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Biomedical subjects

S Sharma

Publications and source records attributed to S Sharma.

At least 451 records · Page 25Linked to original sources
PubMed1999

Role of caspases and possible involvement of retinoblastoma protein during TGFbeta-mediated apoptosis of human B lymphocytes.

In this study, we investigated the involvement of caspases in TGFbeta-induced apoptosis in human B cells. Our results show that TGFbeta-mediated nuclear fragmentation, observed in the Epstein-Barr virus-negative Burkitt's Lymphoma cell line BL41, was abolished in the presence of the tripeptide caspase inhibitor zVAD-fmk or the specific caspase-3 inhibitor DEVD-fmk. Other apoptotic manifestations such as cell shrinkage, surface phosphatidylserine expression and chromatin condensation were strongly inhibited by zVAD-fmk but only partially by DEVD-fmk. This suggests that other caspases in addition to caspase-3 control these apoptotis-associated features. Specific activation of caspase-3 during TGFbeta-induced apoptosis was demonstrated by the DEVD-fmk-sensitive expression of the active p17 subunit of caspase-3 and by in vivo cleavage of PARP. In addition, TGFbeta treatment of BL41 promoted the expression of both dephosphorylated and truncated forms of the retinoblastoma protein. Inhibition of caspase-3 activity abolished both nuclear fragmentation and expression of the truncated retinoblastoma protein, without modifying the G1 cell cycle arrest induced by TGFbeta. Our data thus demonstrate that TGFbeta-induced apoptosis of lymphoma B lymphocytes is dependent on caspase activation and involves caspase-dependent cleavage of the retinoblastoma protein.

Amino Acid Chloromethyl Ketones↗
PubMed1999

Metallopeptide approach to the design of biologically active ligands: design of specific human neutrophil elastase inhibitors.

A series of compounds was designed to inhibit human neutrophil elastase utilizing a modified metallopeptide scheme developed in our laboratory termed metal-ion induced distinctive array of structures (MIDAS). These metallopeptides, synthesized by solution and solid-phase methods, exhibited excellent structural diversity and specificity in inhibiting human neutrophil elastase.

Binding Sites↗
PubMed1999

Disposition of lantadene A, the pentacyclic triterpenoid hepatotoxin, orally administered to guinea pigs.

Lantadene A (LA) administered orally to guinea pigs elicited cholestasis. LA could not be detected in liver, bile, gall bladder, blood and urine. LA and its biotransformation product reduced lantadene A (RLA) could be detected in caecum, large intestine, and faeces. In vitro incubation of LA with liver homogenates under aerobic and anaerobic conditions did not elicit its biotransformation to RLA. On the other hand, in vitro incubation of LA with guinea pig caecal and large intestinal contents under anaerobic conditions elicited conversion of LA to RLA. This is the first report of the biotransformation of LA in the animal system.

Aerobiosis↗
PubMed1999

The importance of qualitative vitreous examination in patients with acute posterior vitreous detachment.

OBJECTIVE: To determine whether patients with acute posterior vitreous detachment with pigmented vitreous granules or hemorrhage have a higher likelihood of retinal tear compared with those with qualitatively normal vitreous examination findings. METHODS: A multicenter cross-sectional study was performed in 3 peripheral ophthalmic clinics. Patients with acute posterior vitreous detachment were examined for the presence or absence of vitreous pigment granules, vitreous hemorrhage, and horseshoe retinal tear. RESULTS: Fifty-nine consecutive patients with acute posterior vitreous detachment met our eligibility criteria. Eight patients had a retinal tear, and thus its prevalence in our study was almost 14%. Thirteen patients (22%) had a high likelihood because they had evidence of either pigmented vitreous granules or hemorrhage. The prevalence of retinal tear in the setting of acute posterior detachment associated with vitreous hemorrhage alone, pigment alone, or vitreous hemorrhage and pigment was 54%. Patients with posterior vitreous detachment with pigmented vitreous granules or hemorrhage were significantly more likely to have a retinal tear (odds ratio, 52.0; 95% confidence interval, 5.4-497.0). Patients with a retinal tear were 7 times more likely to have pigmented vitreous granules or hemorrhage (LR + ve = 7.4, in which LR + ve indicates positive likelihood ratio; 95% confidence interval, 3.3-16.4). CONCLUSION: Patients with posterior vitreous detachment with vitreous pigment granules or hemorrhage are 52 times more likely to have a retinal tear compared with those who have normal findings on qualitative vitreous examination.

Acute Disease↗
PubMed1999

Cryptococcosis of thoracic vertebra simulating tuberculosis: diagnosis by fine-needle aspiration biopsy cytology--a case report.

A rare case of cryptococcosis of sixth thoracic vertebra (T6) along with pulmonary involvement in an old diabetic patient is presented. The infection resulted in lytic lesion of T6 vertebra and girdle pain. A computerized tomographic (CT) guided fine-needle aspiration biopsy (FNAB) cytology was performed, which showed encapsulated fungal spores of Cryptococcus neoformans with granulomatous reaction, later confirmed by fungal culture.

Aged↗
PubMed1999

The transplantation of human fetal neuroretinal cells in advanced retinitis pigmentosa patients: results of a long-term safety study.

The purpose of this study was to determine the long-term safety of transplanting human fetal neuroretinal cells (14 to 18 week gestational age) into a series of patients with advanced retinitis pigmentosa (RP). After obtaining informed consent, both hosts and mothers of donors were screened for transmissible diseases. Pre- and postoperative clinical exams, visual acuity, electroretinograms, and fluorescein angiograms were performed and visual field testing was attempted in each case. Surgically, an anterior approach through pars plana ciliaris was used. A retinotomy was performed in the paramacular area and a two-function cannula was introduced into the subretinal space to deliver a suspension of donor cells. The cell suspension carried approximately 4000 cells/microl; the volume injected did not exceed 150 microl. The patients were examined for periods ranging from 12 to 40 months posttransplantation. To date, no evidence of inflammation, infection, or overt rejection of the graft was noted in the host eye, neither was any change observed in the contralateral, unoperated eye. In conclusion, neuroretinal cells were injected into the subretinal space of 14 patients with advanced RP with no clinical appearance of detrimental effects at the time of surgery or up to 40 months postinjection except in 1 patient who developed retinal detachment. This sets the stage for a phase II clinical trial to determine the possible beneficial effects of this procedure in patients blinded by degenerative retinal disease.

Adult↗
PubMed1999

Biochemical interaction of human neutrophil peptide-1 with Mycobacterium tuberculosis H37Ra.

The biochemical mechanism of action of human neutrophil peptide-1 (HNP-1) against Mycobacterium tuberculosis H37Ra was studied. Mycobacteria grown in the presence of a subinhibitory concentration (IC50) of HNP-1 showed a significant decrease in the biosynthesis of vital macromolecules, as shown by the incorporation of various radiolabeled precursors. Mycobacterial cells grown in the presence of HNP-1 exhibited surface changes, as was evident from the increased number of binding sites for L-anilinonaphthalene 8-sulfonate. Permeability studies carried out with spheroplasts showed a significantly high permeability to a fluorescent probe, N-phenyl naphthylamine, in the presence of HNP-1. Significant changes in the cell wall and cell membrane were observed when HNP-1-grown cells were analysed by transmission electron microscopy. Our results suggest the mycobacterial cell wall/membrane to be the major target(s) of HNP-1.

Anilino Naphthalenesulfonates↗
PubMed1999

Pseudoaneurysm of the superficial femoral artery following accidental trauma: result of treatment by percutaneous stent-graft placement.

Accidental trauma frequently involves the extremities, and can extend to involve their blood supply, causing exsanguinating hemorrhage and pseudoaneurysm in the involved blood vessel. This is traditionally managed by surgical repair. We report a case in which control of life-threatening hemorrhage and exclusion of a large, post-traumatic pseudoaneurysm in the superficial femoral artery was performed by a commercially available stent-graft, without complication. This treatment method may be a safe and effective alternative to surgery in selected patients.

Accidents, Traffic↗
PubMed1999

Utility of coaxial technique for renal angioplasty in patients with a difficult-to-cross stenosis.

The aim of this study was to evaluate the feasibility of coaxial approach in difficult-to-cross lesions in patients with failed percutaneous transluminal renal angioplasty by conventional over-the-wire exchange technique. Twelve stenoses in 10 patients (six women and four men; age range 19 +/- 7 years) with uncontrolled hypertension were treated by this method. The stenosis was caused by nonspecific aortoarteritis in 8 patients and fibromuscular dysplasia in 2 patients. It was ostial in seven and post-ostial in five vessels. Conventional exchange technique was unsuccessful in all of them. All procedures were done by femoral route. Technical success was seen in 11 (92%), without complication. The stenosis improved from 90 +/- 2.1% (range 80-100%) to 6 +/- 7% (range 0-20%), blood pressure decreased from 198 +/- 12.3 mm Hg (range 180-220 mm Hg)/130 +/- 6.7 mm Hg (range 120-140 mm Hg) to 119 +/- 5.7 mm Hg (range 110-130 mm Hg)/83 +/- 3.9 mm Hg (range 80-90 mm Hg), and number of drug treatments for hypertension fell from 3.6 +/- 0.52 (range 3-4) to 1 +/- 0.94 (range 0-3; p < 0.01). Percutaneous transluminal renal angioplasty resulted in "cure" in 3 patients and "improvement" in 7 patients. Follow-up period was 3-21 months (mean 6.4 months). No restenosis was detected. Coaxial approach is safe and effective in treating difficult-to-cross lesions in which renal angioplasty by conventional exchange technique is unsuccessful.

Adult↗
PubMed1999

Evaluation of the Best disease gene in patients with age-related macular degeneration and other maculopathies.

Vitelliform macular dystrophy (VMD2, Best disease, MIM153700) is an early onset, autosomal, dominant macular degeneration characterized by the deposition of lipofuscin-like material within and below the retinal pigment epithelium (RPE); it is associated with degeneration of the RPE and overlying photoreceptors. Recently, we cloned the gene bestrophin, which is responsible for the disease, and identified a number of causative mutations in families with VMD2. Here, we report that the analysis of bestrophin in a collection of 259 age-related macular degeneration (AMD) patients provides evidence that mutations in the Best disease gene do not play a significant role in the predisposition of individuals to AMD. However, our results suggest that, in addition to Best disease, mutations within the bestrophin gene could be responsible for other forms of maculopathy with phenotypic characteristics similar to Best disease and for other diseases not included in the VMD category.

Adult↗
PubMed1999

Microbiologic spectrum and susceptibility of isolates: part I. Postoperative endophthalmitis. Endophthalmitis Research Group.

PURPOSE: To present the microbial spectrum and susceptibilities of isolates in postoperative endophthalmitis. METHOD: Isolates from 206 eyes of 206 patients who underwent vitrectomy for postoperative endophthalmitis were examined. RESULTS: One-hundred twelve (54.4%) of 206 vitreous samples were culture positive and 14 (12.5%) of 112 culture-positive cases were polymicrobial, yielding a total of 126 isolates. Isolates included 59 (46.8%) gram-positive cocci, eight (6.3%) gram-positive bacilli, 33 (26.2%) gram-negative organisms, five (4.0%) Actino-mycetes-related organisms, and 21 (16.7%) fungi. Susceptibilities to amikacin, ceftazidime, chloramphenicol, cefazolin, ciprofloxacin, gentamicin, and vancomycin are reported. CONCLUSIONS: This is the largest, single-center, prospective series on microbial susceptibilities in postoperative endophthalmitis. We report a high prevalence of gram-negative species and fungi, suggesting that empiric therapy should include coverage for gram-negative pathogens and for fungal pathogens in appropriate settings.

Anti-Bacterial Agents↗
PubMed1999

Microbiologic spectrum and susceptibility of isolates: part II. Posttraumatic endophthalmitis. Endophthalmitis Research Group.

PURPOSE: To present the microbial spectrum and susceptibilities of isolates in posttraumatic endophthalmitis. METHOD: Isolates from 182 eyes of 182 patients who underwent vitrectomy for posttraumatic endophthalmitis were examined. RESULTS: One hundred thirteen (62.1%) of 182 vitreous samples were culture-positive, and 23 (20.4%) of 113 culture-positive cases were polymicrobial, including three (2.7%) trimicrobial cases, yielding a total of 139 isolates. Isolates included 63 (45.3%) gram-positive cocci, 24 (17.3%) gram-positive bacilli, 25 (18.0%) gram-negative organisms, seven (5.0%) Actinomycetes-related organisms, and 20 (14.4%) fungi. Susceptibilities to amikacin, ceftazidime, chloramphenicol, cefazolin, ciprofloxacin, gentamicin, and vancomycin are reported. CONCLUSIONS: This study represents a large series on microbial spectrum and susceptibilities in posttraumatic endophthalmitis. We report a high prevalence of gram-positive bacilli species and polymicrobial infections containing gram-negative species, underscoring the importance of broad-spectrum, combination antibiotics in the empiric treatment of posttraumatic endophthalmitis.

Anti-Bacterial Agents↗
PubMed1999

Utility values and diabetic retinopathy.

PURPOSE: To ascertain the utility values associated with diabetic retinopathy and varying degrees of visual loss. METHODS: One hundred consecutive patients with diabetic retinopathy and best-corrected visual acuity decreased to 20/40 or worse in at least one eye occurring primarily as a result of diabetic retinopathy were evaluated in a cross-sectional study. Utility values were ascertained in five groups using both the time trade-off and standard gamble methods: group 1 (best-corrected visual acuity in the better eye of 20/20 to 20/25), group 2 (best-corrected visual acuity in the better eye of 20/30 to 20/50), group 3 (best-corrected visual acuity in the better eye of 20/60 to 20/100), group 4 (best-corrected visual acuity in the better eye of 20/200 to 20/400), and group 5 (best-corrected visual acuity in the better eye of counting fingers to hand motions). RESULTS: The mean utility value for the diabetic retinopathy group as a whole was 0.77 (SD = 0.21; 95% confidence interval [CI], 0.73 to 0.81) with the time trade-off method and 0.88 (SD = 0.20; 95% CI, 0.84 to 0.92) with the standard gamble method. Employing the time trade-off method correlated with the best-corrected visual acuity in the better eye, the mean utility results were as follows: group 1 = 0.85 (95% CI, 0.75 to 0.95), group 2 = 0.78 (CI, 0.72 to 0.84), group 3 = 0.78 (CI, 0.67 to 0.89), group 4 = 0.64 (CI, 0.53 to 0.75), and group 5 = 0.59 (CI, 0.23 to 0.95). Thus, patients in group 1 (best-corrected visual acuity of 20/20 to 20/25 in the better eye) were willing to trade a mean of 15% of their remaining years of life in return for perfect vision in each eye, whereas those in group 5 (best-corrected visual acuity of counting fingers to hand motions in the better eye) were willing to trade a mean of 41% of their remaining years in return for perfect vision in each eye. There was no significant difference in mean utility values between patients who had decreased visual acuity from diabetic retinopathy for 1 year or less compared with those with decreased acuity for more than 1 year. There was also no significant difference in mean utility values between those with a 12th grade education or less compared with those with more than a 12th grade education. CONCLUSION: Visual loss occurring secondary to diabetic retinopathy is associated with a substantial decrease in patient utility value (and quality of life). The utility value is directly dependent on the degree of visual loss associated with the disease. The length of time of visual loss and amount of formal education do not appear to affect the utility value.

Adult↗
PubMed1999

Toward designing the optimal total cavopulmonary connection: an in vitro study.

BACKGROUND: Understanding the total cavopulmonary connection (TCPC) hemodynamics may lead to improved surgical procedures which result in a more efficient modified circulation. Reduced energy loss will translate to less work for the single ventricle and although univentricular physiology is complex, this improvement could contribute to improved postoperative outcomes. Therefore to conserve energy, one surgical goal is optimization of the TCPC geometry. In line with this goal, this study investigated whether addition of caval curvature or flaring at the connection conserves energy. METHODS: TCPC models were made varying the curvature of the caval inlet or by flaring the anastomosis. Steady flow pressure measurements were made to calculate the power loss attributed to each connection design over a range of pulmonary flow splits (70:30 to 30:70). Particle flow visualization was performed for each design and was qualitatively compared to the power losses. RESULTS: Results indicate that curving the cavae toward one pulmonary artery is advantageous only when the flow rate from that cavae matches the flow to the pulmonary artery. Under other pulmonary flow split conditions, the losses in the curved models are significant. In contrast, fully flaring the anastomosis reduced losses over the range of pulmonary flow splits. Power losses were 56% greater for the curving as compared to flaring. Fully flaring without caval offset reduced losses 45% when compared to previous models without flaring. If flaring on all sides was implemented with caval offset, power losses reduced 68% compared to the same nonflared model. CONCLUSIONS: The results indicate that preferentially curving the cavae is only optimal under specific pulmonary flow conditions and may not be efficient in all clinical cases. Flaring of the anastomosis has great potential to conserve energy and should be considered in future TCPC procedures.

Anastomosis, Surgical↗
PubMed1999

Role of autacoids in cardiovascular colapse in anaphylactic shock in anaesthetized dogs.

OBJECTIVE: In anaphylactic shock (AS), the relative effects of the autacoids including histamine, prostaglandins (prost), and leukotrienes (leuk) on causing cardiovascular collapse and the extent to which receptor blocking agents and pathway inhibitors may prevent this collapse are not clear. METHODS: In randomized design, we investigated whether blockade of histamine H1, H2, and H3 receptors or inhibition of the cyclooxygenase (cyclo) and lipoxygenase pathways (lipox) prevented AS in ragweed sensitized dogs. Seven dogs were studied under pentobarbital anesthesia in which the treatment studies were approximately 2 weeks apart. RESULTS: During H1 receptor blockade, the decreases in blood pressure and cardiac output otherwise observed in AS were attenuated (P < 0.05) and the release of prost, thromboxanes, and leuk were reduced as compared with nontreatment studies. Cyclo inhibition also attenuated cardiovascular collapse and mediator release in AS, but the other treatments showed no effects. CONCLUSION: H1 receptor blockade and cyclo may attenuate cardiovascular shock in AS. These agents inhibit autacoid release from mast cells in addition to any specific receptor blocking and pathway inhibition effects.

Analysis of Variance↗
PubMed1999

Stenosis in the aorta caused by non-specific aortitis: results of treatment by percutaneous stent placement.

AIM: To evaluate the short-term results of percutaneous stent placement in treating stenosis in the aorta caused by non-specific aortitis (Takayasu's disease). METHOD: Five patients were treated by this method, all of whom had uncontrolled hypertension, haemodynamically significant stenosis in the aorta and a clinically inactive disease. Stents were placed to treat an obstructing dissection in four and recurrent stenosis in one patient. All procedures were carried out via the percutaneous transfemoral route, utilizing self-expanding stents. RESULTS: The lesion was located in the thoracic aorta in three patients and in the abdominal aorta in two patients. The stenosis decreased from 81+/-2 to 7+/-3%, the pressure gradient fell from 97+/-5 to 9+/-2 mmHg, the blood pressure improved from 200+/-3/124+/-2 to 131+/-2/81+/-2 mmHg, and the drug requirement fell from 4+/-.2 to 1.3+/-.3 (P value for all <0.001). No complication was encountered. At follow-up at 13+/-4 months, all of the patients had improved clinically. Intimal hyperplasia within the stent was seen in two patients who underwent follow-up angiograms. CONCLUSION: Percutaneous aortic stenting is useful in treating selected patients with non-specific aortitis. Further information about the long-term behaviour of intimal hyperplasia and the response of stented segments to the aging process needs to be understood before elective stenting in this young patient population can be advocated.

Adolescent↗
PubMed1999

Joint distribution at presentation in children with pauciarticular arthritis.

The most frequently affected joints in 215 children with pauciarticular arthritis (fewer than 5 joints involved) were knees, ankles, fingers, toes, wrists, elbows, and hips, respectively. Antinuclear antibodies were present in 68% and uveitis in 16%. Small joint arthritis should alert the physician to the possibilities of pauciarticular arthritis.

Antibodies, Antinuclear↗