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Biomedical subjects

D Shaw

Publications and source records attributed to D Shaw.

At least 19 recordsLinked to original sources

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in guinea pig trachealis smooth muscle in both Krebs physiological salt solution and Krebs solution where K+ has been replaced by Rb+.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

Human glandular Kallikrein genes: genetic and physical mapping of the KLK1 locus using a highly polymorphic microsatellite PCR marker.

We describe a highly polymorphic microsatellite repeat sequence, KLK1 AC, which is located 3' to the human glandular kallikrein gene (KLK1) at 19q13.3-13.4. A multiplex PCR was developed to simultaneously genotype the KLK1 AC repeat length polymorphism and a similar repeat at the adjacent APOC2 locus at 19q13.2. Genotypes from these two loci in the 40 large kindred pedigrees from the Centre d'Etude du Polymorphisme Humain were used in conjunction with the background genetic map to establish a multipoint linkage map. The KLK1 locus was also localized physically using somatic cell hybrid DNA templates for polymerase chain reaction analysis. Both genetic and physical mapping studies are consistent with the assignment cen-APOC2-KLK1-D19522-qter. The linkage map places KLK1 approximately 10 cM distal to APOC2. These markers therefore flank the myotonic dystrophy gene and may be useful for diagnosis.

Alleles

NADH measurements in adult rat myocytes during simulated ischemia.

In isolated adult rat myocytes, we tested the hypothesis that metabolic inhibition and simulated ischemia regulate the NADH/NAD+ redox couple with concomitant impairment of energy-dependent process, including contraction and maintenance of high-energy phosphate stores. We developed a method to examine the relationship among the redox couple, ATP content, and contractile performance in single cells under several conditions analogous to myocardial ischemia, with and without reperfusion. Myocytes were paced at 1 Hz while cell contraction and NADH fluorescence were determined simultaneously for single cells at 37 degrees C. Cells were exposed to cyanide and 2-deoxy-D-glucose (metabolic inhibition) or to metabolic inhibition plus 12 mM KCl and 20 mM lactate at pH 6.5 (simulated ischemia). Pyridine nucleotide fluorescence signals from single cells studied in this fashion could be modulated by metabolic inhibitors in a manner similar to that classically described for isolated mitochondria. Metabolic inhibition or simulated ischemia quickly produced maximal reduction of NAD+ to NADH. When cells were exposed to simulated ischemia for 10 min, then superfused with glucose-containing control buffer, 28% of cells exposed to conditions of simulated ischemia developed hypercontracture on reperfusion. Hypercontracture developed despite mitochondrial electron transport being reestablished. When myocyte suspensions in a cuvette were studied spectrofluorimetrically, the pyridine nucleotide fluorescence response to metabolic inhibitors was similar to that for a single cell. This permitted correlation of ATP determinations on cells in suspension with contractile and fluorescence measurements from single myocytes. In the absence of glycolysis there is correspondence among loss of electron transport, decline in high-energy phosphate concentration, and decline in contraction. Irreversible disruption of the electron transport process does not appear to be an early event in ischemic injury.

Adenine Nucleotides

Coliform septicemia and pulmonary disease associated with canine parvoviral enteritis: 88 cases (1987-1988).

Parvovirus infection was confirmed by fluorescent antibody staining or viral culturing in 137 (22%) of 615 necropsy accessions from dogs at the Missouri Veterinary Medical Diagnostic Laboratory from Jan 1, 1987 through Sept 30, 1988. Septicemic colibacillosis was diagnosed in 88 (90%) of the 98 canine parvovirus-positive accessions in which liver or lung was cultured bacteriologically. Pulmonary edema or alveolitis similar to that seen in the human adult respiratory distress syndrome was observed in 63 (69%) of the 91 canine parvovirus-positive accessions in which the lungs were examined histologically.

Animals

Norepinephrine in acute exacerbations of chronic schizophrenia. Negative symptoms revisited.

In recent years the dopamine hypothesis has failed to explain the complexities of schizophrenia. Because both negative symptoms and noradrenergic activity appear to increase with psychotic relapse, we studied negative symptoms, psychosis, cerebrospinal fluid norepinephrine, and cerebrospinal fluid monoamine metabolites in 32 male patients with a DSM-III diagnosis of schizophrenia while both receiving and not receiving long-term haloperidol treatment. Drug-free cerebrospinal fluid norepinephrine and 3-methoxy-4-hydroxyphenylglycol levels correlated significantly with the severity of negative symptoms and psychosis ratings. When the patients were divided into those who did and did not relapse while not receiving the drug, significant positive correlations between negative symptoms and cerebrospinal fluid norepinephrine and 3-methoxy-4-hydroxyphenylglycol were observed only in the patients who relapsed. Non significant but negative correlations were observed between the same variables in the nonrelapsers. Thus, increased norepinephrine activity in drug-free patients is associated with intensification of schizophrenic symptoms without necessarily causing the symptoms.

Acute Disease

Metastatic neuroblastoma: new abnormalities on bone scintigraphy may not indicate tumour recurrence.

Neuroblastoma is a potentially curable childhood malignancy with survival rates of 20% reported even in advanced disease. Technetium-labelled methylene diphosphonate (Tc99m-MDP) scanning is well established as a method of assessing bone disease. We report four patients, with advanced neuroblastoma in complete or partial remission, in whom new abnormalities on bone scintigraphy were due to benign lesions. Correct management depends on the precise diagnosis of such lesions.

Bone Diseases

The initial effects on workload and outcome of a public education campaign on early diagnosis and treatment of malignant melanoma in Leicestershire.

We report our experience of the initial effects of a publicity campaign directed at early presentation of malignant melanoma in Leicestershire. The campaign resulted in a dramatic increase in workload and, at the pigmented lesion clinic, the numbers of new patients rose from 12.3 to 54.5 per clinic. There was a large rise in the number of new melanomas presenting in Leicestershire: from 1.02 per week before the campaign to 1.88 per week in the immediate post-publicity period. This was statistically significant (P less than 0.001). Although there was also an apparently encouraging rise in the percentage of thinner 'good prognosis' tumours, it was not possible to isolate this statistically from a pre-existing trend.

Dermatology

Cerebral blood flow velocity recordings and the prediction of intracranial haemorrhage and ischaemia.

Doppler ultrasound was used to study prospectively cerebral and cardiovascular hemodynamics in a cohort of 120 preterm infants to see whether it was possible to predict infants at increased risk of developing cerebral pathology. The infants were divided into four outcome groups: Group I (n = 65, median gestation = 30 weeks) did not develop periventricular haemorrhage (PVH) nor periventricular leukomalacia (PVL) Group II (n = 43, median gestation = 28 weeks) developed PVH as the first or only cerebral lesion Group III (n = 7, median gestation = 29 weeks) developed PVL as the first or only cerebral lesion Group IV (n = 5, median gestation = 28 weeks) developed PVH and PVL simultaneously. Cerebral blood flow velocity (CBFV) and aorta blood flow velocity (ABFV) recordings made before the onset of PVH or PVL were compared between the four groups on each postnatal day but it was not possible to demonstrate a statistically significant difference between these variables in the four outcome groups. We conclude, therefore, that it is not possible to identify the infants who will go on to develop haemorrhage or ischaemic lesions on the basis of Doppler cerebral haemodynamic studies.

Aorta

[Pathogenesis and treatment of Zencker's diverticulum].

The aims of this study were: 1) To measure pharyngeal and upper oesophageal function manometrically at the same time as recording video images of the patient swallowing barium, in normal controls and patients with Zenker's diverticulum, and, 2) In those patients who progressed to surgery to biopsy the cricopharyngeus and compare the findings with biopsies from normal controls. Subjects were seated in front of a fluoroscope and video images of a barium swallow were synchronised with a multichannel recording catheter which contained 3 perfused side holes 1 cm apart (situated in the pharynx) and a 4 cm long perfused sleeve pressure sensor (positioned across the upper oesophageal sphincter). The coordination of the upper sphincter with swallowing, its relaxation, the pressures generated in the distal pharynx and the maximum luminal area of the open upper sphincter, were calculated for different volumes of barium swallowed in 11 patients with a Zenker's diverticulum (mean age 71 years, range 50-99) and 9 normal controls (mean age 65 years, range 55-86). Seven patients progressed to cricopharyngeal myotomy and their biopsies were compared with biopsies from 9 normal controls. In patients with Zenker's diverticulum intrapharyngeal pressures during barium swallows were significantly greater (p less than .05) and maximal luminal areas of the open sphincter were significantly less (p less than .05) than in control patients. In patients having a cricopharyngeal myotomy, intrapharyngeal pressures and maximum luminal areas returned to normal after surgery. The cricopharyngeus muscle of patients with a Zenker's diverticulum showed significantly increased fibrosis compared with normal controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Efficacy of zinc citrate ascorbate for treatment of canine cataracts.

Efficacy of zinc citrate ascorbate was evaluated in 146 dogs (265 eyes) that had various lens opacities. Zinc citrate ascorbate or saline placebo drops were applied topically once or twice daily for 4 to 31 weeks. Of 138 eyes treated with zinc citrate ascorbate, 86 eyes (62.3%) had no change, 48 eyes (34.8%) had increased lens opacity, and 4 eyes (2.9%) had decreased lens opacity. Of 127 eyes treated with a saline placebo, 99 eyes (77.9%) had no change, 25 eyes (19.7%) had increased lens opacity, and 3 eyes (2.4%) had decreased lens opacity. Zinc citrate ascorbate drops were not significantly (P = less than 0.05) more effective in clearing cataracts than were saline drops. Seemingly, zinc citrate ascorbate drops may have caused lens opacities to increase in area and density.

Animals