Search PubMed⌕ Search

Biomedical subjects

S Gupta

Publications and source records attributed to S Gupta.

At least 415 records · Page 23Linked to original sources

CT in the evaluation of complicated autosomal dominant polycystic kidney disease.

PURPOSE: We retrospectively reviewed the CT findings in 24 cases of autosomal dominant polycystic kidney disease (ADPKD) to assess the role of CT in the diagnostic work-up of patients with complicated ADPKD. MATERIAL AND METHODS: Twenty-four patients with ADPKD underwent unenhanced and contrast-enhanced CT for flank pain, haematuria, or fever. The images were retrospectively reviewed for presence of complicated cysts, their morphological features and associated findings in the perinephric space/retroperitoneum. RESULTS: Cyst haemorrhage was present in all patients, seen as high-density cysts, which were mostly bilateral. Most of these cysts had sharply outlined contours, sharp interfaces with adjacent renal parenchyma, imperceptible walls, and homogeneous density, and did not enhance following i.v. contrast administration. However, a few haemorrhagic cysts (9 cysts in 6 patients) showed inhomogeneous density (n=7), dependent layering of high-density blood leading to fluid-fluid level (n=2), and contour irregularity (n=3). CT revealed presence of cyst infection in 6 cases; the involved cysts were larger (average size 4.2 cm) than adjacent cysts, had only a mildly increased or near water density, and showed wall thickening and enhancement. Other findings included air within the infected cyst (n=1), thickening and enhancement of peri- and paranephric fasciae (n=5), and abscesses in the posterior paranephric space and adjoining psoas muscle (n=2). In 2 other patients, although CT suggested cyst infection because of presence of wall enhancement, diagnostic needle aspiration revealed only sterile haemorrhagic fluid. In 1 case, CT revealed a soft tissue density enhancing mass in one of the cysts; this proved to be a renal cell carcinoma by fine-needle biopsy. Calculi were observed in 7 patients, and cyst wall calcification in 11 cases. CONCLUSION: A combination of unenhanced and contrast-enhanced CT allows correct diagnosis and differentiation amongst the various complications affecting patients with ADPKD. However, in a small subgroup of patients, it may not be possible to differentiate between haemorrhage and infection; such cases require diagnostic needle aspiration for diagnosis.

Abdominal Pain↗

Ultrasound-guided transthoracic co-axial biopsy of thoracic mass lesions.

PURPOSE: To compare the diagnostic yield of fine-needle aspiration biopsy (FNAB) and cutting needle biopsy in thoracic lesions. MATERIAL AND METHODS: Thirty patients with thoracic mass lesions were subjected to ultrasound-guided co-axial FNAB and cutting needle biopsy using 0.7 mm aspirating and 1.0-mm cutting needles, respectively. The diagnostic yield of the individual modalities was compared with the combined yield. RESULTS: A conclusive diagnosis was obtained in 76.6% (n=23) of patients by FNAB and in 66.6% (n=20) by cutting needle biopsy. The combined diagnostic yield of FNAB and cutting needle biopsy was 93.3% (n=28) with a significant statistical difference (p<0.03) as compared to cutting biopsy alone. Of the patients, 23.2% (n=7) had benign and 76.6% (n=23) malignant aetiologies. The diagnostic yield of FNAB versus cutting needle biopsy in benign lesions was 57.1% (n=4) and 100% (n=7), respectively. The diagnostic yield of FNAB versus cutting needle biopsy in malignant lesions was 82.6% (n=19) and 56.5%, (n=13). Two patients remained undiagnosed by either modality. There were no complications. CONCLUSION: FNAB and cutting needle biopsy are complementary to each other and attempts should be made to obtain small tissue cores in addition to routine cytologic specimens in diagnosing thoracic lesions, especially in benign pathologies. US provides a safe guidance modality for lesions abutting the chest wall.

Adolescent↗

Characterization of polyvinylalcohol microspheres of diclofenac sodium: application of statistical design.

Microspheres of polyvinylalcohol (PVA) containing diclofenac sodium were prepared by an emulsion-chemical cross-linking method. A statistical design was used to study the variables that affect the preparation of microspheres and to study the release profile of diclofenac from the microspheres. To account for the drug content, a mass balance study of the process was performed. A high concentration of polyvinylalcohol, a high stirring speed, and a low level of glutaraldehyde were found to be important to obtain spherical and discrete microspheres. The concentration of polyvinylalcohol and the amount of heavy liquid paraffin were found to be critical factors in influencing the t50 value. Almost 98% of the total diclofenac sodium added was accounted for in mass balance studies.

Anti-Inflammatory Agents, Non-Steroidal↗

Total dose iron infusion: safety and efficacy in predialysis patients.

Iron deficiency anemia is not uncommon in predialysis patients. Oral iron often cannot maintain adequate iron stores. Hence we evaluated the safety and efficacy of total dose infusion (TDI) of iron in these patients. Anemic predialysis patients were screened and those with Hb < 7.0 g/dL and serum ferritin < 200 ng/mL were selected. Patients with active bleeding and acute liver disease were excluded. All patients were on oral iron 100 mg/day. None of the patients were on erythropoeitin. 11 patients (6 males and 5 females), aged 45.9 +/- 15 yrs, were suitable. Hb was 5.9 +/- 1.0 g/dL and serum ferritin was 89.5 + 50 ng/mL. The preparation used was iron dextran. A test dose of 25 mg in 100 mL normal saline was administered over 1 hr to all patients. One patient had fever and chills during the test dose and was not given TDI. 10 patients received TDI. None of these patients had any problem during the infusion. The dose of iron administered was 900 + 316.2 mg. One patient who received 1600 mg had arthralgia-myalgia and another patient had thrombophlebitis following TDI. One month after TDI, Hb was 8.0 + 1.0 g/dL and serum ferritin was 362 ng/mL. We feel that TDI is a safe and effective method of correcting iron deficiency in predialysis patients.

Adult↗

Sex differences in diquat-induced hepatic necrosis and DNA fragmentation in Fischer 344 rats.

Redox cycling metabolism of diquat catalyzes generation of reactive oxygen species, and diquat-induced acute hepatic necrosis in male Fischer 344 (F344) rats has been studied as a model of oxidant mechanisms of cell killing in vivo. At equal doses of diquat, female F344 rats sustained less hepatic damage than did male rats, as estimated by plasma alanine aminotransferase (ALT) activities after 6 h. Biliary efflux of glutathione disulfide (GSSG) was greater in male than in female rats at each dose of diquat, but even comparable rates of GSSG excretion were associated with less hepatic injury in female rats. Hepatic activities of superoxide dismutase (SOD) and glutathione peroxidase (GPX) were similar in the two genders, and activities of glutathione reductase (GR) and glutathione S-transferase-alpha (GST-alpha) activities were higher in the male rats. Previous studies in male rats have implicated formation of 2,4-dinitrophenylhydrazine (DNPH)-reactive "protein carbonyls" and related iron chelate-catalyzed redox reactions as mechanisms critical to diquat-induced acute cell death in vivo. However, diquat-treated female rats showed higher levels of DNPH-reactive proteins in livers and in bile than did males, both at identical doses of diquat and at doses that produced similar elevations in plasma ALT activities. In female rats, fragmentation of hepatic deoxyribonucleic acids (DNA) was increased by doses of diquat that did not increase plasma ALT activities, and increased fragmentation was observed prior to elevation of plasma ALT activities. In the present studies, hepatic necrosis was most closely associated with DNA fragmentation, although additional studies are needed to determine the mechanisms responsible for and the pathophysiological consequences of the fragmentation.

Alanine Transaminase↗

Penetrating keratoplasty in children.

PURPOSE: To determine the success of penetrating keratoplasty in the presence of various pediatric corneal abnormalities. METHODS: We performed a retrospective study of pediatric corneal grafts at L.V. Prasad Eye Institute, Hyderabad, India. Outcome of pediatric corneal transplantation was evaluated in terms of anatomic and optical success and factors contributing to poor graft survival. On the basis of the corneal pathology, patients were divided into three categories: congenital, acquired nontraumatic, and acquired traumatic. RESULTS: A retrospective analysis of 154 penetrating keratoplasties performed in 140 children, aged 14 years or younger, was done. The average follow-up was 1.3 years (range, 1 week-5 years). Grafts remained clear in 102 (66.2%) of 154 eyes. Clear grafts were achieved in 30 (63.8%) of 47 eyes with congenital opacities, 12 (54.5%) of 22 eyes with opacities from trauma, and 60 (70.6%) of 85 eyes with acquired nontraumatic opacities. Most (26 of 52) of the graft failures occurred during the first 26 weeks after surgery. Survival analysis revealed the probability of a graft remaining clear at the end of 26 weeks as 80% (SE, 3.39%). Poor graft survival could be correlated with those younger than 5 years (p = 0.0341) and performance of anterior vitrectomy (p = 0.0002). Most grafts failed because of allograft rejection (42.3%), infectious keratitis (26.9%), or secondary glaucoma (13.4%). Postoperatively, 53 eyes had > or =20/400 vision, 29 of which had > or =20/50. Vision could not be assessed in 33 eyes because of the young age. CONCLUSION: Whereas anatomic success of pediatric keratoplasty is increasing, optical success continues to remain less than satisfactory. Early surgical intervention and intensive amblyopia therapy may promote visual recovery.

Adolescent↗

Quantitative study of mucosal wave via videokymography in canine larynges.

OBJECTIVES: Vocal fold mucosal wave movements are thought to be important in determining voice characteristics and quality. To see these movements, high-speed cinematography and videostroboscopy have been used clinically; however, these techniques have disadvantages that make them impractical for quantitative measurement of mucosal wave movements. This study explored the feasibility of using line-scan cameras for mucosal wave analysis. METHODS: An excised larynx bench model was used to examine the effects of elongation and changes in subglottal pressure on the amplitude, frequency, and phase difference of vocal fold mucosal movements as calculated from line-scan images. RESULTS: The data showed a positive and linear relationship between an increase in subglottal pressure and amplitude of the mucosal wave; elongation of the vocal folds appeared to decrease the amplitude of mucosal wave upheaval at each level of subglottal pressure. Similarly, increase in subglottal pressure had a positive and linear relationship with increase in frequency of vibration; elongation of the vocal folds further increased the frequency at any given subglottal pressure. Phase difference between the movements of the upper and lower margins of the mucosal lips was estimated and did not appear to be significantly affected by changes in subglottal pressure and elongation. CONCLUSION: The data presented in this study are consistent with relationships that we would expect to be true from currently accepted models of vocal fold vibration.

Animals↗

Population pharmacokinetic and pharmacodynamic analysis of ribavirin in patients with chronic hepatitis C.

The population pharmacokinetics of ribavirin were assessed in patients with chronic hepatitis C virus (HCV) infection treated with interferon alpha-2b and ribavirin in four clinical efficacy studies. The authors collected 3450 ribavirin serum concentrations from 1105 patients at different treatment weeks for inclusion in the analysis. Population factors included gender, age, body weight, serum creatinine, creatinine clearance, and previous interferon treatment history. Ribavirin apparent clearance (CL/F) was calculated from individual patients' daily doses divided by concentration values, and the influence of these factors was assessed by multiple regression. Body weight, gender, age, and serum creatinine affected CL/F. Population mean CL/F estimates were 17.9 L/h (female) and 21.5 L/h (male) assuming an age of 40 years and body weight of 70 kg. Ribavirin apparent clearance increased as a function of body weight and decreased at ages greater than 40 years. Serum creatinine had little influence on CL/F, which may reflect the relatively normal renal function of these patients. Total CL/F variability was approximately 28%. The four covariates in the model explained 27% of this variability, and were thus of limited clinical significance because of the substantial residual variability not accounted for by the model. In assessing the relationship between pharmacokinetics and pharmacodynamics, the week 4 hemoglobin nadir value was negatively associated with week 4 ribavirin concentrations. The percentage of reduction from baseline was positively associated with ribavirin concentrations, although these data were highly variable. Loss of HCV-RNA at 24 weeks after completion of treatment was considered a response to interferon and ribavirin treatment in a logistic regression analysis of clinical and pharmacokinetic variables and treatment response in the interferon-naive patients. Hepatitis C virus genotype, pretreatment HCV-RNA titer, duration of treatment period, week 4 ribavirin concentration, and patient age affected the likelihood of response. Higher ribavirin concentrations at treatment week 4 were associated with a higher response rate. Variables that have predictive value for treatment outcome in patients treated with interferon and ribavirin are similar to those previously reported for interferon monotherapy.

Adult↗

Long-term adverse effects of novel antipsychotics.

The introduction of novel antipsychotics for the treatment of patients with serious psychiatric illness has alleviated the burden of managing some of the side effects of conventional agents. However, the novel agents may also cause adverse events. The long-term adverse events of concern include weight gain, diabetes, tardive dyskinesia (TD), and those associated with hyperprolactinemia. Recent studies with the novel agents have prompted clinicians to revisit antipsychotic-induced weight gain. Clinically significant weight gain puts patients at risk for coronary heart disease, hypertension, type II diabetes, dyslipidemia, and some types of cancer. More recently, case reports of glucose abnormalities and diabetes have emerged, indicating that some novel antipsychotics may be associated with altered glucose metabolism or insulin sensitivity. The novel antipsychotics may also have a lower propensity for causing TD than the conventional antipsychotics. Side effects associated with hyperprolactinemia include galactorrhea, gynecomastia, and menstrual and sexual dysfunction. All of these adverse events can cause patients to become non-compliant and may thus predispose them to relapse. In this review, the authors summarize the literature on the long-term side effects of the novel antipsychotics and examine the severity of the problem, with recommendations for management. When selecting treatments, clinicians should consider the side-effect profiles of the various antipsychotic agents.

Journal Article↗

Subcutaneous cysticercosis involving the eyelid: sonographic diagnosis.

A 25-year-old man and a 14-year-old boy presented with neurocutaneous cysticercosis involving the eyelid. Both patients had hundreds of scattered subcutaneous cysticerci. They were arranged in clusters over the sternocleidomastoid muscle in the neck. Such clustering of cysticerci is highly suggestive of central nervous system (CNS) involvement, as both the sternocleidomastoid muscle and the CNS are supplied by the carotid artery and cysticerci travel via the hematogenous route. We used ultrasonography to diagnose subcutaneous cysticercosis, which showed characteristic low reflective cysts and high reflective scolices inside. Although subcutaneous cysticerci are inconsequential, their verification is important in the diagnosis of more severe CNS involvement. They may be confused with other painless swellings such as lymphadenopathies, neurofibromas, and epidermoid cysts.

Adolescent↗

Conventional cold excision combined with dermabrasion for rhinophyma.

A 65-year-old man, farmer by occupation, presented with redness and gradual enlargement of the nose. Examination revealed marked nodular enlargement of the nose and loss of normal nasal contours. Sebaceous material could be expressed from widened pores. The patient was diagnosed as rhinophyma of moderate degree. He was treated with cold knife excision combined with dermabrasion. A literature scan revealed that currently there is no evidence of superiority of much popular laser surgery over conventional cold knife surgery combined with dermabrasion for rhinophyma. Conventional surgery is time-tested, and it does not require expensive equipment or special training.

Aged↗

Chemotherapy in recurrent epithelial ovarian cancer (EOC): an analysis of prognostic factors.

OBJECTIVE: Prognosis of patients with recurrent epithelial ovarian cancer (EOC) is generally poor. Cisplatin is the most effective drug. We used three cisplatin based chemotherapeutic (CT) regimens and retrospectively analyzed the data to determine the response rate, toxicity, survival and the impact of various prognostic factors on the outcome. PATIENTS AND METHODS: Between August, 1989 and September, 1997, 102 patients were diagnosed to have recurrent EOC. Sixty-five of 102 patients received CT every 3 weeks using cisplatin 75 mg/m2 i.v. day 1 plus cyclophosphamide 750 mg/m2 i.v. day 1 (CP, Group A, n = 29), cisplatin 75 mg/m2 i.v. day 1, plus adriamycin 40 mg/m2 i.v. day 1 and cyclophosphamide (CAP, Group B, n = 22) and paclitaxel 135 mg/m2 i.v. day 1 plus cisplatin 75 mg/m2 i.v. day 1 (TP, Group C, n = 14). Twelve patients received single agent CT and were not analyzed. Remaining 25 patients refused CT treatment and were followed for survival. RESULTS: The overall response rate (complete and partial) was 59.2% for patients receiving CP (Group A), 45% for CAP (Group B) and 76.9% for those receiving TP (Group C), p = ns. Response rate was significantly higher for patients with platinum sensitive disease compared to those with platinum resistant disease; 55.76 vs 39%, p < 0.007. CT was generally tolerated well; 2 patients died of CT toxicity, one each in Group A (CP) and C (TP), respectively. The median survival from the date of relapse for patients receiving chemotherapy was 15 months compared to 4 months for those who did not receive chemotherapy, p < 0.001. Chemotherapy responders had a significantly higher median survival than chemotherapy non-responders, 24 months vs 10 months, p < 0.01. The median overall survival was not significantly different in the 3 groups; Group A--15 months, Group B--12 months and 15 months in Group C, p = 0.738. On univariate analysis--time since last CT (< 6 months vs > 6 months, p < 0.037, response to previous CT, p < 0.0183, cisplatinum sensitivity vs resistance, p < 0.032, number of sites (< 2 vs > 2) of recurrence, p < 0.004 and response to salvage CT, p < 0.01 were associated with survival benefit. On multivariate analysis, 2 factors--platinum sensitivity and response to salvage CT attained significance. CONCLUSIONS: Our study confirms the benefit of platinum based chemotherapy in recurrent EOC. Patients with platinum sensitive disease, and those responding to salvage chemotherapy benefit most.

Adult↗

Pharmacokinetics of SCH 56592, a new azole broad-spectrum antifungal agent, in mice, rats, rabbits, dogs, and cynomolgus monkeys.

SCH 56592 is a new broad-spectrum azole antifungal agent that is in phase 3 clinical trials for the treatment of serious systemic fungal infections. The pharmacokinetics of this drug candidate were evaluated following its intravenous (i.v.) or oral (p.o.) administration as a solution in hydroxypropyl-beta-cyclodextrin (HPbetaCD) or oral administration as a suspension in 0.4% methylcellulose (MC) in studies involving mice, rats, rabbits, dogs, and cynomolgus monkeys. SCH 56592 was orally bioavailable in all species. The oral bioavailability was higher with the HPbetaCD solution (range, 52 to approximately 100%) than from the MC suspension (range, 14 to 48%) and was higher in mice ( approximately 100% [HPbetaCD] and 47% [MC]), rats ( approximately 66% [HPbetaCD] and 48% [MC]), and dogs (72% [HPbetaCD] and 37% [MC]) than in monkeys (52% [HPbetaCD] and 14% [MC]). In rabbits, high concentrations in serum suggested good oral bioavailability with the MC suspension. The i.v. terminal-phase half-lives were 7 h in mice and rats, 15 h in dogs, and 23 h in monkeys. In rabbits, the oral half-life was 9 h. In species given increasing oral doses (mice, rats, and dogs), serum drug concentrations were dose related. Food produced a fourfold increase in serum drug concentrations in dogs. Multiple daily doses of 40 mg of SCH 56592/kg of body weight for eight consecutive days to fed dogs resulted in higher concentrations in serum, indicating accumulation upon multiple dosing, with an accumulation index of approximately 2.6. Concentrations above the MICs and minimum fungicidal concentrations for most organisms were observed at 24 h following a single oral dose in MC suspension in all five species studied (20 mg/kg for mice, rats, and rabbits and 10 mg/kg for dogs and monkeys), suggesting that once-daily administration of SCH 56592 in human subjects would be a therapeutically effective dosage regimen.

Animals↗

Pharmacokinetics of an everninomicin (SCH 27899) in mice, rats, rabbits, and cynomolgus monkeys following intravenous administration.

The pharmacokinetics of SCH 27899, a novel oligosaccharide compound of the everninomicin class with excellent activity against gram-positive strains, was studied with mice, rats, rabbits, and cynomolgus monkeys following intravenous administration as SCH 27899-N-methylglucamine-hydroxypropyl beta-cyclodextrin. Concentrations of SCH 27899 in mouse serum, rat plasma, and rabbit serum were determined by a high-pressure liquid chromatography method on a poly(styrene-divinyl benzene) column, and those in monkey plasma were determined by a paired-ion chromatographic method. Plasma and serum concentrations of SCH 27899 exhibited a biexponential decline in all species following intravenous administration. The half-lives at beta phase were 3.0 to 7.9 h in mice, rats, and rabbits and 24 h in cynomolgus monkeys. There was a linear relationship between the area under the curve extrapolated to infinity [AUC(I)] in mice and dose. Rabbits also exhibited dose proportionality in AUC(I). However, in rats, increasing the dose from 3 to 60 mg/kg of body weight resulted in a 49-fold increase in AUC(I). When the species was changed from mouse to rat, rabbit, or cynomolgus monkey, AUC(I) increased, whereas clearance (CL) decreased. It was concluded that the pharmacokinetics of SCH 27899 in animals varied with species; CL was the highest in mice and rats, followed by rabbits and cynomolgus monkeys.

Aminoglycosides↗

Carried meningococci in the Czech Republic: a diverse recombining population.

Population and evolutionary analyses of pathogenic bacteria are frequently hindered by sampling strategies that concentrate on isolates from patients with invasive disease. This is especially so for the gram-negative diplococcus Neisseria meningitidis, a cause of septicemia and meningitis worldwide. Meningococcal isolate collections almost exclusively comprise organisms originating from patients with invasive meningococcal disease, although this bacterium is a commensal inhabitant of the human nasopharynx and very rarely causes pathological effects. In the present study, molecular biology-based techniques were used to establish the genetic relationships of 156 meningococci isolated from healthy young adults in the Czech Republic during 1993. None of the individuals sampled had known links to patients with invasive disease. Multilocus sequence typing (MLST) showed that the bacterial population was highly diverse, comprising 71 different sequence types (STs) which were assigned to 34 distinct complexes or lineages. Three previously identified hyperinvasive lineages were present: 26 isolates (17%) belonged to the ST-41 complex (lineage 3); 4 (2.6%) belonged to the ST-11 (electrophoretic type [ET-37]) complex, and 1 (0.6%) belonged to the ST-32 (ET-5) complex. The data were consistent with the view that most nucleotide sequence diversity resulted from the reassortment of alleles by horizontal genetic exchange.

Adolescent↗

Dissection of Ras-dependent signaling pathways controlling aggressive tumor growth of human fibrosarcoma cells: evidence for a potential novel pathway.

Activation of multiple signaling pathways is required to trigger the full spectrum of in vitro and in vivo phenotypic traits associated with neoplastic transformation by oncogenic Ras. To determine which of these pathways are important for N-ras tumorigenesis in human cancer cells and also to investigate the possibility of cross talk among the pathways, we have utilized a human fibrosarcoma cell line (HT1080), which contains an endogenous mutated allele of the N-ras gene, and its derivative (MCH603c8), which lacks the mutant N-ras allele. We have stably transfected MCH603c8 and HT1080 cells with activating or dominant-negative mutant cDNAs, respectively, of various components of the Raf, Rac, and RhoA pathways. In previous studies with these cell lines we showed that loss of mutant Ras function results in dramatic changes in the in vitro phenotypic traits and conversion to a weakly tumorigenic phenotype in vivo. We report here that only overexpression of activated MEK contributed significantly to the conversion of MCH603c8 cells to an aggressive tumorigenic phenotype. Furthermore, we have demonstrated that blocking the constitutive activation of the Raf-MEK, Rac, or RhoA pathway alone is not sufficient to block the aggressive tumorigenic phenotype of HT1080, despite affecting a number of in vitro-transformed phenotypic traits. We have also demonstrated the possibility of bidirectional cross talk between the Raf-MEK-ERK pathway and the Rac-JNK or RhoA pathway. Finally, overexpression of activated MEK in MCH603c8 cells appears to result in the activation of an as-yet-unidentified target(s) that is critical for the aggressive tumorigenic phenotype.

Animals↗