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Biomedical subjects

A Rashid

Publications and source records attributed to A Rashid.

At least 73 records · Page 4Linked to original sources

Factors that mediate and moderate the link between partner abuse and suicidal behavior in African American women.

Findings from a study comparing partner abuse in African American women suicide attempters (n = 148) and nonattempters (n = 137) revealed higher rates of physical and nonphysical partner abuse among attempters than their demographically similar nonsuicidal counterparts. The partner abuse--suicidal behavior link was mediated by psychological distress, hopelessness, and drug use and moderated by social support. Results also revealed that nonphysical partner abuse accounted for unique variance in the prediction of suicide attempt status beyond that attributable to childhood maltreatment. Implications of the findings for assessing both suicidal and abused women are discussed, and recommendations for preventive interventions for women at risk for suicidal behavior are provided.

Adolescent↗

Dysplasia and dysregulation of proliferation in foveolar and surface epithelia of fundic gland polyps from patients with familial adenomatous polyposis.

Fundic gland polyps (FGPs) of the stomach are regarded as hamartomatous or hyperplastic/functional polyps that occur sporadically but at increased frequency in patients with familial adenomatous polyposis syndrome (FAP). There is controversy about the histopathology of FGPs, including occurrence of dysplasia. We, therefore, studied dysplasia in 270 sporadic FGPs from 216 patients and 49 FGPs from 24 patients with FAP. We evaluated dysregulation of epithelial proliferation manifested by loss of the normal inverse topographic distribution of Ki-67 proliferation marker and the cyclin-dependent kinase inhibitor p21(WAF1/CIP1) using immunohistochemistry in 27 sporadic FGPs and in 22 FGPs from patients with FAP. Dysplasia in foveolar and surface epithelia occurred in 12 of 49 (25%) FGPs in patients with FAP but in only 3 of 270 (1%) of sporadic FGPs (p < 0.000001). Fourteen of 49 (29%) of FGPs from patients with FAP were indefinite for dysplasia, as contrasted with 8 of 270 (3%) sporadic FGPs (p < 0.00001). The normal inverse topographic distribution of Ki-67 and p21(WAF1/CIP1) was maintained in 20 of 22 (91%) of FGPs negative for dysplasia but was lost in all (8 of 8) FGPs with dysplasia and in 11 of 19 (58%) FGPs that were indefinite for dysplasia (p = 0.00001). The results indicate that dysplasia can occur in foveolar and surface epithelia of FGPs, especially in patients with FAP, and often is preceded by dysregulation of epithelial proliferation when the morphologic abnormalities are indefinite for dysplasia.

Adenomatous Polyposis Coli↗

What determines competence within a general practice consultation? Assessment of consultation skills using simulated surgeries.

A method for assessing the consultation skills required in general practice using patient simulators within a simulated surgery has been developed in Leicester, aimed at registrars coming to the end of their three-year training programme. This paper addresses the issues of validity, describing the technique as it has evolved over the past three years, and paying particular attention to ways in which the consultation was made to feel 'real' for candidates. As well as testing clinical issues during consultations, simulated surgery incorporates the views of the patient into the assessment process. Feedback from registrars has been positive and the method presents an alternative to video-recording the consultation for the purpose of assessment.

Clinical Competence↗

Dermatophytes and host defence in cutaneous mycoses.

Dermatophytosis is the infection of keratinized tissues such as hair, nails and the stratum corneum of the skin by dermatophyte fungi. These fungi are onygenalean anamorphs and anamorphic species belonging to the genera Trichophyton, Microsporum and Epidermophyton. An important characteristic of the dermatophytes as parasites is their restriction to the dead keratinized tissues, except in rare cases where the patient is immunosuppressed. In contrast to many fungi, including normally non-pathogenic species, which can invade systemically in severely immunocompromised (e.g. neutropenic) patients, dermatophytes appear to be unable to cause systemic infection in this population. Thus, these fungi appear to have an unique interaction with the immune system. A better understanding of this interaction will contribute significantly to our knowledge of mammalian host defences.

Arthrodermataceae↗

Genetic alterations in sporadic and Crohn's-associated adenocarcinomas of the small intestine.

BACKGROUND & AIMS: Small intestinal carcinomas are rare but occur with increased incidence in Crohn's disease. The aim of this study was to elucidate the genetic alterations. METHODS: Mutations and deletions involved in colorectal carcinoma were studied in sporadic and Crohn's-associated intestinal carcinomas and precursors. RESULTS: c-K-ras mutations were present in all four sporadic carcinomas with contiguous adenomas, in only 18% without adenomas (P = 0.01), in 43% of Crohn's-associated carcinomas, and in 14% of dysplasias. Overexpression of p53 gene product and/or 17p allelic loss were present in 47% of sporadic carcinomas and 33% of contiguous adenomas and in 71% of Crohn's-associated carcinomas and 43% of dysplasias. In contrast, allelic losses of 5q (adenomatous polyposis coli [APC] gene region) and 18q (deleted in colorectal cancer [DCC] gene region) were rare. DNA replication errors (RERs) were present in 13% of sporadic carcinomas and in the carcinoma and dysplasias of 1 patient with Crohn's disease (14%), but mutations in the transforming growth factor beta type II receptor (TGFbeta RII) gene were absent. CONCLUSIONS: Accumulation of ras and p53 alterations occurs during the adenoma/dysplasia-carcinoma sequence in small intestinal carcinogenesis, but a ras-independent pathway may also exist. The infrequent loss of the APC and DCC regions and the absence of TGFbeta RII gene mutation in RER-positive neoplasms contrast with colorectal carcinogenesis.

Adenocarcinoma↗

Necrosis of the gastrointestinal tract in uremic patients as a result of sodium polystyrene sulfonate (Kayexalate) in sorbitol: an underrecognized condition.

Sodium polystyrene sulfonate (Kayexalate) in sorbitol given as an enema or orally to treat hyperkalemia has been reported to induce intestinal necrosis in uremic patients. We studied the clinical and pathologic features of 15 patients in whom Kayexalate crystals were observed in specimens from gastrointestinal surgical resections (n = 9) or endoscopic biopsies (n = 7). Oral or nasogastric tube administration of Kayexalate in sorbitol was documented in 10 patients. Among 12 patients with colorectal specimens, necrosis was observed in nine patients (75%), represented by seven of eight surgical resection specimens and three of five endoscopic biopsy specimens. No other cause of colorectal necrosis apart from Kayexalate in sorbitol was apparent in seven patients, and four also had necrosis of the small intestine. Four patients with colonic necrosis in their initial resection specimen developed progressive necrosis of the small intestine or rectum, and five patients (56%) had fatal outcome within 1 day to 6 weeks. Kayexalate crystals were observed in upper gastrointestinal tract specimens from four patients, including one with hemorrhagic gastritis. Our findings provide additional evidence that Kayexalate in sorbitol administered orally or by nasogastric tube can produce necrosis in the gastrointestinal tract.

Adult↗

Elevated expression of fatty acid synthase and fatty acid synthetic activity in colorectal neoplasia.

Expression of the primary enzyme catalyzing the synthesis of fatty acids, ie, fatty acid synthase (FAS), and ex vivo fatty acid synthetic activity were examined in colorectal epithelium and neoplasms, including the relationship to tumor progression and prognosis. Immunohistochemistry for FAS showed only faint staining of native colorectal mucosa, but increased expression was found in all sporadic adenomas (n = 18), adenomas associated with familial adenomatous polyposis (n = 7), hyperplastic polyps (n = 3), dysplasias arising in ulcerative colitis (n = 17), and colorectal carcinomas (n = 130) including 11 with contiguous adenomas. The intensity of staining was strong in 53% of carcinomas, intermediate in 38%, and weak in 9%. Activity of the fatty acid synthetic pathway measured by labeling of six surgical specimens with [U-14C]acetate was 2- to 7-fold higher in colorectal carcinomas than adjacent native mucosa (P = 0.006) and 6- to 16-fold higher than serosal fat (P = 0.01). Activity correlated with immunohistochemical expression (Spearman's rank correlation coefficient = 0.85; P < 0.001). There was no statistically significant association between patient survival and FAS staining intensity of carcinomas. Our study shows that FAS is expressed in all colorectal neoplasms and there is a concomitant increase in fatty acid synthesis. FAS may therefore represent a potential therapeutic target.

Adenoma↗

Genetic alterations and epithelial dysplasia in juvenile polyposis syndrome and sporadic juvenile polyps.

Juvenile polyps are regarded as hamartomatous polyps and occur in sporadic and familial syndromic settings. There is increased risk of gastrointestinal neoplasia in patients with juvenile polyposis syndrome, but the molecular mechanisms are not known. We therefore studied 78 colorectal juvenile polyposis from 12 patients with juvenile polyps syndrome and 34 sporadic juvenile polyps for epithelial dysplasia and genetic changes associated with colorectal neoplasia. Dysplasia occurred in 31% of syndromic juvenile polyps but not in sporadic juvenile polyps (P < 0.0001). Topographic control of proliferation and expression of the cyclin-dependent kinase inhibitor p21(WAFI/CIP1) seen in native colorectal epithelium was lost in 79% of dysplastic juvenile polyps and in 8% of nondysplastic juvenile polyps (P < 0.000001). Somatic mutations in the adenomatous polyposis coli (APC) gene were demonstrated in 50% of dysplastic juvenile polyps (3 of 6) but not in any of 16 juvenile polyps without dysplasia (P = 0.01). Both sporadic and syndromic juvenile polyps had K-ras mutations (14%) and there was no relationship to dysplasia. p53 gene product overexpression identified by immunohistochemical staining occurred rarely in dysplastic juvenile polyps (2 of 24, 8%). Our results indicate that the multiple genetic alterations involved in usual colorectal neoplasia also play a role in neoplastic transformation of juvenile polyps, predominantly in juvenile polyposis syndrome.

Adenomatous Polyposis Coli↗

Patients' knowledge of anatomical location of major organs within the human body: a comparison between Asians and non-Asians.

OBJECTIVE: This study was designed to ascertain lay knowledge of the anatomical location of major organs within the human body amongst the Asian and non-Asian population in Leicester and to explore the relationships of this knowledge to level of education and social class. METHOD: The study was based on a cross sectional random sample stratified by from the FHSA Nominal Index Register and data was collected using a personally administered questionnaire in the preferred language of the respondent. Subjects marked the position of the major organs (heart, lungs, kidneys, bladder, liver, brain and stomach) on an image of the human body. The answers were judged against a correct 'response area' produced from a survey of 20 GPs. RESULTS: The overall response rate to the survey was 88.5% with 449 Asians and 447 non-Asians participating. After adjustment for age, sex, education and social class differences, non-Asians were significantly more likely to correctly identify the position of the lungs (P = 0.01) and less likely than Asians to correctly identify the position of the stomach (P < 0.0001). There were no differences found in the knowledge of the position of the other organs. Higher educational attainment was significantly associated with the ability to locate the kidneys (P = 0.0052) and the liver P = 0.0001) and higher social class was associated with greater ability to locate the position of the lungs P = 0.01). CONCLUSIONS: Patients show considerable lack of knowledge of the position of major organs within the body. Health professionals will need to address this before embarking upon health promotion.

Adolescent↗

New mechanisms of action with fungicidal antifungals.

Morphological modifications of growth forms of dermatophyte fungi, arthroconidia and germ tubes exposed to terbinafine incorporated in the stratum corneum were studied by scanning and transmission electron microscopy. Changes observed in arthroconidial morphology included pores and erosions present in the cell wall, with layers peeling off. The cell membrane was destroyed. Dilated vacuoles and small electron-dense areas were evident in the arthroconidial cytosol. Although germination was partially arrested, inhibition of hyphal extension was seen on all body sites examined. Germ tubes were susceptible to terbinafine, with pores appearing along their length and collapsed hyphae seen following exposure to the drug. This study suggests that the outer and inner layers of the arthroconidial cell wall are the initial targets of terbinafine action, followed by alterations to the cytosol and intracellular organelles.

Adult↗

Views of Asians and non-Asians on sources of drug information and the desirability for medication to be made available over the counter.

Differences do exist between Asians and non-Asians on the range of products they feel should be available over the counter (OTC) and the amount of information they wish to receive. This should be taken into account when considering proposals for changes in the legal status of prescription-only medicines. The profile of the pharmacist as a provider of drug information to patients could be raised in both groups.

Asia↗

The effects of sulindac on colorectal proliferation and apoptosis in familial adenomatous polyposis.

BACKGROUND & AIMS: The mechanism by which sulindac causes regression of adenomas in patients with familial adenomatous polyposis (FAP) is unclear. Conflicting data on the drug's effects on colorectal epithelial proliferation have been reported. An alternative mechanism, and one not previously studied, is via induction of colorectal epithelial cell apoptosis (programmed cell death). This hypothesis was tested by studying the effects of sulindac on colorectal epithelial proliferation and apoptosis in patients with FAP. METHODS: Cell proliferation was studied via immunohistochemistry for cell nuclear antigen in a group of 22 patients randomized to either sulindac (150 mg twice a day) or placebo in a previously published trial. The rectal epithelium from 7 additional patients with FAP treated with sulindac was examined by flow cytometry to assess changes in cell-cycle distribution and apoptosis. RESULTS: Although sulindac caused a significant decrease in polyp size and number, there was no significant change in cytokinetic variables or cell cycle distribution 3 months after treatment. However, the subdiploid apoptotic fraction was increased significantly 3 months after treatment with sulindac (31.3% +/- 4.8% compared with 10% +/- 4.3% at baseline; P = 0.01). CONCLUSIONS: Our findings suggest that sulindac does not affect colorectal epithelial proliferation and that its effects in patients with FAP may instead result from induction of apoptosis.

Adenomatous Polyposis Coli↗

Inhibitory effect of terbinafine on the invasion of nails by Trichophyton mentagrophytes.

BACKGROUND: Terbinafine has a broad spectrum of action in vitro and primary fungicidal action against many pathogenic fungi. Its mode of action against dermatophyte fungi in nail keratin is little understood. OBJECTIVE: Our purpose was to determine the bioavailability of terbinafine in a nail fragment model. METHODS: The effect of terbinafine on adherence and germination of arthroconidia of Trichophyton mentagrophytes on nail fragments was assessed by gross examination and light and electron microscopy. RESULTS: Preexposure of nail fragments to terbinafine concentrations (0.001 to 10 mg/L) inhibited fungal growth and acted as a barrier to dermatophyte invasion. Damaged arthroconidia and distorted hyphae on the surface of nail fragments were observed. CONCLUSION: This in vitro model provides an alternative system for studying the activity of antifungal agents in nail and demonstrates the morphologic changes in dermatophyte fungi after exposure to terbinafine.

Antifungal Agents↗

Continuous warm versus intermittent cold blood cardioplegia for coronary bypass surgery in patients with left ventricular dysfunction.

Between October 1991 and March 1994, 108 consecutive patients with moderate to severe left ventricular dysfunction underwent non-emergency isolated coronary artery surgery under the care of one surgeon (A.R.). They were prospectively randomised to receiving either intermittent cold (Group 1-50 patients) or continuous warm (Group 2-58 patients) blood cardioplegia for myocardial protection. There were no significant differences in clinical outcome between the two groups, as judged by operative mortality, rates of perioperative myocardial infarction, the serum CKMB isoenzyme level at 2 and 18 h after operation, need for circulatory support, postoperative neurological deficit, or duration of hospital stay. Group 2 patients required significantly more potassium (68 vs 29 mmol, P < 0.001) to maintain diastolic arrest and also had higher serum potassium levels after removal of the cross-clamp (P < 0.001). However, sinus rhythm returned spontaneously with greater frequency (91.2% vs 45.8%, P < 0.001) in Group 2 patients. In conclusion this report suggests that retrograde continuous warm blood cardioplegia provides comparable myocardial protection to that achieved with retrograde intermittent cold blood cardioplegia in patients with moderate to severe left ventricular dysfunction undergoing isolated coronary artery surgery.

Aged↗

Early events in the invasion of the human nail plate by Trichophyton mentagrophytes.

A new in vitro model for the study of nail invasion by dermatophyte fungi was developed. The dermatophyte Trichophyton mentagrophytes, and fragments of finger-nails and toe-nails were used. Arthroconidia were inoculated on the ventral surface of the nails. After 6 h, adherence and germination of arthroconidia was observed. By 16 h, small germ tubes with side branches were evident. At about 24 h, micro-colonies had become established. At 48 h, a mycelium had formed, and at about 72 h most of the nail fragment was covered with fungal growth. Nail penetration occurred from the ventral surface through the intercellular spaces, and with longer incubation all three layers were invaded by arthroconidia growing through channels. Nail invasion occurred in the absence of added nutrients. Dermatophyte fungi appeared to invade the nail by a combination of mechanical and chemical factors. The model provides a substrate to study the pharmacokinetics and bioavailability of new antifungal agents in situ.

Humans↗

Evidence that continuous normothermic blood cardioplegia offers better myocardial protection than intermittent hypothermic cardioplegia.

OBJECTIVES: To compare transmyocardial ischaemia and oxidative stress, as well as non-infarction myocardial injury, in patients randomised to intermittent hypothermic cardioplegia or continuous normothermic blood-potassium cardioplegia. DESIGN: Prospective randomised trial. SETTING: Tertiary cardiac referral centre. METHODS: 24 patients undergoing elective coronary artery bypass surgery were randomised to hypothermic (13 patients, mean (SEM) age 59.5 (2.6) years) or normothermic (11 patients, mean (SEM) age 59.7 (3.3) years) cardioplegia. Transmyocardial oxidative stress and ischaemia were assessed by the difference in plasma concentrations of oxidised glutathione and lactate respectively, from samples taken simultaneously from the coronary sinus and aortic root. Blood samples were taken just before cross clamp application and at intervals up to 15 min after cross clamp release. Non-infarction myocardial injury was assessed by measurement of creatine kinase MB isoenzyme activity from peripheral venous blood taken 2 and 18 h after surgery. RESULTS: Intermittent hypothermic cardioplegia resulted in a significant increase in transmyocardial ischaemia (P < 0.001) and oxidative stress (P < 0.001). Evidence of significantly increased myocyte damage was also present (P < 0.01). No significant corresponding changes were present with normothermic cardioplegia. CONCLUSIONS: Normothermic blood cardioplegia seems to avoid significant changes in myocardial ischaemic status and consequent oxidative stress. This study provides direct evidence that normothermic cardioplegia offers enhanced myocardial protection compared with that of hypothermic cardioplegia. Certain subsets of patients may derive more benefit from normothermic cardioplegia, although it is unclear whether this would be the case for all patients.

Cardiopulmonary Bypass↗