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Biomedical subjects

R Shukla

Publications and source records attributed to R Shukla.

At least 37 records · Page 2Linked to original sources

Postictal language dysfunction in complex partial seizures: effect of contralateral ictal spread.

The authors report postictal language evaluation in patients monitored with bitemporal depth electrodes. Patients whose seizures began in the nondominant temporal lobe and propagated to the contralateral temporal lobe had a prolonged postictal language delay (PILD) with paraphasic errors compared with seizures that did not spread. Shorter propagation time was also associated with a longer PILD. Our study suggests that ictal involvement of the dominant temporal lobe is important in postictal language behavior.

Aphasia↗

Platelet 3H ketanserin binding in migraine.

Platelet 3H ketanserin binding was studied in 33 patients of migraine and 30 healthy controls. The binding characteristics: equilibrium dissociation constant (Kd) and maximal number of binding sites (Bmax) determined by Scatchard analysis revealed a significant decrease in Kd and no change in Bmax in migraine cases. No correlation was observed between the Kd and Bmax with the clinical features of migraine. The findings of the present study show that there is a decreased affinity of platelet 5-HT2 receptors in migraine.

Adult↗

Blood nitrite levels in patients with migraine during headache-free period.

OBJECTIVE: To investigate blood nitrite levels after migraine attacks and to assess whether or not the change in nitric oxide levels observed during acute migraine persist after the attacks. BACKGROUND: Involvement of nitric oxide has been suggested in the initiation of acute migraine. Recent studies have shown alteration in the platelet response and platelet nitrite levels during migraine attacks. METHODS: Patients with migraine with aura and patients without aura were included in the study. The study was conducted on 50 patients with migraine and 90 healthy controls. Blood from the patients was collected at least 7 +/- 0.8 days after the last attack of migraine. Nitrite levels in the polymorphonuclear leukocytes, platelets, and plasma were estimated. Platelet aggregation response in some of these patients was also studied. RESULTS: No significant change in the polymorphonuclear leukocyte, platelet, and plasma nitrite levels in patients with migraine compared to controls was observed. Patients with migraine with aura had significantly lower polymorphonuclear leukocyte nitrite levels compared to those without aura (P<.05). In addition, no significant difference in the adenosine diphosphate-induced platelet aggregation was observed in the migraineurs compared to the healthy controls. CONCLUSIONS: Results obtained indicate that the platelet aggregation response and the blood nitrite levels were not altered significantly after an attack in the patients with migraine.

Adult↗

Choosing and using services for sexual health: a qualitative study of women's views.

OBJECTIVE: To explore women's accounts of choosing and using specialist services for sexual health. METHODS: A qualitative study involving semistructured interviews with 37 women screened for Chlamydia trachomatis attending genitourinary medicine and family planning clinics in an East Midlands health authority. RESULTS: In making the decision to seek help, women act on a range of specific prompts, including lay ideas about the significance of symptoms; their own behaviour; their partner's symptoms or behaviour; contact tracing; and health promotion. Some women do not seek help specifically in relation to sexual health but are identified as being at risk of sexually transmitted infections (STIs) during routine consultations. Important influences on women's choice of services include the lay referral system, "insider" knowledge of health services, referral by health professionals, and need to have alternatives to general practice care. Women's willingness to access services is mediated by psychosocial factors such as embarrassment. They may use smear tests as a legitimate opportunity to raise questions about sexual health. Women's priorities for services are that their feelings of stigma and embarrassment are managed appropriately; that staff communicate well and are sensitive to their emotions and comfort during tests and procedures; that they are "in control" when obtaining test results; and that confidentiality is preserved. CONCLUSIONS: A detailed understanding of both lay people's response to symptoms or behaviour that indicates risk of an STI and their needs when using services should inform interventions aimed at encouraging secondary prevention of STIs.

Adolescent↗

Greater Cincinnati/Northern Kentucky Stroke Study: volume of first-ever ischemic stroke among blacks in a population-based study.

BACKGROUND AND PURPOSE: The volume of ischemic stroke on CT scans has been studied in a standardized fashion in acute stroke therapy trials with median volumes between 10.5 to 55 cm(3). The volume of first-ever ischemic stroke in the population is not known. METHODS: The first phase of the population-based Greater Cincinnati/Northern Kentucky Stroke Study identified all ischemic strokes occurring in blacks in the greater Cincinnati region between January and June of 1993. The patients in this phase of the study who had a first-ever ischemic clinical stroke were identified, and the volume of ischemic stroke was measured. RESULTS: There were 257 verified clinical cases of ischemic stroke, of which 181 had a first-ever ischemic infarct. Imaging was available for 150 of these patients, and 79 had an infarct on the CT or MRI study that was definitely or possibly related to the clinical symptoms. For these patients, volumetric measurements were performed by means of the modified ellipsoid method. The median volume of first-ever ischemic stroke for the 79 patients was 2.5 cm(3) (interquartile range, 0.5 to 8.8 cm(3)). There was a significant relation between location of lesion and infarct size (P<0.001) and between volume and mechanism of stroke (P=0.001). CONCLUSIONS: The volume of first-ever ischemic stroke among blacks in our population-based study is smaller than has been previously reported in acute stroke therapy trials. The large proportion of small, mild strokes in blacks may be an important reason for the low percentage of patients who meet the inclusion criteria for tissue plasminogen activator. Further study is necessary to see if these results are generalizable to a multiracial population.

Acute Disease↗

Effect of competing alkali metal cations on neutral Host's anion binding ability

Anion binding by neutral hosts in organic solvents can be inhibited by the presence of alkali metal cations. The binding inhibition is due to salt ion-pairing which increases in the order Cs(+) < K(+) < Na(+). The binding inhibition can be reversed by using heteroditopic hosts that simultaneously bind both the metal cation and the anion. The largest cation-induced enhancements are observed with the less basic anions.

Journal Article↗

Bovine serum albumin-hemoglobin fractionation: significance of ultrafiltration system and feed solution characteristics.

This work investigates the fractionation of similar molecular weight proteins bovine serum albumin (69 kD) and bovine hemoglobin (67 kD) by ultrafiltration. Three different membranes, viz. regenerated cellulose, poly(sulfone) and surface modified poly(acrylonitrile), each with a nominal molecular cutoff rating of 100 kD, were examined. The experiments were conducted in dead end, crossflow and vortex flow filtration modes and the separation was studied as a function of feed pH and ionic strength. Under similar system hydrodynamics, the surface modified poly(acrylonitrile) membrane displayed the highest resolution with minimum membrane fouling. The separation could be improved further by operating at low applied pressure (40 kPa) and high mass transfer (> 20 x 10(-6) m/s) in a vortex flow module. Under these conditions, the highest separation factor of 40 was obtained at the pI of hemoglobin.

Filtration↗

Disability case management: an impact assessment in an automotive manufacturing organization.

A multifaceted disability management program was instituted at an automotive manufacturing organization to control rising workers' compensation costs. A pilot program showed major cost savings over a 9-month period. When total and component disability leave rates were calculated as a percentage of the available workforce and tracked on a weekly basis over the subsequent 3 years, total disability leave rates fell by nearly 50%. This was largely attributable to an approximately 50% decrease in the extended (> 1-year) disability leave rate and a 75% decrease in the workers' compensation leave rate. A novel approach to biostatistical analysis showed a good fit of weekly disability leave rates to a Poisson random variable distribution with an identifiable break point at about 1 1/2 years after observation for extended disability leaves and at 2 years for workers' compensation leaves. This biostatistical approach may prove generalizable to tracking leave rates in other organizations.

Adult↗

Detecting hormesis using a non-parametric rank test.

When a dose-response experiment is conducted, the enhanced responses can be observed at low doses. This phenomenon is often called hormesis. The enhanced responses at low doses does not necessarily mean the existence of hormesis. It is important to conduct statistical analyses to determine whether a departure from monotonic relationships is significantly different from the chance occurrence. This paper introduces a non-parametric rank test to detect hormesis. To illustrate the use of this method, we apply it to the data from a Whole Effluent Toxicity test. We demonstrate that the occurrence of hormesis can be statistically evaluated by using this non-parametric rank test.

Animals↗

The effects of hypergravity and substrate vibration on vestibular function in developing chickens.

We used linear vestibular evoked potentials (VsEPs) to characterize peripheral and central vestibular function in birds following embryogenesis at 2G centrifugation or at elevated levels of vibration (+20dB re: background levels). Additionally, we characterized peripheral and central vestibular adaptation to 2G centrifugation in early post-hatch birds. Linear VsEP response peak latencies, amplitudes, thresholds and input/output functions were quantified and compared between experimental and control animals. Birds vibrated throughout embryogenesis and up to one-week post-hatch revealed no changes in linear VsEP response components compared to control siblings. Birds centrifuged at 2G throughout embryogenesis also evidenced no changes in the linear VsEP measured at hatch (P0). Significant changes were seen, however, for linear VsEPs of post-hatch birds placed at 2G for 7 days beginning on post-hatch day 5. Linear VsEPs for these animals displayed significant reductions in response amplitudes associated with peaks P2, N2 and P3, response peaks generated by central neural relays of gravity receptors. The earliest response components, generated by the peripheral vestibular nerve (i.e., P1, N1), were not significantly altered with the 7-day exposure to 2G. Thus, there was no evidence of generalized changes in peripheral gravity receptor excitability or in the rate of maturation in developing animals under increased levels of gravity or vibration. If gravity level plays a critical role in shaping peripheral vestibular ontogeny at magnitudes between 1 and 2G, then it may serve to stabilize function under changing G-fields or it may operate on physiological features that can not be resolved by the VsEP. In contrast, exposure to elevated gravity during post-hatch periods does alter central vestibular function thus providing direct evidence for central vestibular adaptation to the gravitational environment. The fact that central functional change was observed in hatchlings and not embryos, raises the possibility that the first 2-weeks post-hatch may be a critical period of "heightened developmental sensitivity" to hypergravity.

Adaptation, Physiological↗

Utilization of the nephrectomized mouse for determining threshold effects of MRI contrast agents.

The tissue concentration of an extravascularly distributed MRI contrast agent required to achieve a 20% change in the MRI signal intensity (SI) of skeletal muscle was determined using radiolabeled gadoteridol administered to nephrectomized mice. This minimal change in the quantified SI was reliably detected qualitatively in the MR muscle images. MR images of muscle were acquired following each intravenous injection of six sequential doses of 0.8 micromol of 153Gd-labeled gadoteridol. A 2.0 T imaging spectrometer and a T1-weighted spin-echo pulse sequence were used to acquire the MR images. After imaging, the injected 153Gd in muscle was measured, and the 153Gd assay results were used to determine the gadoteridol concentration in muscle following each injection. The muscle concentrations of gadoteridol were then correlated to the quantified enhanced MR SI of muscle. Using the 20% factor, it was concluded that the amount of gadoteridol necessary to achieve a reliable change in the SI of muscle was 33+/-10 nmol/g-skeletal muscle.

Animals↗

A hypothesis for what conformation of the major adduct of (+)-anti-B[a]PDE (N2-dG) causes G-->T versus G-->A mutations based upon a correlation between mutagenesis and molecular modeling results.

Molecular modeling (simulated annealing) was used to study the conformations in dsDNA of [+ta]-B[a]P-N2-dG (R.E. Kozack and E.L.Loechler, accompanying paper), which is the major benzo[a]pyrene (B[a]P) adduct. Sixteen classes of conformations were identified, and are analyzed herein vis-a-vis the two most prominent B[a]P mutations, G-->T and G-->A base substitutions. Eight conformations seem more relevant to frameshift mutagenesis, so they are excluded, leaving eight conformations as follows. Two conformations (BPmi5 and BPmi3) retain Watson-Crick G:C base pairing having the B[a]P moiety of the adduct in the minor groove. Two conformations (BPma5 and BPma3) have the Hoogsteen orientation with B[a]P in the major groove. Four conformations are base displaced and have B[a]P stacked in the helix with the dG moiety of the adduct displaced into either the major groove (Gma5 and Gma3) or the minor groove (Gmi5 and Gmi3). Three of these eight conformations (BPma5, BPma3 and Gma3) are universally high in energy. The two conformations that retain G:C base pairing potential (BPmi5 and BPmi3) are likely to be non-mutagenic. Of the three remaining conformations, Gmi5 can be relatively low in energy, but is distorted. A correlation exists between the calculated energies for the remaining two base displaced conformations and mutagenesis for [+ta]-B[a]P-N2-dG, leading to the hypothesis that Gma5 is responsible for G-->T mutations and Gmi3 is responsible for G-->A mutations. Gma5 and Gmi3 resemble each other, except that dG is in the major and minor grooves, respectively. An incipient rationale for this hypothesis is discussed: DNA polymerase might be triggered to follow a different mutagenic pathway depending upon whether a non-informational lesion has bulk protruding into the major or minor groove. A pathway for interconversion between these eight conformations is also proposed and its implications are discussed; e.g. four steps are required to interconvert between Gma5 and Gmi3.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

The major, N2-dG adduct of (+)-anti-B[a]PDE induces G-->A mutations in a 5'-AGA-3' sequence context.

Previously, in a random mutagenesis study, the (+)-anti diol epoxide of benzo[a]pyrene [(+)-anti-B[a]PDE] was shown to induce a complex mutational spectrum in the supF gene of an Escherichia coli plasmid, which included insertions, deletions and base substitution mutations, notably a significant fraction of GC-->TA, GC-->AT and GC-->CG mutations. At some sites, a single type of mutation dominated and to understand individual mutagenic pathways these sites were chosen for study by site-specific means to determine whether the major adduct, [+ta]-B[a]P-N2-dG, was responsible. [+ta]-B[a]P-N2-dG was shown to induce approximately 95% G-->T mutations in a 5'-TGC-3' sequence context and approximately 80% G-->A mutations in a 5'-CGT-3' sequence context. (+)-anti-B[a]PDE induced principally GC-->CG mutations in the G133 sequence context (5'-AGA-3') in studies using both SOS-uninduced or SOS-induced E. coli. Herein, [+ta]-B[a]P-N2-dG is shown to induce principally G-->A mutations (>90%) either without or with SOS induction in a closely related 5'-AGA-3' sequence context (identical over 7 bp). This is the first time that there has been a discrepancy between the mutagenic specificity of (+)-anti-B[a]PDE versus [+ta]-B[a]P-N2-dG. Eight explanations for this discordance are considered. Four are ruled out; e.g. the second most prevalent adduct [+ca]-B[a]P-N2-dG also induces a preponderance of G-->A mutations (>90%), so it also is not responsible for (+)-anti-B[a]PDE-induced G133-->C mutations. The four explanations not ruled out are discussed and include that another minor adduct might be responsible and that the 5'-AGA-3' sequence context differed slightly in the studies with [+ta]-B[a]P-N2-dG versus (+)-anti-B[a]PDE. In spite of the discordance, [+ta]-B[a]P-N2-dG induces G-->A mutations in the context studied herein and this result has proven useful in generating a hypothesis for what conformations of [+ta]-B[a]P-N2-dG are responsible for G-->T versus G-->A mutations.

Adenine↗

Polymorphonuclear leukocyte nitrite content and antioxidant enzymes in Parkinson's disease patients.

OBJECTIVE: The present study was undertaken to evaluate the alteration in the peripheral neuronal nitric oxide synthase (NOS) activity in Parkinson's disease patients. Therefore, basal nitrite content in PMNs, platelets and in the plasma of PD and control Indian population were evaluated. MATERIALS AND METHODS: We estimated nitrite, the nitric oxide (NO) metabolite, in neutrophils (PMNs), platelets and in plasma of control and in L-dopa treated Parkinson's disease (PD) patients. We also measured the activity of catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx) in the PMNs. RESULTS: We observed a significant increase in the basal nitrite content in PMNs of PD patients without any alteration in the plasma and platelets. Thus, the change was specific to PMNs. Catalase activity was significantly less in the PMNs of PD patients, but SOD and GPx remained unaltered. CONCLUSION: Results obtained in the PD patients exhibit an increase in the NOS activity in PMNs. Thus, involvement of NO is suggested in PD.

Adult↗

Incidence rates of first-ever ischemic stroke subtypes among blacks: a population-based study.

BACKGROUND AND PURPOSE: The aim of this study was to determine the incidence rates of ischemic stroke subtypes among blacks. METHODS: Hospitalized and autopsied cases of stroke and transient ischemic attack among the 187 000 blacks in the 5-county region of greater Cincinnati/northern Kentucky From January 1, 1993, through June 30, 1993, were identified. Incidence rates were age- and sex-adjusted to the 1990 US population. Subtype classification was performed after extensive review of all available imaging, laboratory data, clinical information, and past medical history. Case-control comparisons of risk factors were made with age-, race-, and sex-matched control subjects. RESULTS: Annual incidence rates per 100 000 for first-ever ischemic stroke subtypes among blacks were as follows: uncertain cause, 103 (95% confidence interval [CI], 80 to 126); cardioembolic, 56 (95% CI, 40 to 73); small-vessel infarct, 52 (95% CI, 36 to 68); large vessel, 17 (95% CI, 8 to 26); and other causes, 17 (95% CI, 9 to 26). Of the patients diagnosed with an infarct of uncertain cause, 31% underwent echocardiography, 45% underwent carotid ultrasound, and 48% had neither. Compared with age-, race-, and sex- (proportionally) matched control subjects from the greater Cincinnati/northern Kentucky region, the attributable risk of hypertension for all causes of first-ever ischemic stroke is 27% (95% CI, 7 to 43); for diabetes, 21% (95% CI, 11 to 29); and for coronary artery disease, 9% (95% CI, 2 to 16). For small-vessel ischemic stroke, the attributable risk of hypertension is 68% (95% CI, 31 to 85; odds ratio [OR], 5.0), and the attributable risk of diabetes is 30% (95% CI, 10 to 45; OR, 4.4). For cardioembolic stroke, the attributable risk of diabetes is 25% (95% CI, 4 to 41; OR, 3.1). CONCLUSIONS: Stroke of uncertain cause is the most common subtype of ischemic stroke among blacks. Cardioembolic stroke and small-vessel stroke are the most important, identifiable causes of first-ever ischemic stroke among blacks. The incidence rates of cardioembolic and large-vessel stroke are likely underestimated because noninvasive testing of the carotid arteries and echocardiography were not consistently obtained in stroke patients at the 18 regional hospitals. Most small-vessel strokes in blacks can be attributed to hypertension and diabetes.

Black or African American↗

Survey of neonatal hepatitis B vaccination in Leicestershire.

Some 121,390 live and still births were recorded in Leicestershire between June 1986 and May 1995. All mothers were offered antenatal screening for hepatitis B and 161 were positive for hepatitis B surface antigen. Examination of case notes from 113 mother and baby pairs identified 70 infants who fulfilled criteria for vaccination in place at the time, 47 of whom (67%) had received the three doses of hepatitis B vaccine then recommended for prevention of neonatal infection.

England↗