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Biomedical subjects

J R Bogner

Publications and source records attributed to J R Bogner.

At least 37 records · Page 2Linked to original sources
PubMed2000

Sequence analysis of the HIV-1 protease coding region of 18 HIV-1-infected patients prior to HAART and possible implications on HAART.

BACKGROUND: The majority of HIV-infected patients are treated with highly active antiretroviral therapy (HAART) consisting of a combination of inhibitors of the protease (PIs) and the reverse transcriptase (RTIs). Analysis of mutations within these enzymes which are associated with development of resistance to the applied inhibitors is of major clinical importance. In particular, pre-existing mutations in previously untreated individuals may adversely influence the efficacy of HAART. OBJECTIVES: The sequences of the protease coding regions of 18 HIV-1-infected patients were analysed prior to HAART. STUDY DESIGN: DNA was extracted from whole blood samples of HIV-1-infected treatment-naive patients. The protease coding region was amplified by nested PCR and sequenced directly. The resulting amino acid substitutions were analysed for known mutations associated with known resistance to PIs. RESULTS: In all 18 analysed individuals we found 1-10 amino acid substitutions per patient in their HIV-1 protease coding region. These mutations occurred altogether at 27 positions of the 99 amino acids of the protease coding region. Seven of these mutated positions are associated with described resistance to PIs. Altogether, 15 of the 18 patients (83%) carried at least one such resistance-conferring alteration in their protease coding region. All patients are currently followed up during their present therapy to detect possible resistance formation to the applied PIs. CONCLUSIONS: A large variety of pre-existing mutations associated with resistance to PIs was observed prior to their treatment. As none of the patients ever received HAART before and infection with resistant viral strains is very unlikely, these amino acid substitutions evidently reflect natural polymorphism of the HIV-1 protease coding region.

Amino Acid Sequence↗
PubMed2000

Evaluation of diagnostic value and epidemiological implications of PCR for Pneumocystis carinii in different immunosuppressed and immunocompetent patient groups.

To evaluate the value of single and nested PCRs for diagnosis of Pneumocystis carinii pneumonia (PCP) in a variety of respiratorily distressed patient groups, 574 respiratory samples from 334 patients (89 human immunodeficiency virus [HIV]-positive patients, 61 transplant recipients, 66 malignancy patients, 34 otherwise immunosuppressed patients, and 84 immunocompetent patients) were prospectively examined by microscopy and single and nested PCRs. The resulting data were correlated with clinical evidence of PCP. Microscopy and single PCR of bronchoalveolar lavage (BAL) specimens from HIV patients were 100% sensitive and specific in detecting PCP, whereas nested PCR, although being 100% sensitive, reached a specificity of only 97.5%. In the three non-HIV immunosuppressed patient groups, both single and nested PCR invariably produced lower positive predictive values than microscopy. Among immunocompetent patients, the positive predictive values of both PCRs were 0%. Therefore, the diagnostic values of the PCR methods tested do not seem to offer any additional advantage compared to that of conventional microscopy for these patient groups. However, nested PCR identified a significant percentage of clinically silent P. carinii colonizations in about 17 to 20% of immunocompetent and immunosuppressed non-HIV patients.

Adolescent↗
PubMed2000

Bacillary angiomatosis in HIV-infected patients--an epidemiological and clinical study.

BACKGROUND: No data were available on the epidemiological and clinical characteristics of bacillary angiomatosis (BA) in Germany. OBJECTIVE: To determine epidemiological and clinical data on HIV-associated BA. METHODS: A chart review of all BA cases between 1990 and 1998 was performed in 23 German AIDS treatment units. RESULTS: A total of 21 cases of BA was diagnosed. During this period, the participating HIV centers treated about 17,000 HIV-infected patients. As a result, a BA prevalence of 1.2 cases/1,000 patients can be assumed. 19 BA were localized in the skin; in 5 cases bones and in 4 cases the liver were involved. Out of 20 patients who received antibiotic therapy, 13 had complete remission. The median time of duration up to complete remission was 32 days (9-82). During the follow-up of the 20 patients, 7 relapses were observed. CONCLUSION: BA is a rare HIV-associated disease with a prevalence of 1,2 cases/1,000 patients in the presented study.

Adult↗
PubMed1999

Endothelin-1 is elevated in the cerebrospinal fluid of HIV-infected patients with encephalopathy.

In a cross-sectional, non-randomized, prospective study in an outpatient clinic a possible relationship between the cerebrospinal fluid (CSF) concentrations of the potent vasoconstrictor peptide endothelin-1 (ET-1) and prevalence and degree of HIV-encephalopathy was studied. Forty-eight CSF samples from HIV-infected patients undergoing lumbar punction for diagnostic reasons were investigated for ET-1 concentrations. In 37 patients ET-1 was also measured in plasma. Patients were investigated clinically and staged with respect to HIV encephalopathy. Patients with arterial hypertension, diabetes or acute opportunistic infections were excluded from the study. In the remaining, 18 of the CSF samples were from patients with normal neurological findings (grade 0-0.5), whereas 30 were from patients with HIV encephalopathy (grade 1-3). The mean CSF ET-1 concentration was significantly elevated (P = 0.001) in patients with HIV encephalopathy (1.97 +/- 2.33 pmol/l) as compared to those patients without encephalopathy (0.57 +/- 0.67 pmol/l). Moreover, there was a significant correlation between ET-1 CSF concentrations and the degree of HIV encephalopathy (r = 0.49, P < 0.001). In addition, there was a significant correlation between ET-1 levels in the CSF and the IgG serum to CSF ratio. However, we found no correlation between HIV encephalopathy and neither CSF total protein, IgG, albumin or the serum to CSF ratio of IgG or albumin. In conclusion, we could demonstrate a close relationship between CSF ET-1 concentrations and the degree of HIV encephalopathy. Thus, by virtue of its long-lasting and potent vasoconstrictor activity ET-1 might contribute to the pathogenesis of HIV encephalopathy.

AIDS Dementia Complex↗
PubMed1999

Hypocalcaemia in HIV infection and AIDS.

OBJECTIVES: To study the prevalence and possible mechanisms of hypocalcaemia in HIV infection and AIDS. SUBJECTS: 828 patients with HIV infection or AIDS and 549 controls. INTERVENTIONS: Measurements of total serum calcium and albumin levels. Parameters of calcium homeostatis were determined in a subgroup of 21 hypocalcaemic AIDS patients. RESULTS: Mean serum calcium was 2.34 +/- 0.13 mmol L-1 in the HIV group vs. 2.46 +/- 0.10 mmol L-1 in controls (P < 0.0001). After adjusting for serum albumin, hypocalcaemia was present in 6.5% of the HIV group vs. 1.1% of controls. Mean serum calcium was declining according to CDC groups, and differed significantly from controls in each group. Regression coefficients of cacium vs. albumin were 0.147 amongst HIV-infected patients and 0.106 for controls. In the subgroup of hypocalcaemic patients with AIDS, 10/21 had vitamin D deficiency, six of these with low ionized calcium levels. Low serum PTH was found in 2/21 patients. Magnesium deficiency in 1/21. Of the remaining eight patients, only one had secondary hyperparathyroidism, while the other seven lacked an adequate PTH response, despite low ionized calcium levels in four subjects. CONCLUSIONS: Mean serum calcium concentrations were lower through all CDC stages, irrespective of albumin, resulting in a higher prevalence of hypocalcaemia in HIV-positive patients compared with controls. In a considerable number, this seems to be caused by vitamin D deficiency and potentially a lack of adequate PTH secretion, but further studies are needed to confirm this.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Lack of absorption of didanosine after rectal administration in human immunodeficiency virus-infected patients.

The feasibility of rectal administration of didanosine (DDI) was studied in six human immunodeficiency virus-infected patients. After oral intake of a DDI solution (100 mg/m2 of body surface area) combined with an antacid (Maalox), pharmacokinetic parametric values were in accordance with previously published data; the mean +/- standard deviation for terminal half-life was 59.5 +/- 15.0 min, that for peak concentration was 5.2 +/- 3.9 mumol/liter, and that for the area under the time-concentration curve (AUC) was 494 +/- 412 min.mumol/liter. After rectal administration of a similarly prepared DDI solution (100 mg/m2 of body surface area), plasma DDI levels were below the detection limit (0.1 mumol/liter) at all time points in five of the six patients, and in the remaining patient the AUC after rectal application was only 5% of that after oral administration. We conclude that oral administration of DDI cannot be easily replaced by rectal application.

Administration, Rectal↗
PubMed1999

First-glance diagnosis of Strongyloides stercoralis autoinfection by stool microscopy.

We report a case of autoinfection due to Strongyloides stercoralis in a 27-year-old Ethiopian AIDS patient living in Germany for nearly 3 years. This case was diagnosed on the basis of a single-view field in microscopy of a freshly obtained formalin-fixed stool specimen showing both rhabditiform and filariform larvae. The diagnosis of autoinfection by microscopy is discussed in detail.

Adult↗
PubMed1998

Treatment with protease inhibitors associated with peripheral insulin resistance and impaired oral glucose tolerance in HIV-1-infected patients.

BACKGROUND: The use of protease inhibitors in the treatment of HIV-1 infection is associated with the new onset of diabetes mellitus, hyperlipidaemia and lipodystrophy. It is unclear whether these findings are coincidental or whether they reflect a causative effect of protease inhibitors. OBJECTIVE: To evaluate the effect of treatment with protease inhibitors on insulin sensitivity, oral glucose tolerance and serum lipids in HIV-infected patients in order to determine whether treatment with protease inhibitors can cause peripheral insulin resistance. DESIGN: Cross-sectional controlled study in HIV-infected patients treated with protease inhibitors to assess insulin sensitivity, oral glucose tolerance and changes in serum lipids. METHODS: Sixty-seven patients treated with protease inhibitors, 13 therapy-naive patients and 18 HIV-negative control subjects were tested for insulin sensitivity (intravenous insulin tolerance test). In a subgroup of 24 treated patients, oral glucose tolerance was determined. Serum lipids prior to and under treatment with protease inhibitors were compared. RESULTS: Patients on protease inhibitors had a significantly decreased insulin sensitivity when compared with therapy-naive patients (median, 75 and 156 micromol/l/min, respectively; P < 0.001). All treated patients with impaired (n=4) or diabetic (n=9) oral glucose tolerance, and four out of 11 patients with normal glucose tolerance showed peripheral insulin resistance; all therapy-naive patients had normal insulin sensitivity. Treatment with protease inhibitors led to a significant increase in total triglycerides and cholesterol in the 67 treated patients (median increase, 113 and 37 mg/ml, respectively). CONCLUSION: Treatment with protease inhibitors is associated with peripheral insulin resistance, leading to impaired or diabetic oral glucose tolerance in some of the patients, and with hyperlipidaemia. Overall, there is a large variation in the severity and clinical presentation of protease inhibitor-associated metabolic side-effects.

Adult↗
PubMed1998

Resolution of severe Kaposi's sarcoma after initiation of antiretroviral triple therapy.

OBJECTIVES: To study the relationship between effective antiretroviral therapy, monitored by CD4 counts, and it s influence on the clinical course of AIDS associated Kaposi's sarcoma. METHODS: Four representative cases with AIDS and advanced Kaposi's sarcoma (KS) showed improvement of histologically proven KS s in various sites, including pulmonary disease, treated with liposomal doxorubicin. CD4 counts increased significantly during administration of triple antiretroviral therapy. In three cases chemotherapy cycles were extended and subsequently discontinued for 4, 14 and 4 months, respectively, without any relapse. In one other case interferonalpha therapy has been started overlapping with doxorubicin prior to permanent discontinuation of doxorubicin. CONCLUSIONS: Data of those patients suggest that in patients with increasing CD4 counts KS's chemotherapy intervals should be extended or even discontinued. In some patients change of therapy to interferon alpha can be considered. A potent combined antiretroviral therapy may enhance efficiency of KS treatment even in patients with high CD4 counts.

Adult↗
PubMed1998

Liposomal doxorubicin in pulmonary Kaposi's sarcoma: improved survival as compared to patients without liposomal doxorubicin.

OBJECTIVE: Pulmonary Kaposi's sarcoma (KS) in HIV-infected patients is characterised by a poor prognosis with a mean survival time of 2 to 6 months. Our goal was to evaluate survival in patients with pulmonary KS treated with Stealth liposomal doxorubicin (SL-DOX) and to compare it with patients without SL-DOX therapy. PATIENTS AND THERAPY: 29 AIDS patients with confirmed pulmonary Kaposi's sarcoma were studied. Group 1 (n = 20): Patients treated with SL-DOX. Group 2 (n = 9): 4 patients who received bleomycin and vinblastine or vincristine and 5 patients without chemotherapy. RESULTS: Survival analysis by Kaplan-Meier plot showed a significant benefit for patients with SL-DOX treatment. Mean survival times were 11.8 +/- 1.78 months (group 1: range 1-28) versus 4.4 +/- 1.68 months (group 2; range 1-17). Average CD4 levels did not differ significantly at diagnosis of pulmonary Kaposi's sarcoma. Clinical response included improvement of general health, particularly cough and dyspnea, of arterial pO2 and radiographic KS pattern in the lung. CONCLUSION: Our analysis suggests a clear survival and quality of life benefit for patients with pulmonary Kaposi's sarcoma on liposomal doxorubicin.

Adult↗
PubMed1998

Ganciclovir and foscarnet efficacy in AIDS-related CMV polyradiculopathy.

Cytomegalovirus (CMV) polyradiculopathy is a rare complication of AIDS in which ascending motor weakness, sensory loss and urinary retention are associated with polymorphonuclear pleocytosis and positive CMV polymerase chain reaction in the cerebrospinal fluid (CSF). We describe three patients with this syndrome. One patient's paresis improved after ganciclovir therapy. Another patient deteriorated despite foscarnet treatment, but improved after ganciclovir was added. The third patient died from ascending paralysis despite ganciclovir-foscarnet combination. Reviewing the literature, we conclude that antiviral treatment reduced mortality from 100 to 22%. In patients with ascending paralysis treatment, failure may be caused by viral drug resistance, at least in some patients. Risk factors for treatment failure are preceding monotherapy for other CMV diseases or persistent CSF pleocytosis on serial CSF analysis. We suggest that these patients should therefore be treated with the alternative drug or a ganciclovir-foscarnet combination therapy.

AIDS-Related Opportunistic Infections↗
PubMed1997

Absorption and elimination kinetics of zidovudine in the cerebrospinal fluid in HIV-1-infected patients.

Current knowledge of zidovudine (ZDV) levels in human cerebrospinal fluid (CSF) is limited to single sample determination and extrapolation to time after administration. Longitudinal studies have not been performed. Pharmacokinetic parameters of ZDV in CSF were determined in six HIV-1-infected patients. CSF samples were collected by an intraspinal catheter over a period of 6 hours after a single intravenous (IV) dose of ZDV (2.5 mg/kg). ZDV concentrations were measured by high-performance liquid chromatography (HPLC). ZDV was cleared rapidly from plasma, with a mean terminal elimination half-life (t 1/2) of 75.5 +/- 4.9 minutes. ZDV penetrated slowly into the CSF, reaching maximal concentration (Cmax) 2 hours after the start of the infusion in all patients. ZDV was cleared from the CSF with a mean t 1/2 of 187.6 +/- 69.3 minutes. Mean Cmax in the CSF was 1.3 +/- 1.2 micromol/l (17% of that of plasma), and mean area under the concentration time curve (AUC) was 358 +/- 200 micromol x minutes/l (75% of that of plasma). There was a significant correlation between plasma and CSF for Cmax (r = 0.88, p = .009) and AUC (r = 0.89, p = .014). Calculated trough levels in CSF for a 12-hour dosing interval were 0.090 +/- 0.065 micromol/l and thus about twice the 50% inhibitory concentration (IC50) of susceptible HIV strains. The CSF-plasma ratio of ZDV increased in a nearly linear fashion with time after drug administration. Thus, ZDV has a distinct pharmacokinetic profile in CSF compared with other compartments of the body.

Absorption↗
PubMed1997

Mild rhabdomyolysis after high-dose trimethoprim-sulfamethoxazole in a patient with HIV infection.

Adverse drug reactions to trimethoprim-sulfamethoxazole (TMP/SMX) are common in HIV-positive patients. However, only one case of TMP/SMX-related rhabdomyolysis has been reported, so far. We report a 55-year old-man with asymptomatic rhabdomyolysis after oral high-dose TMP/SMX for suspected PCP. Laboratory changes settled after discontinuation of the drug.

AIDS-Related Opportunistic Infections↗
PubMed1997

Kaposi's sarcoma: is the hunt for the culprit over now?

Patients suffering from the acquired immune deficiency syndrome (AIDS) have a 20000-fold increased risk of developing a severe form of Kaposi's sarcoma (KS), a previously rare malignancy involving sharply defined nodular lesions of the skin and/or oral mucosa. Epidemiological evidence has long suggested that an infectious agent is the probable cause of KS. Recently sequences from a putative new herpesvirus have been found to be associated with KS in virtually 100% of the cases analyzed. The suspected etiological agent, a new human herpesvirus termed Kaposi's sarcoma associated herpes virus (human herpes virus 8) has now been propagated in cell culture. This significant advance should form the basis for a detailed analysis of the pathogenetic mechanisms involved in the development of KS.

Adult↗
PubMed1997

Detection of antibodies against viral capsid proteins of human herpesvirus 8 in AIDS-associated Kaposi's sarcoma.

Sequences of a new herpesvirus with homology to gammaherpesvirinae were recently identified in AIDS-associated Kaposi's sarcoma (KS). Subsequently this novel virus, called KS-associated virus (KSHV) or human herpesvirus (HHV) 8 was detected in classical KS and AIDS-associated body cavity based lymphomas by polymerase chain reaction. In this report major and minor capsid proteins of HHV-8 were molecularly cloned and produced as recombinant proteins in Escherichia coli. Sera from 69 HIV-1 infected patients with KS, 30 HIV-1 infected patients without KS and 106 control individuals were tested by enzyme-linked immunosorbent assay for anti-HHV-8 capsid IgM and IgG antibodies. Sera from four patients were tested over periods ranging from 18 months to 6 years. IgG antibodies directed against HHV-8 capsid antigens were detected in patients with AIDS-associated KS and in some AIDS patients without KS. Seroconversion with IgM and IgG antibodies directed against HHV-8 capsid proteins occurred more than 1 year prior to diagnosis of KS. In a considerable portion of KS patients no IgM or IgG antibodies against HHV-8 capsid proteins were detected. In these patients there was an inverse relationship between antibodies against HHV-8orf26 and the CD4/CD8 ratio, suggesting that the inconsistency of anti-HHV-8orf26 antibodies is due at least partly to an impaired immune response. No reactivity against HHV-8 capsid antigens was detected in the vast majority of sera from HIV-negative control individuals. Our findings indicate that a specific humoral immune response against capsid proteins is raised in HHV-8 infected individuals, and that anti-capsid antibodies can be used to diagnose HHV-8 infection. The correlation between occurrence of anti-HHV-8 antibodies and KS supports the hypothesis of a causative role of HHV-8.

Amino Acid Sequence↗