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Biomedical subjects

H Thaler

Publications and source records attributed to H Thaler.

At least 37 records · Page 2Linked to original sources
PubMed1996

Pain in ambulatory AIDS patients. II: Impact of pain on psychological functioning and quality of life.

The relationships among pain, psychological distress and other quality of life concerns were examined through a prospective cross-sectional survey of 438 ambulatory AIDS patients recruited from health care facilities in New York City. In this sample, 274 (62.6%) patients reported frequent or persistent pain during the prior 2 wks. Patients with and without pain completed a questionnaire packet that included measures of psychological symptom distress (Brief Symptom Inventory and the Psychological Distress Subscale of the Memorial Symptom Assessment Scale), depression (Beck Depression Inventory and Beck Hopelessness Scale), social support (Social Support Questionnaire), and overall quality of life (Functional Living Index-Cancer, modified for AIDS). Multivariate analyses (MANOVA, multiple regression) revealed significant associations between the presence and intensity of pain and scores on the measures of psychological distress, depression, hopelessness, and quality of life (P < 0.0001 for most analyses). Perceived adequacy of social support was also significantly associated with lower levels of psychological distress and depression, and better quality of life. These results demonstrate the significant relationships between pain, psychological well-being, and quality of life, and affirm the need to provide adequate treatment of pain in patients with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Implementing national standards for cancer pain management: program model and evaluation.

The purpose of this quasi-experimental (pre and posttest) study was to test a model pain management program (PMP) to implement the American Pain Society (APS) quality assurance standards for the management of acute and chronic cancer pain using a continuous quality improvement (CQI) approach to improve professionals' knowledge and skills, patient satisfaction, and to identify areas needing improvement. The sample consisted of 1210 nurse responses and 698 interviews of patients with pain during hospitalization at a major urban cancer center. The PMP provided a structure (standards), educational opportunities, and training in CQI methods. Outcome measures included a patient evaluation questionnaire and concerns checklist; nurse knowledge, attitude and barriers questionnaire; and focus groups to identify areas needing improvement. Significant improvements were found in patients' satisfaction, nurses' knowledge and attitude scores, and reductions in nurses' perceptions of barriers. Focus groups revealed the need for improved communication among disciplines about pain and better assessment of patients unable to self-report. The program met its goal of implementing the APS standards, educating nurses, and identifying "system" problems, and improving overall patient satisfaction.

Evaluation Studies as Topic↗
PubMed1996

Phase I study of continuous-infusion recombinant macrophage colony-stimulating factor in patients with metastatic melanoma.

Macrophage colony-stimulating factor (M-CSF) is a lineage-specific, homodimeric growth factor that supports the proliferation and maturation of bone marrow progenitors and the survival and function of mononuclear/macrophage cells. In vitro studies have demonstrated antitumor activity of macrophage colony-stimulating factor-treated monocytes against melanoma target cells. A Phase I study was conducted by administering the glycosylated form of the protein to patients with metastatic melanoma as two 7-day continuous i.v. infusions separated by a 2-week rest. Cohorts of three patients per dose level received escalating doses of 10-160 microgram/kg/day. Safety, clinical, and biological effects were evaluated. The infusions were well tolerated with occasional maximum grade 2 nonhematological toxicity. Rapidly reversible thrombocytopenia was the major hematological adverse effect. Its etiology may in part be explained by proliferation and activation of monocyte/macrophage cells in bone marrow samples. Evidence for a biological effect on tumors was suggested by the delayed, complete disappearance of multiple lesions in one patient and a decrease in the size of one marker lesion in a second patient with a mixed response. Fasting serum cholesterol levels decreased during the infusions and may represent an additional therapeutic application for this growth factor.

Adult↗
PubMed1994

Radiation dose-dependent changes in tumor metabolism measured by 31P nuclear magnetic resonance spectroscopy.

The effects of radiation dose upon a hypoxic murine mammary carcinoma were followed using 31P nuclear magnetic resonance spectroscopy. Animals were studied before and over the course of 9 days after tumors were irradiated with a single dose of 0, 4, 8, or 17 Gy. The current data is compared to our previous studies of the effects of 32 or 65 Gy on the same tumor model. The energy status of the tumors, as reflected in nucleotide triphosphate:Pi and phosphocreatine:Pi ratios, improved after receiving a dose of 8 to 65 Gy and decreased after receiving 0 or 4 Gy doses. The energy status of the 8- to 65-Gy dose cohorts reached a maximum between 1 and 4 days after irradiation. Additionally, the change in the hypoxic cell fraction 48 h after a 17-Gy dose was determined; it was calculated from changes in the doses required to control 50% of the tumors post radiation for clamped (hypoxic) and unclamped (normoxic) tumors in parallel animal cohorts. A significant decrease compared to preirradiation values was observed in the hypoxic cell fraction following 17 Gy irradiation. This decrease was temporally coincident with increases in tumor energy status measured using nuclear magnetic resonance and was similar to our previously reported results of the change in hypoxic fraction 48 h after a 32-Gy dose. Changes in the relative ratio of phosphomonoesters showed a strong dose dependence after irradiation. The downfield component of the phosphomonoester peak, which consists largely of phosphoethanolamine, increased relative to the upfield component, phosphocholine. This dose-dependent ratio reached a maximum approximately 7 days post radiation. Changes in the levels of membrane phospholipid precursors may be related to alterations in cell proliferation or may be a result of radiation-induced membrane damage.

Animals↗
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.

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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↗