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Biomedical subjects

M Rogers

Publications and source records attributed to M Rogers.

At least 127 records · Page 7Linked to original sources

Cloning of the bovine activin receptor type II gene (ACVR2) and mapping to chromosome 2 (BTA2).

The cDNA for the bovine activin receptor type II (ACVR2) gene has been cloned and sequenced. It encodes a protein of 513 amino acids which is highly homologous (approximately 98% identity) to the human, mouse, and rat proteins. Using PCR analysis of bovine x hamster somatic cell lines, the ACVR2 gene was mapped to syntenic group U17, which has been localised to bovine chromosome 2. Comparative mapping has shown that the genes within U17 are also in a syntenic group on the long arm of human and sheep chromosome 2, as well as on mouse chromosome 1. This group of genes represents an evolutionarily conserved mammalian chromosomal segment. Genotyping a highly polymorphic microsatellite locus, (AT)4(GT)9(AT)11, found within an intron of this gene confirmed the localisation by linking the ACVR2-associated microsatellite to the region of chromosome 2 flanked by CSSM42 and TGLA226. This gene locus, which has the characteristics of a type I and type II mapping locus, represents the first localisation of this gene in any species to date.

Activin Receptors↗

The influence of glucose tolerance tests on subsequent carbohydrate metabolism in pregnancy.

BACKGROUND: This present study was designed to prospectively confirm a previous observational finding that a 75g glucose load exerts an influence on the results of a subsequent 50g glucose tolerance test performed after an interval of one week. METHODS: Pregnant Chinese patients were given both 50g 3-hour and 75g 2-hour oral glucose tolerance test (OGTT) in random order, 7 days apart, between 28 and 32 weeks of gestation. Patients were divided according to whether they received 50g test first (group 1) or 75g test first (group 2). Student's t-test for independent samples and for paired samples were used for between group comparisons and within patient comparisons respectively using SPSS for Windows software. RESULTS: Significant decrease in fasting glucose levels (p<0.0001) between paired 50g and 75g OGTT was found when 75g test was performed first. The mean difference in 2-hour values was also 35% lower. Similar results were also found when individual timed glucose levels were compared between groups. CONCLUSIONS: Differences in the blood glucose levels between OGTTs were confirmed to be related to which glucose load was given first. The 75g test exerts a significant effect on the fasting glucose and the response to a 50g glucose load up to one week later. These effects are consistent with improvement in glucose utilization. The differences observed will not significantly alter current clinical practice but may necessitate modification in the diagnostic crieria of mild abnormal glucose tolerance in pregnancy. We postulate that in some cases of mild glucose intolerance, the response to diet may not be due to caloric reduction but rather stimulation of a previously inadequate insulin response since a proportion of our local pregnant women consistently have calorice intakes significantly below the 1800 kcal per day.

Administration, Oral↗

A randomized, double blind, controlled trial of tocolysis to assist external cephalic version in late pregnancy.

BACKGROUND: External cephalic version at term is not always successful. This trial was done to ascertain whether tocolysis has any effect on the success rate. METHODS: A randomized, double blind, controlled trial, with continuous paired sequential analysis. Fifty-one consecutive patients with a singleton fetus in a breech presentation between 36 and 38 weeks gestation, external version being attempted on each. Ritodrine infusion or placebo was infused before attempt at external cephalic version. SETTING: A university teaching hospital with 8000 confinements annually. RESULTS: Version was successful in 17 of the 25 patients given tocolysis, but in only eight of the 25 given placebo (p < 0.01). A positive benefit for tocolysis was shown after version had been completed in 10 pairs of patients. However the trial was continued until 25 pairs had been analyzed. The benefit deteriorated during analysis of the last 15 pairs suggesting that the initial benefit may reflect a learning curve for the procedure. CONCLUSION: Tocolysis is likely to improve the success rate of external cephalic version in late pregnancy, especially in nulliparous mothers or where doctors are learning the technique.

Adult↗

Unusual electrocardiographic presentation of right ventricular myocardial infarction.

Isolated right ventricular infarction is uncommon, but when it occurs its prompt recognition may alter therapy substantially. Electrocardiographic changes accompanying acute right ventricular infarction are variable and may be difficult to recognize. The case of a 40-year-old man who had right ventricular infarction with unusual electrocardiographic findings is presented. The clinical, hemodynamic, and electrocardiographic findings of right ventricular infarction are discussed.

Adult↗

Clinical experience with atovaquone on a treatment investigational new drug protocol for Pneumocystis carinii pneumonia.

The clinical experience of human immunodeficiency virus (HIV) + patients treated with oral atovaquone for acute Pneumocytstis carinii pneumonia (PCP) under a Treatment Investigational New Drug (IND) protocol (mild or moderate PCP) and an Open-Label Study protocol (severe PCP) was evaluated. A total of 940 patients intolerant of or unresponsive to trimethoprimsulfamethoxazole were enrolled from private practices, clinics, and institutional HIV treatment centers in the United States. Demographics data and the history and severity of PCP were collected at enrollment. The number of therapy days, adverse experiences, clinical response to therapy, and mortality were collected at day 21. Reporting of serious, unexpected adverse experiences attributable to therapy was required. Of the 760 (96%) patients with mild to moderate disease for whom follow-up observation was complete, 591 (78%) responded clinically to treatment, 177 patients (23%) discontinued treatment prematurely, and 50 patients (7%) died. Of the 140 patients (95%) with severe PCP with follow-up data, 79 (56%) responded to treatment, 45 (32%) discontinued treatment early, and 53 patients (38%) died. Adverse events that resulted in temporary or permanent discontinuation of therapy included diarrhea, vomiting, elevated liver enzyme levels, nausea, and fever. No serious unexpected adverse events attributable to the drug were reported. The treatment IND mechanism enabled a large number of patients with acute PCP to be treated with this experimental therapy while the drug was under regulatory view.

AIDS-Related Opportunistic Infections↗

The TTG-2/RBTN2 T cell oncogene encodes two alternative transcripts from two promoters: the distal promoter is removed by most 11p13 translocations in acute T cell leukaemia's (T-ALL).

The TTG-2 gene has been identified at the site of chromosomal translocations in acute T-cell leukemia's (T-ALL). These breakpoints map to a region between 2 and 30 kb upstream of TTG-2 in chromosome 11p13. To establish the role of these translocation breakpoints in the deregulation of TTG-2 in T-ALL we have determined the complete structure of this gene. Isolation of new TTG-2 cDNA clones from fetal liver identified an alternative transcript (TTG-2a) containing two new noncoding 5' exons. Analysis of exon/intron boundaries, identified 6 exons spread over 35 kb in 11p13. The gene encodes two alternative transcripts initiating from two promoters. TTG-2a, from promoter 1 (P1) and TTG-2b, from promoter 2 (P2) differ in the length of the 5' untranslated region, but encode the same protein. A high level of TTG-2a was present in fetal liver and spleen, whereas in adult kidney a low level of TTG-2a and a high level of TTG-2b was found. The transcription start site for TTG-2a was identified by RNase protection experiments and it displayed sequence homology to an initiator element (inr). P1 lacks a TATA box, but binding sites for SP1 and GATA-1 are present. This new genomic organisation revealed that all known chromosomal translocations map upstream of P2, removing P1 and putative upstream regulatory sequences leaving P2 intact. These results show that chromosomal translocations disrupt the TTG-2 gene itself, further confirming its role in the development of T-ALL.

Adaptor Proteins, Signal Transducing↗

Prophylaxis against Pneumocystis carinii pneumonia among children with perinatally acquired human immunodeficiency virus infection in the United States. Pneumocystis carinii Pneumonia Prophylaxis Evaluation Working Group.

BACKGROUND: Pneumocystis carinii pneumonia (PCP) remains a common and often fatal opportunistic infection among children infected with the human immunodeficiency virus (HIV). HIV-infected infants between three and six months of age are particularly vulnerable. Current guidelines recommend prophylaxis in children from birth to 11 months old who have CD4+ counts below 1500 cells per cubic millimeter. METHODS: We used national surveillance data to estimate the annual incidence of PCP among children less than one year old. We reviewed the medical records of 300 children given a diagnosis of PCP between January 1991 and June 1993 to determine why treatment according to the 1991 guidelines for prophylaxis against PCP either was not given or failed to prevent the disease. RESULTS: In our study the incidence of PCP in the first year of life among infants born to HIV-infected mothers changed little between 1989 and 1992. Among 7080 children born to HIV-infected mothers in 1992, PCP developed in 2.4 percent. Of 300 children with PCP diagnosed from January 1991 through June 1993, 199 (66 percent) had never received prophylaxis, and for 118 of those children (59 percent) exposure to HIV was first identified 30 days or less before the diagnosis of PCP. Among 129 children less than one year old, the CD4+ count declined by an estimated 967 cells per cubic millimeter (95 percent confidence interval, 724 to 1210 cells per cubic millimeter) during the three months before the diagnosis of PCP. Among infants in whom CD4+ counts were determined within one month of the diagnosis of PCP, 18 percent (20 of 113) had at least 1500 cells per cubic millimeter, a level higher than the currently recommended threshold for prophylaxis. CONCLUSIONS: In the United States the incidence of PCP among HIV-infected infants has not declined. If this infection is to be prevented, infants exposed to HIV must be identified earlier, and prophylaxis must be offered to more children than the guidelines currently recommend.

AIDS-Related Opportunistic Infections↗

Discordance between macrophage arachidonate metabolic phenotype and the expression of cytosolic phospholipase A2 and cyclooxygenase.

Macrophages (M phi s) exhibit variations in their ability to release and metabolize arachidonate (AA) depending on their state of activation, differentiation, and tissue origin. In order to understand these variations on a molecular level, we determined whether differences in AA release and metabolism by murine peritoneal M phi s could be explained in terms of cytosolic phospholipase A2 (cPLA2) and cyclooxygenase (COX) expression. Resident M phi s exhibited greater COX capacity (conversion of exogenous AA to PGE2) but lower phospholipase (PLase) activity (release of endogenous AA) than elicited M phi s. Activation of resident M phi s in vivo with endotoxin increased both their PLase activity and COX capacity. Despite the observed differences in PLase activity, peritoneal M phi s under all conditions expressed similar amounts of cPLA2 mRNA and protein. All M phi s exhibited COX-1 mRNA and protein (i.e., the constitutive isoform of COX), although elicited M phi s exhibited increased mRNA for COX-1 but decreased levels of protein, relative to resident M phi s. Elicited (but not resident) cells also exhibited COX-2 mRNA but not COX-2 protein (i.e., the inducible form of COX). Despite the increased COX capacity of resident cells with in vivo activation, their expression of COX-2 mRNA and protein was equivalent to that of unactivated cells, becoming apparent only after cell adherence in vitro. In sum, there is no simple relationship between the ability of M phi s to release and metabolize AA, and the expression of cPLA2 or COX isoforms. Moreover, adherence appears to be important for the expression of COX-2 by M phi s.

Analysis of Variance↗

Retrograde intubation training using a mannequin.

The purpose of this study was to determine the efficacy of a mannequin for training emergency caregivers in the technique of retrograde intubation. This was a descriptive study using duration of time needed for completion of intubation as a measure of success. A cohort of 88 Emergency Medical Service (EMS) personnel included prehospital caregivers, registered nurses, and respiratory care practitioners. Participants were trained in retrograde intubation by modeling. Students practiced before they were tested. Every subject successfully completed intubation on the first timed effort. Subjects performed retrograde intubation in a mean time of 71 seconds (95% confidence interval +/- 4 seconds), with a range of 42 to 129 seconds. It was concluded that retrograde intubation can be taught easily with a mannequin and that this skill can be learned by emergency caregivers by modeling. Bag-valve-mask ventilation can be performed at any time without the need to restart or interrupt the procedure. Retrograde intubation can be introduced as an intubation technique for the difficult airway encountered by EMS personnel.

Adult↗

Comparison of quantitative calcium flux through NMDA, ATP, and ACh receptor channels.

NMDA receptors, ATP receptors, and nicotinic ACh receptors respond to agonist by undergoing conformational changes that open weakly selective cationic channels that are permeable to calcium. We determined the fraction of the current carried by calcium by simultaneously measuring membrane current using whole-cell patch-clamp techniques and intracellular Ca2+ using the fluorescent indicator Fura-2. The Fura-2 response to free Ca2+ was calibrated individually for each cell. Two different calibration methods are compared: one uses voltage-activated Ca2+ channels, and the other uses the same ligand-gated channels that are being tested but in a pure Ca2+ solution. The two methods give quantitatively different results. The method using pure Ca2+ currents through ligand-gated channels calibrates the Fura-2 signal through the same influx pathway that generates the test response, thus controlling for the distribution of channels and ensuring a similar interaction between the incoming Ca2+ and Fura-2. In a physiologic solution containing 2.5 mM Ca2+ at a holding potential of -50 mV, the percentage of inward current carried by Ca2+ through NMDA receptors in hippocampal neurons is 12.4%. By comparison, in sympathetic neurons the percentage of current carried by Ca2+ through neuronal nAChRs is 4.7%, and through ATP-activated purinergic receptors it is 6.5%. These percentages can be used to estimate the amount of Ca2+ entry through these receptors during synaptic activation, but care must be exercised in considering the many subtypes of each receptor.

Adrenal Medulla↗

Hair shaft abnormalities: Part I.

The light microscopic and electron microscopic appearances of the normal hair are briefly described. The major hair shaft abnormalities are reviewed in two parts, discussing clinical characteristics, light and electron microscopy and, where information is available, the pathogenesis of these rare conditions. Part I describes monilethrix, pili torti and trichorrhexis nodosa.

Hair↗

Fetomaternal haemorrhage after external cephalic version at term.

The incidence of fetomaternal haemorrhage after external cephalic version was 1.8% in 167 patients. The occurrence of this complication was not found to be associated with difficult or unsuccessful version, or with any adverse perinatal outcome. We conclude that routine assessment of fetomaternal haemorrhage after external version is not necessary, except in rhesus negative women to detect the 2% in whom the routine dose of 500 iu (100 micrograms) of anti-D immunoglobulin is inadequate.

Female↗

Screening criteria for beta thalassaemia trait in pregnant women.

AIMS: To establish suitable screening criteria for beta thalassaemia trait during pregnancy using an automated blood counter incorporating light scattering technology. METHODS: Pregnant women (n = 857) at a London antenatal clinic were investigated for beta thalassaemia trait if the Technicon H.2 full blood count showed either a mean corpuscular volume (MCV) < 85 fl or a mean corpuscular haemoglobin (MCH) < 27 pg. Results were then analysed to establish which of these variables was more suitable for screening and to determine suitable cut off points for calculating the haemoglobin A2 percentage. RESULTS: The MCH was superior to the MCV for thalassaemia screening as it was a more stable measurement and fewer unnecessary tests were performed. A MCH less than 27 pg is a suitable cut off point for screening. This screening criterion was equally applicable to a Coulter impedance counter. CONCLUSIONS: Pregnant women presenting at an antenatal clinic with a MCH < 27 pg should be investigated further to confirm or exclude a diagnosis of beta thalassaemia trait.

Erythrocyte Indices↗