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Sanjay Sharma

Publications and source records attributed to Sanjay Sharma.

At least 37 records · Page 2Linked to original sources
PubMed2006

Update on utilities and cost-utility analyses.

PURPOSE OF REVIEW: The purpose of this review is to summarize the recent and noteworthy utility studies and cost-utility analyses in the area of retina/vitreous during the period January 2004 to January 2006. RECENT FINDINGS: This review considers the cost-effectiveness of treatments for wet age-related macular degeneration, dry age-related macular degeneration, telemedicine in diabetic retinopathy, and utilities and patients with age-related macular degeneration and diabetic retinopathy. SUMMARY: Utilities are being used increasingly to measure health-related quality of life. Cost-utility analyses are becoming more readily available for comparing the incremental cost-effectiveness of different ophthalmic interventions.

Cost-Benefit Analysis↗
PubMed2006

Manual exfoliation plus immunomagnetic bead separation as an initial step toward translational research.

CONTEXT: The development of biotechnologic platforms capable of high throughput analysis has ushered in a promising new era of translational medicine. However, most studies to date are based on in vitro cell lines or substitute models for human disease. Although these model systems have proven insightful, it is readily becoming apparent that human clinical tissue must be studied in order to fully understand all the nuances of human disease. Studies that are based on human tissue, however, are limited by qualitative and quantitative issues, factors often precluding their use in high throughput studies. OBJECTIVE: To develop a simple and rapid tissue procurement protocol for use in obtaining a homogeneous epithelial cell population from clinical tissue and the recovery of nucleic acids and proteins of high quality and quantity. Also, to determine if the technique preserves tissue, thereby allowing morphologic correlation with molecular findings. DESIGN: Performance of manual exfoliation to procure cells from clinical resection specimens and use of immunomagnetic beads embedded with the antibody ber-Ep4 for the positive enrichment of a homogeneous epithelial cell population. Nucleic acids and proteins are then separated using a phenol plus guanidine thiocyante solution. Nucleic acids and proteins are quantitated and qualitatively analyzed using standard laboratory techniques. RESULTS: Nucleic acids and proteins of high quality and quantity were recovered following manual exfoliation and immunomagnetic bead separation. Tissue architecture was not destroyed, thus permitting histologic and molecular correlation. CONCLUSIONS: A simple and reproducible protocol is presented that may enable the molecular profiling of clinically resected tissue. Although the technique is currently limited to certain tissue and tumor types, further research will broaden its overall application.

Adenocarcinoma↗
PubMed2006

Gastric adenocarcinoma presenting with intestinal pseudoobstruction, successfully treated with octreotide.

Intestinal pseudoobstruction has been reported as a paraneoplastic manifestation of several cancers, including those of gastrointestinal tract. Octreotide, a somatostatin analogue, has been used successfully in the treatment of idiopathic and scleroderma-associated intestinal pseudoobstruction. We report a 65-year-old man with carcinoma stomach presenting with intestinal pseudoobstruction, which responded to octreotide.

Adenocarcinoma↗
PubMed2005

Aging affect the anti-tumor potential of dendritic cell vaccination, but it can be overcome by co-stimulation with anti-OX40 or anti-4-1BB.

It has been well established that there is a decline in immune function with age resulting in a diminished capacity to respond to infections or tumors. Although many studies have demonstrated the efficacy of autologous dendritic cells (DC) vaccines in stimulating an anti-tumor immune response in the young, almost none of these reports consider the effect that aging has on the immune system or test whether DC-vaccination is effective in old hosts. In this study we compared the efficacy of DC-vaccination in young and old mice. Our results showed that DC-vaccination in young animals induced an anti-tumor response resulting in approximately 60% tumor growth inhibition, while minimal protection was observed in old animals. DC vaccination plus rIL-2 further enhanced the anti-tumor response in young animals (approximately 70-75% inhibition), while ineffective in old animals. In contrast, co-administration of anti-OX-40 or anti-4-1BB mAbs vigorously enhanced the anti-tumor immune response in both young (approximately 85-90% inhibition) and old mice (approximately 70-75% inhibition). Our data indicate that although old mice have a decline in immune function, they have the capacity to develop strong anti-tumor responses as long as they are provided with efficient co-stimulation.

Adenocarcinoma↗
PubMed2005

Pharmacodynamic evaluation of warfarin and rosuvastatin co-administration in healthy subjects.

OBJECTIVE: To determine whether co-administration of rosuvastatin alters the pharmacodynamics of warfarin, thereby requiring additional monitoring of the anticoagulant effects of warfarin. METHODS: In this open-labeled, placebo-controlled, randomized, two-period, crossover trial with a washout period of 15 days, 12 healthy male volunteers were administered daily oral doses of 5 mg warfarin for 14 days. Either rosuvastatin 40 mg/day (treatment A) or placebo (treatment B) was concomitantly administered on days 8-14. The pharmacodynamic parameters prothrombin time (PT) and international normalized ratio (INR) were evaluated on all 14 days pre-dose during both study periods. On the 8th, 10th, 12th, and 14th days of each study period, PT and INR were also measured at 4 h post-dose of rosuvastatin or placebo. Bleeding time and clotting time were assessed on the 1st, 8th, and 14th days pre-dose. RESULTS: Data of 10 subjects have been analyzed. No significant effect of rosuvastatin was seen on the steady-state pharmacodynamics of warfarin during concomitant administration. CONCLUSION: Rosuvastatin did not significantly alter the anticoagulant effects of warfarin in this study.

Administration, Oral↗
PubMed2005

Cancer cell adaptation to chemotherapy.

BACKGROUND: Tumor resistance to chemotherapy may be present at the beginning of treatment, develop during treatment, or become apparent on re-treatment of the patient. The mechanisms involved are usually inferred from experiments with cell lines, as studies in tumor-derived cells are difficult. Studies of human tumors show that cells adapt to chemotherapy, but it has been largely assumed that clonal selection leads to the resistance of recurrent tumors. METHODS: Cells derived from 47 tumors of breast, ovarian, esophageal, and colorectal origin and 16 paired esophageal biopsies were exposed to anticancer agents (cisplatin; 5-fluorouracil; epirubicin; doxorubicin; paclitaxel; irinotecan and topotecan) in short-term cell culture (6 days). Real-time quantitative PCR was used to measure up- or down-regulation of 16 different resistance/target genes, and when tissue was available, immunohistochemistry was used to assess the protein levels. RESULTS: In 8/16 paired esophageal biopsies, there was an increase in the expression of multi-drug resistance gene 1 (MDR1) following epirubicin + cisplatin + 5-fluorouracil (ECF) chemotherapy and this was accompanied by increased expression of the MDR-1 encoded protein, P-gp. Following exposure to doxorubicin in vitro, 13/14 breast carcinomas and 9/12 ovarian carcinomas showed >2-fold down-regulation of topoisomerase IIalpha (TOPOIIalpha). Exposure to topotecan in vitro, resulted in >4-fold down-regulation of TOPOIIalpha in 6/7 colorectal tumors and 8/10 ovarian tumors. CONCLUSION: This study suggests that up-regulation of resistance genes or down-regulation in target genes may occur rapidly in human solid tumors, within days of the start of treatment, and that similar changes are present in pre- and post-chemotherapy biopsy material. The molecular processes used by each tumor appear to be linked to the drug used, but there is also heterogeneity between individual tumors, even those with the same histological type, in the pattern and magnitude of response to the same drugs. Adaptation to chemotherapy may explain why prediction of resistance mechanisms is difficult on the basis of tumor type alone or individual markers, and suggests that more complex predictive methods are required to improve the response rates to chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

Visual outcomes and complications of epiretinal membrane removal secondary to rhegmatogenous retinal detachment.

PURPOSE: To examine visual outcomes after surgery for removal of epiretinal membrane after retinal detachment (RD) repair, and to identify possible complications. DESIGN: Retrospective case series. PARTICIPANTS: Seventy-five patients who underwent surgery for removal of an epiretinal membrane after RD repair. METHODS: Retrospective chart review of 75 patients who underwent surgery for removal of an epiretinal membrane after RD repair over a 10-year period. Follow-up ranged from 6 to 124 months (mean, 49). MAIN OUTCOME MEASURES: Measurement of final visual acuity (VA). RESULTS: After epiretinal membrane removal, VA increased 0.43 logarithms of the minimum angle of resolution (95% confidence interval, 0.27-0.58; t = 5.47, P = 0.000). Sixty-six patients (88%) had a VA at final follow-up greater than their preoperative VA. Forty-nine patients (70%) had a final VA equal to or greater than their best VA after RD repair. Final VA of 20/60 or better was achieved in 65.3% of eyes. Of the 43 eyes that were phakic at the beginning of the study, 34 (79.1%) underwent cataract extraction before final follow-up. Five eyes (6.7%) had a recurrent RD after membrane removal. Sixteen eyes (21.3%) developed a recurrent epiretinal membrane, 1 of which (1.3% of all eyes) was visually significant, requiring repeat surgery. CONCLUSIONS: Epiretinal membrane development is a known complication of RD repair. Visual acuity can be improved in these patients by removal of the epiretinal membrane, with excellent results. In this series, recurrent membrane formation is not visually significant. Careful follow-up is needed to detect recurrent RD.

Adolescent↗
PubMed2005

Progression of visual loss and time between initial assessment and treatment of wet age-related macular degeneration.

PURPOSE: To determine whether the time elapsed from initial (referral) diagnosis of neovascular (wet) age-related macular degeneration (AMD) to assessment and treatment by a retinal specialist is associated with visual deterioration in the intervening period. METHODS: A prospective pilot study of 38 consecutive AMD patients who presented with newly diagnosed subfoveal choroidal neovascularization was conducted in a tertiary care retinal practice. All eligible subjects underwent clinical examination and digital fluorescein angiography at the time of assessment by a retinal specialist. Correlations were performed to assess the association between continuous independent variables and any visual deterioration since initial diagnosis. Multivariate linear regression models with stepwise techniques were used to evaluate any association between visual progression and time elapsed, while controlling for potential clinical covariates. RESULTS: Of the 38 patients, 32 (84%) met the inclusion and exclusion criteria; no differences in important variables were noted between those included and those excluded. The median time between initial diagnosis and referral assessment and treatment was 28 days (interquartile range=36.5 days); some degree of visual loss developed in 14 (44%) of the subjects. The elapsed time was correlated with progression of visual loss (r=0.50, p=0.003). Multivariate linear regression demonstrated that only time elapsed and lesion type based on fluorescein angiography were associated with progression of visual loss (R2=0.491, F(4,28)=6.744, p=0.001); lesion size, age and sex were not significantly associated with progression of visual loss. INTERPRETATION: Delay in assessment and treatment of new-onset wet AMD by a retinal specialist is associated with a higher risk of visual loss.

Aged↗
PubMed2005

Drug pricing for a novel treatment for wet macular degeneration: using incremental cost-effectiveness ratios to ensure societal value.

OBJECTIVE: Health economic models can assist policy-makers in determining the value of novel treatments from the viewpoint of society. In this context, value is defined as the benefit of treatment, given its cost. A new treatment for wet age-related macular degeneration (AMD), juxtascleral administration of anecortave acetate, 15 mg for depot suspension (Retaane), is now in a late-phase clinical trial. In a theoretical analysis, we sought to determine the cost at which this treatment might offer economic value to society, using incremental cost-effectiveness ratios (ICERs). METHODS: A series of 1-year cost-utility models was created for the investigational treatment and standard treatment (photodynamic therapy [PDT] with verteporfin [Visudyne]). Value to society was defined in terms of theoretical associated ICERs (in US dollars): $100,000 per quality-adjusted life-year (QALY), $50,000/QALY, $20,000/QALY and $0/QALY, the point of economic indifference. Models were created from the societal perspective and included a patient-derived utility assessment involving regression equations to estimate time trade-off preferences, event probabilities derived from a randomized clinical trial comparing the safety and efficacy of anecortave administration and PDT with verteporfin, decision analysis and relevant costing information. RESULTS: An ICER of $100,000/QALY would be associated with an anecortave cost of $3022/vial, an ICER of $50,000/QALY with an anecortave cost of $2986/vial and an ICER of $20,000/QALY with an anecortave cost of $2964/vial. The point of economic indifference between anecortave administration and standard therapy would occur with an anecortave cost of $2950/vial. INTERPRETATION: In theory, an anecortave cost of $2986/vial is associated with an ICER of $50,000/QALY, the threshold used by many health technology assessment and reimbursement agencies.

Clinical Trials, Phase III as Topic↗
PubMed2005

Comparison of the different approaches to saphenous nerve block.

BACKGROUND: The authors compared the efficacy of the different approaches to saphenous nerve block. METHODS: The following approaches to saphenous nerve block were compared in 10 volunteers: perifemoral, transsartorial, block at the medial femoral condyle, below-the-knee field block, and blockade at the level of the medial malleolus. Each volunteer underwent all five blocks, and the interval between blocks was 3-7 days. The sequence of injection was randomized by Latin square design. Sensory blockade at the medial aspects of the leg and foot and the strength of the anterior thigh muscles were noted. RESULTS: The transsartorial, perifemoral, and below-the-knee field block approaches were more effective than block at the medial femoral condyle in providing sensory anesthesia to the medial aspect of the leg. The transsartorial approach was more effective than block at the medial femoral condyle and below-the-knee field block in providing sensory anesthesia to the medial aspect of the foot. Compared with the perifemoral approach, the transsartorial approach did not cause weakness of the hip flexors and the knee extensors. In volunteers with partial numbness in the medial aspect of the foot, supplemental block of the medial dorsal cutaneous branch of the superficial peroneal nerve resulted in complete sensory blockade. CONCLUSIONS: Sensory blockade in the medial aspects of the leg and foot is best achieved with the transsartorial approach. In some subjects, supplementary block of the medial dorsal cutaneous branch of the superficial peroneal nerve may have to be performed to assure complete numbness of the medial aspect of the foot.

Adult↗
PubMed2005

Rapid up-regulation of cyclooxygenase-2 by 5-fluorouracil in human solid tumors.

Inhibition of cyclooxygenase (COX)-2 has been associated with reduced growth of malignant cells. Current therapy of gastrointestinal carcinomas involves the use of 5-fluorouracil (5-FU)-based chemotherapy and we have therefore studied the effect of this agent on the expression of COX-2. COX-2 expression was measured by quantitative RT-PCR in biopsies from a series of 14 esophageal carcinomas, six of which had paired samples taken before and after chemotherapy, and in tumor-derived cells exposed to 5-FU in vitro from a series of 44 tumors, including breast, ovarian, esophageal and colonic carcinomas. COX-2 expression was increased by exposure to 5-FU or 5-FU combination chemotherapy in all the tumor types studied, whether measured in biopsies taken before and after 5-FU-based chemotherapy (4-fold increase, p<0.015) or in primary cells exposed to drugs in vitro (24-fold increase, p<0.001). A modest increase of COX-2 mRNA was also seen after in vitro treatment of cells with cisplatin. In contrast, doxorubicin and paclitaxel caused no up-regulation in vitro, while irinotecan caused inhibition of COX-2 (2.7-fold decrease, p<0.01). These data provide a molecular rationale for clinical trials of combination chemotherapy with COX-2 inhibitors.

Adult↗
PubMed2005

Photodynamic therapy for juxtafoveal choroidal neovascularization due to ocular histoplasmosis syndrome.

PURPOSE: To report the use of photodynamic therapy with verteporfin in patients with juxtafoveal choroidal neovascularization (CNV) for ocular histoplasmosis syndrome (OHS). METHODS: Retrospective review. Data regarding the following variables were extracted from patient charts: demographic characteristics, previous surgeries, angiographic features, number and time of treatments, follow-up time, and change in visual acuity. RESULTS: This study sample consisted of 23 eyes of 23 consecutive patients who were treated with photodynamic therapy for the management of juxtafoveal CNV. When post-treatment visual acuity (mean logMAR acuity=0.321) was compared to baseline acuity (mean logMAR visual acuity=3.89) vision improved by more than three Snellen lines in 30% of eyes, remained the same (+/-2 Snellen lines) in 52% of eyes, and worsened (greater than a two-line loss in visual acuity) in 18% of eyes. Although this series was uncontrolled, the patients had a trend toward a therapeutic benefit when compared to published natural history of similar cases (OR=0.292, P value=0.071 when compared to data from the Macular Photocoagulation Study for treatment of juxtafoveal lesions). CONCLUSION: Photodynamic therapy with verteporfin may be beneficial in patients with juxtafoveal CNV secondary to OHS in terms of both visual stabilization and improvement.

Adult↗
PubMed2005

The impact of diabetic retinopathy on health-related quality of life.

PURPOSE OF REVIEW: To review recent evidence evaluating the effect of diabetic retinopathy and diabetic macular edema on health-related quality of life. RECENT FINDINGS: A search of PubMed was conducted according to a strategy that combined the text words 'diabetic retinopathy' and 'quality of life' (n = 91; November 11, 2004) and 'diabetic macular edema' and 'quality of life' (n = 6; November 22, 2004). The Methods sections of all abstracts were reviewed for valid generic or disease-specific instruments used to evaluate health-related quality of life. In addition, abstracts were reviewed to ensure that the study sample was made up predominantly of diabetic individuals. Recent data suggest that persons with diabetic retinopathy are willing to trade off significant time to eliminate their ocular condition (mean time tradeoff score = 0.77-0.8) and that laser photocoagulation can improve health-related quality of life (significant improvement noted in 8 of 11 domains in the National Eye Institute Visual Function Questionnaire). In addition, recent research has noted that health-related quality of life can become affected in persons with diabetic retinopathy prior to visual loss, primarily because of anxiety about the future and emotional reaction to diagnosis and treatment. SUMMARY: From a search of the literature, several recent articles could be identified that demonstrated both a qualitative and a quantitative reduction in health-related quality of life in persons with diabetic retinopathy. With many novel treatments being explored for the management of diabetic retinopathy and diabetic macular edema, measuring health-related quality of life will likely play an important role both in the decision to offer treatment and in monitoring relevant health gains that may be derived from intervention.

Diabetic Retinopathy↗