Scots first with drug advice team.
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Family Practice↗
Biomedical subjects
S Ross
Publications and source records attributed to S Ross.
Pharmacokinetic and therapeutic outcome in melanoma cells, of the administration of symmetric and asymmetric cationic photosensitizers.
The response of melanoma cell lines to a range of novel cationic photosensitizers based on either a protoporphyrin or a mesotetra(4-carboxylphenyl)porphine molecule, has been examined. The drugs varied in terms of either their symmetry or their side chain configuration. The effect of these variables on drug uptake and photodynamic cell kill were tested. The absorption wavelengths for the drugs were measured and a shift to the red was seen in the presence of cells. Drug uptake was measured and the cationic sensitizers had a relatively high uptake when compared to anionic HpD. The efficiency of the drugs in causing cell kill was expressed in terms of clonogenic cell survival. The asymmetric photosensitizers were more efficient in destroying mouse and human melanoma cells than the clinically used anionic HpD, which was in turn more efficient than the symmetric sensitizers tested.
Animals↗
Optimum method for urinary drainage in major abdominal surgery: a prospective randomized trial of suprapubic versus urethral catheterization.
The outcome of suprapubic and urethral catheterization in abdominal surgery was compared in a prospective randomized trial. Twenty-eight patients received a suprapubic and 29 a urethral catheter. The groups were similar in terms of age, sex, operation performed and postoperative analgesia. There was no difference in the duration of catheterization (suprapubic: median 5 (range 4-10) days; urethral: median 4 (range 2-11) days). Urinary sepsis occurred in three patients in each group. Urethral catheters caused pain in significantly more patients (urethral 13; suprapubic two; chi 2 = 8.6, 1 d.f. P < 0.01), on more days (suprapubic: 6 of 142 catheter days; urethral: 37 of 126 catheter days; chi 2 = 29.5, 1 d.f. P < 0.001). Two men with urethral catheters and one with a suprapubic catheter failed to void urethrally when required to do so. Suprapubic catheterization is the method of choice for urinary drainage when this is required in abdominal surgery.
Abdomen↗
Symptomatic outcome 1 year after laparoscopic and minilaparotomy cholecystectomy: a randomized trial.
In a randomized controlled trial, 299 patients were sent a symptoms questionnaire 1 year after laparoscopic (n = 151) or minilaparotomy (n = 148) cholecystectomy for symptomatic cholelithiasis. The response rate to the questionnaire from contactable patients was 86 per cent. In both groups, at least 90 per cent of patients reported that their symptoms were improved, and at least 93 per cent rated the success of their operation as 'excellent', 'good', or 'fair'. However, over half the patients reported abdominal pain, a quarter reported flatulence, and a quarter dyspepsia. The only difference between treatment groups was that a higher proportion of patients who underwent minilaparotomy reported heartburn (35 per cent versus 19 per cent, P = 0.005). Patients who reported a 'poor' outcome were more likely to have suffered a postoperative complication, had lower quality of life scores, and higher anxiety and depression scores. Both laparoscopic and minilaparotomy cholecystectomy result in symptomatic benefit in at least 90 per cent of patients with symptomatic cholelithiasis.
Abdominal Pain↗
High incidence of asymptomatic brain lesions in metastatic renal cell carcinoma.
The metastatic pattern of renal cell carcinoma has been well established. Studies have revealed a relatively high incidence of spread to lung, liver, bone and brain. A retrospective review of the records of ninety patients with metastatic renal cell carcinoma showed seven to have evidence of brain metastases. Six of the seven were asymptomatic at time of diagnosis. This study shows a significant incidence of asymptomatic brain metastases in patients with metastatic renal cell carcinoma. Subsequent to our chart review, an additional two patients have presented to our institution with asymptomatic brain lesions from metastatic renal cell carcinoma.
Brain Neoplasms↗
Sympathoadrenal progenitors in embryonic chick sympathetic ganglia show distinct responses to glucocorticoid hormones.
The sympathoadrenal cell lineage originates from the neural crest and comprises the neurons of sympathetic ganglia, adrenal and extra-adrenal chromaffin cells, and the so-called small intensely fluorescent cells. In vitro studies using mammalian immature chromaffin cells, adrenal or sympathetic ganglionic progenitors, or ganglionic small intensely fluorescent cells, have suggested that glucocorticoid hormones are essential for inhibiting neuronal differentiation of sympathoadrenal progenitors and promoting the chromaffin cell phenotype. In avian systems, however, the distinct cellular phenotypes in this lineage and the molecular cues underlying their differentiation have not been fully explored. In the chick embryo, early sympathetic ganglion anlagen are populated by granule-containing cells that morphologically resemble small intensely fluorescent cells and chromaffin cell progenitors. These cells subsequently disappear from the ganglia, by death and by transition into fully differentiated sympathetic neurons, as indicated by the appearance of cells that are ultrastructurally intermediate between granule-containing cells and fully differentiated neurons (granule-containing cells in transition). In the present study, we show that treatment of cultured sympathetic cells dissociated from embryonic day (E) 7, 9, or 11 lumbar sympathetic ganglia with the glucocorticoid hormones hydrocortisone or corticosterone has neither an inhibitory nor an inductive effect on phenotypes of granule-containing cells or granule-containing cells in transition. In cell cultures of E15 ganglia, however, glucocorticoid treatment induces a granule-containing cell resembling the granule-containing phenotype. These results suggest that the early granule-containing cells and granule-containing cells in transition in chick sympathetic ganglia are not the counterparts of glucocorticoid-responsive mammalian small intensely fluorescent or chromaffin progenitor cells, despite their morphological similarity. However, E15 sympathetic ganglia apparently contain a glucocorticoid-responsive progenitor population that can differentiate into chromaffin-like cells. These progenitors seem to require a systemic or intraganglionic developmental signal or undergo a temporal switch that renders them susceptible to glucocorticoids.
Adrenal Medulla↗
The aetiology of severe community-acquired pneumonia and its impact on initial, empiric, antimicrobial chemotherapy.
Of 259 patients admitted to an intensive care unit with severe acute community-acquired pneumonia, 173 had primary infections and 86 had secondary infections. The commonest organism isolated in each group was Streptococcus pneumoniae (51.3 and 36.6% of known isolates in each group respectively). Klebsiella pneumoniae was the next most common isolate (31.9 and 29.3% respectively). A variety of other Gram-negative organisms and Staphylococcus aureus accounted for most of the remaining pathogens. Based on retrospective analysis of data, there appeared to be no difference in the alcohol consumption of patients with infection due to S. pneumoniae and K. pneumoniae. The overall mortality rate for the primary infections was 47.4%, with 68.4% of these infections due to K. pneumoniae and 33.9% due to the pneumococcus (P < 0.002). Among the secondary infections, the overall mortality rate was 40.8% (not significantly different to that of primary infections) with 45.5% due to K. pneumoniae and 23.1% due to the pneumococcus (not significantly different on statistical analysis, probably due to low patient numbers). Our investigation confirms that severe community-acquired pneumonia due to K. pneumoniae is extremely common, even in patients without obvious risk factors for Gram-negative colonization. This organism is contributing to the high mortality rate seen in our intensive care unit among patients with pneumonia, and our empiric therapy for such cases routinely includes a combination of agents active against this organism (e.g. a cephalosporin and an aminoglycoside).
Acute Disease↗
Heparin and haematoma: does ice make a difference?
Subcutaneous heparin injections are frequently prescribed for the prevention of deep vein thrombosis. One of the most commonly encountered adverse physiological responses to this intervention is the formation of a haematoma at the injection site. This creates a challenge for the nurse attempting to minimize haematoma formation and/or patient discomfort during the treatment regime. The purpose of this study was to determine if the application of ice to subcutaneous heparin injection sites decreases the incidence and size of haematoma formation and/or minimizes patient discomfort. The study used a quasi-experimental design with the subjects as their own control. A convenience sample of 70 subjects was each given two injections of subcutaneous heparin, 12 hours apart. Ice was applied pre- and post-injection to one of the sites. Immediately following each injection, the subjects were asked to rate the level of perceived discomfort at the time of the injection using a visual analogue scale. Forty-eight hours post-injection, the nurse inspected the injection sites for the presence of haematoma. Results showed that when ice was applied there was no significant difference in the incidence or size of haematoma; however, the subject's perception of pain was significantly less.
Adolescent↗
Asthma trends. Causes of wheeze and asthma may differ.
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Adolescent↗
Dynamics of signal transduction after aggregation of cell-surface receptors: studies on the type I receptor for IgE.
Many ligands stimulate cellular responses by aggregating the cell-surface receptors to which they are bound. We investigated several mechanistic questions related to aggregation of receptors by using the high-affinity receptor for IgE (Fc epsilon RI) on mast cells as a model system. We briefly exposed cells to covalently cross-linked oligomers of IgE and then added excess monomeric IgE to prevent further aggregation. Early events were examined by monitoring the phosphorylation of protein tyrosines; later events were examined by monitoring secretion. We found that aggregated receptors continue to signal both late and early events in the absence of formation of new aggregates. Additional experiments suggested that the clustered receptors undergo a dynamic process of phosphorylation and dephosphorylation. Our findings suggest that for these and related receptors that function by aggregation, the persistence of signal transduction is directly related to the intrinsic affinity of the ligand for the individual receptor.
Animals↗
Laparoscopic versus minilaparotomy cholecystectomy: a randomised trial.
Although laparoscopic cholecystectomy has rapidly become routine practice in the UK, there has been no rigorous comparison of it with open cholecystectomy. In our trial, 302 patients were randomised to laparoscopic or minilaparotomy cholecystectomy. Recovery after surgery was assessed by length of hospital stay, outpatient review at 10 days and 4 weeks, and patient questionnaires 1, 4, and 12 weeks after surgery. The mean operation time was 14 min shorter for minilaparotomy, while median post-operative hospital stay was 2 days shorter after laparoscopic cholecystectomy. The hospital costs were about 400 pounds greater for the laparoscopic procedure. Laparoscopic patients returned to work in the home sooner; at 1 week, they had better physical and social functioning, were less limited by physical problems, and had less pain and depression. At 4 weeks, only physical functioning and depression scores were better in the laparoscopic group, and by 3 months there were no differences. Laparoscopic patients were more satisfied with the appearance of their scars. The incidence of complications after both procedures was 20%. Compared to minilaparotomy cholecystectomy, laparoscopic cholecystectomy results in shorter hospital stay, less postoperative dysfunction, and quicker return to normal activities, but is more costly.
Activities of Daily Living↗
Vitamin A in epithelial differentiation and skin carcinogenesis.
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Animals↗
Outcome of wheeze in childhood. Symptoms and pulmonary function 25 years later.
The outcome after 25 yr was studied for three groups of children classified in a random community survey in 1964 as having asthma (121 subjects), wheeze in the presence of infection (167 subjects), or no respiratory symptoms (167 comparison subjects). Approximately 80% of the subjects in each group, now aged 34 to 40 yr, were successfully traced. Current symptoms and smoking habit were recorded by questionnaire, and ventilatory function, peak flow variability, and bronchial reactivity to inhaled methacholine were measured. Subjects who had asthma in childhood were more likely to wheeze (odds ratio [OR] 14.4) or produce phlegm (OR 3.3) than comparison subjects. They also had significantly lower FEV1 values and greater bronchial reactivity than comparison subjects. Adult FEV1 correlated with childhood FEV1 (both expressed as % of predicted) (r = 0.44, p < 0.01). The prognosis for those children who were classed as having wheeze in the presence of infection in 1964 was better than for those who had asthma. Although they also were more likely to report wheeze (OR 3.8) or phlegm (OR 4.4) than comparison subjects, the wheezy symptoms were unlikely to interfere with activities and the ventilatory function and bronchial reactivity to methacholine did not differ from those of comparison subjects. Smokers were more likely to report wheeze (OR 2.0), cough (OR 7.2), and phlegm (OR 3.1) than never-smokers, and current smokers with current wheezy symptoms had significantly reduced FEV1 values, although smoking was not associated with increased methacholine reactivity.(ABSTRACT TRUNCATED AT 250 WORDS)
Asthma↗
Characterization of the novel brown adipocyte cell line HIB 1B. Adrenergic pathways involved in regulation of uncoupling protein gene expression.
The HIB 1B cell line, derived from a brown fat tumor of a transgenic mouse, is the first established brown adipocyte cell line capable of expressing the brown fat-specific mitochondrial uncoupling protein (UCP). UCP gene expression, which was virtually undetectable under basic conditions, was stimulated by acute catecholamine or cyclic AMP treatment to levels comparable to primary cultures of brown adipocytes. Elevation of UCP mRNA levels following stimulation was very rapid but transient, decreasing after about 4 hours with a half-life between 9 and 13 hours. Immunoblotting showed the presence of UCP in HIB 1B mitochondria, but expression was much lower than observed in BAT or primary cultures of brown adipocytes. Upon transfection of HIB 1B cells with a reporter gene containing the UCP promoter, the activity of the transgene was regulatable by cAMP and norepinephrine. Investigation of the possible adrenergic receptors involved in UCP stimulation showed that specific beta 3-adrenergic agonists were much less effective than nonspecific beta-adrenergic agonists and that mRNA levels of the atypical, fat-specific beta 3-adrenoceptor were lower than those observed in brown adipocytes differentiated in primary culture. From pharmacological evidence we conclude that beta 3-adrenergic receptors account for approximately 30-40% of catecholamine induced UCP gene stimulation, whereas about 60-70% is stimulated via the classical beta 1/2 adrenergic pathway. We conclude that HIB 1B cells represent a functional system for the study of mechanisms related to brown adipose thermogenesis.
Adipocytes↗
The competence progression model in CHO-K1 cells: the relationship between protein kinase C and immediate early gene expression in the insulin mitogenic signal.
CHO-K1 cells grow in a defined medium with insulin, at physiological concentrations, as the only hormone. IGF-I can substitute for insulin. Quiescent cells require a 9-10-h lag, subsequent to the addition of insulin, to synthesize DNA. The phorbol ester, 12-O-tetradeconoylphorbol 13-acetate (TPA), cannot support growth of these cells, is a more effective inducer than insulin of c-fos, c-myc, c-jun, jun-B, Krox-20, Krox 24, fra-1 and JE, and induces fra-1, JE and c-myc with different kinetics from those of insulin. The addition of insulin + TPA to quiescent cells produces a synergistic effect on DNA synthesis but not on the expression of immediate early genes. Pretreatment of these cells with TPA or insulin decreases the required lag time for DNA synthesis by 3 h in a protein-synthesis-independent manner. These results, together with other experiments, demonstrate that [1] the insulin signal is independent of PKC, [2] insulin acts as a weak competence and a strong progression factor, while TPA behaves as a strong competence factor, and [3] the 9-10-h lag is made up of a 3-h period which is independent of protein synthesis, advancing the cells to a post-G(o) state of 'competence'.
Animals↗
CD45-associated kinase activity requires lck but not T cell receptor expression in the Jurkat T cell line.
The earliest biochemical event known to be associated with T cell receptor (TCR) engagement is the activation of a protein tyrosine kinase thought to be a member of the src family. Expression of CD45, the major receptor tyrosine phosphatase present on T cells, is required for efficient coupling between the TCR and its signaling machinery. One model to explain the role of CD45 in regulating TCR signaling is that the phosphatase dephosphorylates the regulatory C-terminal tyrosine of lck. In the present report we confirm the finding of a trimolecular complex containing CD45, lck, and a 34-kDa protein (p34) in the Jurkat T cell line. Additionally, we extend this work with the observation that specific in vitro kinase activity associated with CD45 requires the expression of lck in Jurkat-derived clones as does the in vivo phosphorylation of p34. The association between CD45 and lck is shown not to require the expression of or activation of the TCR. Finally, we demonstrate that even in the absence of lck p34 associates with CD45, implying a direct association between this molecule and the phosphatase. These data suggest strongly that lck is the relevant protein tyrosine kinase found in CD45 immunoprecipitates in the Jurkat T cell line and that there is an additional association between CD45 and p34 which does not require the presence of the protein tyrosine kinase.
Cell Line↗