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Biomedical subjects

A Conrad

Publications and source records attributed to A Conrad.

At least 19 recordsLinked to original sources
PubMed1996

Improved control of nausea and emesis with a new bromazepam-containing ondansetron regimen in ovarian cancer patients receiving chemotherapy with carboplatin and cyclophosphamide.

BACKGROUND: Ondansetron was found to be effective as an antiemetic in numerous clinical trials of highly emetogenic combination-chemotherapy regimens that included cisplatin. Its role in milder emetogenic regimes has not been fully defined. METHODS: This study investigated the efficacy of two different antiemetic regimes in thirty-five patients with ovarian cancer receiving 68 cycles of chemotherapy with carboplatin (350 mg/m2) and cyclophosphamide (600 mg/m2). Ondansetron (3 x 8 mg i.v.) was compared to a bromazepam-containing ondansetron regimen. RESULTS: Nausea was absent in 65% of chemotherapy courses in patients receiving the combination of ondansetron and bromazepam and in 38% of chemotherapy courses in patients receiving ondansetron alone. Complete control of emesis was achieved in 93% of the courses in patients receiving the combination and in 81% of the courses using ondansetron alone. CONCLUSIONS: The addition of bromazepam to ondansetron, and the extension of antiemetic prophylaxis to the day before and the day after chemotherapy improves the control of nausea and emesis compared to ondansetron monotherapy in patients with ovarian cancer.

Antiemetics↗
PubMed1995

In vitro determination of creatine kinase substrate fluxes using 31P-nuclear magnetic resonance.

Forward (kf) and reverse (kr) rate constants and the corresponding flux rates of the creatine kinase catalysed reaction between creatine phosphate (CrP) and adenosine triphosphate (ATP); CrP + ADP<-->kf kr ATP + Cr were measured in vitro at 295 K. Both rate constants were determined using magnetic resonance saturation transfer techniques. To study the dependence of kr and kf on the creatine kinase concentration, the creatine kinase activity was varied from 2400 to 75 U.ml-1. At equilibrium and high creatine kinase activities, the forward to reverse flux rate ratios are close to 1. A dispersion in the reaction rate constants was observed at activities < or = 600 U.ml-1. We measured kr > kf for all enzyme activities below 600 U.ml-1. This observation could partially be explained by the presence of ATPase contamination in the enzyme. These findings are relevant for the in vivo studies of creatine kinase activity in the presence of multi-site phosphate exchange in cellular ATP-pools. As mitochondrial creatine kinase is not in equilibrium these results are also of interest in this area.

Adenosine Triphosphate↗
PubMed1994

Clinical significance of concomitant hepatitis C infection in patients with alcoholic liver disease.

The significance of antibodies to hepatitis C virus in patients with chronic alcoholic liver disease is unclear. Prior studies have utilized the first-generation enzyme-linked immunosorbent assay, which is limited by problems with sensitivity and specificity. Hepatitis C virus infection in 137 patients with biopsy-proven alcoholic liver disease was assessed with second-generation hepatitis C virus antibody assays and reverse transcription-polymerase chain reaction for detection of hepatitis C virus RNA in the serum. The patients were categorized into three groups according to results of serological testing. Discriminant-function analysis was used to determine which factors (risk, biochemical and histological) could best differentiate the three groups. Thirty-three patients were reactive on second-generation enzyme-linked immunosorbent assay/second-generation recombinant immunoblot assay and RNA positive (group 1). Twelve were reactive on second-generation enzyme-linked immunosorbent assay/second-generation recombinant immunoblot assay but RNA negative (group 2). Eighty-six were nonreactive on second-generation enzyme-linked immunosorbent assay, and six were reactive on second-generation enzyme-linked immunosorbent assay but negative on second-generation recombinant immunoblot assay and negative for hepatitis C virus RNA (group 3). Seventy-six percent of patients in group 1 and 58% in group 2 had parenteral risk factors, compared with only 1% in group 3 (p < 0.00001). The mean ALT level was higher in group 1 patients (p < 0.05). The mean histologic activity index was significantly higher in group 1 (p = 0.0007).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Intrathecal IgG synthesis and albumin leakage are increased in subjects with HIV-1 neurologic disease.

We analyzed matched cerebrospinal fluid and blood samples from 139 subjects enrolled in a study of the effects of human immunodeficiency virus type 1 (HIV-1) on the nervous system. Mean total intrathecal IgG synthesis rate was significantly higher in subjects with HIV-1-related neurologic disease (NeuroPos) than in HIV-1-seropositive (HIV+) subjects without neurologic disease (NeuroNeg) or at-risk seronegative controls (SNC). Mean trans-blood-brain barrier (BBB) albumin leakage (AL) rate increased significantly across groups (SNC < NeuroNeg < NeuroPos). AL was significantly higher in subjects with absolute CD4 counts < 100/mm3 versus those with > or = 100 cells/mm3 and significantly higher in AIDS compared with asymptomatic HIV+. Elevated total intrathecal IgG synthesis rate could not be accounted for solely by the presence of a damaged BBB, because 79% of subjects with elevated IgG synthesis rates had a normal BBB as assessed by the AL formula. Furthermore, the Tourtellotte formula inherently corrects for BBB leakage. We confirmed, using state-of-the-art albumin and IgG determinations, that intrathecal IgG synthesis is prevalent in all stages of HIV-1 disease. In the absence of a CNS opportunistic infection or tumor, mean total intrathecal IgG synthesis rate and trans-BBB AL are significantly higher in subjects with clinical HIV-1 CNS disease than in neurologically normally HIV+ subjects.

Adult↗
PubMed1994

Quantifying HIV-1 proviral DNA using the polymerase chain reaction on cerebrospinal fluid and blood of seropositive individuals with and without neurologic abnormalities.

To quantify the number of human immunodeficiency virus type 1 (HIV-1) proviral copies per 1,000 CD4+ cells in cerebrospinal fluid (CSF) and blood in relationship to stage of infection and HIV-1 neurologic disease (HND), 87 HIV-1 seropositive men without CNS opportunistic infections, tumors, or neurosyphilis, 9 high-risk, and 14 not-at-risk seronegative controls underwent a structured interview, and physical and neurologic examination followed by blood and CSF collection. A custom-designed, fully automated polymerase chain reaction (PCR) system performed amplification with use of two HIV-1 gag primer pairs, Southern blotting, and hybridization with product-specific probes. Image analysis was used to quantify band intensities relative to a dilution series. Eighty-one of 87 (93%) seropositive patients, 1 of 9 high-risk patients, (11%) and none of 14 seronegative controls had PCR-detectable HIV-1 in their blood. Fifty-seven of 63 (90%) seropositive patients, 2 of 5 (40%) high-risk seronegative patients, and none of 14 controls had HIV-1 in their CSF. The proviral load in seropositive patients, all stages, was significantly greater in CSF than blood [median 25 vs. 0.6 copies/1,000 CD4+ cells (p = 0.0001)]. The median proviral load in blood was 0.09 copies/1,000 CD4+ cells in seropositive, asymptomatic subjects, 10.7 in patients with AIDS, and 1.4 in patients with AIDS-related complex (p = 0.0281). CSF proviral load was greater in seropositive patients with HND than those without HND, median 43.5 vs. 17.6 copies/1,000 CD4+ cells (p = 0.0614). Proviral load was greater in the blood and CSF of subjects with more advanced systemic disease and HND. There was a substantial penetration of HIV-1 into the CNS/CSF in both systemically and neurologically asymptomatic HIV-1 disease.

AIDS Dementia Complex↗
PubMed1994

[Pathologic appendix findings in gynecologic operations].

We report our experiences on three cases with pathologic findings of the appendix vermiformis diagnosed during gynecological operations including mucocele, carcinoid and adenocarcinoma. Mucocele of the appendix is a descriptive term for an abnormal mucous accumulation distending the appendiceal lumen, which can be complicated by pseudomyxoma peritonei. Carcinoid tumours arise from the neuroendocrine system and present a characteristic morphologic picture. Predilicted sites are the appendix and the small bowel. Adenocarcinomas of the appendix that are not associated with mucoceles have a clinical course resembling large bowel cancer. Patients with pathological findings of the appendix may be asymptomatic or present with a palpable right lower quadrant mass and/or pain. We discuss differential diagnosis and present a spectrum of histologic findings.

Adult↗
PubMed1994

Laboratory evaluations in HIV-1-associated cognitive/motor complex.

Laboratory tests can provide useful information about the presence and effects of HIV-1 in the CNS, but have thus far not yielded definitive diagnostic or prognostic markers of HIV-1-related cognitive and motor complex. The most clinically useful laboratory procedures are MR imaging and CSF examinations. The routine clinical use of MR imaging and CSF examinations, however, is still restricted to providing information for detecting and excluding secondary effects of HIV-1 infection. MR imaging and CT do not appear to be sensitive enough at current resolutions to provide early detection of HIV-1 CNS effects nor to follow disease progression. Several CSF variables are extremely promising as early markers of primary HIV-1 infection of the brain, and may provide preclinical indications for onset of treatment and for evaluation of treatment efficacy. These include CSF quinolinic acid levels, acid dissociated p24 antigen levels, neopterin or beta 2m, intrathecal IgG synthesis rate, and possibly quantitated PCR levels of HIV-1 viral load. Procedures such as nuclear magnetic resonance spectroscopy, SPECT, PET, computerized EEG, EP, and ERPs are all promising candidates for early detection or localization of HIV-1-related brain dysfunction, but at this time all must still be considered primarily research tools. Before any of these procedures can provide reliable diagnostic and prognostic information about primary HIV-1 neurologic disease, currently on-going longitudinal evaluations of large numbers of asymptomatic HIV-1-infected individuals as they progress to neurologically symptomatic disease must be completed. There is currently no laboratory marker in blood or CSF that definitively predicts the risk for HIV-1-associated cognitive/motor complex. HIV-1-associated cognitive/motor complex remains a clinical diagnosis, which is made on the basis of positive neurologic signs and symptoms and abnormal neuropsychological findings after other causes of neurologic disease are excluded. Laboratory measures, such as the electrophysiologic methods and some CSF variables, are likely to remain adjuncts to the diagnosis because, with few exceptions, they provide data that are nonspecific as to etiopathogenesis. Dynamic imaging, electrophysiologic methods, and CSF indices provide presumptive evidence for the presence of HIV-1-associated CNS damage, and with clinical and neuropsychological evidence, could be used to establish a new definition of primary HIV-1-associated CNS disease along the lines used in establishing a diagnosis of multiple sclerosis.(ABSTRACT TRUNCATED AT 400 WORDS)

AIDS Dementia Complex↗
PubMed1993

[New oncologic therapeutic approaches with hematopoietic growth factors].

The haematopoietic growth factors interleukin-3 (IL-3), erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF, Neupogen) and granulocyte macrophage colony-stimulating factor (GM-CSF) are highly effective endogenous regulators of blood cell proliferation and differentiation. The results of initial clinical studies with these substances show a stimulation of haematopoiesis for numerous dysfunctions of the bone marrow, whereby the therapy of cytostatic-induced myelosuppression is of particular significance for the gynaecologist, specializing in oncology. After further experience with the individual substances, future development in this field will probably focus on the combined use of these growth factors, to stimulate all early developmental stages of haematopoiesis in the bone marrow and--in view of the line-specific effect--to achieve an effect on several lines of differentiation. Of the cytokines quoted, G-CSF (Neupogen) is so far the only growth factor, which is available for oncological indications. The approval of GM-CSF, IL-3 and EPO for oncological indications is pending. If the currently available results are confirmed by further clinical studies, it will be possible--over and above the improvement of cytostatic tolerance--to raise the current cytostatic doses limited by myelodepression, and to analyse, whether better oncological results can be achieved by more intensive chemotherapy, shorter application intervals, or by using previously impossible cytostatic combinations. The employment of haematopoietic growth factors could, in this way, lead to new oncological therapy concepts.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Human neuro-specimen banking 1961-1992. The National Neurological Research Specimen Bank (a donor program of pre- and post-mortem tissues and cerebrospinal fluid/blood; and a collection of cryopreserved human neurological specimens for neuroscientists).

The National Neurological Research Specimen Bank (The Bank) was established in 1961 to provide a vital service to neuroscientists. Our purpose is to support medical research which seeks the etiopathogenesis for devastating neurological disorders with no known cause, treatment or precise animal model. It serves as a bridge between the neurology clinician who diagnoses and cares for patients with incurable disease and the basic scientist who has need for specimens to find their etiopathogenesis. In the long run this service should advance neurologic diagnoses and serve as the basis for designing treatment. The Bank has grown to be the largest, most diverse neurological specimen bank of its kind in the world. It is a type of "tissue bank" where donor members "will" their central nervous system tissues to science. Then we collect, photograph, seal in air tight bags, quick freeze, cryogenically store and distribute on request the donated tissue to research scientists around the world. All tissue diagnoses are confirmed by clinical records and neuropathologic examination; further histology is conducted on request. In addition to brain and spinal cord tissues, the Bank has samples of other tissues. There are also samples of pre- and post-mortem CSF and sera from normal individuals and patients with various neurological disorders, especially serial specimens on multiple sclerosis patients and HIV-1 seropositive and at risk individuals. This paper outlines the global operations of our human brain bank, based on protocols developed and used by the authors. These operations include donor solicitation, tissue acquisition and documentation, tissue processing and storage, specimen dissemination to users, outcome assessment of banking, quality control, cost of our operation, table of organization and the future.

Blood Donors↗
PubMed1992

The role of the mitochondrial creatine kinase system for myocardial function during ischemia and reperfusion.

The subcellular distribution of ATP, ADP, creatine phosphate and creatine was studied in normoxic control, isoprenaline-stimulated and potassium-arrested guinea-pig hearts as well as during ischemia and after reperfusion. The mitochondrial creatine phosphate/creatine ratio was closely correlated to the oxidative activity of the hearts. This was interpreted as an indication of a close coupling of mitochondrial creatine kinase to oxidative phosphorylation. To further investigate the functional coupling of mitochondrial creatine kinase to oxidative phosphorylation, rat or guinea-pig heart mitochondria were isolated and the mass action ratio of creatine kinase determined at active or inhibited oxidative phosphorylation or in the presence of high phosphate, conditions which are known to change the functional state of the mitochondrial enzyme. At active oxidative phosphorylation the mass action ratio was one-third of the equilibrium value whereas at inhibited oxidative phosphorylation (N2, oligomycin, carboxyatractyloside) or in the presence of high phosphate, the mass action ratio reached equilibrium values. These findings show that oxidative phosphorylation is essential for the regulation of the functional state of mitochondrial creatine kinase. The functional coupling of the mitochondrial creatine kinase and oxidative phosphorylation indicated from the correlation of mitochondrial creatine phosphate/creatine ratios with the oxidative activity of the heart in situ as well as from the deviation of the mass action ratio of the mitochondrial enzyme from creatine kinase equilibrium at active oxidative phosphorylation in isolated mitochondria is in accordance with the proposed operation of a creatine shuttle in heart tissue.

Animals↗
PubMed1991

[Methanol kinetics in chronic alcoholism].

Blood tests from 39 persons, who had been admitted to a local hospital for alcoholics, were analysed. The methanolconcentrations at the reception time lay between 10 and 82 mg/kg and the BAC between 2.00 and 3.83%. In all cases, when Ethanol existed in a sufficient concentration the Methanolconcentration showed a horizontal trend. A Methanolelimination was not observed. Only after exceeding a limiting value of Ethanol, which fluctuated between 0.8 and 0.2%, in most of the cases under 0.2%, the Methanolcurves increased significantly. An Ethanolelimination was observed between 0.15 and 0.25% per hour, the average was about 0.19%.

Adult↗
PubMed1990

The detection of HIV by in situ hybridization.

A simplified method of in situ hybridization is described for the detection of HIV targets. This standardized method can be applied to sections of formalin-fixed paraffin-embedded tissues, cell blocks, and smears of cultured cells using 3H- or 35S-labeled DNA and 35S-labeled RNA probes. In order to use elevated stringencies in the hybridization and wash steps, tissue sections and cells are covalently bonded to silanated glass slides without their subsequent loss from the slides. Routine hematoxylin and eosin or Romanovsky's stains enable the identification of the cells detected by in situ hybridization. HIV-infected neuroblastoma and lymphoid cell lines, lymph nodes, bone marrow, kidney, as well as brain tissue from patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex are used to demonstrate the generality of the procedure. The standardized method described widens the ease and applicability of in situ hybridization in the investigation of pathologic tissues with the use of diverse specimens and probes.

DNA Probes↗
PubMed1990

Study of preneoplastic changes of liver cells by immunohistochemical and molecular hybridization techniques.

The status of hepatitis B virus DNA was investigated by in situ hybridization in multifocal areas of a noncancerous hepatitis B virus-associated cirrhosis. This liver exhibited a marked degree of dysplasia and adenomatous hyperplasia. The results of these studies were correlated with the histopathology and immunohistochemical stains for hepatitis B core and surface antigens. There was clear evidence of a marked reduction to absence of hepatitis B viral DNA by in situ hybridization and absence of HBc and HBsAg in the foci of liver cell dysplasia and adenomatous hyperplasia. These results support the hypothesis that liver cell dysplasia and adenomatous hyperplasia are preneoplastic in nature.

DNA, Viral↗
PubMed1990

A randomized double blind study of a new ready-for use prostaglandin gel (Org 2436) for cervical ripening prior to first trimester pregnancy termination.

In a placebo-controlled double-blind randomized study involving 50 primigravidae scheduled for termination of first trimester pregnancy 500 micrograms PGE2 gel or placebo gel were applied intracervically 6 hours before curettage. The priming effect was verified in all patients by means of comparative examinations with a special tonometer before application of the gel and immediately before the surgical procedure. No abortion or vaginal bleeding occurred in any of the patients. After 500 micrograms PGE2 gel the mean free passability (i.e. force less than or equal to 1 Newton) was 7.8 (+/- 2.0) mm, the corresponding value for the placebo group 5.2 (+/- 1.2) mm (p less than 0.0001). The prostaglandin pretreatment led to a significant increase in dilation of 5.9 +/- 2.3 mm versus 2.0 +/- 1.2 mm in the placebo group (p less than 0.0001). 17 of the 25 PGE2-treated patients complained of lower abdominal pain, gastrointestinal side effects were observed in one of these patients. In the placebo group there were no undesired concomitant symptoms. No intra- or postoperative complications occurred in the PGE2 gel-treated group. After application of the placebo gel cervical lesions and incomplete curettages were demonstrated in 4 cases. According to this preliminary experience, the intracervical application of the new ready-for-use-PGE2 gel represents a practicable and efficient method for preoperative cervical priming. In view of the intraoperative complications in the placebo group the frequency of side effects after PG application are within tolerable limits.

Abortion, Induced↗
PubMed1987

Hippocampal pyramidal cell orientation in schizophrenia. A controlled neurohistologic study of the Yakovlev collection.

The finding of marked disorganization of the hippocampal pyramidal cell layer in the brains of schizophrenic patients has recently been reported. The present study was undertaken to determine whether similar abnormalities could be found in the brains of a population of schizophrenic patients, most of whom were never exposed to neuroleptics. Though statistical analysis of 2808 pyramidal cells failed to reveal significantly greater disorganization in a group of seven alleged schizophrenic brains than in brains of age-matched, nonpsychotic controls, the data suggest a relationship between the degree of pyramidal cell disarray and the severity of behavioral impairment due to psychosis. The implications and pitfalls in interpreting these findings are discussed.

Adult↗
PubMed1987

[Prevention of anuria in uretero-sigmoidostomy without catheter].

The development of anuria following catheter-less uretero-sigmoidostomy performed between 1977 and 1982 has led to a modification of the intra-operative and post-operative intensive care. During the period 1983 to 1985, the systematic intra-operative administration of furosemide immediately after performing the uretero-colonic anastomosis, the use of intra- and post-operative filling with control of filling pressures by a pulmonary arterial catheter, resulting in considerable diuresis, have been able to prevent anuria following this type of surgery.

Anuria↗
PubMed1986

Electrophysiologic effects of an acute beta-blockade induced by bisoprolol in patients with supraventricular tachycardia as assessed by His-bundle electrograms.

The acute electrophysiologic effects of 10 mg bisoprolol (B, given intravenously) were evaluated during an electrophysiological study in 10 patients with a history of paroxysmal tachycardia. Drug administration resulted in a significant decrease of sinus rate (Control [C]; 70.8/min; B: 59.4), and in an increase in sinus node recovery time (+20%). AV-nodal depression was marked at high heart rates during incremental atrial pacing. A second-degree AV-block occurred at a pacing cycle length (CL) of 329 ms (182/min) before and at a CL of 378 ms (158/min) after drug administration. Depression of AV-nodal conduction was negligible at low heart rates; the AH-interval at sinus rhythm was not affected (C: 84 ms, B: 86 ms); and functional and effective refractory periods of the AV-node were only slightly prolonged. Conduction intervals and refractory periods on atrial and ventricular level did not change. In 5 of 6 patients with accessory AV-pathways, circus movement tachycardia (CMT) could be elicited prior to as well as after B. Due to AV-nodal delay, CMT CL was slightly prolonged after B. Echozone and refractoriness of accessory pathways were not affected. In 1 of 2 patients with ectopic atrial tachycardia, B prevented the induction of paroxysms. In one patient with paroxysmal atrial fibrillation, the ventricular response decreased from 128/min to 94/min. The findings suggest that the electrophysiologic effects of B are due to a selective beta-adrenergic antagonism. Therapeutic efficacy is only to be expected if an increased adrenergic drive is a prerequisite for induction and continuation of a tachycardia.

Adrenergic beta-Antagonists↗