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Biomedical subjects

H Thaler

Publications and source records attributed to H Thaler.

At least 19 recordsLinked to original sources
PubMed1992

Problems of geriatric pharmacotherapy.

No one dies of old age by itself; death is always due to a disease of some kind. This means that safe and effective therapy for old people is a matter of great practical importance. From what has been said above it will be obvious that the effects of drugs in old people are similar to their effects in the young, but there may be differences in degree in their susceptibility to adverse reactions. The existing data are by no means abundant, sometimes contradictory and of limited evidential value. Looking at the picture as a whole, one cannot but agree with those authors who state that the available results are insufficient to substantiate the general opinion that old age in itself heightens the risk of all forms of pharmacotherapy. From the practical point of view it is nowadays essential that no drug should be prescribed for an elderly patient without strict scrutiny of the need for it, that such drugs should not be administered for any longer than is absolutely necessary, that treatment should normally be started with smaller doses than those usually given to younger adults and, lastly, that surveillance for possible side effects should be particularly close. The author states that it must not be forgotten that geriatric patients frequently consult specialists in addition to their family doctors and that they are perhaps overinclined to listen to advice on drug treatment from those about them. One of the duties of the family doctor is to check the assortment of drugs which his patient is consuming--often an alarming total--and to cut down their number to those which are really necessary.

Aged↗
PubMed1990

Identification of cytochrome P450IA2 as a human autoantigen.

Autoantibodies occurring in a patient with idiopathic autoimmune type chronic active hepatitis (CAH) were found to react with purified rabbit cytochrome P450IA2 and to a much lesser extent with P450IA1. Both cytochrome P450s are known to be inducible by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the rabbit, and the expression of the microsomal protein recognized by the patient serum was induced in adult rabbit livers after treatment with TCDD. This protein is only weakly detected in liver microsomes from neonatal rabbits exposed to TCDD in utero, which is consistent with the age-dependent induction of P450IA2 by TCDD. The serum specifically reacted with a protein of similar size in microsomes prepared from COS-1 cells transfected with an expression vector containing the full length human P450IA2 cDNA. This reactivity was not detected in the cells transfected with the vector alone, indicating that the antibody recognizes human P450IA2. In addition, the serum extensively inhibited 7-ethoxyresorufin O-deethylation catalyzed by isolated human liver microsomes. This catalytic activity is associated with class IA P450s in other species. A screen of sera from patients with various hepatic and nonhepatic diseases indicates that the autoantibody to P450IA2 occurs rarely in CAH. Cytochrome P450IA2 becomes the third P450 identified as an autoantigen in inflammatory liver diseases.

Adult↗
PubMed1990

Chronic active hepatitis associated with vitiligo, nail dystrophy, alopecia and a new variant of LKM antibodies.

In this report we describe the case of a 7-year-old boy, suffering from autoimmune-type chronic active hepatitis (AI-CAH) associated with vitiligo, nail dystrophy, alopecia areata and a variant of liver kidney microsomal (LKM) autoantibodies. This patient's antibodies are different from LKM-1 which are directed against cytochrome P450 db1. They react predominantly with perivenous hepatocytes in contrast to LKM-1 antibodies which homogeneously stain the whole liver lobule in immunofluorescence. In Western blot analysis this LKM variant reacts with a liver microsomal protein of approx. 50 kDa, but not with recombinant LKM-1 (cytochrome P450 db1) antigen. Immunosuppressive treatment led to a normalization of liver histology after 1 year and a significant improvement of vitiligo and alopecia areata. In summary, a case of autoimmune-type chronic active hepatitis is presented which is associated with a new variant of LKM antibodies reacting with a 50 kDa microsomal protein different from cytochrome P450 db1. Furthermore, this patient suffers from extrahepatic syndromes (alopecia, nail dystrophy) that have not been described previously in LKM antibody-positive chronic active hepatitis.

Alopecia↗
PubMed1990

Expression in cultured human neuroblastoma cells of epitopes associated with affected neurons in Alzheimer's disease.

Of three human neuroblastoma lines tested, IMR32K (and IMR32 parental line) was the only cell line that, after its exposure to a differentiation medium, consistently developed materials recognized immunocytochemically by a panel of antibodies against paired helical filaments (PHF). Ultrastructurally, these cells accumulated, at their perikarya and neuritic extensions, spatially discrete arrays of fibrils, which occasionally occurred in twisted pairs. When these fibrillar structures appeared as paired helices, they exhibited dimensions and configurations reminiscent of PHF found in affected Alzheimer neurons, although less compact. Immunoelectron microscope examinations of the fibrillar structures in these neuroblastoma cells with one of these anti-PHF immunoprobes revealed that only subsets of fibrillar structures that appeared thickened or aggregated to form bundles were selectively immunolabeled. Cultures of these immortal neuroblastoma lines may provide a convenient model for studying aspects of PHF formation that are hard to examine in Alzheimer brain obtained at autopsy.

Alzheimer Disease↗
PubMed1990

Clonal analysis of infiltrating T lymphocytes in liver tissue in viral hepatitis A.

The pathogenic mechanism leading to liver tissue injury in hepatitis caused by hepatitis A virus is unclear. We have randomly established T-cell clones from liver biopsies from four patients with hepatitis A. A total of 578 clones was phenotypically analysed. During the acute phase of the disease CD8+ clones dominated over CD4+ clones, whereas in a biopsy taken late after onset of clinical syndromes more CD4+ than CD8+ clones were obtained. Interestingly, in a patient with a second exacerbation of the disease, more than 20% of all clones had the CD3+ WT31- CD4- CD8- 'NK-like' phenotype. All CD8+ clones had cytotoxic activity and approximately 50% of all CD8+ clones showed specific cytotoxicity against autologous fibroblasts infected with hepatitis A virus. The CD8+ cells also produced IFN-gamma in response to these target cells. Variable IFN-gamma production was observed with all types of T-cell clones. These results suggest that the liver injury in hepatitis A is not caused by a viral cytopathogenic effect but is due to an immunopathological reaction of sensitized cytotoxic T lymphocytes against infected hepatocytes. In addition, these studies show an enrichment of CD4-8-T-cell receptor alpha beta-chain-negative T lymphocytes at the site of an inflammation and suggest a role of these cells in an anti-viral reaction.

Acute Disease↗
PubMed1989

Positron emission tomographic measurement of blood-to-brain and blood-to-tumour transport of 82Rb. I: Error analysis and computer simulations.

Unidirectional blood-to-brain and blood-to-tumour transport rate constants (K1) for 82Rb (half-life 76 s) and plasma water volume per unit mass of brain/tumour tissue (Vp) can be estimated in vivo using dynamic positron emission tomography (PET). The accuracy of these estimates depends upon the accuracy of PET measurements of regional brain/tumour radioactivity and scintillation well detector measurements of whole-blood radioactivity, which, in turn, depend upon the time course of arterial blood radioactivity. A two-compartmental model has been employed to derive estimates for K1, k2 (efflux rate constant) and Vp from 82Rb/PET data. Errors in these parameter estimates have been studied (1) qualitatively using sensitivity function analysis and (2) quantitatively using computer simulations. The effect of adding a third irreversible compartment and its unidirectional rate constant, k3, has also been investigated. The advantages and disadvantages of bolus injection vs continuous infusion protocols are discussed. Precision in estimated parameters from actual patient data is compared to that obtained from computer simulations in part II of this paper.

Blood↗
PubMed1988

Thiamine and Alzheimer's disease. A pilot study.

As a test of the significance of previously described biochemical abnormalities in thiamine-dependent enzymes in brains and other tissues in patients with Alzheimer's disease, a double-blind, placebo-controlled, crossover, outpatient pilot study compared the effects of 3 g/d of oral thiamine hydrochloride for three months with those of a niacinamide placebo. Eleven moderately impaired patients with "probable Alzheimer's disease" by the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria completed the study. All patients were well nourished and had no stigmata of dietary thiamine deficiency. Their initial mean +/- SEM Mini-Mental State Examination score was 14.2 +/- 1.4, and the mean age was 72 years. Global cognitive rating by the Mini-Mental State Examination was higher during three months with 3 g/d of oral thiamine hydrochloride than with niacinamide placebo. Behavioral ratings, however, did not differ significantly, nor did clinical state when it was judged subjectively.

Alzheimer Disease↗
PubMed1988

Fatty change.

Explore the source record for details and available documents.

Chemical and Drug Induced Liver Injury↗
PubMed1988

Morbidity and mortality of craniotomy for excision of supratentorial gliomas.

Extensive surgical resection of supratentorial gliomas increases survival. However, some reports suggest that the perioperative morbidity and mortality outweigh the potential benefit of the procedure. We examined prospectively morbidity and mortality in 104 consecutive patients who underwent surgery for supratentorial glioma, as well as other factors that might affect the short-term outcome. To determine if our experience was unusual, we compared these results with those obtained from another academic neurosurgical center by a review of the records of 109 patients also treated surgically for supratentorial glioma. Mortality was 3.3% and the medical plus neurologic morbidity was 31.7%. Functionally significant neurologic worsening occurred in 42 (19.7%) patients. Complications were more frequent in patients with moderate or severe preoperative disabilities than those with mild or no preoperative disability. Patients with complete resection had fewer acute neurologic complications, and no greater risk of being neurologically impaired at 1 week, than patients with biopsy or less extensive procedures. Morbidity and mortality correlated with location: deep-midline lesions had a higher overall rate of perioperative complications (p = 0.032) and mortality (p = 0.019) and bilateral lesions a higher rate of hemorrhage (p = 0.017) and hydrocephalus (p = 0.010). Older patients (greater than 55 years) and those receiving high daily dose of preoperative dexamethasone (greater than or equal to 24 mg) had a significantly higher risk of surgical mortality. Reoperation for recurrent tumor carried no greater risk of mortality, neurologic deterioration, and infection than a first operation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

The role of infection in the etiology of preterm birth.

The hypothesis that infection induces or is a precursor to preterm birth or premature rupture of the membranes was examined in a prospective study of 193 randomly selected pregnant women. We investigated the prognostic significance of factors that suggest infection of the uterine cavity before pregnancy, such as a history of pelvic inflammatory disease, a history of intrauterine contraceptive device (IUD) use, multiple sex partners, and the presence of antisperm antibodies, in relation to premature rupture of the membranes and preterm birth. Sexual activity, a potential vehicle for bacterial exchange, was also charted throughout pregnancy via monthly interviews. We performed immunologic tests on each patient and obtained cultures of the cervix for aerobic and anaerobic bacteria and chlamydia at the first visit, occurring at six to 14 weeks' gestation, and again at 36 weeks. The results suggest that infection may indeed play a causative role in premature rupture of the membranes or preterm birth. A strong correlation was found between preterm birth and both a history of pelvic inflammatory disease (P = .004) and a history of IUD use (P = .0015). Amnionitis was associated with the presence of immunoglobulin G (IgG) antisperm antibodies (P = .02), as well as with a history of pelvic inflammatory disease (P = .0006). There was also a correlation between premature rupture of the membranes and a history of multiple sex partners (P = .02). This collective evidence implicates preexisting infection of the uterine cavity as a predisposing factor in premature rupture of the membranes, preterm delivery, and amnionitis.

Chorioamnionitis↗
PubMed1986

[Immunohistochemical studies on the occurrence of HBs antigen in alcoholic fatty liver and alcoholic fatty liver hepatitis].

120 liver biopsies of alcoholic fatty liver, alcoholic hepatitis and cirrhosis were studied immunohistochemically with regard to the occurrence of HBs-antigen. In no instance HBs-antigen was detected. These findings suggest neither a major influence of hepatitis B-virus on the progression of alcoholic liver cell damage nor a defect in immunologic responsiveness to hepatitis B-virus component in the alcoholic.

Adult↗