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Biomedical subjects

R Varma

Publications and source records attributed to R Varma.

At least 19 recordsLinked to original sources

Changes in optic disk characteristics and number of nerve fibers in experimental glaucoma.

We compared the change in cup/disk ratio and neuroretinal rim area-to-disk area to estimated change in the number of optic nerve fibers in 12 cynomolgus monkeys with unilateral experimental glaucoma. Changes in the cup/disk ratios and neuroretinal rim area-to-disk area were estimated from stereoscopic optic disk photographs that were obtained before and after the development of increased intraocular pressure. Change in the number of optic nerve fibers in the glaucomatous nerves was estimated by comparing them to their fellow normal nerves. A significant linear correlation was present between change in the cup/disk ratios and neuroretinal rim area-to-disk area, and estimated change in the number of optic nerve fibers (r > or = .85; P < .0002). In optic disks with initial cup/disk ratios of 0.2 to 0.3 and neuroretinal rim area-to-disk area of 0.9, an increase in the cup/disk ratio of 0.1 and a decrease of 0.1 in the neuroretinal rim area-to-disk area is associated with a 10% and 9% loss of optic nerve fibers, respectively.

Animals

Expert agreement in evaluating the optic disc for glaucoma.

The authors studied intraobserver and interobserver agreement, under monoscopic and stereoscopic conditions, in estimating vertical cup-to-disc ratios and in assessing whether a disc had glaucomatous damage. Six glaucoma experts evaluated 75 optic disc photographs under both viewing conditions. The experts also re-evaluated 25 photographs. Intraobserver agreement in estimating vertical cup-to disc ratios was high (median weighted kappa, 0.79). Interobserver agreement in estimating vertical cup-to-disc ratios was moderate (stereoscopic median weighted kappa, 0.67); individual experts differed by as much as 0.2 disc diameters (DD) monoscopically and 0.16 DD stereoscopically. The observers estimated larger vertical cup-to-disc ratios when evaluating the same discs under stereoscopic conditions than under monoscopic conditions. Intraobserver agreement in assessing glaucomatous disc damage was substantial (median kappa, 0.76). Interobserver agreement in assessing glaucomatous damage was moderate (stereoscopic median kappa, 0.50). This study confirms the ability of experts to reliably evaluate the optic disc within themselves and emphasizes the need for developing standardized methods for interobserver evaluation of the optic disc in glaucoma.

Adult

Single agent high-dose cisplatin (200 mg m-2) treatment in ovarian carcinoma.

Twenty patients with epithelial ovarian carcinoma were treated with high-dose cisplatin 200mg m-2. Patients were to receive three cycles at 21 day intervals. Treatment was stopped if severe myelosuppression or any neurotoxicity occurred. Overall, eight (40%) of patients responded with a complete response in five (25%). Four of 16 (25%) previously treated patients responded. The median duration of response was 44 weeks (range 6-130). In patients previously treated there was a significant association (P < 0.002) between response and a remission free interval of 52 weeks or more from primary chemotherapy. Toxicity was assessable in 18 patients. Alopecia and nausea/vomiting were common. Myelosuppression was recorded in nine patients delaying planned administration in eight of 35 cycles. Five patients developed anaemia and six thrombocytopenia. Neurotoxicity affected seven patients and varying degrees of tinnitus six patients. Neurotoxicity and myelosuppression were indications for cessation of treatment in 8 patients receiving less than three cycles. Analysis revealed no significant association between toxicity and prior cisplatin exposure, age or the amount of high-dose cisplatin administered. This series reveals that it is possible to achieve good response rates using high-dose cisplatin without encountering debilitating neurotoxicity.

Adult

Effect of a single replacement of one of Ringer lactate, hypertonic saline/dextran, 7g% albumin, stroma-free hemoglobin, o-raffinose polyhemoglobin or whole blood on the long term survival of unanesthetized rats with lethal hemorrhagic shock after 67% acute blood loss.

This study is based on an unanesthetized lethal hemorrhagic shock rat model (67% blood volume bled in 2 stages). The 8 groups studied were as follows. 1. Control--no resuscitation fluid. 2. Reinfusion of rat's own shed whole blood. 3. Ringer lactate solution--3 times shed blood volume. The following 4 fluids were each given as equal to the shed blood volume. 4. 7.5g% NaCl hypertonic saline/6% Dextran 70, followed by 3 volumes Ringer lactate dextran. 5. Ringer lactate solution. 6. Human albumin 7g% in Ringer lactate. 7. Stroma-free hemoglobin in Ringer lactate 8. o-raffinose polyhemoglobin in Ringer Lactate. Blood pressure and other vital signs were recorded continuously during the control period, bleeding periods, infusion period and 60 minutes after infusion. After this all surviving animals were followed for 14 days with no other special treatments. Group 4 had transient (10 minutes) returned of blood pressure to control levels. The 3 groups with sustained blood pressure at control level when followed for 1 hour were groups 2, 6 and 7. The 2 groups with 100% survival on days 14 were group 2 and group 7.

Animals

Immunological effects of hemoglobin, encapsulated hemoglobin, polyhemoglobin and conjugated hemoglobin using different immunization schedules.

Repeated subcutaneous immunizing injections into rats of Freund's adjuvant containing rat hemoglobin or o-raffinose rat polyhemoglobin did not result in increase in IgG antibody titers. However, heterologous hemoglobin injected as above is antigenic (49.50 + 6.70 % CPM). Crosslinking heterologous hemoglobin into o-raffinose polyhemoglobin further increased its antigenicity (75.60 + 4.08). Thus, unlike homologous hemoglobin, cross-linking of heterologous hemoglobin increased its antigenicity. Liposome encapsulated homologous hemoglobin injected subcutaneously with or without Freund's adjuvant did not show antigenicity. Encapsulated heterologous hemoglobin resulted in a minimal increase in antibody titers (10.73 + 4.64) only with Freund's adjuvant, but no increase when injected without Freund's adjuvant. Conjugated heterologous hemoglobin (PEG-Hb) injected intravenously by itself at weekly intervals did not result in significant increase in antibody titers on the 5th week.

Animals

Spatial contrast sensitivity is reduced in bilateral Parkinson's disease.

We studied the contrast sensitivity functions of 41 patients with idiopathic Parkinson's disease (PD) with a wide range of parkinsonian symptomatology (Hoehn and Yahr stages 1 to 4) and 22 age-matched control subjects in a parametric design. Results demonstrated reduced contrast sensitivity in PD patients but only in those patients who had progressed beyond Hoehn and Yahr stage 1. Furthermore, there were deficits in contrast sensitivity related to the severity of PD.

Aged

Feasibility and outcome of complete secondary tumor resection for patients with advanced ovarian cancer.

From November 1981 to July 1985, 124 women with International Federation of Gynecology and Obstetrics (FIGO) stage III ovarian cancer were treated in prospective studies of surgery and chemotherapy in our institution. Patients with no macroscopic cancer after primary surgery (n = 16) received five cycles of adjuvant cis-platinum; those with residual cancer after primary laparotomy (n = 108) underwent a second surgical debulking after three or five cycles of cis-platinum-based cytoreductive chemotherapy. Total macroscopic tumor clearance was achieved in 26 of these 108 patients. Fourteen patients with total tumor excision at primary laparotomy remain in complete clinical remission a minimum of 36 months after diagnosis, but the median progression-free interval for the other two groups was 9 and 17 months, respectively. The survival for women who have total tumor clearance only at secondary surgery after chemotherapy is inferior to that for women with primary macroscopic tumor excision followed by chemotherapy.

Adult

Tumour cell activity markers in epithelial ovarian cancer: are biochemical and cytometric indices complementary?

Flow cytometry has enabled the objective assessment of cellular morphology and activity, which can also be biochemically evaluated by measuring products of cellular metabolism, such as cyclic 3'5' guanosine monophosphate (cGMP). Using paraffin-embedded formalin-fixed material obtained from the primary operation, an analysis of the correlation between nuclear ploidy and the proliferative index (PI) as quantified by flow cytometry with pre-treatment urinary cGMP was performed in 40 epithelial ovarian cancer (EOC) patients. The majority of the study group had advanced disease (28 FIGO III/IV) and residual disease (31). All but three (stage I) patients received single agent high dose cisplatinum as first-line therapy (100 mg m-2 x 5); in patients with evaluable disease there was a response rate of 64%. Thirty-one patients have died; the median survival of the study population being 27 months. There was a significant association between cGMP and PI. Significantly more aneuploid tumours had elevated PI values (P = 0.02). No variable predicted response. An initial univariate log rank analysis identified stage, the amount of residual disease, cGMP and PI as prognostic factors. Because of the interrelation between these and other factors and because PI did not conform to the proportional hazards model, a multivariate stepwise discriminant analysis was performed using survival at 36 months (the minimum follow-up for surviving patients) as the end-point. On the basis of this analysis, stage and residual disease were the most important prognostic factors, but cyclic GMP continued to have prognostic value even when these other factors were entered into the predictive model. However, the additional information gained has little clinical relevance.

Biomarkers, Tumor

Early second surgery in ovarian cancer--improving the potential for cure or another unnecessary operation?

The presence and amount of residual disease after primary surgery is a major adverse prognostic factor in epithelial ovarian cancer [EOC]. Rapid initial cytoreduction employing second surgery early in the primary chemotherapeutic management of patients with gross residual disease has been advocated as a means of improving outcome. To evaluate the prognostic value of such an approach we have reviewed the outcome of 24 patients with gross residual disease, who were debulked to less than 2 cm residuum at a second operation, performed after three cycles of cis-platinum-based chemotherapy (a median of 14 weeks from the initial laparotomy), and compared this with an historical series of 195 patients with residual disease (70 patients with less than 2 cm residuum) who received cis-platinum but no early secondary surgery. In the control series, stage and residual disease status were important prognostic factors. There was no significant difference in patient or disease characteristics between those patients in the early second surgery group and control patients with greater than 2 cm disease (n = 125). Initially the survival curve for the early second surgery group was similar to the less than 2 cm disease group, but at about 18 months, there was a rapid deterioration until the survival parallels that of the patients with bulky disease at presentation. Early secondary surgery did not significantly prolong survival in patients with greater than 2 cm of residual disease.

Aged

Phenobarbital treatment and major depressive disorder in children with epilepsy: a naturalistic follow-up.

Of an original cohort of 39 epileptic patients, 28 were observed for a median of 26.5 months after an initial psychiatric interview. As had been noted in the original cohort, treatment with phenobarbital, as compared with treatment with carbamazepine or no anticonvulsant, was associated with higher rates of depression (38% vs 0%, P = .04). Depression associated with phenobarbital treatment at intake did not remit spontaneously on follow-up as long as phenobarbital use continued. Those patients treated with phenobarbital who were previously depressed and whose medication was changed to either carbamazepine or no medication showed nonsignificant trends toward declines in both the frequency and severity of depressive symptoms. These results provide further evidence that treatment with phenobarbital increases the risk for depression in epileptic patients and should be avoided when clinically feasible, particularly in patients with a personal or family history of affective disorder. Epileptic patients who receive phenobarbital because of clinical considerations should be monitored closely for symptoms of an affective disorder, and if depression is detected, a change to an alternative anticonvulsant may result in amelioration of depressive symptomatology.

Adolescent

Agreement between clinicians and an image analyzer in estimating cup-to-disc ratios.

We studied optic disc photographs of 35 eyes to determine the level of agreement between estimates of vertical and horizontal cup-to-disc ratios (CDRs) provided by two clinicians and estimates of these ratios obtained using an image analyzer. We also evaluated the agreement of each clinician with himself and with the other clinician to provide a relative standard by which to judge agreement between the clinicians and the image analyzer. Agreement between the clinicians and the image analyzer was moderate. Differences of more than 0.2 disc diameters (DD) between the CDR estimates of clinicians and those obtained using the image analyzer were limited to discs having small (CDR of 0.4 DD or lower) or very large (CDR of 0.9 DD or higher) cups. The clinicians' agreement with themselves and with each other was substantial to near perfect.

Adolescent

Risk factors for the development of Tenon's capsule cysts after trabeculectomy.

Tenon's capsule cysts (TCCs) are a complication of glaucoma filtering surgery. They are frequently associated with substantial elevations in intraocular pressure (IOP) beginning 2 to 8 weeks postoperatively. To determine the incidence and possible risk factors for the development of TCCs, case records of all patients who received trabeculectomy over a 4-year period at the Wills Eye Hospital were reviewed. The incidence of TCCs was 28% in those who underwent trabeculectomy. Characteristics of patients after trabeculectomy in whom TCCs developed were compared with patients after trabeculectomy in whom TCCs did not develop. Both univariate and multivariate techniques were used to assess the association of characteristics associated with the development of TCCs. Factors associated with increased risk (P less than 0.05) were: history of prior TCCs, argon laser trabeculoplasty, male gender, and the use of preoperative sympathomimetics. The use of a compression shell was associated with decreased risk (P less than 0.05).

Adult

A comparative evaluation of three methods of analyzing optic disc topography.

Topographical evaluations of the optic discs of 17 eyes obtained using a clinical planimeter, the Rodenstock video-ophthalmograph, and the IS 2000 image analyzer were compared. The parameters studied were vertical and horizontal cup-to-disc ratios, cup volumes, rim areas, disc areas, and rim area-to-disc area ratios. There was good correlation between the measurements obtained by the three methods (correlation coefficients ranged from 0.46 to 0.88). For various parameters, the correlations between clinical planimetry and image analysis were higher than either those between image analysis and video-ophthalmography, or those between clinical planimetry and video-ophthalmography. The mean horizontal cup-to-disc ratios and rim areas as measured by clinical planimetry were significantly higher than those measured by image analysis. Image analysis measured significantly higher disc area and rim areas and lower cup volumes than video-ophthalmography.

Aged

Quantification of progressive diabetic macular nonperfusion.

We used the IS-2000 Image Analyzer to estimate the extent of progressive diabetic macular nonperfusion in a patient by means of an automatic clustering algorithm applied to digitized fluorescein angiograms of the patient's macula taken over time. This method may provide an objective and reproducible quantification of progressive macular nonperfusion.

Adult