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Biomedical subjects

D Wolf

Publications and source records attributed to D Wolf.

At least 19 recordsLinked to original sources
PubMed1998

Vitamin E: the radical protector.

Since its discovery and isolation the importance of vitamin E in maintaining normal physiologic processes and its value in treating various disease states have been the subject of much controversy. It was our intention to review and highlight some of the arguments and problems regarding the usefulness of vitamin E and to try to put them into proper perspective. The major area of interest concerning vitamin E lies essentially in its role in preventing damage caused by free radicals. The latter are now known to play an important role in radiation induced carcinogenesis, photoaging and photosensitization. The chemistry of vitamin E, its physiological function as a major antioxidant and its interaction with other antioxidants are described by the sum of animal studies, in vitro research and epidemiological investigations. In preparing the current data, it appeared that despite the controversy and conflicting results the body of literature as a whole judges vitamin E to be useful as an antioxidant. Although, in principle, the use of vitamin E can be quite advantageous, the manner of its administration, especially regarding topical application, remains unclear.

Animals↗
PubMed1997

Combined lesions of perirhinal and entorhinal cortex impair rats' performance in two versions of the spatially guided radial-arm maze.

The present study examined the effects of combined lesions of the entorhinal and perirhinal cortex (PRER) on performance of two versions of the spatially guided eigh-tarm radial maze. In the first version, all arms were baited and in each session the rats were allowed to explore the maze freely until they retrieved all of the reinforcers. PRER subjects were profoundly impaired in performance of this task, making fewer correct choices and more total errors than control subjects. In the second task, a delayed nonmatching to sample version of the radial-arm maze, each daily session was separated into two phases. In the first, predelay phase, four arms were open and the remaining four arms were blocked with clear Plexiglas barriers; subjects were permitted to visit each of the four arms and retrieve the reinforcers. In the second, postdelay phase, the subject was placed on the maze with free access to all eight of the arms, but only those arms that were blocked in the predelay phase contained reinforcers. Delays of either 10 min or 30 s separated the pre- and postdelay phases. PRER subjects were significantly impaired in their performance of this task at both delays, making fewer correct choices and more errors than controls; the magnitude of this deficit was not dependent on length of delay. These data suggest that, along with the hippocampal formation, the entorhinal and perirhinal cortices actively participate in the acquisition and performance of appetitively motivated spatial memory tasks.

Analysis of Variance↗
PubMed1997

Characterization of the muscarinic receptor subtype(s) mediating contraction of the guinea-pig lung strip and inhibition of acetylcholine release in the guinea-pig trachea with the selective muscarinic receptor antagonist tripitramine.

1. The muscarinic receptor subtypes mediating contraction of the guinea-pig lung strip and inhibition of the release of acetylcholine from cholinergic vagus nerve endings in the guinea-pig trachea in vitro have previously been characterized as M2-like, i.e. having antagonist affinity profiles that are qualitatively similar but quantitatively dissimilar compared to cardiac M2 receptors. The present study sought to establish definitely the identity of these receptor subtypes by using the selective muscarinic receptor antagonist, tripitramine. Guinea-pig atria and guinea-pig trachea (postjunctional contractile response) were included for reference. 2. It was found that tripitramine antagonized methacholine-induced contractions of the guinea-pig lung strip with pKB value of 8.76 +/- 0.05. Both the parallel shifts of the concentration-response curves and the slope of the Schild plot begin not significantly different from unity (when antagonist preincubation was for 2 h) indicated the involvement of a single population of receptors in the contractile response. From the pKB values obtained with tripitramine and a range of other selective muscarinic receptor antagonists (cf. Roffel et al., 1993), this single population of receptors can only be classified as M2-like. 3. Tripitramine antagonized methacholine-induced chronotropic and inotropic responses in guinea-pig right and left atria with apparent pKB values of 9.4-9.6. However, such values were only obtained when antagonist preincubation was relatively long and/or antagonist concentration relatively high (e.g with 1 h at 100 or 300 nM but 3 h at 30 nM). It thus appears that low concentrations of tripitramine do not readily equilibrate with M2 receptors in guinea-pig atria nor with M2-like receptors in the guinea-pig lung strip. 4. Tripitramine increased electrical field stimulation-induced cholinergic twitch contractions in guinea-pig trachea in concentrations of 0.3-100 nM, by blocking prejunctional muscarinic inhibitory autoreceptors; with higher concentrations, twitch contractions were progressively diminished, as a result of blocking postjunctional M3 receptors (apparent pKB value 6.07 +/- 0.15). The pEC20 value (-log concentration that increases twitch by 20% maximum) was 8.29 +/- 0.08, which would suggest that M4 receptors are involved in this response. 5. Oxotremorine-induced inhibition of the release of prelabelled [3H]-acetylcholine from guinea-pig trachea, under conditions where there is no auto-feedback, was blocked by tripitramine (2 h preincubation) with a pKB value of 8.56 +/- 0.06. The slope of the corresponding Schild plot was not significantly different from unity, which together with the parallel shifts of the concentration-response curves indicated the involvement of a single muscarinic receptor subtype. 6. Since the pKB value for tripitramine at prejunctional receptors in guinea-pig trachea is in between the affinities towards M2 and M4 receptors, correlation plots were constructed to compare the pKB values obtained with tripitramine and a range of other selective muscarinic receptor antagonists (cf. Kilbinger et al., 1995) to reported affinities at M1-M4 receptors. This showed rather similar distribution patterns of the data points around the line of equality in the case of M2 and M4 receptor subtypes. However, the correlation coefficient was markedly better for M2 (0.9667) than for M4 (0.5976). Since recent evidence suggests that M4 receptors are not expressed in cholinergic nerves from guinea-pig trachea, it is concluded that prejunctional muscarinic autoinhibitory receptors in this tissue exhibit an atypical M2 type character, with a pharmacological profile distinct from cardiac M2 receptors.

Acetylcholine↗
PubMed1997

Antiviral therapy for recurrent herpes simplex reconsidered.

The purpose of this paper is to present our long-time concern about the safety of using antiherpetic drugs over extended periods of time as a preventive therapy for recurrent herpetic attacks. It has been shown that when herpes simplex virus (HSV) is inactivated and has thus lost its cytolytic activity by exposure to certain chemicals or ultraviolet irradiation, it can cause neoplastic changes in mammalian cells. Therefore, substances that inhibit (but not absolutely eliminate) HSV replication for prolonged periods of time might be of potential danger for the development of cancer. It becomes incumbent upon us to ask ourselves whether the prolonged inhibitory effect of prophylactic antiviral drugs might not carry with it the same risks as has been proposed for other substances known to inhibit viral replication.

Animals↗
PubMed1997

The long-term tolerability of enalapril in hypertensive patients with renal impairment.

There has been some concern raised regarding the safe use of ACE-inhibitors in patients with severe renal insufficiency, including the development of hyperkalaemia in these patients. Therefore, the objective of the current analysis was to evaluate the long-term safety of enalapril in patients with severe renal sufficiency and hypertension. Three protocols with similar randomized, double blind, placebo-controlled designs were selected for analysis. A total of 153 patients, enrolled at six sites, were treated for up to 3 years with enalapril; 164 patients served as controls. One protocol used a fixed dose (5 mg/day) of enalapril, while the other two protocols allowed open titration up to 40 mg/day. The primary comparison was between the enalapril and control populations. For the analysis, patients, by treatment, were grouped according to the degree of renal insufficiency (serum creatinine > or < 3 mg/dl) at baseline. The incidence of the most common, as well as important, clinical and laboratory adverse events for this patient population were summarized. In addition, trends in important laboratory adverse events and the incidence of first-dose events, cough and angioedema were evaluated. The incidence of clinical adverse events was similar for both treatment groups, regardless of the severity of renal insufficiency. Seven patients died, four in the control group and three in the enalapril treatment group; none was considered related to treatment. Enalapril appeared to be well-tolerated in this group of patients with severe renal impairment.

Adult↗
PubMed1996

Antibiotic-associated colitis in orthopaedic patients.

Antibiotic-associated colitis was diagnosed in 23 orthopaedic patients: 17 had abdominal symptoms, 3 had a fever and the remaining 3 had no symptoms but increasing C-reactive protein values or white blood count. The antibiotic was clindamycin in 19, cephalosporins in 3 and a combination of vancomycin and fusidic acid intravenously in one. The antibiotics were stopped in 12, changed in 5 and continued in the remaining 5. Oral treatment for colitis was given in 21 patients, and in one patient the only treatment was stopping the antibiotics. One patient died after a myocardial infarct; the remaining 22 were discharged after successful treatment of their primary condition and the colitis.

Adult↗
PubMed1996

Quantifying apoptosis in banked human brains using flow cytometry.

Fragmentation of genomic DNA, a major biochemical feature of programmed cell death (apoptosis), is easily detected when apoptosis is prevalent. In brain tissue apoptotic cells are usually scarce and detection requires more sensitive techniques. We describe a highly sensitive method to quantify apoptosis in frozen human brain tissue using flow cytometry. Nuclei from homogenized brain specimens were isolated to purity using discontinuous isopyknic centrifugation through 2.2 M sucrose. DNA strand breaks in apoptotic nuclei were conjugated with biotinylated-dUTP using terminal deoxynucleotidyl transferase (TdT) and tagged with streptavidin-conjugated FITC (TUNEL). Negative controls excluding the TdT step, and positive controls using DNAase pretreatment to create 3'-OH strand breaks were run in parallel. The proportion of nuclei with TdT-dependent labeling in adult brain specimens was < 0.01% in 6 out of 7 specimens. In 3 fetal brains it averaged 0.86 +/- 0.11%. Apoptotic cells were readily detected in 2 malignant glial neoplasms and in a patient with HIV encephalitis. Comparable frequencies of stained nuclei were present in adjacent specimens embedded in paraffin and labeled in situ. By screening millions of nuclei cytometry detected very rare apoptotic events, producing quantitative results using banked frozen brains. The method has potential applications to studies of human brain development, neurodegenerative diseases, and brain tumors.

Adult↗
PubMed1996

Eosinophilic gastrojejunitis associated with connective tissue disease.

We report a case of eosinophilic enteritis associated with an ill-defined connective tissue disorder. The case was complicated by intestinal perforation and managed successfully without surgical intervention. No peripheral blood eosinophilia was present. Histologic examination of an intestinal biopsy revealed bands of eosinophils and mast cells at the base of the crypts with limited chronic inflammatory cell infiltrate.

Connective Tissue Diseases↗
PubMed1995

Promoting hospital discharge of infants in safety seats.

In 1990, the American Academy of Pediatrics (AAP) Committee on Injury and Poison Prevention issued a policy statement, "Safe Transportation of Newborns Discharged from the Hospital," recommending that hospitals adopt comprehensive policies, procedures and education programs for the discharge of newborns in child safety seats (CSSs). The purpose of this project was to determine if a statewide educational intervention based on the AAP statement would be effective in bringing about those recommendations in Nebraska hospitals. All hospitals providing newborn services in Nebraska were surveyed prior to and after the intervention to determine the nature and extent of their CSS discharge policies, patient education programs and loan programs. Post-intervention data indicate significant increases in the percentage of hospitals having formal infant CSS discharge policies (from 25.9% to 88%), providing CSS patient education (from 51% to 95%), and having safety seat loan/give-away programs (from 59% to 76%). It is concluded that a comprehensive, statewide educational program can influence hospitals to promote usage of, access to, and education with infant CSSs.

Accidents, Traffic↗
PubMed1995

Molecular detection of human cytomegalovirus and determination of genotypic ganciclovir resistance in clinical specimens.

The data presented in this article demonstrate how the polymerase chain reaction (PCR) can be used to detect human cytomegalovirus (HCMV) DNA in the plasma and cerebrospinal fluid (CSF) of infected individuals. Detection of HCMV DNA in plasma of transplant recipients and persons infected with human immunodeficiency virus identifies people with acute visceral disease and those at highest risk for development of HCMV disease. The detection of HCMV DNA in CSF is of particular help in identifying persons with HCMV-related central nervous system disease. In addition, specific mutations within the UL97 region, which encodes for a HCMV protein kinase, have been found to confer ganciclovir resistance and can be detected in plasma and CSF by direct sequencing of PCR products. These data will help provide tools for clinicians to better diagnose, manage, and treat persons with HCMV disease.

AIDS-Related Opportunistic Infections↗
PubMed1994

Prototype implementation of the integrated genomic database.

We aim to develop an open software system to handle human genome data. The system, called Integrated Genomic Database (IGD), will integrate information from many genomic databases and experimental resources into a comprehensive target-end database (IGD TED). Users will access front-end client systems (IGD FRED) to download data of interest to their computers and merge them with their own local data. FREDs will provide persistent storage of, and instant access to, retrieved data; a friendly graphical interface; tools for querying, browsing, analyzing, and editing local data; interface to external analysis; and tools for communicating with the outside world. The TED will be accessible over the network (online and offline) as a read-only resource for multiple clients. It collects data from major databases for nucleotide and protein sequences and structures, genome maps, experimental reagents, phenotypes, and bibliographic data, and sets of raw data produced at genome centers and laboratories. Beside character-based access via Gopher, WAIS, FTP, and several query language interfaces to the TED, we will develop a specialized front-end client, IGD FRED, with its own database manager, based on the ACEDB program. The FRED will support graphical display methods for sequence feature maps, chromosomal genetic and physical maps, and experimental objects like clone grids, etc. FRED will also provide an interface to important analysis software packages and tools for submitting data to external databases in their own format.

Computer Communication Networks↗
PubMed1994

Increase by NO synthase inhibitors of acetylcholine release from guinea-pig myenteric plexus.

The effects of nitric oxide (NO) synthase inhibitors on the electrically evoked release of [3H]acetylcholine were studied in guinea-pig myenteric plexus preparations preincubated with [3H]choline. NG-monomethyl-L-arginine (EC50 5.3 mumol l-1) and NG-nitro-L-arginine (EC50 1.3 mumol l-1) concentration-dependently increased the evoked release of [3H]acetylcholine without affecting the basal outflow. The facilitatory effect of NG-mono-methyl-L-arginine was prevented by L-arginine but not by D-arginine. The results suggest that endogenous NO inhibits the depolarisation-evoked release of acetylcholine.

Acetylcholine↗
PubMed1994

A comparative study of prothrombinase and thrombin inhibitors in a novel rabbit model of non-occlusive deep vein thrombosis.

A quantitative and non-occlusive deep vein thrombosis model was developed in rabbits. We used this model to test the antithrombotic activity of the prothrombinase complex inhibitors factor rXai and its chemical analog glutamyl-glycyl-arginyl chloromethyl ketone inactivated human factor Xa (EGR-Xai), along with the thrombin inhibitors D-phenylalanyl-prolyl-arginyl chloromethyl ketone (PPACK) and heparin. Dose dependent effects of the inhibitors during constant infusion were monitored. Measurements included thrombus weights, hemostatic parameters and both cuticle and ear bleeding times. In this model, factor rXai and EGR-Xai had comparable in-vivo efficacy, and showed 80%-93% inhibition at plasma levels of 6.5 nM (rXai) and 8 nM (EGR-Xai). Effects on ex-vivo clotting times varied among the inhibitors. At 80-100% thrombus inhibition, factor rXai and EGR-Xai had no statistically significant effect, while PPACK extended thrombin clotting time (TCT) times 2.3-fold, and heparin prolonged both activated partial thromboplastin time (APTT), prothrombin time (PT) and TCT ex-vivo clotting times 6.9-, 1.2-, and 7-fold respectively. At these dosages, cuticle and ear bleeding times were prolonged for all inhibitors and showed increases of 177%-389% (cuticle) and 45%-129% (ear). Our results demonstrate that direct inhibition of prothrombinase complex assembly is effective in arresting venous thrombosis.

Amino Acid Chloromethyl Ketones↗
PubMed1993

Granted publications: taken for granted?

Highly respected journals now relatively rarely publish independent research which is not grant-supported. This may lead to a reduction in the publication of innovative work.

Australia↗