Accurate intraocular pressure measurement-the myth of modern ophthalmology?
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Cornea↗
Biomedical subjects
S Shah
Publications and source records attributed to S Shah.
Adolescent suicide and household access to firearms in Colorado: results of a case-control study.
PURPOSE: To determine whether, compared with age- and sex-matched controls who did not commit suicide, adolescents who committed suicide by firearms were more likely to have had household access to firearms (after adjusting for significant risk factors for adolescent suicide). METHODS: A case-control study design was used; case subjects were Colorado adolescents who committed suicide between 1991 and 1993; controls were sex- and age-matched adolescents who were randomly selected from the same school the subjects had attended. Interviews were conducted with the parent or guardian of cases and controls. RESULTS: Of the 36 case subjects in this study, 67% committed suicide using a gun obtained from their home. Adolescent suicide victims who committed suicide by firearms were significantly more likely to have a firearm in their home (72%) than age- and sex-matched community controls (50%), after adjusting for significant risk factors. Conduct disorder and previous mental health treatment were also found to be independent risk factors for adolescent firearm suicide. CONCLUSIONS: Two types of public health interventions to prevent adolescent firearm suicides are likely to be successful: (a) limiting household access to firearms, and (b) identifying adolescents at high risk of firearm suicide.
Adolescent↗
High throughput screening of gene expression signatures.
This paper focuses on microarray image analysis and discusses a completely automated approach to image processing, which eliminates human intervention. A system for automated image processing is described, which is capable of processing image files in a batch-mode thus allowing high-throughput of microarray image analysis. Grid-placement and spot finding are achieved without operator's help. The software eliminates noise signals from the data analysis process and minimizes operator's involvement in the procedure.
Algorithms↗
Induction of apoptosis in p16INK4A mutant cell lines by adenovirus-mediated overexpression of p16INK4A protein.
The tumor suppressor gene p16INK4A is a cyclin-dependent kinase inhibitor (CDKI) and an important cell cycle regulator. We have previously constructed a recombinant adenovirus which expresses p16 (Adp16) and shown that infection in a variety of human tumor cell lines with this recombinant virus results in high levels of p16INK4A protein expression resulting in cell cycle arrest and loss of cyclin-cdk activity. Furthermore, adenoviral-mediated overexpression of wild-type p16INK4A is more toxic in cancer cells which express mutant forms of p16INK4A compared to cancer cell lines containing endogenous wild-type p16. TUNEL assay and DAPI staining following infection of MDA-MB 231 breast cancer cells with Adp16 indicate that p16INK4A-mediated cytotoxicity was associated with apoptosis. This is supported by studies demonstrating a decrease in cpp32 and cyclinB1 protein levels and induction of poly (ADP-ribose) polymerase (PARP) cleavage following infection of MDA-MB-231 cells with Adp16. These results suggest that gene therapy using Adp16 may be a promising treatment option for human cancers containing alterations in p16 expression.
Adenoviridae↗
Validation of the ISAAC video questionnaire (AVQ3.0) in adolescents from a mixed ethnic background.
BACKGROUND: The International Study of Asthma and Allergies in Childhood (ISAAC) has developed an international version of the asthma video questionnaire (AVQ3.0) to measure asthma prevalence. This questionnaire has not been validated in adolescents from a mixed ethnic background. OBJECTIVE: The aims of this study were to compare the video questionnaire with a written questionnaire in the detection of airway hyperresponsiveness to hypertonic saline in a population of adolescents from a mixed ethnic background, and to establish the repeatability and psychometric properties of the asthma video questionnaire. METHODS: The study was conducted in four secondary schools in Sydney, an area with a high proportion of people from a non-English speaking background. Four hundred and seventy-five students from schools 1 and 2 completed the video questionnaire and a subgroup of these students (n = 170) completed the written questionnaire and a hypertonic saline inhalation challenge. Reproducibility of the questionnaire was evaluated by administering the questionnaire to a subsample of students 2 weeks later. The psychometric properties of the video questionnaire were examined in 852 students at two other schools (schools 3 and 4). RESULTS: One hundred and sixty-nine students aged 13.5 (sd 1.3) years completed both written and video questionnaires, and the hypertonic saline challenge. The students had widely different cultural backgrounds including Asian, South Pacific, Middle Eastern, European and African countries. There was good agreement between the questionnaires for wheeze (kappa 0.42). Questions on the video questionnaire concerning wheezing had good sensitivity (90%) and specificity (68%) for airway hyperresponsiveness to hypertonic saline. The video questionnaire was reproducible (kappa 0.82), had good internal consistency (Cronbach's alpha 0.81) and each question pertained to a single construct explaining 58% of the variance in total score. CONCLUSION: This study has validated the international version of the ISAAC video questionnaire against airway hyperresponsiveness to hypertonic saline in adolescents from a mixed ethnic background, and identified that the questionnaire has good psychometric properties. The ISAAC video has proved to be a valuable tool for the assessment of asthma prevalence in populations of ethnic diversity.
Adolescent↗
Increased drug delivery to the brain by P-glycoprotein inhibition.
BACKGROUND: Although the antidiarrheal loperamide is a potent opiate, it does not produce opioid central nervous system effects at usual doses in patients. On the basis of in vitro studies demonstrating that loperamide is a substrate for the adenosine triphosphate-dependent efflux membrane transporter P-glycoprotein, we postulated that inhibition of P-glycoprotein with quinidine would increase entry of loperamide into the central nervous system with resultant respiratory depression. METHODS: To test this hypothesis, a 16-mg dose of loperamide was administered to eight healthy male volunteers in the presence of either 600 mg quinidine, a known inhibitor of P-glycoprotein, or placebo. Central nervous system effects were measured by evaluation of the respiratory response to carbon dioxide rebreathing as a measure of opiate-induced respiratory depression. RESULTS: Loperamide produced no respiratory depression when administered alone, but respiratory depression occurred when loperamide (16 mg) was given with quinidine at a dose of 600 mg (P < .001). These changes were not explained by increased plasma loperamide concentrations. CONCLUSION: This study therefore demonstrates first the potential for important drug interactions to occur by a new mechanism, namely, inhibition of P-glycoprotein, and second that the lack of respiratory depression produced by loperamide, which allows it to be safely used therapeutically, can be reversed by a drug causing P-glycoprotein inhibition, resulting in serious toxic and abuse potential.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Activity of the tea component epicatechin gallate and analogues against methicillin-resistant Staphylococcus aureus.
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Antioxidants↗
Patterns of phenotypic resistance to the macrolide-lincosamide-ketolide-streptogramin group of antibiotics in staphylococci.
Phenotypes of resistance to the macrolide-lincosamide-ketolide-streptogramin (MLKS) group of antibiotics have been determined in 540 clinical isolates of staphylococci (210 Staphylococcus aureus and 330 coagulase-negative species). Results of disc diffusion tests using erythromycin A, oleandomycin, rokitamycin, clindamycin, telithromycin, quinupristin and dalfopristin delineated four main groups corresponding to those defined classically using erythromycin and clindamycin only, but with sub-divisions. Resistance to erythromycin was more common in coagulase-negative strains (56%) than in S. aureus (16%); telithromycin, clindamycin, quinupristin-dalfopristin and rokitamycin were active against >97% of S. aureus strains and >88% of the coagulase-negative strains. The commonest resistance phenotype was 'inducible MLS(B)' (12% in S. aureus, 31% in coagulase-negative strains); this group could be divided in terms of the different inducing abilities of erythromycin and oleandomycin. 'Constitutive MLS(B)' and 'MS' phenotypes were more often found in coagulase-negative strains (11 and 13%, respectively) than in S. aureus (2 and 1%). Novel phenotypes were found during the isolation of constitutively resistant mutants from inducible strains, and of resistant mutants from 'MS' strains. This extended phenotyping scheme has revealed further complexities and evolutionary possibilities in patterns of resistance to this group of antibiotics.
Anti-Bacterial Agents↗
Gastric acid suppression does not promote clostridial diarrhoea in the elderly.
Gastric acid prevents bacterial colonization of the stomach and suppression of its secretion might predispose to Clostridium difficile (CD) diarrhoea. We retrospectively studied elderly patients admitted to medical wards of an acute hospital to determine whether the incidence of CD diarrhoea was greater among those previously treated with gastric acid suppressants. From records of stool CD toxin tests undertaken in 1995 and 1996, we found 126 cases with positive results, and selected 126 controls with negative results. Information about pre-morbid illness, predisposing factors for CD and medication received in the preceding 16 weeks was obtained from case-notes. A greater number of CD positive cases had received antibiotics such as Cefuroxime, ciprofloxacin or macrolides with or without metronidazole, were more severely disabled, required assistance for feeding, or had hypoalbuminaemia before the onset of diarrhoea. A greater number of controls had received lactulose, suggesting either that its laxative effect resembled CD infection prompting frequent stool tests, or that it offered protection against CD in this group. Both groups were similar for the use of proton-pump inhibitors or H2-receptor antagonists, suggesting that susceptible elderly patients are not more likely to develop CD diarrhoea after receiving gastric acid suppression therapy.
Activities of Daily Living↗
Surgically induced astigmatism after photorefractive keratectomy with the excimer laser.
PURPOSE: To evaluate retrospectively the effect of spherical excimer laser photorefractive keratectomy (PRK) on astigmatism. METHODS: Four hundred seventy consecutive eyes of patients who had PRK for the treatment of myopia without astigmatic keratotomy, PRK reoperation, or other surgical procedures were evaluated in a retrospective clinical study. PRK was performed using the Summit Apex excimer laser with attempted corrections from 1 to 7 diopters (D) of myopia. Preoperative and postoperative astigmatism was determined by manifest refraction refined with a 0.25-D Jackson cross cylinder and evaluated with vector analysis. RESULTS: Eighty-five ( 18%) eyes continued to have a spherical refraction after PRK, 53 (11%) eyes had the same preoperative astigmatism, and 332 (71%) eyes had a change in magnitude of astigmatism > or =0.25 D after spherical PRK. The absolute change in astigmatism magnitude irrespective of axis was +0.4 +/- 0.4 (standard deviation) D at 6 months after PRK. Eyes with change in astigmatism power tended to have higher preoperative myopia and higher preoperative astigmatism. Vector analysis revealed surgically induced astigmatism was 0.68 +/- 0.50 D (range, 0-3.25 D) at 1 month and 0.56 +/- 0.47 D (range, 0-3.1 D) at 12 months after spherical PRK. CONCLUSION: Spherical excimer laser PRK is associated with significant surgically induced astigmatism that is likely related to decentration of the ablation, excimer laser beam irregularities, and variations in wound healing across the ablated zone. Surgically induced astigmatism will complicate attempts to correct astigmatism simultaneously at the time of PRK and suggest that such attempts are likely to be problematic for lower levels of astigmatism.
Adult↗
Laparoscopic repair of a chronic diaphragmatic hernia.
Diaphragmatic injuries that remain undetected after an acute traumatic event may lead to the formation of a diaphragmatic hernia. Symptoms of a chronic diaphragmatic hernia are related to the incarceration of abdominal contents in the defect or to impingement of the lung, heart, or thoracic esophagus by abdominal viscera. A 49-year-old woman with a symptomatic chronic diaphragmatic hernia from an unrecognized iatrogenic injury to the left hemidiaphragm sought treatment. The diaphragmatic injury occurred 2 years earlier when a low, left-sided chest tube was placed for a persistent pleural effusion 2 weeks after a lower lobectomy for an aspergilloma. The patient's diaphragmatic hernia was diagnosed after an upper gastrointestinal series and an esophagogastroduodenoscopy. Approximately 75% of her stomach was incarcerated in the diaphragmatic defect. The diaphragmatic hernia was repaired laparoscopically using a 9 cm x 10-cm polytetrafluoroethylene patch sewn with nonabsorbable, interrupted, horizontal mattress sutures. Improvement of video technology, laparoscopic instruments, and surgical skills has allowed surgeons to expand the boundaries of advanced therapeutic laparoscopy. These factors facilitated the authors' standard tension-free prosthetic repair of a chronic diaphragmatic hernia using minimally invasive techniques.
Chronic Disease↗
The efficacy of ECT in mixed affective states.
ECT is efficacious in the treatment of both the depressed and manic phases of bipolar disorder. While ECT is believed to be equally efficacious in the treatment of mixed affective states, to our knowledge there are no empirical studies on this issue. A chart review study was conducted to compare treatment response and clinical course in three groups of patients who received ECT in a general hospital service: bipolar depressed (n = 38), bipolar manic (n = 5), and bipolar mixed (n = 10), diagnosed by DSM-IV criteria. All three groups showed robust response rates, but the number of days of hospitalization was significantly longer in the mixed group (mean 30, SD 19.0 days) compared with the depressed group (mean 19.0, SD 10.9 days, t = 2.4, p < 0.03). There was a trend for the number of ECT treatments to be greater in the mixed compared with the depressed group. These findings indicate that patients with mixed affective states do respond well to a course of ECT, but the longer hospital stays and greater number of ECT treatments suggest that they may be more difficult to treat with ECT than patients with pure bipolar depression or bipolar mania.
Adult↗
Teaching asthma management: an evidence-based educational approach.
BACKGROUND: Asthma management plans and asthma education have been incorporated into recent guidelines, and implementation of these reduces asthma morbidity. Junior doctors are frequently involved in asthma management, but teaching about asthma in medical school is seldom assessed. We studied asthma knowledge, confidence in practical asthma management, and the effectiveness of an interactive asthma education workshop in final year medical students. Thirty-five students attended the workshop, with 26 returning questionnaires on both of the two sessions. METHODS: Students attended a two hour asthma workshop comprising interactive teaching sessions on management of acute and stable asthma, and a practical session using asthma devices. Theoretical knowledge was assessed by a 20 item questionnaire, completed immediately prior to the workshop and after two weeks, at a feedback session. Practical knowledge was assessed by confidence scores in use of asthma devices on a five point scale (not at all confident to very confident), before, immediately after the workshop, and after two weeks. RESULTS: Students scored poorly in questions on: predictors of asthma mortality, nebuliser and Turbuhaler use, asthma management plans, and physical signs in acute asthma. Mean (SE) knowledge score increased significantly from 64.4% (6.1) to 74.2% (5.6) (p<0.05; paired t-test) at two weeks. Confidence scores rose significantly for all practical aspects of asthma management (p<0.01; Wilcoxon matched pairs test), and declined at two weeks, but still remained significantly higher than at baseline (p<0.05). CONCLUSIONS: Medical students had poor knowledge about several important features of asthma care. The asthma workshop was effective in increasing knowledge and confidence in management of asthma in the short term, and could be useful in optimising implementation of asthma guidelines in clinical practice and potentially later in training of junior medical officers.
Adult↗
Three-dimensional contrast-enhanced MR angiography with real-time fluoroscopic triggering: design specifications and technical reliability in 330 patient studies.
Technical reliability was determined for triggering three-dimensional (3D) contrast material-enhanced magnetic resonance (MR) angiography with MR fluoroscopy. Technical requirements for high reliability were also identified. Reliability was evaluated in 330 consecutive patient studies of the neck, thorax, abdomen, and pelvis. Contrast material arrival was detected fluoroscopically in 325 of the 330 studies (98.5%), and the 3D sequence was successfully triggered in 321 of 330 studies (97.3%). Fluoroscopic triggering of centrically encoded 3D MR angiographic acquisitions is a highly reliable means of obtaining 3D MR angiograms with high spatial resolution.
Abdomen↗
Desmin knockout muscles generate lower stress and are less vulnerable to injury compared with wild-type muscles.
The functional role of the skeletal muscle intermediate filament system was investigated by measuring the magnitude of muscle force loss after cyclic eccentric contraction (EC) in normal and desmin null mouse extensor digitorum longus muscles. Isometric stress generated was significantly greater in wild-type (313 +/- 8 kPa) compared with knockout muscles (276 +/- 13 kPa) before EC (P < 0.05), but 1 h after 10 ECs, both muscle types generated identical levels of stress ( approximately 250 kPa), suggesting less injury to the knockout. Differences in injury susceptibility were not explained by the different absolute stress levels imposed on wild-type versus knockout muscles (determined by testing older muscles) or by differences in fiber length or mechanical energy absorbed. Morphometric analysis of longitudinal electron micrographs indicated that Z disks from knockout muscles were more staggered (0.36 +/- 0. 03 microm) compared with wild-type muscles (0.22 +/- 0.03 microm), which may indicate that the knockout cytoskeleton is more compliant. These data demonstrate that lack of the intermediate filament system decreases isometric stress production and that the desmin knockout muscle is less vulnerable to mechanical injury.
Age Factors↗
Gastrointestinal motility during pregnancy: role of nitrergic component of NANC nerves.
This study evaluated whether increased release of nitric oxide (NO) from the nitrergic component of the nonadrenergic, noncholinergic (NANC) nerves may be partly responsible for the decrease in gastrointestinal motility observed during pregnancy. Segments of fundal strip, ileum, and colon were obtained from nonpregnant rats, rats in midpregnancy (days 9-11), and rats in late pregnancy (days 18-20). NANC activity was studied by assessing changes in tone after application of electric field stimulation (EFS). The role of NO was determined by observing the effects of EFS in the presence and absence of the NO synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) and the reversibility of the effects of L-NAME by L-arginine. The magnitude of change in cGMP levels in the tissues after application of EFS was also assessed. Our studies indicate that there was increased magnitude of relaxation of isolated strips of rat gastric fundus and rat colon, after application of EFS to tissues obtained only from animals in late pregnancy. These results paralleled the changes in cGMP levels in tissues. NOS activity in the gastric fundus was significantly increased in animals in late pregnancy compared with nonpregnant controls. Our studies suggest that the delay in gastric emptying and increase in colonic transit time observed in rats during pregnancy may be caused in part by increased activity of the nitrergic component of the NANC nerves innervating these organs.
Acetylcholine↗
Re-survey of the Whitehall study of London civil servants: changes in risk factors for cardiovascular disease during 29 years of follow-up.
BACKGROUND: Substantial uncertainty persists about the relevance of blood pressure and cholesterol to the risk of cardiovascular disease in the elderly. OBJECTIVE: To investigate the determinants of cardiovascular risk in old age, and the relevance of such risk factors when recorded in middle and old age. METHODS: A re-survey in 1997 of 8537 survivors of a cohort of men who were originally examined in 1967-1970 when aged 40-69 years. RESULTS: Completed questionnaires were received from 7050 (82%) of the survivors, and blood pressure and blood samples from 5427 (64%). The response rate declined with increasing age, was inversely related to markers of socioeconomic status in 1967-70 and in 1997, and was lower in those who had been current smokers or had a higher blood pressure level in 1967-70. After excluding those with reported cardiovascular disease (25% of respondents), the mean levels of total cholesterol and apolipoprotein B were lower in older age groups, whereas apolipoprotein A1 levels did not vary much with age. Among those with risk factors recorded both in 1967-70 and 1997, the prevalence of smoking had declined by two-thirds (32% in 1970 and 12% in 1997), the prevalence of diabetes had increased (0.3% versus 4.5%), and the mean systolic blood pressure had increased by 16 mmHg (130 versus 146 mmHg), but the diastolic blood pressure had not changed materially (80 versus 81 mmHg), and the measured levels of total cholesterol had increased by 0.5 mmol/l (although that change may be artefactual). CONCLUSION: Follow-up of vital status in this cohort should permit an assessment of the relevance of risk factors recorded in middle and old age to cardiovascular disease in old age.
Adult↗
Outcome measurement in brain injury rehabilitation--towards a common language.
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Brain Injuries↗