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Biomedical subjects

S Tuli

Publications and source records attributed to S Tuli.

14 recordsLinked to original sources
PubMed2002

High-dose methylprednisolone for acute closed spinal cord injury--only a treatment option.

BACKGROUND: A systematic review of the evidence pertaining to methylprednisolone infusion following acute spinal cord injury was conducted in order to address the persistent confusion about the utility of this treatment. METHODS: A committee of neurosurgical and orthopedic spine specialists, emergency physicians and physiatrists engaged in active clinical practice conducted an electronic database search for articles about acute spinal cord injuries and steroids, from January 1, 1966 to April 2001, that was supplemented by a manual search of reference lists, requests for unpublished additional information, translations of foreign language references and study protocols from the author of a Cochrane systematic review and Pharmacia Inc. The evidence was graded and recommendations were developed by consensus. RESULTS: One hundred and fifty-seven citations that specifically addressed spinal cord injuries and methylprednisolone were retrieved and 64 reviewed. Recommendations were based on one Cochrane systematic review, six Level I clinical studies and seven Level II clinical studies that addressed changes in neurological function and complications following methylprednisolone therapy. CONCLUSIONS: There is insufficient evidence to support the use of high-dose methylprednisolone within eight hours following an acute closed spinal cord injury as a treatment standard or as a guideline for treatment. Methylprednisolone, prescribed as a bolus intravenous infusion of 30 mg per kilogram of body weight over fifteen minutes within eight hours of closed spinal cord injury, followed 45 minutes later by an infusion of 5.4 mg per kilogram of body weight per hour for 23 hours, is only a treatment option for which there is weak clinical evidence (Level I- to II-1). There is insufficient evidence to support extending methylprednisolone infusion beyond 23 hours if chosen as a treatment option.

Acute Disease↗
PubMed2002

p38 MAP kinase regulation of AP-2 binding in TGF-beta1-stimulated chondrogenesis of human trabecular bone-derived cells.

Collagenase-treated, explanted human trabecular-bone chips are an excellent source of osteoblast-like cells. We have recently shown the multiple differentiation potential of these cells; in addition to osteogenesis and adipogenesis, these cells also undergo chondrogenesis when maintained as high-density pellet cultures (250,000 cells/pellet) in a serum-free, chemically defined medium stimulated with TGF-beta1 (10 ng/mL). In this investigation, we have analyzed how transactivating nuclear transcription factors, specifically AP-2 and SP-1, may interact with common cis-acting elements found in the regulatory region of cartilage-specific genes as part of the signal transduction mechanism of TGF-beta1 and p38 during chondrogenesis of human trabecular bone-derived multipotential cells. Both TGF-beta1 stimulation and p38 MAP kinase activation affect the binding of AP-2 as well as SP-1 to oligonucleotides with sequence similarity to the overlapping AP-2/SP-1 sites found in the putative 52-bp immediate upstream regulatory region and the 5'-untranslated region of the human aggrecan gene. Electrophoretic mobility shift assays show that TGF-beta1 treatment of the bone-derived cells inhibits AP-2 DNA binding but enhances the DNA binding ability of SP-1. Additionally, treatment of these TGF-beta1-stimulated cells with p38 MAP kinase inhibitor, SB203580, rescued the AP-2 DNA binding but did not affect SP-1 DNA binding. These findings indicate that AP-2 DNA binding is the target of both TGF-beta1 and p38 MAP kinase signaling pathways and suggest a possible signal transduction cascade whereby TGF-beta1 induction of chondrogenesis involves the activation of p38 MAP kinase and the subsequent inhibition of DNA binding by AP-2, thereby preventing the transcriptional repression of the aggrecan gene.

Bone Development↗
PubMed2001

Long-term survival of allogeneic donor cell-derived corneal epithelium in limbal deficient rabbits.

PURPOSE: To investigate the capability of cultivated allogeneic epithelial stem cells to restore a functional ocular surface in a limbal deficient cornea; to verify the long term survival of epithelial allograft; and to examine the host immune response to heterologous cell transplant in a rabbit model. METHODS: Limbal deficiency was established by performing limbectomy on rabbits (n = 100). Corneal epithelial stem cells were obtained from the limbus and replicated in vitro without a supporting layer. The cell (3 x 10(5)) suspension was then transplanted via topical application as eye drops. Animals were divided into allograft, autograft, and control groups. Females were used as recipients and males as donors for the allograft. Corneas were collected at 7, 14, 21, 40 days as well as 2, 3, 7 and 8 months after cell transplantation. Experimental corneas were evaluated by histology, immunofluorescence, immunohistochemistry and Y chromosome analysis. RESULTS: A well-differentiated corneal epithelium was recognized at 14 to 40 days after cell transfer overlying an infiltrated corneal stroma. Corneal re-epitheliazation was confirmed in 31 of 36 allograft corneas. No significant immune rejection was noted. Stromal abnormality caused by previous limbal deficiency was mostly resolved three months after the regeneration of corneal epithelium. CONCLUSIONS: Transplanted corneal epithelial stem cells were able to differentiate into normal corneal epithelium in vivo without the use of membrane scaffolding. This non-autologous donor cell-derived corneal epithelium survived up to 8 months without immunosuppression and was able to reverse the stromal scarring. Thus, cultivated epithelial stem cells have great potential as an alternative to multiple-surgical procedures in the treatment of limbal deficiency states.

Animals↗
PubMed2000

Molecular characterization of prostate carcinoma tumor antigen-1, PCTA-1, a human galectin-8 related gene.

The galectin family of proteins has been associated with several diverse cellular processes. More than 30 years since the discovery of the first member, precise biological functions for the family as a whole, or for individual members has proven elusive. The isolation of Prostate Carcinoma Tumor Antigen-1 (PCTA-1), a cDNA closely related to rat and human Galectin-8, as a surface marker associated with prostate cancer was achieved using a previously described immunological subtraction approach, Surface Epitope Masking (SEM) approach, in combination with expression screening. It appears that PCTA-1 expression is almost ubiquitous in normal human tissues and could alter in specific contexts such as transformation or metastasis. Multiple expression isoforms of PCTA-1 at the mRNA level are observed. PCTA-1 maps to 1q42-43, a locus associated with predisposition to prostate cancer. We have determined the genomic structure of PCTA-1 to account for the several observed isoforms, performed expression analysis to determine distribution in normal and transformed contexts at the RNA and protein level and conducted over-expression studies to determine effects on cellular phenotype.

3' Untranslated Regions↗
PubMed2000

CSF shunts 50 years on--past, present and future.

Cerebrospinal fluid (CSF) shunts were invented almost 50 years ago. While their introduction revolutionized the treatment of hydrocephalus, their complications have become legendary, and the focus of much investigation and development of new devices. New devices have been based upon improved understanding of the pathophysiology of hydrocephalus or shunt complications. Despite the rational, or frequently "more physiological," functioning of these devices, all too often unexpected complications have ensued, and the initial enthusiasm for the devices has waned. Assessing the efficacy of the devices has been difficult, owing to the lack of properly conducted studies. Nevertheless, the overall impact of shunt design improvements has seemed very limited. A recent randomized trial of CSF shunt design, examining the failure rates of two new and widely used valves (the Cordis Orbis Sigma and the Medtronic PS Medical Delta valves) failed to find any advantage of these over standard valve designs, many of which have been used almost since the inception of CSF shunts. A search for risk factors for failure, in a post hoc analysis of the data, indicated only that the etiology of the hydrocephalus and the position and local environment of the ventricular catheter tip were probably important. Remarkably, the rate of change in the size of the ventricles and the final ventricular size were not different despite the substantial differences in flow characteristics of the two new valves. Shunt failure rates of less than 5% at 1 year, with infection rates of less than 1%, seem like reasonable goals for the next decade in the new millenium. This can be achieved through basic research into the pathophysiology of shunt failure with improved mathematical models, and perhaps animal models of shunt failure. Efficacy of new devices or treatments must be scrutinized scientifically so as not to waste valuable resources and time on unproven treatments. Uncontrolled series and testimonial assertions about new treatments or devices, especially from proponents with a vested interest, should be regarded with great skepticism. Nevertheless, our best efforts are likely to result in a major advance in the management of pediatric hydrocephalus, which now seems tantalizingly close.

Animals↗
PubMed2000

Risk factors for repeated cerebrospinal shunt failures in pediatric patients with hydrocephalus.

OBJECT: Repeated cerebrospinal fluid (CSF) shunt failures in pediatric patients are common, and they are a significant cause of morbidity and, occasionally, of death. To date, the risk factors for repeated failure have not been established. By performing survival analysis for repeated events, the authors examined the effects of patient characteristics, shunt hardware, and surgical details in a large cohort of patients. METHODS: During a 10-year period all pediatric patients with hydrocephalus requiring CSF diversion procedures were included in a prospective single-institution observational study. Patient characteristics were defined as age, gender, weight, head circumference, American Society of Anesthesiology class, and cause of hydrocephalus. Surgical details included whether the procedure was performed on an emergency or nonemergency basis, use of antibiotic agents, concurrent surgical procedures, and duration of the surgical procedure. Details on shunt hardware included: the type of shunt, the valve system, whether the shunt system included multiple or complex components, the type of distal catheter, the site of the shunt, and the side on which the shunt was placed. Repeated shunt failures were assessed using multivariable time-to-event analysis (by using the Cox regression model). Conditional models (as established by Prentice, et al.) were formulated for gap times (that is, times between successive shunt failures). There were 1183 shunt failures in 839 patients. Failure time from the first shunt procedure was an important predictor for the second and third episodes of failure, thus establishing an association between the times to failure within individual patients. An age younger than 40 weeks gestation at the time of the first shunt implantation carried a hazard ratio (HR) of 2.49 (95% confidence interval [CI] 1.68-3.68) for the first failure, which remained high for subsequent episodes of failure. An age from 40 weeks gestation to 1 year (at the time of the initial surgery) also proved to be an important predictor of first shunt malfunctions (HR 1.77, 95% CI 1.29-2.44). The cause of hydrocephalus was significantly associated with the risk of initial failure and, to a lesser extent, later failures. Concurrent other surgical procedures were associated with an increased risk of failure. CONCLUSIONS: The patient's age at the time of initial shunt placement and the time interval since previous surgical revision are important predictors of repeated shunt failures in the multivariable model. Even after adjusting for age at first shunt insertion as well as the cause of hydrocephalus, there is significant association between repeated failure times for individual patients.

Adolescent↗
PubMed1999

Change in ventricular size and effect of ventricular catheter placement in pediatric patients with shunted hydrocephalus.

OBJECTIVE: The multicenter, randomized pediatric cerebrospinal fluid shunt valve design trial found no difference in the rate of shunt failure between a standard valve, a siphon-reducing valve (Delta; Medtronic PS Medical, Goleta, CA), and a flow-limiting valve (Orbis Sigma; Cordis, Miami, FL); however, the valves were expected to have different effects on ultimate ventricular size. Also, the catheter position or local environment of the ventricular catheter tip might have affected shunt failure. Therefore, we performed a post hoc analysis to understand what factors, other than valve design, affected shunt failure and to identify strategies that might be developed to reduce shunt failure. METHODS: Ventricular size was measured at as many as six different intervals, using a modified Evans' ratio (with incorporation of the frontal and occipital dimensions), in 344 patients. Ventricular catheter location was defined as being in the frontal horn, occipital horn, body of the lateral ventricle, third ventricle, embedded in brain, or unknown. The ventricular catheter tip was described as surrounded by cerebrospinal fluid, touching brain, or surrounded by brain parenchyma within the ventricle (slit ventricle). Repeated measures analysis of variance for unbalanced data was used to analyze ventricular size. A Cox model (with incorporation of time-dependent covariates) was used to evaluate the contribution of age, etiology, shunt design, ventricular size, ventricular catheter location, and environment among the cases. RESULTS: Ventricular volume decreased in an exponential fashion, forming a plateau at 14 months, and was similar for the three valves (P = 0.4). Frontal and occipital ventricular catheter tip locations were associated with a reduced risk of shunt failure (hazard ratios, 0.60 [P = 0.02] and 0.45 [P = 0.001], respectively). Ventricular catheter tips surrounded by cerebrospinal fluid or touching the brain were associated with a reduced risk of failure (hazard ratios, 0.21 and 0.33, respectively; P = 0.0001). Patients with myelomeningocele or large ventricles had increased risk of malfunction (hazard ratios, 1.78 [P = 0.006] and 2.33 [P = 0.03], respectively). CONCLUSION: Decline of ventricular size over time is not affected by these different shunt valve designs. This suggests that the mechanical models of hydrocephalus on which the designs were based are inadequate. Ventricular catheter tip location and ventricular catheter environment are important. Techniques to accurately place ventricular catheters and new valve designs that effectively control ventricular size might reduce shunt malfunction.

Catheters, Indwelling↗
PubMed1999

Third ventriculostomy versus cerebrospinal fluid shunt as a first procedure in pediatric hydrocephalus.

BACKGROUND: Third ventriculostomy (TV) has been reported to be efficacious for diverse causes of obstructive hydrocephalus in pediatric patients, and preferable to a first CSF shunt (CS) in those eligible. We reviewed the respective failure rates in a prospective cohort of patients at our institution. METHOD: All patients having either TV or CS (i.e ventriculoperitoneal shunt) over the period 1987 to 1997 were prospectively entered into a database. To compare homogeneous patients, only diagnoses of either aqueductal stenosis or tumor were considered. Failure was defined as any subsequent surgical procedure for CSF diversion. Kaplan-Meier curves were constructed to determine survivorship. A multivariable Cox model using time-dependent covariates was constructed. RESULTS: There were 32 TV and 210 CS patients: 14 (44%) and 95 (45%) failed, respectively. TV patients were older (median age = 8.1 vs. 3.6 years) and had a higher incidence of aqueductal stenosis (53 vs. 25%). There was no statistically significant difference between the two procedures based on bivariate analysis (p = 0.87) and on multivariable analysis using the Cox model after adjusting for the potential confounders (p = 0.66, hazard ratio = 1.19, 95% confidence interval = 0.55-2.56). CONCLUSION: Failure from TV is not unlike that of CS when analyzed by survival methods. Larger prospective series are needed to look at specific subgroups who may benefit from TV. Quality of life and clinical outcome measures are also required to analyze the difference between these two procedures.

Adolescent↗
PubMed1998

Photorefractive keratectomy for residual myopia after radial keratotomy. PRK After RK Study Group.

PURPOSE: To evaluate the visual outcomes in patients having photorefractive keratectomy (PRK) to correct residual myopia after radial keratotomy (RK). SETTING: Nine refractive surgery centers in the United States and one in South Korea. METHODS: This retrospective analysis comprised 38 eyes of 32 patients treated with PRK after RK and followed for 12 months. Analysis was based on pre-RK and pre-PRK refraction as well as response to RK (pre-RK minus pre-PRK refractions). RESULTS: Mean pre-RK and pre-PRK refractions were -8.11 diopters (D) +/- 2.92 (SD) and -4.28 +/- 2.08 D, respectively. One month after PRK, mean refraction was +0.42 +/- 1.56 D and regressed to -0.95 +/- 1.24 D at 12 months. At 12 months, 65% of eyes had an uncorrected visual acuity of 20/40 or worse, and 11.1% lost 2 or more lines of best corrected acuity. Of eyes with an original erro of -6.00 or less, 81.8% were within +/- 1.00 D of intended correction at 12 months and of those with an original error of -9.12 to -20.00 D 50.0% (P = .004). All eyes with residual (pre-PRK) errors of -3.00 D or less and 42.9% with a residual error of -6.12 to -9.00 D were within +/- 1.00 D of intended correction (P = .07). There were no statistically significant differences in the response to PRK between eyes that had an RK response of 0 to 3.00, 3.12 to 6.00, or 6.12 to 12.00 D. CONCLUSION: Patients with lower original and residual myopia achieved better visual outcomes after PRK than those with higher myopia. The amount of myopic correction achieved using RK was not predictive of the amount of myopic correction using PRK.

Adult↗
PubMed1998

Frontal and occipital horn ratio: A linear estimate of ventricular size for multiple imaging modalities in pediatric hydrocephalus.

OBJECTIVE: Measurement of ventricular size is important in pediatric patients with hydrocephalus, especially those who are being followed with cerebrospinal fluid (CSF) shunts. While volumetric techniques are a more accurate estimate of true ventricular volume, they are often impracticable when multiple modalities including ultrasound are used. Volumetric area and linear measurements were compared to find the most reasonable measurement method. METHODS: Sixty-four computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound (US) scans from 25 children aged 0-17 years with hydrocephalus, before and after treatment, were measured. Measurements included ventricular volume, a ventricular/brain ratio, and four standard linear measures (Evans' ratio, Huckman's measurement, minimal lateral ventricular width, and lateral ventricular span at the body). We also included a new ratio, which accounts for often disproportionate occipital horn expansion in pediatric patients, called the frontal and occipital horn ratio. Volume and linear measurements were compared using the Spearman's correlation coefficients and correlations were further differentiated using a Z test statistic. The frontal and occipital horn ratio was also measured on CT, MRI, and US scans from 44 normal children aged 0-17 years to identify normal values. The effect of age was determined by linear regression. RESULTS: The best linear correlation with ventricular size was the frontal + occipital horn ratio (r = 0.852) and was equivalent to the ventricular/brain ratio (r = 0.891), previously shown to have the highest correlation with ventricular volume. Evans' ratio correlates less well (r = 0.423). The normal frontal and occipital horn ratio is 0.37 and is independent of age. CONCLUSIONS: The frontal and occipital horn ratio is a simple method of evaluating ventricular size in pediatric hydrocephalus patients with CSF shunts.

Adolescent↗
PubMed1997

Lhermitte-Duclos disease: literature review and novel treatment strategy.

BACKGROUND: Lhermitte-Duclos disease (LDD) is a rare pathologic entity involving the cerebellum. The fundamental nature of the entity and its pathogenesis remain unknown, and considerable debate has centered on whether it represents a neoplastic, malformative or hamartomatous lesion. The cell or cells of origin remain incompletely defined. Previous reports of cases in the English literature have dealt predominantly with the clinical and pathological aspects yet few address issues of treatment. METHODS: A case of Lhermitte-Duclos disease (LDD) in a 54-year-old female leading to local compressive symptoms and obstructive hydrocephalus is presented. A craniectomy, in addition to a C1 laminectomy followed by a decompressive duroplasty (using autologous fascia lata graft) was performed. RESULTS: The patient clinically improved and follow-up MRI 11 months post-operatively revealed improvement in hydrocephalus. CONCLUSION: The histological and immunohistochemical features of the lesion are described, emphasizing the role of an abnormal dysplastic granule cell layer. The evidence in favor of each of the major theories of pathogenesis, malformative and neoplastic is discussed. Based on these facts a form of surgical intervention involving decompressive duroplasty is proposed.

Cerebellar Diseases↗
PubMed1997

Occipital condyle fractures.

OBJECTIVE: Occipital condyle fractures (OCFs) are infrequently recognized. Three recent cases of OCF in our center prompted a review of the incidence, clinical presentation, diagnosis, and treatment of this entity. METHODS: A retrospective review of medical records and radiographic results was performed for 93 of 316 consecutive patients who were victims of trauma, who presented at the Toronto Hospital during a 13-month period, and who had undergone computed tomography of the occiput. RESULTS: A review of the literature regarding OCF revealed that cranial nerve deficits occurred in 31% of the patients with OCFs; of those, the deficits were delayed in 38%. Three new cases of OCF, with neck pain but without cranial nerve deficits, have been reported. The cervical spine x-rays revealed nothing abnormal in 96% of the reported cases. In our retrospective review, asymptomatic OCF was revealed by computed tomography for 1 of the 93 patients. CONCLUSION: OCF is a diagnostic challenge. We suggest that computed tomographic scans of O-C2 be obtained in the following circumstances: presence of lower cranial nerve deficits, associated head injury or basal cranial fracture, or persistent severe neck pain despite normal radiographic results. We propose a new classification system for the management and treatment of OCF based on the stability of the O-C1-C2 joint complex reflected by the presence of displacement of the condyle, computed tomographic or radiographic evidence of O-C1-C2 instability, and magnetic resonance evidence of ligamentous injury. OCFs are divided into the following types: Type 1 (stable), undisplaced fracture; Type 2A (stable), displaced fracture with no ligamentous instability; and Type 2B (unstable), displaced fracture with ligamentous instability.

Aged↗