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Biomedical subjects

S Poser

Publications and source records attributed to S Poser.

At least 19 recordsLinked to original sources

Differential diagnosis of HTLV-I-associated myelopathy and multiple sclerosis in Iranian patients.

Two Iranian patients with chronic progressive spastic paraparesis and urinary dysfunction were referred to our hospital with the presumptive diagnosis of multiple sclerosis (MS). Routine CSF analysis and magnetic resonance imaging of the two patients were only partially characteristic of MS. Testing for antibodies to human T-cell leukemia virus type I [HTLV-I] in serum using a radioimmune precipitation assay revealed antibodies to HTLV-I in both patients. The infection with HTLV-I was confirmed by polymerase chain reaction (PCR) and liquid hybridization analysis using primers to the tax/rex region and a corresponding probe, demonstrating proviral DNA in peripheral blood mononuclear cells of both patients. On the basis of these findings demonstrating the presence of proviral HTLV-I DNA in the two Iranian patients, the initial diagnosis of MS was corrected to that of HTLV-I-associated myelopathy (HAM). In contrast, several patients with definite MS (nine from Germany, two from Iran) with a relapsing and remitting form of the disease were tested for HTLV-I infection by enzyme-linked immunosorbent assay and PCR, which yielded negative results. However, the mother of one HAM patient was found to be infected with HTLV-I. To support an association between HTLV-I infection and CNS disease in the two HAM patients, we analyzed the production of specific IgG antibodies within the CNS based on a simple enzyme immunoassay for viral IgG antibodies in CSF and serum. In the two HAM patients there was significant intrathecal antibody production directed against HTLV-I, but this was not found in any of the samples from MS patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Deltaretrovirus Antibodies

Mortality in patients with dependence on prescription drugs.

In 1974 we started a follow-up of patients with different psychoactive substance use disorders (PSUD) according to DSM-III; 2082 cases out of 2127 were analyzed; 1370 patients had taken legal drugs (i.e. prescription drugs and/or over-the-counter drugs); 444 patients suffered from abuse or dependence of legal drugs alone; 678 combined legal drugs and ethanol, and 248 cases combined legal and illegal drugs, often together with ethanol. A group of 712 alcoholics were included for comparison. Mean time under observation was 6.5 +/- 5.4 years, and 269 patients died. Mortality and survival were calculated and compared with expected survival from the normal population of the former Federal Republic of Germany. Mortality in all subgroups of PSUD was increased, the standardized mortality ratio (SMR) for patients on legal drugs alone being 2.1. Patients with legal plus illegal drugs had a SMR as high as 20.7; those with legal drugs plus ethanol 3.4; and alcoholics 4.2. The increased mortality seemed to be constant over the years. Mortality decreased in patients with stable abstinence. There was no clear sex difference. Abuse had a better prognosis than dependence. An estimation of potential life lost by the different PSUDs was attempted. Patients on legal drugs died from suicides, malignancies or accidents (including intoxication). In alcoholics or patients on legal drugs plus ethanol malignoma, liver cirrhosis, accident and suicide were the most prominent causes of death.

Adult

Early prognostic factors for disability in multiple sclerosis, a European multicenter study.

The effects of initial clinical variables on short-term prognosis are analyzed in a cross-sectional study of 574 multiple sclerosis patients from 7 centers in 5 European countries. Patients with a primary progressive course had a 2.3 higher mean disability score (EDSS) than the primary remittent group after a mean duration of disease of 6.6 years. High age at onset was associated with a primary progressive course, and was also related to increased risk of a rapid shift to a secondary progressive course. Among the remittent patients without a secondary progressive course a high age at onset was significantly correlated to a higher disability score. In the whole remittent group the presence of pyramidal and cerebellar symptoms at onset predicted both a high disability score and a rapid shift to a secondary progression, while the effect was reverse for sensory and visual symptoms. No difference between the sexes was found.

Adult

Acute demyelinating disease. Classification and non-invasive diagnosis.

Five young patients are described with biopsy-proven acute demyelinating disease. Two cases are classified as Schilder's disease, a particular childhood form of multiple sclerosis (MS) with atypical clinical manifestation, normal or atypical CSF-findings and large bilateral lesions in magnetic resonance imaging (MRI). Two further cases presented with a fulminant bout of MS with typical clinical picture and CSF-findings; they are classified as Marburg's disease. The last case was an acute second bout of classical MS. The biopsy seemed to be justified in 4 cases, but unnecessary in the last case. Localized proton magnetic resonance spectroscopy (MRS) performed in one case allowed us to examine the focal cerebral abnormalities directly and non-invasively. The spectra revealed a pattern typical of acute demyelination suggesting potential for a replacement of biopsy in the future.

Adult

The use of recombinant antigens in ELISA procedures for the quantification of intrathecally produced HIV-1-specific antibodies.

An ELISA procedure is described for the quantification of intrathecally synthesized immunoglobulin G antibodies to human immunodeficiency virus (HIV) antigens. Recombinant p17, p24, endonuclease (END), reverse transcriptase (RT), a peptide from the transmembrane region of gp41 (ENV80) and a fusion protein containing HIV-1 and HIV-2 epitopes were compared with a commercially available ELISA. Using a reference serum, antibodies in serum and cerebrospinal fluid (CSF) to all of the antigens could be measured quantitatively in a reliable and reproducible fashion. Despite the fact that the titer varied up to 10(5)-fold between CSF and serum, interassay variability ranged from 3.87% for p17 to 8.41% for RT and intra-assay variability varied from 3.9% +/- 1.2% for p17 to 14.3% +/- 3.9% for the commercial ELISA. Antibody specificity indices (ASI) obtained by relating CSF/serum titers with reference to the corresponding IgG concentrations can be used to detect intrathecal synthesis of virus specific antibodies.

Enzyme-Linked Immunosorbent Assay

Impact of magnetic resonance imaging (MRI) on the epidemiology of MS.

The availability of MRI has turned out to have less impact on the epidemiology of MS than originally expected. Only 3/69 patients diagnosed between 1986 and 1990 in the epidemiologic area of South Lower Saxony (Germany) would have been missed without MRI. However in 18/50 patients the diagnostic classification changed, mostly from possible to probable MS. As we included possible cases from the beginning of our studies, the overall figures remain essentially unchanged. Epidemiologists who excluded possible cases from their surveys may experience more problems with the introduction of MRI.

Brain

Analysis of oligoclonal antibody bands against individual HIV structural proteins in the CSF of patients infected with HIV.

Intrathecal antibody responses to HIV were investigated by a highly sensitive immunoblot assay. Serum and CSF specimens were tested for reactivity with the recombinant HIV gag proteins p15, p17 and p24 and with the recombinant transmembrane protein p41. Autochthonous production of virus-specific IgG to one or more HIV structural proteins was seen in 8 of 10 asymptomatic seropositive subjects, in 3 of 4 men with AIDS-related complex, and in 9 of 13 patients with AIDS. These results were consonant with an elevated CSF/serum antibody ratio to total HIV antigen. The high frequency of local HIV-specific antibody synthesis in seropositive individuals without related clinical symptoms indicates an early involvement of the CNS in HIV infections.

Acquired Immunodeficiency Syndrome

Survival in multiple sclerosis.

Survival from onset of symptoms was calculated for two series of MS patients, a population-based epidemiologic series from southern Lower Saxony of 224 cases, and a revised hospital series of 1429 cases from 11 neurologic centers throughout the Federal Republic of Germany. Median survival for the epidemiologic series was 35-42 years, with no finer estimate possible. Observed survival was 3/5 expected survival after 35 years of illness. Survival in this series was similar to that from two other population-based reports. No significant difference was found between the sexes, though patients with onset at age 35 + had a significantly shorter survival than those with onset at age under 35 years. The much larger hospital series, where median survival was 30 years, demonstrated significant differences separately favoring females and young onsets. However, the ratios of observed to expected survival from population life tables were strikingly similar among all four subgroups defined by sex and age at onset. While overall there is a substantial reduction in the expectation of life in MS, the differential survival by sex and age appears to be a reflection of the expected survival by sex and age per se, and not that of the disease.

Adult

Increasing incidence of multiple sclerosis in South Lower Saxony, Germany.

In the epidemiological area of South Lower Saxony the prevalence of multiple sclerosis increased from 51/100,000 in 1969 to 99 in 1986. The mean annual incidence increased from 2.6 for the period from 1964-1974 to 4.6 for 1975-1985. This trend is significant (p = 0.0068). Diagnostic criteria, methods of case finding and analysis of the data remained stable. Minor necessary changes as for example due to new data protection laws and new handling of early cases by practising physicians can hardly explain this significant increase. In consideration of similar reports from all over the world biological exogenous factors are suspected but remain to be identified.

Adult

Chronic HIV encephalitis--I. Cerebrospinal fluid diagnosis.

To establish a reliable procedure for the early detection of central nervous system involvement in HIV infection, paired cerebrospinal fluid and serum samples of 59 patients were analysed. Fifteen were HIV antibody positive without clinical symptoms (stage I), 12 had lymphadenopathy syndrome or AIDS-related complex (stage II), and 32 had AIDS (stage III). Intrathecal synthesis of HIV antibodies was determined by a modified ELISA. Antibodies in CSF and serum were evaluated at identical immunoglobulin G levels to correct for the actual blood-CSF-barrier permeability. A CSF/serum quotient above 1.5 is indicative of intrathecal antibody synthesis, which was found in 47% of the patients in stage I, 67% in stage II, and 84% in stage III. These findings indicate an early and frequent invasion of the CNS.

Acquired Immunodeficiency Syndrome

Chronic HIV encephalitis--II. Clinical aspects.

Combined medical, neurological, and serological investigations were carried out in 59 patients infected with human immunodeficiency virus (HIV). In stage I clinical and neuropsychiatric testing did not reveal evidence for HIV encephalitis as diagnosed by local antibody production in CSF. Neuropsychiatric abnormalities, brain atrophy, memory and cognitive impairment reliably indicated HIV encephalitis in later stages. The commonest symptoms were cerebellar and brainstem signs, followed by dementia. Epileptic fits and hemiparesis always were associated with cerebral toxoplasmosis. A polyneuropathy was frequently found but other causes have to be considered.

Acquired Immunodeficiency Syndrome

Cyclosporine versus azathioprine in the long-term treatment of multiple sclerosis--results of the German multicenter study.

In a double-blind controlled trial of 194 patients with clinically definite active multiple sclerosis, 98 were randomized to treatment with cyclosporine (CyA, 5 mg/kg/day), and 96 to treatment with azathioprine (Aza, 2.5 mg/kg/day). Eighty-five patients in the CyA group and 82 in the Aza group completed a treatment period of 24 to 32 months in accordance with the study protocol. No significant differences could be detected between the two treatment groups at the end of the trial. Assessment was done by serial quantitative neurological examinations and Kurtzke's Expanded Disability Status Scale. Frequency of relapse and patient self-evaluation also failed to show significant differences. Overall deterioration observed in both groups during the trial was only minor. The incidence of side effects in the CyA group was more than two times that in the Aza group. We conclude that CyA as a single agent cannot be the drug of final choice in long-term immunosuppressive treatment of relapsing-remitting and relapsing-progressive multiple sclerosis.

Adolescent

Magnetic resonance imaging in the evaluation of treatment in multiple sclerosis.

Magnetic resonance scans of 74 patients with multiple sclerosis participating in a controlled trial were compared 6 months before and at the end of a 24-32 months-treatment period with either Cyclosporin A (n = 31) or Azathioprine (n = 43). Both qualitative rating and computation of lesion volume showed deterioration in more than 40% of the patients, while by clinical criteria only 10-30% were worse. No significant difference was noted when the two treatment groups were compared. If careful repositioning and standardized image parameters are used, MRI is an indispensable tool for the objective determination of disease progression in MS although it cannot replace clinical examination.

Azathioprine