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R Luthra

Publications and source records attributed to R Luthra.

At least 55 records · Page 3Linked to original sources
PubMed1994

Rigor of research methods in studies of the effectiveness and safety of cataract extraction with intraocular lens implantation. Cataract Patient Outcome Research Team.

OBJECTIVE: To assess the rigor of research methods reported in studies of the safety or effectiveness of contemporary cataract surgery. DESIGN: Formal systematic identification of pertinent studies and critical appraisal of each study's research methods. SUBJECTS: From 6113 unique, potentially relevant citations that we identified, 90 original studies published between 1979 and 1991 that addressed visual acuity or complications following standard extracapsular cataract extraction with posterior chamber intraocular lens implantation, phacoemulsification with posterior chamber intraocular lens implantation, or intracapsular cataract extraction with flexible anterior chamber intraocular lens implantation. MAIN OUTCOME MEASURES: Strength of study design, performance, and reporting in 11 methodologic areas assessed with a standardized abstraction form by two reviewers masked to authors, their institutions, and the journal of publication. Results of reviews were tallied to produce an overall quality score (measure of rigor in research methods) for each study. RESULTS: The mean (+/- SD) quality score was 43.1 +/- 20.1 out of a maximum possible score of 100. Studies received intermediate scores on description of baseline ocular disease and low scores on descriptions of other characteristics of enrolled patients, standardization of outcome assessment and follow-up duration, and handling of patient attrition. Eighty-three studies (92%) lacked a comparison group. The rigor of research methods in studies varied by the journal of publication, did not improve over time, and was no greater for studies with larger vs smaller sample sizes. CONCLUSIONS: The rigor of research methods in studies of cataract surgery can be improved if more attention is paid to fundamental principles of study design, data analysis, and reporting.

Cataract Extraction↗
PubMed1994

Synthesis of the literature on visual acuity and complications following cataract extraction with intraocular lens implantation. Cataract Patient Outcome Research Team.

OBJECTIVE: To better define the effectiveness and risks of modern cataract surgery. DESIGN: Meta-analysis (formal systematic identification, selection, review, and synthesis) of published literature. PATIENTS: Patients described in 90 studies published between 1979 and 1991 that addressed visual acuity (n = 17,390 eyes) or complications (n = 68,316 eyes) following standard extracapsular cataract extraction with posterior chamber intraocular lens implantation, phaco-emulsification with posterior chamber intraocular lens implantation, or intracapsular cataract extraction with flexible anterior chamber intraocular lens implantation. MAIN OUTCOME MEASURES: The proportion of eyes with postoperative Snellen visual acuity of 20/40 or better and the proportion of eyes with each of 18 complications. RESULTS: The pooled percentage of eyes (weighted by sample size) with postoperative visual acuity of 20/40 or better was 95.5% (95% confidence interval [CI], 95.1% to 95.9%) among eyes without preexisting ocular comorbidity and 89.7% (95% CI, 89.3% to 90.2%) for all eyes. The pooled percentage of eyes experiencing complications (weighted by sample size and, when pertinent, by quality score of the individual studies but not adjusted for variation in duration of follow-up) ranged from 0.13% for endophthalmitis to 19.7% for posterior capsule opacification. Pooled proportions of eyes with other complications were as follows: bullous keratopathy, 0.3%; intraocular lens malposition/dislocation, 1.1%; clinically apparent cystoid macular edema, 1.5%; and retinal detachment, 0.7%. Pooled results for postoperative Snellen visual acuity and most complications were similar for surgery performed via phacoemulsification vs standard extracapsular cataract extraction, although comparisons of the outcomes between these procedures should be interpreted with caution. CONCLUSIONS: The published literature indicates that modern cataract surgery yields excellent visual acuity and, although not free of complications, is a very safe procedure regardless of the extraction technique used.

Aged↗
PubMed1994

Variation in ophthalmic testing before cataract surgery. Results of a national survey of ophthalmologists.

Little information is available either for the clinical value of many ophthalmic tests performed preoperatively in the evaluation of patients for cataract surgery or for variation in ophthalmologists' use of such tests. To assess variation in ophthalmologists' use of ophthalmic tests, we conducted a national survey of American Academy of Ophthalmology members. Thirty-three percent, 17%, 37%, and 19% of the respondents reported that they "frequently" or "always" perform glare testing, contrast sensitivity testing, potential acuity measurement, and specular microscopy, respectively, in patients being considered for cataract surgery who have no history of eye disease other than cataract. In contrast, 27%, 54%, 24%, and 48% of respondents reported that they never perform each of these four tests in such patients. Two ophthalmologist characteristics--a surgical volume of greater than 200 cataract extractions per year and performance of surgery in an ambulatory surgical center or private office (as opposed to a hospital)--were independently associated with an increased probability of performing each of these four tests frequently or always. Ten percent or less of the respondents reported that they frequently or always perform electroretinography, visual evoked response testing, photography of fundus or anterior segment, B-scan ultrasonography, formal color vision testing, and formal visual field testing in such patients. Thus, there is considerable variation in ophthalmologists' use of glare testing, contrast sensitivity testing, potential acuity measurement, and specular microscopy. A small percentage of ophthalmologists may be overusing several other tests in the evaluation of patients being considered for cataract surgery.

Adult↗
PubMed1994

Protein kinase C activity is reduced in epidermal cells from energy-restricted SENCAR mice.

Female SENCAR mice were pre-fed a control or 40% energy-restricted (ER) diet with energy removed from fat and carbohydrate, or a control, balanced high fat (BHF, with similar energy from fat and carbohydrate), 35% energy restricted from fat (HCR) or 35% energy restricted from carbohydrate (HFR) diet. Epidermal cells were isolated by trypsin digestion for measurement of protein kinase C (PKC) activity, lipid composition or lipid metabolism. Dietary restriction of fat or carbohydrate energy (HFR or HCR group) reduced particulate PKC activity in epidermal cells compared with cells from control mice. The ratio of soluble particulate PKC activity was higher in epidermal cells from mice fed the HCR diet compared with those fed the HFR diet. Diet did not affect soluble PKC activity. Inositol accumulation was measured in the water- or lipid-soluble fractions of prelabeled ([3H]inositol) epidermal cells following a 1-h incubation in media with LiCl. Phosphatidylinositol, inositol biphosphate and inositol triphosphate fractions were more heavily labeled in cells from mice fed the ER diet. Energy restriction did not modify epidermal total lipid or phospholipid composition, but 1,2-diacylglycerol levels were elevated in relation to cell number in epidermal cells from mice fed the ER diet. These data suggest that dietary energy restriction modified PKC activity through a pathway other than alteration in membrane lipid composition or inositol lipid metabolism.

Animals↗
PubMed1994

Primary mediastinal large cell lymphoma is characterized by an inverted pattern of large tumoral mass and low beta 2 microglobulin levels in serum and frequently elevated levels of serum lactate dehydrogenase.

BACKGROUND: Primary mediastinal large cell lymphoma (PMLCL) is an emerging entity. New parameters can help define it. MATERIALS AND METHODS: Retrospective analysis of medical records from 35 patients treated at The University of Texas M.D. Anderson Cancer Center from 1985 to 1990. Immunohistochemical evaluation of tissue specimens. Determination of survival (S) and time to treatment failure (TTF). RESULTS: The median age was 34 years and 69% were females. Eight-three percent presented with symptoms of mediastinal involvement. While 100% of the patients presented with bulky mediastinal disease and 72% had elevated pretreatment serum lactate dehydrogenase, only 6% presented with an elevated pretreatment serum beta 2 microglobulin. The lymphoma cells lacked CD21 staining. For the 18 patients treated initially at M.D. Anderson Cancer Center, S and TTF curves rates after doxorubicin-based regimens (plus radiotherapy in 14 cases) were 72% and 61%, respectively, at 5 years follow-up (median, 42 months). Four out of six patients who received autologous bone marrow transplant as salvage therapy are currently alive without disease at follow-up times of 21, 25, 32, and 54 months. CONCLUSION: Primary mediastinal large cell lymphoma has characteristic clinicopathological features to which another can be added, that of an inverted pattern of bulky disease, high LDH and low beta 2 M in serum. The response to therapy is comparable to that of intermediate-grade lymphomas, although the numbers in the study are small. Our preliminary data suggest a possible role for autologous bone marrow transplantation (ABMT) as salvage therapy.

Adult↗
PubMed1993

Geraniol dehydrogenase: a determinant of essential oil quality in lemongrass1.

Geraniol dehydrogenase, the specific enzyme involved in geraniol to citral TRANS (geranial) transformation, activity was monitored in various lemongrass cultivars differing in amounts and relative percentages of citral and geraniol in their essential oils. The enzyme activity had a positive and significant association with citral to geraniol, and geranial to geraniol ratios. The results are suggestive of a strong relationship between the enzyme activity and essential oil quality in lemongrass cultivars.

Journal Article↗
PubMed1993

The clinical relevance of t(14;18)/BCL-2 rearrangement and DEL 6q in diffuse large cell lymphoma and immunoblastic lymphoma.

BACKGROUND: t(14;18)/bcl-2 gene rearrangement (R) is claimed to impart a worse rate of complete remission and disease-free survival in diffuse large cell lymphoma (DLCL). DEL 6q has also been associated with poor outcome. DESIGN: Retrospective study of 54 patients with either diffuse large cell or immunoblastic lymphoma who had cytogenetics and/or molecular studies performed. RESULTS: Patient characteristics, complete remission rate, and time to treatment failure (TTF) were similar at three year follow-up for groups with and without t(14;18)/BCL-2R. Survival was worse for the former but the difference was not statistically significant. For DEL 6q, patient characteristics and survival rates were similar at three year follow-up for patients with and without the abnormality. TTF was worse for the former but this was not statistically significant. CONCLUSION: This study, with equal or greater number of patients with t(14;18) than previous reports, fails to show a worse prognosis for patients with the t(14;18) chromosomal abnormality. A definite association will await further accrual of patients and a meaningful multivariate analysis.

Adolescent↗
PubMed1992

Protein kinase C is activated and diacylglycerol is elevated in epidermal cells from Sencar mice fed high fat diets.

Studies reported here determined the effect of dietary fat level on membrane phospholipid composition, phosphoinositide labeling, 1,2-sn-diacylglycerol and protein kinase C activity in epidermal cells from female Sencar mice. Animals were fed either high fat (24.6 g/100 g diet) or control (5 g/100 g diet) diets at constant energy intake for 6 to 7 wk or 15 to 22 wk, and epidermal cells were isolated. The level of phosphatidylinositol was significantly lower in the animals fed the control diet than in the animals fed the high fat diet (0.6 vs. 1.2 nmol/10(6) cells). The fatty acid composition of the phospholipids showed significantly lower arachidonic acid level in phosphatidylinositol when the animals were fed the high fat diet. Protein kinase C activity in the solubilized particulate and soluble fraction of the cells was 131 +/- 18% and 62 +/- 14% greater, respectively, in animals fed the high fat diet compared with animals fed control diet. The level of 1,2-sn-diacylglycerol was significantly higher in animals fed the high fat diet (mean nmol/mg lipid +/- SEM: control, 4.5 +/- 0.5; high fat, 7.0 +/- 0.5). Incorporation of [3H]inositol into inositol lipid was not altered by diet. Because protein kinase C and 1,2-sn-diacylglycerol have been implicated in tumor promotion, the increase in protein kinase C activity and the elevation of 1,2-sn-diacylglycerol in cells from animals fed the high fat diet may be important in the high cancer rate observed with these diets.

Animals↗
PubMed1989

Assessment in rats of the gonadotoxic and hepatorenal toxic potential of dibromochloropropane (DBCP) in drinking water.

This investigation was undertaken to assess the potential of ingested 1,2-dibromo-3-chloropropane (DBCP) to cause testicular and hepatorenal injury, in light of the paucity of data applicable to risk assessment of DBCP in drinking water. Adult male Sprague-Dawley rats were supplied ad libitum with water containing 0, 5, 50, 100, and 200 ppm DBCP for 64 days. A dose-related decrease in water consumption occurred during the study. The 200-ppm animals drank less than half as much water as controls, consumed less food, and subsequently exhibited significantly lower body weight gain. DBCP ingestion thus was not directly proportional to the level of chemical in the water, although daily and cumulative intake of DCP were concentration dependent. Average daily intake of DBCP for the 64-day exposure period was as follows: 5 ppm = 0.4 mg/kg/day; 50 ppm = 3.3 mg/kg/day; 100 ppm = 5.4 mg/kg/day; 200 ppm = 9.7 mg/kg/day. Blood samples were taken after 2, 4, and 6 weeks of exposure and at the terminal sacrifice and assayed for serum glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, sorbitol dehydrogenase, and ornithine-carbamyl transferase activities and BUN levels. No evidence of liver damage at any exposure level was indicated by either the clinical chemistry indices or histopathology. Histologic examination revealed an apparent increase in the number of nuclei per renal proximal tubule cross-section in the 200-ppm group, possibly indicative of an increased turnover of proximal tubular cells. A slight, but statistically significant, decrease in absolute testicular weight was manifest in the 200-ppm animals, although the decrease was not significant when testicular weight was calculated as g/100 g body wt. Epididymal sperm counts and serum luteinizing hormone, follicle stimulating hormone, and intratesticular testosterone levels were not altered by any dose of DBCP. A qualitative histopathological examination of the testicular seminiferous epithelium failed to reveal any abnormalities in the spermatogenic process.

Animals↗
PubMed1986

Oral toxicity of carbon tetrachloride: acute, subacute, and subchronic studies in rats.

This investigation was conducted to characterize the acute, subacute, and subchronic toxic potency of ingested carbon tetrachloride (CCl4). In the first acute and subacute toxicity study, male Sprague-Dawley rats of 300-350 g were gavaged with 0, 20, 40, or 80 mg CCl4/kg once daily for 5 consecutive days, rested for 2 days, and dosed once daily for 4 additional days. Rats of 200-250 g were gavaged with 0, 20, 80, or 160 mg CCl4/kg according to the same dosage regimen in the second acute and subacute study. In the first and second studies one group of rats at each dosage level was sacrificed for clinical chemistry and histopathological evaluation at 24 hr, 4 days, and 11 days after initiation of dosing. Single 20- and 40-mg/kg doses had no apparent toxic effect at 24 hr, although 80 mg/kg caused mild hepatic centrilobular vacuolization and significant increases in some serum enzyme levels. In general, there was progressively severe hepatic injury at each dosage level over the 11-day period. CCl4 was more hepatotoxic to the 200-250-g rats than to the 300-350-g rats. In the subchronic study, rats initially 200-250 g were gavaged 5 times weekly for 12 weeks with 0, 1, 10, or 33 mg CCl4/kg. Body weight and clinical chemistry indices were monitored during the 12 weeks of dosing and 2 weeks after cessation of dosing. A dose of 1 mg/kg had no apparent adverse effect; 10 mg/kg produced slight, but statistically significant increases in sorbitol dehydrogenase activity and mild hepatic centrilobular vacuolization; 33 mg/kg caused marked hepatotoxicity. Serum enzyme levels remained elevated during the 12-week dosing period, but returned toward normal within 13 days of cessation of CCl4 exposure. Microscopic examination of livers of the 33-mg/kg rats revealed cirrhosis, characterized by bile duct proliferation, fibrosis, lobular distortion, parenchymal regeneration, hyperplastic nodules, and single-cell necrosis. The fibrosis was not reversed within the 13-day recovery period.

Alanine Transaminase↗
PubMed1983

Assessment of functional, morphological, and enzymatic tests for acute nephrotoxicity induced by mercuric chloride.

The relative merits of a comprehensive series of contemporary methods for detection of acute nephrotoxicity were evaluated. Male Sprague-Dawley rats were given 0, 0.25, 0.5, 1.0, or 3.0 mg mercuric chloride (HgCl2)/kg body weight by ip injection. Indices of nephrotoxicity were examined 8, 24, 48, 72, and 96 h later. Alterations in urine osmolality, volume, and protein levels were seen within 24 h in response to 1 mg/kg or more of HgCl2. Administration of 0.5-3.0 mg/kg produced dose-dependent increases in urinary excretion of maltase activity and glucose by 24 h, the period of peak effect. There was no increase in maltase or alkaline phosphatase (AP) activity in the serum of these animals. Enzymuria was not apparent in rats that had marked elevations in serum AP, argininosuccinate lyase, and ornithine carbamyl transferase activities as a result of physical (i.e., dichlorodifluoromethane-frozen) or chemical (carbon tetrachloride-induced) damage of the liver. Morphological alterations, in the proximal tubular epithelium of perfusion-fixed kidneys from HgCl2-dosed rats, paralleled the changes in enzyme excretion with respect to time of onset and dose-effect. There was a dose-dependent inhibition of tetraethylammonium (TEA) and p-aminohippurate (PAH) uptake by renal cortical slices at 24 h. Interestingly, increases in uptake of TEA and PAH were seen 8 h after a 1-mg/kg dose. Clearance of inulin and PAH in vivo were altered at 8 h by 0.5 and 1 mg/kg. Marked depression of these functional indices was seen at 24 h, by which time blood urea nitrogen (BUN) levels were increased. The 0.5- and 1.0-mg/kg doses also produced time- and dose-dependent increases in intracellular Na+ content which were maximal at 24 h. These results illustrate the importance of using a combination of biochemical and functional tests to elucidate the sequence of events in the kidney following toxic insult. Nevertheless, some of the simpler, traditional techniques (e.g., histopathology, urinalyses, BUN) were sensitive and organ-specific, and should continue to be very useful in nephrotoxicity testing/screening.

Animals↗
PubMed1976

Studies of mitochondrial calcium movements using chlorotetracycline.

1. The association of calcium with isolated rat liver mitochondrial membranes under various metabolic conditions was monitored using the fluorescent chelate probe, chlorotetracycline. Chlorotetracycline fluorescence increased markedly during energized calcium uptake in the absence of a permeant anion. Uncoupler and a respiratory chain inhibitor caused a rapid decrease in chlorotetracycline fluorescence when added either before or after calcium. During calcium uptake experiments concentrations of calcium exceeding 100 muM caused a transient fluorescence increase followed by an extensive decrease in fluorescence. 2. Changes in the chlorotetracycline-associated fluorescence of the mitochondrial suspensions were correlated with the uptake of exogenous 45Ca. A positive correlation was observed between fluorescence and energized 45Ca uptake in the absence of permeant anions. Addition of the permeant anion, phosphate, caused an extensive decrease in chloretetracycline fluorescence but an enhanced uptake of exogenous 45Ca. 3. The interaction of endogenous mitochondrial calcium with the fluorescent chelate probe was studied under a number of experimental conditions using mitochondria labeled during preparation with 45Ca. Endogenous 45Ca was lost rapidly from the mitochondria upon treatment with uncoupler, antimycin A, and A23187. Potassium phosphate and EGTA had no effect on the endogenous calcium as measured by either the 45Ca content of the mitochondria or the fluorescence of the probe. 4. Mitochondria treated with antimycin A lost most of their endogenous 45Ca within 3 min; subsequent energization of the mitochondria resulted in a partial uptake of the released 45Ca but caused nearly a complete return of the chlorotetracycline fluorescence to the original level. Addition of phosphate did not change the fluorescence level but resulted in an almost complete accumulation of the 45Ca previously released. 5. Following this energized uptake of 45Ca, EGTA, p-trifluoromethoxyphenyl hydrazone of carbonyl cyanide, A23187 and calcium chloride all caused a nearly complete loss of the 45Ca from the mitochondria and, with the exception of calcium chloride, caused an extensive decrease in the fluorescence level. Hence, the apparent location and/or properties of the endogenous calcium in this rat liver mitochondrial system were altered significantly by manipulation of the energetic state of the mitochondrial membrane.

Animals↗
PubMedDate not supplied

Discordant genetic changes in ovarian and endometrial endometrioid carcinomas: a potential pitfall in molecular diagnosis.

Endometrioid carcinoma simultaneously involving ovaries as well as the uterine corpus may present a diagnostic dilemma because of the difficulty in determining whether the lesions are separate primary tumors or metastases. It has been reported that the detection of clonality using microsatellite markers may be useful in solving this dilemma. To determine the usefulness of this technique, we compared the genetic alterations in microsatellite markers present in matched pairs of ovarian tumors from 12 patients. The study includes four ovarian cancer FIGO stage I and eight stage III/IV patients, and four patients also with independent endometrial carcinoma of the uterus. DNA from paraffin-embedded tissue was extracted and amplified using a multiplex polymerase chain reaction, after which the status of microsatellite instability and loss of heterozygosity in four microsatellite loci (BAT25, BAT26, D17S250, and D5S346) were determined. In the four patients with stage I ovarian cancer, four microsatellite markers were identical in one patient and three were identical in the remaining three patients. In high-stage patients, three markers were identical in at least 4/8 cases. In three of four patients with uterine involvement, three of the four markers were identical in the uterine tumor and one of the corresponding ovarian tumors. These results suggest that genetic discordance does not indicate independent origin or metastasis of the tumor but instead a progression of genetic changes at separate sites probably due to the marked genetic instability existing in these tumors. Because of these discordant genetic changes, great caution should be taken when distinguishing between primary and metastatic tumors on the basis of microsatellite markers.

Adult↗