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Biomedical subjects

J Murray

Publications and source records attributed to J Murray.

At least 181 records · Page 10Linked to original sources
PubMed1997

Lung cancer in relation to exposure to silica dust, silicosis and uranium production in South African gold miners.

BACKGROUND: A nested case-control study for lung cancer was performed on a cohort of 2260 South African gold miners in whom an association between exposure to silica dust and risk of lung cancer was previously reported. The objective was to investigate an expanded set of risk factors and also cancer cell type. METHODS: The 78 cases of lung cancer found during the follow up period from 1970 to 1986 were matched with 386 controls. Risk of lung cancer was related to smoking, exposure to silica dust, incidence of silicosis, and uranium production and the uranium content of the mine ore. RESULTS: The risk of lung cancer was associated with tobacco smoking, cumulative dust exposure, duration of underground mining, and with silicosis. The best predictive model included pack years of cigarette consumption (adjusted relative risk (RR) = 1.0 for < 6.5 pack years, 3.5 (95% confidence interval (CI) 0.7 to 16.8) for 6.5-20 pack years, 5.7 (95% CI 1.3 to 25.8) for 21-30 pack years, and 13.2 (95% CI 3.1 to 56.2) for more than 30 pack years) and silicosis (RR = 2.45 (95% CI 1.2 to 5.2)). No association was found with uranium production. The lung tumour cell type distribution was 40.3% small cell carcinoma, 38.8% squamous cell, 16.4% adenocarcinoma, and 4.5% large cell carcinoma. Small and large cell cancer combined were associated with exposure to dust. CONCLUSIONS: The results cannot be interpreted definitively in terms of causal association. Possible interpretations are: (1) subjects with high dust exposure who develop silicosis are at increased risk of lung cancer; (2) high levels of exposure to silica dust on its own is important in the pathogenesis of lung cancer and silicosis is coincidental; and (3) high levels of silica dust exposure may be a surrogate for the exposure to radon daughters.

Adenocarcinoma↗
PubMed1997

Preclinical studies of indium-111-labeled IgM: a human monoclonal antibody for infection imaging.

UNLABELLED: Indium-111-labeled plasma proteins, such as albumin, transferrin and IgG, have been proven useful to image infection. We reported previously that 111In-labeled human monoclonal antibody, IgM 16.88 (In-IgM) also would localize at the site of infection. However, the kinetics of blood clearance, distribution and infection uptake have not been investigated. We compared the kinetics of distribution and infection uptake of In-IgM 16.88 with that of in-polyclonal IgG in rats with focal infection. METHODS: Both IgM 16.88 and polyclonal IgG were labeled with 111In using a bifunctional chelating agent, LiLo. The labeling efficiency was > 95%. Focal infection was induced in rats by an intramuscular injection of E. Coli in the right thigh. In-IgM (30-40 microCi) was injected into five groups of rats (five rats/group). The rats were killed at 4, 8, 16, 24 and 36 hr. The percent injected dose (%ID) in blood, infection muscle, control muscle, liver, spleen and kidney were determined. Similar studies were performed with In-IgG. RESULTS: The In-IgM activity in blood at 4 hr postinjection was 27% which decreased to 2% by 36 hr. In contrast, the In-IgG blood activity was 40% at 4 hr and 20% at 36 hr. The infection/ muscle (I/M) ratios are higher with In-IgM at all time points postinjection compared to that of In-IgG. At 24 hr, the I/M ratio was 22 compared to 9 with In-IgG. At the same time point, the infection/ blood (I/B) ratio with In-IgM was 2.7 compared to only 0.8 with that of In-IgG. In-IgM was taken up mostly by the liver compared to diffuse abdominal uptake of IgG. CONCLUSION: These result indicate that In-IgM produces higher lesion to background ratio when compared to In-IgG and, therefore, is potentially useful to image infection in patients.

Animals↗
PubMed1997

Factors predicting prolonged mechanical ventilation in critically injured patients: introducing a simplified quantitative risk score.

Our objective was to identify a set of readily available and easily obtainable parameters that would predict prolonged mechanical ventilation in the critically injured patient. A surgical intensive care unit of an academic Level I trauma center. Prospectively collected data were retrospectively analyzed on all critically injured patients receiving mechanical ventilation for more than 2 days between January and December 1994. Prolonged mechanical ventilation (PMV) was defined as the need for mechanical ventilatory support for more than 7 days. One hundred and nineteen patients entered the final analysis. Of these, 63 remained on the ventilator for 7 days or less and 56 for more than 7 days. The Injury Severity Score (ISS), partial arterial oxygen tension (PaO2)/inspired fraction of oxygen (FiO2), net fluid balance, and use of Swan-Ganz were significantly different between the two groups when calculated 48 hours after surgical intensive care unit admission. Furthermore, we dichotomized these four variables across cutpoints that were determined by statistical analysis (ISS more or less than 20, PaO2/FiO2 more or less than 250, fluid retention more or less than 2000 cc, and presence or absence of Swan-Ganz). Again, significantly more patients required PMV if they had any one of the following: Swan-Ganz, ISS more than 20, PaO2/FiO2 less than 250, or fluid retention more than 2000 cc at 48 hours. An easily calculated five-point risk score (0-4 points) for predicting PMV based on these four variables was developed. Among the 35 patients at the extremes of the risk score (0 or 4 points), 33 (94.3%) were correctly prognosticated as to their needs for PMV. The need for an easily calculated score, which is derived from readily available parameters and can reliably identify patients with prolonged needs for ventilatory support, is obvious in the trauma setting. We describe a five-point risk score by which we can predict the need for PMV early in the course of the disease. Resource utilization and personnel allocation issues, as well as important therapeutic procedures, can be planned based on this score.

Adolescent↗
PubMed1997

A T-cell model for the biological role of selenium-dependent glutathione peroxidase.

The cytosolic form of selenium-dependent glutathione peroxidase detoxifies both hydrogen and lipid peroxides and therefore represents a major component of the cellular anti-oxidant defenses. In order to study the biological role of this enzyme, we generated an expression construct in a retroviral vector, which when introduced into immortalized human T-cells, resulted in significant increases in the activity of this important enzyme. This effect is stable over extended maintenance in culture. The anti-oxidant defenses in these same cells are also shown to be attenuated by chemically reducing cellular glutathione levels. Collectively, the ability to both increase and decrease the anti-oxidant defenses in human T cells results in a useful model system for the study of oxidative stress and signaling in this cell type.

Cell Line↗
PubMed1997

Screening for fragile X syndrome.

BACKGROUND AND AIM OF REVIEW. In 1991, the gene responsible for fragile X syndrome, a common cause of learning disability, was discovered. As a result, diagnosis of the disorder has improved and its molecular genetics are now understood. This report seems to provide the information needed to decide whether to use DNA testing to screen for the disorder. HOW THE RESEARCH WAS CONDUCTED. A literature search of electronic reference databases of published and 'grey' literature was undertaken together with hand searching of the most recent publications. RESEARCH FINDINGS. NATURAL HISTORY. Physical characteristics of fragile X syndrome include facial atypia, joint laxity and, in boys, macro-orchidism. Most affected males have moderate-to-severe learning disabilities with IQs under 50 whereas most females have borderline IQs of 70-85. Behavioural problems are similar to those seen with autism and attention-deficit disorders. Although fragile X syndrome is not curable there are a number of medical, educational, psychological and social interventions that can improve the symptoms. About 6% of those with learning disabilities tested in institutions have fragile X syndrome. Population prevalence figures are 1 in 4000 in males and 1 in 8000 in females. GENETICS. The disorder is caused by a mutation in a gene on the X chromosome which includes a trinucleotide repeat sequence. The mutation is characterized by hyper-expansion of the repeat sequence leading to down-regulation of the gene. In males an allele with repeat size in excess of 200, termed a full mutation (FM), is always associated with the affected phenotype, whereas in females only half are affected. Individuals with alleles having repeat size in the range 55-199 are unaffected but in females the sequence is heritably unstable so that it is at high risk of expansion to an FM in her offspring. This allele is known as a pre-mutation (PM) to contrast it with the FM found in the affected individual. No spontaneous expansions directly from a normal allele to an FM have been observed. SCREENING STRATEGIES. The principal aims of screenng for fragile X syndrome is to reduce the birth prevalence of the disorder, by prenatal diagnosis and selective termination of pregnancy, or by reducing the number of pregnancies in women who have the FM or PM alleles. Possible screening strategies are: routine antenatal testing of apparently low risk pregnancies, preconceptual testing of young women, and systematic testing in affected families ('cascade' screening). A secondary aim is to bring forward the diagnosis of affected individuals so that they might benefit from early treatment. Active paediatric screening and neonatal screening could achieve this but there is no direct evidence of any great benefit from early diagnosis. SCREENING TESTS. Cytogenetic methods are unsuitable for screening purposes. Southern blotting of genomic DNA can be used but is inaccurate in measuring the size of small PMs, there is a long laboratory turnaround time, and it is relatively expensive. The best protocol is to amplify the DNA using polymerase chain reaction on all samples, and when there is a possible failure to amplify, a Southern blot.(ABSTRACT TRUNCATED)

Costs and Cost Analysis↗
PubMed1996

Characterisation of secondary metabolites associated with neutrophil apoptosis.

We studied changes in secondary metabolites in human neutrophils undergoing constitutive or tumour necrosis factor (TNFalpha) stimulated apoptosis by a combination of high-performance liquid chromatography (HPLC) and NMR spectroscopy. Our results show that in contrast to freshly isolated neutrophils, neutrophil cells aged for 20 h in vitro had marked differences in the levels of a number of endogenous metabolites including lactate, amino acids and phosphocholine (PCho). There was no change in the concentration of taurine or glutamate and the ATP/ADP ratio was not affected. Levels of glutamine and lactate actually decreased. Identical changes were also observed in neutrophils stimulated to undergo apoptosis over a shorter time period (6 h) in the presence of TNFalpha and the phosphatidylinositol-3-kinase inhibitor wortmannin (WM). The changes in the concentration of PCho suggest possible activation of phospholipase associated with apoptosis or a selective failure of phosphatidycholine synthesis. The increased levels of apoptosis obtained with WM+TNFalpha, compared to TNFalpha by itself, suggest a synergistic effect by these compounds. The acceleration in rate of apoptosis probably arises from suppression by WM of pathway(s) that normally delay the onset of apoptosis. Changes in PCho and other endogenous metabolites, if proven to be characteristic of apoptosis in other cell systems, may permit non-invasive quantification of apoptosis. '

Adenosine Diphosphate↗
PubMed1996

Hereditary spherocytosis with spectrin deficiency due to an unstable truncated beta spectrin.

Red cell membrane protein analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and direct quantitation by radioimmunoassay or cytofluorometry defines four distinct subsets of patients with hereditary spherocytosis: Patients with isolated spectrin deficiency, combined spectrin and ankyrin deficiency, band 3 deficiency, and protein 4.2 deficiency. In regard to the first group, only one mutation of beta spectrin has been reported in the literature. We describe a spectrin variant characterized by a truncated beta chain, and associated with hereditary spherocytosis and isolated spectrin deficiency. The clinical phenotype consists of a moderate hemolytic anemia with spherocytosis and frequent spiculation of the red cells. We present the biochemical characteristics of this mutant protein and show that it constitutes only 12% of the total spectrin on the membrane. We show that the truncation of the protein is the result of a single point mutation at position +1 (G-->A) of the donor consensus splice site of intron 17 leading to an aberrant beta spectrin transcriptional message lacking exons 16 and 17. To elucidate the basis for the decreased amount of the truncated protein on the membrane and the overall spectrin deficiency, we provide evidence that the mutated gene is transcribed but its mRNA is less abundant than its normal counterpart in reticulocytes; we also show that the mutant protein is synthesized in decreased amounts in the cytoplasm of erythroid progenitor cells, and appears to be susceptible to proteolytic degradation. This mutant spectrin underscores the importance of the regulatory role played by the beta spectrin molecule in the assembly of alphabeta spectrin heterodimers on the membrane.

Base Sequence↗
PubMed1996

Centenary year of scientific papers in the British Dental Journal.

N J Ainsworth, in his paper on mottled teeth, published in 1933, was the first person in the UK responsible for identifying the presence of fluoride in water supplies and quantifying the amount of caries in areas with mottled teeth. As well as a brief summary of the paper by Mike Grace, John Murray writes a critical examination of this landmark paper.

Child↗
PubMed1996

Gastrointestinal transit during endotoxemia: the role of nitric oxide.

We hypothesized that the disrupted gastrointestinal transit that occurs during endotoxemia is mediated by nitric oxide (NO) and that the inhibition of NO synthesis will normalize intestinal transit and gastric emptying. To determine the effects of endotoxin and steroids on the activity of gastrointestinal smooth muscle NO synthase, rats underwent placement of an intravenous (iv) line and then were given Escherichia coli lipopolysaccharide (LPS) 10 mg/kg/iv; LPS, 10 mg/kg/iv + dexamethasone, 3 mg/kg/iv; or saline. The activity of nitric oxide synthase in the stomach, small intestine, and colon were determined by measuring the conversion of L-[3H]arginine to L-[3H]citrulline. To determine intestinal transit and gastric emptying, gavage feedings of nonabsorbable liquid markers were given and rats divided into eight groups: 0.9% NaCl, 1 ml/hr x 5 hr (control); LPS, 10 mg/kg/iv; LPS + N-omega-nitro-L-arginine methyl ester (L-NAME), 10 mg/kg/hr x 5 hr; LPS + N-omega-nitro-D-arginine methyl ester (D-NAME), 10 mg/kg/hr x 5 hr; LPS + L-arginine, 100 mg/kg/hr x 5 hr; LPS + L+NAME + L-arginine; LPS + N-omega-nitro-L-arginine (L-NNA) 10 mg/kg/hr; or LPS + L-NNA + L-arginine. LPS increased the enzymatic activity of both the constitutive and the inducible forms of NO synthase in the small intestine and fundus of the stomach. The acceleration of intestinal transit produced by endotoxemia was reversed with both L-NAME and L-NNA but not with D-NAME. Endotoxemia slowed gastric emptying but this effect was not reversed with either L-NAME or L-NNA. We conclude that NO plays a major role in mediating the rapid intestinal transit during endotoxemia.

Animals↗
PubMed1996

Loop electrocautery excisional procedure: therapeutic effectiveness as an ablation and a conization equivalent.

This study was designed to compare the effectiveness of loop excision procedures as ablation and conization equivalents, and their use in recurrent cervical high-grade dysplasia patients. We retrospectively reviewed patients undergoing loop procedures between January 1992 and April 1994. Conization equivalents were defined as procedures performed for unsatisfactory colposcopy, positive endocervical curettage, discordant cytology and histology, and cytology suggestive of invasion. Effectiveness in high-grade recurrent lesions was evaluated separately. Therapeutic failure was defined as any recurrence of high-grade dysplasia. One hundred sixty-two patients underwent loop procedures, of which 123 (75.9%) had follow-up examinations and are included. Mean follow-up was 17.9 months. Seventy-six patients (61.8%) had the loop procedure performed as an ablation equivalent, 29 (23.6%) as a conization equivalent, and 18 (14.6%) for recurrent disease. Overall effectiveness was 82.1 % and for ablation and conization equivalent procedures was 82.9 and 82.8%, respectively. There was no significant difference between effectiveness when performed for initial therapy (82.9%) and for recurrent disease (72.2%) (P = 0.46). In conclusion, loop excision procedures are effective as ablation and conization equivalents and as treatment for recurrent high-grade dysplasia.

Conization↗
PubMed1996

The significance of accumulated oropharyngeal secretions and swallowing frequency in predicting aspiration.

This study retrospectively investigated the value of both endoscopically visible oropharyngeal secretions in the hypopharynx and swallowing frequency in the prediction of aspiration of food and liquid. Fiberoptic endoscopic evaluation of swallowing (FEES) was performed on a total of 69 individuals that included hospitalized elderly, nonhospitalized elderly, and young normal subjects. A four-level rating scale for determining the severity of accumulated oropharyngeal secretions was developed and employed to rate subjects prior to the presentation of food or liquid during the FEES. Spontaneous dry swallows were also counted during the observation period of the FEES. It was found that the accumulation of endoscopically visible oropharyngeal secretions located within the laryngeal vestibule was highly predictive of aspiration of food or liquid. There were significantly fewer spontaneous swallows in hospitalized subjects when compared with nonhospitalized subjects. There was also a significant decrease in the frequency of spontaneous swallows in aspirating hospitalized subjects when compared with nonaspirating hospitalized subjects. Results are discussed in terms of integrating this information with clinical bedside examination techniques.

Aged↗
PubMed1996

Subfascial endoscopic perforator vein surgery: a preliminary report.

Although the open Linton subfascial perforator vein interruption operation succeeded, for the most part, in preventing recurrent venous ulceration, it was associated with morbidity and prolonged hospitalization. We have attempted to obtain the beneficial effects of perforator interruption by the less invasive procedure of subfascial endoscopic perforator vein surgery using laparoscopic instrumentation and limited or no hospitalization. A total of 31 consecutive operations were performed in 30 patients. Sixteen women and 14 men were entered into the study, and all of them had severe chronic venous insufficiency with either open or healed ulcers. Operations were carried out without gas insufflation, in 17 without a hemostatic tourniquet, and in 13 entirely on an outpatient basis. The 18 hospitalizations produced a total of 49 days of inpatient care (mean 2.72 days). One to six perforating veins were encountered in these operations, and veins identified as perforators were electrocoagulated or clipped and sectioned. Sixteen limbs had severe chronic venous insufficiency or healed ulcers, and 15 had open ulcers. In 13 limbs, ulcers were intermittently present for 1 to 5 years. Seven of these healed within 4 weeks of operation and four others within 8 weeks. Two healed more than 8 weeks after surgery. In two limbs with ulcers that were present for 1 to 6 months, healing took place within 4 weeks of the operation in both. Complications included atelectasis in one patient, cellulitis requiring antibiotic therapy in three, wound hematomas not requiring intervention in two, and wound seroma not requiring therapy in one. This preliminary experience suggests that perforator vein interruption can be accomplished using existing instrumentation and a variety of technical modifications to achieve the objectives of the Linton operation without the attendant morbidity. Videoscopic instrumentation obtains benefits of subfascial perforator vein interruption without morbidity of the open operations. This preliminary study suggests that the operative procedure is attended by minimum morbidity without the need for rehospitalization. Long-term observation will be required to assess the procedure definitively, but the short-term objectives can be safely accomplished with minimum use of inpatient facilities.

Ambulatory Surgical Procedures↗