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Biomedical subjects

J G Williams

Publications and source records attributed to J G Williams.

At least 145 records · Page 8Linked to original sources

Randomised cross-over comparison of five inhaler systems for bronchodilator therapy.

The pharmacological efficacy of beta-2 agonists such as bronchodilators is well established, yet many patients fail to obtain optimum benefit from conventional metered-dose inhalers. This is usually because of difficulty in achieving adequate co-ordination between activation of the aerosol and inhalation. To some extent this problem can be alleviated by detailed personal instruction and re-instruction, but the medical or paramedical staff needed to do this may be unavailable and in any case their time is expensive. To increase the benefit obtained from bronchodilators, therefore, pharmaceutical companies have produced a variety of devices, eg, large-volume (750 ml) spacers (Nebuhaler, Volumatic) which enclose a cloud of aerosol, obviating the need for actuation-inhalation co-ordination, and breath actuated dry-power inhalers with (Rotahaler, Diskhaler) or without (Turbohaler) carrier powders. Subsequent compliance with treatment is dependent upon the acceptability of the inhaler device to the patient.

Adolescent↗

Collecting, communicating and using information: the educational issues. A report from the Royal College of Physicians Committee on Medical Information Technology.

Few of the major advances in information science and technology have yet been successfully introduced in health care. Their implementation could improve both quality of care and the working environment of clinicians, but this will not be achieved by investing in hardware and software alone. Investment in education is also required.

Attitude to Computers↗

Ketoconazole inhibits alveolar macrophage production of inflammatory mediators involved in acute lung injury (adult respiratory distress syndrome).

BACKGROUND: Acute inflammatory lung injury (adult respiratory distress syndrome [ARDS]) causes significant morbidity and death in surgical patients. The alveolar macrophage elaborates proinflammatory mediators implicated in acute pulmonary injury. The macrophage products, leukotriene B4 (LTB4), thromboxane A2 (TXA2), and procoagulant activity (PCA), initiate inflammatory cascades that lead to microvascular thrombosis and neutrophil infiltration, two common features of ARDS. One potential method of preventing or attenuating lung injury is to inhibit the production of inflammatory mediators. Preliminary studies indicate that ketoconazole, known primarily for its antifungal properties, may prevent ARDS. METHODS: LTB4, TXB2, and PCA production by rabbit alveolar macrophages was measured after treatment with endotoxin or Ca ionophore and ketoconazole or selective 5-lipoxygenase (MK 886) and thromboxane synthetase (imidazole) inhibitors. RESULTS: Ketoconazole significantly inhibits alveolar macrophage production of LTB4, TXB2, and PCA. Ketoconazole inhibition of PCA is independent of effects on 5-lipoxygenase and thromboxane synthetase. CONCLUSIONS: Ketoconazole inhibition of alveolar macrophage proinflammatory mediators may be of benefit in preventing ARDS by minimizing neutrophil infiltration and microvascular thrombosis. Inhibition of 5-lipoxygenase and thromboxane synthetase, without affecting cyclooxygenase, may offer a selective advantage by allowing production of other homeostatic eicosanoids.

Animals↗

Effects of cervical collars on standing balance.

The effect of cervical collars on standing balance in two age groups was examined. Twenty healthy women aged 60 to 78 years and 20 healthy women aged 18 to 29 years stood on a Kistler force platform with and without a cervical collar. Total, lateral and anteroposterior sway velocity were measured in each of three positions; long-base stance and eyes open, wide-base stance and eyes open, and wide-base stance and eyes closed. Analysis of variance showed no significant difference (p < .05) between the collar and no collar conditions for any of the standing balance measures. Older women had significantly more sway velocity (p < .001) than younger women during long-base standing both with and without the collar. Also they showed significantly more sway velocity in both the total (p < .01) and the anteroposterior (AP) directions (p < .001) of wide-base standing. There were no significant lateral sway velocity differences (p < .05). With eyes closed, sway velocity was greater in all age groups. In the wide-based condition there were significant differences in sway velocity between AP (p < .001) and total and lateral (p < .01). These results indicate that a cervical collar does not disturb standing balance in healthy women in the age groups tested.

Adult↗

Long-term functional results of colon resection and rectopexy for overt rectal prolapse.

We reviewed the long-term functional results of colon resection and suture rectopexy for complete rectal prolapse in 47 patients followed for more than 3 yr (mean 65 months). Thirty-three patients underwent sigmoidectomy, eight patients underwent subtotal colectomy, and four patients underwent sigmoidectomy with subsequent subtotal colectomy. Three patients (6.3%) developed recurrent full-thickness prolapse, and four patients (8.5%) developed rectal mucosal prolapse. Twenty patients presented with constipation, 10 (50%) of whom improved after surgery. Constipation improved in seven (70%) patients who underwent subtotal colectomy. Twenty-one patients presented with incontinence, eight (38%) of whom improved. Continence worsened in six patients, and four patients developed significant diarrhea. These complications did not correlate with the extent of bowel resection. Three patients required subsequent stomas. Colon resection and rectopexy provides long-term control of rectal prolapse with an acceptable recurrence rate. Subtotal colon resection is frequently helpful in patients with associated constipation. However, colon resection of any magnitude entails a small risk of chronic diarrhea and/or diminished continence.

Colectomy↗

Expression of adult and tadpole specific globin genes from Xenopus laevis in transgenic mice.

Transgenic mice were generated which carried the adult alpha and beta-globin genes and the major tadpole specific beta-globin gene of Xenopus laevis. The adult specific alpha and beta genes were found to express in erythroid tissues in adult mice, while the major tadpole specific beta gene (beta T1) was expressed in blood from 12.5 day embryos. The pattern of expression of the beta T1 gene during mouse development was consistent with its being regulated as an embryonic globin gene in the mouse. This observation suggests that some of the factors mediating globin switching have been conserved during the evolution of modern amphibia and mammals and raises interesting questions concerning the evolution of vertebrate globin gene switching.

Aging↗

Selective induction of gene expression and second-messenger accumulation in Dictyostelium discoideum by the partial chemotactic antagonist 8-p-chlorophenylthioadenosine 3',5'-cyclic monophosphate.

During development of the cellular slime mold Dictyostelium discoideum, cAMP induces chemotaxis and expression of different classes of genes by means of interaction with surface cAMP receptors. We describe a cAMP derivative, 8-p-chlorophenylthioadenosine 3',5'-cyclic monophosphate (8-CPT-cAMP), which inhibits cAMP-induced chemotaxis at low concentrations but induces chemotaxis at supersaturating concentrations. This compound, moreover, selectively activates expression of aggregative genes but not of postaggregative genes. 8-CPT-cAMP induces normal cGMP and cAMP accumulation but in contrast to cAMP, which increases inositol 1,4,5-trisphosphate levels, 8-CPT-cAMP decreases inositol 1,4,5-trisphosphate levels. The derivative induces reduced activation of guanine nucleotide regulatory proteins, which may cause its defective activation of inositol 1,4,5-trisphosphate production. Our data suggest that disruption of inositolphospholipid signaling impairs chemotaxis and expression of a subclass of cAMP-regulated genes.

Journal Article↗

Positively and negatively acting signals regulating stalk cell and anterior-like cell differentiation in Dictyostelium.

The Dictyostelium ecmB gene encodes an extracellular matrix protein and is inducible by the stalk cell morphogen DIF. It is expressed in a subset of prestalk (pstB) cells in the slug and surrounding pstA cells first express it at culmination. A region of the ecmB promoter can direct transcription in all anterior prestalk cells, but a separate, downstream region acts to prevent its expression in pstA cells prior to culmination. This may be the site of interaction of a repressor, regulated by an extracellular antagonist to DIF. At culmination, expression of the ecmB gene also becomes greatly elevated in anterior-like cells as they move to surround the spore mass. A distal region of the ecmB promoter directs increased expression in those anterior-like cells that surmount the spore head. This divergence in gene expression suggests that anterior-like cells and anterior prestalk cells experience different inductive conditions at culmination.

Base Sequence↗

Rapid identification of markers linked to a Pseudomonas resistance gene in tomato by using random primers and near-isogenic lines.

An approach to isolating DNA sequences that are linked to important plant genes is described. The strategy is based upon a recent modification of the polymerase chain reaction in which synthetic primers are used to amplify random sequences from genomic DNA. This technique, used in conjunction with near-isogenic lines (which differ only by the presence or absence of the target gene and a small region of surrounding DNA), leads to the rapid identification of sequences linked to the gene of interest. The feasibility of this method has been demonstrated by analyzing a pair of tomato near-isogenic lines that differ for a region on chromosome 5 that contains a gene (Pto) conferring resistance to Pseudomonas syringae pv. tomato. One hundred forty-four random primers were screened on these lines, and seven amplified products were identified that were present in one but not the other line. Of four products that were further investigated, three were confirmed by segregation analysis to be tightly linked to the Pto gene. Linked sequences identified by this method are useful for detecting the presence of the target gene in plant populations (e.g., in plant breeding) and, if very tightly linked, as starting points for a chromosome walk to isolate the gene. Since near-isogenic lines are a typical product of plant breeding and classical genetic studies, this method is applicable to a wide variety of species.

Base Sequence↗

Recurrence of Crohn's disease after resection.

Recurrent Crohn's disease develops in most patients after surgical resection if the patient is followed for sufficient time. This review examines various aspects of recurrent Crohn's disease. It is concluded that Crohn's disease is a diffuse condition of the gastrointestinal tract and that radical resection of Crohn's disease does not prevent recurrence. Assorted factors thought to be associated with recurrence are examined and the relevance of these factors to the surgeon treating Crohn's disease is discussed.

Adolescent↗

Seton treatment of high anal fistulae.

Seventy-four patients who underwent seton treatment of high anal fistulae over a 6-year period have been reviewed. Four different techniques were used: staged fistulotomy (n = 24), cutting seton (n = 13), short-term seton drainage (n = 14) and long-term seton drainage in patients with Crohn's disease (n = 23). Recurrence developed in two patients (8 per cent) undergoing two-stage fistulotomy; two patients (14 per cent) undergoing short-term drainage and nine (39 per cent) of the patients with Crohn's disease. Three patients with Crohn's disease required proctectomy for progressive perianal disease. The remaining 11 patients with Crohn's disease (48 per cent) obtained a good result. None of the patients treated with a cutting seton developed a recurrence. Minor incontinence developed in 13 patients (54 per cent) undergoing two-stage fistulotomy and seven patients (54 per cent) treated with a cutting seton. When sphincter muscle was not divided, five patients (36 per cent) undergoing short-term drainage and six patients (26 per cent) undergoing long-term drainage developed minor incontinence. High complex fistulae can be successfully treated with only minor loss of continence using different seton techniques. In high Crohn's fistulae, long-term seton drainage preserves sphincter function, but recurrence is common if the seton is removed.

Adult↗

Fistula-in-ano in Crohn's disease. Results of aggressive surgical treatment.

The outcome of aggressive surgical treatment of 64 symptomatic anal fistulas in 55 patients with Crohn's disease has been studied. Forty-one fistulas, in 33 patients, were treated by conventional fistulotomy (17 subcutaneous, 19 intersphincteric, 5 low transsphincteric fistulas). Thirty wounds (73 percent) healed within 3 months and eight more wounds (93 percent) healed within 6 months. Three wounds did not heal within 12-18 months. Two of these patients subsequently required proctocolectomy. Wound healing was not influenced by the presence of rectal Crohn's disease or granulomatous inflammation in the tract. No change in continence was experienced by 26 of the 33 patients who underwent fistulotomy. Three patients required proctocolectomy and the remaining four patients experienced minor degrees of incontinence postoperatively. Sixteen high transsphincteric, five suprasphincteric, and one extrasphincteric fistula in 22 patients were treated by laying open external tracts and placing a noncutting seton through the sphincter, which was left in place for prolonged periods to maintain drainage. During follow-up (6 months to 10 years, median 2.5 years), three fistulas healed and seven remained quiescent. Nine patients required further treatment by a new seton and three patients required proctocolectomy. Eight of the 22 patients who had a seton inserted had no change in continence, and six patients in this group developed minor changes in continence, mostly related to diarrhea associated with intestinal disease. Anal fistulas in Crohn's disease, which involve minimal sphincter muscle, can be successfully treated by fistulotomy. High fistulas should be treated with seton drainage to limit recurrent suppuration and preserve sphincter function.

Adolescent↗

Incontinence and rectal prolapse: a prospective manometric study.

A prospective, manometric study has been performed on 23 female patients with rectal prolapse and varying degrees of incontinence. Seven of the 14 incontinent patients regained continence after surgery, and a further two patients improved. Improvement in internal and external sphincter function follows correction of rectal prolapse. Preoperative resting anal pressure was significantly higher in continent patients than in incontinent patients (P less than 0.05), as was the maximum voluntary contraction pressure (P less than 0.027). Postoperatively there was a significant increase in the resting anal pressure (P less than 0.0001) and maximum voluntary contraction pressure (P less than 0.003) in the whole group. The preoperative resting anorectal angle was significantly more acute (P less than 0.028) in continent patients than in incontinent patients. There was no significant change in the resting anorectal angle following prolapse repair. Patients who remained incontinent had a significantly lower preoperative resting anal pressure (P less than 0.01) than patients who improved or regained continence. Similarly, maximum voluntary contraction pressure was lower preoperatively in these patients (P less than 0.02). Preoperative resting anal pressure below 10 mm Hg and maximum voluntary contraction pressure below 50 mm Hg are associated with persisting incontinence after surgery.

Adult↗

Experience with alcohol and ability to discriminate legal intoxication status: a field study.

The research on blood alcohol level (BAL) discrimination training indicates that normal social drinkers can be taught to estimate successfully their level of intoxication. These studies show, however, that prior to training, skills for estimating intoxication are poor. The current study was undertaken to demonstrate that a sample of individuals in an actual drinking setting would have difficulty in estimating their blood alcohol level. It was expected that greater experience with alcohol would be associated with poorer abilities to discriminate legal intoxication. Subjects were 99 volunteers selected from the patrons of two bars. Participants completed a brief questionnaire assessing their typical alcohol use, the number of drinks consumed on this particular occasion, and whether they believed that they were currently over the legal limit for intoxication. A breathalyzer was used to determine actual level of intoxication. Results generally supported the hypotheses. Situational factors, including experimenter and drinking location, affected accuracy of estimations. Actual BAL also had a significant effect on accuracy. Errors in estimation were most often in the direction of overestimating intoxication. There was also a sex of subject effect, with males being heavier drinkers and estimating intoxication more poorly than females. Results are discussed in terms of situation and expectancy effects.

Adult↗

Knowing when you're drunk: a cluster analysis of cues to intoxication.

The present study was conducted to determine what cues to intoxication untrained subjects report using and how subjects see relationships among these cues. One hundred subjects were asked to list 5 cues that they use to determine their level of intoxication. These responses were tabulated, and the 18 most frequent responses were retained for further analyses. To assess the relationships among cues, all possible pairs of cues were rated for similarity. Mean similarity ratings were collapsed across subjects to form a mean similarities matrix that was subjected to cluster analysis. A taxonomy of cues to intoxication is discussed.

Adult↗

Regulation of cellular differentiation during Dictyostelium morphogenesis.

In Dictyostelium there are multiple prestalk cell types that have a complex pattern of directed cell movement during slug formation and culmination. Three extracellular signals, cyclic AMP, DIF and ammonia, control cell type differentiation. Recently there has been considerable progress in understanding their modes of action and interaction.

Ammonia↗

Iron absorption during normal human pregnancy: a study using stable isotopes.

The absorption of iron has been determined in nine healthy women studied serially during pregnancy and once post delivery. Following the oral administration of 5 mg aqueous 54FeSO4 plus ascorbic acid and the intravenous injection of 200 micrograms 57FeSO4, the isotope ratios of 54Fe: 56Fe and 57Fe: 56Fe in serum were measured by the use of inductively-coupled-plasma mass spectrometry whereby metal ions are vaporized into an argon plasma without previous blood sample preparation. Mean oral Fe absorption was 7.6 (range 1-22)% at 12 weeks gestation, 21.1 (range 9-58)% at 24 weeks, 37.4 (range 18-56)% at 36 weeks and 26.3 (range 8-54)% at 12 weeks post delivery. All the other biochemical and haematological indices were within normal limits for pregnancy. The significant increase (P less than 0.01) in Fe absorption during normal pregnancy suggests that most women would have the potential to meet the Fe demands of pregnancy without the need for supplementation if dietary Fe has similar availability to the aqueous preparation.

Absorption↗