Biomedical subjects
Publications and source records attributed to R Sinha.
Four women underwent transvaginal endoscopic oophorectomy during vaginal hysterectomy. The adnexa were visualized with a laparoscope inserted into the upper vagina. Bilateral salpingo-oophorectomy or oophorectomy was carried out with standard laparoscopic instruments introduced through the vagina without a pneumoperitoneum; Endoloop sutures and bipolar electrocoagulation were used for hemostasis.
Heterocyclic aromatic amines are sometimes formed during the cooking of muscle meats, and their mutagenic and carcinogenic effects are of potential concern in the aetiology of human cancer. In a large survey of the heterocyclic amine content of foods, fried or charbroiled hamburgers, fried chicken, chicken breast sandwiches, fish sandwiches and breakfast sausages were purchased from fast-food restaurants. At least three different chains were visited per product and samples from five stores from each chain were pooled. The solid-phase extraction and HPLC method was used to analyse pooled samples for heterocyclic amine content and mutagenic activity with the Ames/Salmonella assay. Samples were analysed in a blind study which also contained quality control samples of two types, one high and one low in heterocyclic amine content and mutagenic activity. Results from the fast-food products showed undetectable levels of heterocyclic amines in 10 of 17 samples and only low levels [< or = 1 ng/g total of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx)] in the remaining samples. Compared with literature values based primarily on laboratory and home cooking conditions, fast-food meat products appear to contribute only a small percentage of the estimated daily dietary intake of heterocyclic amines.
Heterocyclic aromatics amines (HAAs), such as 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), are metabolically activated by cytochrome P4501A2 (CYP1A2) and N-acetyltransferase (NAT2). We examined the relationship between CYP1A2 and NAT2 activity and the excretion of total unconjugated MeIQx in 66 healthy subjects. The subjects ate a control diet for 7 days containing lean ground beef cooked at low temperature. On day 8, they were tested for CYP1A2 and NAT2 activity by caffeine phenotyping. On the evening of day 8, subjects consumed lean ground beef cooked at high temperature containing 9.0 ng of MeIQx/g of meat. The subjects ate 3.1-4.0 g meat/kg body wt. Twelve-hour urine samples were collected and MeIQx was measured by gas chromatography-mass spectrometry. Using linear regression analyses, we found that higher CYP1A2 activity was associated with lower levels of total unconjugated MeIQx in the urine (P = 0.008) when adjusted for amount of meat eaten, while NAT2 activity showed no relationship with the latter. This suggest that a greater percentage of MeIQx is converted to metabolites such as the N-hydroxy derivative when CYP1A2 activity is higher. This finding supports the concept that inter-individual variation is CYP1A2 activity may be relevant for cancers associated with exposure to HAAs.
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Heterocyclic aromatic amines (HAAs) are formed when meat juices are pyrolyzed. In humans HAAs are activated in vivo by cytochrome P4501A2 (CYP1A2) and N-acetyltransferase (NAT2) to mutagens or carcinogens. While activity of NAT2 is noninducible, exposure to cigarettes, polycyclic aromatic hydrocarbons, and cruciferous vegetables has been shown to induce CYP1A2 activity in humans. To date, it is unknown if pan-fried meat, which is consumed at high levels in the United States, is capable of inducing CYP1A2. In order to address this issue, we measured CYP1A2 and NAT2 activities in 66 healthy nonsmokers (33 males and 33 females) in a controlled metabolic feeding study. The study was designed to minimize the influence of known inducers of CYP1A2. Subjects consumed meat pan-fried at a low temperature (100 degrees C) for 7 days followed by 7 days of meat pan-fried at a high temperature (250 degrees C). The low temperature-cooked meat had undetectable levels of HAAs while the high temperature-cooked meat contained high amounts of HAAs [9.0 ng/g of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2.1 ng/g of 2-amino-3,7,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx), and 32.8 ng/g of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)]. In contrast, total polycyclic aromatic hydrocarbon content was similar in both meat samples (10.7 ng/g in low temperature-cooked meat and 10.1 ng/g in high temperature-cooked meat). At the end of each period, subjects were tested for CYP1A2 and NAT2 enzyme activity by caffeine metabolism phenotyping. NAT2 activity remained unchanged throughout the study while CYP1A2 activity increased in 47 of 65 (72%) of the subjects after consuming high temperature-cooked meat (P < 0.0002), suggesting induction by some compound(s) formed during high temperature cooking. If HAAs are shown to be human carcinogens in epidemiological studies, then meat cooked at high temperatures may pose an increased cancer risk because it contains both inducers of CYP1A2 and procarcinogens MeIQx, DiMeIQx, and PhIP known to be activated by this enzyme.
Potential recovery of electrophysiological and neuropsychological functions was investigated in alcoholics completing treatment and controls. Event-related potentials (ERPs) and neuropsychological tests were administered initially and repeated 14 months later. Alcoholics were classified as resumers or abstainers based on consumption patterns before retest. Resumers (n = 28), abstainers (n = 44), and controls (n = 44) differed significantly on ERP measures. No test-retest or group x test-retest interactions were found, indicating little recovery or change in ERPs over time. Differences between groups could not be attributed to family history factors. For neuropsychological efficiency (Accuracy/Time) measures, significant group differences were found. All groups improved from test to retest, with resumers showing the greatest improvement. Analysis of the separate efficiency components indicated resumers' improvement was due to a decrease in performance time, whereas accuracy scores remained significantly impaired. Whether the continued deficits in ERPs and neuropsychological performance at retest is a permanent effect of alcohol abuse, or would remit over longer periods of time, or reflects premorbid deficits, remains to be investigated.
To determine whether T cells, like B cells, can become clonally expanded in normal individuals as a function of age, we compared the T cell V beta repertoire of cord blood to that of peripheral blood from normal donors over 65 yr of age. T cells from elderly subjects contained expanded subsets (greater than the mean+three standard deviations) of T cell receptor (TCR) V beta populations. These expanded subsets were observed primarily among CD8, but not CD4 cells, represented up to 37.5% of all CD8 cells, and were present in most elderly subjects. An expanded V beta 5.2/3 CD8 subset and a V beta 6.7a CD8 subset from separate donors were analyzed by reverse transcriptase-polymerase chain reaction, cloning and sequencing of the TCR beta chain VDJ junction. In both cases the expanded subsets were mono- or oligoclonal while control CD4 populations were polyclonal. Using two-color flow cytometry it was possible to identify the expanded V beta 6.7a subset as CD8+ CD28-CD11b+ cells. In three of five random old subjects similar expansions of V beta subsets were found specifically in the CD8+ CD28- subpopulation, an interesting subset of cytotoxic T lymphocytes, known to lack proliferative responses to TCR stimuli. It is common practice to use the demonstration of clonality as a diagnostic indicator for T cell lymphoma/leukemia. In view of the high frequency of expanded T clones of T cells in normal elderly subjects the diagnostic usefulness of this test should be reexamined.
Lower extremity electromyograms (EMGs), ground reaction forces, and body motion were measured during the brisk initiation of forward walking performed by 12 healthy adults, aged 20 to 82 years. Gait was initiated 20 times in response to a visual cue. During gait initiation, the body rotated about the ankles like a flexible inverted pendulum. The muscles of the lower extremities were activated stereotypically so as to create moments of force about the ankles that propelled the body toward the stance foot and into forward motion. All volunteers exhibited similar patterns of gait initiation, which were so reproducible that computer averaging of multiple steps by each person was possible. Gait initiation is a stereotyped sequence of postural shifts that culminates in a forward step. Disturbances of gait initiation could result from abnormalities in postural control, movement, or their integration.
The effect of ethanol on human sensorimotor reactivity was assessed by examining the acoustic startle response. Twelve healthy normal subjects participated in a startle reflex experiment in which placebo or ethanol were given on separate days. Three types of startle probes were used. They consisted of pulse-alone bursts of white noise at 108 dB(A) and 99 dB(A) to explore startle reactivity, and of a 108 dB(A) pulse preceded by a 85 dB(A) prepulse stimulus (prepulse+pulse) to assess prepulse inhibition. Startle amplitude was larger to the 108 dB(A), compared to the 99 dB(A) pulse-alone probes. The prepulse stimulus significantly reduced the amplitude of the startle reflex elicited by the subsequent 108 dB(A) stimulus. The amplitude of the startle response was dramatically reduced by acute ethanol. The effects of ethanol on prepulse inhibition could not be assessed because the startle response was too small in the ethanol condition.
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The incidence of renal allograft rupture among 237 live donor renal transplant patients was 6.3%. The most common association was with acute rejection. The graft salvage rate was 73% and the longest graft function was 10 years.
Classification of individuals by their vitamin C intake was investigated in 493 control subjects from a cervical cancer case-control study. The influence of dietary and supplemental sources of vitamin C, as well as demographic and life-style factors, on serum ascorbic acid were examined. Usual dietary intakes of vitamin C were determined from a food frequency questionnaire and recent intakes from a 24-hour recall taken at the time of blood collection. Vitamin supplement information was obtained at both times. In a regression analysis, the factors found to predict serum ascorbic acid were total recent vitamin C intake, an indicator variable for supplement use, body mass index, number of cigarettes smoked per day, race, education, and age. Higher levels of serum ascorbic acid were found among older nonsmoking highly educated leaner white women. Consideration of supplements, in addition to dietary sources of vitamin C, improved correlation coefficients between serum ascorbic acid and usual vitamin C intake from 0.19 to 0.32 and between serum ascorbic acid and recent intake from 0.36 to 0.56. Furthermore, whereas only a twofold difference between the first and fourth quartiles of serum ascorbic acid was observed using recent dietary vitamin C without supplements, this range increased to sixfold with addition of supplement data. Epidemiological studies should consider use of total vitamin C intakes from supplement and food sources to permit accurate classification of individuals.
The role of nutrient intake in disease outcome is often examined in epidemiologic studies. Most such studies conducted in the United States, however, have not included fortified foods or vitamin supplements. In the United States, these are important sources of vitamins C and E, but not of beta-carotene. In addition, the importance of these nutrient sources varies by race, sex, and age. Failure to include these sources produces errors in nutrient estimates, notable misclassification of individuals with regard to their total intake, and rankings of intake that bear little or no relationship to blood concentrations of those nutrients. Implications for statistical analysis are also considered. Risk analyses in which nutrients from supplements are handled as control variables or are analyzed separately may impair the ability to detect associations between total nutrient intake and disease risk. The additional source of misclassification of nutrient status for vitamins C and E and other nutrients derived from fortified foods or supplements would make it more difficult to obtain significant and consistent results in etiologic studies of these nutrients; this has not been a factor for beta-carotene, which is derived almost exclusively from fruits and vegetables.
OBJECTIVE: The authors determined if the diagnosis of acute cholecystitis can be accurately made or reliably eliminated by the use of morphine-augmented radionuclide cholescintigraphy (morphine cholescintigraphy [MC]) in hospitalized patients in whom the diagnosis is in doubt. SUMMARY/BACKGROUND DATA: Diagnosis of acute cholecystitis, calculous or acalculous, may be difficult in patients hospitalized for abdominal pain or other illnesses. Clinical signs often are obscure, and routine imaging studies are nonspecific or associated with a high incidence of false-positive tests. The authors report the use of MC in the evaluation of 163 hospitalized patients for acute cholecystitis over an 8-year period. METHODS: All patients suspected to have acute cholecystitis initially had standard cholescintigraphy performed, which showed nonvisualization of the gallbladder, and then were given morphine sulfate (0.05-0.1 mg/kg, intravenously). Patients were divided into the following three groups: I--acute abdominal pain (N = 53); II--hospitalized for associated illness (N = 49); and III--critically ill (N = 61). RESULTS: Overall, MC confirmed the diagnosis of acute cholecystitis in 75 patients (46%), including 23 cases of acalculous cholecystitis. Visualization of the gallbladder occurred within 60 minutes of intravenous administration of morphine sulfate in all patients. Cystic duct obstruction and, presumably, the diagnosis of acute cholecystitis was excluded in 79 patients, including 38 who were critically ill. There were eight false-positive and one false-negative studies. Morphine cholescintigraphy had a sensitivity of 99%, a specificity of 91%, a positive predictive value of 0.9, a negative predictive value of 0.99, and an overall accuracy of 94%. CONCLUSIONS: In hospitalized patients with nonvisualization of the gallbladder after standard cholescintigraphy, MC is highly accurate, especially in predicting the absence of acute cholecystitis in patients with known risk factors.
Data on 41 kala-azar patients were collected and the series of serological tests employed to diagnose the disease were compared depending upon their sensitivity and specificity indices. The indirect fluorescent antibody test (IFAT) was found to be 100% sensitive and specific. The direct agglutination test (DAT) involving detection of agglutinating antibodies against Leishmania donovani was 97.2% efficient. The enzyme-linked immunosorbent assay (ELISA) had a specificity of 75% while other tests such as counter-immunoelectrophoresis (CIEP), aldehyde and the Sia water test ranged from 84.3 to 97.2% in efficiency. On the basis of the costs and ease of the tests, the use of DAT along with CIEP is highly recommended for early detection of kala-azar.
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The vitamin C content of foods was examined from two national databases and new values were obtained by HPLC. HPLC values were lower in four of the five highest vitamin C contributors to the US diet (orange juice, grapefruit, tomatoes and tomato juice, and potatoes), as well as in broccoli, red peppers, and cooked collard and mustard greens, compared with values from the other databases. When HPLC values were substituted in the Health Habits and History Questionnaire, the resulting estimates of dietary intake of vitamin C in two studies were lower. Despite these lower estimates of absolute intake, in one study the correlation between dietary vitamin C and plasma ascorbic acid was similar. In conclusion, the accuracy of the vitamin C content of foods is important for estimating the absolute amount of vitamin C intake in the population but may not change the ranking of people in epidemiological studies.