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Biomedical subjects

D Reichelt

Publications and source records attributed to D Reichelt.

At least 19 recordsLinked to original sources

Neurophysiological abnormalities in HIV-infected long term survivors.

BACKGROUND: HIV is a neurotropic virus causing neuronal damage independent of opportunistic infections. A subgroup of patients suffer from long-term infection without developing significant disease symptoms requiring antiretroviral therapy (long-term survivors, LTS). We investigated the prevalence and severity of neurophysiological abnormalities in LTS. METHODS: The outpatient database of the Dept. of Neurology, University of Münster, was searched for HIV-infection LTS (infection for more than 9 years, no antiretroviral therapy since infection, stable CD4-positive lymphocyte count of more than 400/ul). Their neurophysiological test results (nerve conduction studies, event-related potentials, EEG) were compared to a control group of patients with similar disease duration not fulfilling the criteria for LTS. RESULTS: Sixteen LTS patients and 22 control patients were investigated. Median age at examination was 35 years. There were no significant differences between the groups regarding age, sex, duration of the disease and way of infection. By definition, CD4+-lymphocyte counts differed between LTS and both control groups. Standard nerve conduction studies of the peroneal or the sural nerve were abnormal in 1 LTS patient and 3 control patients. Sural nerve paired stimulation amplitude showed abnormal findings in 4 LTS patients and 4 control patients. P300 latency was prolonged in 4 LTS patients and 4 control patients. EEG background frequency was normal in all but one patient (LTS). There were no differences between groups regarding any of the parameters. CONCLUSION: Sensitive methods showed subtle affection of the nervous system in HIV-infected outpatients infected for more than 9 years. However, there was no difference between patients fulfilling accepted criteria of LTS, and those who did not. LTS most likely form the extreme end of a continuum of disease severity.

Adult↗

Carbachol increases Na+-HCO3- cotransport activity in murine colonic crypts in a M3-, Ca2+/calmodulin-, and PKC-dependent manner.

The Na(+)-HCO(3)(-) cotransporter (NBC) mediates HCO(3)(-) import into the colonocyte via its pNBC1 isoform. Whereas renal kNBC1 is inhibited by increased cAMP levels, pNBC1 is stimulated. Cholinergic stimulation activates renal NBC, but the effect on intestinal NBC is unknown. Therefore, crypts were isolated from the murine proximal colon by Ca(2+) chelation and loaded with the pH-sensitive dye 2',7'-bis-carboxyethyl-5,6-carboxyfluorescein. Na(+)-HCO(3)(-) cotransport activity was calculated from the dimethylamiloride-insensitive (500 microM) intracellular pH recovery from an acid load in the presence of CO(2)-HCO(3)(-) and the intracellular buffering capacity. Carbachol strongly increased Na(+)-HCO(3)(-) cotransport activity compared with control rates. Ca(2+) chelation with BAPTA-AM, blockade of the M(3) subtype of muscarinergic receptors with 4-diphenylacetoxy-N-methylpiperidine methiodide, and inhibition of Ca(2+)/calmodulin kinase II with KN-62 all caused significant inhibition of the carbachol-induced NBC activity increase. Furthermore, PKC inhibition with Gö-6976 and Gö-6850 significantly reduced the carbachol effect, which may be related to the unique NH(2)-terminal consensus site for PKC-dependent phosphorylation of pNBC1. We conclude that NBC in the murine colon is thus activated by carbachol, consistent with its presumed function as an anion uptake pathway during intestinal anion secretion, but that the signal transductions pathways are distinct from those involved in the cholinergic activation of renal NBC1.

Animals↗

Highly active antiretroviral therapy (HAART) improves survival in HIV-associated Hodgkin's disease: results of a multicenter study.

BACKGROUND: The purpose of the study was to evaluate the outcome of Hodgkin's disease (HD) in patients infected with the human immunodeficiency virus (HIV) with respect to the use of highly active antiretroviral therapy (HAART). MATERIALS AND METHODS: This cohort study included patients with HIV-HD diagnosed from June 1984 to February 2004. Patients treated in the pre-HAART era (1984-1996) were compared with those belonging to the HAART era (1997-2004). RESULTS: Of 66 patients with HIV-HD, 47 (71%) presented with stage III/IV disease and 38 patients (58%) with an AIDS-defining illness. Fifty-nine of 66 patients (89.4%) underwent curative intended chemotherapy. Patients receiving HAART (n = 34) had a significantly better 2-year overall survival (OS) than those not receiving HAART (74% versus 30%, P <0.001). The 2-year OS of HAART-responders was 88% compared with 19% in patients without HAART-response (P = 0.0002). By multivariate analysis patients without HAART had a 5.6-fold higher risk for 3-year mortality [HR 5.6, 95% confidence interval (CI) 2.20-14.26]. Three-year mortality was significantly higher in patients without complete remission (HR 4.40, CI 1.77-10.99), with stage III/IV HD (HR 4.64, CI 1.31-16.49) and with CD4 cells <200/microl (HR 2.69, CI 0.99-7.33). CONCLUSIONS: Use of HAART significantly improved the overall survival in patients with HIV-HD.

Acquired Immunodeficiency Syndrome↗

[Correlation between clinical apparatus-based differential diagnosis and neuropathological diagnosis in patients with AIDS].

BACKGROUND: During the course of HIV infection, the majority of patients develop opportunistic cerebral neuro-manifestations. If conventional diagnostic tools are not sufficient, a stereotactic biopsy is often necessary. PATIENTS AND METHODS: In order to evaluate the correctness of the clinical diagnosis of cerebral neuro-manifestations in HIV-infected patients, we compared the results of cerebral biopsy or autopsy with the previous clinical diagnosis. A total of 19 biopsies and 49 autopsies could be analyzed. RESULTS: Except for HIV-associated encephalopathy, we detected a very high conformity between the clinical and the neuropathological diagnoses. We obtained the best sensitivity for progressive multifocal leukoencephalopathy (PML), whereas for cerebral toxoplasmosis the worst sensitivity and specificity was identified. CONCLUSION: We conclude that the diagnosis of PML can be made on clinical grounds alone, whereas the diagnosis of cerebral toxoplasmosis and lymphoma often requires a biopsy, which should be performed early.

AIDS Dementia Complex↗

[Cerebrospinal fluid parameters in various stages of HIV infection. Results of cross-sectional and longitudinal analysis].

In up to 50% of all human immunodeficiency virus (HIV) patients, the nervous system is clinically involved. Primary or secondary manifestations of the nervous system have been found in even 90% by neuropathological investigations. We present a retrospective analysis of cerebrospinal fluid (CSF) and serum data of 238 HIV patients. Data of cross-sectional analysis in 208 patients and longitudinal analysis in 30 patients are given. In addition, the viral load in CSF and serum was determined in 29 patients. The HIV patients without opportunistic infections showed increased levels of immunoglobulins and more oligoclonal bands. In later stages of the infection, beta-2 microglobulin as a marker of HIV-associated encephalopathy was increased. In the longitudinal study with an observation period of 1 year, an increase could be observed in total CSF proteins of patients who did not receive antiretroviral treatment. In patients with new opportunistic infections of the central nervous system, similar changes in CSF parameters were noted as in comparison to patients not infected by HIV but with the same opportunistic infections. Analysis of CSF is mandatory for the diagnosis and control of opportunistic infections.

AIDS-Related Opportunistic Infections↗

Immunoglobulin deposition in sural nerves of AIDS patients with distal-symmetric HIV-associated polyneuropathy.

The most frequent neurological diagnosis in peripheral nerve function of HIV-positive individuals is distal-symmetric polyneuropathy (DSPN). In this study we investigated the histopathology as well as the immunohistochemical expression of immunoglobulins IgA, IgG and IgM in post-mortem sural nerve tissue gained from 11 patients who had suffered from DSPN in the clinical course of AIDS (CDC 3C). We found that all 11 sural nerves showed signs of demyelination while in 6 out of 11 cases axonal degeneration could also be detected. Immunohistochemical expression of at least one immunoglobulin was found in all but two cases with deposits uniformly being located immediately beneath the basement membrane of capillary blood vessels and within the perineurium while endoneurial staining was discernable in three cases. The most commonly expressed immunoglobulin was IgA which was identified in 7 cases, followed by IgG and IgM which were positive in 6 and 5 cases, respectively. All three immunoglobulins were found to be expressed simultaneously in only two cases. Thus, our study shows that immunoglobulin deposits among other factors may be implicated in altering the function of sural nerves or enhance their vulnerability. In peripheral nerves they may be responsible for some of the common alterations in the development of AIDS-associated distal symmetric polyneuropathy.

Acquired Immunodeficiency Syndrome↗

[HIV-associated cerebral toxoplasmosis -- review and retrospective analysis of 36 patients].

Highly active antiretroviral therapy (HAART) has resulted in a reduction of morbidity and mortality in HIV-associated cerebral opportunistic infection. Before HAART, up to 50% of all HIV-infected patients in Europe developed cerebral toxoplasmosis, an encephalitis caused by reactivation of Toxoplasma gondii infection. Although potent therapeutical options exist, the prognosis is still poor. We describe the course of 36 AIDS patients with cerebral toxoplasmosis and present a review of clinical signs, diagnosis, therapy, and survival times. The main criteria for differential diagnosis from other secondary neuromanifestations such as primary CNS lymphoma, progressive multifocal leukencephalopathy, abscesses, and ischemic infarctions are described. Indications and problems of stereotactic biopsy are discussed.

AIDS-Related Opportunistic Infections↗

[Primary central nervous system lymphoma as a neurological manifestation of AIDS stage].

In patients infected with human immunodeficiency virus (HIV), the risk of developing non-Hodgkin's lymphoma is over 100 times greater than with noninfected persons. Primary central nervous system lymphoma as a complication of the acquired immunodeficiency syndrome (AIDS) occurs in up to 2.4% of all cases and is strongly associated with the Epstein-Barr virus. The prognosis is very poor, with a mean survival time of 21 to 27 days without therapy and up to 119 days with radiation therapy. We describe the course of seven AIDS patients with histologically proven primary central nervous system lymphoma and present a review of clinical symptoms, diagnosis, and therapy. The main criteria for differential diagnosis from other secondary neuromanifestations such as cerebral toxoplasmosis, progressive multifocal leukoencephalopathy, abscesses, and infarctions are described.

AIDS-Related Opportunistic Infections↗

[Progressive multifocal leukoencephalopathy in AIDS. Overview and retrospective analysis of 17 patients].

We describe retrospectively the course of 17 AIDS patients with progressive multifocal leukoencephalopathy (PML) and give a review of their clinical symptoms and survival times. The relative frequency of PML in our cohort of AIDS patients was 2.6%. The mean of CD4-positive cells was 80.5 +/- 82.5/microliter. CD4-positive cells were > 200/microliter only in one patient and increased significantly under a combination of three antiretroviral drugs whereas, with the other patients, CD4-positive cells did not increase with a maximum of two antiretroviral drugs. The mean survival time was 6.6 (1.5-20) months and correlated positively with the number of CD4-positive cells. The diagnosis of PML can be regarded as confirmed when JC-virus DNA is detectable in cerebrospinal fluid, typical changes can be seen in MRI and typical clinical symptoms occur. No effective therapy is known to date. Single case reports on therapy with cidofovir, as in one of the cases described here, showed positive results.

AIDS-Related Opportunistic Infections↗

The impact of HIV infection on primary headache. Unexpected findings from retrospective, cross-sectional, and prospective analyses.

Headache is one of the most important factors influencing the quality of life in patients infected with the human immunodeficiency virus type 1 (HIV). However, only symptomatic headache but not changes or primary headache types during HIV infection have been studied to date. Therefore, we aimed to determine the impact of an HIV infection on frequency and semiology of different primary headache types. Patients with confirmed HIV type 1 infection underwent a neurological examination, neuroimaging or EEG, and a standardized interview. Time pattern and symptoms of headaches (cross-sectional analysis), changes of headaches preexisting to their infection (longitudinal retrospective analysis), and changes of primary headaches during a 2-year follow-up (longitudinal prospective analysis) were evaluated as were the correlations between these headache patterns and different markers of HIV infection. One hundred thirty-one consecutive HIV-infected patients without evidence of a cerebral manifestation except mild encephalopathy were enrolled. The point prevalence of migraine was 16.0% (confidence interval (CI) 10.1-25.4%), of headache with a semiology of tension-type headache 45.8% (CI 33.7-62.2%), and of other headache types 6.1% (CI 3.0-12.5%). During the natural course of infection, the migraine frequency significantly decreased in the retrospective and in the prospective analyses, whereas the frequency of the headache with a semiology of tension-type headache significantly increased in all three analyses. In 20% of all patients, the tension-type headache could be considered as symptomatic due to the infection but not due to focal or general cerebral lesions. Changes of primary headache were significantly associated with different stages of the infection and with the presence of mild encephalopathy but not with antiretroviral treatment or CD4 cell count. HIV infection seems to be associated with a progressive decrease in migraine frequency and intensity which probably is related to the immunological state of the patients. Tension-type headache becomes more frequent during HIV infection. However, this can in part be related to secondary headache caused by the HIV in less than 50% of patients with tension-type headache. The progressing immunological deficiency of HIV-infected patients seems to influence pain processing of primary headache types in different ways.

Adult↗

Screening for HIV-associated distal-symmetric polyneuropathy in CDC-classification stages 1, 2, and 3.

OBJECTIVES: A total of 670 patients were screened for distal symmetric HIV-associated polyneuropathy during CDC stages 1-3 and its correlation to immunological deterioration. MATERIAL AND METHODS: Clinical examinations of 670 patients admitted to the neurological outpatient clinic at the Department of Neurology, University of Munster. Neurophysiological investigations were performed on the sural and peroneal nerve for detection of axonal and myelin lesion. RESULTS: Clinical examination proved progressive clinical signs and symptoms indicating distal symmetric polyneuropathy from CDC 1 (32%) to CDC 3 (55%). At least one neurophysiological result was impaired in CDC 1 in 25% and in CDC 3 in 45%. Significant correlation between neurophysiological changes and CDC4(+)-cells and beta-microglobuline were detected for stage CDC 3 C. CONCLUSION: Results show stage related prevalence of distal symmetric polyneuropathy already in early stages. In late stages of HIV-infection prevalence of distal symmetric polyneuropathy seems to be directly correlated to immunodeficiency syndrome. The pathogenesis of distal symmetric polyneuropathy during HIV-infection is up to now incompletely understood, but results indicate a clear dependency between progressive immunological dysfunction and neuropathy. High active antiretroviral therapy in patients suffering from distal symmetric polyneuropathy is a main topic of future studies.

Adult↗

[Cryptococcal meningoencephalitis in HIV infected immigrants. Diagnostic and therapeutic aspects with reference to evidence-based medicine"--an overview].

Cryptococcal meningitis is one of the most frequent forms of meningoencephalitis in AIDS patients. Before the introduction of triazole antibiotics like difluconazole, the frequency of this meningitis among AIDS patients was 5-10%, yet declined during the last years. Clinically, nonspecific signs of a meningeal inflammation predominate while focal neurological signs are rare. Rapid institution of high-dose antimycotic therapy is the keystone to improve prognosis and decrease mortality. Antimycotics of choice are amphotericin B, fluconazole, and flucytosin. Diagnosis is established by detection of cryptococcal antigen in cerebrospinal fluid, microscopic demonstration of cryptococci using India-ink, and cryptococcal cultures. Recent developments aim to improve antimycotic therapies. During the last years, lifelong secondary prevention with difluconazole was established. Cryptococci which are resistant against fluconazole and amphotericin B are a special challenge, yet fortunately are rare. Longterm outcome of patients is determined by the progression of the underlying immunosuppression. Therefore, combination of secondary prophylaxis with modern antiviral substances is important. Clinical decision analysis in patients with suspected cryptococcal meningitis is presented using methods from evidence-based medicine.

AIDS-Related Opportunistic Infections↗

[Cidofovir (vistide) in therapy of progressive multifocal leukoencephalopathy in AIDS. Review of the literature and report of 2 cases].

The progressive multifocal leukoencephalopathy (PML), a complication of the acquired immunodeficiency syndrome (AIDS) in 4%-5% of all cases, is an encephalitis caused by the JC papovavirus. The prognosis is very poor with a mean survival time after diagnosis of 3 to 6 months. No effective therapy is known to date. Therapeutic trials in small groups of patients with alpha-interferon, didanosine, and arabinoside were of minor success. A controlled study with cytarabine did not show any efficacy. Single case reports on a therapy with cidofovir (Vistide), an approved nucleotide-analogone in the therapy of cytomegalovirus-retinitis in AIDS-patients without renal dysfunction, showed positive results. We describe 2 more cases of a therapy of cidofovir in AIDS-associated PML. Out of 22 cases described in the literature, including these 2 cases, with a therapy of cidofovir in AIDS-associated PML, 16 patients improved under therapy, 2 remained stable, and only 4 patients still worsened fulminantly. These results indicate an additive antiviral effect of cidofovir against JC-virus. This may be used in the therapy of PML in AIDS-patients because no alternative antiviral therapy of PML is available at present. The efficacy of cidofovir for the therapy of PML is suggested by case reports. The exact mechanisms leading to an improvement under a therapy with cidofovir in the 16 cases described so far should be evaluated in a randomised, controlled study with an adequate size of cohorts.

AIDS-Related Opportunistic Infections↗

Cerebral vasculopathy in HIV infection revealed by transcranial Doppler: A pilot study.

BACKGROUND AND PURPOSE: There is growing evidence for affection of cerebral vessels during human immunodeficiency virus (HIV) infection. We prospectively evaluated cerebrovascular reserve capacity (CRC) in HIV-seropositive patients by transcranial Doppler sonography (TCD) after systemic administration of acetazolamide. We hypothesized that a disturbed vasoreactivity would reflect the cerebral arteries' involvement in HIV infection. METHODS: We assessed the mean blood flow velocity (BFV) of the middle cerebral artery and its increase after intravenous administration of 1 g acetazolamide (CRC) in 31 HIV-infected individuals without symptoms of cerebrovascular disease (mean+/-SD age, 39+/-11 years). Stenotic or occlusive lesions of the large brain-supplying arteries were excluded by color-coded duplex and transcranial imaging. BFV and CRC were also measured in an age-matched group of 10 healthy control subjects. Patients were classified according to clinical, laboratory, and neurophysiological parameters. We also performed cerebral MRI (n=25) and rheumatological blood tests (n=26). RESULTS: Baseline BFV and CRC both were significantly reduced in HIV-infected patients as compared with control subjects (P<0.05, Student's t test). These findings did not correlate with duration of seropositivity, helper cell count, or other clinical, rheumatological, and neuroradiological findings. CONCLUSIONS: Our findings support the hypothesis of a cerebral vasculopathy etiologically associated with HIV infection.

AIDS Dementia Complex↗

Progressive peripheral and central sensory tract lesion in HIV-infected patients evidenced by evoked potentials (a three-year follow-up study).

OBJECTIVE: To investigate progression of peripheral and central sensory tract lesion and its correlation to immunological deterioration. METHODS: Clinical and neurophysiological investigation (evoked potentials of the median and tibial nerve) and immunological parameters (CD4-cells, beta 2-microglobuline) were followed up in 160 patients (24 females, 136 males, HIV infection for 2.7 +/- 2.3 years, mv +/- 1 sd) up to four times over approximately 3 years regardless of disease stage and evidence of neurological symptoms. Recordings were done using needle electrodes over the Th12 and C7 spinous process and from the scalp (10/20 system) in the conventional manner. Statistical analysis was performed intraindividually and in comparison to normal laboratory values (n = 96). RESULTS: All parameters deteriorated during the follow-up period. Statistical analysis showed significant differences between probands and patients for evoked potentials, but also a significant deterioration for evoked potentials after three years at the end of the follow-up study. A significant correlation between progressive impairment of evoked potentials and laboratory data was found. CONCLUSION: HIV infection induces a progressive lesion of the ascending sensory tracts. The results indicate a peripheral neuropathy as well as a progressive lesion of the ascending central sensory tracts. Pathogenesis of polyneuropathy and of central sensory tract lesion is up to now conjectural. Laboratory investigations indicate a clear-cut correlation between immunological alterations induced by HIV infection and its neurologic manifestation on ascending sensory tracts.

Adult↗

Impact of antiretroviral treatment on AIDS dementia: a longitudinal prospective event-related potential study.

We investigated the impact of antiretroviral treatment on event-related potentials (ERP) as a possible marker of AIDS dementia. A total of 154 HIV-infected patients without central nervous system (CNS) neoplasm or opportunistic infection were examined and randomized to receive either zidovudine 500 mg/day or no antiretroviral treatment. The participants were prospectively examined by visually evoked ERP in a longitudinal design. Latencies and amplitudes of ERP were evaluated at the beginning of the study, after 1 year, and after 2 years. After 1 year, 98 patients could be analyzed, 47 of whom were taking zidovudine. In the treatment group, P3 latency was 419 +/- 55 msec at baseline and 424 +/- 52 msec at follow-up (not significant). In the patients without treatment, P3 latency was 437 +/- 42 msec at baseline and 462 +/- 53 msec at follow-up (p < .0001, Wilcoxon test). A significant inverse correlation existed between P3 latency and CD4 cell count in both groups. The increase of P3 latency in untreated patients and a stable P3 latency in treated patients could be confirmed in a subgroup analysis of 21 patients with a follow-up of three examinations in a 2-year period. Our data suggest that zidovudine has a positive impact on AIDS dementia as measured by ERP. This finding was observed in patients in different stages of HIV infection, thus suggesting that zidovudine is indicated in all stages of HIV infection to treat encephalopathy.

AIDS Dementia Complex↗

High-signal lesions in the midbrain on T1-weighted MRI in an HIV-infected patient.

In addition to opportunistic infections, neoplasms or cerebrovascular complications, metabolic encephalopathies are a classical cause of diffuse brain dysfunction in HIV infection and are frequent in the terminal stage. We report an HIV-infected patient with symmetrical, focally increased signal in the midbrain on proton density-and T1-weighted MRI without corresponding high signal on T2-weighted images or on CT. While the precise nature and cause of this uncommon finding is not fully understood, the available evidence suggests that these lesions might represent a novel metabolic encephalopathy.

AIDS Dementia Complex↗