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Biomedical subjects

D Shaw

Publications and source records attributed to D Shaw.

At least 145 records · Page 8Linked to original sources

Toxicological problems resulting from exposure to traditional remedies and food supplements.

The National Poisons Unit, London, carried out a pilot survey to investigate the frequency and severity of adverse effects/toxicity from exposure to traditional medicines and food supplements reported to the Unit. Enquiries related to suspected poisoning events were reviewed retrospectively from January 1983 to March 1989, and prospectively in 1991. Further information about cases identified by the prospective review was obtained, when appropriate, by follow-up questionnaire, clinical consultation by a consultant toxicologist, toxicological analyses of samples from patients and from products, and botanical identification of dried plant material. In total, 5536 enquiries were identified. Symptoms were reported in 657 (12%) of these. There was a large number of reports of accidental ingestion of vitamin preparations by children under 5 years. Appropriate assessment was possible in only relatively few cases, due to insufficient documentation, and poor labelling of certain products. A probable link between exposure and adverse effects was identified in 42 cases, and was highly probable in two. Heavy metal poisoning resulting from use of contaminated traditional remedies was confirmed in 5 cases. There was evidence that some patients took excessive doses of food supplements, without realising that this might result in toxic effects. The results of this pilot study suggest that there is a need for further surveillance to provide an appropriate risk assessment of food supplements and herbal remedies, improved quality control and labelling of these products, and increased awareness of their potential hazard.

Adolescent↗

Complement inhibition with soluble complement receptor type 1 in cardiopulmonary bypass.

Although complement activation during cardiopulmonary bypass (CPB) is well documented, its pathogenic role in postperfusion organ injury is unproven. In this study, soluble human complement receptor type 1 (sCR1), a potent inhibitor of complement activation, was used to determine the contribution of complement activation to pulmonary injury in a porcine model of CPB. In vitro experiments demonstrated that sCR1 inhibits both classic and alternative complement pathways in the pig. Seven control piglets and 6 piglets treated with sCR1 (12 mg/kg intravenously) underwent 2 hours of hypothermic (28 degrees C) CPB followed by 2 hours of observation. In control piglets, total hemolytic complement activity and functional activities of C3 and C5 declined to 61.3%, 67.8%, and 61.4% of prebypass values, respectively, after 2 hours of CPB. Plasma from animals treated with sCR1 had virtually no hemolytic activity (total hemolytic complement activity < 5% of baseline), demonstrating effective complement inhibition. Similar degrees of neutropenia developed in the two groups during CPB, and there was no difference in post-CPB lung tissue myeloperoxidase level. Two hours after CPB, pulmonary vascular resistance increased 338% in control piglets but only 147% in piglets pretreated with sCR1 (p < 0.05); the alveolar-arterial gradient was not significantly different between controls (331 +/- 52 mm Hg) and piglets receiving sCR1 (290 +/- 85 mm Hg). Histologic examination revealed similar degrees of pulmonary edema in both groups. These data constitute direct evidence that complement activation plays a pathogenic role in lung injury after CPB.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The DM mutation; diagnostic applications in the Finnish population.

A pair of marker loci, D19S63 and D19S51, which are tightly linked to the myotonic dystrophy (DM) locus, were used to evaluate diagnostic applicability in the Finnish population. Results were then compared to direct detection of the mutation. The D19S63 locus revealed a linkage disequilibrium, since in 16 DM families as many as 75% of DM chromosomes carried the same allele 3 for D19S63, and 25% carried allele 1. However, when the data for D19S51 and D19S63 were considered together as a haplotype, the statistical significance of this linkage disequilibrium was considerably reduced. As expected, the best method for reliable evaluation of the carrier risk was direct analysis of the mutation. Thirteen particularly difficult cases were resolved and in 46% of them the decision could be made only by direct visualization of the mutation. However, in a few cases where the size of the CTG-repeat expansion was close to the normal size range, linked markers proved to be useful to determine the affected chromosomes. Present findings indicate that analysis of the D19S63 locus coupled to direct demonstration of the mutation provides the basis for DNA diagnostics of DM in the Finnish population.

Alleles↗

The handedness of Kerrs and Carrs.

The surnames Kerr and Carr have been claimed, on the basis of folkloric and etymological evidence, to be associated with an increased incidence of left-handedness. In 1974 a survey by the Royal College of General Practitioners suggested that the incidence of left-handedness was nearly three times as high in Kerr/Carr families as in controls. That survey was however potentially flawed by response biases. In the present study, which used better controls, no evidence was found for an increased incidence of left-handedness in Kerrs and Carrs.

Adolescent↗

An informative panel of somatic cell hybrids for physical mapping on human chromosome 19q.

A panel of 22 somatic cell hybrids divides the q arm of human chromosome 19 into 22 ordered subregions. The panel was characterized with respect to 41 genetic markers. In most cases, a single fragment of chromosome 19 was present in each hybrid. In two cell lines the presence of multiple fragments of the chromosome was demonstrated by segregation of these fragments in subclones. On the basis of the results of marker analysis in this panel, the most likely order of the markers tested is MANB-D19S7-PEPD-D19S9-GPI-C/EBP-TGFB1++ +-(CYP2A,BCKDHA,CGM2,NCA)-PSG1-(D19S8, XRCC1)-(ATP1A3,D19S19)-(D19S37,APOC2)-C KM-ERCC2-ERCC1-(D19S116,D19S117)- (D19S118,D19S119, D19S63,p36.1,D19S112,D19S62,D19S51,D19S54, D19S55)-pW39-D19S6-(D19S50,TNNT1)-D19S2 2-(HRC,CGB,FTL,PRKCG)-qter. This gene order is generally consistent with published physical and genetic mapping orders, although some discrepancies exist. By means of a mapping function that relates the frequency of cosegregation of markers to the distance between them, estimates were made of the sizes, in megabases, of the 19q subregions. The relative physical distances between reference markers were compared with published genetic distances for 19q. Excellent correlation was observed, suggesting that the physical distances calculated by this method are predictive of genetic distances in this region of the genome and, therefore, are just as useful in estimating relative positions of markers.

Animals↗

Effect of Rb+ on cromakalim-induced relaxation and ion fluxes in guinea pig trachea.

The effects of cromakalim, verapamil and salbutamol have been examined in guinea pig trachealis smooth muscle in both Krebs physiological salt solution and Krebs solution where K+ has been replaced by Rb+. Cromakalim-induced relaxation in the presence of Rb+ was reduced in extent and became transient, whilst the relaxation response to verapamil was enhanced and that to salbutamol unaffected. The transient relaxation occurring in Rb+ was blocked by quinidine and glibenclamide. The presence of extracellular Rb+ also prevented cromakalim-stimulated efflux of both 86Rb+ and 42/43K+. There was, however, no effect on cromakalim-stimulated 86Rb+ uptake. It is proposed that cromakalim is opening two populations of potassium channel in guinea pig tracheal smooth muscle, one of which is susceptible to blockade by Rb+ and one of which is not. The latter channel appears to play the dominant role in cromakalim-stimulated uptake, and is responsible for the transient relaxation response in the presence of rubidium, whilst the former is responsible for the maintained relaxation.

Albuterol↗

Mycobacterium bovis (BCG) vaccination. Progressive disease in a patient asymptomatically infected with the human immunodeficiency virus.

OBJECTIVE: To report a case of progressive disease caused by Mycobacterium bovis after BCG vaccination in a patient asymptomatically infected with the human immunodeficiency virus (HIV). CLINICAL FEATURES: A 34-year-old white man about to commence employment as a developmental care worker had a BCG vaccination. Five months later, he had a positive result to a serological test for HIV antibody. Nine months after BCG vaccination, he presented with fever (38.7 degrees C), a large left axillary lymph node and a small left pleural effusion. The lymph node was biopsied and acid-fast bacilli observed in Ziehl-Neelsen stained smears. Culture grew Mycobacterium bovis (BCG). TREATMENT AND OUTCOME: He was successfully treated with isoniazid, rifampicin and ethambutol for a period of nine months. CONCLUSION: BCG vaccination of asymptomatic HIV-positive patients is not recommended. The detection of those at risk for HIV infection before vaccination administration is essential. Self-exclusion based on information supplied to all potential recipients is likely to be the most effective method.

Adult↗

Characterization of a YAC and cosmid contig containing markers tightly linked to the myotonic dystrophy locus on chromosome 19.

Myotonic dystrophy (DM) is caused by a defect in an unknown gene that maps to 19q13.3, flanked by the tightly linked markers ERCC1 on the proximal side and D19S51 on the distal side. We report the isolation and characterization of overlapping YAC and cosmid clones around D19S51 for the construction of a physical map around this locus. The resulting contig contains the markers D19S51 and D19S62 (another new marker tightly linked to the DM locus) and the distal breakpoint of a radiation hybrid cell line used in the physical mapping of the DM region. We have compared the restriction maps of the YACs and cosmids with that of the genome to investigate the fidelity of these clones.

Base Sequence↗

Oxygen therapy in sickle cell disease.

The effect of oxygen therapy on the number of irreversibly (ISC) and reversibly (RSC) sickled cells was studied in patients with sickle cell anemia. Inhalation of 50% oxygen in patients who were not in crisis produced a significant fall in RSCs and a lesser fall in ISCs. Twenty-five subjects in sickle cell crisis were chosen at random to receive either oxygen (15 patients) or air (10 patients). Those who received oxygen showed a significant reduction in RSCs, but not in ISCs. No significant change in RSCs or ISCs occurred in the group who received air. Despite the reduction in RSCs in the oxygen-treated group, there was no significant difference between the air and oxygen groups in the duration of severe pain, opioid administration, and hospitalization. It was also observed that crisis was associated with arterial desaturation and a reduction in the number of RSCs. We conclude that, although RSCs may be involved in the pathophysiology of sickle cell crisis, reduction in RSCs by oxygen therapy in these studies did not result in any reduction in the duration of crisis.

Adolescent↗

Chorionic villus sampling: analysis of fetal losses to delivery, placental pathology, and cervical microbiology.

A population of 1639 patients were seen for chorionic villus sampling (CVS). Embryonic death was identified at ultrasound in 5.3 per cent of patients. The number of patients undergoing CVS was 1551, with 1416 transcervical procedures and 135 transabdominal procedures. The most common indication for CVS was advanced maternal age. Spontaneous pregnancy losses identified by increased risk of pregnancy loss with increasing aspiration attempts. The total fetal loss for this population was 5.4 per cent with the pregnancy loss estimated due to procedure being 1.2 per cent. Analysis of placentae from patients having CVS and amniocentesis showed no differences. Microbiological assessment prior to CVS was similar to previous publications.

Adult↗