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N H Brockmeyer

Publications and source records attributed to N H Brockmeyer.

At least 55 records · Page 3Linked to original sources
PubMed1999

Effect of fusidic acid on the hepatic cytochrome P450 enzyme system.

OBJECTIVE: To investigate the effects of fusidic acid therapy on the hepatic cytochrome P450 (CYP450) enzyme system. METHODS: Thirty HIV-seropositive L-methadone-substituted i.v. drug abusers (stage CDC/WHO B2 - 3 with CD4+-counts ranging from 65 to 293/microl) were randomized into 3 groups (A - C). Ten patients were treated with fusidic acid 500 mg/day over a period of 14 (group A) or 28 days (group B), respectively. Patients in group C served as a control group and did not receive any medication apart from L-methadone. In order to investigate the hepatic monooxygenase system, pharmacokinetics were determined in all patients before initiation and 14 and 28 days after starting therapy with fusidic acid. The concentration of antipyrine and its 3 main metabolites (norantipyrine (NORA), 4-hydroxyantipyrine (OHA), 3-hydroxymethylantipyrine (HMA)) in plasma and urine were measured by high-performance liquid chromatography (HPLC). RESULTS: No effects on antipyrine pharmacokinetics and pharmacokinetics of antipyrine metabolites were found in group A after 14 days of fusidic acid intake and in the control group without therapy. However, in contrast an activation of the CYP450 enzyme system was observed in group B after 28 days of fusidic acid therapy with an increase of total antipyrine clearance (43.0 +/- 7.62 ml/min to 51.0 +/- 9.03 ml/min) as well as clearances to all metabolites (NORA 7.11 +/- 1.75 to 8.60 +/-2.10 ml/min, OHA 11.5 +/- 2.89 to 14.0 +/- 3.97 ml/min, HMA 4.05 +/- 0.99 to 4.94 +/- 1.27 ml/min). Antipyrine half-life was significantly reduced (12.3 +/- 2.8 h to 9.4 +/- 2.2 h) and some patients developed clinical signs of L-methadone underdosage. CONCLUSIONS: Our results suggest that fusidic acid has a time-dependent activating effect on the CYP450 enzyme system. Especially in treatment of patients who are frequently under multidrug regimens such as HIV-positive patients drug interactions should be taken into consideration.

Anti-Bacterial Agents↗
PubMed1998

Effects of antipsoriatic therapies on hepatic microsomal enzyme activity in patients with psoriasis.

OBJECTIVE: The influence of several antipsoriatic therapies on microsomal enzyme activity was assessed by comparing measurements of antipyrine kinetics prior to and two weeks after initiation of therapy. METHODS: Serum and urine analysis was carried out by means of high performance liquid chromatography (HPLC). Each form of therapy was examined separately. 10 patients were treated with etretinate. The groups treated with 8-methoxypsoralene (8-MOP) in combination with UVA irradiation (PUVA), etretinate in combination with PUVA (RePUVA), anthralin, or combined UVA and UVB irradiation (SUP) consisted of 7 patients each. RESULTS: Neither anthralin nor SUP therapy led to any significant changes in antipyrine kinetics. Antipyrine clearance under the other regimens was, however, reduced. It was 23% lower in PUVA-treated patients, 20% lower in those receiving retinoids and 28% lower in those under RePUVA (p<0.05 - 0. 01). CONCLUSIONS: PUVA, etretinate and RePUVA inhibit microsomal enzyme activity in the liver. Possible drug interactions with other P subset450 inducing or inhibiting agents should be considered in the therapy of psoriatic patients.

Administration, Topical↗
PubMed1998

Changes of antipyrine pharmacokinetics during influenza and after administration of interferon-alpha and -beta.

OBJECTIVE: During viral infections serum levels of interferons are elevated. In this study we wanted to observe the effects of endogenous interferon (IFN) during an acute viral infection (influenza) and after external application of interferons on the pharmacokinetics of antipyrine which is a parameter of hepatic cytochrome P450 enzyme activity. METHODS: Endogenous plasma levels of interferons and the antipyrine pharmacokinetics in 10 otherwise healthy volunteers were investigated before outbreak and in the symptomatic interval of an acute viral respiratory infection. The serum interferon levels were determined by RIA. In another trial 2 groups of 9 HIV patients each in stage CDC/WHO B2/3 received low-dose interferon therapy with 0,75 Mio. I.U. interferon-alpha or -beta s.c./die. The concentrations of antipyrine in serum were measured by HPLC. The antipyrine kinetics were determined before the infection or the interferon therapy, respectively, and during viral infection or during interferon or after interferon therapy, respectively. RESULTS: The plasma levels of IFNalpha and IFNgamma were significantly elevated from 4.7 U/ml to 12.6 U/ml and 0.3 U/ml to 3.4 U/ml, respectively, whereas the antipyrine clearance showed a decrease from 57.9 ml/min to 45 ml/min in the symptomatic interval of an acute viral infection. During therapy with low-dose interferons we observed a significant difference after 12 week treatment with IFNalpha or IFNbeta, respectively. In the first group we observed a decreased antipyrine clearance from 49.0 ml/min to 41.7 ml/min; in the second group the antipyrine clearance decreased from 49.0 ml/min to 41.7 ml/min. CONCLUSION: Viral infections (influenza) are able to inhibit the hepatic monooxygenase system due to elevated serum interferon levels. Low doses of exogenous interferons inhibit the cytochrome P450 monooxygenase system.

Adult↗
PubMed1997

Pharmacokinetic interaction of fluconazole and zidovudine in HIV-positive patients.

To investigate the interaction of fluconazole and zidovudine in HIV-positive non-smoking male patients with AIDS categorized as CDC group IV we studied two groups, each consisting of 10 male, non-smoking, HIV-positive patients with CDC group IV disease, with the patients in the first group additionally suffering from candida esophagitis. In the first group, the pharmacokinetics of 500 mg oral zidovudine were determined both before and after 7 days of treatment with fluconazole 400 mg/d. In the second group, the pharmacokinetics of 200 mg oral fluconazole were determined before and after 14 days of treatment with zidovudine 4 x 250 mg/d. In order to determine the microsomal enzyme activity, the 6-beta-hydroxycortisol/17-hydroxycorticosteroid ratio and antipyrine pharmacokinetic parameters were determined. 6-beta-hydroxycortisol was quantitated by RIA. The 17-hydroxycorticosteroids were determined by a colorimetric method. Zidovudine (ZDV) and zidovudine glucuronide (GZDV), and the fluconazole and antipyrine plasma and urine concentrations were measured by HPLC. Administration of fluconazole resulted in a significant increase in the half-life of zidovudine and antipyrine (0.97 +/- 0.17 h prior to vs. 1.11 +/- 0. 14 h after fluconazole administration and 11.9 +/- 1.9 h prior to vs. 13.7 +/- 3.0 h after fluconazole, respectively) while the 6-beta-hydroxycortisol excretion decreased significantly (472.3 +/- 80.6 microg/24 h before and 340.6 +/- 82.1 microg/24 h after administration of fluconazole). No changes were found in the GZDV plasma kinetics and the ZDV and GZDV urinary excretion. Treatment with ZDV did not have any impact on the half-life of fluconazole. Administration of zidovudine did, however, result in a significant reduction in antipyrine half-life (11.7 +/- 2.0 h before vs. 9.9 +/- 2.3h after ZDV) and a significant increase in 6-beta-hydroxycortisol excretion (438,7 +/- 138.2 microg/24 h before and 684.6 +/- 157.3 microg/24 h after ZDV). Since the antipyrine clearance is altered after administration of ZDV, it is assumed that zidovudine induces cytochrome P450 enzymes. This effect, however, does not alter the pharmacokinetics of fluconazole. High doses of fluconazole can inhibit the plasma elimination of both antipyrine and zidovudine, but the extent of this inhibitory effect is so small that no clinically relevant accumulation is to be expected.

17-Hydroxycorticosteroids↗
PubMed1997

Expression of HHV-8 latency-associated T0.7 RNA in spindle cells and endothelial cells of AIDS-associated, classical and African Kaposi's sarcoma.

Analysis by polymerase chain reaction (PCR) and serological studies have demonstrated a close association between the novel human herpes virus, Kaposi's sarcoma-associated herpes virus (KSHV) or human herpes virus-8 (HHV-8) and the development of Kaposi's sarcoma (KS). To clarify the role of HHV-8 in KS pathogenesis, we investigated at the cellular level by in situ hybridization the expression of a recently described 0.7-kb HHV-8-encoded mRNA (T0.7 mRNA) in KS tissues of different epidemiological origin (AIDS-KS, African endemic KS and classical KS). The T0.7 mRNA likely encodes a small membrane protein, supposedly expressed in latently HHV-8-infected cells. Indeed, we detected T0.7 mRNA in virtually all cells of the cell line BCBL-1 established from a body cavity-based lymphoma (BCBL) and latently infected with HHV-8. In all KS biopsies examined, independent of their epidemiological type, the late-stage (nodular) KS tissues showed a high level of T0.7 mRNA expression in typical KS spindle cells but also in endothelial cells lining blood vessels, indicating latent HHV-8 infection of these cells. The presence of T0.7-expressing cells was restricted to KS tumor tissue and therefore appears to indicate an important role of latent HHV-8 infection in KS pathogenesis.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Combination of chemotherapy and antiviral therapy for Epstein-Barr virus-associated non-Hodgkin's lymphoma of high grade malignancy in cases of HIV infection.

Two HIV patients with Epstein-Barr virus (EBV)-associated B cell lymphoma of high grade malignancy enjoyed prolonged remission after therapy with COPBLAM and the antiviral agent Acyclovir. After 3, respectively 5 cycles of treatment, the patients (stage C3 according to CDC) responded to the administered drugs by achieving complete remission. Under maintenance therapy with Acyclovir for 32, respectively 31 months, both patients still remain free of lymphoma as of today.

Acyclovir↗
PubMed1997

Monocytes in Kaposi's sarcoma lesions are productively infected by human herpesvirus 8.

PCR analysis and serological studies demonstrated a close association between Kaposi's sarcoma (KS)-associated herpesvirus, or human herpesvirus 8 (HHV-8), and the development of Kaposi's sarcoma (KS). The majority of the KS cells were shown to be latently infected by the virus. In this study we investigated which type of cell is productively infected in KS lesions. In situ hybridization was performed with strand-specific RNA probes complementary to the sequences coding for the minor capsid protein (VP23) of HHV-8. The VP23 gene is specifically expressed during the lytic or replicative period of the virus life cycle, and therefore it is a useful marker to detect productively infected cells. By in situ hybridization of KS lesions, a strong hybridization signal was detected only in a small subset of the KS cells of the lesions. Simultaneous application of immunohistochemical staining and in situ hybridization identified the virus-replicating cells to be of monocytic origin. Productively infected monocytes may be an important reservoir for transmission of the virus and for the increase and maintenance of the high load of HHV-8 generally observed in nodular KS lesions during late stages of infection.

Biomarkers↗
PubMed1997

Patterns of mycobacterium avium culture and PCR positivity in immunodeficient HIV-infected patients: progression from localized to systematic disease, German Aids Study Group (GASG/IDKF).

Our aim was to establish the frequency and the longitudinal pattern of MAC culture positivity in late stage HIV-infected patients. Two other aims were to analyse risk factors for progression from localized to systemic disease and the value of PCR diagnosis using blood specimens. A total of 107 patients were recruited to be followed for 32 weeks. Prior MAC treatment and CD4 > 100/microliters were exclusion criteria. A total of 56 patients showed M. avium in at least 1 culture. 10/37 patients with MAC detected by culture first in 'non-sterile' specimens (stool, sputum) and urine progressed to systemic disease as determined by positive blood culture. Risk factors associated with this progression were a high symptom score at baseline, lymphadenopathy, anaemia, and low platelets. PCR was less sensitive than culture in detection of M. avium in blood specimens: Only 7/29 patients with positive blood cultures had a positive PCR at the same time. We conclude that symptomatic patients with advanced HIV-infection have a high frequency of MAC detection. Progression from localized to systemic culture positivity is associated with risk factors. Early 'pre-emptive' therapy is discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Oligosymptomatic neurosyphilis with false negative CSF-VDRL in HIV-infected individuals?

The true prevalence of neurosyphilis in HIV-infection is unknown, since a sufficiently sensitive and specific test is lacking. In a prospective study we found reactive serum TPHA and FTA-ABS IgG tests in 95 (31%) of 307 HIV-infected patients. Three of 11 patients with latent syphilis revealed reactive CSF-VDRL tests, six others only demonstrated CSF abnormalities. Resolution of CSF abnormalities during a six month follow up after high dose antibiotic therapy led to the diagnosis of oligosymptomatic or asymptomatic neurosyphilis in all nine patients. Thus, the specificity of the CSF-VDRL was 100%, but the sensitivity was only 33%. The overall prevalence of neurosyphilis was 2.9%, increasing to 9.5% in patients with a reactive serum TPHA. Our study emphasizes the importance of antibiotic therapy for presumptive neurosyphilis in HIV-infected patients with latent syphilis and CSF abnormalities but nonreactive CSF-VDRL tests, even if they are neurologically asymptomatic or present with complaints inconclusive of neurosyphilis.

Adult↗
PubMed1996

Increased neuropeptide Y-like immunoreactivity in cerebrospinal fluid and plasma of human immunodeficiency virus-infected patients: relationship to HIV encephalopathy.

Neuropeptide Y (NPY) is one of the most abundant and phylogenetically best conserved peptides in the mammalian central and peripheral nervous system where it plays an important role in the regulation of cardiovascular, metabolic, endocrine, immunological and cognitive functions. In a prospective study we determined neuropeptide Y-like immunoreactivity (NPY-LI) in cerebrospinal fluid (CSF) and plasma of 95 HIV-seropositive (n = 49) or seronegative (n = 46) patients who underwent diagnostic CSF examination. CSF and plasma NPY-LI but not noradrenaline concentrations were higher in seropositive than in seronegative patients indicating that raised levels of NPY-LI did not result from a non-specific activation of the sympathetic nervous system. Increased CSF NPY-LI was positively correlated with the degree of HIV encephalopathy (P < 0.01, Kruskal-Wallis test). Inflammatory disorders of the central nervous system and dementia due to other causes in HIV-seronegative patients were not associated with increased CSF NPY-LI. Our data suggest that increased CSF NPY-LI is a relatively specific phenomenon of HIV encephalopathy and may be involved in the pathogenesis of HIV-related neurological dysfunction. The links between retroviral infection and increased expression of neuropeptide Y and their pathophysiological implications remain to be determined.

AIDS Dementia Complex↗
PubMed1996

Oxymetholone promotes weight gain in patients with advanced human immunodeficiency virus (HIV-1) infection.

The effect of the testosterone derivative oxymetholone alone or in combination with the H1-receptor antagonist ketotifen, which has recently been shown to block tumour necrosis factor alpha (TNF alpha), on weight gain and performance status in human immunodeficiency virus (HIV) patients with chronic cachexia was evaluated in a 30-week prospective pilot study. Thirty patients were randomly assigned to either oxymetholone monotherapy (n 14) or oxymetholone plus ketotifen (n 16). Patients receiving treatment were compared with a group of thirty untreated matched controls, who met the same inclusion criteria. Body weight and the Karnofsky index, which assesses the ability to perform activities of daily life, and several quality-of-life variables were measured to evaluate response to therapy. The average weight gain at peak was 8.2 (SD 6.2) kg (+ 14.5% of body weight at study entry) in the oxymetholone group (P < 0.001), and 6.1 (SD 4.6) kg (+10.9%) in the combination group (P < 0.005), compared with an average weight loss of 1.8 (SD 0.7) kg in the untreated controls. The mean time to peak weight was 19.6 weeks in the monotherapy group and 20.8 weeks in the combination group. The Karnofsky index improved equally in both groups from 56% before to 67% after 20 weeks of treatment (P < 0.05). The quality of life variables (activities of daily life, and appetite/nutrition) improved in 68% (P < 0.05) and 91% (P < 0.01) of the treated patients respectively. Oxymetholone was safe and promoted weight gain in cachectic patients with advanced HIV-1 infection. The addition of ketotifen did not further support weight gain. These results suggest the need for a randomized, double-blind, placebo-controlled multicentre trial.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Active syphilis in HIV infection: a multicentre retrospective survey. The German AIDS Study Group (GASG).

OBJECTIVE: To study syphilis in HIV infection focusing on immunocompromised patients with an atypical or aggressive clinical course of syphilis, inappropriate serological reactions or an unreliable response to therapy. STUDY DESIGN: A multicentre retrospective chart review using a standardised questionnaire for all patients with active syphilis. SETTINGS: Thirteen dermatological and medical centres throughout Germany, all members of the German AIDS Study Group (GASG). PATIENTS: Clinical data of 11,368 HIV infected patients have been analysed for cases of active syphilis requiring treatment. Asymptotic patients with reactive serological parameters indicating latent syphilis without a need for treatment were excluded. RESULTS: Active syphilis was reported in 151 of 11,368 HIV infected patients (1.33%, range per centre 0.3%-5.1%). Most of the 151 syphilis patients were male (93%) and belonged to the homosexual or bisexual exposure category for HIV infection (79%); another 6% were iv drug users. Among the 151 syphilis patients primary syphilis was diagnosed in 17.2%, maculopapular secondary syphilis in 29.1%, ulcerating secondary syphilis in 7.3%, neurosyphilis in 16.6% and latent seropositive syphilis without clinical symptoms but serological abnormalities indicating active syphilis in 25.2%. A history of prior treatments for syphilis was reported in 50%. At the time of syphilis diagnosis 26.5% of the patients were in CDC stage II, 33.8% in stage III and 24.5% in stage IV of HIV disease (CDC classification 1987). CD4 cell count was lowest in those with ulcerating secondary syphilis (mean 307, SD 140/microliters) and neurosyphilis (351, SD 235/ microliters). The highest CD4 count was found in patients with early primary and early secondary syphilis (444, SD 163/microliters and 470, SD 355/microliters). Inappropriate serological response to syphilis infection was found in 81 of 151 patients (54%). Remarkable findings were false negative VDRL titres (11 patients with non primary syphilis), false negative TPHA (1) or 19S-IgM-FTA-ABS-tests (16), and strongly reactive VDRL (> or = 512, 8) or TPHA titres (> or = 10 240, 47). Treatment failures were reported in at least 6 of 151 cases (4%). CONCLUSIONS: Atypical clinical and serological courses of syphilis were observed in HIV infected patients. Ulcerating secondary syphilis with general symptoms ("malignant syphilis") was 60 times more frequent than in historic syphilis series. Neurosyphilis was found in one sixth of those with active syphilis. Therefore lumbar puncture should be considered a routine in coinfections with HIV and syphilis. Treatment efficacy should be monitored carefully.

Adult↗
PubMed1996

[HIV-1 associated autonomic dysfunction (HIVAD)].

In a controlled prospective study we used peripheral autonomic surface potentials (PASP) and an autonomic test battery (valsalva, 30:15 ratio, deep breathing, sustained handgrip, Schellong test) to evaluate HIV-1 associated autonomic dysfunction (HIVAD) in 38 HIV-seropositive patients. Criteria of exclusion were drug or alcohol abuse, concurrent infections, neoplasms, wasting syndrome and neurotoxic medication. We found increased PASP onset latencies and lower PASP amplitudes even in asymptomatic HIV-infected patients (p < 0.0125, Bonferroni corrected p-value). A mild or marked HIVAD was detected in 21% of the patients each. Heart rate and blood pressure responses were similarly affected. HIVAD was not related to HIV-1 associated changes in sural and tibial nerve conduction parameters. Our data suggest that HIVAD is a frequent complication of HIV-1 infection and that HIV-1 plays a direct role in its pathogenesis. Sympathetic and parasympathetic divisions of the ANS appear to be similarly affected.

Adult↗
PubMed1995

Identification of interleukin-1 and platelet-derived growth factor-B as major mitogens for the spindle cells of Kaposi's sarcoma: a combined in vitro and in vivo analysis.

By means of a combined in vitro and in vivo analysis we provide evidence that IL-1 beta and PDGF-B, but not OSM (oncostatin M) or IL-6, are major mitogens for the spindle cells of Kaposi's sarcoma (KS) in vivo. PDGF-B and IL-1 beta stimulated proliferation of cultivated KS spindle cells in vitro. Analysis of gene expression in vivo revealed that both factors as well as the PDGF beta-receptor are present in KS lesions. By contrast, IL-6 had no effect and OSM inhibited proliferation of cultivated KS spindle cells. Again, the effect of these factors on cultivated KS spindle cells in vitro was reflected by the gene expression observed in KS lesions in vivo. Neither the expression of IL-6 receptor nor of OSM could be detected in KS lesions by in situ hybridization. Moreover, in situ hybridization revealed an identical pattern of gene expression in cultivated KS spindle cells and KS spindle cells in vivo with respect to the above-mentioned cytokines [PDGF-B, IL-1 beta, IL-1 alpha, IL-6, OSM] and their receptors [PDGF beta-receptor, gp130, IL-6 receptor, leukemia inhibitory factor (LIF) receptor]. This further supported the suitability of cultivated KS spindle cells as an in vitro model in order to determine which cytokines may activate proliferation of KS spindle cells in vivo.

Cell Division↗
PubMed1994

Successful treatment of meningoencephalitis caused by Mycobacterium avium intracellulare in AIDS.

A wide variety of pathologies afflicting the CNS is see in patients infected with the human immunodeficiency virus. We report the case of relapsing meningoencephalitis caused by Mycobacterium avium intracellulare (MAI) in a homosexual male with the acquired immunodeficiency syndrome in whom repeated use of polymerase chain reaction was required to detect MAI-specific DNA in the cerebrospinal fluid. Successful responses to early empirical antibiotic combination treatment, including the drugs clarithromycin and rifabutin, were demonstrated by clinical, EEG, and CSF improvement during an 8-month period. To our knowledge, this study presents the first known patient with the acquired immunodeficiency syndrome effectively treated for MAI meningoencephalitis and suggests that modern antimycobacterial combination therapy may improve the poor prognosis of CNS infections with nontuberculous mycobacteria.

AIDS-Related Opportunistic Infections↗
PubMed1994

Elevation of intracranial pressure in acute AIDS-related cryptococcal meningitis.

Prior to the AIDS-era, elevation of intracranial pressure was known to be a typical complication of cryptococcal meningitis associated with an increased risk of early death. In AIDS-patients, however, the prevalence and clinical significance of this complication are as yet unclear. We analysed clinical features and courses, CSF findings, serological results and neuroimaging scans in acute cryptococcal meningitis in eight patients with AIDS. Five showed symptoms and signs compatible with raised intracranial pressure, which was life-threatening in one and the most probable cause of death in another. Serial monitoring of intracranial pressure together with repeated CSF analysis revealed that severe intracranial pressure elevation in AIDS related cryptococcal meningitis can occur in spite of effective antimycotic treatment, does not depend on an increased CSF/serum osmolality ratio or CSF overproduction and can be associated with normal cranial computed tomography and magnetic resonance imaging findings. Our data support the hypothesis that CSF reabsorption failure plays the crucial role in the pathophysiological mechanism. External lumbar drainage may be of benefit in selected cases of acute AIDS related cryptococcal meningitis with persisting life threatening elevation in intracranial pressure and normal computed tomogram.

AIDS-Related Opportunistic Infections↗