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Biomedical subjects

M Schwartz

Publications and source records attributed to M Schwartz.

At least 325 records · Page 18Linked to original sources
PubMed1995

Circulating ICAM-1 is increased in septic shock.

Adhesion molecules play a critical role in the interaction of circulating neutrophils with vascular endothelium during inflammation. Increased quantities of soluble, circulating intercellular adhesion molecule-1 (cICAM-1) are present in various inflammatory conditions. The purpose of this investigation was to measure cICAM-1 levels in septic adults, as well as to examine the relationship between this potential marker of endothelial-cell activation and the consequences of sepsis (i.e., multiple organ failure and death). Using a sandwich-type enzyme-linked immunosorbent assay (ELISA), we measured cICAM-1 in blood samples obtained within 12 h of admission to an intensive care unit (ICU) for sepsis and other conditions. We found cICAM-1 levels to be increased in 25 septic patients (1,259 +/- 159 ng/ml, mean +/- SEM) as compared with 12 healthy volunteers (355 +/- 41 ng/ml, p < 0.0001) and four ICU patients without systemic inflammatory response syndrome (SIRS) (585 +/- 76 ng/ml, p < 0.001). Twenty-five patients with SIRS but no evidence of causative infection also had elevated levels of cICAM-1 (937 +/- 144 ng/ml, p = 0.12 versus sepsis). Serial measurements over the first week of sepsis demonstrated persistent elevation in most patients. Day 1 cICAM-1 levels were higher (p = 0.017, ANOVA) in 16 patients with septic shock than in seven with severe sepsis and two with sepsis but without hypotension or hypoperfusion. There was a positive correlation (r = 0.50, p = 0.009) between Day-1 cICAM-1 measurements and severity of shock as determined by the presence of hypotension and vasopressor use.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Prospective evaluation of hydrocortisone and suramin in patients with androgen-independent prostate cancer.

PURPOSE: To assess efficacy of intermittent infusion of suramin in patients with androgen-independent prostate cancer who have had disease progression on hydrocortisone. PATIENTS AND METHODS: Chemotherapy-naive patients with progressive androgen-independent prostate cancer were given hydrocortisone 40 mg/d and monitored for treatment effect. At the time of disease progression, suramin was administered on a pharmacokinetically derived, 2-week dosing schedule. RESULTS: Thirty patients with a median Karnofsky performance status (KPS) of 90% were treated with hydrocortisone. No responses were seen in 12 patients with measurable disease or 29 patients with abnormal bone scans. Thirty patients had an increasing prostate-specific antigen (PSA) level before treatment and six (20%) had a more than 50% decline in PSA from the baseline value for a median of 16 weeks (range, 12 to 52+). Twenty-eight patients had disease progression after a median of 7 weeks (range, 3 to 23), and two patients have continued to receive hydrocortisone for 44 and 52 weeks. Twenty-eight patients received hydrocortisone and suramin, with median suramin concentrations of 97 to 170 micrograms/mL for 4 weeks. No responses in measurable disease and no improvements in bone scans were seen. Five patients (18%) showed a more than 50% decline in PSA levels from baseline, of whom three had previously responded to hydrocortisone. Only two of 24 patients who did not show a posttherapy decline in PSA levels after hydrocortisone had a reduction in PSA levels with the addition of suramin. Toxicity profiles were acceptable with each agent, although a higher proportion of subjects showed hematologic, cardiac, and neurologic events when suramin was added. CONCLUSION: Suramin has limited efficacy in patients with androgen-independent prostate cancer who have had disease progression after hydrocortisone.

Aged↗
PubMed1995

Suramin and hydrocortisone: determining drug efficacy in androgen-independent prostate cancer.

PURPOSE: The combination of suramin and hydrocortisone has shown clinical benefit in patients with androgen-independent prostate cancer. Widespread use was limited by the complex dose schedules and the need for pharmacologic monitoring. This study reports three sequential pharmacokinetically derived treatment regimens that simplified the administration of suramin and hydrocortisone with reduced toxicity. PATIENTS AND METHODS: Three cohorts of patients with advanced prostate cancer that progressed despite castrate levels of testosterone received oral hydrocortisone plus suramin administered in the following manners: (1) a loading dose of suramin followed by a continuous infusion using an adaptive control program (cohort A); (2) an intermittent schedule using a simplified adaptive control schedule (cohort B); and (3) an empiric dosing regimen (cohort C). Drug concentrations were monitored along with the toxicities associated with each regimen. Efficacy was assessed using measurable-disease criteria, radionuclide scans, and posttherapy changes in prostate-specific antigen (PSA) levels. RESULTS: Fifty-six patients were treated and plasma suramin concentrations were similar for each regimen. A partial response was observed in 4% (one of 28; 95% confidence interval, 0% to 18.4%) of patients with measurable disease, while 12% (six of 50; 95% confidence interval, 4.5% to 24.3%) had a greater than 80% decline in the baseline PSA level. The median duration of response was 12 months. No responses on radionuclide scans were seen. Anemia and lymphocytopenia were the most common toxicities, while 7% of patients developed a sensory or motor neurotoxicity. In the sequential regimens, the frequency of renal insufficiency (P = .04) and coagulopathy (P < .0001) decreased, while transaminase elevations (P = .05) were more common using intermittent infusions (cohorts B and C) versus continuous infusion schedules (cohort A). CONCLUSION: The administration of suramin was simplified and the drug concentrations were maintained. In this cohort of patients with advanced prostate cancer, the clinical activity of suramin using these dosing schedules was limited. Pharmacodynamic issues, patients selection, and criteria to assess efficacy could have effected the clinical outcome.

Adaptation, Physiological↗
PubMed1995

Spatial regulation of Drosophila snake protease activity in the generation of dorsal-ventral polarity.

Positional information along the dorsal-ventral axis of the Drosophila embryo is acquired through a signal transduction pathway which employs a extracellular protease cascade. The sequential activation of serine protease zymogens results in the ventrally localized production of a ligand in the perivitelline space of the embryo. Snake is one of several serine proteases which function in generating the ventralizing signal. Here, we investigate the biochemical properties of Snake in vivo and in vitro using recombinant forms of the protease. Wild-type Snake zymogen completely rescues embryos from snake null females when microinjected into the perivitelline space. Biochemical evidence for a covalently associated two-chain form of the activated protease is presented. The contribution of the activation peptide region to zymogen activation was addressed using site-directed mutagenesis. The phenotypic rescue properties of an autoactivated form of Snake reveal that the covalently associated proenzyme polypeptide chain suppresses a dominant effect associated with the activated catalytic chain alone. Recombinant active catalytic chain was produced and found to be short lived as a recombinant protein. These results suggest a model in which the proenzyme polypeptide both stabilizes and targets the Snake catalytic chain to a ventrally localized activation complex within the perivitelline space.

Animals↗
PubMed1995

Magnetic resonance image-directed stereotactic neurosurgery: use of image fusion with computerized tomography to enhance spatial accuracy.

Distortions of the magnetic field, such as those caused by susceptibility artifacts and peripheral magnetic field warping, can limit geometric precision in the use of magnetic resonance (MR) imaging in stereotactic procedures. The authors have routinely found systematic error in MR stereotactic coordinates with a median of 4 mm compared to computerized tomography (CT) coordinates. This error may place critical neural structures in jeopardy in sme procedures. A description is given of an image fusion technique that uses a chamfer matching algorithm; the advantages of MR imaging in anatomical definition are combined with the geometric precision of CT, while eliminating most of the anatomical spatial distortion of stereotactic MR imaging. A stereotactic radiosurgical case is presented in which the use of MR localization alone would have led to both irradiation of vital neural structures outside the desired target volume and underdose of the intended target volume. The image fusion approach allows for the use of MR imaging, combined with stereotactic CT, as a reliable localizing technique for stereotactic neurosurgery and radiosurgery.

Algorithms↗
PubMed1995

Detection of ten new mutations by screening the gene encoding factor IX of Danish hemophilia B patients.

Hemophilia B is caused by a wide range of mutations. In order to characterize the mutations among patients in Denmark, we have systematically screened the entire coding region, the promoter region and exon flanking sequences of the gene encoding factor IX using single strand conformation and heteroduplex analyses. Patients from 32 different families were examined, and point mutations (23 different) were found in all of them. Ten of the mutations have not been reported by others; they include a splice site mutation, a single base pair deletion, and missense mutations. Notably, the study contains a female patient and a previously described Leyden mutation. In ten families with sporadic cases of hemophilia B, all 10 mothers were found to be carriers. The origin of two of these mutations was established.

Base Sequence↗
PubMed1995

PCR amplification of animal DNA with human X-Y amelogenin primers used in gender determination.

The X-Y homologous-gene amelogenin has been described for use as a PCR sex typing test for humans. Previous studies have revealed that appropriate primers yield a 106 and 112 bp fragment from the human X and Y chromosome respectively. Our studies have found that a PCR product is also obtained from DNA isolated from a number of common animals. This animal PCR product is very close in size to that of the human female PCR derived product and may be confused as human under routine agarose gel electrophoresis. In this report we detail the variety of animals examined and a method that can maximize the usefulness of this system.

Amelogenin↗
PubMed1995

Cost-effectiveness and predictors of early extubation.

BACKGROUND: This study examined predictors and cost-effectiveness of early extubation after coronary artery bypass grafting. METHODS: Six hundred forty-five patients admitted to intensive care units after coronary artery bypass grafting at our institutions in 1993 were reviewed. There were 455 male and 190 female patients, which included all patients in DRG 106 and DRG 107. The patients were categorized into three groups: group A (269 patients) were extubated in less than 12 hours (7.55 +/- 2.5 hours), group B (291 patients) were extubated between 12 and 24 hours (16.85 +/- 3.3 hours), and group C (376 patients) were extubated any time after 12 hours. RESULTS: The reintubation rate for the entire group was less than 1%. Univariate preoperative analyses revealed small differences between groups A and B: only 6 of 25 variables were found to reach statistical significance. Stepwise logistic regression analyses were carried out in 269 patients of group A and 376 patients of group C. Older patients (log of age, p = 0.0001), female sex (p = 0.0129; odds ratio = 1.634), use of preoperative diuretics (p = 0.0010; odds ratio = 1.965) and unstable angina (p = 0.0301; odds ratio = 1.544) were noted to be clinical factors associated with late extubation (> or = 12 hours). Early extubation was accomplished in 42%; however, further analysis revealed that many patients who were intubated overnight should have been extubated sooner. CONCLUSIONS: Early extubation shortened the postoperative length of stay, resulting in reduction of cost and resource utilization. The average hospital charge per patient was approximately $6,000 less in the early extubation group.

Aged↗
PubMed1995

The use of DAPI as a replacement for ethidium bromide in forensic DNA analysis.

Ethidium bromide is used extensively for the visualization of DNA in forensic applications. This is usually accomplished by the addition of dye to the gel and buffer before electrophoresis or by staining the gel after the run. In both procedures considerable ethidium bromide containing buffer is generated that must be decontaminated. We demonstrate that another fluorescent DNA binding dye, 4',6-diamidino-2-phenylindole dihydrochloride (DAPI), can be used in place of ethidium bromide for yield and restriction gels, and to stain the visual marker of analytical gels. A low concentration of DAPI is added directly to the DNA. Most of the stain is immediately bound to the DNA and remains bound during electrophoresis.

DNA↗
PubMed1995

No difference in the effect of biperiden and amantadine on parkinsonian- and tardive dyskinesia-type involuntary movements: a double-blind crossover, placebo-controlled study in medicated chronic schizophrenic patients.

BACKGROUND: There are few objective guidelines for the clinician in the choice of antiparkinsonian drugs, even though these drugs are a heterogeneous group. We compared the effect of biperiden (M1 selective anticholinergic) and amantadine (dopaminergic) on neuroleptic-induced parkinsonian extrapyramidal symptoms (EPS) and tardive dyskinesia (TD)-type involuntary movements. METHOD: Thirty-two schizophrenic (DSM-III-R) inpatients on long-term stable antipsychotic and trihexyphenidyl treatment entered the study. Antipsychotics were kept constant, but trihexyphenidyl was replaced by placebo under single-blind conditions for 1 week, and the the patients were randomly assigned to either amantadine 100 mg b.i.d. or biperiden 2 mg b.i.d. treatment under double-blind conditions for 2 weeks. After a second 1-week placebo period, the test drugs were crossed over under double-blind conditions. Assessments of tardive dyskinesia (Abnormal Involuntary Movement Scale [AIMS]) and of parkinsonian extrapyramidal side effects (Simpson-Angus Neurologic Rating Scale) were made pretreatment and posttreatment. RESULTS: Twenty-six patients completed all study procedures. Amantadine and biperiden were equally effective in relieving neuroleptic-induced EPS and did not exacerbate TD-type movements. AIMS scores during treatment were significantly lower than during placebo period. The findings were similar in patients with diagnosable TD. CONCLUSION: Amantadine and biperiden have similar effects on neuroleptic-induced EPS and TD and may ameliorate mild TD.

Adult↗
PubMed1995

Six different point mutations in seven Danish families with symptomatic protein C deficiency.

Six different point mutations of the protein C gene are described in seven Danish families with protein C deficiency associated with an increased risk of venous thromboembolism. All affected family members are heterozygotes for the mutated protein C genotype. One mutation is a G2992-->A transition at position +5 in the 5' splice site of intron D. The other five mutations affect the protein coding region. One is a C1432-->T transition in exon III converting the highly conserved Arg15 to Trp in the Gla-domain. Another mutation is a G3157-->C transversion in exon V converting the non-conserved Gly72 to Arg in the epidermal growth factor domain. The remaining three mutations are located in non-conserved amino acid positions in exon IX and affect the serine proteinase domain. The first is a G8559-->C transversion converting Gly282 to Arg. The second is a C8571-->T transition (present in two families) converting Arg286 to Cys. The third is a C8695-->T transition converting Pro327 to Leu. In each family the protein C deficiency cosegregates or probably cosegregates (one family, G8559-->C) with the mutation. All affected family members exhibit a reduction of both the antigen and the functional plasma concentration of protein C to approximately 50% of normal indicating that the mutated protein C is not present (type 1 deficiency) or only present in low amounts in plasma. Agarose gel electrophoresis followed by Western blotting shows that the Arg15-->Trp substitution is associated with a normal as well as an abnormal migrating plasma protein C band.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Macroregenerative nodules in a series of adult cirrhotic liver explants: issues of classification and nomenclature.

Macroregenerative nodules (MRNs), probably representing a pathway for human hepatocarcinogenesis, are generally classified into type I MRNs (or ordinary adenomatous hyperplasia) and type II MRNs (or atypical adenomatous hyperplasia), on the basis of imprecise definitions of cytological and architectural atypia. It is currently believed that type II MRNs are probably true precursors of hepatocellular carcinoma (HCC), whereas type I lesions may simply represent large regenerative nodules. A series of 155 consecutive adult cirrhotic liver explants were examined for evidence of MRNs, HCC, and liver cell dysplasia (LCD) of large and small cell types, and their appearance, in terms of proposed classification schemes, was reviewed. There was evidence indicating that the presence of either type of MRN was associated with an increased incidence of HCC (all MRNs, P < .00019; type I MRNs, P < .067; type II MRNs, P < .012) compared with cirrhotic livers without MRNs. A subset of younger patients with a large (uncountable) number of MRNs in their livers, who did not show any increased incidence of carcinoma, was identified. Excluding these cases from statistical analysis, all associations were strengthened, implying either that malignant progression had not had time to occur in this younger population or that these nodules were simply large regenerative nodules without malignant potential. MRNs from these livers were histologically indistinguishable from MRNs occurring in more limited numbers, although atypical changes other than large cell type LCD were less frequent. No independent association between LCD of large cell type and HCC was found in the entire series.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Brain neurons and glial cells express Neu differentiation factor/heregulin: a survival factor for astrocytes.

Neu differentiation factor (NDF, also called heregulin) was isolated from mesenchymal cells on the basis of its ability to elevate phosphorylation of ErbB proteins. Earlier in situ hybridization analysis showed that NDF was transcribed predominantly in the central nervous system during embryonic development. To gain insights into the role of NDF in brain we analyzed its distribution by immunohistochemistry and in situ hybridization. Late-gestation (day 17) rat embryos displayed high NDF immunoreactivity in both motor (e.g., putamen) and limbic (e.g., septum) regions. Lower levels of the factor were exhibited by adult brain, except for the cerebellum, where NDF expression was increased postnatally. Both neurons and glial cells were identified by immunohistochemistry as NDF-producing cells (e.g., pyramidal neurons in the cerebral cortex and glial cells in the corpus callosum). By establishment of primary cultures of rat brain cells we confirmed that NDF was expressed in neurons as well as in astrocytes. In addition, by using such primary cultures we observed that NDF treatment exerted only a limited mitogenic effect, which was accompanied by significant acceleration of astrocyte maturation. Furthermore, long-term incubation with the factor specifically protected astrocytes from apoptosis, implying that NDF functions in brain as a survival and maturation factor for astrocytes.

Animals↗