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Biomedical subjects

R Lewis

Publications and source records attributed to R Lewis.

At least 73 records · Page 4Linked to original sources

Diabetic emergencies: Part 1. Hypoglycaemia.

Diabetes mellitus is a chronic, lifelong condition which can affect people of all ages, and is increasing in prevalence. Hypoglycaemia is probably the most common acute problem suffered by patients with diabetes. It is also a serious medical emergency with potentially fatal outcomes, and is the most common reason for patients with diabetes attending an accident and emergency (A&E) department. It is also a major source of anxiety for diabetics, particularly those controlled on insulin, and unfortunately, in the move towards ever tighter glycaemic control, it is inevitable that diabetics will continue to suffer from hypoglycaemia. This article examines the pathophysiology of hypoglycaemia and some of its main causes, and will look at the clinical management of the patient with hypoglycaemia, both in the community and in the A&E department. The importance of the recognition and prompt treatment of hypoglycaemia, and of the investigation of hypoglycaemia with no obvious cause are also discussed. Part 2 of the series will explore the pathophysiology and clinical management of diabetic emergencies involving hyperglycaemia, including both diabetic ketoacidosis and the rarer hypernatremic, non-ketotic coma.

Diabetes Mellitus, Type 1↗

Comparison of two regimens of beta-adrenergics in acute asthma.

BACKGROUND AND METHODS: Inhaled adrenergics and steroids are the main agents used in acute asthma. Dosing recommendations for adrenergics, while generally becoming more aggressive, lack prospective validation. A double blind, randomized trial of two regimens of nebulized metaproterenol was conducted in patients presenting to an Emergency Department with an acute asthma exacerbation. Asthmatics age 16-55, with no other cardio-pulmonary disease, presenting with peak expiratory flow rate (PEFR) < 30% of predicted and greater than 80 L/m were enrolled. All patients received 125 mg of methylprednisolone and theophylline, if needed, to reach therapeutic levels. The experimental group received 0.3 cc metaproterenol in 2.5 cc of saline at times 0, 20", 40", 1', 2', 3', 4', 5', 6', and 7'. The control group received metaproterenol at times 0, 1 hr, and hours 3, 5, and 7. Placebo was given to control group patients at 20", 40", 2', 4', and 6'. PEFR and vital signs were measured 10 min after each treatment. Study end points included discharge upon reaching set criteria or admission if patients were not discharged following the hour 7 treatment. RESULTS: Seventy one patients were enrolled, 40 in experimental group and 31 in the control group. The group characteristics did not differ at entry in any significant way, and the groups began with mean expected PEFR of 23.4% and 24.5%, respectively. There were no significant differences at any point in PEFR outcomes, time to discharge, or admission rate. The experimental group showed a greater increase in pulse rate and a reduced diastolic blood pressure at 20, 40 and 60 min. The experimental group had a 12- and 8-fold increase in the risk of a pulse rate > 140 at 40 and 60 min, respectively. This group also had two moderate complications, both near the 60-minute mark. These were an induction of atrial fibrillation in one patient and ischemic electrocardiographic changes in another. CONCLUSION: Three treatments in the first hour, and hourly thereafter showed no benefit over treatments initially, at one hour, and every other hour in acute, moderate, or severe exacerbation of asthma. Side effects were markedly increased in the control group. Such dosing should not be recommended as routine therapy.

Acute Disease↗

Use of a clinical Escherichia coli isolate expressing lux genes to study the antimicrobial pharmacodynamics of moxifloxacin.

Escherichia coli isolate 16,906 expressing lux genes was used for real-time monitoring of moxifloxacin effects on bacterial metabolism compared with effects on cell replication. Viable counts showed concentration-dependent killing by moxifloxacin; real-time measurement of bioluminescence on the same cultures showed metabolic activity over 54 h, but with greater inhibition at 1 x MIC than with higher MIC multiples. Post-antibiotic effect was longer when determined using bioluminescence than by viable counts. The control-related effective regrowth time was consistent with both methods. Bioluminescent bacteria provide a rapid and sensitive means for measuring antimicrobial effects on bacterial metabolism.

Anti-Bacterial Agents↗

Comparison of in-vitro pharmacodynamics of once and twice daily ciprofloxacin.

The pharmacodynamics of ciprofloxacin were explored in an in-vitro continuous bacterial culture model of infection, by simulating two oral dosing regimens; 0.5 g 12-hourly (bd) and 1 g 24-hourly (od). Three strains of Escherichia coli (ciprofloxacin MICs 0.03, 0.5 and 2 mg/L); two strains of Pseudomonas aeruginosa (MICs 0.09 and 1.5 mg/L), two strains of Staphylococcus aureus (MICs 0.12 and 1 mg/L) and two strains of Streptococcus pneumoniae (MICs 0.5 and 2 mg/L) were used. Three pharmacodynamic parameters, T > MIC, C(max)/MIC and AUC/MIC (T = time, C(max) = peak serum concentration, AUC = area under the curve), were compared with area under the bacterial-kill curve (AUBKC) (after transformation of the AUBKC) using a simple E(max) or sigmoidal E(max) model. AUBKC was taken to be the main antibacterial effect measure. The models were compared by inspection of residuals and Akaike information criterion. E(max) models adequately described the relationship between AUC/MIC and AUBKC and between C(max)/MIC and AUBKC, but not between T> MIC and AUBKC. All three pharmacodynamic parameters are related to each other but multiple regression analysis indicated that AUC/MIC was the best individual predictor of AUBKC. Despite this, comparison of od and bd regimens indicates some advantage to od in terms of early antibacterial effect. Serum concentration-time curve shape has some importance in determining antibacterial effect. These data indicate that for ciprofloxacin AUC/MIC ratio is not the sole determinant of antibacterial effect.

Anti-Infective Agents↗

Who contracts for primary care?

The implications of the 1997 NHS (Primary Care) Act have been largely overlooked in the rush to establish Primary Care Groups. Allowing health authorities to develop local contracts for primary care has far-reaching implications and is an important departure from the national system of negotiation that has characterized general practice to date. This paper describes a content analysis of a sample of Personal Medical Services (PMS) pilot contracts. In the first year little attention has been given to achieving cost savings or greater efficiency and few contracts promote clinical guidelines. The difficulties of specifying services sensitive to local health needs are highlighted and the national Statement of Fees and Allowances (the 'Red Book') may not be swiftly supplanted. However, the pilots have introduced innovations such as salaried general practitioners, nurse-led services and NHS trust-managed care. The development of local contracts provides a valuable learning experience for general practitioners and health authorities in advance of the establishment of Primary Care Trusts.

Contract Services↗

Serotonin 5-HT2 receptors in schizophrenia: a PET study using [18F]setoperone in neuroleptic-naive patients and normal subjects.

OBJECTIVE: Several postmortem studies have reported a decreased density of serotonin 5-HT2 receptors in the prefrontal cortex in schizophrenia. The purpose of this study was to investigate this in patients with schizophrenia by means of [18F]setoperone and positron emission tomography (PET) imaging. METHOD: Thirteen neuroleptic-free patients with schizophrenia, 10 of whom were also neuroleptic-naive, were compared with a group of 26 normal subjects in the same age range. The density of 5-HT2 receptors was assessed with the use of [18F]setoperone and PET in standardized cortical regions of interest. RESULTS: Increasing age was associated with similar declines in 5-HT2 receptors in all cortical regions in the patient group and in the normal comparison group. After control for the effect of age, there was no statistically significant difference between the patients and the comparison subjects in 5-HT2 receptor density in any of the cortical regions. CONCLUSIONS: This study failed to find the decrease in 5-HT2 receptors reported in postmortem studies of schizophrenia. The study had the power to detect a decrease of 25% or more in 5-HT2 receptors, which was anticipated on the basis of the previous postmortem studies. Thus, a primary serotonergic abnormality in schizophrenia, if one exists, is either small or unlikely to be at the level of the 5-HT2 receptors. This finding does not rule out a therapeutic role for 5-HT2 antagonists in schizophrenia, but it does suggest that the therapeutic contribution is likely to be an indirect one.

Antipsychotic Agents↗

Chronic treatment with finasteride daily does not affect spermatogenesis or semen production in young men.

PURPOSE: Finasteride, an oral type 2, 5alpha-reductase inhibitor, is used in 1 mg. daily doses for the treatment of male pattern hair loss. A dose of 5 mg. finasteride daily reduces ejaculate volume by approximately 25%, and reduces prostate volume by approximately 20% and serum prostate specific antigen (PSA) by approximately 50% in men with benign prostatic hyperplasia. To our knowledge no data exist on the effect of 1 mg. finasteride daily on ejaculate volume or other semen parameters, or on the prostate in young men. Therefore, we studied the potential effect and reversibility of effect of 1 mg. finasteride daily on spermatogenesis, semen production, the prostate and serum PSA in young men. MATERIALS AND METHODS: In this double-blind, placebo controlled multicenter study 181 men 19 to 41 years old were randomized to receive 1 mg. finasteride or placebo for 48 weeks followed by a 60-week off-drug period. Of the 181 men 79 were included in a subset for the collection and analysis of sequential semen samples. RESULTS: There were no significant effects of 1 mg. finasteride on sperm concentration, total sperm per ejaculate, sperm motility or morphology. Ejaculate volume in subjects on finasteride decreased 0.3 ml. (-11%) compared to a decrease of 0.2 ml. (-8%) for placebo, with a median between treatment group difference of -0.03 ml. (1%, 90% confidence interval -10.4 to 13.1, p = 0.915). There were significant but small decreases in prostate volume (-2.6%) and serum PSA (-0.2 ng./ml.) in the finasteride group, which reversed on discontinuation of the drug. CONCLUSIONS: Treatment with 1 mg. finasteride daily for 48 weeks did not affect spermatogenesis or semen production in young men. The effects of 1 mg. finasteride daily on prostate volume and serum PSA in young men without benign prostatic hyperplasia were small and reversible on discontinuation of the drug.

Adult↗

Effects of castration and testosterone replacement on veno-occlusion during penile erection in the rat.

AIM: To determine if androgens directly regulate veno-occlusion or if androgens act indirectly to maintain the penile structures which control outflow. METHODS: Using CASTRATE and TESTO rats, measurement was made of mean arterial pressure (MAP), intracavernosal pressure (CCP), and intracavernosal flow (CCF) during erection resulting from stimulation of the autonomic innervation of the penis. CCP and CCF were also measured during saline infusion into the cavernosal sinuses before and after treatment with sodium nitroprusside (SNP, a nitric oxide donor drug) to fully relax cavernosal smooth muscle. Penile tissue was also collected to measure the content of alpha actin and proline and hydroxyproline to determine if brief withdrawal of androgenic support led to changes in the number of smooth muscle cells or the collagen content of the tissue. RESULTS: Infusion of saline into the cavernosal sinuses demonstrated that veno-occlusion was defective in CASTRATE rats while veno-occlusion was fully functional in TESTO animals. Furthermore, veno-occlusion could be induced in CASTRATE rats if they were first treated with SNP. This observation suggests that failure of veno-occlusion in the CASTRATE rats is due to a deficiency in the production of NO resulting in a reduction in the degree of relaxation of the penile smooth muscle. The measurements of smooth muscle a actin and proline and hydroxyproline content of collagen showed that both were unaffected by castration and that the basic structure of the penis did not degenerate after one week without androgenic support. CONCLUSION: These results can be interpreted to mean that androgens control the veno-occlusive mechanism indirectly via a NO dependent mechanism and not by maintaining the structures of the penis which are essential to veno-occlusion.

Animals↗

Primary care. LIZ (London Initiative Zone): a legacy for London.

More than half the LIZ funding has been spent on improving GP premises and practice staffing. But many premises are still below standard. The programme has had no effect on reducing the number of GPs over 65 working in London. In some areas of London the proportion has increased. Almost half (46 per cent) of practices in London still consist of a doctor working alone. Nationally, the figure is 30 per cent. London GPs' lists are significantly higher than in the rest of the country. Further improvements in London's primary care are vital.

Age Distribution↗

Trillion virion delay: time from testing positive for HIV to presentation for primary care.

BACKGROUND: Human immunodeficiency virus (HIV)-infected individuals' initial presentation to medical care frequently occurs at a point of advanced immunosuppression. OBJECTIVES: To investigate the time between HIV testing and presentation to primary care. Also to examine factors associated with delayed presentation. METHODS: One hundred eighty-nine consecutive outpatients without prior primary care for HIV infection were assessed at 2 urban hospitals: Boston City Hospital, Boston, Mass, and Rhode Island Hospital, Providence. Sociodemographics, alcohol and drug use, social support, sexual beliefs and practices, and HIV testing issues were examined in bivariate and multivariate analyses for association with delay in presentation to primary care after positive test results for HIV. RESULTS: Of 189 patients, 74 (39%) delayed seeking primary care for more than 1 year, 61 (32%) delayed for more than 2 years, and 35 (18%) for more than 5 years after an initial positive HIV serologic evaluation. The median CD4+ cell count of subjects was 0.28 x 10(9)/L (range, 0.001-1.71 x 10(9)/L). In multiple linear regression analysis the following characteristics were found to be associated with delayed presentation to primary care after HIV testing: history of injection drug use (P<.001); not having a living mother (P=.01); not having a spouse or partner (P=.08); not being aware of HIV risk before testing (P<.001); and being notified of HIV status by mail or telephone (P=.002). An interaction effect between sex and screening for alcohol abuse was significant (P=.03) and suggested longer delays for men with positive screening test results (CAGE [an alcoholism screening questionnaire containing 4 structured questions], 2+) compared with men without positive screening test results or women. CONCLUSIONS: Patients with positive HIV test results often delay for more than a year before establishing primary medical care. Information readily available at the time of HIV testing concerning substance abuse, social support, and awareness of personal HIV risk status is useful in identifying patients who are at high risk of not linking with primary care. Patients who were notified of their HIV status by mail or telephone delayed considerably longer than those notified in person. Efforts to ensure primary care linkage at the time of notification of positive HIV serostatus are necessary to maximize benefits for both individual and public health and should be an explicit task of posttest counseling.

Alcohol Drinking↗

Amplitude regulation of vocalizations in noise by a songbird, Taeniopygia guttata.

Bird vocalizations are produced under various noise conditions. It could therefore benefit birds to alter the amplitude of their signals as noise conditions change. We tested this by recording male and female zebra finches, Taeniopygia guttata, as they were subjected to various levels of white noise. Both sexes increased amplitude levels of vocalization in response to increased levels of noise. Similar results were obtained with humans (the 'Lombard effect'). The results are discussed in terms of the 'active space' of bird song and honest signalling. Copyright 1998 The Association for the Study of Animal Behaviour.

Journal Article↗

Significant changes in VLDL-triacylglycerol and glucose tolerance in obese subjects following ten days of training.

We characterized the effect of ten days of training on lipid metabolism in 6 [age 37.2 (2.3) years] sedentary, obese [BMI 34.4 (3.0) kg x m(-2)] males with normal glucose tolerance. An oral glucose tolerance test was performed prior to and at the end of the 10 d of training period. The duration of each daily exercise session was 40 min at an intensity equivalent to approximately 75% of the age predicted maximum heart rate. Blood measurements were performed after an overnight fast, before and at the end of the 10 d period. Plasma triacylglycerol was significantly (p < 0.05) reduced following exercise training (2.15+/-0.29 vs. 1.55+/-0.28 mmol x l(-1)). Very low density lipoprotein-triacylglycerol was also significantly (p < 0.05) reduced (1.82+/-0.3 vs. 1.29+/-0.29 mmol x l(-1)). No significant changes in high density lipoprotein-cholesterol were observed as a result of training. Following training fasting plasma glucose and fasting plasma insulin were significantly reduced [Glucose: 5.9 (0.2) mmol x l(-1) vs. 5.3 (0.22) mmol x l(-1) (p < 0.05); Insulin 264.3 (53.8) rho x mol x l(-1) vs. 200.9 (30.1) rho x mol x l(-1), p=0.05]. The total area under the glucose curve during the OGTT decreased significantly (p < 0.05). These preliminary data suggest that short-term exercise, without concomitant loss of body mass, induces favorable changes in plasma triacylglycerol, and very low density lipoprotein-triacylglycerol and glucose tolerance but has no effect on high density lipoprotein-cholesterol.

Adult↗

The rarity of clinically significant rise in intraocular pressure after laser peripheral iridotomy with apraclonidine.

OBJECTIVE: To determine the incidence of intraocular pressure (IOP) rise of varying degrees after laser peripheral iridotomy (LPI) in patients with and without glaucoma treated perioperatively with pilocarpine and apraclonidine. DESIGN: A retrospective chart review. PARTICIPANTS: A total of 289 eyes in 179 patients with narrow occludable angles (NOA) (N = 148), open-angle glaucoma or ocular hypertension (OAG) (N = 115), or chronic-angle closure glaucoma (CACG) (N = 26) were reviewed. MAIN OUTCOME MEASURES: The difference between preoperative and postoperative IOP, absolute postoperative IOP, and the need for acute IOP-lowering treatment was noted. RESULTS: Only 1.1% (95% confidence interval [CI], 0.03%-5.8%; 1 of 94) of patients and 0.7% (95% CI, 0.02%-3.7%; 1 of 148) of eyes with NOA experienced a rise of more than 10 mmHg 1 to 2 hours after LPI. The incidence of postoperative IOP greater than 25 mmHg and acute postoperative IOP-lowering management was 0% (95% CI, 0%-3.8%). Intraocular pressure in 1 of 115 eyes (0.9%, 95% CI, 0.02%-4.7%) with OAG rose more than 10 mmHg, requiring acute treatment. None of the 26 CACG eyes experienced a rise of more than 10 mmHg (95% CI, 0%-13.2%). CONCLUSION: The IOP rise that requires further intervention after LPI with the perioperative use of pilocarpine and apraclonidine is very uncommon. In patients with NOA, routine postiridotomy IOP monitoring may not be required.

Adrenergic alpha-Agonists↗

Mild closed-head injury in children and adolescents: behavior problems and academic outcomes.

The issue of whether mild head injuries (HIs) in children cause behavior problems and poor scholastic performance is controversial. This study included 119 children (range = 8-16 years old) with HI, 114 with other injuries, and 106 with no injury (NI). Behavioral functioning was assessed with the Child Behavior Checklist; academic functioning, with school grades and standardized testing. Higher T scores were found for both injury groups versus NI participants on preinjury behavioral status. All 3 groups' behavioral scores decreased relative to baseline at 1 year. HI and NI groups did not differ in school grades or achievement testing either pre- or postinjury. These results are consistent with the conclusion that head injury of the mildest type does not increase the probability of new overt behavioral or academic problems.

Adolescent↗

Dementia in older minority populations. Issues of prevalence, diagnosis, and treatment.

Dementia continues to be a major disease that affects older Americans. It has been estimated that up to 25% of all community-dwelling elderly individuals in the United States suffer from signs or symptoms of dementia. Little, however, has been written on dementia as it relates to older minority populations. The purpose of this article is to discuss the prevalence of dementia in elderly minority populations, describe some of the unique issues related to the diagnosis and treatment of dementia in these populations, and make recommendations aimed toward improving the quality of life for elderly minority individuals with dementia.

Black or African American↗

Comparison of methods of identifying Helicobacter hepaticus in B6C3F1 mice used in a carcinogenesis bioassay.

In a long-term rodent bioassay evaluating the carcinogenicity of triethanolamine, there was equivocal evidence of carcinogenic activity in male B6C3F1 mice, based on a marginal increase in the number of hepatocellular adenomas and hepatoblastomas. Interpretation was complicated by the presence of Helicobacter hepaticus in selected silver-stained liver sections which also had histological evidence of karyomegaly and oval cell hyperplasia. An increase in numbers of liver tumors, as evidence of carcinogenic activity, was also noted in female mice. However, H. hepaticus was not considered a complicating factor, because the livers of the female mice did not have histological features compatible with H. hepaticus infection. A retrospective analysis of 51 liver tissue samples from the original carcinogenicity study was conducted to determine the incidence of H. hepaticus infection and to evaluate different diagnostic approaches for assessing the presence of H. hepaticus in livers lacking characteristic lesions. In an initial evaluation of seven mice with liver tumors, argyrophilic bacteria resembling H. hepaticus were observed in liver sections, associated with characteristic liver lesions of hepatocytic karyomegaly and oval cell hyperplasia. Frozen liver tissue was available from four of these mice; all were confirmed to be infected with H. hepaticus by culture and PCR. In a larger subsequent analysis using frozen liver tissues from 44 mice without characteristic hepatic lesions, H. hepaticus-specific DNA was amplified from the livers of 21 of 44 of the mice (47%), compared to 14 of 44 of the mice (32%) having H. hepaticus cultured from their frozen liver tumors. The results of H. hepaticus culture and H. hepaticus-specific PCR concurred (i.e., both positive and negative results) in 84% of the cases. Microscopic detection of immunofluorescence-labeled or silver-stained bacteria in liver sections was relatively insensitive compared to either culture or PCR detection. This study confirms the widespread prevalence of H. hepaticus in mice, its potential to confound experimental results, and the need to include diagnostic testing for H. hepaticus in a murine health monitoring program.

Animals↗