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Biomedical subjects

R Shukla

Publications and source records attributed to R Shukla.

At least 145 records · Page 8Linked to original sources
PubMed1989

Regulation of carcinogens in terms of life shortening.

Because of the difficulty in using the results of conventional quantitative risk assessment in the regulation of carcinogens, an approach to setting carcinogen standards is presented based on the reduction of cancer-induced life span shortening to statistically nonsignificant levels. An argument is made that the time of cancer occurrence is more important than the risk of cancer. The rationale is that the objective of carcinogen control is to delay the single-risk time of cancer occurrence. Whether this benefit is associated with a decrease, increase or no change in the risk of dying of cancer depends on concomitant changes in the temporal pattern of other causes of death. For indispensable carcinogens the permissible exposure is the level which shortens the time to background cancer by an amount equal to the uncertainty in the time of background cancer occurrence. This approach is illustrated by the use of the ED01 2-FAA bioassay on mice.

Animals↗
PubMed1989

Fetal and infant lead exposure: effects on growth in stature.

The growth of a cohort of 260 infants was prospectively followed up from birth. Blood lead and stature measurements were obtained every 3 months until 15 months of age. Fetal lead exposure was indexed by measuring lead in maternal blood during pregnancy. A longitudinal analysis revealed that covariate adjusted growth rates in stature were negatively related to the infants' postnatal blood lead concentration, as indexed by increase in average blood lead values from 3 to 15 months. However, this relationship between growth rate and change in blood lead concentration was evidenced only among those infants whose mothers had prenatal blood lead levels greater than the maternal cohort median of 7.7 micrograms/dL is about 2 cm shorter at 15 months of age if, postnatally, the infant incurred a 10-micrograms/dL blood lead increase during the 3- to 15-month interval of life, compared with an infant who has no increase.

Cohort Studies↗
PubMed1989

Characterization of histamine receptors in tracheal smooth muscle of Mastomys natalensis.

The tracheal smooth muscle of Mastomys natalensis contracted with carbachol administration while histamine (H) caused concentration-dependent relaxation. The Specific H2-receptor agonists 4-methyl histamine, dimaprit, impromidine and a high concentration of 2-methyl histamine (H1-agonist) caused relaxation similar to H which was selectively blocked by cimetidine. Low concentrations (10(-5)-10(-4) mol/L) of 2-methyl histamine and of H (10(-8)-10(-7) mol/L) occasionally produced small contractions. Mepyramine (pyrilamine) blocked the contraction but did not modify the relaxant effect of H and its agonists. The results suggest a preponderance of histamine H2-inhibitory receptors in the trachea of this animal.

Animals↗
PubMed1988

Loss of evoked potentials during spinal surgery due to spinal cord hemorrhage.

The cortical somatosensory evoked potential (SEP) disappeared during corrective spinal surgery in a patient with muscular dystrophy. The patient died 18 hours after surgery. Autopsy revealed an intramedullary hemorrhage 4 mm in diameter in the posterior horn of the cervical spinal cord. Microscopically, hypoxic neurons were seen adjacent to the hemorrhagic area, implying that the lesion was at least 6 hours old. The hemorrhage corresponded to the loss of SEPs and confirms that spinal cord monitoring can detect such lesions.

Adolescent↗
PubMed1988

Age-related differences in receptors for Escherichia coli heat-stable enterotoxin in the small and large intestine of children.

Escherichia coli that produce heat-stable enterotoxin are a worldwide cause of diarrheal disease, especially in children. We examined small and large intestinal specimens from children of various ages for the presence of E. coli heat-stable entero-toxin receptors and determined whether the number of receptors or the binding affinity of these receptors was related to the age of the child. We observed specific binding of 125I-heat-stable enterotoxin to all small intestinal and colonic specimens. However, a greater number of receptors per microgram of membrane protein were present in infants and the number of receptors rapidly decreased with increasing age. We also observed that increased heat-stable enterotoxin stimulation of guanylate cyclase was correlated with increased receptor density. We suggest that a greater number of gastrointestinal receptors for heat-stable enterotoxin, capable of activating more guanylate cyclase, may contribute to the increased severity of diarrhea noted in young children exposed to enterotoxigenic E. coli.

Adolescent↗
PubMed1988

Effects of short duration exposures to acetone and methyl ethyl ketone.

Workers are commonly exposed to mixtures or combinations of chemical agents, and these mixtures often consist of solvents. One group of solvents that has been extensively studied for its neurotoxic properties has been the ketones. However, previous research has focused on neuropathies produced by extended exposures and not on the simple pharmacokinetics or the reversible central nervous system (CNS) effects from short-duration exposures. In this research, 137 volunteers were recruited and tested for neurobehavioral performance changes and biochemical indicators during and after a short-duration (4-h) exposure to either acetone at 250 ppm, methyl ethyl ketone (MEK) at 200 ppm, acetone at 125 ppm with MEK at 100 ppm, or a chemical-placebo. Ethanol (95%, 0.84 ml/kg) was used as a positive control. Testing took place in an environmental chamber with four test stations. The computer-controlled test regimen took 10 h, and several measures were collected: (1) biochemical measurements of venous blood and alveolar breath; (2) psychomotor tests of choice reaction time, visual vigilance, dual task (auditory tone discrimination and tracking), and memory scanning; (3) one sensorimotor (postural sway) test; and (4) one psychological (Profile of Mood States [POMS]) test. Blood and breath concentrations during and after exposure did not demonstrate any interaction between the two solvents, nor were statistically significant sex differences present during uptake or elimination. The 250-ppm acetone exposure produced small but statistically significant differences from controls in two measures of the auditory tone discrimination task, and on the anger-hostility scale (males only) of the POMS test. The other chemical exposure conditions, MEK at 200 ppm and combination MEK with acetone, produced no consistent statistically significant results, which suggests there was no potentiation of the acetone effects with the co-exposure to MEK or vice versa under these test conditions. Ethanol at 0.07-0.08% blood alcohol concentration (BAC) caused significant decrements on both the auditory tone and tracking tests in the dual task.

Acetone↗
PubMed1988

Comparison of the cardiac output and stroke volume response to upright exercise in children with valvular and subvalvular aortic stenosis.

Cardiac output and stroke volume were evaluated in 17 children (mean age 11.5 +/- 3 years) with discrete, membranous subvalvular (Group I, n = 7) and valvular (Group II, n = 10) aortic stenosis during submaximal and maximal (greater than 75% predicted maximal oxygen consumption) upright cycle ergometry. Patients with valvular aortic stenosis were further subdivided on the basis of their aortic valve gradient at rest determined by cardiac catheterization (Group IIA, gradient less than 40 mm Hg; Group IIB, gradient greater than or equal to 40 mm Hg). These patients were matched with 17 control subjects on the basis of age, sex, height and intensity of exercise during maximal exertion. Cardiac and stroke indexes were determined by the acetylene rebreathing method at each exercise level. Stroke volume index in Group I was significantly greater at rest when compared with that in control subjects (69 +/- 13 versus 53 +/- 11 ml/m2, alpha = 0.01, p less than 0.05) and that in patients in Group II (69 +/- 13 versus 47 +/- 12 ml/m2, alpha = 0.01, p less than 0.05). Patients with subvalvular aortic stenosis were unable to increase their stroke volume index from rest to submaximal exercise and also decreased their stroke volume index at maximal exercise levels. In contrast, patients with mild valvular aortic stenosis (Group IIA) displayed a normal exercise response. Patients with severe valvular aortic stenosis (Group IIB) had a blunted stroke volume response at rest and at each level of exercise, as well as signs of myocardial ischemia (ST segment depression) during maximal exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Postural disequilibrium quantification in children with chronic lead exposure: a pilot study.

Previous studies reported that some children who survive acute lead encephalopathy suffer from ataxia and have difficulties maintaining postural equilibrium. More recent studies have failed to quantify postural imbalance in association with lower levels of lead exposures, perhaps due to the insensitivity of the clinical measure. In our study, we noninvasively measured postural disequilibrium with a microprocessor-based force platform. The test provides a real time quantification of the body's center of gravity movement pattern. Measurements were made in a cohort of 33 inner city children (mean age: six years +/- 0.4 SD) with well documented blood lead histories. The average maximum blood lead of these children during their first six years of life was 23.5 micrograms/dl (range = 8.5 to 49.4). The children performed four postural tests [i.e., standing eyes open (EO) and closed (EC), on firm surface and standing on a compliant foam surface with eyes open (FO) and closed (FC)]. The results indicated that the maximum blood lead incurred during the second year of life was significantly positively related to postural sway, and the body balance was most affected in the EC test where visual cues were eliminated and proprioceptive feedback was not modified. Fetal Pb exposure levels as well as Pb exposures during the first year of life were not correlated with postural sway of six year olds. However, the maximum blood lead concentration beyond two years of life was significantly associated with the postural sway at six years of age.

Child↗
PubMed1987

Plasma norepinephrine levels in infants and children with congestive heart failure.

To characterize the sympathetic nervous system response to congestive heart failure (CHF) in infants and children, plasma catecholamine levels were measured in 102 subjects undergoing routine cardiac catheterization (mean age 3.3 years, range 0.1 to 14.7), including 61 with left-to-right shunts. Plasma norepinephrine levels were significantly higher (p less than 0.0001) in children with CHF than in those without CHF. A highly significant association (p less than 0.0001) was found between the level of plasma norepinephrine and severity of CHF symptoms. This relation was found for CHF secondary to lesions producing a left-to-right shunt and CHF resulting from primary myocardial dysfunction. In congenital lesions with a left-to-right shunt, plasma norepinephrine levels correlated well with size of the shunt (Qp/Qs) (r = 0.75, p less than 0.001) and degree of pulmonary arterial hypertension (r = 0.70, p less than 0.001). Elevation of plasma norepinephrine concentrations in infants and children are seen with severe CHF regardless of its origin.

Adolescent↗
PubMed1987

Non-invasive estimation of afferent inputs for postural stability under low levels of alcohol.

The maintenance of human equilibrium is a complex process. Several physiological systems provide afferent information for postural stabilization. This study describes a noninvasive methodology to estimate the relative roles of interacting afferent inputs relevant for postural control. A multiaxis force platform in conjunction with specially designed test procedure provided semi-quantitative insight into the roles of vision, proprioceptors and vestibular apparatus in controlling postural sway when it was perturbed by a central nervous system perturbator such as alcohol. Experiments were conducted on 10 male and 10 female subjects. The males did not show statistically significant increases in body sway at these low levels of alcohol. For the females, the present methodology could detect subtle changes in postural sway at low blood alcohol levels ranging between 0.015% and 0.03%. At these low levels of alcohol, the results from females show that when the vision was excluded and the proprioception was modified, the postural sway was most affected. The postural instability experienced in this condition is probably due to inappropriate responses to proprioceptive inputs and lack of vision. Both male and female subjects showed a strong "eyes by standing surface" interaction. The proprioceptor manipulation alone did not affect the postural stability.

Adult↗
PubMed1987

Alteration of effective exposure of dam and embryo to caffeine and its metabolites by treatment of mice with beta-naphthoflavone.

The effect of treatment of pregnant C57BL/6J (B6) and AKR/J (AKR) mice with the cytochrome P-450 inducing agent beta-naphthoflavone (beta NF) on caffeine metabolism and on exposure of dam and embryo to caffeine and to its metabolites theophylline (TP), theobromine (TB), paraxanthine (PX), and trimethyluric acid (TMUA) was investigated. Treated dams were given either 20 or 80 mg beta NF/kg ip on Days 9 and 10 of gestation. Caffeine, 175 mg/kg, was given ip on Days 11 and 12 of gestation. Concentrations of caffeine and its metabolites were monitored in maternal plasma and in embryo homogenates at 0.083, 0.25, 0.5, 1, 2, 4, and 6 hr after the second caffeine injection. Effective exposure was expressed as the area under the concentration-time curve from 0 to 6 hr. Caffeine loss in B6 mice was best described by an expression incorporating capacity-limited kinetics. Pretreatment induced formation of TB and PX, while it induced elimination of all three of the monodemethylated metabolites, in B6 mice. Consequently, pretreatment caused marked reductions in exposure of B6 dams and embryos to both caffeine and TP. Exposure to TB and PX was less consistently affected, although it was reduced by pretreatment with 80 mg beta NF/kg. In contrast, exposure of AKR dams and embryos to caffeine and its metabolites was only slightly affected by beta NF pretreatment. The prevalence of paw malformations in the offspring of treated mice correlated well with effective exposure to both caffeine and TP, but not at all with the administered caffeine dose.

Animals↗
PubMed1987

Antibody response to herpes simplex virus glycoprotein D: effects of acyclovir and relation to recurrence.

We developed an enzyme-linked immunosorbent assay (ELISA) for measuring the antibody response to herpes simplex virus (HSV) glycoprotein D (gD). The ELISA was specific and more sensitive than immunoblotting techniques. Antibody to HSV gD was detected in 10 of 12 sera (geometric mean titer, 36.3) obtained from HSV-2-infected guinea pigs 14 days after intravaginal inoculation, and the titer increased to greater than or equal to 5,120 on day 60. Therapy with acyclovir delayed and diminished the antibody response to gD, although by day 60 the titers of antibody to gD in acyclovir-treated animals were not significantly different from those in controls. An increased titer of antibody to gD seemed to be associated with a reduced number of recurrent episodes and to a reduced number of days with recurrent lesions.

Acyclovir↗
PubMed1987

Serotonin in tension headache.

Serotonin (5-hydroxytryptamine, 5-HT) is implicated in the pathogenesis of migraine; however, its role in tension headache has not yet been studied. The uptake of 5-HT by platelets in patients of tension headache was significantly higher compared with migraineurs as well as controls. The basal platelet 5-HT levels did not show a significant difference. The study implicates the role of serotonin in tension headache.

Adult↗
PubMed1986

Evidence of sympathetic augmentation mediated increase in the blood and the plasma volume following vagotomy.

Cervical vagotomy was performed bilaterally in three series, i.e. normal (untreated), atropine treated and propranolol treated animals. The classical effect of the nerve section on heart rate, arterial blood pressure and respiration respectively were verified in the three series to confirm the reproducibility of the findings. The pre- and post-vagotomy plasma volume and haematocrit were estimated and thus the blood volume was calculated in each animal. The investigation indicated that: The interruption of vagal sensory information reflexively expanded the plasma and blood volume. This information was normally tonically active and inhibitory in nature. The volume expansion after vagotomy was brought about by stimulation of autonomic nerves, most probably the sympathetic nerves. These three conclusions suggested that expansion of vascular capacity as well as blood and plasma volume was controlled through vagal sensory information.

Animals↗