Fewer needlestick injuries than expected occurred during immunisation campaign.
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Biomedical subjects
Publications and source records attributed to A Sharma.
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Mice are fed by gavage crude garlic extract (100 mg/kg b.wt.) for 30 consecutive days. One set was administered sodium arsenite (0.1 mg/kg b.wt.) simultaneously. Another set was treated with sodium arsenite only. Mice given distilled water were kept as negative control. Exposed mice from each set were sacrificed and bone marrow preparations examined for chromosomal aberrations and damaged cells. Sodium arsenite is a strong clastogen and the effects were reduced to a significant level by prolonged administration of garlic extract. For F1 studies, exposed male mice were mated with exposed female mice, and the progeny examined. In the progeny, clastogenic effects of sodium arsenite persisted in a lower degree, indicating that the metal is able to cross the transplacental barrier. There was no statistically significant difference between the effect in progeny of parents only given sodium arsenite when given simultaneously for prolonged periods in the parents; however, the effect is meagre in the next generation.
Platelet activating factor (PAF; 1-0-alkyl-2 acetyl-sn-glycerol-3 phosphocholine) has been shown to have a wide range of biological activities. In this study, PAF was used to induce acrosome reactions in fresh as well as frozen-thawed buffalo spermatozoa at different incubation periods and PAF levels. As the period of incubation increased, there was a gradual decrease in motility and increase in acrosome reaction in both fresh and frozen-thawed spermatozoa. With increasing PAF levels, the motility of fresh spermatozoa decreased and acrosome reaction increased whereas in frozen-thawed semen, motility remained almost constant, and the increase in acrosome reaction was not pronounced. Differences in motility and acrosome reaction among different bulls, types of semen, periods of incubation and PAF levels were significant (P < 0.01). A PAF level of 100 microM and an incubation period of 15 min were found to be optimum for inducing acrosome reaction in buffalo spermatozoa, since at this combination acrosome reaction increased significantly (P < 0.01) over that of the control without much loss of motility.
BACKGROUND: High-dose melphalan (HDM) is now a standard treatment for multiple myeloma (MM). Stem cell transplants are fast evolving as an alternative to bone marrow transplants because they are less traumatic and easier to perform. A study was undertaken to test if whole blood harvested after mobilizing peripheral blood stem cells with granulocyte-colony stimulating factor (G-CSF) reinfused as such (without stem cells being processed or concentrated through a cell separator) for rescue after HDM (dose 140-180 mg/m2) in MM accelerates hematopoietic recovery. METHODS: Eight consecutive patients with MM were given HDM after receiving 4-5 courses of infusional vincristine, doxorubicin, and dexamethasone (VAD) chemotherapy. Approximately 6 weeks after the last course of chemotherapy, at the start of the procedure, G-CSF (Neupogen) was given at a dose of 10 microgram/kg subcutaneously daily for 4 days to mobilize stem cells. All of the patients had brisk leukocytosis (18.4-64.6 x 10(9)/L). On day 0 (fifth day after G-CSF), 1 L of blood was removed by phlebotomy and kept at room temperature for 24 hours. This was followed by a rapid intravenous (i.v.) bolus of melphalan at a dose of 140 mg/m2 in the first three patients, 155 mg/m2 in the 4th, 170 mg/m2 in the 5th, and 180 mg/m2 in the 6th, 7th, and 8th patients, applies to all patients along with hydration and diuresis. Twenty-four hours later, I L of blood previously removed was transfused back to the patient without any processing through the cell separator. The numbers of mononuclear cells reinfused was between 0.76 and 3.2 x 10(8)/kg (mean: 1.82 x 10(8)/kg). The number of CD 34+ cells infused in 4 patients ranged from 1.9 to 2.8 x 10(6)/kg (mean: 2.35 x 10(6)/kg). G-CSF was restarted on day 2 at a dose of 5 microgram/kg and given daily until the granulocyte count was 0.5 x 10(9)/L or more for 3 consecutive days. Antibiotics were given whenever a patient developed pyrexia. Platelets were transfused if below 20 x 10(9)/L or for incidences of overt bleeding. RESULTS: Granulocyte counts touched 0 between Days 6 and 10, lasting for an average of 3.4 days. Duration of granulocyte count below 0.5 x 10(9)/L was 6.5 days (range: 5-9), and these rose to 1.0 or more x 10(9)/L by Day 13.7 (range: 13-16). The number of platelet transfusions given per patient was 2.5 (range: 0-4). Intravenous antibiotics were used for 9 days (range: 4-12), and patients were discharged on Day 19 (range: 16-22). Follow-up ranged from 45 to 380 days. CONCLUSIONS: Hematopoietic recovery was rapid in all patients, including those who received doses of melphalan higher than 140 mg/m2. This resulted in less need for platelet transfusions or antibiotics, and hospitalization was short. Our results are historically similar to conventional peripheral blood stem cell transplants but much better than autologous bone marrow transplants, indicating that whole blood after G-CSF provided sufficient progenitor cels for early engraftment. The procedure is less labor intensive insofar as it does not require separation and concentration of stem cells. It has the potential of becoming an alternative to autologous marrow and peripheral blood stem cell transplantation in patients with MM.
Murine splenic T cells undergo apoptosis when the TCR complex is re-cross-linked in the absence of costimulation during a primary immune response. However, if the CD28 complex is also cross-linked, growth continues without induction of apoptosis. Prevention of apoptosis by CD28 costimulation was associated with increased expression of bcl-xL, while overexpression of bcl-2 in T cells from bcl-2 transgenic mice was not protective. In both situations, surviving cells can be recovered in a growth arrested state following the primary response, many more if CD28 was also religated. When these cells were restimulated in secondary response, those surviving TCR religation without CD28 costimulation could not be induced to proliferate further. In contrast, cells given CD28 costimulation during the primary response proliferated well after restimulation. Thus, the CD28 signaling pathway may function not only in the initial activation of naive T cells, but also in maintaining their viability and responsiveness during a primary immune response. In addition, the results further suggest that bcl-2 and bcl-xL regulate T cell survival under different conditions, with bcl-xL being perhaps more important in maintaining viability of activated T cells traversing the cell cycle.
Dietary consumption of green vegetables has been associated with protection against mutagenic and clastogenic activity of genotoxicants. Chlorophyll, being present in all green plants, had earlier been suggested to be the principal factor involved. Mice were administered (i) crude aqueous extract of leaf of Indian spinach, Beta vulgaris L. var.benghalensis Hort., and equivalent amounts of (ii) chlorophyll extracted from the leaf; (iii) purified chlorophyll, (iv) chlorophyllin, a sodium-copper derivative of chlorophyll; daily for 7 days. On day 7, one set of mice from each treatment was administered potassium dichromate-a known metallic clastogen. The mice were sacrificed after 24 hours. Chromosome preparations were made from bone marrow following the usual colchicine-air dry-Giemsa schedule. The cytogenetic endpoints scored were chromosomal aberrations and damaged cells. Crude leaf extract and chlorophyllin were nonclastogenic and reduced the clastogenic effects of potassium dichromate to the control distilled water level. Chlorophyll alone, whether extracted from the leaf or obtained in commercially purified form, was clastogenic and could reduce the effects of the chromium salt only to its own level. The protective action of the crude leaf extract may be attributed to the total effect of the interaction between the different components within the leaf extract, in which the clastogenicity of chlorophyll had been neutralized.
Pearl millet (Pennisetum typhoideum) grains were fermented with Lactobacilli and yeast alone, in combination and with natural flora at 30 degrees C for 48 h after giving various processing treatments viz, fine and coarse grinding, soaking, debranning, dry heat treatment, germination and autoclaving after adding of water. Fermentation was carried out with Lactobacillus acidophilus and Rhodotorula isolated from naturally fermented pearl millet and Lactobacillus acidophilus, Candida utilis and natural fermentation using freshly ground pearl millet flour as inoculum. All the processing treatments except coarse grinding improved the protein and starch digestibility. Autoclaving enhanced the digestibilities of processed samples which was further improved by different types of fermentation, the maximum being in case of germinated and naturally fermented pearl millet. A combination of Lactobacilli and yeast was more effective in increasing the protein as well as starch digestibility as compared to pure culture fermentation.
Although the acute toxicity of methanol is well documented, few studies have addressed the consequences of perinatal exposures to the low concentrations that are expected to arise from its proposed use as a component of automobile fuel. This report describes the general research design of a series of studies, the effects of methanol exposures on blood concentrations in dams and neonates, and indices of brain development. Four cohorts of Long-Evans pregnant rats, each cohort consisting of an exposure (n = 12) and a control (n = 12) group, were exposed whole-body to 4500 ppm methanol vapor or air for 6 hr daily beginning on Gestation Day 6. Both dams and pups were then exposed through Postnatal Day 21 (PND 21). Blood methanol concentrations determined by gas chromatography from samples obtained immediately following a 6-hr exposure reached approximately 500-800 micrograms/ml in the dams during gestation and lactation. Average concentrations for pups attained levels about twice those of the dams. Selected offspring from Cohort 4 were exposed for one additional 6-hr session at ages that extended out to PND 52. Regression analyses showed that the blood methanol concentrations of the pups declined until about PND 48, at which time their levels approximated those of their dams. Such pharmacokinetic differences might increase the risks posed to developing organisms. Light-microscopic analysis showed no significant abnormalities in the brains of the methanol-treated animals. However, assays of neural cell adhesion molecules (NCAMs) in brains of pups sacrificed on PND 4 showed staining for both the 140 and the 180 kDa isoforms to be less intense in the cerebellum of exposed animals. NCAM differences were not apparent in animals sacrificed 15 months after their final exposure.
Selective left ventricular hypoplasia is a recognized feature of congenital diaphragmatic hernia (CDH). It is speculated that the herniated viscera act as a space occupying lesion that inhibit normal cardiac development. The purpose of this study was to determine the effect of two separate fetal surgical interventions on subsequent cardiac development in CDH. CDH lambs were created at 80 days gestation and underwent either tracheal ligation (CDH + TL) or diaphragmatic repair (CDH + repair) at 110 days gestation. At term (141 days gestation) the hearts were harvested and fixed in 4% paraformaldehyde solution. Anatomic dissections were performed and component heart weights determined. Fresh specimens were analyzed for DNA and protein content. All weights are expressed in grams/kilogram body weight and all data as mean +/- SEM. All measurements are compared to control and CDH tissues. There were seven CDH lambs, five control lambs, five CDH + TL lambs, and five CDH + repair lambs. There were no differences in body weight (kg) between CDH, CDH + TL, CDH + repair, and control littermates. CDH lambs have significantly decreased total heart (4.88 +/- .25* vs 6.75 +/- .49, P < 0.05), left ventricular (1.65 +/- .11* vs 2.15 +/- .19, P < 0.05), septal (1.29 +/- .11* vs 1.99 +/- .21, P < 0.05), and combined atrial (0.68 +/- .06* vs 1.14 +/- .15, P < 0.05) weights (g/kg lamb) without differences in RV weights (1.26 +/- .07 vs 1.57 +/- .17, P = NS) when compared to littermate controls. No differences were found in total heart (4.82 +/- 0.38 vs 4.88 +/- 0.25), left ventricular (1.48 +/- 0.13 vs 1.65 +/- 0.11), septal (1.26 +/- 0.17 vs 1.29 +/- 0.11), combined atrial weights (0.56 +/- 0.07 vs 0.68 +/- 0.06), and right ventricular (1.52 +/- 0.12 vs 1.26 +/- 0.07) between CDH + TL and CDH lambs. There were no differences in total heart (6.60 +/- 0.29 vs 6.75 +/- 0.49), left ventricular (2.10 +/- 0.15 vs 2.15 +/- 0.19), septal (1.97 +/- 0.18 vs 1.99 +/- 0.21), combined atrial (1.10 +/- 0.10 vs 1.14 +/- 0.15), or right ventricular (1.52 +/- 0.12 vs 1.57 +/- 0.17) weights between CDH + repair and control lambs. LV and RV wall thicknesses (cm), as well as total protein and DNA content, and DNA/total protein ratios were identical in all groups. CDH lambs have a significant reduction in total heart weights mainly caused by hypoplasia of the left ventricle (left ventricular "smallness") and the interventricular septum. Removal of the herniated viscera and repair of the diaphragmatic defect correct this abnormality, but tracheal ligation does not. We speculate that although tracheal ligation reverses pulmonary hypoplasia, the enlarging lungs act as space occupying lesions that adversely affect cardiac development. Further investigations are necessary to determine the functional significance of these findings.
The 93D, or hsr-omega (heat-shock RNA-omega), locus of Drosophila melanogaster and other species of Drosophila, besides being induced as a member of the heat shock gene family, is also selectively and singularly inducible by a variety of agents, notably benzamide, colchicine and vitamin B6 (in species other than D. melanogaster). The genomic structure of this locus is highly conserved in all species, although the primary base sequence has diverged rapidly between species. Three transcripts (two nuclear and one cytoplasmic) are produced by this locus but none of them has any significant protein coding capacity. The profile of the three transcripts varies in a developmental and inducer-specific manner. This locus is developmentally active in nearly all cell types and is essential for viability of flies. Its induction during heat shock is independent of the other members of the heat shock gene family. The other selective inducers act on this locus through separate response elements. hsr-omega activity has a characteristic effect on transcription/turnover of the heat shock induced hsp70 and the alpha-beta transcripts in D. melanogaster. It appears that the hsr-omega locus has important house-keeping functions in transport and turnover of some transcripts and in monitoring the 'health' of the translational machinery of the cell.
Pearl millet (Pennisetum typhoideum) was fermented with Lactobacilli or yeasts alone and in combination, and with natural microflora after various processing treatments, as grinding, soaking, debranning, dry heat treatment, autoclaving and germination. Fermentation was carried out at 30 degrees C for 48 hours with Lactobacillus plantarum (LP) and Rhodotorula (R) isolated from naturally fermented pearl millet and Lactobacillus acidophilus (LA), Candida utilis (CU) and natural microflora (NF). Germination and autoclaving, and debranning and autoclaving were the most effective processing treatments to reduce the phytic acid, amylase inhibitors and polyphenols. There was a further reduction in these antinutrients due to fermentation. Phytic acid and amylase inhibitors were completely eliminated after fermentation in some of the samples especially in soaked, debranned and germinated ones. Polyphenols were altered non-significantly in general but fermentation with Lp + R and NF caused a significant increase in polyphenols.
The present study was undertaken to determine the incidence and related risk factors for coronary heart diseases and hypertension in the rural population of Kheda district, Gujarat (India). The observations from the first five years of this ongoing project (May 1987-May 1992) are described in this paper. Out of an initial sample of 750 individuals in the age group 30-62 years, who were selected by stratified random sampling, 714 persons (males = 429; females = 285) were actually studied, after excluding those suffering from coronary heart diseases (CHD). Initially, all the included subjects were examined clinically and appropriate laboratory investigations were done. A detailed socio-economic history was also obtained. Subsequently all of them were followed up and biannual clinical and laboratory investigations were performed. Cases of CHD were diagnosed according to the recommendations of the New York Heart Association. The overall five-year incidence of CHD was 25.17 per thousand persons. The incidence in males was 3 times higher than in females. More males suffered from myocardial infarction (MI), while in the females the incidence of sudden death was higher (33.3%). The average yearly mortality rate due to CHD was 2.46 per thousand persons. CHD was significantly associated with increased blood pressure (both diastolic and systolic), smoking, and family history of heart disease, and was weakly associated with body weight (p = 0.06).
Malignancy accounts for 40%-60% of pericardial effusions. Two individuals with malignant pericardial effusions secondary to lung, cancer, managed with the help of a percutaneous balloon pericardial window (PBPW), are discussed in this report. Clinical benefits in terms of reduction of breathlessness and improved diastolic function of the heart were documented in both. There were no procedure-related complications. The PBPW provides quick relief, appears diagnostically superior to an invasive technique and has a low rate of recurrence and complications.
OBJECTIVE: To study the usefulness of three electro-encephalographic descriptors, the average median frequency, the average 90% spectral edge frequency, and a bispectral variable were used with the anesthetic concentrations in estimating the depth of anesthesia. METHODS: Four channels of raw EEG data were collected from seven mongrel dogs in nine separate experiments under different levels of halothane anesthesia and nitrous oxide in oxygen. A tail clamp was used as the stimulus and the dog was labeled as a non-responder or responder based on its response. A bispectral variable of the EEG (just before a tail clamp) and the estimated MAC level of halothane and nitrous oxide combined were the two features used to characterize a single data point. A neural network analysis was done on 48 such data points. A second neural network analysis was done on 47 data points using average 90% spectral edge frequency and the estimated MAC level. The average median frequency of EEG was also evaluated, although a neural network analysis was not done. RESULTS: The first neural network needed nine weights in order to train and correctly classify all of the 12 points in the training set under a training tolerance of 0.2. It could correctly classify all of the remaining 36 data points as either belonging to responders or non-responders. A cross-validation procedure, which estimated the overall performance of the network against future data points, showed that the network misclassified two out of the 48 data points. The second neural network needed 25 weights in order to train and classify correctly all of the 26 points in the training set under a tolerance of 0.2. It was later able to classify all of the 21 points of the test group correctly. CONCLUSIONS: The bispectral variable seems to reduce the non-linearity in the boundary separating the class of non-responders from the class of responders. Consequently, the neural network based on the bispectral variable is less complex than the neural network that uses a power spectral variable as one of its inputs.
Four basic models of indirect pharmacodynamic responses were characterized in terms of changing dose, Imax or Smax, and IC50 or SC50 to examine the effects of these fundamental drug properties on response profiles. Standard pharmacokinetic parameters were used for generating plasma concentration, and response-time profiles using computer simulations. Comparisons to theoretical expectations were made. In all four models, the maximum response (Rmax) (inhibition or stimulation) and the time of its occurrence (TRmax) were dependent on the model, dose, Imax or Smax, and IC50 or SC50 values. An increase in dose or a decrease in IC50 or SC50 by the same factor produced, as theoretically expected, identical and superimposable pharmacodynamic response patterns in each of the models. Some parameters (TRmax, ABEC) were nearly proportional to log dose, while others (Rmax, CRmax) were nonlinear. Assessment of expected response signature patterns as demonstrated in this report may be helpful in experimental designs and in assigning appropriate models to pharmacodynamic data.
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Humans who are high sensation seekers and cats who demonstrate comparable behavioral traits show increasing amplitudes of the early components of the cortical visual evoked potential (VEP) to increasing intensities of light flash; low sensation seekers show VEP reducing. Roman high-avoidance (RHA) and Roman low-avoidance (RLA) rats have behavioral traits comparable to human and cat high and low sensation seekers, respectively. Previously, we showed that RHA and RLA rats are cortical VEP augmenters and reducers, respectively. The goal of this study was to determine if augmenting-reducing is in fact a property of the visual cortex or if it originates at the lateral geniculate nucleus and is merely reflected in recordings from the cortex. EPs to five flash intensities were recorded from the visual cortex and dorsal lateral geniculate of RHA and RLA rats. As in the previous study, the slope of the first cortical component as a function of flash intensity was greater in the RHA than in the RLA rats. The amplitude of the geniculate component that has a latency shorter than the first cortical component was no different in the two lines of rats. The finding from the cortex confirms the earlier finding of augmenting and reducing in RHA and RLA rats, respectively. The major new finding is that the augmenting-reducing difference recorded at the cortex does not occur at the thalamus, indicating that it is truly a cortical phenomenon.
Three concentrations (25, 50 and 100 mg/kg body weight) of fresh garlic (Allium sativum L.) were administered daily by gavage to Swiss albino mice for different durations up to 60 days. These concentrations had been observed to protect significantly against effects of known clastogens. The endpoints scored were frequencies of chromosomal aberrations and damaged cells induced in bone marrow preparations. These parameters were found to be directly dose dependent and after an initial enhancement at 7 days, were reduced following prolonged exposure for 30 and 60 days to the low level observed at 24 hr. Therefore, administration of a low concentration of garlic extract daily is suggested for at least 30 days to obtain the maximum benefit of the extract in protecting against the clastogenic effects of known genotoxicants.