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Biomedical subjects

R Varma

Publications and source records attributed to R Varma.

At least 55 records · Page 3Linked to original sources
PubMed1995

Measurement of optic disc compliance by digitized image analysis in the normal monkey eye.

PURPOSE: To characterize the compliance of the normal monkey optic disc under conditions of induced short-term fluctuations in intraocular pressure (IOP). METHODS: In 10 monkeys, one eye was compliance tested on three separate days followed by a single test of the contralateral eye (40 compliance tests). In a testing session, the optic disc was imaged at 2 and 47 minutes (baseline time point) after IOP was lowered to 10 mmHg; then at 2, 17, 32, and 47 minutes after IOP was elevated to 45 mmHg; then at 2, 47, and, in some cases, 92 minutes after IOP was lowered back to 10 mmHg. Eight digitized images were analyzed at each time point, yielding two parameters to characterize the position of the disc: the Mean Position of the Disc (MPD) and the Change from MPDBaseline (the value of MPD at a given time point minus the value for MPD at the baseline time point of that testing session). Analysis of variance (ANOVA) testing was used to evaluate the overall effect of IOP on both parameters while taking into account the effects of variability due to different monkeys and repetitions of the test as well as differences between the two eyes of an individual monkey. With the addition of data from 11 compliance tests performed on eight additional monkeys, the overall results were calculated in terms of the mean Change from MPDBaseline at each time point for a total of 51 compliance testing sessions. RESULTS: The mean Change from MPDBaseline was -28 microns (95% confidence interval, -23 to -33 microns) 47 minutes after elevation of IOP. The disc surface returned to its baseline position 92 minutes after IOP was lowered back to 10 mmHg. Elevation of IOP within a compliance test had a significant effect on the position of the optic disc surface (P = 0.0002, ANOVA), as characterized by the parameter Change from MPDBaseline. Neither the difference in the amount of movement between the two eyes of an individual monkey nor the variability within the three repetitions of the test in a given eye was statistically significant. CONCLUSION: Small, reversible (elastic) posterior deformations of the optic disc surface follow acute elevations of IOP in the normal monkey eye. Detection of acute IOP-induced deformations of the optic disc surface may represent a means by which to mechanically test the deeper load-bearing tissues of the optic nerve head.

Analysis of Variance↗
PubMed1995

Antineoplastic agents 322. synthesis of combretastatin A-4 prodrugs.

Combretastatin A-4 (1a), the principal cancer cell growth-inhibitory constituent of the Zulu medicinal plant Combretum caffrum, has been undergoing preclinical development. However, the very limited water solubility of this phenol has complicated drug formation. Hence, derivatives of the combretastatin A-4 (1a) 3'-phenol group were prepared for evaluation as possible water-soluble prodrugs. As observed for combretastatin A-4, the sodium salt (1b), potassium salt (1c) and hemisuccinic acid ester (1e) derivatives of phenol 1a were essentially insoluble in water. Indeed, these substances regenerated combretastatin A-4 upon reaction with water. A series of other simple derivatives (1d, 1f-j) proved unsatisfactory in terms of water solubility or stability, or both. The most soluble derivatives evaluated included the ammonium (1l), potassium (1m) and sodium (1n) phosphate salts, where the latter two proved most stable and suitable. Both the potassium (1m) and sodium (1n) phosphate derivatives of combretastatin A-4 were also found to exhibit the requisite biological properties necessary for a useful prodrug. Sodium salt 1n was selected for drug formulation and further pre-clinical development.

Animals↗
PubMed1994

Primary oculomotor nerve synkinesis caused by an extracavernous intradural aneurysm.

Primary oculomotor nerve synkinesis is almost always caused by an intracavernous meningioma or aneurysm. We treated a patient who had signs of primary oculomotor nerve synkinesis from an unruptured extracavernous aneurysm located at the junction of the internal carotid artery and the posterior communicating artery. The aneurysm was successfully clipped, resulting in some improvement in ocular motility and alignment. Although most aneurysms affecting the subarachnoid portion of the oculomotor nerve cause an acute, painful oculomotor nerve paresis, such aneurysms may rarely produce painless primary oculomotor synkinesis and therefore should be considered in the differential diagnosis of this phenomenon.

Carotid Artery Diseases↗
PubMed1994

Global and regional detection of induced optic disc change by digitized image analysis.

OBJECTIVE: To evaluate two new strategies for the detection of optic disc change within individual eyes by digitized image analysis. METHODS: Eleven normal optic discs of 11 monkeys were imaged with a digital imaging system (Topcon Imagenet, Topcon Instrument Corporation of America, Paramus, NJ) at two intraocular pressures (10 and 45 mm Hg). To detect global change in the disc, we compared conventional optic disc parameters with a new optic disc parameter: mean position of the disc. To detect regional change, the 95% confidence interval for change was calculated for each data point and mapped for each disc. RESULTS: Posterior deformation of the disc surface was detected in seven of 11 eyes using conventional parameters and in 10 of 11 eyes using mean position of the disc. Regions of posterior deformation were detected by 95% confidence interval for change mapping in all 11 discs as localized areas of confluent, posteriorly displaced points. CONCLUSIONS: Mean position of the disc outperformed conventional measurements in the detection of global optic disc change. Ninety-five percent confidence interval for change mapping may allow individual data point-based focal and regional analysis of the disc.

Animals↗
PubMed1994

Race-, age-, gender-, and refractive error-related differences in the normal optic disc.

OBJECTIVE: To determine race-, age-, gender-, and refractive error-related differences in the size and topography of the optic disc in healthy Americans. DESIGN: Population-based study. SETTING: Eastern and southeastern health districts of Baltimore, Md. PARTICIPANTS: A population-based sample of 4877 non-institutionalized black and white individuals aged 40 years or older without evidence of optic nerve disease. MAIN OUTCOME MEASURE: Race-, age-, gender-, and refractive error-related differences in optic disc measurements: disc area, neural rim area, cup area, cup-to-disc ratio, and neural rim area-to-disc area ratio. RESULTS: We analyzed simultaneous stereoscopic optic disc photographs from 3387 (1534 black and 1853 white) of the 4877 healthy individuals using an image analyzer (Topcon Image Analyzer, Topcon Instrument Corporation, Paramus, NJ). A total of 1490 individuals were excluded owing to the absence of good-quality images from either eye. The image analyzer defined the cup margin 150 microns below the surface of the disc margin. On average, blacks had significantly larger disc areas (blacks, 2.94 mm2; whites, 2.63 mm2), larger cup areas (blacks, 1.04 mm2; whites, 0.71 mm2), larger cup-to-disc ratios (blacks, 0.56; whites, 0.49), similar neural rim areas (blacks, 1.90 mm2; whites, 1.92 mm2), and smaller neural rim area-to-disc area ratios (blacks, 0.66; whites, 0.74) compared with whites. There were no age-related differences in any of the disc measurements. Male subjects had 2% to 3% larger optic discs compared with female subjects. No association between refractive error and any of the optic disc measurements studied was detected. CONCLUSIONS: Racial differences in the normal optic disc are present among urban Americans, and these differences must be considered in evaluation of the optic disc for glaucoma and other optic neuropathies. Among the individuals in our study, all of whom were 40 years of age or older, no progressive age-related decline in neural rim area was detectable. Neither gender nor refractive error were associated with any significant differences in the size and topography of the normal optic disc.

Adult↗
PubMed1994

Agreement among optometrists, ophthalmologists, and residents in evaluating the optic disc for glaucoma.

PURPOSE: To determine the agreement among optometrists, ophthalmologists, and ophthalmology residents in assessing glaucomatous optic nerve damage. The authors also determined the sensitivity of each group of observers for identifying glaucomatous optic nerve damage. METHODS: Six optometrists, six general ophthalmologists, and six third-year ophthalmology residents evaluated 75 stereoscopic optic disc photographs. Observers estimated the vertical cup:disc ratio (C:D) and assessed the presence of glaucomatous damage. Agreement among and within observers was estimated by the kappa statistic (KW, k). The sensitivity and specificity for the identification of glaucomatous optic nerve damage were determined for each group of participants. RESULTS: Intraobserver agreement (KW 0.69-0.79) was greater than interobserver agreement (KW 0.56-0.68) in assessing the C:D ratio and glaucomatous optic nerve damage for optometrists, ophthalmologists, and residents. Interobserver agreement for ophthalmologists (KW 0.68) was substantial and significantly higher than for optometrists (KW 0.56) and residents (KW 0.56) when estimating the C:D ratio. Ophthalmologists and residents had higher sensitivity (78%) in identifying glaucomatous optic nerve damage than did optometrists (56%). The specificity for all three groups was relatively poor (range, 47%-60%). CONCLUSION: The moderate interobserver agreement across all three groups of observers suggests the need to develop standardized criteria for assessing glaucomatous optic disc damage. Ophthalmologists in this study have a higher interobserver agreement in estimating the C:D ratio and are more sensitive than optometrists in assessing glaucomatous optic nerve damage.

Adult↗
PubMed1994

Radiation tolerance of the transplanted liver. A histopathologic study in three cases.

Three patients with multifocal recurrence of hepatocellular carcinoma following liver transplantation received palliative irradiation. Hyperfractionated irradiation (150 cGy/fraction b.i.d.) was delivered in two cases to the entire liver using parallel opposed oblique portals to a total dose of 30 Gy. Conventional irradiation (180 cGy/fraction) totaling 45 Gy was administered to the liver hilus with concomitant infusional 5-fluorouracil chemotherapy in the third case. Clinicopathologic correlations were performed. At autopsy all patients had massive tumor burden within the liver. Veno-occlusive changes were observed in two patients 1 and 2 months following completion of conventional and hyperfractionated irradiation, respectively. Liver transplantation in these two patients had been performed 18 and 16 months prior to palliative hepatic irradiation. In the third patient, no veno-occlusive changes were pathologically observed at autopsy 1 month after completing hyperfractionated radiation, which was delivered 6 months following liver transplantation. No significant differences in prior immunosuppressive therapy were identified among patients. Veno-occlusive changes are not spared by hyperfractionated radiation. Transplanted livers exhibit responses to radiation similar to those normally observed.

Adult↗
PubMed1994

Intervention debulking surgery in advanced epithelial ovarian cancer.

OBJECTIVE: To study whether intervention debulking surgery improves survival in patients with advanced ovarian cancer who have bulky (> 2 cm) residual disease after primary surgery. DESIGN: A prospective multicentre randomised study. SETTING: Hospitals in the West Midlands. SUBJECTS: Ovarian cancer patients with bulky residual disease after primary surgery who are considered well enough to receive cis-platinum based chemotherapy and further surgery. METHODS: Eligible patients were randomised to receive combination chemotherapy alone or combined with intervention debulking surgery. MAIN OUTCOME MEASURE: Survival was assessed using product limit method and log-rank test. RESULTS: Seventy-nine patients were entered into the study. Thirty-seven patients were randomised to intervention debulking surgery, 25 (67%) of whom underwent intervention debulking surgery, which was performed a median of 13 weeks after primary surgery. The median survival for the intervention debulking surgery group was 15 months (95% CI 10-20 mo) and that of those randomised to chemotherapy alone, which was 12 months (95% CI 8-16 mo), were not significantly different (hazard ratio = 0.71; 95% CI 0.44-1.13). CONCLUSION: Intervention debulking surgery may not improve survival in patients with advanced ovarian cancer.

Adult↗
PubMed1994

Assessment of blood substitutes: I. Efficacy studies in anesthetized and conscious rats with loss of 1/3, 1/2 and 2/3 blood volume.

Acute and long-term recovery (14 days) studies were conducted in conscious rats bled 1/3, 1/2, and 2/3 blood volume, and in anesthetized rats bled 1/3 volume. Study I: bled 1/3 blood volume. Study Ia: Anesthetized rats bled 1/3 blood volume were in shock and most died within 1 hour; the group which received infusion of 3x volume Ringer's lactate regained blood pressure with 100% long-term recovery. Study Ib: In conscious rats bled 1/3 blood volume, blood pressure did not fall to shock levels, and the long-term recovery in both the control group and the group which received 3x volume Ringer's lactate was 100%. Study II: Bled 1/2 blood volume. In conscious rats bled 1/2 volume, the blood pressure of the control group was slightly above 70 mmHg. Infusion of 3x volume Ringer's lactate or 7 gm% human albumin in Ringer's lactate increased blood pressure to above 90 mmHg in the acute study. Long-term recovery and survival rate was 80% in both the controls and the Ringer's lactate group, and 100% in the albumin group. Study III: bled 2/3 blood volume. In conscious animals, loss of 2/3 blood volume resulted in fall of blood pressure to shock levels and death of the animal within 1 hour. Infusion of 3x volume Ringer's lactate did not increase blood pressure to above shock level. Stroma-free hemoglobin and polyhemoglobin increased blood pressure, and whole blood returned blood pressure to normal. In long-term recovery, poly-hemoglobin, but not SFHb, was as effective as whole blood with 100% long term recovery. Animal models in Study I and II are suitable only for studies of volume replacement. Animal models in Study III, especially using long-term recovery studies, are more suitable for studying both volume and red blood cells replacements.

Anesthesia, General↗
PubMed1993

Raf-1 is required for T cell IL2 production.

Engagement of the T cell receptor/CD3 complex activates the serine/threonine kinase, Raf-1, but the physiologic consequences of its activation have not been determined. The effects of Raf-1 on interleukin 2 (IL2) production in T cells were examined using activated and inhibitory forms of Raf-1. A truncated active form of Raf-1 was expressed constitutively from the metallothionein promoter in a malignant T cell line, Jurkat. Treatment of the cells with zinc and cadmium greatly increased active Raf-1 expression. This increase in Raf-1 expression allowed antibodies to CD3 and to CD28 to stimulate IL2 production in the absence of phorbol myristate acetate (PMA) and enhanced IL2 production stimulated by these antibodies in the presence of PMA. The action of active Raf-1 was to increase IL2 gene transcription as it enhanced transcription of a reporter gene linked to IL2 promoter. Finally, the dominant negative form of Raf-1 inhibited transcription directed by the IL2 promoter that was induced by the mitogen phytohemagglutinin (PHA) and PMA. We conclude that Raf-1 activity is necessary for IL2 gene transcription and secretion. These data indicate a role for Raf-1 in the immune response.

CD28 Antigens↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗