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Biomedical subjects

M Desai

Publications and source records attributed to M Desai.

At least 37 records · Page 2Linked to original sources
PubMed2004

Molecular characterisation of an outbreak strain of multiresistant Salmonella enterica serovar Typhimurium DT104 in the UK.

A major national outbreak of multiresistant Salmonella enterica serovar Typhimurium definitive phage type 104 (MR DT104) occurred in England and Wales in the summer of 2000. Isolates of MR DT104 were characterised by antimicrobial resistance type (R-type), pulsed-field gel electrophoresis (PFGE), plasmid profiling and fluorescent amplified fragment length polymorphism (fAFLP) analysis. Results of R-type, PFGE and fAFLP showed that summer 2000 outbreak-associated isolates were indistinguishable from most MR DT104 isolates collected in England and Wales during the 1980s and 1990s. However, outbreak-associated isolates all had an additional 2-MDa plasmid (PP D), and this distinct profile allowed outbreak cases to be distinguished from background MR DT104 infections, thereby facilitating the epidemiological investigation by improving the specificity of the case definition. The study demonstrated the highly clonal nature of MR DT104 and the importance of a hierarchical approach to molecular subtyping for outbreak investigations.

Animals↗
PubMed2004

Cough plate versus cough swab in patients with cystic fibrosis; a pilot study.

BACKGROUND: Accurate identification of lower respiratory tract pathogens is important in the management of cystic fibrosis patients. AIM: To evaluate the cough plate as an alternative method of obtaining respiratory samples for microbiological culture. METHODS AND RESULTS: Using sputum culture as the "gold standard", the cough plate method identified significantly more positive cases than either dry or moistened cough swabs. Of 20 patients who had a positive sputum culture, 16 had a positive culture on cough plate compared to seven positive cultures each on moistened swab and on dry swab respectively. CONCLUSIONS: In this study cough plates were more sensitive than cough swabs in isolating respiratory pathogens in sputum producers. As patients prefer it, the cough plate merits further evaluation, particularly in non-sputum producers.

Adolescent↗
PubMed2004

Normal tension glaucoma is not associated with the common apolipoprotein E gene polymorphisms.

BACKGROUND: /aims: In normal tension glaucoma (NTG) factors other than raised intraocular pressure have a role in the pathogenesis of the optic neuropathy. Because particular apolipoprotein E (ApoE) gene polymorphisms have been associated with cell death and survival in neurological degenerative diseases, the purpose of this study was to determine the ApoE allele frequencies in patients with normal tension glaucoma. METHODS: The apolipoprotein E genotype of 155 patients with normal tension glaucoma was compared to that of 349 non-affected, control subjects from the same geographical area. A similar comparison was made between 53 patients with normal tension glaucoma who demonstrated progressive visual field loss, and control subjects. The frequencies of genotypes was compared with the chi(2) test and Mantel-Haenszel coefficent. RESULTS: There was no significant difference in the frequency of ApoE alleles or genotypes in the normal tension glaucoma population compared to the control group. The ApoE alleles and genotypes in NTG patients with progressive disease were not different from the control group. CONCLUSION: ApoE gene polymorphisms are not linked to normal tension glaucoma, suggesting that this gene does not have a role in the pathogenesis of optic neuropathy in this disease.

Adult↗
PubMed2004

Attitudes to self-sampling for HPV among Indian, Pakistani, African-Caribbean and white British women in Manchester, UK.

OBJECTIVE: To examine attitudes to self-sampling for human papillomavirus (HPV) testing among women from contrasting ethnic groups. SETTING: Manchester, UK. METHODS: Two hundred women of Indian, Pakistani, African-Caribbean and white British origin were recruited from social and community groups to participate in a questionnaire survey. The questionnaire included items on attitudes to self-sampling and intention to use the test. RESULTS: Willingness to try to use the test was high, and women did not foresee religious or cultural barriers to self-sampling; however, a large proportion of women were concerned about doing the test properly. This concern was greatest in the Indian and African-Caribbean groups. CONCLUSIONS: Although women's willingness to try self-sampling for HPV is encouraging, worries about carrying out the procedure correctly must be addressed if women are to feel confident about the results of self-sampling methods and reassured by a negative result.

Adult↗
PubMed2004

Carcinomatous meningitis mimicking Creutzfeldt-Jakob disease.

We report a case of carcinomatous meningitis diagnosed at autopsy that was clinically diagnosed as a case of Creutzfeldt-Jakob disease (CJD) because of rapidly evolving dementia. Pathological study revealed diffusely spreading carcinomatous meningitis, infiltrating into cortex along Virchow Robin space. Immunostaining for Prion protein was negative. Despite advances in clinical diagnosis, tissue diagnosis remains a pre-requisite for confirmation of CJD.

Creutzfeldt-Jakob Syndrome↗
PubMed2003

Management of women who test positive for high-risk types of human papillomavirus: the HART study.

BACKGROUND: Certain types of human papillomavirus (HPV) are the primary cause of almost all cervical cancers. HPV testing of cervical smears is more sensitive but less specific than cytology for detecting high-grade cervical intraepithelial neoplasia (CIN2+). HPV testing as a primary screening approach requires efficient management of HPV-positive women with negative or borderline cytology. We aimed to compare the detection rate and positive predictive values of HPV assay with cytology and to determine the best management strategy for HPV-positive women. METHODS: We did a multicentre screening study of 11085 women aged 30-60 years. Women with borderline cytology and women positive for high-risk HPV with negative cytology were randomised to immediate colposcopy or to surveillance by repeat HPV testing, cytology, and colposcopy at 12 months. FINDINGS: HPV testing was more sensitive than borderline or worse cytology (97.1% vs 76.6%, p=0.002) but less specific (93.3% vs 95.8%, p<0.0001) for detecting CIN2+. Of 825 randomised women, surveillance at 12 months was as effective as immediate colposcopy. In women positive for HPV at baseline, who had surveillance, 73 (45%) of 164 women with negative cytology and eight (35%) of 23 women with borderline cytology were HPV negative at 6-12 months. No CIN2+ was found in these women, nor in women with an initial negative HPV test with borderline (n=211) or mild (32) cytology. INTERPRETATION: HPV testing could be used for primary screening in women older than 30 years, with cytology used to triage HPV-positive women. HPV-positive women with normal or borderline cytology (about 6% of screened women) could be managed by repeat testing after 12 months. This approach could potentially improve detection rates of CIN2+ without increasing the colposcopy referral rate.

Adult↗
PubMed2003

Attitudes towards HPV testing: a qualitative study of beliefs among Indian, Pakistani, African-Caribbean and white British women in the UK.

This study examined attitudes to human papillomavirus (HPV) testing among a purposively selected sample of women from four ethnic groups: white British, African Caribbean, Pakistani and Indian. The design was qualitative, using focus group discussion to elicit women's attitudes towards HPV testing in the context of cervical cancer prevention. The findings indicate that although some women welcomed the possible introduction of HPV testing, they were not fully aware of the sexually transmitted nature of cervical cancer and expressed anxiety, confusion and stigma about HPV as a sexually transmitted infection. The term 'wart virus', often used by medical professionals to describe high-risk HPV to women, appeared to exacerbate stigma and confusion. Testing positive for HPV raised concerns about women's sexual relationships in terms of trust, fidelity, blame and protection, particularly for women in long-term monogamous relationships. Participation in HPV testing also had the potential to communicate messages of distrust, infidelity and promiscuity to women's partners, family and community. Concern about the current lack of available information about HPV was clearly expressed and public education about HPV was seen as necessary for the whole community, not only women. The management of HPV within cervical screening raises important questions about informed participation. Our findings suggest that HPV testing has the potential to cause psychosocial harm to women and their partners and families.

Adult↗
PubMed2003

Apolipoprotein E genotype, islet amyloid deposition and severity of Type 2 diabetes.

Islet amyloid is found in 90% of patients with Type 2 (non-insulin-dependent) diabetes at post-mortem. More extensive amyloidosis is associated with decreased islet function and requirement for insulin therapy. Severity of cerebral amyloidosis in Alzheimer's disease (AD) is increased in subjects with the apolipoprotein E (ApoE) epsilon 4 allele. To determine if ApoE genotype was associated with severity of islet amyloidosis and diabetes, samples were genotyped from 32 specimens of post-mortem pancreas and from patients classified by disease progression. DNA was extracted from blood samples from Caucasian patients diagnosed with Type 2 diabetes, at age >40 years, classified according to disease progression: group 1 on oral therapy for at least 10 years from diagnosis, (n=147) and group 2, requiring insulin within 6 years from diagnosis, (n=187). ApoE genotype was determined by restriction-fragment length polymorphism analysis. DNA in pancreatic extracts (23 diabetic; 9 non-diabetic subjects) showed no association of ApoE polymorphisms with either degree of islet amyloidosis or disease severity. The distributions of ApoE epsilon 2, epsilon 3 and epsilon 4 were similar in both clinical patient groups and in the non-diabetic group and unrelated to progression of disease. It is unlikely that the common polymorphisms for the ApoE gene are linked to amyloid formation or progression of islet dysfunction in Type 2 diabetes.

Adult↗
PubMed2003

Pharmacokinetics and QT interval pharmacodynamics of oral haloperidol in poor and extensive metabolizers of CYP2D6.

We studied the pharmacokinetics and QT interval pharmacodynamics of a single 10 mg dose of oral haloperidol in a randomized, double-blind, placebo-controlled, crossover trial of healthy poor (PMs) and extensive (EMs) metabolizers of CYP2D6. There was a statistically significant greater mean QT(c) on haloperidol (421.6+/-20.1 ms) than on placebo (408.4+/-18.5 ms, P=0.0053) occurring 10 h post haloperidol/placebo administration. Men and women had similar ranges of QT(c) changes from placebo. Despite a statistically significant greater mean elimination half-life (19.1+/-3.6 vs 12.9+/-4.0 h, P=0.04) and lower mean apparent oral clearance (12.8+/-4.1 vs 27.0+/-11.3 ml/min/kg, P=0.02) of haloperidol in CYP2D6 PMs than in EMs, this exposure change did not translate into marked QT(c) changes from baseline that could be considered clinically important. Although the magnitude of the mean QT(c) prolongation on haloperidol relative to placebo is relatively small, it may assume significance in the presence of other risk factors for QT prolongation.

Adult↗
PubMed2003

Reversal of pregnancy-mediated plasma hypotonicity in the near-term rat.

OBJECTIVE: Maternal plasma hypotonicity occurs early in rat and human pregnancy with resetting of the plasma osmolality threshold for vasopressin secretion and thirst. In humans, amniotic fluid volume reaches maximum levels in the mid-third trimester and decreases thereafter. We hypothesized that a reversal of maternal plasma hypotonicity occurs near term, contributing to reduced fetal and amniotic fluid water content. METHODS: Maternal plasma and amniotic fluid osmolality and sodium levels, including amniotic fluid volume, were measured at 16, 18 and 20 days of rat gestation. Additionally, maternal and fetal brains were analyzed for water and electrolyte content. Non-pregnant adult female rats represented controls. RESULTS: Compared to non-pregnant adults, 16-day and 18-day pregnant rats had significantly lower plasma osmolality (301.0 +/- 2.3 vs. 295.4 +/- 2.8 and 289.7 +/- 3.3 mOsm/kg, respectively) and sodium levels (140.3 +/- 1.0 vs. 135.7 +/- 0.8 and 133.4 +/- 1.4 mEq/l, respectively). Conversely, 20-day pregnant rats showed no significant difference in plasma osmolality (298.4 +/- 3.1 mOsm/kg) or sodium levels (137.6 +/- 1.0 mEq/l) from non-pregnant adults. With advancing gestation, the amniotic fluid volume decreased whereas the osmolality and sodium levels increased significantly. Maternal brain water content was significantly higher in 16-day and 18-day pregnant rats compared to control rats (78.7 +/- 0.1 and 78.1 +/- 0.2 vs. 76.9 +/- 0.2% wet weight) and returned to non-pregnant values in the 20-day pregnant rats (76.6 +/- 0.2%). In association with the maternal changes, fetal brain water and electrolyte content significantly decreased from 16-day to 18-day to 20-day fetuses. CONCLUSION: These findings indicate a reversal of maternal plasma hypotonicity and reduced maternal brain water content in the near-term pregnant rat. We speculate that relative maternal plasma hypertonicity near term may contribute to reduced amniotic fluid volume.

Amniotic Fluid↗
PubMed2002

Human calcium/calmodulin-dependent protein kinase II gamma gene (CAMK2G): cloning, genomic structure and detection of variants in subjects with type II diabetes.

AIMS/HYPOTHESIS: Ca(2+)/calmodulin-dependent protein kinase II, is expressed in the pancreatic beta cells and is activated by glucose and other secretagogues in a manner correlating with insulin secretion. The activation of Ca(2+)/calmodulin-dependent protein kinase II mediates some of the actions of Ca(2+) on the exocytosis of insulin. We therefore investigated the gene encoding the gamma isoform ( CAMK2G) which has been shown to be expressed in human beta cells as a candidate gene for Type II (non-insulin-dependent) diabetes mellitus. METHODS: Human CAMK2G was cloned from a total human P1 artificial chromosome library using a partial Ca(2+)/calmodulin-dependent protein kinase gamma(E) cDNA probe. Positive PAC clones were localised to chromosome 10q22 by fluorescence in situ hybridisation. To obtain structural information and the sequences of the exon-intron boundaries, the published genomic structures of the rat and mouse genes allowed the putative exon-intron boundaries of human CAMK2G to be amplified by vectorette polymerase chain reaction and sequenced. Sequence variants in each exon were identified using single stranded conformational polymorphism analysis. RESULTS: The human CAMK2G gene comprises 22 exons which range in size between 43 to 230 bp. Screening of the exons and exon-intron boundaries identified two single nucleotide polymorphisms. These did not show association with diabetes in 122 patients and 144 control subjects. CONCLUSIONS/INTERPRETATION: We have identified the genomic structure of CAMK2G to enable further study of this potential candidate gene. Variation in this gene is not strongly associated with diabetes in Caucasians in the United Kingdom. We have identified two single nucleotide polymorphisms which, with appropriately large case control studies, can be used to assess the role of CAMK2G in the susceptibility to Type II diabetes.

Alleles↗
PubMed2002

Creon 10,000 Minimicrospheres vs. Creon 8,000 microspheres--an open randomised crossover preference study.

Creon 10,000 Minimicrospherestrade mark (Creon) 10,000 MMS) is a pancreatic enzyme formulation that contains smaller spheres of pancreatin in a 50% smaller capsule than conventional microspheres (Creon) 8,000). This three-centre study investigated the preference of cystic fibrosis (CF) patients for these products. In one centre, 72 h stool fat excretion and coefficient of fat absorption (CFA) were also compared. Fifty-nine patients with a mean age 10 years (range 3-17) took Creon 8,000 ms for 14 days and were then randomised to 28 days of Creon 8,000 ms followed by 28 days of Creon 10,000 MMS, or vice versa. Dosing was lipase for lipase according to the labelled declaration. At the end of the second treatment period, 51 of 54 patients who completed the study expressed a preference, with a statistically significant preference in favour of Creon 10,000 MMS (47/51; 87%) vs. Creon 8,000 ms (4/51; 7.4%; P<0.0001). Stool fat (g/day) and CFA (%) were measured in 24 patients at the end of each treatment period: the products were therapeutically equivalent (Creon 10,000: 8.4 g/day, 91.3% CFA; Creon 8,000: 6.7 g/day, 93.5% CFA). Both products were well tolerated. In conclusion, in CF children we found a clear preference for Creon 10,000 MMS compared with Creon 8,000 ms with no difference in fat absorption between the two products. Creon 10,000s smaller capsules are easier to take and should aid patient compliance.

Administration, Oral↗
PubMed2001

The relationship between hemodynamics and inflammatory activation in women at risk for preeclampsia.

OBJECTIVE: This study evaluated: 1) whether women with risk factors for preeclampsia had a hyperdynamic circulation and increased markers of endothelial and inflammatory activation; and 2) whether hemodynamically directed therapy was associated with a change in markers. METHODS: A controlled experimental study was performed for two groups: 1) women at risk for preeclampsia (high risk); and 2) women at low risk (controls). Tumor necrosis factor-alpha (TNF-alpha), TNF-alpha receptors 1 and 2, vascular cell adhesion molecule-1, cellular fibronectin, and cardiac output were measured at or before 24 weeks' gestation and at 6-8 week intervals. High-risk subjects with cardiac output greater than 7.4 L/minute were treated with atenolol. Atenolol therapy was not randomized. Therefore, the longitudinal data were descriptive. Data were analyzed by the t test, Wilcoxon rank sum test, chi(2) test, multivariable linear regression, and the standard two-stage test. RESULTS: There were 46 high-risk subjects and 25 controls. Maternal age, gestational age, and parity did not differ between the groups. Cardiac output (P <.001) and vascular cell adhesion molecule-1 (P =.02) at baseline were significantly increased in the high-risk group. A total of 42 women in the high-risk group received atenolol for high cardiac output. There was a slower rise in TNF-alpha receptor 1 in the treated group compared with the controls (P <.001). CONCLUSION: Women with risk factors for preeclampsia had a hyperdynamic circulation and endothelial activation. Hemodynamically directed therapy in women at risk was associated with a slower rise in TNF-alpha receptor 1 compared with low-risk women who were not treated, suggesting a relationship between hemodynamics and inflammatory activation.

Adult↗
PubMed2001

Cultural influences on the prevalence of common mental disorder, general practitioners' assessments and help-seeking among Punjabi and English people visiting their general practitioner.

BACKGROUND: Culture influences symptom presentation and help-seeking and may influence the general practitioner's assessment. METHODS: We recruited Punjabi and English GP attenders to a two-phase survey in London (UK) using the Amritsar Depression Inventory and the General Health Questionnaire as screening instruments. The Clinical Interview Schedule was the criterion measure. General practitioners completed Likert assessments. RESULTS: The second phase was completed by 209 Punjabi and 180 English subjects. The prevalence of common mental disorders was not influenced by culture. Punjabi cases more often had 'poor concentration and memory' and 'depressive ideas' but were not more likely to have somatic symptoms. General practitioners were more likely to assess Punjabis with common mental disorder as having 'physical and somatic' symptoms or 'sub-clinical disorders'. Punjabi cases with depressive ideas were less likely to be detected compared with English ones. In comparison to English men, English women were under-detected by Asian general practitioners. Help-seeking English subjects were more likely to be correctly identified as cases. CONCLUSIONS: The prevalence of common mental disorders and somatic symptoms does not differ across cultures. Among English subjects, general practitioners were more likely to identify correctly pure psychiatric illness and mixed pathology; but Punjabi subjects with common mental disorders were more often assessed as having 'sub-clinical disorders' and 'physical and somatic' disorders. English women were less well detected than English men. English help-seeking cases were more likely to be detected.

Adolescent↗
PubMed2001

In vivo target promoter-binding activities of a xenobiotic stress-activated TGA factor.

Xenobiotic chemicals induce the expression of nuclear detoxification genes. A full understanding of this protective response will require characterization of its transcriptional regulatory machinery. We describe here the use of a recently developed plant chromatin immunoprecipitation (ChIP) assay to define nuclear promoter targets of TGA1a, a tobacco basic/leucine zipper transcription factor whose activity is potentiated by herbicide-induced xenobiotic stress. TGA1a selectively binds as-1-type cis-elements, which regulate transcription of putative detoxification and defense genes. With ChIP, we show that endogenous TGA1a binds as-1-containing promoter sequences of two tobacco glutathione S-transferase genes, GNT1 and GNT35. This binding activity is strongly enhanced by xenobiotic stress, as is expression of these genes. In contrast, TGA1a apparently does not bind in vivo to functional as-1 elements in promoters of PR-1a and PG13, genes whose expression is insensitive to this stimulus. The findings here thus discriminate between a number of possible functional promoter binding sites for a trans-regulatory factor, within the context of a signal response pathway.

Antibodies↗
PubMed2001

Unusual causes of hemifacial spasm.

Hemifacial spasm (HFS) has been defined as consisting of brief clonic jerking movements of the facial musculature, beginning in the orbicularis oculi with downward spreading to other facial muscles. HFS, perhaps the most common of the abnormal involuntary facial movements, has been classically ascribed to vascular loop compression at the root exit zone of the facial nerve. Causes other than such vascular loops are rare in the medical literature. Here we present three case studies in which the phenomenology of the HFS was atypical in onset and evolution. Using these three patients as introduction to the topic, we reviewed the literature of all cases of HFS with causes other than the vascular loop. In these three cases, HFS was caused by (1) a parotid gland tumor, (2) a cerebellopontine angle meningioma, and (3) an acoustic schwannoma. We also discuss the radiological findings as well as possible differences in the genesis of HFS and phenomenology in such cases and present recommendations on how to evaluate these patients.

Adenocarcinoma↗
PubMed2001

Association of hyperglycemia with increased mortality after severe burn injury.

BACKGROUND: Hyperglycemia is commonly associated with the hypermetabolic stress response. However, persistent hyperglycemia may adversely affect wound healing and immunity. The purpose of this study was to assess any relationship between hyperglycemia and clinical outcome after severe burn injury. METHODS: Survey of the medical records from January 1996 to July 1999 identified 58 pediatric patients with burns > or = 60% body surface. Patients were categorized as having poor glucose control (n = 33) if > or = 40% of all plasma glucose determinations were > or = 7.8 mmol/L (140 mg/dL) and compared with patients deemed to have adequate glucose control (n = 25) in whom > or = 40% of all glucose values were > or = 7.8 mmol/L. RESULTS: Despite similar age, burn size, caloric intake, and frequency of wound infection, patients categorized with poor glucose control had a significantly greater incidence of positive blood cultures (positive blood cultures/length of stay days, 0.42 +/- 0.04 for hyperglycemia patients vs. 0.30 +/- 0.03 for normoglycemia patients; mean +/- SEM, p > or = 0.05). This finding was especially prominent for blood cultures positive for yeast. Hyperglycemia patients had significantly less percentage of skin graft take than did the normoglycemic patients (percent take/operative procedure, 64 +/- 9 for hyperglycemia patients vs. 88 +/- 5 for normoglycemia patients; p < 0.05). Nine patients (27%) with persistent hyperglycemia died compared with only one death (4%) in patients with adequate glucose control (p > or = 0.05). CONCLUSION: This association between poor glucose control, bacteremia/fungemia, reduced skin graft take, and subsequent mortality in severely burned children may be related to a hyperglycemia-induced detriment in antimicrobial defense. Although this report fails to establish cause and effect, these findings suggest that aggressive maneuvers to normalize plasma glucose in critically injured patients may be warranted.

Bacteremia↗