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Biomedical subjects

S Smith

Publications and source records attributed to S Smith.

At least 613 records · Page 34Linked to original sources
PubMed1992

New water-soluble pilocarpine derivatives with enhanced and sustained muscarinic activity.

The synthesis of an homologous series of new water-soluble derivatives of pilocarpine is described. The new compounds, referred to as soft quaternary salts, are water soluble by virtue of a cationic ammonium head and their lipophilicity can be modulated by manipulating the size and the nature of the substituent in the inactive portion of the molecule. The miotic activity of the compounds was evaluated after administration to normotensive New Zealand White rabbits. Changes in pupil size indicated a substantial cholinergic effect on the iridal sphincter musculature. The best candidate, compound 20, which has a 16-carbon side chain, was evaluated for reduction of the intraocular pressure in genetically glaucomatous Beagles. Compound 20 is superior to pilocarpine in both tests, with a potency 10 to 20 times that of the parent compound and a longer duration of action. It is suggested that the new compounds are prodrug forms of pilocarpine which greatly enhance the corneal bioavailability of the parent compound.

Animals↗
PubMed1992

A germline mutation in the androgen receptor gene in two brothers with breast cancer and Reifenstein syndrome.

Breast cancer in men is rare--among the risk factors that have been identified are a family history of breast cancer and evidence of androgen insufficiency. We report a family in which two brothers who both developed breast cancer had clinical and endocrinological evidence of androgen resistance. Sequence analysis revealed a mutation in the androgen receptor gene on the X chromosome, within the region encoding the DNA binding domain. This is the first report of a germline mutation in a member of the steroid/thyroid hormone receptor superfamily associated with the development of cancer.

Aged↗
PubMed1992

Serum growth factors and oncoproteins in firefighters.

Firefighters are potentially at increased risk for cancer and non-malignant respiratory disease due to their toxic exposures on the job. Growth factors and oncogene proteins are thought to play a role in the development of various malignancies and pulmonary fibrotic diseases. Therefore, a cohort of firefighters and matched controls have been screened for the presence of nine different growth factors and oncoproteins using an immunoblotting assay. Fourteen of the firefighters were found to be positive for beta-transforming growth factor (beta-TGF) related proteins compared to no positives in the controls (P = 0.0017). These results suggest that beta-TGF may be a possible biomarker for monitoring firefighters and other exposed workers for the potential development of cancer or non-malignant respiratory disease.

Amino Acid Sequence↗
PubMed1992

Predictors of blinding or serious eye injury in blunt trauma.

Multivariate analysis was used to identify factors predicting injury and visual outcome in 94 blunt trauma patients evaluated for eye injuries among 6700 admissions to a level I trauma center over a 29-month period. Patients with penetrating eye injuries were excluded from this review. Eye injury was detected in 93% or 87 of the patients evaluated. Seven percent of eye injuries resulted in blindness, 22% were serious (visual acuity between 20/40 and 20/200 or eye injury requiring surgery), and 71% were temporary (final visual acuity of 20/40 or better). The presence of an afferent pupillary defect or a nonreactive pupil was the most important factor in predicting the severity of eye injury (p = 0.0023), followed by facial fractures (p = 0.0084), and no eye opening or eye opening to pain within the Glasgow Coma Scale (p = 0.02). Eye injury is an infrequent complication of blunt trauma. Appropriate consultation for evaluation of this problem can be obtained based on findings from the initial history and screening physical examination.

Adolescent↗
PubMed1992

The esterification of fatty acids by Staphylococcus aureus fatty acid modifying enzyme (FAME) and its inhibition by glycerides.

Fifty-five randomly selected Staphylococcus aureus strains were examined for fatty acid modifying enzyme (FAME) production. Of these, 20.4% did not elaborate the enzyme. Amongst the remaining strains, the lowest level produced in culture was 0.1 unit/10(9) cocci and the maximum was 2.01 U/10(9) cocci; the median level was 0.4 U/10(9) cocci. In a series of straight-chain saturated fatty acids with 11-24 carbons, all could be esterified by FAME. However, those with 15-19 carbons were generally better substrates than the others. For a particular chain length, the unsaturated forms were better substrates than the saturated form. Triglycerides with unsaturated fatty acid side chains were potent inhibitors of FAME. Diglycerides were almost as active as triglycerides, but monoglycerides were much less inhibitory. FAME was purified by gel filtration followed by hydrophobic interaction chromatography on hexyl agarose. FAME and lipase may have a role in determining the survival of S. aureus in lesions.

Acyltransferases↗
PubMed1992

Longitudinal changes in skin-prick test reactivity over 2 years in a population of schoolchildren with respiratory symptoms.

As part of a larger epidemiological study, 114 children with respiratory symptoms, born between 1978 and 1980, were skin-prick tested to Dermatophagoides pteronyssinus (DP), mixed grass pollens (G) and cat dander (C), and to histamine and saline controls (Bencard, U.K.) using 1 mm prick-lancets (Dome/Hollister-Stier), between July and September 1987 and again in October 1989. A weal > or = 2 mm to one or more allergens was regarded as a positive result. Each child was tested by the same investigator on each occasion, using similar techniques. Three children were excluded from analysis as they had failed to respond to histamine testing on one of the two occasions. In 1987, of the 111 children analysed, 58 (52%) children were skin-test positive, and 53 (48%) skin-test negative, while in 1989 62 (56%) were positive and 49 (44%) negative. Twelve children (11%) changed status from negative to positive, while eight (7%) changed from positive to negative. For the group as a whole the percentage agreement between the results obtained 2 years apart was 82%. In comparison to previous studies a greater number of subjects in this population than expected changed atopic status. We therefore further examined the data from those who had changed status and classified as borderline those subjects with no difference in weal size of greater than 2 mm for any allergen between 1987 and 1989. Only five children then changed status from negative to positive, none from positive to negative and 15 demonstrated only borderline changes. The coefficients of repeatability for the 106 children who did not change status were 3.37 mm, 2.80 mm and 2.33 mm for D. pteronyssinus, mixed grass pollens and cat dander respectively. The good short-term repeatability of the testing method was demonstrated in a group of 29 similar children; the coefficients of repeatability were 0.38 mm for DP and G, and 0.72 mm for C. These data demonstrate that, in a population of children with respiratory symptoms, skin-prick testing within individuals is highly repeatable over the short term, but poorly repeatable over a 2 year period. However, the percentage agreement in skin-prick test status for the group as a whole was high (82%). While no child became unequivocally skin-test negative having been previously positive, a small number of children changed status from negative to unequivocally positive, suggesting a genuine but small (4%) increase in the prevalence of skin-test positivity in this population.

Allergens↗
PubMed1992

Modulation of human T cell functions by surface sulphydryl groups: differential effects on IL-2 production and responsiveness.

An impermeable thiol blocker has been used to investigate the role of sulphydryl (SH) groups in the production of and responsiveness to IL-2 by normal human T lymphocytes. Surface SH blockade of mononuclear cells prior to incubation with mitogen (phytohaemagglutinin, concanavalin A, CD3 MoAb) had no effect on production of IL-2 but markedly impaired cellular responsiveness to exogenous IL-2. Studies using MoAbs indicated that this effect was accompanied by decreased expression of both the CD25 and p75 subunits of the IL-2 receptor. Blocking surface SH groups did not affect binding of IL-2 to p75 on unstimulated mononuclear cells, but inhibited binding to high-affinity receptors on a T lymphoma cell line. The data are consistent with the hypothesis that sulphydryl groups on the IL-2 receptor are required for its function and may be involved in the interaction of the CD25 and p75 subunits leading to generation of the high-affinity binding site. The surface thiol identified on the IL-2 receptor may be a candidate for oxidation on cells from patients with chronic inflammatory diseases such as rheumatoid arthritis and thus contribute to the aberrant function of T cells in these patients.

Arthritis, Rheumatoid↗
PubMed1992

Application of echocardiographic color flow Doppler mitral regurgitation to the diagnosis of acute cardiac transplantation rejection.

Numerous noninvasive techniques have been examined for the detection of acute rejection following cardiac transplantation, but none has proven sufficiently sensitive to replace the endomyocardial biopsy. A prospective study was performed in 92 heart transplant patients in order to test the hypothesis that mitral regurgitant ratio by two-dimensional echocardiography with Doppler flow mapping could detect moderate or severe acute allograft rejection. There were 82 rejection episodes identified, of which 40% were associated with mitral regurgitation by echo-Doppler at the beginning of the episode. With augmentation of immunosuppression during a rejection episode, there was a progressive fall in the degree of mitral incompetence (P = 0.03). The sensitivity of color Doppler studies in identifying rejection was low (60% of all rejection episodes had no associated mitral incompetence at the beginning of the episode), but the likelihood of rejection progressively increased with higher degrees of mitral regurgitation (P less than 0.01), approaching 60% when the echo-Doppler regurgitant ratio exceeded 15%. Echo-Doppler studies do not provide sufficient sensitivity to be useful as a screening technique for acute cardiac rejection, but high or increasing echocardiographic mitral regurgitant ratio is predictive of acute rejection and should indicate prompt endomyocardial biopsy.

Adolescent↗
PubMed1992

Respiratory epithelial cell invasion by group B streptococci.

Group B streptococci (GBS) are the most common cause of pneumonia and sepsis during the neonatal period; however, the pathogenesis of this infection is poorly understood. We investigated the ability of GBS to enter epithelial cells in culture. Two strains of GBS were capable of invading immortalized respiratory epithelial cell lines in vitro at different levels, suggesting strain differences in invasiveness. Intracellular replication was not observed. Invasion required actin microfilaments but not microtubular cytoskeletal elements. Active bacterial protein, DNA, and RNA syntheses were required for invasion. These findings are consistent with our previous observation of intracellular GBS in the lungs of infected primates. We hypothesize that this organism may access the bloodstream by direct invasion of the epithelial cell barrier.

Adult↗
PubMed1992

Human airway macrophages. A technique for their retrieval and a descriptive comparison with alveolar macrophages.

We developed a technique to isolate and lavage a segment of a large human airway in vivo. Airway lavage and BAL were performed without significant complications 18 times on 17 normal volunteers. The mean +/- SEM volume of instillate used on all subjects totaled 31.3 +/- 2.7 ml with 47.1 +/- 3.8% of the fluid recovered. A total of 1.5 +/- 0.3 x 10(6) cells were retrieved. Cell viability averaged 71.3 +/- 4.6%. The majority of the cells were macrophages, 27.9 +/- 2.7%, and neutrophils, 28.4 +/- 6.0%. A descriptive comparison of airway macrophages using transmission electron microscopy with those retrieved from paired bronchoalveolar lavage (BAL) samples revealed that airway macrophages possessed more vacuoles (p less than 0.0001), fewer long microvilli (p less than 0.0001), and more membrane undulations (p less than 0.0001). In contrast, macrophages from both lavage locations demonstrated similar staining characteristics when stained with a panel of monoclonal antibodies. During lavage, all subjects experienced mild dyspnea that was relieved when the lavage was completed. One of three subjects tested during the procedure revealed O2 desaturation that was prevented by the inhalation of O2. We conclude that viable macrophages can be retrieved safely from airways of normal subjects and that, compared with macrophages present in BAL, these cells bear both similarities and dissimilarities that may portend differing functional capabilities.

Adult↗
PubMed1992

Psychiatrists and their patients--confidential information in the wake of spycatcher.

This article examines a recent decision of the English Court of Appeal. It concerned a psychiatrist who examined and reported on a convicted murderer in a secure hospital. The report was commissioned by the patient's solicitors as evidence in support of his release. The report was emphatically unfavourable and the doctor insisted that it be revealed to the hospital authorities. The solicitors refused and litigation ensued. The courts were forced to rule on the conflict between the patient's right to privacy and the public interest in revealing the report.

Adult↗
PubMed1992

Adult domestic violence.

Adult domestic violence in Leicestershire was reviewed by examining the clinical notes of all patients aged 14 years and over attending the Accident and Emergency Department of the Leicester Royal Infirmary in 1988 with a history of assault. Of the 341 patients so classified, 297 victims were identified. This paper describes the results of the review, including the age and gender of the victims, and the nature and cost of the violence. Suggestions are made to improve the management of adult domestic violence.

Adult↗
PubMed1992

Incidental finding of endolymphatic stromal myosis during luteinizing hormone releasing hormone agonist therapy for suspected benign uterine myomata. A case report.

A 39-year-old woman with an enlarging myomatous uterus underwent a three-month course of luteinizing hormone releasing hormone (LHRH) agonist treatment. Despite a 50% reduction in uterine size, pathologic examination after uncomplicated hysterectomy revealed a low-grade endometrial stromal sarcoma. As the use of LHRH agonists for myoma reduction increases, delay in the diagnosis of sarcomatous disease will become more widespread. With current available diagnostic modalities, differentiation between sarcomatous and myomatous growth within the uterus is difficult. The possibility of delay in the diagnosis of unsuspected sarcoma when using LHRH agonists is an inherent and apparently unavoidable complication in some cases.

Adult↗