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Biomedical subjects

S Verma

Publications and source records attributed to S Verma.

At least 289 records · Page 16Linked to original sources
PubMedDate not supplied

Nonsteroidal anti-inflammatory drugs and bone metabolism in spinal fusion surgery: a pharmacological quandary.

The use of nonsteroidal anti-inflammatory drugs (NSAIDs) is ubiquitous in contemporary medical practice and these agents are efficacious in a number of clinical contexts. In particular, NSAIDs have proven to be highly effective adjuncts in the amelioration of postoperative pain in the subset of patients undergoing spinal surgery requiring fusion. NSAIDs act through inhibition of cyclooxygenase enzymes and therefore diminish prostaglandin production. However, prostaglandins are intimately involved in the modulation of bone metabolism and the balance of data, from both clinical and laboratory contexts, indicate that prostaglandins preferentially favor bone anabolism. Most recently, limited emerging evidence suggests that NSAID administration in patients undergoing spinal fusion surgery may increase nonunion rates, which in turn, has important ramifications to the patient, their family and the entire medical system. Hence, disparate views have evolved regarding the use of NSAIDs in postoperative pain control in patients undergoing spinal surgery requiring fusion. NSAIDs have proven efficacy in the management of postoperative pain in these patients, however, this must be weighed against the risk of nonunion and its associated consequences. In this review, the role of prostaglandins in bone metabolism, the pharmacology of NSAIDs and the modulation of bone metabolism by NSAIDs are discussed. Additionally, the current evidence examining the use of NSAIDs in spinal surgery is presented. As rates of spinal surgery continue to rise, it is imperative that the apparent pharmacological quandary surrounding the administration of NSAIDs in patients undergoing spinal surgery requiring fusion be addressed, both to guide present clinical practice and to outline further directions for investigation.

Animals↗
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Kinetic evaluation of a metalated diglycine conjugate as a functional mimetic of phosphate ester hydrolase.

The crucial role of phosphate ester hydrolysis in various biological processes has spurred vigorous research activities to understand mechanisms of phosphate ester hydrolysis and to develop model systems that assist the above-mentioned reaction in a catalytic fashion. In the present study, we describe a novel, metalated peptide conjugate 4 possessing phosphate ester hydrolyzing activity against a phosphate monoester, diester, and a RNA chemical model. The design of conjugate 4 is inspired by the ATCUN binding tripeptide motif of serum albumin and involves tethering of two diglycine units by a flexible 1,3-diaminopropane linker. Detailed kinetic investigations of phosphate ester hydrolysis using model substrates and efforts to decipher underlying mechanisms are presented.

Amino Acid Motifs↗
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Interactions of cytosine derivatives with T.A interruptions in pyrimidine.purine.pyrimidine DNA triplexes.

The ability of triplex-forming oligopyrimidines to interact with duplex targets which contain a single pyr.pur interruption in their homopurine triplex binding site was studied. These oligonucleotides contain either N4-(3-carboxypropyl)deoxycytidine (3) or N4-(5-carboxytriazolyl)deoxycytidine (4) to target the pyr.pur interruption. The 3-carboxypropyl and the 5-carboxytriazolyl groups of these cytosine derivatives are designed to span the major groove of the duplex target. Molecular models suggest that the carboxyl group of 3 or 4 can serve as a hydrogen bond acceptor for the N6-amino hydrogen of A in a T.A base pair. Additional contacts are possible between the N4-amino hydrogen of 3 or 4 and the O4-carbonyl oxygen of T. UV melting experiments showed that a 15-mer, I(3), containing nucleoside 3 formed a stable triplex with duplex targets containing a single T.A interruption. The melting temperature of this triplex was 7 degrees C higher than that of a similar triplex containing a single G.T.A triad when a Tris buffer was employed. Oligomer I(3) also formed a triplex of lower stability with a target containing a G.C base pair but not with targets containing C.G, U.A, or A.T base pairs. A similar 15-mer, II, containing nucleoside 4 was found to be less selective than I(3) in its interaction with duplex targets. Thus, gel mobility shift experiments showed that in addition to interacting with T.A, oligomer II also formed triplexes with duplex targets containing U.A and C.G interruptions. These studies suggest that nucleoside derivatives which can potentially contact both bases of a pyr.pur interruption might provide a means to extend the range of sequences which can be recognized by triplex-forming oligonucleotides.

Base Sequence↗
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Recognition of trophoblast HLA class I molecules by decidual NK cell receptors--a review.

During placentation the extravillous trophoblast (EVT) cells migrate through the decidua towards the maternal spiral arteries. The walls of the arteries are then destroyed by trophoblast resulting in an increased blood flow to the fetus. These EVT express HLA-G, HLA-E and HLA-C, an unusual combination of two non-classical and one classical MHC class I molecules. The decidua is infiltrated by distinctive uterine natural killer (NK) cells during the time of trophoblast invasion. These cells express a variety of receptors (CD94/NKG2, KIR and ILT) which are known to recognize HLA class I molecules. There is, therefore, a mechanism for molecular recognition of the placental trophoblast cells. The possible functional consequences of this uterine NK cell-trophoblast interactions are uncertain. One possible result is in an altered NK cell cytokine profile which modulates the invasive proclivity of the EVT. In this way placentation could be controlled.

Decidua↗
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Human uterine lymphocytes.

During the luteal phase and the early months of pregnancy, there is a dense mucosal infiltration of CD56+ natural killer (NK) cells. These uterine NK cells have a phenotype (CD56bright, CD16-, mCD3-) which distinguishes them from peripheral blood NK cells (CD56dim, CD16bright, mCD3-). The uterine NK cells are in close association with extravillous trophoblast (EVT) cells which infiltrate into the decidua and maternal spiral arteries. This subpopulation of trophoblast expresses two human leukocyte antigen (HLA) class I molecules, HLA-G and HLA-C. Circulating NK cells express receptors for HLA class I molecules. We have recently found evidence that similar receptors are present on decidual NK cells belonging to both the Killer Inhibitory Receptor (KIR) and CD94 families. The repertoire of NK receptors expressed varies between different women. The findings indicate that decidual NK cells do have receptors for trophoblast HLA class I molecules. Experiments are underway to determine the effects of this interaction on NK cell function.

Antigens, CD↗
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Acute spinal cord injury, part I: pathophysiologic mechanisms.

Spinal cord injury (SCI) is a devastating and common neurologic disorder that has profound influences on modern society from physical, psychosocial, and socioeconomic perspectives. Accordingly, the present decade has been labeled the Decade of the Spine to emphasize the importance of SCI and other spinal disorders. Spinal cord injury may be divided into both primary and secondary mechanisms of injury. The primary injury, in large part, determines a given patient's neurologic grade on admission and thereby is the strongest prognostic indicator. However, secondary mechanisms of injury can exacerbate damage and limit restorative processes, and hence, contribute to overall morbidity and mortality. A burgeoning body of evidence has facilitated our understanding of these secondary mechanisms of injury that are amenable to pharmacological interventions, unlike the primary injury itself. Secondary mechanisms of injury encompass an array of perturbances and include neurogenic shock, vascular insults such as hemorrhage and ischemia-reperfusion, excitotoxicity, calcium-mediated secondary injury and fluid-electrolyte disturbances, immunologic injury, apoptosis, disturbances in mitochondrion function, and other miscellaneous processes. Comprehension of secondary mechanisms of injury serves as a basis for the development and application of targeted pharmacological strategies to confer neuroprotection and restoration while mitigating ongoing neural injury. The first article in this series will comprehensively review the pathophysiology of SCI while emphasizing those mechanisms for which pharmacologic therapy has been developed, and the second article reviews the pharmacologic interventions for SCI.

Acute Disease↗
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Acute spinal cord injury, part II: contemporary pharmacotherapy.

Spinal cord injury (SCI) remains a common and devastating problem of modern society. Through an understanding of underlying pathophysiologic mechanisms involved in the evolution of SCI, treatments aimed at ameliorating neural damage may be developed. The possible pharmacologic treatments for acute spinal cord injury are herein reviewed. Myriad treatment modalities, including corticosteroids, 21-aminosteroids, opioid receptor antagonists, gangliosides, thyrotropin-releasing hormone (TRH) and TRH analogs, antioxidants and free radical scavengers, calcium channel blockers, magnesium replacement therapy, sodium channel blockers, N -methyl-D-aspartate receptor antagonists, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid-kainate receptor antagonists, modulators of arachadonic acid metabolism, neurotrophic growth factors, serotonin antagonists, antibodies against inhibitors of axonal regeneration, potassium channel blockers (4-aminopyridine), paclitaxel, clenbuterol, progesterone, gabexate mesylate, activated protein C, caspase inhibitors, tacrolimus, antibodies against adhesion molecules, and other immunomodulatory therapy have been studied to date. Although most of these agents have shown promise, only one agent, methylprednisolone, has been shown to provide benefit in large clinical trials. Given these data, many individuals consider methylprednisolone to be the standard of care for the treatment of acute SCI. However, this has not been established definitively, and questions pertaining to methodology have emerged regarding the National Acute Spinal Cord Injury Study trials that provided these conclusions. Additionally, the clinical significance (in contrast to statistical significance) of recovery after methylprednisolone treatment is unclear and must be considered in light of the potential adverse effects of such treatment. This first decade of the new millennium, now touted as the Decade of the Spine, will hopefully witness the emergence of universal and efficacious pharmacologic therapy and ultimately a cure for SCI.

Acute Disease↗
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A double-blind clinical comparison of Hexabrix and Renografin-76 for intravenous digital subtraction angiography.

A double-blind comparison of Hexabrix and Renografin-76 for intravenous digital subtraction angiography (IV-DSA) revealed a slightly greater percentage of patients with good or satisfactory examinations who received Hexabrix. There were fewer perturbations of the ECG, less alteration in the diastolic blood pressure, and no serious adverse reactions noted in the Hexabrix group. However, the differences between the groups were not statistically significant. When used for IV-DSA, the lower osmolality associated with Hexabrix offers the theoretic advantages of (1) reduced osmotic load and (2) diminished alteration in central blood volume.

Adult↗
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Fetal brain transplantation in kainic acid lesioned caudate nucleus of adult rats.

This study confirmed that bilateral kainic acid (KA) injection at the caudate produces aphagia and adipsia in rats. The reduction in food and water intake was fatal after a higher dosage of the drug. To test the effect of transplantation on the mortality rate, KA was first injected in the left caudate, in one set of rats. After a gap of three days, fetal striatal tissue was unilaterally transplanted at this lesioned site, along with a second injection of KA in the right caudate. Successful transplantation, as ascertained morphologically, did not significantly alter the mortality rate. The morphometric study revealed that the neurons of the transplant were larger in size, and their numerical density lower than those of the caudate of normal rats. Only very few neurons of the transplant developed functional connectivity with the host, as demonstrated by electrophysiological studies.

Animals↗
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Insulin action in the vasculature: physiology and pathophysiology.

Studies to date have provided convincing evidence that insulin has an important role in the normal functioning of the vasculature from the perspective of the regulated delivery of nutrients to a tissue bed. This is mediated by an effect on the endothelium analogous to other endothelial responses, and insulin resistance is reflected in, and in part due to, impaired vasodilatory actions of insulin. Because insulin normally stimulates the net production of nitric oxide, which is beneficial in both the short term for vasomotion and antithrombosis, and the long term for inhibition of smooth muscle cell growth and migration, vascular insulin resistance also has important implications for vascular pathophysiology. Further, recent evidence suggests that the hyperinsulinemia accompanying insulin resistance may aggravate this situation by augmenting the endothelial production and release of endothelin-1. The investigation of insulin resistance in the vasculature provides not only a unique and physiologically relevant window onto vascular pathology, but also an opportunity for therapeutic targeting in individuals affected by the clinical states of insulin resistance. The present review highlights the importance of insulin sensitivity in the maintenance of endothelial function and explores the relationships between vascular insulin resistance and whole body glucose disposal. In addition, the recent evidence linking insulin to endothelin-1 production is discussed. Improving insulin sensitivity with insulin sensitizers such as rosiglitazone may represent an important advance in our ability to improve vascular dysfunction in diabetes.

Animals↗
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Primary vitrectomy for rhegmatogenous retinal detachment: an analysis of failure.

PURPOSE: To find the cause of failure in primary vitrectomy for rhegmatogenous retinal detachment. METHODS: Retrospective review of 171 consecutive cases of RRD treated by primary pars plana vitrectomy (PPV) from a tertiary referral centre to identify the 25 cases in which surgery had failed. Detachments with giant or macula breaks at initial presentation, with proliferative diabetic retinopathy or with PVR greater than grade B were excluded. RESULTS: The failure rate after the first operation was 14.6% and the commonest cause of failure was missed retinal breaks, accounting for 64.3% of failures. CONCLUSION: Missed retinal breaks are the commonest cause of failure of primary PPV for RRD although proliferative vitreoretinopathy may contribute to surgical failure. This re-emphasises the importance of assiduous peroperative retinal examination.

Adult↗
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A comparative study of the duration and efficacy of tetracaine 1% and bupivacaine 0.75% in controlling pain following photorefractive keratectomy (PRK).

OBJECTIVE: To evaluate if topical bupivacaine 0.75% provides better pain control after excimer laser over topical tetracaine 1% without affecting corneal wound healing, refractive outcome of visual function. DESIGN: A prospective, double-masked trial was conducted in which 38 patients were randomized to receive either tetracaine or bupivacaine every 30 minutes for 24 hours post-operatively. Pain was recorded over a four day period using a Visual Analogue Pain Scale. The rate of epithelial healing was assessed during digitized retro-illumination photography. Visual performance was recorded using best corrected Snellen acuity, objective measurements of haze, halo and glare over a six month period. RESULTS: Tetracaine afforded better pain control (p = 0.05). Full epithelial closure occurred in all patients within 72 hours and no statistically significant difference was recorded in any of the parameters measured. CONCLUSIONS: Contrary to our expectation, the longer acting anaesthetic, bupivacaine, was inferior to tetracaine. Limited and supervised use of topical anaesthetics is recommended in controlling pain following photorefractive keratectomy.

Adult↗
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Effect of estrogen on hypoglycemia-induced neurological impairment in ovariectomized rats.

The risk of hypoglycemia and the resulting functional derangement of the brain are one of the major complications with stringently controlled diabetes mellitus. Ovarian steroid hormones, particularly estradiol, play a modulatory role in the ability of the female brain to utilize glucose. In the present study, the effects of estrogen on hypoglycemia-induced neurological impairment were done in ovariectomized rats. Animals received either vehicle or estradiol benzoate treatment. Hypoglycemia (Blood glucose levels <50 mg/dl) was induced in all the rats by insulin (2 U/kg, IP). Neurological functions were assessed using an 18 point scale at different time intervals of hypoglycemia. Estradiol benzoate (100 microg/kg IP) significantly (p<0.05) deteriorated the neurological functions in ovariectomized rats during hypoglycemia. The present study thus reveals that estradiol benzoate is responsible for further aggravation of neurological impairment induced by insulin hypoglycemia in female rats.

Animals↗
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Quality of life in women with urinary tract infections: is benign disease a misnomer?

BACKGROUND: The objective of this study was to undertake an exploratory evaluation of quality-of-life indicators for women suffering from urinary tract infections. METHODS: The RAND 36-Item Health Survey 1.0 (SF-36) was administered to 47 women with a diagnosed urinary tract infection who were being cared for in the Family Medicine Center, Student Health Services, or Urology Outpatient Clinic. A control population of 71 women was obtained from the female members of an undergraduate geography class, a community basketball league, and a local women's choir. RESULTS: All subsections of the SF-36 quality-of-life indices were significantly decreased in the subject population compared with the control population (lower score indicates lower quality of life): patient general health perception (63.3 vs 78.9, P < .001) physical functioning (76.6 vs 87.6, P = .012), role limitation owing to physical health (53.8 vs 93.0, P < .001) and emotional health (67.4 vs 88.3, P < .001), vitality (43.0 vs 64.9, P < .001), emotional well-being (64.4 vs 80.2, P < .001), pain (58.7 vs 91.5, P < .001), and social functioning (60.4 vs 90.4. P < .001). CONCLUSION: Suffering from an urinary tract infection has a detrimental influence on patient quality of life. The effect of urinary tract infections on women and their perception of quality of life have not been hitherto reported in the medical literature. The significant findings in this study call into question whether acute, non-life-threatening illness should be regarded as benign.

Adolescent↗
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Effects of ablation diameter, depth, and edge contour on the outcome of photorefractive keratectomy.

PURPOSE: To investigate the effects of the ablation diameter, depth, and edge contour on the outcome of excimer laser photorefractive keratectomy (PRK). METHODS: A prospective study was conducted in which 60 patients (60 eyes) were randomly allocated to 5.00-mm, 6.00-mm, or 5.00 to 6.00-mm multizone treatment groups. All eyes underwent a -6.00 diopter (D) correction using a Summit Omnimed excimer laser. RESULTS: In eyes treated with 6.00-mm diameter zones, the initial hyperopic shift was reduced, with significant differences at 1 and 4 weeks (p < 0.01). At 6 and 12 months, the refractive changes were closer to the intended correction with 6.00-mm diameters. The predictability of PRK was improved with 6.00-mm zones, with a significant reduction in variance of the refractive changes, at all stages postoperatively (p < 0.05 to p < 0.001). Objective measurements of haze were significantly less at 1, 3, and 6 months with 6.00-mm ablations (p < 0.05). There were no differences between the 5.00-mm and the 5.00- to 6.00-mm multizone groups. Computerized measurements of "night" halo were significantly smaller in the 6.00-mm treatment group at 1 week and 1 month (p < 0.05). At 12 months, two patients treated with 5.00-mm zones and three with the 5.00- to 6.00-mm multizone complained of severe night vision disturbances. No 6.00-mm eyes were similarly affected. CONCLUSIONS: Treatment with a 6.00-mm spherical ablation diameter produced less initial overcorrection, improved predictability, and was associated with a reduction in postoperative halos and night vision disturbances. Creating a superficial blend zone with a 5.00- to 6.00-mm multizone treatment had no beneficial effect on the outcome.

Adult↗
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Control of pain after photorefractive keratectomy.

BACKGROUND: The inadequate control of pain after photorefractive keratectomy remains an important issue for both patients and clinicians. METHOD: A survey of postoperative pain regimens used in excimer centers worldwide was carried out. A pilot study to assess the temporal basis of pain after photorefractive keratectomy was done by using a visual analog pain score in 30 patients. A comprehensive literature search was undertaken to ascertain the suitability of topical ophthalmic anesthetics in controlling pain after photorefractive keratectomy. RESULTS: Many drugs, both oral and topical, are used worldwide to control pain after photorefractive keratectomy, but no group has shown satisfactory pain control in all patients. The pilot study revealed that the pain was most severe in the first 24 hours after photorefractive keratectomy and declined to low levels thereafter. Topical anesthetics cause corneal complications when used excessively and for prolonged periods. CONCLUSION: Pain after photorefractive keratectomy is most severe in the first 24 hours. Topical anesthetics would only be needed for this short time and would guarantee pain relief in all patients. We do not anticipate any corneal complications if the anesthetics are used for short times and under close medical supervision.

Anesthetics, Local↗
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Corneal optical aberrations induced by photorefractive keratectomy.

BACKGROUND: Photorefractive keratectomy causes marked alteration to anterior corneal topography, and is likely to induce major changes to the optical aberrations of the eye. METHODS: Six diopters (D) of myopia correction was attempted on one eye of 50 patients, randomly allocated to one of three different treatments: 5-mm or 6-mm single ablation zone, or a double ablation (multizone; -5.00 D correction over 4.6 mm and -1.00 D over 6 mm). Topographic data was used to estimate corneal aberration coefficients. These were compared for effect of ablation zone, before and 1 year after photorefractive keratectomy. The coefficients were used to derive modulation transfer functions for the anterior corneal surface. RESULTS: Corneal spherical aberrations and coma-like aberrations both increased significantly following photorefractive keratectomy (p < 0.001). The mean spherical aberration coefficient increased from 0.36 +/- 0.11 before, to 0.91 +/- 0.37 after treatment, while the mean coma-like aberration coefficient changed from 0.28 +/- 0.16 before, to 0.60 +/- 0.31 after treatment. Ablation zone form had a significant effect on spherical aberration (p = 0.030), but not for coma (p = 0.96). The spherical aberration coefficient increased least for the 6-mm ablation (by 0.38 +/- 0.17), compared with the 5-mm ablation (0.69 +/- 0.45) and the multizone (0.62 +/- 0.38). Corneal modulation transfer functions were reduced significantly following the photorefractive procedure. The effect was greatest for large pupil diameters and for spatial frequencies between 2 and 15 cycles per degree. CONCLUSIONS: Corneal modulation transfer function calculations suggest that a significant loss of visual performance should be anticipated following photorefractive keratectomy, the effect being greatest for large pupil diameters. Results for three ablation zones show that induced aberrations are least for the largest (6 mm) ablation zone.

Adult↗