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M Desai

Publications and source records attributed to M Desai.

At least 55 records · Page 3Linked to original sources

Effects of ethnicity on the distribution of clinically relevant endothelial nitric oxide variants.

Polymorphisms in the endothelial nitric oxide synthase (eNOS) gene have been associated inconsistently with cardiovascular diseases. A maldistribution of eNOS variants among ethnic groups may explain interethnic differences in nitric oxide (NO)-mediated vasodilation and response to drugs. To test this possibility, we examined the distribution of genetic variants of three clinically relevant eNOS polymorphisms (T-786C in the promoter, the variable number of tandem repeats (VNTR) in intron 4, and the Glu298Asp variant in exon 7) in 305 ethnically well-characterized DNA samples (100 Caucasians, 100 African-Americans, and 105 Asians). We estimated the haplotype frequency, and evaluated associations between these variants. The Asp298 variant was more common in Caucasians (34.5%) than in African-Americans (15.5%) or Asians (8.6%)(P < 0.0001). The C-786 variant was also more common in Caucasians (42.0%) than in African-Americans (17.5%) or Asians (13.8%) (P < 0.0001). The 4a variant in intron 4 was more common in African-Americans (26.5%) than in Caucasians (16.0%) or Asians (12.9%) (P < 0.0001). The most common predicted haplotype in the three groups combined only wild-type variants. Asians had the highest frequency of this haplotype (77% in Asians v. 46% in the other groups). In Caucasians, the Asp298 and C-786variants were associated, and this haplotype was predicted to have a frequency of 24%. In African-Americans, the second most common haplotype included the variant 4a and wild-type variants; the Asp298 and 4a variants were associated negatively in this group. The C-786 and 4a variants were associated in Asians (P < 0.0001). The marked interethnic differences that we found in the distribution of eNOS variants, in the estimated haplotype frequency, and in the association between variants may help us to understand how the combination of these genetic variants may influence cardiovascular diseases.

Alleles↗

A study of the dental treatment needs of children with disabilities in Melbourne, Australia.

A selected population of children with disabilities in Melbourne, Australia, was studied with reference to their oral disease and treatment needs. A total of 300 children (aged 9-13 years), 150 attending special developmental schools (SDS) and 150 attending special schools (SS), received an oral examination and the parent/guardian completed a questionnaire. Six levels of function were defined, based on the child's independence for five self-care activities (brushing teeth, feeding self, dressing self, walking and performing toilet). The caries experience of children in the SS was lower than in SDS (d + D: 1.3 +/- 1.6 versus 1.5 +/- 2.4; dmft + DMFT: 2.0 +/- 2.3 versus 2.5 +/- 3.1); those attending SDS had higher unmet preventive and restorative needs. Significant associations were seen between the number of decayed teeth, the dmft + DMFT index, and the level of function (p < 0.005). Periodontal disease was prevalent; significant associations were seen between periodontal status, the need for periodontal therapy, and the level of function (p < 0.005). Assessment of the level of function by staff could assist in triaging individuals for urgent dental examination. Despite 41 per cent of children requiring simple treatment, the preventive and treatment needs of many remained unmet. Following examination, diagnosis and treatment planning by a dentist, much of the preventive, simple treatment and oral health promotion could be performed by trained dental auxiliaries. An epidemiological survey followed by the implementation and evaluation of a long-range public dental health care plan for children and adolescents with disabilities is needed urgently.

Adolescent↗

Fluorescent amplified-fragment length polymorphism subtyping of the Salmonella enterica serovar enteritidis phage type 4 clone complex.

Fluorescent amplified-fragment length polymorphism (FAFLP) analysis, a high-resolution PCR-based genome fingerprinting method, was used to subtype Salmonella enterica serovar Enteritidis phage type 4. This single phage type is responsible for the majority of salmonellosis in Europe. Twenty strains isolated from nine outbreaks, five isolates from sporadic cases of human infection, four strains of poultry origin, and one laboratory-derived strain were comparatively studied by pulsed-field gel electrophoresis (PFGE) and FAFLP analysis. Following macrorestriction with XbaI, PFGE classified 73% of PT4 strains as a single type. FAFLP analysis was carried out with the primer pair EcoRI+0 and MseI+C, by simultaneously sampling 170 to 190 loci throughout the PT4 genome. Twenty-three FAFLP profiles, with 1 to 61 amplified-fragment differences, were found among the 30 strains. The index of discriminatory power of FAFLP analysis was 0.98, compared to 0.47 for PFGE. FAFLP analysis assigned genotypes to each PT4 outbreak, as well as sporadic PT4 infections, a significant development for the epidemiology and control of this zoonotic enteric pathogen.

Animals↗

Genome sequence-based fluorescent amplified fragment length polymorphism of Campylobacter jejuni, its relationship to serotyping, and its implications for epidemiological analysis.

The published genome sequence of Campylobacter jejuni strain NCTC 11168 was used to model an accurate and highly reproducible fluorescent amplified fragment length polymorphism (FAFLP) analysis. Predicted and experimentally observed amplified fragments (AFs) generated with the primer pair HindIII+A and HhaI+A were compared. All but one of the 61 predicted AFs were reproducibly detected, and no unpredicted fragments were amplified. This FAFLP analysis was used to genotype 74 C. jejuni strains belonging to the nine heat-stable (HS) serotypes most prevalent in human disease in England and Wales. The 74 C. jejuni strains exhibited 60 FAFLP profiles, and cluster analysis of them yielded a radial tree showing genetic relationships between and within 13 major clusters. Some clusters were related, and others were unrelated, to a single HS serotype. For example, all strains belonging to serotypes HS6 and HS19 grouped into corresponding single genotypic clusters, while strains of serotypes HS11 and HS18 each grouped into two genotypic clusters. Strains of HS50, the most prevalent serotype infecting humans, were found both in one large (multiserotype) cluster complex and dispersed throughout the tree. The strain genotypes within each FAFLP cluster were characterized by a particular combination of AFs, and among the cluster there were additional differential AFs. Identification of such AFs could act as a search tool to look for potential associations with disease or animal hosts, when applied to large number of human isolates. Genome-sequence based FAFLP, thus, has the potential to establish a genetic database for epidemiological investigations of Campylobacter.

Animals↗

Laparoscopic cross-trigonal Cohen ureteroneocystostomy: novel technique.

PURPOSE: We describe a novel technique of laparoscopic transvesical cross-trigonal Cohen anti-reflux ureteroneocystostomy. MATERIALS AND METHODS: A 10, an 11 and a 32-year-old patient with symptomatic unilateral vesicoureteral reflux underwent laparoscopic cross-trigonal ureteral reimplantation. Two 5 mm. balloon tip ports were suprapubically inserted into the bladder. Using a transurethral resectoscope with a Collins knife a 4 to 5 cm. cross-trigonal submucosal trough was created from the refluxing ureteral orifice to the contralateral side of the bladder. The refluxing ureteral orifice and intramural ureter were completely mobilized intravesically, advanced transtrigonally and secured to the detrusor muscle at the apex of the trough with 3 deep interrupted sutures. The elevated mucosal flaps of the trough were suture approximated over the ureter to create a submucosal tunnel. All suturing was performed by freehand laparoscopic technique. RESULTS: Operative time was between 2.5 and 4.5 hours and blood loss was 10 to 50 cc. Adequate submucosal trough creation, ureteral extravesical mobilization and intravesical advancement, and bladder mucosal flap reapproximation were done to create a submucosal tunnel in all cases. Satisfactory transtrigonal anchoring of the neoureteral orifice to the detrusor muscle and mucosa was achieved with 3 stitches. Hospital stay was 2, 2 and 1 days in the 3 cases, and the Foley catheter remained in place for 3, 1 and 1 week, respectively. At 6 months reflux had resolved in 2 patients, while in 1 grade II reflux persisted, which was improved from grade IV preoperatively. All patients have remained infection-free without antibiotics. CONCLUSIONS: Laparoscopic transvesical cross-trigonal antireflux ureteral reimplantation is technically feasible. Intravesical laparoscopic suturing is possible. Potential advantages include a decreased hospital stay, decreased narcotic requirement and better cosmesis. Further experience is necessary to refine the technical nuances and evaluate outcomes compared to the open technique.

Adult↗

The decomposition of peroxynitrite to nitroxyl anion (NO-) and singlet oxygen in aqueous solution.

The mechanism of decomposition of peroxynitrite (OONO(-)) in aqueous sodium phosphate buffer solution at neutral pH was investigated. The OONO(-) was synthesized by directly reacting nitric oxide with superoxide anion at pH 13. The hypothesis was explored that OONO(-), after protonation at pH 7.0 to HOONO, decomposes into (1)O(2) and HNO according to a spin-conserved unimolecular mechanism. Small aliquots of the concentrated alkaline OONO(-) solution were added to a buffer solution (final pH 7.0-7.2), and the formation of (1)O(2) and NO(-) in high yields was observed. The (1)O(2) generated was trapped as the transannular peroxide (DPAO(2)) of 9, 10-diphenylanthracene (DPA) dissolved in carbon tetrachloride. The nitroxyl anion (NO-) formed from HNO (pKa 4.5) was trapped as nitrosylhemoglobin (HbNO) in an aqueous methemoglobin (MetHb) solution. In the presence of 25 mM sodium bicarbonate, which is known to accelerate the rate of decomposition of OONO(-), the amount of singlet oxygen trapped was reduced by a factor of approximately 2 whereas the yield of trapping of NO(-) by methemoglobin remained unaffected. Because NO(3)(-) is known to be the ultimate decomposition product of OONO(-), these results suggest that the nitrate anion is not formed by a direct isomerization of OONO(-), but by an indirect route originating from NO(-).

Animals↗

A xenobiotic-stress-activated transcription factor and its cognate target genes are preferentially expressed in root tip meristems.

In plants, as-1-type cis elements and their trans-acting factors confer tissue-specific and signal-responsive activities to the promoters of several glutathione S-transferase (GST) genes. Regulation of as-1 is widely thought to involve trans-acting factors that belong to a family of basic/leucine-zipper 'TGA factors' that selectively bind this element. We have previously shown that TGA 1a, a highly conserved TGA factor of tobacco, enhances transcription through as-1 in response to xenobiotic-stress cues. To better understand the functional contribution of this transcription factor to the expression of as-1-regulated genes, we have studied its tissue- and cell-specific localization in tobacco seedlings. We show here that the relative amount of TGA1a transcripts expressed in roots and shoots correlate with the as-1-regulated, basal-level expression of a GUS transgene and two putative target GST genes. In situ hybridization of intact seedlings demonstrated that TGA1a and these GST genes are preferentially expressed in root tip meristems. Similar findings were made with a gene-specific probe for PG13, a homologue of TGA1a, demonstrating that both factors are likely to be present in the same root meristem cells. Furthermore, TGA1a protein was immunologically detected exclusively in the primary root and its meristem. Collectively, these studies suggest that TGA1a, and perhaps PG13, may contribute to the expression of GST isoenzymes, especially in root tip meristems. The biological significance of these observations is discussed.

Basic-Leucine Zipper Transcription Factors↗

Sexual behaviour and smoking as determinants of cervical HPV infection and of CIN3 among those infected: a case-control study nested within the Manchester cohort.

To distinguish risk factors for acquisition of cervical human papillomavirus (HPV) infection from the determinants of neoplasia among infected individuals we have conducted a three-arm case-control study nested within a large population-based cohort of women (the Manchester cohort) screened for HPV at entry using L1 consensus primer PCR. The study includes 181 HPV-positive controls who did not develop high-grade cervical intraepithelial neoplasia (CIN3) during follow-up, 203 HPV-negative controls, and 199 HPV-positive cases with histologically confirmed CIN3. Detailed information on sexual, reproductive and gynaecological history, oral contraceptive use and smoking was obtained at face-to-face interview. There was a striking division between risk factors for infection and those predictive of disease. Comparing the HPV-positive against the HPV-negative controls, the only risk factors for infection were number of sexual partners (OR for six or more = 3.89; 95% Cl = 1.99-7.62), a relatively recent new sexual relationship (OR for a new partner within the previous 2 years = 4.17; 95% Cl = 2.13-8.33), and a history of previous miscarriage (OR = 2.59; 95% Cl = 1.28-5.21). The determinants of CIN3 among infected women were, in contrast, early age at first intercourse (OR for 16 years old or less = 3.23; 95% Cl = 1.33-7.69), a long time since starting a new sexual relationship (OR for 6 years or more = 4.94; 95% Cl = 2.51-9.71), and cigarette smoking, with strong evidence for a dose- response (OR for current smoking habit 20+ per day = 2.57; 95% Cl = 1.49-4.45). Oral contraceptive use was not significantly associated with either HPV infection or CIN3.

Adult↗

Outbreak of vancomycin-resistant enterococci in a burn unit.

OBJECTIVE: To investigate and control an outbreak of colonization and infection caused by vancomycin-resistant enterococci (VRE) in a burn intensive care unit (BICU). DESIGN: Epidemiological investigation, including multiple point-prevalence culture surveys of patients and environment, cultures from hands of healthcare workers (HCWs), pulsed-field gel electrophoresis (PFGE) typing of patient and environmental isolates, case-control study, and institution and monitoring of control measures. SETTING: BICU in an 800-bed university medical center in Galveston, Texas. RESULTS: Between June 6, 1996, and July 14, 1997, 21 patients were colonized by VRE, and 4 of these patients developed bacteremia. Of 2,844 environmental cultures, 338 (11.9%) were positive, but all hand cultures from HCWs were negative. PFGE typing indicated that the outbreak was clonal, with VRE isolates from patients differing by < or =4 bands from the index case. Thirteen of 14 environmental isolates varied by < or =4 bands from the pattern of the index case. A case-control study analyzed by exact logistic regression identified diarrhea (odds ratio [OR], 43.9; 95% confidence interval [CI95], 5.5-infinity; P=.0001) and administration of an antacid (OR, 24.2; CI95, 2.9-infinity; P=.002) as independent risk factors for acquisition of VRE. During a 5-week period in October and November 1996, all patient and 317 environmental cultures were negative for VRE. The outbreak recurred from a contaminated electrocardiogram lead that had not been identified during the prior 5 weeks. VRE were finally eradicated from the BICU in July 1997, using barrier isolation and a very aggressive environmental decontamination program. CONCLUSIONS: A VRE outbreak in a BICU over 13 months was caused by a single clone. After apparent eradication of VRE from a BICU, recrudescence of the outbreak occurred, evidently from a small inapparent source of environmental contamination. Changes in gastrointestinal (GI) tract function (motility) and administration of medications, other than antibiotics, that have an effect on the GI tract may increase the risk of GI tract colonization by VRE in burn patients. Application of barrier isolation and an aggressive environmental decontamination program can eradicate VRE from a burn population.

Adult↗

Influence of glucose kinetics on plasma lactate concentration and energy expenditure in severely burned patients.

BACKGROUND: In critically ill patients, elevation in the plasma lactate concentration has traditionally been interpreted as indicating a deficiency in oxygen availability and is often an impetus to increase oxygen delivery clinically. However, another possible basis for increased lactate concentrations may be simply a mass effect from increased pyruvate availability (i.e., accelerated glycolysis). METHODS: In six hypermetabolic burned patients, the rates of glucose production and oxidation were quantified using a tracer infusion of 6,6 d2 glucose combined with indirect calorimetry. Measurements were obtained after a 9-hour fast and after a 3-hour infusion of unlabeled glucose at 30 micromol/kg/min. No patient was overtly septic, hypoxic, or hypovolemic. RESULTS: The infusion of glucose significantly increased the arterial glucose concentration and rate of glucose oxidation, with a corresponding increase in the arterial plasma concentration of lactate and pyruvate. Resting energy expenditure and oxygen consumption were not affected by the infusion of glucose. CONCLUSIONS: These findings show that elevations in plasma lactate in severely injured patients may, in part, be related to increases in glucose flux and not entirely a reflection of any deficit in oxygen availability. Such findings highlight a potential pitfall for interpreting plasma lactate concentrations as an index of tissue oxygen availability in hypermetabolic patients.

Adult↗

Evaluating the role of botulinum toxin in the management of focal hypertonia in adults.

OBJECTIVES: To investigate the effects of EMG guided botulinum toxin (BTX-A) on impairment and focal disability in adults presenting with focal hypertonia. METHODS: A prospective, randomised, double blind, placebo controlled, parallel group trial was carried out with standardised assessment before and at 3 week intervals until 12 weeks after injection, in patients with focal hypertonia affecting upper or lower limbs. Botulinum toxin or placebo was injected with EMG guidance after multidisciplinary assessment. The modified Ashworth scale of spasticity, percentage passive range of joint motion, subjective rating of problem severity, the Rivermead motor assessment scale, a timed 10 metre walk (lower limb patients), nine hole peg test (upper limb patients), and a modified goal attainment scale were used as outcome measures. The patients were 52 adults; 34 male, 18 female; mean age 40.31, range 16-79 years; mean duration of symptoms 35 months (range 3 months to 22 years). Diagnoses included cerebrovascular accidents (23), head injury (12), incomplete spinal cord injury (six), tumour (five), cerebral palsy (three), and anoxic episodes (three). RESULTS: For each variable an overall score for the treatment period was computed by summing the scores from the 3, 6, 9, and 12 week assessments. These overall scores were significantly better in the treated group for the Ashworth scale, percentage passive range of movement, Rivermead lower limb, and subjective rating of problem severity. The significant treatment effect on the Ashworth scale was seen on analysis of variance (ANOVA) at 3 weeks and the subjective rating of problem severity at 3 and 6 weeks. The goal attainment scale score in both groups was similar at 12 weeks. CONCLUSION: Selective use of botulinum toxin to weaken muscles can lead to a reduction in resistance to passive movement about a distal limb joint. This allows for improvements in passive range of movement and focal disability, particularly in patients presenting with focal spasticity of the lower limb.

Adolescent↗

Impact of noninvasive imaging on increased incidental detection of renal cell carcinoma.

OBJECTIVE: To determine the impact of non-invasive imaging, specifically ultrasound imaging and computed tomography, on the incidental detection of renal cell carcinoma during two consecutive time periods, one prior and one subsequent to the acquisition of imaging equipment. METHODS: All located patient charts (83% of 207) of renal cell carcinoma cases (n = 172) were reviewed, and categorized by presentation method as 'incidental' or 'nonincidental' cases, based on defined criteria. Clinical information was recorded, cases were staged, and survival estimates were calculated. RESULTS: More than a third of the 172 cases were categorized as incidentally detected, most of which (82.5%) were detected during the latter time period. Either ultrasound or CT imaging was credited with detecting over 80% of the incidentally detected tumors. CONCLUSION: Ultrasound and CT imaging have contributed to the incidental detection of renal cell carcinomas during the two time periods. Stage significantly predicted survival (p<0.001) in a Cox proportional hazard model that also controlled for presentation, sex, and age.

Carcinoma, Renal Cell↗

Uneventful use of tirofiban as an adjunct to coronary stenting in a patient with a history of abciximab-associated thrombocytopenia 10 months earlier.

A 52-year-old male undergoing a percutaneous coronary intervention after an inferior infarction treated with thrombolytic therapy was given abciximab with development of early severe reversible thrombocytopenia (platelet count nadir of 50,000 per mm3). The same patient underwent another percutaneous coronary intervention 10 months later and was given tirofiban without development of thrombocytopenia. This observation suggests that the development of thrombocytopenia with abciximab is not necessarily generalizable to other unique IIb/IIIa receptor antagonists. Tirofiban may be an appropriate consideration for patients who would benefit from a IIb/IIIa receptor antagonist and who are not candidates for abciximab therapy due to an episode of abciximab-associated thrombocytopenia. Further investigation of thrombocytopenia associated with IIb/IIIa receptor antagonists is warranted to determine appropriate approaches to the management of patients with a history of abciximab-associated thrombocytopenia.

Abciximab↗

Zonation of gluconeogenesis, ketogenesis and intracellular pH in livers from normal and diabetic ketoacidotic rats: evidence for intralobular redistribution of metabolic events in ketoacidosis.

The intralobular distribution of metabolism was examined in the livers from rats with severe diabetic ketoacidosis (DKA), perfused at pH 6.8, and compared with that in livers from normal starved animals perfused at either pH 7.4 or 6.8. With lactate and palmitate as substrates, the perivenous uptake of periportally synthesized glucose seen in normal livers at pH 7.4 was abolished during DKA; indeed, gluconeogenesis was most active in the perivenous region. Whereas in normal livers perfused at pH 7.4 the periportal region showed a markedly elevated intracellular pH (pH(i)) compared with the perivenous zone, this distribution of pH(i) was reversed in DKA, with an intermediate distribution in normal livers perfused at pH 6. 8. 3-Hydroxybutyrate was generated throughout the lobule. Some acetoacetate generated periportally was converted to 3-hydroxybutyrate more perivenously. A steep gradient of oxygen uptake along the radius of the lobule was apparent in all three groups; oxygen uptake was greatly decreased perivenously despite adequate oxygen supply. These findings are consistent with our previous observations of the lobular co-location of high pH(i) and gluconeogenesis, and might offer an explanation of how high gluconeogenic rates can continue in spite of severe systemic acidosis in DKA. The findings provide direct evidence for a marked redistribution of intralobular metabolism in DKA.

Animals↗

False positive rates of randomized phase II designs.

The randomized Phase II design for the purpose of selecting a treatment for eventual Phase III testing has recently gained popularity in cancer clinical research. Unfortunately, along with its wider use also come frequent misapplications. The major misuse of the design is the treatment of the Phase II results as ends in themselves without further, definitive evaluation. For binary and censored exponential survival data, we quantify the chance of observing "impressive" between-group differences when underlying distributions are exactly the same in 2-, 3-, and 4-arm selection designs. Depending on one's view of what is impressive, the "false-positive" rates range from 20% to over 40%. We stress that randomized Phase II results are pilots to Phase III evaluations. One should not regard them as conclusive. We caution especially against the inclusion of control arms in such designs because of the propensity for erroneous inferences. We also discuss the inappropriate practice of performing post-hoc hypothesis testing and presenting p-values that are less than 0.05.

Clinical Trials, Phase II as Topic↗

Attempted suicide in west London, I. Rates across ethnic communities.

BACKGROUND: Two previous studies from the United Kingdom have suggested that rates of attempted suicide in Asian women are higher than in the native population. METHOD: Over a 1-year period we identified 434 patients presenting from one catchment area to four hospitals, after episodes of self-harm. These patients were assessed using the GHQ, CIS-R, and Life Events Inventory, and by collecting details of the attempt itself. RESULTS: Asian women had the highest overall rates; 1.6 times those in White women and 2.5 times the rate among Asian men. The rates were lowest among older women. Among younger Asian women (less than 30 years) the rates were 2.5 times those of White women and seven times those of Asian men. The rates among black groups were lower than expected. Self-poisoning was the commonest method of self-harm. CONCLUSIONS: Younger Asian women are vulnerable to increased rates of attempted self-harm and deserve to be studied further.

Adolescent↗

Attempted suicide in west London, II. Inter-group comparisons.

BACKGROUND: Previous studies of attempted suicide have suggested that cultural and social factors play a significant role in the causation of deliberate self-harm. METHOD: In order to measure elements of culture conflict two inter-group comparisons were undertaken. In the first, 27 Asian women who had presented to hospital services following attempted suicide (Asian group) were matched with a group of similar age Asian women attending GP surgeries for other reasons (Asian GP attenders group). The second comparison was between the Asian and 46 White attempters. RESULTS: On comparing Asian attempters with Asian GP attenders group the former were more likely to have a history of previous suicidal behaviour, to have a psychiatric diagnosis, and be unemployed. Their parents were more likely to have arrived in the United Kingdom at an older age. In addition, those who attempted suicide were more likely to have been in an inter-racial relationship and to have changed religions. In the second inter-group comparison, the characteristics of Asian and White suicide attempt patients were examined. White attempters were more likely to have mental illness, and were more likely to use alcohol as part of the method of attempted suicide. By contrast, Asian attempters had experienced life events pertaining to relationships, took fewer tablets and yet expressed greater regret at not succeeding in the attempt. CONCLUSIONS: Although numbers are small, social stress and other cultural factors play an important role in the act of deliberate self-harm.

Adolescent↗

A comparison of performances of four enzymes used in ELISA with special reference to beta-lactamase.

Horse radish peroxidase, alkaline phaosphatase and beta-D-galactosidase are widely used as labels in the development of enzyme immunoassays (EIAs). Enzyme beta-lactamase, though introduced as a label in late seventies has not yet become very popular inspite of having the necessary features of an enzyme to be used in EIAs. The present article reviews assays developed with this enzyme, highlights its salient features and brings out an argument in favour of its wide spread use in EIAs.

Alkaline Phosphatase↗