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Biomedical subjects

D Patel

Publications and source records attributed to D Patel.

At least 91 records · Page 5Linked to original sources

Oral midazolam compared with diazepam-droperidol and trimeprazine as premedicants in children.

Ninety children were assigned randomly to one of three groups for premedication with oral midazolam 0.5 mg.kg-1, diazepam 0.25 mg.kg-1 with droperidol 0.25 mg.kg-1, or trimeprazine 2 mg.kg-1. On arrival at the anaesthetic room, anxiolysis was satisfactory in 26 out of 29 (90%) children who received midazolam compared with 23 out of 29 (79%) who received diazepam-droperidol and 18 out of 29 (62%) who received trimeprazine (P < 0.05); at induction of anaesthesia these proportions were 24 out of 29 (83%), 16 out of 29 (55%) and 11 out of 29 (40%) respectively (P < 0.001). When individual groups were compared, anxiolysis was significantly greater in the midazolam group compared with the trimeprazine group on arrival in the anaesthetic room (P < 0.05) and significantly greater in the midazolam group than in either the diazepam-droperidol or the trimeprazine groups at induction of anaesthesia (P < 0.05 and P < 0.001 respectively). There were no significant differences in times to early recovery between the groups (25.4, 24.4 and 28.5 min). Analysis of behavioural questionnaires completed two weeks after hospitalization showed a trend towards fewer postoperative behavioural disturbances in children who received midazolam or diazepam-droperidol compared with trimeprazine (47 and 44% vs 75%); when the results for the benzodiazepine-containing premedicants were combined, the difference between these groups and trimeprazine was statistically significant (P < 0.05).

Adjuvants, Anesthesia↗

Coronary vasodilator reserve in primary and secondary left ventricular hypertrophy. A study with positron emission tomography.

OBJECTIVES: Coronary vasodilator reserve is reduced in hypertrophic cardiomyopathy and secondary left ventricular hypertrophy despite angiographically normal coronaries. The aim of the present study was to assess whether quantitative differences exist between these conditions. METHODS: Using positron emission tomography with H2(15)O, myocardial blood flow was measured at baseline and following intravenous dipyridamole (0.56 mg.kg-1) in 12 hypertrophic cardiomyopathy patients (age 34 (11) years, mean (SD), all male), 16 secondary left ventricular hypertrophy patients (age 58 (20) years, P < 0.01 vs hypertrophic cardiomyopathy; 10 female) and 40 normal controls (age 54 (20), 13 female). In view of the known decline of post-dipyridamole myocardial blood flow with age, myocardial blood flow was compared between the patient groups and appropriately matched subsets of the total control group. RESULTS: Baseline myocardial blood flow in the hypertrophic cardiomyopathy patients was 0.82 (0.23) ml.min-1.g-1 vs 0.94 (0.14) ml.min-1.g-1 in its matched control group, P = ns. For the secondary left ventricular hypertrophy patient group, baseline myocardial blood flow was 1.17 (0.40) ml.min-1.g-1 vs 1.06 (0.28) ml.min-1.g-1 for the secondary left ventricular hypertrophy matched control group, P = ns. Following dipyridamole, myocardial blood flow was 1.64 (0.44) ml.min-1.g.-1 in hypertrophic cardiomyopathy patients vs 3.50 (0.95) ml.min-1.g-1 for the hypertrophic cardiomyopathy matched control group, P = 0.0001. For the left ventricular hypertrophy patients, post-dipyridamole myocardial blood flow was 2.27 (0.60) ml.min-1.g-1 vs 2.94 (1.29) ml.min-1.g-1 for the left ventricular hypertrophy controls, P = 0.06. Coronary vasodilator reserve (dipyridamole-myocardial blood flow/baseline-myocardial blood flow) was 2.05 (0.61) for hypertrophic cardiomyopathy patients vs 3.81 (0.98) for the hypertrophic cardiomyopathy controls (P = 0.0001, patients vs controls) and 2.06 (0.62) for left ventricular hypertrophy patients vs 2.90 (1.38) for the left ventricular hypertrophy controls, P < 0.03 patients vs controls. After correction of baseline myocardial blood flow for baseline heart rate x systolic pressure product, coronary vasodilator reserve for the hypertrophic cardiomyopathy patients was 2.06 (1.06) vs 4.34 (1.54) for the hypertrophic cardiomyopathy controls. P = 0.0002 and in the secondary left ventricular hypertrophy patients, the values were 2.13 (0.64) vs 2.89 (1.42) in the secondary left ventricular hypertrophy controls, P < 0.05. CONCLUSION: In both hypertrophic cardiomyopathy and secondary left ventricular hypertrophy, the computed coronary vasodilator reserve is impaired, even after correction for baseline cardiac work. However, the extent of the reduction is greater in the hypertrophic cardiomyopathy patients. In the blunting of vasodilator reserve of secondary left ventricular hypertrophy, the patients' greater hyperaemic response is partly offset by the higher baseline myocardial blood flow.

Adult↗

Altered platelet function detected by flow cytometry. Effects of coronary artery disease and age.

Platelet activation state and responsiveness to physiological agonists were measured in 65 patients with documented coronary artery disease (54 male and 11 female; mean age, 58 years). Twelve patients (mean age, 52 years), selected at random from the male cohort, were compared with 12 age-matched male control subjects (mean age, 52 years) and with 10 normal, young male subjects (mean age, 25 years). Whole-blood flow cytometry was used to measure platelet activation status ex vivo and platelet responsiveness to physiological agonists in vitro. Peripheral blood samples were analyzed for bound fibrinogen and expression of P-selectin, GPIb, and GPIIb-IIIa at rest and in response to ADP (0.1 to 10 mumol/L) and thrombin (0.02 to 0.32 mu/mL). No significant differences were seen in the basal levels of fibrinogen binding between any of the groups, but P-selectin expression was significantly lower in patients compared with age-matched control subjects (P = .0005). When stimulated with agonists, patients' platelets had significantly decreased fibrinogen binding (P < .03) but no difference in P-selectin expression compared with the age-matched group. Both agonist-induced fibrinogen binding and P-selectin expression were, however, higher in the young subjects compared with either the older control group or the patients (P < .05). GPIb and GPIIb-IIIa expression were lowest in the patients with angina and highest in the young control subjects, with levels in the age-matched control subjects falling between these values. Data from the total patient cohort (n = 65) were identical to those in the smaller cohort (n = 12). In conclusion, atherosclerosis impairs platelet aggregatory responses (fibrinogen binding) over and above the decreased response seen with age. Platelet degranulation (P-selectin expression) is also impaired in patients with coronary artery disease, but only in comparison with younger subjects, not age-matched controls.

Adult↗

Base dynamics in a UUCG tetraloop RNA hairpin characterized by 15N spin relaxation: correlations with structure and stability.

Intramolecular dynamics of guanine and uracil bases in a 14-nt RNA hairpin including the extraordinarily stable UUCG tetraloop were studied by 15N spin relaxation experiments that are sensitive to structural fluctuations occurring on a time scale of picoseconds to nanoseconds. The relaxation data were interpreted in the framework of the anisotropic model-free formalism, using assumed values for the chemical shift anisotropies of the 15N spins. The rotational diffusion tensor was determined to be symmetric with an axial ratio of 1.34 +/- 0.12, in agreement with estimates based on the ratio of the principal moments of the inertia tensor. The model-free results indicate that the bases of the G x U pair in the tetraloop are at least as rigid as the interior base pairs in the stem, whereas the 5'-terminal guanine is more flexible. The observed range of order parameters corresponds to base fluctuations of 19-22 degrees about the chi torsion angle. The results reveal dynamical consequences of the unusual structural features in the UUCG tetraloop and offer insights into the configurational entropy of hairpin formation.

Base Composition↗

Epidemiologic paradox in multiple births among Asians in Illinois. Correlation between risk factors and outcomes.

OBJECTIVE: To determine if the plural birth rate, maternal risk factors and neonatal outcomes among Asian American populations residing in Illinois are homogeneous or heterogeneous with regard to maternal risk factors and neonatal outcomes and to attempt to establish correlations between maternal risk factors and neonatal outcomes. STUDY DESIGN: A total of 1,145,962 computerized birth certificate files were analyzed for 11 Asian subgroups giving birth in Illinois in the years 1989-1994. RESULTS: The multiple birth rates varied between 6 per 1,000 (Vietnamese) to 15 per 1,000 (Cambodian) (heterogeneity among all groups, P < .005). The percent of neonates born at gestational ages 22-33 weeks varied between 0 (Cambodian) to 28 (Thai). Japanese women showed the highest rate of neonates with birth weight less than 2,500 g after adjustment for race: 15.38 per 1,000. Women from Cambodia and Laos had the highest sum of maternal risk factors; those from the Philippines and Thailand had the least. The lowest collective adverse neonatal outcomes were in infants born to women from Cambodia and Laos. CONCLUSION: The 11 subgroups of Asians living in Illinois demonstrate heterogeneity with respect to multiple birth rate, selected maternal risk factors and adverse neonatal outcomes. After considering all maternal risk factors and neonatal outcomes, the two groups (Cambodians and Laotians) with the poorest maternal risk factors had the lowest rate of poor neonatal outcomes. This is the first time that this epidemiologic paradox has been observed in twins of Asian ancestry.

Adolescent↗

Multiple births among adolescent women in Illinois.

OBJECTIVE: To examine the occurrence of multiple births among adolescents using birth as the unit of analysis and to examine the association between maternal race/ethnicity and parity and the occurrence of multiple births among women less than 20 years of age. STUDY DESIGN: Computerized birth certificate files without personal identifiers were obtained from the Illinois Department of Public Health totaling 1,103,333 live births from 1989 to 1994. RESULTS: A total of 13.3% of births during this time were to mothers less than 20 years of age. The overall maternal multiple birth rate was 8.2/1,000 births. There were statistically significant differences in the numbers of pregnancies resulting in live, multiple births among black, Hispanic and white teenage mothers. There was a linear increase in maternal multiple birth rates among black (P < .0001) and Hispanic (P < .001) teenage mothers by parity as well as a linear increase among black (P < .0001), Hispanic (P < .0236) and white (P < .049) populations by age of the mother. The age- and parity-specific maternal multiple birth rate ranged from 4.4 per 1,000 pregnancies for Hispanic teenage mothers less than 18 years of age to 11.9 per 1,000 pregnancies for black teenage mothers 19 years of age. At 0 and 1 parity, black women less than 20 years of age were at the highest risk for multiple births as compared to Hispanic and white mothers. CONCLUSION: This is the first study showing ethnic and racial differences in the rates of multiple births among teenage mothers. As in older women, increased age and a higher parity were associated with a higher probability of multiple birth among adolescents.

Adolescent↗

Nuclear magnetic resonance solution structure of the human Hsp40 (HDJ-1) J-domain.

The J-domain is a highly conserved domain found in all members of the DnaJ family of molecular chaperones. The three-dimensional structure of a recombinant, uniformly 15N-labeled 77-residue polypeptide containing the complete J-domain from human Hsp40 (HDJ-1) has been determined by nuclear magnetic resonance (NMR) spectroscopy in solution. On the basis of 876 upper distance constraints derived from nuclear Overhauser effects (NOE) and 173 dihedral angle constraints, a group of 20 conformers representing the solution structure of the HDJ-1 J-domain was computed with the program DIANA and energy-minimized with the program OPAL. The average of the pairwise root-mean-square deviations of the individual NMR conformers relative to the mean coordinates for the backbone atoms N, C2 and C' of residues 4 to 54 and 4 to to 66 is 0.88 and 0.99 A respectively. The molecular architecture includes four helices composed of residues 5 to 9, 15 to 28, 40 to 54 and 60 to 66. A turn composed of residues 10 to 14 links helices I and II, and a loop composed of residues 29 to 39 containing a highly conserved tripeptide HPD (residues 31 to 33) connects the antiparallel helices II and III. The tertiary fold formed by helix I-turn-helix II-loop-helix III forms a closed structural core; the less defined helix IV stands away from the core of the domain. The side-chains of the tripeptide HPD extend out from the core of the structure in the opposite direction from helix IV. The structure supports the hypothesis that the highly conserved tripeptide could play a key role in the interaction of Hsp40 with the molecular chaperone, Hsp70.

Amino Acid Sequence↗

31P nuclear magnetic resonance study of phospholipids in ischemia/reperfusion injury in a rat fatty liver model.

Obese Zucker rats are susceptible to increased hepatic ischemia/reperfusion (I/RP) injury. Increased lipid peroxidation occurs in this model with warm ischemia. We hypothesized that a severe depletion of phospholipids (PL) occurs with warm I/RP in fatty livers. Obese (Ob) and lean (Ln) Zucker rats were subjected to 90 min of in vivo partial hepatic warm I followed by RP. Total lipids extracted from one gm of liver (median lobe) taken at the end of 1, 2 and 6 hr of RP and sham (Sh) surgery (n=5 Ln & Ob) were analyzed by 202.3 MHz 31P NMR, which provided good resolution of individual PL. Obese (Sh) rats contained 22% more PL than Ln (P= < 0.01). Ischemia caused similar decreases in PL in both Ob (to 67% Sh) and Ln rats (62%). Following 2 hr RP, PL in Ob rats decreased further (46% Sh) and recovered only marginally at 6 hr (53%), in marked contrast to the rapid recovery in Ln to preischemic levels (110% Sh at both 2 and 6 hr; P=<0.001). Mole percents of individual PL did not change significantly except for lysophosphatidylcholine, which increased from 0.43 to 1.3% (Sh vs. 6 hr RP) in the Ob, but decreased from 0.98 to 0.52% in Ln animals (P = <0.001). Fatty livers thus are more vulnerable to phospholipid depletion in response to warm ischemia/reperfusion than normal livers.

Animals↗

The human papillomavirus type 16 E7 gene product interacts with and trans-activates the AP1 family of transcription factors.

The E7 gene product of human papillomavirus type 16 (HPV16) binds to the retinoblastoma gene product (pRb) and dissociates pRb-E2F complexes. However, the observation that the ability of E7 to bind pRb is not required for the HPV16-induced immortalization of primary keratinocytes prompted a search for other cellular factors bound by E7. Using a glutathione-S-transferase (GST) fusion protein system, we show that E7 complexes with AP1 transcription factors including c-Jun, JunB, JunD and c-Fos. The ability of E7 to complex with c-Jun in vivo is demonstrated by co-immunoprecipitation and the yeast two-hybrid system. An analysis of E7 point mutants in the GST system indicates that the E7 zinc-finger motif, but not the pRb binding domain, is involved in these interactions. Using c-Jun deletion mutants, E7 binding maps between amino acids 224 and 286 of c-Jun. E7 trans-activates c-Jun-induced transcription from a Jun responsive promoter, and this activity correlates with the ability of E7 mutants to bind Jun proteins. Finally, a transcriptionally inactive c-Jun deletion, which can bind E7, interferes with the E7-induced transformation of rat embryo fibroblasts in cooperation with an activated ras, indicating that the Jun-E7 interaction is physiologically relevant and that Jun factors may be targeted in the E7 transformation pathway.

Animals↗

Tamoxifen aziridine labeling of the estrogen receptor-potential utility in detecting biologically aggressive breast tumors.

Expression of estrogen receptor (ER) is a helpful predictor of response to endocrine therapy and disease free survival in breast cancer patients. The presence of variant estrogen receptors has been demonstrated at the RNA/DNA level and might represent an escape of tumors from hormonal control mechanisms. However, the demonstration that the corresponding peptides do exist is a real challenge. Denaturing polyacrylamide gel electrophoresis (SDS-PAGE) of covalently bound [3H]tamoxifen aziridine ([3H]TAZ) to ER demonstrates a specific, multiband peptide pattern recognized by anti-ER monoclonal antibodies (anti-ER Mo Abs). The native 66 kDa ER form identified through its hormone binding domain by the H-222 Mo Ab was the most prominent one followed by 50, 35, and 28 kDa forms on fluorography. Such patterns from early human breast tumors were compared to the ones of more advanced disease, namely large primary breast cancers, metastatic lymph nodes, and soft tissue relapses: in these cases, molecular forms of 43 and 35 kDa were identified with a remarkable consistency. The 43 kDa peptide was more frequently identified by the H-226 Mo Ab (which maps a region near the DNA binding domain)-albeit with low labeling intensity as compared to H-222 Mo Ab. In addition, the 43 kDa peptide was inversely correlated to ER levels. This altered ER or related peptide could potentially be a marker of biologically aggressive breast tumors.

Antibodies, Monoclonal↗

Eye manifestations of congenital toxoplasmosis.

PURPOSE: To determine the natural history of treated and untreated congenital toxoplasmosis and impact of this infection on vision. METHODS: In this prospective, longitudinal study, 76 newborns were treated with pyrimethamine and sulfadiazine for approximately one year, and 18 individuals not treated during their first year of life entered the study after age 1 year (historical patients). RESULTS: Chorioretinal scars were the most common eye finding in all patients and were most common in the periphery (58% of treated and 82% of historical patients). Macular scars were present in 54% of the treated patients; 41% were bilateral. Macular scars were present in 76% of the historical patients; 23% were bilateral. Visual acuity in the presence of macular lesions ranged from 20/20 to 20/400. Of the patients followed up from the newborn period and treated, 29% had bilateral visual impairment, with visual acuity for the best eye of less than 20/40. Causes for this visual impairment in eyes with quiescent lesions included macular scars, dragging of the macula secondary to a peripheral lesion, retinal detachment, optic atrophy, cataract, amblyopia, and phthisis. There were recurrences in both treated (13%, 7/54) and previously untreated historical patients (44%, 8/18). The total, median, and range of years of follow-up during which recurrences were observed were, for treated patients, 189 years (total), five years (median), and three to ten years (range) and, for historical, untreated patients, 160 years (total), 11 years (median), and three to 24 years (range). New lesions occurred in previously normal retinas and also contiguous to older scars. Active lesions appeared to become quiescent within ten to 14 days after beginning pyrimethamine and sulfadiazine therapy. CONCLUSION: Many children with congenital toxoplasmosis have substantial retinal damage at birth and consequent loss of vision. Nonetheless, vision may be remarkably good in the presence of large macular scars. Active lesions become quiescent with treatment.

Adolescent↗

Objective assessment of the response to treatment of severe heart failure using a 9-minute walk test on a patient-powered treadmill.

BACKGROUND: No previous studies have demonstrated the changes in exercise capacity that occur during treatment of decompensated severe heart failure. The authors assessed the efficacy and safety of using a patient-powered treadmill to objectively measure exercise capacity and its relationships, if any, to symptom scores and body weight. METHODS AND RESULTS: Changes in time-limited exercise capacity on a patient-powered treadmill were assessed during inpatient treatment of 12 patients with decompensated chronic heart failure (New York Heart Association classes III and IV). Patients performed a 9-minute walk test daily for 7 days and again at the 6-week follow-up examination. They also completed a 24-item symptom score questionnaire. After treatment, there was a rapid, significant increase in total distance walked, with the increase beginning as early as the second day after admission (mean distance walked +/- SEM, 54 +/- 27 m and 174 +/- 54 m on admission and on day 2, respectively, P < .05). Improvement was maintained throughout the period in the hospital and at 6 weeks (P < .001). Patients reported symptomatic improvement, but this did not reach significance until 4 days after admission (P < .05). Weight loss was not significant. Improved exercise capacity correlated with reduced symptoms and weight loss, but preceded these by several days. CONCLUSIONS: In patients with decompensated chronic heart failure, this exercise test provides a safe, practical, inexpensive, and objective assessment of functional capacity, providing certain advantages over other indices of response to therapy, such as symptom scores and weight loss. Improvement of exercise capacity does not occur concurrently with relief of symptoms and weight loss.

Adult↗

Treatment of vancomycin-resistant Enterococcus faecium infections with an investigational streptogramin antibiotic (quinupristin/dalfopristin): a report of fifteen cases.

New therapies for vancomycin-resistant Enterococcus faecium (VREF) infections are urgently needed. We describe the treatment of 15 patients with VREF infection with quinupristin/dalfopristin (RP 59500), a new injectable streptogramin antibiotic. Primary infections treated were bacteremia (4), urinary tract (4), intraabdominal (5), otitis externa (1), and meningitis (1). Minimum inhibitory concentrations for quinupristin/dalfopristin ranged from 0.5 microgram/ml or less to 2 micrograms/ml, and minimum bactericidal concentrations were greater than 64 micrograms/ml for all VREF isolates tested. Peak serum inhibitory titers following infusion of quinupristin/dalfopristin ranged from 1:8 to 1:64; all bactericidal titers were less than 1:2. Development of resistance to quinupristin/dalfopristin during therapy was not observed. The only drug-related adverse effect noted was phlebitis in 4 patients; all had received quinupristin/dalfopristin by peripheral venous infusion. Three patients had clinical and bacteriologic cures. Relapses occurred in 5 patients with recovery of VREF from infected sites in post-treatment cultures. Ten patients died of severe underlying disease; VREF was believed to contribute directly to the death of only 1 patient. While evaluation of clinical efficacy was complicated by the severity of underlying disease in patients with VREF infection, our experience suggests that quinupristin/dalfopristin is a safe and potentially useful agent for the treatment of VREF infections.

Adult↗

Congenital toxoplasmosis transmitted from an immunologically competent mother infected before conception.

Congenital transmission of Toxoplasma gondii from a mother who was apparently immunologically competent and who had toxoplasmic lymphadenitis 2 months before conception is described. Since no T. gondii-specific serological data were available for this mother from the time her lymph node biopsy specimen was obtained, the specimen was studied by polymerase chain reaction (PCR) to determine whether the T. gondii B1 gene was present. The predictive diagnostic value of histologic findings previously considered to be classic signs of T. gondii lymphadenitis also was studied. This was done by correlation of serological tests diagnostic of acute acquired T. gondii infection and presence of characteristic findings in biopsy specimens from persons without known immunocompromise. Both PCR and review of the characteristic features of her lymph node biopsy specimen confirmed the diagnosis of preconceptual infection in the mother. We also discuss two other cases in which apparently immunologically competent mothers with preconceptually acquired infection transmitted this parasite to their fetuses.

Animals↗

Women with chest pain: is exercise testing worthwhile?

OBJECTIVE: To determine the diagnostic value of the exercise tolerance test (ETT) in women presenting with chest pain. DESIGN: Prospective study of all women presenting to a centre with chest pain between 1987 and 1993 who were assessed by an ETT and coronary angiography. SETTING: The outpatient clinic of one consultant cardiologist in a tertiary referral centre. PATIENTS: All women referred to this outpatient clinic with chest pain were screened. For inclusion, patients had to perform ETT and undergo coronary angiography. Of the 347 referred during this period, 142 were excluded because they were unable to perform ETT or because of Q waves or other abnormalities on their resting electrocardiogram. RESULTS: Overall the sensitivity of the ETT was 68% and the specificity was 61%, with a positive predictive value of 0.61 and a negative predictive value of 0.68. There were 42 false positive and 31 false negative ETT results (36% of the study group). The predictive value of a negative test was higher in younger women (< 52 years) than in the older group (> or = 52 years) (P = 0.004), but the positive predictive value in the two groups was not significantly different. The predictive value of a negative test was also higher in those with two or fewer risk factors than in those with three or more risk factors (P = 0.001). The negative predictive value for those women above 52 years with three or more risk factors (24% of the study group) was only 0.25. Lack of chest pain during ETT was associated with a higher negative predictive value in the younger group than in the older women (P = 0.006). CONCLUSIONS: In women with chest pain use of the ETT was a misleading predictor of the presence or absence of coronary disease in 36% of these patients. In particular, a negative test in older women with three or more risk factors had a very low predictive value. The inclusion of risk factors and division by age can, however, be used to identify a population at intermediate risk for coronary artery disease in whom the ETT result has the highest diagnostic utility.

Adult↗