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Biomedical subjects

L Binder

Publications and source records attributed to L Binder.

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

Association of intravenous phenytoin toxicity with demographic, clinical, and dosing parameters.

Previous studies investigating intravenous phenytoin toxicity have been largely anecdotal, and have inferred an association with older patients, cardiovascular disease, and higher doses, concentrations, and infusion rates of phenytoin. This investigation sought to elucidate both the incidence and nature of acute intravenous phenytoin toxicity in emergency department patients, and to identify any demographic, clinical, or dosing associations with toxicity, by analyzing a retrospective case series over 3 years in a municipal teaching hospital. A consecutive series of 164 patients who received intravenous phenytoin loading in the emergency department following acute seizure presentation was identified. Demographic, clinical, and dosing data were collected, and the nature of toxicity was noted. Data were then analyzed statistically for potential associations with toxicity. Eight cases of hypotension and no apnea or arrhythmias were noted in the 164 patients (4.9% incidence). Analysis of demographic, clinical, and dosing data found statistically significant associations between hypotension and both a lower phenytoin dose administered (537 mg in hypotensive patients v 787 mg in normotensive patients, P = .00046) and the presence of abnormal neurological signs at initial presentation (20% incidence when abnormal signs present v 3.5% incidence when absent, P = .026). No other associations were found between toxicity and other variables. This sample size could detect differences ranging from 4% to 11% in complication rate (hypotension) for the various demographic, clinical, and dosing parameters with a statistical power of 80%. It was concluded that the incidence of hypotension from intravenous phenytoin administration in this study population was approximately 5%, and the incidence of apnea and cardiac arrhythmia in this series was 0%. No associations with age, comorbidities, or infusion rates were found, in contrast to other studies. Association of intravenous phenytoin toxicity with lower phenytoin dose is likely related to prompt cessation of the drug once signs of toxicity occur. The possible association of toxicity with abnormal initial neurological signs has not previously been reported and may possibly define a population at risk if validated by prospective research in additional populations.

Adult↗
PubMed1996

Expression of Bax in relation to Bcl-2 and other predictive parameters in breast cancer.

BACKGROUND: It has been suggested that modification of the physiological susceptibility to induction of programmed cell death in transformed cells contributes to the pathogenesis of cancer. One of the major regulators of cell death is the bcl-2 family. In breast cancer, altered expression of Bcl-2 has been described. Distribution of its counterpart Bax and the differential expression pattern have still to be evaluated. PATIENTS AND METHODS: Bax expression was investigated by immunohistochemistry in 122 primary breast cancers. Results were correlated with expression of Bcl-2 and other variables of predictive value. RESULTS: There was a positive association between Bax expression and histological grading, (over)expression of c-erbB-1 and -2 and proliferative activity. The correlation was most significant in cases where no concomitant Bcl-2 expression could be detected. In the same subgroup an inverse correlation with positivity for estrogen (and progesterone) receptors was observed. The presence of Bax was not significantly associated with either tumor type and size, nodal status or expression of c-erbB-3. CONCLUSION: Expression of Bax was coupled with negative histopathological features, especially when expression of Bcl-2 was downregulated concomitantly. It may appear that alterations of the differential Bax/Bcl-2 expression pattern take part in deregulation of proliferation and loss of differentiation, thus playing an important role in malignant progression.

Breast Neoplasms↗
PubMed1995

[Necrotizing herpes simplex encephalitis as the cause of a progressive dementia syndrome].

HISTORY AND FINDINGS: A 65-year-old woman was twice hospitalized because of disorientation and insomnia with depression. In the course of antidepressive treatment the symptoms regressed each time so that the diagnosis was made of pseudo-dementia during depression. About a year after the first admission the symptoms recurred, despite continued antidepressive treatment. Clinical criteria now suggested Alzheimer-type dementia as the diagnosis. COURSE AND TREATMENT: The symptoms of dementia increased markedly and generalized seizures requiring anticonvulsive drugs occurred after 4 months. Although IgG antibodies against Herpes simplex virus (HSV) were demonstrated in cerebrospinal fluid (CSF), no antiviral treatment was instituted because HSV encephalitis appeared unlikely at this stage. But the patient's mental and physical state further deteriorated in subsequent months. During an attack of pneumonia the patients became somnolent and went into status epilepticus. Repeat virological examination of CSF now revealed IgG and IgM antibodies against HSV, confirming encephalitis. Her condition markedly improved over 12 days on aciclovir, 750 mg 3 times daily intravenously. 6 weeks later the pneumonia recurred, as did the encephalitis, with apnoeic phases and massive left heart failure. The patient died a few days later. Immunohistochemical tests of brain tissue were positive for HSV type II. CONCLUSIONS: This case report demonstrates that an investigation on dementia must include a complete liquor analysis. If HSV encephalitis is suspected, an antiviral therapy must be administered immediately. Even in adults who seem to have normal immunity HSV type II can cause HSV encephalitis.

Aged↗
PubMed1995

Rapid reversible phosphorylation of rat brain tau proteins in response to cold water stress.

The effect of cold water stress (CWS) on the phosphorylation of tau proteins in rat brain was studied using monoclonal antibodies to phosphorylated (PHF-1) and non-phosphorylated (TAU-1) epitopes. CWS induced an immediate 2-3-fold increase of PHF-1 signal in the soluble fraction of rat brain cortex, hippocampus and cerebellum. A maximal 3-4-fold increase occurred in 30-90 min. The soluble TAU-1 signal decreased following the CWS and at 60 min became significantly lower (P < 0.05) than in the control. Both signals returned to the normal range within 3 h. CWS induced a similar increase in PHF-1 signal in adrenalectomized animals and in animals subchronically treated with cortisone. These data indicate that stress induces rapid phosphorylation of soluble rat brain tau without direct involvement of the hypothalamic-pituitary-adrenal axis.

Adrenalectomy↗
PubMed1995

Bcl-2 protein expression in breast cancer in relation to established prognostic factors and other clinicopathological variables.

BACKGROUND: Bel-2 inhibits most kinds of programmed cell death and provides a selective survival advantage to various cell types. Bcl-2 is physiologically expressed in ductal epithelia of the normal breast. The biological significance of Bcl-2 (over)expression for the development and progression of breast cancer has still to be evaluated. PATIENTS AND METHODS: A series of 133 primary breast cancers was investigated for expression of the Bcl-2 protein by immunohistochemistry of paraffin-embedded tissue sections. Results were correlated with other variables of established or presumed predictive value. RESULTS: A significant positive correlation was observed between Bcl-2 expression and positivity for estrogen and progesterone receptors (p < 0.001). High proliferative activity as assessed by Ki-67 staining correlated inversely with Bcl-2 expression (p < 0.001). Bcl-2 immunostaining was not related to positivity for c-erbB-1. It was negatively associated with overexpression of c-erbB-2 (p = 0.04), whereas a strong positive correlation was found with expression of c-erbB-3 (p = 0.01). There was a significant inverse correlation between histological grading and immunoreactivity for Bcl-2 (p < 0.001). N0 tumors tended to be Bcl-2 positive, but differences were not statistically significant. CONCLUSION: Bcl-2 was detected predominantly in differentiated tumors. Expression was associated with other favorable histopathological features and predictors of positive clinical outcome. Loss of Bcl-2 expression seems to be linked to loss of hormonal regulatability, increased dedifferentiation and deregulated proliferation.

Breast Neoplasms↗
PubMed1994

Yersinia enterocolitica septicemia in autologous blood transfusion.

BACKGROUND: Increasingly, autologous blood transfusions are used in elective surgical procedures to avoid the risk of infection due to allogeneic blood transfusion. CASE REPORT: A 64-year-old patient had to undergo the implantation of a total right hip endoprosthesis. During the transfusion of 1 unit of autologous packed red cells, the patient experienced high temperature and shock, which necessitated his observation in the intensive care unit for several days. Yersinia enterocolitica (type O:9) was isolated from the packed red cells, from the unit of fresh-frozen plasma separated from the same donation, and from one blood culture drawn from the patient. With appropriate therapy, the patient recovered without sequelae. CONCLUSION: Although autologous blood transfusions are safe with respect to transmission of human immunodeficiency virus or hepatitis B and C infections, the risk of bacterial septicemia remains.

Blood Transfusion, Autologous↗
PubMed1993

Determination of a fragment of the c-erbB-2 translational product p185 in serum of breast cancer patients.

Concentrations of a fragment of the c-erbB-2 translational product (p185 fragment) were measured in serum of 70 breast cancer patients, 19 healthy blood donors, and 18 pregnant women using a heterogenic enzyme immunoassay. The serum concentrations of blood donors and pregnant women were below 30 kU/l. Breast cancer patients showed serum concentrations up to 578 kU/l. All 9/70 patients with serum concentrations higher than 30 kU/l had clinical evidence of metastatic disease and the serum levels of all 35/70 patients without metastasis lay within the normal range. From 9/37 patients with p185 overexpression of the primary tumor in immunohistochemical analysis 3/9 patients with metastatic disease had elevated serum levels higher than 30 kU/l. In all, 6/9 patients without metastasis serum levels were below 30 kU/l. The data of the present study suggest that determination of serum p185 fragment concentrations may be useful as a diagnostic tool in postoperative follow-up of breast cancer patients with c-erbB-2 overexpression of the primary tumor.

Biomarkers, Tumor↗
PubMed1991

Poisonings in laboratory personnel and health care professionals.

A case report of an unresponsive chemist presenting to the emergency department is presented; in retrospect, the patient was discovered to have intentionally ingested cyanide. A review of literature regarding ingestions in laboratory and health care personnel reveals five common points encountered in these personnel: barbiturates, carbon monoxide, cyanide, azides, and methemoglobin-inducing chemicals. Key diagnostic findings, in the absence of history of exposure, are discussed for these five agents.

Adult↗
PubMed1991

Predictors of one-year pretransplant survival in patients with cirrhosis.

The aim of this prospective study was to examine the usefulness of flow-dependent dynamic liver function tests and conventional methods of evaluating liver function as predictors of pretransplant survival in patients with advanced cirrhosis. Patients who underwent orthotopic liver transplantation within the follow-up period of 365 days were excluded. One hundred one patients with histologically confirmed cirrhosis were studied. Fifty-eight patients had post-hepatitic cirrhosis, 13 had cryptogenic cirrhosis and 30 had biliary cirrhosis. During follow-up, 28 patients died of their liver diseases. At entry, we recorded indocyanine green half-life, monoethylglycinexylidide formation from lidocaine, bilirubin and albumin serum concentrations, activities of cholinesterase and alkaline phosphatase, prothrombin time, clinical complications of ascites and encephalopathy and the Pugh score. These variables were subjected as covariates to a stepwise survival analysis by use of the Cox proportional-hazards model. At the final step, Pugh score, monoethylglycinexylidide formation and indocyanine green half-life were found to be the only independent variables significantly related to 1-yr survival. The parallel combination of Pugh score and monoethylglycinexylidide test yielded the highest prognostic sensitivity (82%). The series approach combining either the Pugh score and indocyanine green test or the monoethylglycinexylidide and indocyanine green tests was associated with the highest specificity (96%/97%) and high predictive values of a positive result (81%/82%). These findings suggest that appropriate combinations of the studied flow-dependent dynamic liver function tests and the Pugh score could be useful in improving transplant candidate selection and the timing of transplantation.

Humans↗
PubMed1990

Mitogenic and binding properties of monoclonal antibodies to the prolactin receptor in Nb2 rat lymphoma cells. Selective enhancement by anti-mouse IgG.

Three monoclonal antibodies (mAbs) (T6, U5, and U6) against prolactin (PRL) receptors in rat liver were studied in the rat lymphoma lactogen-dependent (Nb2-11C) and autonomous (Nb2-SP) cell lines. The mAbs had strong affinity for lactogen receptors (Ka = 12-14 nM-1), similar to that of human growth hormone (hGH) which is a lactogenic hormone. T6 and hGH competed for the same binding site, while U5 and U6 interacted with another epitope. The 125I-hGH-receptor complex could be immunoprecipitated by either U5 or U6, but not by T6. Affinity labeling and immunoblotting revealed that hGH and U6 bind to a protein of 63-65 kDa. T6, U5, and U6 were mitogenic in Nb2-11C cells but their respective potencies were 185-, 70-, and 4700-fold lower than that of hGH. Anti-mouse IgG enhanced the mitogenic effect of all three mAbs and almost completely abolished the differences between them, although their mitogenic activity was still 60-120-fold lower than hGH. Des-13-hGH, a competitive antagonist of hGH which hardly effected the binding of 125I-U5, inhibited the U5-stimulated proliferation of Nb2-11C cells in a noncompetitive manner, indicating that simultaneous binding of both ligands fixed the receptor in a nonactive conformation. A Fab fragment of T6 was not mitogenic, and inhibited the hGH-induced mitogenesis in a competitive manner, but its mitogenicity could be restored by anti-mouse IgG. We suggest that the dimerization or oligomerization of the lactogen receptor in Nb2-11C cells is an obligatory step in the transduction of the mitogenic signal. It may be induced by binding of the mAb to a site, which can be either identical or may even be distinct from that which binds the lactogenic hormone.

Animals↗
PubMed1990

Effect of student loan indebtedness and repayment on resident physicians' cash flow. An analytic model.

Cumulative figures of "average medical student indebtedness," although meaningful, do not convey the effect of loan repayments on residents' cash flow, effect on a resident's value system and residency performance, and effect on trends in health care manpower allocation. Using a computer-based cash flow model, a "typical" house officer with $20,000 in undergraduate indebtedness who is training in a less expensive city will realize a $2390 deficit during internship and negative cash flow throughout a 5-year residency. House officers with extreme indebtedness (greater than $80,000) who are training in an expensive metropolitan area would accumulate an overall deficit approaching $75,000 or more, in excess of their undergraduate indebtedness, during a 5-year residency program. Effects of these findings on residency education and health care manpower issues, along with potential solutions for alleviating residents' cash flow problems, are discussed.

Computer Simulation↗
PubMed1990

A model preclinical, clinical, and graduate educational curriculum in emergency medicine for medical students and rotating residents.

The Society for Academic Emergency Medicine model curriculum for medical students and rotating residents was developed over a two-year period. The document was created as a complementary work to the undergraduate Core Content to provide appropriate emphasis, structure, and suggestions on the teaching of emergency medicine core curriculum topics at all levels. Consensus on the curriculum contents was reached from a national sample of emergency medicine educators. An educational matrix format was used to enhance flexibility based on the educational level of the learner and the instructional strengths of the teacher, and allowing for incorporation of a problem-based learning format. An outline of document contents and representative samples from each section are included; the entire document is available from SAEM.

Curriculum↗
PubMed1990

Resistance of gram-negative bacilli and staphylococci from blood cultures to aminoglycoside antibiotics. Comparison of 3 in vitro investigations from Austria 1982-1988.

A total of 790 blood culture isolates was collected during 3 study periods in 1982/83, 1984/85 and 1987/88. Staphylococci were the most frequent bacteria in the first two periods (56.5% and 63%, respectively). During the last period, E. coli was the most frequent of all species (27%). Differences in the distribution of bacteria between the laboratories were considerable. In one laboratory in Vienna, coagulase-negative staphylococci dominated in all 3 study periods (32%, 33% and 47%). Susceptibility against gentamicin, tobramycin and netilmicin (MIC less than or equal to 4 mg/l), as well as against amikacin (MIC less than or equal to 8 mg/l) were determined by a microdilution method. The resistance rates against gentamicin (G) were 25%, 21% and 25%, against tobramycin (T) 27%, 19% and 25%, against netilmicin (N) 6%, 4% and 19%, and against amikacin (A), 5%, 2% and 19%. Most resistant strains were staphylococci (G 26%-41%, T 26%-46%, N 3%-31%, A 3%-36%), whereas gram-negative bacilli were more susceptible (G 12%-14%, T 7%-11%, N 7%-9%, A 1%-7.5%). The increase of resistance against netilmicin and amikacin in staphylococci was most striking. Nearly all those strain could be attributed to one laboratory in Vienna. Most of them were coagulase-negative staphylococci. In the first study period, the most frequent pattern was resistance against gentamicin and tobramycin, whereas in the last period resistance to all 4 aminoglycosides dominated. The study demonstrates considerable local differences in antibiotic resistance. Monitoring of antibiotic resistance in collaborative studies using standardized methods should be a valuable tool in planning strategies for controlling an epidemic spread of resistance.

Amikacin↗
PubMed1990

Site-directed mutations of human growth hormone that selectively modify its lactogenic activity and binding properties.

Two novel analogs of human (h) GH, 1) Des-7-hGH (Arg8Met, Asp11Ala) in which the Arg8 was substituted by Met and Asp11 by Ala, and 2) bovine (b) GH/hGH hybrid II (MetAla 1-13/14-191, Ala11Asp) composed of 13 N-terminal amino acid of bGH and elongated by two amino acids (Met-Ala-1-13) and 14-191 amino acids of hGH, were constructed and expressed in Escherichia coli. CD spectra indicated that the alpha-helix content of the purified proteins was similar to that of the native hormone. Both analogs retained their full ability to stimulate the proliferation of Nb2 lymphoma cells, and their binding to the lactogen receptors in homogenate of Nb2 cells and in microsomal fraction from bovine lactating mammary gland was only slightly reduced. However, their ability to bind to the somatogen receptors in intact IM-9 lymphocytes and bovine liver was reduced by 7- to 11-fold (bGH/hGH hybrid II) and 20- to 30-fold (Des-7-hGH). Both analogs were able to down-regulate the respective lactogen and somatogen receptors in intact Nb2 and IM-9 cells. The galactopoietic activity of both analogs in the lactating bovine mammary explants bioassay was almost completely abolished, and the bGH/hGH hybrid II exhibited a remarkable antagonistic activity. These results further indicate that the lactogen receptors in different species or organs are not identical. We have shown that the new recombinant analogs of hGH that recognize both somatogen and lactogen receptors but have modified postreceptor effects are helpful in elucidating these differences.

Base Sequence↗
PubMed1990

Inhibition of mitochondrial carnitine acylcarnitine translocase by hypoglycaemia-inducing substances.

The rate of mitochondrial carnitine-carnitine exchange mediated by carnitine acylcarnitine translocase was measured in the presence of the two hypoglycaemia-inducing drugs, 2-(3-methyl-cinnamyl-hydrazono)-propionate and 2-(3-phenylpropoxyimino)-butyric acid (BM 13.677). Both substances caused a concentration-dependent decrease in the rate of carnitine uptake in guinea pig liver mitochondria. Apparent initial influx rates were decreased by 75% and 80% at a concentration of 2 mmol/l 2-(3-methyl-cinnamyl-hydrazono)-propionate and 2-(3-phenylpropoxyimino)-butyric acid, respectively. Intraperitoneal injections of 212 mumol 2-(3-phenylpropoxyimino)-butyric acid or 21 mumol 2-(3-methyl-cinnamyl-hydrazono)-propionate per kg body weight caused a noticeable decrease in blood glucose concentration. A significant fall of the blood ketone body concentration was achieved with 2-(3-methyl-cinnamyl-hydrazono)-propionate or 2-(3-phenylpropoxyimino)-butyric acid, at dosages of 21 and 255 mumol/l, respectively. Furthermore there was a dose-dependent increase in the plasma free fatty acid concentration in the presence of 2-(3-methyl-cinnamyl-hydrazono)-propionate. This increase, however, was much less pronounced with 2-(3-phenylpropoxyimino)-butyric acid. Metabolic effects of 2-(3-methyl-cinnamyl-hydrazono)-propionate are consistent with an inhibition of long-chain fatty acid transport, whereas an additional mechanism of action has to be assumed for 2-(3-phenylpropoxyimino)-butyric acid.

Animals↗