Antiviral susceptibilities of herpes simplex virus from immunocompetent subjects with recurrent herpes labialis: a UK-based survey.
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Journal Article↗
Biomedical subjects
A Connolly
Publications and source records attributed to A Connolly.
Urinary tract infections in pregnancy.
Although pregnancy does not increase the prevalence of ASB in women, it does enhance the progression rate from asymptomatic to symptomatic disease. Furthermore, ASB is associated with preterm delivery. Given the fact that identification and eradication of ASB in pregnant women can lower the likelihood of pyelonephritis and prevent preterm delivery, every gravida should be systematically screened for ASB and appropriately treated. In the authors' opinion, a first-trimester urine culture remains the screening test of choice; reliance on symptoms to prompt screening is inadequate because the state of pregnancy can provoke frequency and nocturia. Multiple antibiotic regimens for ASB are safe during pregnancy and effective.
Anti-Infective Agents, Urinary↗
Prevalence of serious eye disease and visual impairment in a north London population: population based, cross sectional study.
OBJECTIVE: To estimate the magnitude of serious eye disorders and of visual impairment in a defined elderly population of a typical metropolitan area in England, and to assess the frequency they were in touch with, or known to, the eye care services. DESIGN: Cross sectional survey using two stage cluster random sampling. SETTING: General practices in north London. SUBJECTS: Random sample of people aged 65 and older, drawn from a defined population of elderly people registered with 17 general practice groups. MAIN OUTCOME MEASURES: Proportions and population prevalence estimates were determined for visual acuity, assessed with the person's own spectacles (if any), classified into four categories: prevalence of cataract, age related macular degeneration, and refractive error causing visual impairment and of definite primary open angle glaucoma; and status of contact with eye services. RESULTS: 1547 of 1840 (84%) eligible people were examined. The population prevalence of bilateral visual impairment (visual acuity <6/12) was 30%, of which 72% was potentially remediable. 92 of these 448 cases (21%) had visual acuity <6/60 ("blindness") in one or both eyes. Prevalence of cataract causing visual impairment was 30%; 88% of these people were not in touch with the eye services. The prevalence of vision impairing, age related macular degeneration was 8% and of glaucoma (definite cases) was 3%. Three quarters of the people with definite glaucoma were not known to the eye services. CONCLUSIONS: Untreated visual impairment and eye disorders affect a substantial proportion of people aged 65 years and older. These findings should contribute to the setting up of future strategies for preservation of sight and eye health services in general.
Age Distribution↗
'External' Mustarde suture technique in otoplasty.
Although preferences may vary in otoplasty surgery the antihelical fold is frequently created using Mustarde sutures. Technically it is important to insert the needle through the cartilage at right angles and to take a good 'bite' of cartilage. These technical objectives are easily achieved by bringing the needle out through the skin and then placing it in a redirected course through exactly the same needle hole from which it exited the skin. The technique is simple and easily learnt.
Dermatologic Surgical Procedures↗
Statistical analysis of data for three British ethnic groups from a new STR multiplex.
Data have been collected from 602 Caucasians, 190 Afro-Caribbeans and 257 Asians of Indo/Pakistani descent who have been profiled using a new six locus short tandem repeat (STR) multiplex. The data have been analysed by conventional significance testing methods: the exact test, homozygosity, and conventional goodness of fit to Hardy-Weinberg proportions. Frequency tables are given and the expected performance in British forensic casework is discussed.
Chromosome Mapping↗
Evaluation of student performance in combined baccalaureate-MD degree programs.
BACKGROUND: Among the innovations in medical education during the 1960s and early 1970s was the emergence of combined baccalaureate-MD degree programs. Viewed as educational experiments, an evaluation of performance outcomes for these programs is needed. SUMMARY: Performance outcomes of students in combined-degree programs, reported in the literature 1966-1996, are reviewed. Attrition rates are lower for combined-degree students than for traditional premedical students, and there are usually no differences in attrition between combined-degree and traditional students in the medical phase of their education. All measures of performance indicate that students in combined-degree programs achieve a level of competency comparable to traditional medical students. CONCLUSIONS: The support systems of the Baccalaureate-MD degree programs facilitate retention in a medical career. The educational experiment of the combined-degree programs has demonstrated that future physicians can be successfully selected from high school.
Journal Article↗
Molecular cloning, expression and potential functions of the human proteinase-activated receptor-2.
We used PCR to amplify proteinase activated receptor-2 (PAR-2) from human kidney cDNA. The open reading frame comprised 1191 bp and encoded a protein of 397 residues with 83% identity with mouse PAR-2. In KNRK cells (a line of kirsten murine sarcoma virus-transformed rat kidney epithelial cells) transfected with this cDNA, trypsin and activating peptide (AP) corresponding to the tethered ligand exposed by trypsin cleavage (SLIGKV-NH2) induced a prompt increase in cytosolic calcium ion concentration ([Ca2+]i). Human PAR-2 (hPAR-2) resided both on the plasma membrane and in the Golgi apparatus. hPAR-2 mRNA was highly expressed in human pancreas, kidney, colon, liver and small intestine, and by A549 lung and SW480 colon adenocarcinoma cells. Hybridization in situ revealed high expression in intestinal epithelial cells throughout the gut. Trypsin and AP stimulated an increase in [Ca2+]i in a rat intestinal epithelial cell line (hBRIE 380) and stimulated amylase secretion in isolated pancreatic acini. In A549 cells, which also responded to trypsin and AP with mobilization of cytosolic Ca2+, AP inhibited colony formation. Thus PAR-2 may serve as a trypsin sensor in the gut. Its expression by cells and tissues not normally exposed to pancreatic trypsin suggests that other proteases could serve as physiological activators.
Adenocarcinoma↗
Conserved structure and adjacent location of the thrombin receptor and protease-activated receptor 2 genes define a protease-activated receptor gene cluster.
BACKGROUND: Thrombin is a serine protease that elicits a variety of cellular responses. Molecular cloning of a thrombin receptor revealed a G protein-coupled receptor that is activated by a novel proteolytic mechanism. Recently, a second protease-activated receptor was discovered and dubbed PAR2. PAR2 is highly related to the thrombin receptor by sequence and, like the thrombin receptor, is activated by cleavage of its amino terminal exodomain. Also like the thrombin receptor, PAR2 can be activated by the hexapeptide corresponding to its tethered ligand sequence independent of receptor cleavage. Thus, functionally, the thrombin receptor and PAR2 constitute a fledgling receptor family that shares a novel proteolytic activation mechanism. To further explore the relatedness of the two known protease-activated receptors and to examine the possibility that a protease-activated gene cluster might exist, we have compared the structure and chromosomal locations of the thrombin receptor and PAR2 genes. MATERIALS AND METHODS: The genomic structures of the two protease-activated receptor genes were determined by analysis of lambda phage, P1 bacteriophage, and bacterial artificial chromosome (BAC) genomic clones. Chromosomal location was determined with fluorescent in situ hybridization (FISH) on metaphase chromosomes, and the relative distance separating the two genes was evaluated both by means of two-color FISH and analysis of YACs and BACs containing both genes. RESULTS: Analysis of genomic clones revealed that the two protease-activated receptor genes share a two-exon genomic structure in which the first exon encodes 5'-untranslated sequence and signal peptide, and the second exon encodes the mature receptor protein and 3'-untranslated sequence. The two receptor genes also share a common locus with the two human genes located at 5q13 and the two mouse genes at 13D2, a syntenic region of the mouse genome. These techniques also suggest that the physical distance separating these two genes is less than 100 kb. CONCLUSIONS: The fact that the thrombin receptor and PAR2 genes share an identical structure and are located within approximately 100 kb of each other in the genome demonstrates that these genes arose from a gene duplication event. These results define a new protease-activated receptor gene cluster in which new family members may be found.
Amino Acid Sequence↗
A genetic model for absent chylomicron formation: mice producing apolipoprotein B in the liver, but not in the intestine.
The formation of chylomicrons by the intestine is important for the absorption of dietary fats and fat-soluble vitamins (e.g., retinol, alpha-tocopherol). Apo B plays an essential structural role in the formation of chylomicrons in the intestine as well as the VLDL in the liver. We have developed genetically modified mice that express apo B in the liver but not in the intestine. By electron microscopy, the enterocytes of these mice lacked nascent chylomicrons in the endoplasmic reticulum and Golgi apparatus. Because these mice could not form chylomicrons, the intestinal villus enterocytes were massively engorged with fat, which was contained in cytosolic lipid droplets. These mice absorbed D-xylose normally, but there was virtually no absorption of retinol palmitate or cholesterol. The levels of alpha-tocopherol in the plasma were extremely low. Of note, the absence of chylomicron synthesis in the intestine did not appear to have a significant effect on the plasma levels of the apo B-containing lipoproteins produced by the liver. The mice lacking intestinal apo B expression represent the first genetic model of defective absorption of fats and fat-soluble vitamins and provide a useful animal model for studying nutrition and lipoprotein metabolism.
Animals↗
Alveolar soft part sarcoma presenting as a pulsating tumour of the arm in a young woman.
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Adult↗
First-year residents' performances compared with their medical school class ranks as determined by three ranking systems.
Difficulties encountered with deans' letters have prompted residency directors to rely on performance indicators, including class rank, that indicate the comparative positions of applicants. However, the validity of class rank as a predictor of performance in residency is not well established. The present investigation studied the relationship of class ranks to residents' performances, the systems of class ranking that correlated with residents' performances, and procedures that strengthened the relationship between ranking information and residents' performances. Three systems of class ranking are described. With each system, the authors used the same study group of 124 graduates (classes of 1986 and 1987) from a midwestern medical school with a baccalaureate-M.D. degree program; by 1991, each graduate had completed his or her first year of residency. All three systems were reliable for assignment of class rank. All three systems showed modest correlations with residents' performances. Multiple regression analysis revealed that a weighted combination of clinical performance measures bore the strongest relationship to performances in residency. Thus, the authors conclude that the formal computational ranking of students is not essential for the generation of reliable and valid deans' letters that can predict residents' performances. An in-depth evaluation that includes comparative information based on statistically generated formulas, as well as information based on personal qualities, may be a superior alternative.
Clinical Competence↗
Fluid shear stress modulates cytosolic free calcium in vascular endothelial cells.
Cytosolic free Ca2+ concentration ([Ca2+]i) was monitored in single and groups of fura-2-loaded bovine aortic endothelial cells (BAEC) during exposure to laminar fluid shear stress. Application of a step increase in shear stress from 0.08 to 8 dyn/cm2 to confluent BAEC monolayers resulted in a transient increase in [Ca2+]i, which attained a peak value in 15-40 s, followed by a decline to baseline within 40-80 s. The magnitude of the [Ca2+]i responses increased with applied shear stress over the range of 0.2-4 dyn/cm2 and reached a maximum at greater than 4 dyn/cm2. Transient oscillations in [Ca2+]i with gradually diminishing amplitude were observed in individual cells subjected to continuous high shear stress. Elimination of extracellular Ca2+ with ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, blockade of Ca2+ entry with lanthanum, depolarization of the cell membrane with high K+, and preconditioning of BAEC in steady laminar flow had little effect on the [Ca2+]i response. In the presence of ATP or ADP, application of shear stress caused repetitive oscillations in [Ca2+]i in single BAEC, whose frequency was dependent on both agonist concentration and the magnitude of applied shear stress. However, apyrase, an ATPase and ADPase, did not inhibit the shear-induced [Ca2+]i responses in standard medium (no added ATP or ADP), suggesting that the shear-induced [Ca2+]i response is not due to ATP released by endothelial cells.
Adenosine Triphosphate↗
Uptake of exogenous and endogenous eicosapentaenoic acid by cultured human mononuclear cells.
1. Peripheral blood mononuclear cells from eight healthy volunteers were cultured, with or without concanavalin A (Con A), in a medium containing (ml/l) 100 normal autologous serum, 100 experimental autologous serum or 100 heterologous (fetal calf) serum. 2. The control and experimental autologous sera were obtained from the volunteers, before and after 15 d supplementation with 15 g fish oil (MaxEPA)/d to provide 1.5 g eicosapentaenoic acid (EPA; 20:5n-3)/d. The sera were frozen at -20 degrees. The level of EPA increased from trace quantities in the control autologous serum to 14.3% w/w free fatty acids and between 6.9 and 8.1% w/w lipoprotein phospholipids in the experimental autologous serum. The heterologous fetal calf serum was enriched with EPA, complexed with bovine serum albumin, to provide a final concentration of 15 micrograms/ml. All culture medium contained 10 ml fresh autologous serum/l and cells were obtained from the volunteers for the culture studies about 60 d after the end of EPA supplementation. 3. Portions of cells were removed from culture at 36, 48 and 72 h for phospholipid fatty acid analysis. 4. The level of EPA in phospholipids of cells cultured with exogenous EPA in fetal calf serum was increased significantly (P less than 0.05) at all sampling times, both with and without Con A. By 48 h the levels had peaked at 15.8 (SE 2.7) and 18.4 (SE 4.5)% w/w respectively. 5. Resting cells, i.e. with no Con A present, failed to accumulate EPA when cultured in the experimental autologous serum containing 8.6% w/w total lipids as endogenous EPA.(ABSTRACT TRUNCATED AT 250 WORDS)
Cells, Cultured↗
Teaching communication skills to medical students.
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Communication↗
Metabolic control of insulin dependent diabetes after pancreas transplantation.
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Denervation↗
The effects of dimethyl sulfoxide on the osmotic properties of a rat megakaryocytopoietic cell line.
Dimethyl sulfoxide (DMSO) at 0.6 M alters the osmotic state of intracellular water in a line of rat megakaryocytopoietic cells. The response is a function of temperature. Maximal structuring of water occurs at 24.7 degrees C, while disorganization occurs at 30 and 37 degrees C. Little effect occurs at 3 and at 18 degrees C. Parallel measurements of membrane permeability to water indicate that DMSO inhibits the osmotic exit of water at all temperatures. Maximal inhibition occurs at 24.7 degrees C, the same temperature at which maximal organization of water occurs. These findings emphasize the possible role which water may play in explaining the diverse functions of DMSO as cryogenic substance, promoter of cell fusion, and stimulator of cell differentiation.
Animals↗