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Biomedical subjects

A Bhandari

Publications and source records attributed to A Bhandari.

At least 19 recordsLinked to original sources

Miglustat has no apparent effect on spermatogenesis in normal men.

BACKGROUND: In mice, administration of the glycosphingolipid biosynthesis inhibitor miglustat results in reversible infertility, characterized by impaired sperm motility and markedly abnormal sperm morphology. This observation suggested that miglustat might have utility for fertility control in man. To ascertain the impact of miglustat on human spermatogenesis, we conducted a pilot study of miglustat administration in normal men. METHODS: After a 2-week baseline period, seven normal men were administered miglustat 100 mg, orally, twice daily for 6 weeks. During treatment, subjects had frequent seminal fluid analyses to assess the impact of treatment on sperm concentration, motility and morphology and the ability to undergo the acrosome reaction by in vitro assays. RESULTS: Five subjects completed all aspects of the study. In these subjects, there was no apparent effect of miglustat on sperm concentration, motility or sperm morphology after 6 weeks of therapy. In addition, no changes in acrosome structure or function were observed with treatment, despite therapeutic concentrations of miglustat in the serum and seminal plasma. All subjects experienced gastrointestinal upset, diarrhoea and mild weight loss during treatment. No other abnormalities in blood counts, serum chemistries, vision or overall health were observed. CONCLUSION: In contrast to the observations in mice, the oral administration of miglustat does not appear to affect human spermatogenesis. Further elucidation of the mechanism underlying the species specificity of miglustat may improve our understanding of the role of glycosphingolipids in spermatogenesis and result in alternative approaches to male fertility control.

1-Deoxynojirimycin↗

The technique of apical dissection of the prostate and urethrovesical anastomosis in robotic radical prostatectomy.

OBJECTIVE: To describe the technique of dissecting the apex of the prostate and a modified single running-suture urethrovesical anastomosis in patients undergoing robot-assisted radical prostatectomy for organ-confined prostate cancer. PATIENTS AND METHODS: Over 550 robot-assisted radical prostatectomies have been undertaken using Vattikuti Institute Prostatectomy (VIP) technique in patients with localized carcinoma of the prostate. We present a critical analysis of the first 120 procedures by one surgeon (M.M.) at our institution using this newly developed technique of urethrovesical anastomosis preceded by dissecting the apex of the prostate. RESULTS: The mean time for the urethrovesical anastomosis was 13 min. All but 24 patients had their catheter removed 4 days after surgery, as indicated by a cystogram. The catheter was removed successfully at 7 days in the remaining 24 patients who had a mild leak on cystography. Two patients had urinary retention within a week of removing the catheter and had to be re-catheterized. Continence was evaluated using standardized criteria before and after the procedure. The patients also replied to a mailed validated questionnaire survey; 96% were continent at 3 months and the remaining 4% used a thin pad for security. CONCLUSIONS: We report a technique of dissecting the apex of the prostate and prostatovesical junction for dividing the bladder neck, and a modified single running-suture urethrovesical anastomosis, in patients undergoing robot-assisted radical prostatectomy for organ-confined cancer of the prostate. The same principles can also be applied for the anastomosis during pure laparoscopic procedures and for urethro-neovesical anastomosis in patients undergoing robotic radical cystoprostatectomy for carcinoma of the bladder.

Anastomosis, Surgical↗

Impact of peroxidase addition on the sorption-desorption behavior of phenolic contaminants in surface soils.

The impact of peroxidase addition on sorption-desorption of phenol, o-cresol, 2,4-dichlorophenol (DCP), and 1-naphthol was evaluated using two surface soils. Target chemicals were added to soils as single solutes or binary mixtures. Seven-day adsorption studies were followed by sequential fill-and-draw extractions with synthetic groundwater. Addition of horseradish peroxidase (HRP) with H2O2 was the primary treatment evaluated. HRP-mediated sorption enhancementwas related to contaminant solubility and increased in the order: naphthol < DCP < cresol < phenol. Little or no competition was observed in the presence of cosolutes. Contaminant desorption from soils was dramatically reduced upon HRP addition. Reduction in desorption was quantified using the Hysteresis Index and interpreted as attenuation of contaminant mobility. Desorption data predicted that mobility reductions followed the order: naphthol < DCP < cresol < phenol. It is believed that enzyme addition resulted in the production of hydrophobic polymers that, due to their low aqueous solubilities, readily partitioned on to the solid-phase. The adsorbed polymers were less likely to partition into the aqueous phase than the parent phenols resulting in a reduced risk to the environment.

Absorption↗

Evidence for stunned myocardium in humans: a 2001 update.

This article describes clinical situations in which stunning occurs and updates previous reviews on the topic. Stunning following angioplasty, angina and exercise-induced ischemia, infarction, and after cardiac surgery are described. In addition, newer concepts regarding stunning, including neurogenic stunned myocardium, are discussed. Left atrial stunning following cardioversion is a recently recognized phenomenon with important clinical implications, but differs from the original concept of post-ischemic stunning.

Angina, Unstable↗

Fellow eye prognosis in patients with severe visual field loss in 1 eye from chronic open-angle glaucoma.

OBJECTIVES: To examine the prognosis for the fellow eye of patients with severe visual field loss in 1 eye from chronic forms of open-angle glaucoma, and to identify risk factors for visual field progression in such eyes. METHODS: Review of 36 patients followed in an academic medical center with monocular severe visual field loss (Advanced Glaucoma Intervention Study score > or =12) from open-angle glaucoma either at initial Humphrey visual field testing or during follow-up. Change in Advanced Glaucoma Intervention Study visual field score and clinical evaluation were used to determine visual field progression. Kaplan-Meier survival analysis and Cox proportional hazards survival regression were used to estimate visual field progression in fellow eyes and assess possible risk factors. RESULTS: During 67+/-32 months (mean +/- SD), 12 of 36 first-affected eyes (33%) and 6 fellow eyes (17%) had significant visual field progression. The Kaplan-Meier estimate of visual field progression in the fellow eye was 12.4% at 5 years after severe visual field loss in the first eye. Compared with stable fellow eyes, fellow eyes with visual field progression had significantly larger initial cupdisc ratio, smaller between-eyes difference in the initial Advanced Glaucoma Intervention Study score, and lower calculated ocular perfusion pressure. Ocular perfusion pressure was the only variable significantly associated with visual field progression by Cox proportional hazards survival regression (P = .019). During an average of 10.2 years of disease, 2 patients (6%) became bilaterally blind from glaucoma. CONCLUSIONS: In this predominantly white population, fellow eyes of patients with severe visual field loss in 1 eye from open-angle glaucoma were not at particularly high risk for further visual field progression, and few patients became bilaterally blind. Fellow eye visual field progression was associated with lower calculated ocular perfusion pressure.

Adult↗

Effect of respiratory muscle training on GLUT-4 in the sheep diaphragm.

PURPOSE: Endurance exercise training is associated with enhanced glucose uptake and hence improvement in carbohydrate metabolism. Glucose transport (GLUT) membrane proteins are regulated by a variety of physiological stimuli, including exercise. In limb muscle, both acute exercise and endurance training enhance the expression of the skeletal muscle transporter, GLUT-4. The purpose of this study is to determine whether chronic loading enhances GLUT-4 expression in the diaphragm. METHODS: The effect of chronic inspiratory flow resistive (IFR) loading on diaphragm GLUT-4 was studied in a model of respiratory muscle endurance training in sheep. IFR loads (resistance 50-100 cm H2O x L(-1) x s(-1)) were maintained for 3 h x d(-1), 5-6 d x wk(-1) for 3 wk. Loading was adjusted so that PaO2 was >60 Torr and PaCO2 <45 Torr in room air. Six untrained sheep were used as controls. GLUT-4 protein and mRNA were analyzed by Western and Northern analysis respectively. RESULTS: GLUT-4 protein levels were two-fold greater in trained animals when compared with controls (P < 0.01). GLUT-4 mRNA levels in the trained muscles was not significantly different from controls. CONCLUSIONS: We conclude that in the sheep diaphragm, chronic IFR loading increases GLUT-4 protein levels. This increase may be one of the mechanisms contributing to the improved respiratory muscle endurance previously demonstrated in this animal model of respiratory muscle training.

Animals↗

Effects of contact lenses on scanning laser polarimetry of the peripapillary retinal nerve fiber layer.

PURPOSE: To determine the effects of contact lenses on scanning laser polarimetry of the peripapillary nerve fiber layer. METHODS: In a prospective study using the Nerve Fiber Analyzer (Laser Diagnostic Technologies, San Diego, California), retinal nerve fiber layer thickness in 22 subjects (51 eyes) was imaged with and without contact lenses (disposable and nondisposable daily wear soft and rigid gas permeable). Measurements of the circumference and of each quadrant were compared using paired Student t test. RESULTS: Nerve Fiber Analyzer measurements with and without contact lenses were not significantly different for any of the contact lens types tested (P > or = .11), using either hyperopic (to +4 diopters) or myopic (to -8.5 diopters) lenses. CONCLUSION: Contact lens wear and refractive power of the eye within the range tested do not significantly affect scanning laser polarimetry of the peripapillary nerve fiber layer.

Adult↗

Effect of brimonidine on optic nerve blood flow in rabbits.

PURPOSE: Brimonidine is a highly selective alpha2-adrenoreceptor agonist that lowers intraocular pressure. The aim of the present study was to analyze in vivo the vasomotor effects and the influence of brimonidine on blood flow within the optic nerve, by means of intraluminal microvascular corrosion casting technique and intravascular injection of colored microspheres. METHODS: New Zealand white rabbits received either brimonidine tartrate 0.2% or placebo (vehicle) topical drops in one eye for 4 weeks. Intraocular pressures were measured at baseline and 4 weeks. The anterior optic nerve microvasculature of four rabbits was examined with corrosion castings for regions of focal vasoconstriction. Optic nerve blood flow was determined in 16 rabbits by means of nonradioactive colored microspheres. RESULTS: The vasoconstriction values of the short posterior ciliary arterial branches in the brimonidine eyes were 16.7%+/-3.7%. In the fellow untreated eyes, the mean vasoconstriction was 16.6%+/-2.4%. In the placebo-treated eyes, the average constriction was 15.9%+/-3.2%; the fellow eyes showed a mean constriction value of 16.1%+/-5.3%. There was no statistical difference between any of the groups (P = .2). The optic nerve blood flow in the brimonidine-treated rabbits was 0.18+/-0.06 ml/mg/min and 0.17+/-0.04 ml/mg/min in the treated and the fellow eyes, respectively. The difference between the optic nerve blood flow in the brimonidine-treated eyes and the optic nerve blood flow in all of the untreated eyes (0.19+/-0.06 ml/mg/min) also was not statistically different (P = .82). CONCLUSIONS: Long-term application of brimonidine 0.2% does not affect the blood flow or vasomotor activity of the anterior optic nerve.

Adrenergic alpha-Agonists↗

The effects of compression sutures on filtering blebs in rabbit eyes.

PURPOSE: To investigate the effect of compression sutures on filtering bleb cellularity in rabbit eyes. METHODS: Six New Zealand rabbits had bilateral filtering surgery. In the study eye, on postoperative day 14 a 10-0 nylon suture was placed that compressed the bleb. Five-bromo-2'-deoxyuridine (BrdU) was injected intravenously on days 15, 16, and 18. On day 21 histologic sections of the blebs were obtained. The total cell count was compared to the number of actively dividing cells (marked by anti-BrdU antibody). RESULTS: Study eyes had higher total cell counts (P = .004) on postoperative day 21, but the proportion of proliferating cells was not significantly different (P = .11). CONCLUSION: In rabbit eyes, bleb compression sutures were associated with more cellular components in the bleb compared to control eyes, but did not induce a higher level of cellular proliferation.

Animals↗

Exploring structure-activity relationships around the phosphomannose isomerase inhibitor AF14049 via combinatorial synthesis.

Phosphomannose Isomerase (PMI) has been shown by genetic methods to be an essential enzyme in fungal cell wall biosynthesis. The PMI inhibitor AF14049 was discovered as an unanticipated side product from high-throughput library screening against the enzyme from C, albicans. Solid-phase synthetic methods were developed and a series of libraries and discrete analogs synthesized to explore SAR around AF14049.

Amides↗

In vivo morphometry of the lamina cribrosa and its relation to visual field loss in glaucoma.

PURPOSE: The lamina cribrosa has been proposed as a site of origin of the optic nerve damage in glaucoma. The purpose of this study was to investigate, in vivo, the clinical features of the lamina cribrosa pores of glaucomatous patients and to relate their morphometric characteristics to the extent of their visual field loss. METHODS: Images of the internal lamina cribrosa surface of 60 glaucomatous patients and 15 normal subjects were acquired, in vivo, using a scanning laser ophthalmoscope (SLO). A purposely developed technique of image processing was employed to objectively evaluate pore morphometry, with particular regard to their geometrical characteristics (circularity and elongation). Visual function was assessed by automated perimetry (Humphrey Field Analyser). RESULTS: Normal subjects showed approximately round lamina pores. In glaucomatous patients, pores become more elongated and less circular with increasing field loss (p = 0.009 and p < 0.001, respectively). CONCLUSIONS: Scanning laser ophthalmoscopy and a new technique of image processing were employed, for the first time, to the investigation in vivo of the lamina cribrosa of glaucomatous patients, in relation to the extent of visual field loss. The results indicated differences in the lamina cribrosa pore morphometry associated with increasing severity of the disease. These changes may represent the result of compressing and shearing forces applied to the laminar plates.

Adult↗

Respiratory rates of Indian infants under 2 months of age.

There are few data from developing countries, including India, on the normal range of the respiratory rate (RR) recorded by observation. To determine the normal range of RR in infants up to 8 weeks of age and to define tachypnoea, we studied 100 healthy infants, 50 of normal birthweight and 50 of low birthweight) at 1, 2, 4, 6 and 8 weeks of age. The RR was recorded by observation and auscultation simultaneously for 60 seconds on each visit when the baby was either asleep or awake and content. The median RRs ranged between 42 and 43 breaths/min in infants of normal birthweight and 40 and 44 breaths/min. in low birthweight infants. Inter-age variability up to 8 weeks of age was very slight and statistically insignificant. Only 2-10% of the infants at any given age had a RR > or = 60/min. At all ages, RR by observation was higher than that by auscultation (p < 0.001). Neither birthweight nor gender significantly influenced the RR. When awake, infants had significantly higher RRs than when asleep. The RR extrapolated from a 15-second breath count was significantly lower (p < 0.05-0.01), whereas results from 30-second counts were similar to 60-second counts. Our data endorse the use of a RR > or = 60 breaths/min. counted for 1 minute as a cut-off to define tachypnoea in infants < 2 months of age.

Auscultation↗

Effect of surgery on visual field progression in normal-tension glaucoma.

PURPOSE: The effect of intraocular pressure-lowering surgery on the rate of visual field progression in normal-tension glaucoma (NTG) was studied. METHODS: Seventeen patients with NTG who underwent trabeculectomy in one eye for worsening visual field loss were included in the first part of the study. All patients had Humphrey 24-2 visual fields at the rate of 2-3 fields per year. Pointwise linear regression analysis of the visual field data was done separately for the preoperative and postoperative periods. This was performed for both operated and fellow eyes. The mean slope (MS), which indicates rate of visual field progression, was calculated. Change in MS was correlated with change in intraocular pressure (IOP). For the second part of the study, 11 patients who had a minimum of 4 visual fields and 18 months of follow-up before surgery were identified. Using the preoperative fields, the rate of sensitivity loss for each visual field location in the operated eye was ascertained for every patient. This rate of loss was extrapolated to generate the expected visual fields, assuming an unchanged rate of progression. The mean sensitivity of the expected visual field was compared with that of the actual field at the last follow-up. RESULTS: The MS in the operated eyes improved from -2.97 +/- 3.21 (mean +/- SD) in the preoperative period to 0.53 +/- 3.83 (P < 0.005; Student's t test) postoperatively. In the fellow eyes the MS changed from -1.78 +/- 2.55 to -1.43 +/- 3.01 (P = 0.754). There was a weak correlation between change in MS and percentage IOP decrease (correlation coefficient 0.39). The difference in mean sensitivity between the expected and actual visual fields was -3.72 dB (P = 0.002), and was better in the actual field. CONCLUSIONS: In this study, surgical lowering of IOP resulted in a slower rate of visual field loss in the operated eye.

Aged↗

Quantitative analysis of the lamina cribrosa in vivo using a scanning laser opthalmoscope.

PURPOSE: Structural changes in the lamina cribrosa have been implicated in the pathogenesis of glaucomatous optic nerve atrophy. The purpose of this study was to develop a method for morphometric analysis of the lamina cribrosa pores in vivo, using a scanning laser ophthalmoscope. METHODS: A prototype Zeiss confocal laser scanning ophthalmoscope was used to acquire images of the lamina cribrosa. The images were digitised and aligned to compensate for eye movements. Thirty-two consecutive images were averaged to reduce noise. The images were processed to adjust for luminance gradients prior to segmentation and analysis. Details of the image processing are described. RESULTS: The end result of processing the images was a binary (black and white) image that can be used for automated computer assisted measurements. The pores of the lamina cribrosa are well represented and retain their overall shape in the binary image, as judged by superimposing the binary image on the unprocessed image. We also established the repeatability, reproducibility and intercession variability of this technique. Repeated images of the internal lamina cribrosa of 10 patients were acquired by two observers in two separate visits, and the images were processed before automated computer measurements. The parameters evaluated were number of pores, area covered by the pores and area covered by the visible lamina cribrosa. The coefficient of variation for number of pores, pore area and lamina area was 6.9%, 2.1% and 4.3% for observer A and 5.5%, 2.1% and 5.8% for observer B. Pearson product moment correlation coefficient between the two observers was 0.94, 0.99 and 0.97 for the above parameters respectively. There was no significant difference between the measurements on visit 1 and 2 for both observers. CONCLUSIONS: The technique described allows, for the first time, in vivo morphometry of the internal lamina cribrosa surface. This method has good reproducibility, suggesting future clinical applications.

Aged↗

A multicenter, randomized trial comparing an active can implantable defibrillator with a passive can system. Jewel Active Can Investigators.

Replacing one defibrillation electrode lead by the defibrillator can may simplify implantation of the ICD. In this multicenter study, 304 patients were randomized to receive either the biphasic active can (AC) (model 7219C system, Medtronic, Inc.) or the passive can (PC) (model 7219D system). The AC and PC systems were compared with respect to their ability to meet the implant defibrillation criterion and to defibrillate VF, and to DFTs, implant time, patient adverse events, and survival rates. A higher percentage fulfilled the implant defibrillation criterion on the first configuration with the AC (86.3% vs 75.9% for PC; P = 0.023), and the first shock success for terminating induced VF was 94% for AC compared to 89% for PC (P = 0.026). DFTs were significantly lower (10.9 vs 12.7 J; P = 0.031), and implant time was significantly shorter for the AC patients (99.2 vs 112.0 min; P = 0.002). The two groups showed no significant differences in 3-month adverse event rates, 3-month survival, and hospital stay.

Adolescent↗

Measurement of optic nerve blood flow with nonradioactive colored microspheres in rabbits.

The objective of this study was to establish a nonradioactive technique to accurately assess blood flow in a small tissue such as the anterior optic nerve. Colored microspheres, 10.2 +/- 0.23 microns in diameter, were injected into the left atrium in each of 17 anesthetized rabbits. The rabbits were divided into four groups injected, respectively, with 5, 10, 50, or 100 million microspheres. Microsphere quantification in the tissue was performed after postmortem dissection and alkaline corrosion of the anterior optic nerve. Blood flow was evaluated by means of reference sample comparison method. While the relative interocular difference (range, 15.3-162.8%) was not significantly different between the rabbits injected with 5, 10, or 50 million microspheres (Kruskal-Wallis test, P = 0.11), injection with 100 million microspheres yielded a significantly lower relative interocular differences (range 2.3-12.8%) compared to the other three groups (Kruskal-Wallis test, P = 0.0048). In addition, reproducibility of microsphere counts was evaluated by ranking the difference between right and left optic nerve in percentage of the average number of microspheres per milligram of tissue in both optic nerves. The correlation between the relative interocular difference (range, 2.3-162.8%) and the average number of microspheres per milligram of tissue (1.2-78.7 microspheres/mg optic nerve tissue) was statistically significant (Spearman R, -0.90; P < 0.0001). The interocular variability in microsphere counts and interocular difference in intraocular pressure did not correlate (Spearman R, 0.33; P = 0.20). The rabbits injected with 100 million microspheres showed the highest average number of microspheres (range, 31.8-78.7 microspheres/mg optic nerve tissue). The optic nerve blood flow ranged between 0.14 and 0.24 microliters/mg/min among the rabbits injected with 100 million microspheres. The present experimental technique of optic nerve blood flow measurement is relatively inexpensive, highly reproducible, and obviates disposal of radioactive materials.

Animals↗

Choroidal hypoperfusion in acute posterior multifocal placoid pigment epitheliopathy. An indocyanine green angiography study.

BACKGROUND: The pathogenesis of acute posterior multifocal placoid pigment epitheliopathy remains obscure. The placoid lesions and characteristic findings on fluorescein angiography have been interpreted as representing either primary disease of the retinal pigment epithelium or disease of the choroidal vasculature. This study used indocyanine green (ICG) choroidal videoangiography to investigate this controversy. METHODS: Sequential choroidal videoangiography was performed with ICG and a scanning laser ophthalmoscope on patients with acute posterior multifocal placoid pigment epitheliopathy. Image analysis was used to differentiate between masking and ischemia as to the cause of hypofluorescence on the angiograms. RESULTS: Indocyanine green angiograms of acute posterior multifocal placoid pigment epitheliopathy showed areas of hypofluorescence in both the early and late pictures that correlated with the placoid lesions. Image analysis identified these as areas of choroidal hypoperfusion. Successive films showed partial or complete resolution of these hypofluorescent areas. CONCLUSIONS: Indocyanine green choroidal videoangiography has shown choroidal hypoperfusion to underlie the pathogenesis of acute posterior multifocal placoid pigment epitheliopathy.

Acute Disease↗