Clara cells and Clara cell 10 kD protein (CC10).
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Animals↗
Biomedical subjects
G Singh
Publications and source records attributed to G Singh.
An audit of the problems in management of patients with gonorrhoea.
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Ampicillin↗
Neurocysticercosos in South-Central America and the Indian subcontinent. A comparative evaluation.
Neurocysticercosis is an important public health problem in South-Central American and South Asia. A review of the differences in epidemiological and clinical attributes of cysticercosis and taeniasis in South Central America and India, respectively, is undertaken in the present communication. Intestinal taeniasis is hyperendemic in several American countries. In comparison, the prevalence of Taenia solium infestation is lower in India. The clinical manifestations in several American neurocysticercosis series comprise epilepsy, intracranial hypertension and meningeal-racemose cysticercosis, in roughly equal proportions. An overwhelming majority of the Indian subjects present with seizures. The commonest pathological substrate of the disorder in Indian patients is the solitary parenchymal degenerating cyst. The reasons for the predominance of solitary forms in India, and of multilesional forms in South Central America are discussed. The magnitude of Taenia solium infestation and the frequency of pork consumption in a given population appear to influence the quantum of cyst load in affected individuals.
Central America↗
Response to therapy in rheumatoid arthritis is influenced by immediately prior therapy.
OBJECTIVE: Clinicians do not often employ washout periods before prescribing a change in therapy for rheumatoid arthritis (RA). As a result, the observed effectiveness or lack of effectiveness of a new drug actually represents the effectiveness of that drug had the patient been taking placebo minus the residual effectiveness of the old drug. METHODS: We studied new starts of selected disease modifying antirheumatic drugs (DMARD) and prednisone in 2,898 patients with RA from 8 ARAMIS data bank centers, broken into subgroups on the basis of immediately prior therapy. Therefore, we examined the hypothesis that the chances of a treatment being observed effective depend upon the immediately preceding treatment. Using intent-to-treat analysis, we analyzed the effects upon Health Assessment Questionnaire (HAQ) disability and pain scores an average of 9 months after the new drug start. RESULTS: Methotrexate reduced disability significantly except after intramuscular gold or hydroxychloroquine and it reduced pain significantly after all prior therapies. Hydroxychloroquine reduced disability significantly after nonsteroidal antiinflammatory drugs (NSAID) only, but disability increased after intramuscular gold; pain was decreased only after NSAID only. Prednisone had no consistent effect upon disability but was consistently associated with decreased pain. Greatest effectiveness was always seen with a new drug start after NSAID only treatment versus after DMARD treatment. CONCLUSION: The effectiveness of a newly started RA treatment after 9 months may be substantially influenced by immediately prior treatment. This finding provides an additional reason for concern about direct extrapolation of clinical trial data into clinical practice.
Anti-Inflammatory Agents↗
Regression analysis of the effect of full and partial lactation on post-partum amenorrhoea in lower middle class Indian females.
This study presents a simple regression analysis of the impact of full and partial breast feeding on post-partum amenorrhoea (PPA) in lower middle class Indian women. The study has been done on a sample of hospital based data collected in 1992. The analysis shows a highly significant correlation. Further, the impact of lactation on PPA was notably less in case with partial breast feeding as compared to those with full breast feeding.
Amenorrhea↗
Endoscopic management of pancreatic diseases.
Endoscopic management has recently been used for a variety of chronic pancreatic diseases. We used this approach in five patients with pancreatic diseases (calcific pancreatitis 2, pancreatic pseudocyst 3). Nasocystic drain was placed in a patient with pancreatic pseudocyst at the tail end of the pancreas; a 5 Fr stent was placed over 0.021"/0.035" guide wire in the main pancreatic duct in the others. All patients had relief of pain. Nasocystic drain led to resolution of pseudocyst, perisplenic collection and pleural effusion. Endoscopic treatment is safe and effective in various pancreatic disorders.
Adolescent↗
Conjunctival impression cytology in xerophthalmia among rural children.
The advent of Conjunctival Impression Cytology (CIC) has opened a new chapter in the detection of Vitamin A deficiency as it is a simplified field technique. The need for such a technique was of paramount importance in India where as estimated 5 to 7 percent children suffer from eye signs of Vitamin A deficiency. In the present study the results of clinical evaluation of apparently healthy children and those having clinical sings and symptoms of Vitamin A deficiency have been compared with CIC results. Serum Vitamin A levels have also been estimated wherever possible. The findings indicate that CIC results are superior to the clinical assessment and it is suggested that CIC can be used as screening tool for children of school going age (and earlier) for early detection and correction of Vitamin A deficiency.
Child↗
Use of tetracycline as an inhibitor of matrix metalloproteinase activity secreted by human bone-metastasizing cancer cells.
Bone metastases are a common complication in prostate and breast cancer patients. It leads to extensive morbidity and eventually mortality. Matrix metalloproteinases are implicated in various steps of development of metastasis, through their ability to degrade the extracellular matrix. Increased matrix metalloproteinase activity of tumor cells has been associated with a higher metastatic potential. Inhibitors of metalloproteinases have been shown to effectively reduce or prevent the formation of metastases. The family of tetracyclines is able to inhibit matrix metalloproteinase activity through chelation of the zinc ion at the active site of the enzyme. Using tumor cell lines relevant to bone metastases, i.e. PC-3, MDA-MB-231, Hs696, B16/F1, we showed that tetracycline and derivatives of tetracycline, namely doxycycline and minocycline, also induced cytotoxicity. The effective concentrations are relatively high for plasma, but are clinically achievable in the bone, since tetracyclines are osteotropic. All four bone-metastasizing tumor cells produced and secreted various matrix metalloproteinases. Doxycycline was able to inhibit the activity of 72- and 92-kDa type IV collagenase secreted by bone-metastasizing cells by 79-87%. These characteristics could make tetracycline a unique candidate as a therapeutic agent to prevent bone metastases in cancer patients with a high likelihood for development of bone metastasis. Studies using animal models of experimental bone metastasis will be necessary to confirm this.
Adenocarcinoma↗
Effect of Material Properties on the Drainage of Symmetric, Plane Parallel, Mobile Foam Films
Drainage of a mobile, symmetric, plane parallel thin liquid film between two gas bubbles is studied. An analytical solution for the rate of thinning of such a liquid film with an insoluble surfactant and having both film elasticity and surface viscosity is presented for the first time. Analysis is extended to the more general case of a soluble surfactant and compared with previous analyses. Surfactant material parameters affecting the rate of thinning are identified and grouped into a single dimensionless parameter which describes the transition from a mobile to an immobile film. Significant deviation from the Reynolds velocity is found when this dimensionless parameter is small.
Journal Article↗
Famotidine to prevent peptic ulcer caused by NSAIDs.
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Anti-Inflammatory Agents, Non-Steroidal↗
Mechanism of topoisomerase II inhibition by staurosporine and other protein kinase inhibitors.
Topoisomerase II is an essential enzyme for proliferation of eukaryotic cells. It is also a target for many antineoplastic drugs that promote stabilization of covalent complexes between topoisomerase II and DNA. Topoisomerase II and protein kinases both catalyze the transfer of phosphoester bonds from nucleotides to proteins. This similarity suggests that inhibitors may affect both classes of enzymes. In the present study, we have examined the mechanism of topoisomerase II inhibition by three different classes of protein kinase inhibitors. We report that staurosporine inhibited the catalytic activity of topoisomerase II by blocking the transfer of phosphodiester bonds from DNA to the active tyrosine site, a mechanism of inhibition not previously reported for this enzyme. In contrast, other kinase inhibitors, such as methyl 2,5-dihydroxycinnamate, most likely inactivated topoisomerase II by alkylation of essential amino acids, whereas the mechanism of inhibition of bis-indolylmaleimide possibly involved a direct interaction with DNA.
Adenosine Triphosphate↗
Racial and gender differences in endothelin-1.
In summary, ET-1 levels were significantly increased in black men compared with white men. This racial difference could have important research implications if increased ET-1 levels are linked to left ventricular hypertrophy and other cardiovascular diseases, and it may serve as a foundation for future studies.
Adolescent↗
Gastrointestinal tract complications of nonsteroidal anti-inflammatory drug treatment in rheumatoid arthritis. A prospective observational cohort study.
BACKGROUND: Gastrointestinal tract (GI) complications associated with nonsteroidal anti-inflammatory drug (NSAID) use are the most common serious adverse drug reactions in the United States. Nonsteroidal anti-inflammatory drugs cause both minor GI side effects such as abdominal pain and vomiting and serious GI events such as ulcers and bleeding. This study evaluates the event rates for all NSAID-induced GI complications in patients with rheumatoid arthritis, describes the time course of these events, and evaluates the role of prophylactic therapy with antacids and H2 receptor antagonists. METHODS: We studied 1921 patients with rheumatoid arthritis from 8 ARAMIS (Arthritis, Rheumatism, and Aging Medical Information System) centers. Patients were selected for the study if they were treated with NSAIDs and had at least 2.5 years of observation available. Information on GI complications attributed to NSAIDs was obtained from validated patient self-reports collected every 6 months and supplemented by review of hospital records for all hospitalizations. RESULTS: Approximately 15% of the 1921 patients reported an NSAID-induced GI side effect during the 2.5 year observation period. Forty-two patients had a serious GI complication requiring hospitalization; 34 of these 42 patients did not have a preceding GI side effect. Patients who were taking antacids and H2 receptor antagonists did not have a significantly lower risk for serious GI complications than did those not taking such medications. Asymptomatic patients taking these medications had a significantly higher risk for GI complications compared with those who did not take these medications (standardized odds ratio, 2.14;95% confidence interval, 1.06-4.32). CONCLUSIONS: A large majority of patients with serious GI complications do not have preceding mild side effects. Prophylactic treatment with antacids and H2 receptor antagonists is of questionable value and may increase the risk for subsequent serious GI complications.
Aged↗
Prevention and reversal of renal allograft rejection by antibody against CD45RB.
Rejection continues to be the single largest impediment to successful organ transplantation. Antilymphocyte globulin, which contains antibodies that react with the leukocyte common antigen known as CD45, has proved to be one of the most effective agents for preventing rejection. We have shown earlier that a monoclonal antibody directed against the RB isoform of CD45 substantially inhibits the alloreactivity of human CD4+ lymphocytes in vitro. Here we investigate whether CD45RB could be an appropriate target for preventing renal allograft rejection in mice. Mice treated with two injections of a monoclonal antibody (MB23G2) raised against CD45RB protein all survived and had normal renal function. Furthermore, this antibody reversed acute rejection when therapy was delayed until day 4, and the mice survived for their natural lifespan. The immunosuppression achieved may find application in the prevention and treatment of transplant rejection in man.
Animals↗
Acute acidosis elevates malonaldehyde in rat brain in vivo.
Oxidative stress in brain tissue was measured experimentally in situ using microdialysis to sample the extracellular environment for a lipid peroxidation breakdown product and antioxidants. The extracellular concentrations of the lipid peroxidation product malonaldehyde (MDA) and the antioxidants ascorbic acid (AA) and uric acid (UA) were measured in rat cortex and striatum in vivo using microdialysis coupled to HPLC with UV detection. Tissue acidosis following ischaemia and epileptic seizures may contribute to neuronal damage, which may be mediated by reactive oxygen species. Perfusion of microdialysis probes with acidic artificial cerebrospinal fluid (pH 6) led to a significant increase in the sampled concentration of MDA and the antioxidant ascorbic acid. Simultaneous perfusion of ascorbate (5 mM) with acidic ACSF (pH 6) completely attenuated the rise in lipid peroxidation. This study provides in vivo evidence for acidosis induced oxidative stress in brain tissue and an antioxidant action of ascorbate. The methodology described here can provide direct in vivo information in respect of oxidative stress in experimental situations. The method could equally be applied to the assessment of oxidative stress in a number of pathological models not necessarily confined to the CNS.
Acidosis↗
Neoadjuvant chemotherapy in locally advanced breast cancer.
Thirty-eight patients with locally advanced breast cancer (Stage III) were treated over a 3-year period. All patients initially received two cycles of CMF (cyclophosphamide, 100 mg/m2 p.o. d1-14; methotrexate 40 mg/m2 intravenously (i.v.), d1 and d8., 5 Fluorouracil 500 mg/m2 i.v. d1 and d8). They were then subjected to surgery and external beam irradiation to the chest field and drainage areas. Four more cycles of chemotherapy completed the treatment protocol. A response to initial chemotherapy was seen in 75.7% patients, with two patients achieving a complete response. No patient had disease progression while on chemotherapy. Tumor reduction of a degree to allow breast conservation procedures was seen in eight patients. The chemotherapy was well tolerated. Twelve patients failed to complete the treatment protocol. Follow-up for the remaining 26 ranges from 9-40 months (mean 18 months). Ten patients developed a recurrence. Of those, only one had isolated local recurrence, two had local and systemic recurrence, and seven had systemic disease alone. Patients with recurrence were salvaged with further chemotherapy (Adriamycin and cyclophosphamide).
Alopecia↗
Relationship of running to musculoskeletal pain with age. A six-year longitudinal study.
OBJECTIVE: To determine, by longitudinal study, whether long-distance running, maintained for many years, is associated with increased musculoskeletal pain with age. METHODS: A 6-year prospective longitudinal study of 410 runners' club members and 289 community controls, age 53-75 years at study initiation, was conducted. Subjects were also categorized as ever-runners (n = 488) and never-runners (n = 211). The primary dependent variable was pain score as indicated on a horizontal double-anchored analog scale; data for this variable were available beginning in 1987. Statistical adjustment for age, education level, smoking, alcohol consumption, history of arthritis, and presence of other major medical conditions was done by analysis of covariance. Further analyses of previously reported associations of regular vigorous physical activity with decreased disability and mortality after 9 years were performed. RESULTS: The degree of musculoskeletal pain was slightly lower in the exercise group compared with controls, and the difference was statistically significant for women but not for men. Average adjusted pain scores for men were 18.3 (SEM 0.8) in runners' club members, 20.2 (1.2) in controls, 18.6 (0.8) in ever-runners, and 20.3 (1.6) in never-runners. For women, these scores were 17.5 (1.8) in runners' club members versus 22.8 (1.4) in controls (P < 0.05), and 17.2 in ever runners versus 23.7 (1.5) in never-runners (P < 0.002). Disability had continued to develop in runners' club members at a rate only one-third that in the controls after 9 years of observation. Mortality over 9 years consisted of 51 deaths, of which 41 were in the control group and only 10 were among runners' club members. CONCLUSION: Vigorous running activity over many years is not associated with an increase in musculoskeletal pain with age, and there may be a moderate decrease in pain, particularly in women. Vigorous physical activity is associated with greatly decreased levels of disability and with decreased mortality rates.
Age Factors↗
Reduction in long-term disability in patients with rheumatoid arthritis by disease-modifying antirheumatic drug-based treatment strategies.
OBJECTIVE: Therapeutic strategies for rheumatoid arthritis (RA) have been evolving from the traditional "pyramid" approach toward one based upon early and sustained use of disease-modifying antirheumatic drugs (DMARDs), in the hope of improving long-term health outcomes. However, few data to have been presented to document the effects of this approach. We sought to directly assess associations between consistent DMARD use and long-term functional outcomes. METHODS: We studied 2,888 RA patients who were followed up prospectively for up to 20 years (average 9 years) at 8 databank centers. The independent variable was the proportion of patient encounters that resulted in treatment with > or = 1 DMARD (hydroxychloroquine, sulfasalazine, auranofin, intramuscular gold, D-penicillamine, methotrexate, and/or azathioprine). The dependent variable was each patient's last recorded Disability Index value from the Health Assessment Questionnaire (HAQ). RESULTS: Increased DMARD use was strongly associated with better long-term Disability Index values (P < 0.0001). The association was strengthened when restricted to more seriously affected (rheumatoid factor (RF)-positive) patients. The magnitude of the effect, unadjusted, was a difference of 0.53 HAQ Disability units (scale 0-3) between 100% DMARD use and 0%. Correlation coefficients ranged up to 0.26. Effects were similar for all disease duration periods (0-4, 5-9, 10-14, 15-19, and 20+ years). "Control" correlations, with variables computed to represent the proportion of time in which patients were taking either nonsteroidal anti-inflammatory drugs or prednisone, failed to show positive associations. A multiple linear regression model, which controlled for age, disease duration, sex, RF positivity, proportion of visits under a prednisone regimen, and initial disability level, included the proportion of time in which patients were taking DMARDs (P < 0.0001), with a model R2 of 0.54. These results were obtained despite an adverse selection bias in which more severely affected individuals were given DMARDS more frequently, and despite absence of data on drug use early in the disease course of many patients. Thus, these results, which suggest up to a 30 percent reduction in long term disability with consistent DMARD use, are most likely conservative. CONCLUSION: An association between consistent DMARD use and improvement in long-term functional outcomes in RA is supported by these data.
Antirheumatic Agents↗