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Biomedical subjects

A Watson

Publications and source records attributed to A Watson.

At least 235 records · Page 13Linked to original sources

Effects of nonsteroidal anti-inflammatory drugs on the bronchial hyperresponsiveness of middle-aged male smokers.

Bronchial hyperresponsiveness (BHR) in smokers is believed to be a consequence of airway wall inflammation. We have examined the effects of treatment with nonsteroidal anti-inflammatory drugs (NSAID) on BHR to inhaled histamine, measured as the provocative concentration reducing forced expiratory volume in one second (FEV1) by 20% (PC20), in middle-aged male cigarette smokers in two separate double-blind, placebo-controlled, cross-over trials. Baseline FEV1 in these smokers ranged from 41-117% predicted values. In the first study 15 men (mean age 58 yrs, FEV1 2.20 l) were examined before and one hour after a single dose of 1.2 g aspirin. There was no significant change in PC20 (geometric mean 1.88 mg.ml-1 pre-aspirin, 1.89 mg.ml-1 post-aspirin) or baseline FEV1 and we observed no tachyphylaxis to the effects of inhaled histamine at one hour after placebo. In the second study 10 men (mean age 60 yrs, FEV1 2.53 l) were examined before and after three days' treatment with the NSAID flurbiprofen 50 mg t.d.s. Baseline PC20 was higher in this group than in the first study. There was no relationship between the excretion of urinary thromboxane metabolites and the intensity of BHR under baseline conditions; flurbiprofen greatly reduced the urinary excretion of thromboxane metabolites, but baseline FEV1 was not altered. Analysis of change in PC20 was complicated by a difference in baseline PC20 before the two treatments, but treatment with flurbiprofen did not significantly attenuate BHR. The results suggest that thromboxane or other cyclo-oxygenase products of arachidonic acid metabolism do not play an important role in the short-term maintenance of BHR to histamine in middle-aged male cigarette smokers.

Aged↗

Effects of smoking on changes in respiratory resistance with increasing age.

1. The oscillation method for measuring total respiratory resistance (Rrs) is a simple method of assessing airway dimensions which can be applied in epidemiological surveys and potentially might be useful for detecting mild airway disease in smokers. However, it is not known whether abnormalities in Rrs are only present when there are also abnormalities in simple spirometric tests. 2. We have compared values of Rrs and its frequency-dependence (fR) using the oscillation technique applied over the frequency range 6-26 Hz in 42 healthy, non-asthmatic men who were never-smokers (aged 26-61 years) and in 41 male cigarette smokers (aged 32-64 years). The results were compared with those for spirometry and the single-breath N2 test which are the most commonly used techniques in epidemiological surveys for detecting the effects of smoking on the lungs. 3. There was a strong trend for Rrs (especially at lower oscillation frequency) and fR to increase with increasing age in smokers. Increases in Rrs and fR were usually present when forced expiratory volume in 1 s was less than 80% of predicted and the forced expiratory volume in 1 s/vital capacity ratio was less than 65%, but abnormal fR was present in some smokers whose spirometry was within conventional normal limits. 4. Abnormalities in Rrs and fR were weakly associated with abnormality of the single-breath N2 manoeuvre.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The HDCR: demand and supply.

This article is intended to indicate that, despite the difficulties which exist, the revised format of the HDCR is a success. The major area of concern has undoubtedly been module F. Up to 21 July 1988, over 100 initial submissions had been approved by the board of studies and about 20 successfully completed dissertations were held in the college library. In future, the title of the dissertation will accompany the publication of the names of those successful in all modules of the HDCR. It is intended that those who submit outstanding dissertations will be invited to present them at the annual conference or teachers and superintendents' seminars. These various measures will publicise work which has been done and which may be of interest to those undertaking postgraduate research degrees. Thus the college and the profession will be seen to own a body of scientific and professional knowledge. Consequently, it is now only a matter of time before the college is able to approach higher education institutions and validating bodies to argue that the qualification represents an educational and professional standing that justifies radiographers access to advanced degree courses. Thus the Higher Diploma of the College of Radiographers will have achieved its justified status.

Certification↗

Symptoms and endoscopic findings--can they predict abnormal nocturnal acid gastro-oesophageal reflux?

Nocturnal gastro-oesophageal reflux is known to be particularly damaging to the oesophageal mucosa, being associated with stricture formation and columnarisation. At present, this can only be detected by prolonged intra-oesophageal pH monitoring. A total of 50 patients with endoscopic oesophagitis were evaluated by ambulatory pH monitoring to detect the presence of nocturnal reflux. Whether certain symptoms in the presence of a hiatal hernia would identify those patients with reflux at night was investigated. Thirty-three patients had nocturnal reflux, two-thirds of whom had a hiatal hernia. Heartburn at night was of limited value (specificity = 65%) in detecting acid reflux whereas regurgitation and cough showed greater specificity (88% and 100% respectively) but lacked sensitivity (45% and 12% respectively). The combination of nocturnal symptoms and a hiatal hernia in patients with endoscopic oesophagitis correctly identified 58% of patients with nocturnal reflux and was highly specific (100%). This study has confirmed that symptoms and endoscopic findings can detect a significant proportion of 'at risk' patients, but the remainder will require pH monitoring to assess their pattern of acid exposure.

Cough↗

Investigation of the effects of heat shock and agents which induce a heat shock response on the induction of differentiation of HL-60 cells.

A heat shock of 42.5-43.5 degrees C for 1 h applied to HL-60 promyelocytic leukemia cells induced the appearance of between 13 and 34% (n = 6) of cells which showed characteristics of mature metamyelocytes/granulocytes. This is the first time a physical agent has been shown to induce the differentiation of this leukemic cell line. The treatment of HL-60 cells with a variety of agents which have been documented to stress cells and induce thermotolerance or a heat shock-like response also induced granulocyte-like differentiation: continuous treatment for 4 days with ethanol (213 mM), sodium arsenite (6 microM), cadmium sulfate (60 microM), lidocaine (3 mM), and procaine (5 mM) induced 73, 54, 14, 54, and 55% of cells, respectively, to reduce the dye nitro blue tetrazolium. They were also capable of the phagocytosis of yeast particles. Examination of differentiated cells showed that those treated with ethanol, arsenite, lidocaine, and procaine also expressed nonspecific esterase activity, typical of monocytes, but did not adhere to plastic and had a cellular and nuclear morphology consistent with differentiation to metamyelocytes. Analysis of protein synthesis of HL-60 cells treated with 170 mM N-methylformamide, by the pulse labeling of cells for 2 h with [14C]leucine at various times, showed that the constitutive synthesis of both the Mr 90,000 and 70,000 heat shock proteins fell substantially after 2 h of exposure to N-methylformamide. When HL-60 cells were incubated with 1 M N-methylformamide, a toxic concentration of this agent, or were heat shocked, the synthesis of both the Mr 70,000 and Mr 90,000 proteins was induced. We propose that changes in heat shock protein synthesis may be an important element of the induction of differentiation of HL-60 cells, particularly as these proteins have recently been shown to regulate the stability of oncogene proteins, such as myc (Lüscher, B., and Eisenman, R. N., Mol. Cell Biol., 8: 2504-2512, 1988).

Cell Differentiation↗

Familial clustering of scleroderma spectrum disease.

This is the second case report of familial scleroderma (systemic sclerosis) in South Carolina. The family includes two cases of scleroderma meeting American Rheumatism Association criteria, one of systemic sclerosis sine scleroderma, and two other cases of undifferentiated connective tissue disease with features of scleroderma spectrum disorders; there are also two cases of Raynaud's phenomenon (one associated with rheumatoid arthritis), for a total of seven affected relatives. Evidence of scleroderma spectrum disorders was sought in six siblings of the two co-index cases and in 23 of the 35 offspring. Laboratory studies included antinuclear antibody determinations and typing for the following genetic markers: HLA (A, B, C, DR), complotypes, Gm and Km allotypes, and alpha-1 antitrypsin phenotypes. No common genetic markers restricted to affected members of this family were found, and no environmental exposures were detected that could explain this familial clustering of cases. This report should, however, add to the slowly accumulating information on the genetic characteristics of families at unusually high risk for scleroderma spectrum disorders. Positive antinuclear antibody tests at a titer of 1/40 or higher were present in 57 percent of the first-degree relatives of the affected cases.

Adult↗

Murine chromosomal regions correlated with longevity.

In this longevity analysis of 360 BXD recombinant inbred female mice (20 different strains), 2 strains had very significantly shorter survival and 1 strain had very significantly longer survival than the other 17 strains; 4 other strains had less significant lengthening of survival compared to the other 13 strains in a proportional hazards model of survival. Mean survival on the shortest lived strain was 479 days; on the longest lived strain the mean survival was almost double (904 days). Ranges of survival within strain were very large (averaging 642 days), and strain accounted for only 29% of the variation in survival, showing that there are important environmental and/or special developmental effects on longevity even in this colony housed in a single room. Each strain had been typed for markers of 141 regions on 15 chromosomes; 101 of these markers had distinguishable distributions on the 20 strains. The two shortest lived strains had the same alleles for 63% of the markers. The single region most significantly correlated with survival (marked by P450, Coh, Xmmv-35 on chromosome 7) divided the mice into two groups with survival medians which differed by 153 days (755 days for mice with a B genotype; 602 days for mice with a D genotype). Evaluated individually, 44% of the genetic markers (including some markers on 11 of 15 chromosomes with any markers typed) were found to be significantly correlated with survival (P less than 0.05) although one would only expect 5% of the markers to be significant by chance. While studies of many markers should adjust for the multiple comparisons problem, one interpretation of these crude P values is that any experiment with only one of these "significant" markers typed would be likely to conclude that the marker was a significant predictor of survival. Two types of multiple regression models were used to examine the correlation with survival of groups of genes. When a proportional hazards model for survival was done in terms of genotype regions, a six genetic region model best correlated with survival: that marked by P450, Coh, Xmmv-35 on chromosome 7 (B allele lives longer), Ly-24 on chromosome 2 (B allele lives longer), beta 2M and H-3 on chromosome 2 (D allele lives longer) Lamb-2 on chromosome 1 (D allele lives longer), Ltw-4 on chromosome 1 (B allele lives longer), and the Igh area of chromosome 12 (Igh-Sa4, Igh-Sa2, Igh-Bgl, Igh-Nbp, Igh-Npid, Igh-Gte, Odc-8, and Ox-1; D allele lives longer).(ABSTRACT TRUNCATED AT 400 WORDS)

Alleles↗

Gastro-oesophageal reflux associated with nifedipine.

A 57-year-old woman presented with a 3-week history of dysphagia for solids, 6 months after starting treatment with nifedipine. Endoscopy demonstrated oesophagitis and a benign oesophageal stricture. Twenty-four-hour ambulatory pH monitoring demonstrated decreased acid reflux 8 weeks after withdrawal of nifedipine, with coincidental symptomatic and endoscopic improvement. Nifedipine may induce, or aggravate, pre-existing, gastro-oesophageal reflux.

Adult↗

Changes in bronchial responsiveness to inhaled histamine over four years in middle aged male smokers and ex-smokers.

Bronchial hyperresponsiveness to inhaled histamine in smokers is associated with an accelerated annual decline in FEV1 and low baseline FEV1 values. The evolution of bronchial hyperresponsiveness and whether it precedes or follows the accelerated decline in FEV1 and reduction in FEV1 is unknown. Measurements of the provocative concentration of inhaled histamine required to reduce FEV1 by 20% (PC20) were repeated after a four year interval in 27 male smokers (mean age 59 years, smoking on average 27 cigarettes a day in 1986) and 16 men who were ex-smokers in 1982 and who remained non-smokers until 1986 (mean age 53 years in 1986). These men were originally recruited to a prospective study in 1974 and had their first PC20 measurement in 1982. PC20 was positively related to baseline FEV1 in both smokers and ex-smokers in both 1982 and 1986 (r ranging from 0.56 to 0.76, p less than 0.01). In smokers mean FEV1 fell from 83% to 77% predicted (p less than 0.001) and geometric mean PC20 from 7.11 to 3.27 mg/ml (p less than 0.001) between 1982 and 1986. The change in PC20 in individual smokers over the four years was related to change in FEV1 (p = 0.012). In ex-smokers mean FEV1 was 93% predicted both in 1982 and in 1986 and there was no significant difference in geometric mean PC20 between 1982 (6.68 mg/ml) and 1986 (5.98 mg/ml). Thus in smokers there was an accelerated annual decline in FEV1 and an increase in bronchial hyperresponsiveness as FEV1 fell. The ex-smokers had comparable levels of bronchial hyperresponsiveness in 1982. Mean PC20 values were unchanged in 1986 in these men, who showed a normal age related decline in FEV1. These longitudinal results emphasise the importance of baseline airway geometry in influencing bronchial hyperresponsiveness to histamine in middle aged smokers and ex-smokers.

Airway Resistance↗

Childhood leukaemia in the West Berkshire and Basingstoke and North Hampshire District Health Authorities in relation to nuclear establishments in the vicinity.

During the years 1972-85, 89 children aged 0-14 were registered with leukaemia in the West Berkshire and Basingstoke and North Hampshire District Health Authorities. Two nuclear establishments are located within the health authorities, and a third is situated nearby. Fifty of the 143 electoral wards in the two district health authorities lie wholly within, or have at least half their area lying within, a circle of radius 10 km around the establishments. In those 50 electoral wards 41 children aged 0-14 were registered with leukaemia, 28.6 registrations being expected on the basis of leukaemia registration rates in England and Wales (incidence ratio = 1.4, p less than 0.05). This excess was confined to children aged 0-4, among whom there were 29 registrations of leukaemia, 14.4 being expected (incidence ratio = 2.0, p less than 0.001). In the remaining 93 electoral wards there was a small and non-significant increase in the number of registrations of leukaemia at age 0-14 (48 observed, 40.8 expected; incidence ratio = 1.2). There was no obvious trend in the incidence of childhood leukaemia over the 14 years and the overall occurrence of the malignancy in the 143 electoral wards was consistent with a random distribution. In the surrounding Oxford and Wessex Regional Health Authorities the number of registrations of leukaemia at age 0-14 was virtually identical with that expected on the basis of registration rates in England and Wales (362 observed, 372.5 expected; incidence ratio = 1.0). These data indicate that in the two district health authorities studied there was an excess incidence of childhood leukaemia during 1972-85 in the vicinity of the nuclear establishments. In the West Berkshire and Basingstoke and North Hampshire District Health Authorities an average of 60,000 children aged 0-14 lived within a 10 km radius of a nuclear establishment each year. The normal expectation of leukaemia in these children was two cases a year, whereas the recorded incidence was three cases per year, representing one extra case of leukaemia each year among these 60,000 children.

Adolescent↗

Reflux stricture of the oesophagus.

Benign oesophageal stricture remains a common problem. Following accurate diagnosis, early treatment allows dilatation in the great majority of patients. Resection can frequently be avoided and in fit patients dilatation should be combined with an anti-reflux operation plus gastroplasty where necessary. Frail elderly patients may be managed by continued dilatation and medical means to reduce and combat the effects of reflux. Resection should now be necessary in only about 5 per cent of patients and colonic interposition offers good long-term results. It must be remembered that adenocarcinoma is a small but real risk in patients with reflux stricture.

Dilatation↗

Percutaneous transcatheter recanalization in the management of acute renal failure due to sudden occlusion of the renal artery to a solitary kidney.

Percutaneous angioplasty was attempted in 5 patients with acute renal failure due to occlusion of the artery to a solitary functioning kidney. Angioplasty was technically successful in all patients. Renal function was completely restored in 3 and renal perfusion improved in 1 patient. In the fifth patient, renal function did not return despite ultrasound and radionuclide scan evidence of renal reperfusion. Transcatheter thrombolytic therapy was attempted in 2 patients, 1 of whom also underwent angioplasty. In this patient, perfusion was restored to most of the kidney. In the other patient an infrarenal aortic occlusion was present. During thrombolytic therapy, intrarenal microembolization occurred from lysis of the aortic thrombus, leading to irreversible renal damage.

Acute Kidney Injury↗