulation of cytokines has been implicated in the pathogenesis of HIV infection. Therefore, we determined tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-4, IL-10, and interferon-gamma (IFN-gamma) mRNA and serum levels in HIV-infected patients under nonstimulated conditions. MATERIAL AND METHODS: Blood samples of 32 HIV-infected patients and 10 healthy HIV-negative controls were analyzed. Cytokine serum levels were quantified by enzyme-linked immunosorbent assay (ELISA). Cytokine mRNA levels were determined semiquantitatively by competitive reverse transcriptase polymerase chain reaction (RT-PCR) and expressed as ratios relative to those of beta-actin. RESULTS: Competitive RT-PCR was shown to be more sensitive than protein ELISA in analyzing cytokine production. We found a significant correlation between steady-state mRNA ratios and serum protein levels for TNF-alpha. Significantly higher cytokine mRNA ratios were found in those patients with IL-10 and IFN-gamma levels detectable by ELISA. Steady-state mRNA ratios of TNF-alpha, IL-4, and IL-10 were significantly increased in patients with highly replicative HIV-infection. Furthermore, elevated IL-4:IFN-gamma ratios were related to both high viral load and loss of CD4 cells. DISCUSSION: Determination of steady-state mRNA ratios by semiquantitative RT-PCR represents a sensitive method to analyze cytokines in peripheral blood of HIV-infected patients under nonstimulated conditions. The data obtained with this technique provide further evidence for a T(H)1 to T(H)2 cytokine shift with progressive HIV disease.

CD4 Lymphocyte Count↗

Influence of protease inhibitor therapy on lipoprotein metabolism.

OBJECTIVES: Protease inhibitors are efficient drugs as part of highly active antiretroviral therapy. They have been shown to cause hyper- and dyslipoproteinemia. Since antiretroviral therapy is able to delay disease progression and possibly extend life expectancy in HIV-infected individuals, the precise nature of serum lipid disturbances may become of clinical interest with respect to its atherogenicity and to finding treatment options. DESIGN: We investigated prospectively, in 19 subsequent HIV-positive male patients (mean age 42 +/- 13 years), multiple lipid parameters in plasma, before and during treatment with a protease inhibitor (nelfinavir, ritonavir, or indinavir) and two nucleoside analogue reverse transcriptase inhibitors (NRTI). The median (range) treatment duration was 22 (7-40) weeks. 12 patients were treatment-naive; 7 had already NRTI medication at baseline. RESULTS: Total cholesterol increased by 28 mg dL-1 (95% CI: + 7 to + 48, baseline 158 +/- 53, P = 0.01), triglycerides increased by 96 mg dL-1 (+ 22 to + 170, baseline 152 +/- 91, P = 0.014), HDL cholesterol was unchanged, LDL cholesterol was slightly but not significantly elevated, VLDL cholesterol increased by 20 mg dL-1 (+ 9 to + 31, baseline 33 +/- 21, P = 0.001), VLDL triglycerides increased by 86 mg dL-1 (+ 22 to + 150, baseline 128 +/- 91, P = 0. 01). The ratio of total cholesterol to HDL cholesterol increased by 1.2 (+ 0.7 to + 1.7, baseline 4.8 +/- 1.5, P = 0.0001) and the ratio of HDL2 to HDL3 decreased by 0.06 (-0.02 to -0.09, baseline 0.47 +/- 0.11, P = 0.005). (Conversion factors, mg dL-1 to mmol L-1: 0.0259 for cholesterol, 0.0114 for triglycerides.) CONCLUSIONS: The data indicate that the predominant feature of dyslipidemia under protease inhibitors is an increase in triglyceride-containing lipoproteins. This observation is in accordance with the hypothesis of increased apoptosis of peripheral adipocytes, release of free fatty acids and subsequent increased synthesis of VLDL. The lipid profile, based on the ratio of total cholesterol to HDL cholesterol and the ratio HDL2 to HDL3, is significantly more atherogenic.

Adult↗