Adsorption-desorption, persistence, and leaching behavior of flufenacet in alluvial soil of India.
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Biomedical subjects
Publications and source records attributed to S Gupta.
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This laboratory is evaluating phosphorothioate deoxyribonucleic acids (DNAs) and peptide nucleic acids (PNAs) for a variety of nuclear medicine applications. Morpholinos (MORFs) are a new class of oligomers with a nuclease-resistant, nonionic and water-soluble phosphorodiamidate backbone. We now report on the in vitro and in vivo properties of MORFs labeled with technetium-99m. Both 15-mer and 18-mer MORFs were obtained, each with a primary amine attached to the 3' equivalent end via a three-carbon beta-alanine linker. The amine was used to conjugate with NHS-MAG3 for 99mTc radiolabeling. By surface plasmon resonance at room temperature, the association rate constant for hybridization of the 18-mer MORF to its complementary oligomer (cMORF) was equivalent to that of DNAs and PNAs of comparable length. Hybridization of 99mTc-MORF in vitro to free cMORF, to a cMORF polymer and to cMORF beads was nearly quantitative under a variety of conditions. Kinetic studies in vitro at room temperature showed rapid (2-5 min) and nearly quantitative (90%) binding to cMORF beads. Using size-exclusion high-performance liquid chromatography, the stability of the 99mTc-MORF was found to be greater than 85% over 24 h in 37 degrees C serum with minimal protein binding. In normal mice, the 99mTc-MORF showed rapid pharmacokinetics, with only 21% and 8% remaining in the whole body at 3 and 24 h post administration, respectively. In vivo targeting with 99mTc-MORF of cMORF beads in one thigh of normal mice compared to control beads in the other thigh showed target/control thigh ratios of 2-10 between 3 and 24 h. These results demonstrate that MORF oligomers are capable of in vivo hybridization. Their properties of hybridization affinity and kinetics and their in vivo stability and pharmacokinetics make them suitable subjects for in vivo studies.
In two newborn boys an accessory rudimentary phallus and scrotal sacs were present on the surface of a midline perineal swelling. Both boys had an associated high anorectal anomaly (ARA), a small phallus, and a bifid scrotum with absence of the scrotal raphé. One also had penile torsion with hypospadias and an accessory anal dimple. During definitive surgery for the ARA in one patient, excision of the perineal soft-tissue mass and overlying duplicated penoscrotal tissue was performed. The embryogenesis of this condition is discussed.
Hepatocyte transplantation represents an alternative strategy for treating liver disease. Liver repopulation following acute liver failure could, potentially, eliminate the requirement for orthotopic liver transplantation. Similarly, the ability to repopulate the liver with disease-resistant hepatocytes offers new opportunities for correcting genetic disorders and treating patients with chronic liver disease. Recent advances concerning the fate of transplanted cells in the recipient liver, the efficacy of cell therapy in outstanding animal models of human disease. and the isolation of progenitor liver cells capable of differentiating into mature hepatocytes have renewed optimism in regard to treating people with hepatocyte transplantation. Recruitment of an increasing number of investigators to the field and the success of recent pilot studies indicate that hepatocyte transplantation will become routine clinical practice in the near future.
PURPOSE: To report a unique finding of metastatic tumor cells in the lumen of a superficial temporal artery biopsy specimen in a patient with severe visual loss and optic neuropathy. METHODS: Case report. RESULTS: A 69-year-old man presented with anorexia, pancranial headaches, and acute unilateral visual loss. Ophthalmic examination showed a visual acuity of no light perception and an amaurotic pupil in the left eye. Fundus examination was normal. A superficial temporal artery biopsy, performed for presumed arteritic posterior ischemic optic neuropathy, demonstrated intraluminal cells with irregular nuclei and prominent nucleoli suggestive of metastatic malignancy. Further systemic evaluation uncovered a poorly differentiated adenocarcinoma of the lung with intravascular infiltration and multiple distant metastases. CONCLUSION: Extensive systemic intravascular tumor embolization may be associated with optic neuropathy.
We present here a human cell model for examination of mutant N-ras function. The HT1080 human fibrosarcoma cell line is pseudodiploid and contains a single endogenous mutant N-ras allele. MCH603c8 cells are a variant of HT1080 cells, in which the mutant allele has been deleted. The two cell lines differ dramatically in the constitutive levels of activation of downstream members of the Ras signaling pathways, and in biological features of transformation and tumorigenicity. Downregulation or activation of individual Ras-dependent pathways can be accomplished via transfection of dominant negatives or activated mutant cDNAs into HT1080 and MCH603c8 cells, respectively. The biochemical and biological consequences of expression of these mutant cDNAs can be assessed. There are dramatic effects on both the transformed and tumorigenic phenotype, depending on the cell line and mutant cDNA that is transfected.
BACKGROUND: Significant cardiac toxicity has been associated with some older antihistamines (eg, terfenadine and astemizole) when their plasma concentrations are increased. There is thus a need for a thorough assessment of the cardiac safety of newer antihistamine compounds. OBJECTIVE: This study was undertaken to assess the effects of coadministration of desloratadine or fexofenadine with azithromycin on pharmacokinetic parameters, tolerability, and electrocardiographic (ECG) findings. METHODS: Healthy volunteers aged 19 to 46 years participated in this randomized, placebo-controlled, parallel-group, third-party-blind, multiple-dose study. Subjects received desloratadine 5 mg once daily, fexofenadine 60 mg twice daily, or placebo for 7 days. An azithromycin loading dose (500 mg) followed by azithromycin 250 mg once daily for 4 days was administered concomitantly starting on day 3. Group 1 received desloratadine and azithromycin, group 2 received desloratadine and placebo, group 3 received placebo and azithromycin, group 4 received fexofenadine and azithromycin, and group 5 received fexofenadine and placebo. RESULTS: The results of the pharmacokinetic analysis revealed little change in mean maximum concentration (Cmax) and area under the concentration-time curve (AUC) values for desloratadine with concomitant administration of azithromycin: Cmax ratio, 115% (90% CI, 92-144); AUC, ratio 105% (90% CI, 82-134). The corresponding ratios for 3-hydroxydesloratadine were 115% (90% CI, 98-136) and 104% (90% CI, 88-122), respectively. A substantial increase was observed in mean Cmax and AUC values for fexofenadine when administered with azithromycin: Cmax, ratio, 169% (90% CI, 120-237); AUC ratio, 167% (90% CI, 122-229). Compared with the group receiving desloratadine and azithromycin, subjects receiving fexofenadine and azithromycin also displayed greater variability in pharmacokinetic parameters for the antihistamine. Mean Cmax and AUC values of azithromycin were slightly higher when administered with desloratadine (Cmax ratio, 131% [90% CI, 92-187]; AUC ratio, 112% [90% CI, 83-153]) but were lower when given in combination with fexofenadine (Cmax ratio, 87% [90% CI, 61-124]; AUC ratio, 88% [90% CI, 65-1201). The most common adverse event for all regimens was headache, reported in 20 (22%) subjects. All combinations of desloratadine or fexofenadine with and without azithromycin were well tolerated, and no statistically significant changes in PR, QT, or QT, interval, QRS complex, or ventricular rate were observed. CONCLUSIONS: Small increases (<15%) in mean pharmacokinetics of desloratadine were observed with coadministration of azithromycin. By contrast, peak fexofenadine concentrations were increased by 69% and the AUC was increased by 67% in the presence of the azalide antibiotic. Based on the reported adverse-events profile and the absence of changes in ECG parameters, the combination of desloratadine and azithromycin was well tolerated. This study suggests that desloratadine has a more favorable drug-interaction potential than does fexofenadine.
PURPOSE: To assess the outcomes of cataract surgery in rural northwest India. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: A total of 549 cataract-operated persons (723 operated eyes). METHODS: Cluster sampling was used in randomly selecting a cross-sectional sample of persons 50 years of age or older for visual acuity measurement, refraction, and slit-lamp and direct ophthalmoscope examination early in 1999. Those operated on for cataract were queried as to the date and place of surgery. The principal cause of reduced vision was identified for all examined eyes with presenting visual acuity worse than 6/18. MAIN OUTCOME MEASURES: Presenting and best-corrected visual acuity and cause of vision loss. RESULTS: Presenting visual acuity was less than 6/60 in the better eye in 33.7% of cataract-operated persons and greater than or equal to 6/18 in both eyes in 8.2%; 31.7% were bilaterally operated on. Of cataract-operated eyes, 44.1% initially had visual acuity less than 6/60 and 31.5% greater than or equal to 6/18; with best correction, the corresponding percentages were 14.0% and 61.5%. Intracapsular cataract extraction was used in 92% of cases, and 66% had been operated on in surgery camps. Surgical complications were common and a major cause of vision impairment. In multiple logistic regression modeling, female gender and residence in a rural area were associated negatively with both presenting and best-corrected visual acuity outcomes, and surgery conducted before 1990 was associated negatively with best-corrected visual acuity. Place of surgery and subject schooling were not associated with vision outcomes. CONCLUSIONS: Cataract surgery subjects in rural areas of India that are without adequately equipped facilities and skilled surgeons, and lack of availability of intraocular lenses, are not realizing the full sight-restoring potential of modern-day surgery. Emphasis on the quality of cataract surgery outcomes must be increased to keep pace with that being given to increasing surgical volume.
PURPOSE: To assess the prevalence of central vision blindness and cataract surgery in older adults in rural northwest India. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: A total of 4284 examined persons 50 years of age or older. METHODS: A random selection of village-based clusters was used to identify a population sample in the predominantly rural Bharatpur district of Rajasthan. Eligible subjects in the 25 selected clusters were enumerated through a door-to-door household survey and invited to village sites for visual acuity testing and eye examination early in 1999. The principal cause of reduced central vision was identified for eyes that had visual acuity worse than 6/18. Independent replicate testing for quality assurance monitoring took place in participants with reduced vision and in a sample of those with normal vision in five of the study clusters. MAIN OUTCOME MEASURES: Presenting and best-corrected visual acuity and lens status. RESULTS: A total of 4728 eligible persons in 2821 households were enumerated, and 4284 (90.6%) were examined. The prevalence of presenting and best-corrected visual acuity worse than 6/60 in both eyes was 11.9% (95% confidence interval: 10.0%-13.9%) and 6.1% (95% CI: 4.7%-7.4%), respectively. Presenting blindness was associated with increasing age, female gender, lack of schooling, and rural residence. Cataract was the principal cause of blindness in one or both eyes in 67.5% of blind persons, with uncorrected aphakia and other refractive error affecting 18.4% in at least one eye. The prevalence of cataract surgery was 12.8% (95% CI: 11.6%-14.0%), with an estimated 65.7% of the cataract blind operated on; low surgical coverage was associated with lack of schooling. CONCLUSIONS: Blindness, particularly blindness because of cataract, continues to be a significant problem among the elderly living in remote areas of rural northwest India. Increased attention should be given to reaching women and the illiterate.
Several reports have indicated that the sewage-fed vegetables of the Dhapa area, near the city of Calcutta, contain a very high amount of heavy metals. Currently 800 ha of land is being utilised throughout the year to cultivate more than eight types of vegetables, with a production of about 147 tonnes per day. A major population of Calcutta consumes these vegetables grown in the Dhapa area. Recently there has been huge pressure on the State Government to ban vegetables grown in the Dhapa area for human consumption. For this reason, we have studied the genotoxic effects of some of the most commonly used vegetable extracts from the Dhapa area after in vivo acute exposure in mice as measured by chromosomal aberrations (CA) and sister chromatid exchanges (SCE) to find out the minimum threshold dose to induce CA and SCE. Three different concentrations of the three most commonly used vegetable extracts (cauliflower, spinach, radish) were fed by gavage to mice for the study of CA and SCE. A significant increase in CA was observed only at the highest concentration of all the vegetable extract-treated groups when compared with the solvent control. A significant increase in SCE were observed in the middle and high doses of spinach and only the high dose of cauliflower and radish extract-treated series when compared with distilled water control. The lowest dose was equivalent to approximately 1 kg of vegetables consumed by a human (60 kg body weight) in a day. The middle and high doses of each vegetable extract were much higher than the normal amount of vegetables that a human can consume per day. So the minimum dose for inducing SCE and CA was much higher than the amount a human can consume in a day. Therefore this study indicates that these vegetables are safe for human consumption up to a certain limit, and attention should be given to reducing the heavy metal contents in the soil and sewage of the Dhapa area to thus reduce the heavy metal concentrations in the vegetables.
A retrospective study was carried out based on 110 paediatric burns (0-14 years) seen at the Burn unit, Choithram Hospital & Research Centre, Indore over a period of 7 years (1993-1999). Epidemiological data included age, sex, seasonal variation, place of burn and the cause and mode of burn. Hospitalised paediatric burns constituted 13.5% of total burn accidents. These children were categorised into three groups, the infants and toddlers (0-2 years), early childhood (>2-6 years) and late childhood (>6-14 years). In the first two groups scalding was the predominant cause of injury while in late childhood there were many more flame and electric burns. Males were mainly affected. Most of the burns (53.6%) occurred in the winter season between October and February. Ninety-five percent of accidents occurred at home. The overall mortality rate was 21.8%. An intense campaign to make people aware of the risk factors and their avoidance is required to reduce the number of burn accidents in children.
Pathogen biodiversity is an under-exploited source of inference regarding disease processes and the evolution of pathogens and pathogenesis. In addition, the structure of pathogen populations, especially for diverse organisms such as the meningococcus, has implications for public health interventions including vaccination and antibiotic use. The predominant paradigm for interpreting bacterial diversity has been the clonal population structure, which has been modified by the incorporation of the effects of horizontal genetic exchange. Multilocus models of variable antigens, which explore the effects of immune selection, provide alternative explanations for structured diversity in pathogen populations.
Non-penetrating, arcuate-legged clips facilitate vascular reconstructions and significantly reduce the incidence of anastomotic neointimal hyperplasia. Though originally developed as a microvascular-approximating instrument, by far the largest application has been for hemodialysis vascular access. Long-term studies comparing suture to clip for access creation have demonstrated the clear technical and biological superiority of the clip for this procedure. This "sutureless" vascular anastomotic technique is more demanding than conventional suturing, requiring precise vessel preparation and supervised training.
Arsenic is widely distributed in nature in air, water and soil in the form of either metalloids or chemical compounds. It is used commercially, as pesticide, wood preservative, in the manufacture of glass, paper and semiconductors. Epidemiological and clinical studies indicate that arsenic is a paradoxical human carcinogen that does not easily induce cancer in animal models. It is one of the toxic compounds known in the environment. Intermittent incidents of arsenic contamination in ground water have been reported from several parts of the world. Arsenic containing drinking water has been associated with a variety of skin and internal organ cancers. The wide human exposure to this compound through drinking water throughout the world causes great concern for human health. In the present review, we have attempted to evaluate and update the mutagenic and genotoxic effects of arsenic and its compounds based on available literature.
The medical records of 110 patients receiving conventional antipsychotics at two geographically distinct Veterans Administration hospitals (Syracuse, New York, and Omaha, Nebraska) were reviewed. The most common reasons for continuation of conventional antipsychotics were good response and patient or physician choice. Frequently, physicians did not discuss the reasons for continuing conventional antipsychotics or the availability of alternative therapies with their patients. Geographic differences in physicians' prescribing practices of conventional antipsychotics were apparent.
Since the introduction of clozapine, several novel antipsychotic agents have been introduced and more are in Phase II/III studies. Because these agents are used clinically as first-line treatment, we need to be more familiar with their side-effect profiles. This manuscript reviews the cardiovascular side effects of currently available novel antipsychotics. The medications reviewed include clozapine, risperidone, olanzapine, quetiapine, and ziprasidone. Guidelines are suggested for the use of these medications in clinical practice.
A patient with type I cryoglobulinemia and monoclonal gammopathy of uncertain significance was found to have acute gallbladder vasculitis. The most prominent manifestation was upper abdominal pain in the setting of normal liver tests. An abdominal ultrasound demonstrated a thickened gallbladder wall, along with gallstones. HIDA scanning showed a nonfunctioning gallbladder with an edematous and thickened wall. There was characteristic leukocytoclastic vasculitis affecting the gallbladder. The patient recovered uneventfully subsequent to cholecystectomy. Gallbladder vasculitis should be considered in patients with unexplained upper abdominal pain and systemic vasculitis.
A casual association between Chlamydia pneumoniae infection and atherosclerosis remains unresolved but plausible. Evidence comes from sero-epidemiological data, pathological specimen examinations, animal models and in vitro experiments. A number of prospective antibiotic intervention trials targeted against C. pneumoniae infection in patients with coronary heart disease are now underway. We remain wary that C. pneumoniae infection can persist in cell lines (associated with atherosclerosis) despite antibiotic therapy and also that reactivation of infection can occur. Issues such as delineating the patient group that could be targeted for treatment, choice of optimal antibiotic regimens, duration of therapy and effective methods of monitoring treatment response remain controversial and, as yet, unresolved. The relevance of persistence of C. pneumoniae infection and potential antimicrobial resistance will require equal consideration.