Biomedical subjects
Publications and source records attributed to A Kumar.
A male infant presenting with respiratory distress was found to have primary thoracic neuroblastoma. This method of presentation in the newborn period is rare. His symptoms resolved spontaneously with conservative management. Full staging revealed a poorly differentiated stage 2 tumour with favourable cytogenetic markers.
PURPOSE: To evaluate the effect of trans-scleral cyclophotocoagulation (TSCP) on intraocular pressure (IOP) in eyes with medically uncontrolled secondary glaucoma persisting after intravitreal silicone oil removal. METHODS: Clinical records of 21 eyes of 21 patients who underwentTSCP for medically uncontrolled glaucoma persisting after the removal of intravitreal silicone oil, injected during vitreoretinal surgery for proliferative vitreoretinopathy (PVR), were reviewed retrospectively. Diode laser contactTSCP was applied at a power setting of 1.5-2.5 W, for a maximum duration of 2 s, and a total of 40 spots (10 spots each quadrant). All the patients were evaluated for visual acuity, IOP and number of medications used. RESULTS: The patients were followed up for a mean +/- SD period of 39.9 +/- 4.27 weeks (range 36-48 weeks). The IOP was found to have decreased significantly from a pretreatment value of 34.5 +/- 5.37 mmHg (range 24-44 mmHg) to 20.47 +/- 4.49 mmHg at 6 months of follow up (range 12-30 mmHg, P < 0.01, Student's paired t-test). The total number of glaucoma medications being used reduced from 3.38 +/- 0.5 to 1.08 +/- 0.80 postoperatively (P < 0.01, Wilcoxon's rank sum test). There was no significant difference in the visual acuity before and after the procedure. Thirteen eyes required a second sitting of TSCP, and five of these required a third sitting. For a successful outcome (IOP < 24 mmHg), a mean of 1.56 sittings (range 1-3 sittings) per eye were needed. CONCLUSION: Patients with medically uncontrolled glaucoma persisting after intravitreal silicone oil removal can be treated with TSCP; however, the reduction of IOP is variable. The IOP usually falls after a mean of 2-3 sittings of
OBJECTIVE: To investigate the utility of "late" pressure-flow studies in predicting the outcome of prostatectomy for acute urinary retention. PATIENTS AND METHODS: Fifty-eight patients with acute urinary retention were prospectively assessed using the International Prostate Symptom Score and pressure-flow studies at a median (range) of 24 (13-60) days after the episode of retention, and before transurethral resection of the prostate. Bladder outlet obstruction and bladder contractility were graded using a modified adaptation of Schäfer's passive urethral linear resistance relation. RESULTS: Fifty-six (97%) patients generated a voluntary detrusor contraction, with a mean (range) detrusor pressure at maximum flow of 72.7 (5-144) cmH2O, and 43 (75%) patients were deemed to be obstructed. Eight (16%) patients failed to void after prostatectomy and required clean intermittent catheterization. There were statistically significant differences between successful and unsuccessful patients in mean (SD) age, at 66.30 (6.9) vs 78.8 (2.6) years (P = 0.001), detrusor instability (49% vs 0%, P = 0.01), inability to void during pressure study (8% vs 75%, P = 0.001), and maximal detrusor pressure in the voiding phase, at 80 (36.0) vs 19 (11.2) cmH2O (P = 0.001). CONCLUSIONS: In patients with acute urinary retention, pressure-flow studies undertaken after a period of adequate bladder rest (> 3 weeks) are useful in predicting the surgical outcome. Old age, absence of bladder instability, inability to void during the pressure-flow study and a maximal detrusor pressure of < 20 cmH2O are associated with a poor outcome after prostatectomy.
Variant human cystatin C (L68Q) is an amyloidogenic protein. It deposits in the cerebral vasculature of Icelandic patients with cerebral amyloid angiopathy, leading to stroke. Wild-type and variant cystatin C are cysteine proteinase inhibitors which form concentration dependent inactive dimers; however, variant cystatin C dimerizes at lower concentrations and has an increased susceptibility to a serine protease. We studied the effect of the L68Q amino acid substitution on cystatin C properties, utilizing full length cystatin C purified in mild conditions from media of cells stably transfected with either the wild-type or variant cystatin C genes. The variant cystatin C forms fibrils in vitro detectable by electron microscopy in conditions in which the wild-type protein forms amorphous aggregates. We also show by circular dichroism, steady-state fluorescence and Fourier-transformed infrared spectroscopy that the amino acid substitution modifies cystatin C structure by destabilizing alpha-helical structures and exposing the tryptophan residue to a more polar environment, yielding a more unfolded molecule. These spectral changes demonstrate that variant cystatin C has a three-dimensional structure different from that of the wild-type protein. The structural differences between variant and wild-type cystatin C account for the susceptibility of the variant protein to unfolding, proteolysis and fibrillogenesis.
Explore the source record for details and available documents.
We report a case of osseous metaplasia of an autologous anterior cruciate ligament (ACL) reconstruction that was implicated in blocking extension of the knee. Nonoperative treatment was unsuccessful. Arthroscopic excision of the ACL and osseous metaplasia abolished the fixed flexion deformity. The osseous metaplasia was an additional factor in causing the block to extension along with an anteriorly placed femoral tunnel, raising the question that nonisometry of the graft may be involved in the pathogenesis of the osseous metaplasia.
A case of chondral injury after medial meniscal repair with a headless bioabsorbable screw is reported. As these implants can take a long time to be absorbed, all arthroscopic surgeons should be aware of possibility of this complication during this period.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
BACKGROUND: Carvedilol has been shown to improve morbidity and mortality in patients with congestive heart failure (CHF). There are limited data of carvedilol use in patients on inotrope therapy. We present our experience with carvedilol titration in New York Heart Association (NYHA) class IIIb/IV patients stabilized on milrinone therapy, as a nonrandomized study with a parallel control group of patients never on inotropes. These patients achieved volume control and stabilization of their symptoms during the course of milrinone therapy. METHODS AND RESULTS: Seventeen patients in class IIIb/IV CHF (group 1) on intermittent intravenous milrinone therapy and 15 patients in class II/IIIa compensated CHF (group 2) on standard triple heart failure therapy were titrated on carvedilol. Success and adverse events during titration were compared between the 2 groups. Fifteen (88%) patients in group 1 and 14 (93%) patients in group 2 were successfully titrated on carvedilol over 8.1 +/- 1.8 weeks and 6.7 +/- 2.8 weeks, respectively. The target dose of carvedilol (25 or 50 mg twice daily) was achieved in 13 (87%) patients (group 1) and 14 (93%) patients (group 2). Seven (47%) patients in group 1 and 4 (28%) patients in group 2 had adverse events during carvedilol titration. Eight (53%) patients in group 1 were weaned off milrinone over a period of 8.4 weeks after carvedilol titration, whereas the rest of the patients had reduction in the frequency of infusion. Ten (63%) patients in group 1 improved by one or more functional classes. CONCLUSIONS: Patients in NYHA class IIIb/IV who are treated with inotropic therapy can be titrated on carvedilol after reaching a stable state while on milrinone and standard oral drugs. Most of these patients can be successfully weaned off of milrinone or have decreased frequency of infusions and demonstrate improved functional status. Prospective randomized trials are required to evaluate these observations made in a limited number of patients in class IIIb and IV CHF because the combination of milrinone and beta-blockers has never been adequately evaluated.
A single-point substitution of the O4' oxygen by a CH2 group at the sugar residue of A6 (i.e. 2'-deoxyaristeromycin moiety) in a self-complementary DNA duplex, 5'-d(C1G2C3G4A5A6T7T8C9G10C11G12)2(-3), has been shown to steer the fully Watson-Crick basepaired DNA duplex (1A), akin to the native counterpart, to a doubly A6:T7 Hoogsteen basepaired (1B) B-type DNA duplex, resulting in a dynamic equilibrium of (1A)<==>(1B): Keq = k1/k(-1) = 0.56+/-0.08. The dynamic conversion of the fully Watson-Crick basepaired (1A) to the partly Hoogsteen basepaired (1B) structure is marginally kinetically and thermodynamically disfavoured [k1 (298K) = 3.9 0.8 sec(-1); deltaHdegrees++ = 164+/-14 kJ/mol; -TdeltaS degrees++ (298K) = -92 kJ/mol giving a deltaG degrees++ 298 of 72 kJ/mol. Ea (k1) = 167 14 kJ/mol] compared to the reverse conversion of the Hoogsteen (1B) to the Watson-Crick (1A) structure [k-1 (298K) = 7.0 0.6 sec-1, deltaH degrees++ = 153 13 kJ/mol; -TdeltaSdegrees++ (298K) = -82 kJ/mol giving a deltaGdegrees++(298) of 71 kJ/mol. Ea (k-1) = 155 13 kJ/mol]. Acomparison of deltaGdegrees++(298) of the forward (k1) and backward (k-1) conversions, (1A)<==>(1B), shows that there is ca 1 kJ/mol preference for the Watson-Crick (1A) over the double Hoogsteen basepaired (1B) DNA duplex, thus giving an equilibrium ratio of almost 2:1 in favour of the fully Watson-Crick basepaired duplex. The chemical environments of the two interconverting DNA duplexes are very different as evident from their widely separated sets of chemical shifts connected by temperature-dependent exchange peaks in the NOESY and ROESY spectra. The fully Watson-Crick basepaired structure (1A) is based on a total of 127 intra, 97 inter and 17 cross-strand distance constraints per strand, whereas the double A6:T7 Hoogsteen basepaired (1B) structure is based on 114 intra, 92 inter and 15 cross-strand distance constraints, giving an average of 22 and 20 NOE distance constraints per residue and strand, respectively. In addition, 55 NMR-derived backbone dihedral constraints per strand were used for both structures. The main effect of the Hoogsteen basepairs in (1B) on the overall structure is a narrowing of the minor groove and a corresponding widening of the major groove. The Hoogsteen basepairing at the central A6:T7 basepairs in (1B) has enforced a syn conformation on the glycosyl torsion of the 2'-deoxyaristeromycin moiety, A6, as a result of substitution of the endocyclic 4'-oxygen in the natural sugar with a methylene group in A6. A comparison of the Watson-Crick basepaired duplex (1A) to the Hoogsteen basepaired duplex (1B) shows that only a few changes, mainly in alpha, sigma and gamma torsions, in the sugar-phosphate backbone seem to be necessary to accommodate the Hoogsteen basepair.
We have carried out 1 nanosecond (ns) Molecular Dynamics (MD) simulations of the drug Y3 (4-acetylamino-5-hydroxynaphthalene- 2, 7-disulfonic acid) complexed with catalytic domain of Avian sarcoma virus Integrase (ASV-IN), both in vacuum and in the presence of explicit solvent. Starting models were obtained on the basis of PDB co- ordinates (1A5X) of ASV-IN-Y3 complex. Mn(2+) cation was present in the active site. To neutralize the positive charge in the presence of explicit solvent, eight Cl(-)anions were added. Energy Minimization (EM) and MD simulations, for both the systems, were carried out using Sander's module of AMBER5.0 with all atom force field. We also carried out 1 ns MD simulation on two flexible loops--L1 (Gly54-Gln62) and L2 (Trp138-Met155) playing crucial role in interaction of IN with the drug, under differing environmental conditions (vacuum, aqueous and organic solvent methanol). Comparison of the conformational changes in the loops, monomer and dimer is presented in the paper. Our results showed that the conformation of the loop region was closest to crystallographic data in case of monomer and constrained loops in aqueous environment. However, the dimer in vacuum was more stable than monomer. The beta sheet structure of the monomer in aqueous environment was unstable. Latter also took long time for equilibration. The box formed by loops L1 and L2 from two sub units (IINA and INB) of the dimer satisfies prerequisites for ligand recognition site and seems to be the functional biological unit.
A radiation incident took place inside an open-top radiography enclosure involving an Amertest-676 exposure device containing a cobalt-60 source of activity 2.15 TBq. The exposure device was being checked after receipt of a fresh source. The source assembly having been projected out could not be brought back into the exposure device. After thorough planning, the situation was brought under control by driving the disengaged source assembly into the exposure device. During the incident, the maximum individual whole body dose was 3.1 mSv.
BACKGROUND: Endopyelotomy is a minimally invasive surgical alternative for primary ureteropelvic junction (UPJ) obstruction. However, its success in poorly functioning kidneys is controversial. PATIENTS AND METHODS: In this retrospective study, 34 endopyelotomies performed on poorly functioning kidneys between January 1993 and December 1997 were reviewed. Of these, 13 patients had a glomerular filtration rate (GFR) <15 mL/min (Group I) and 21 had a GFR of 15 to 25 mL/min (Group II). All the patients insisted on endopyelotomy to avoid open surgery. Antegrade endopyelotomy was performed by the twin guidewire rail technique with a cold knife. An indwelling stent was kept for 2 to 6 weeks. Patients were followed up with assessment of symptoms and diuretic renograms at 3, 6, and 12 months postoperatively. RESULTS: Endopyelotomy was considered successful in 8 of 13 patients (62%) in Group I. Success was achieved in 19 of 21 patients (90%) in Group II. CONCLUSION: Endopyelotomy can be performed for improvement of symptoms. Stabilization or improvement in GFR is less pronounced in poorly functioning kidneys with primary UPJ obstruction.
BACKGROUND AND PURPOSE: Urinary incontinence secondary to intrinsic sphincter deficiency is a debilitating condition for the patient and an ordeal for the urologist. Because of the complexity of reconstructive surgical techniques and the prohibitive cost of the prosthetic devices used, there is a need for a simple procedure. We herein report our experience in managing urinary incontinence secondary to sphincteric incompetence in nine consecutive patients using a modified bulbar urethral sling procedure over a period of 2 years. PATIENTS AND METHODS: In eight patients, the incontinence followed open prostatectomy or transurethral resection for benign prostatic hyperplasia, and one patient had incontinence following fulguration of posterior urethral valves. Our procedure uses bolsters that are suspended from the rectus fascia, and a hammock made of a folded Dacron patch is placed beneath the bulbospongiosus muscle to form a sling. RESULTS: All patients were continent postoperatively, with only mild stress leakage in the erect posture, during a mean follow-up of 12.2 months (range 6-22 months) and required one or two improvised pads per day to remain continent during the daytime. Persistent perineal infection necessitated removal of the sling in one patient. One patient required clean intermittent catheterization for a short period postoperatively. CONCLUSION: This modified bulbar urethral sling procedure is a simple yet effective method to treat sphincteric deficiency of any cause.
BACKGROUND AND PURPOSE: Laparoscopic cholecystectomy (LC) is associated with a higher incidence of bile duct injury than is open cholecystectomy. We reviewed our experiences with the management of laparoscopic bile duct injuries. PATIENTS AND METHODS: From October 1992 through August 1998, 34 patients with bile duct injuries (BDI) following LC were seen. The presentation, type of injury (Strasberg classification), management, and outcome were analyzed in these patients. RESULTS: Of the 16 patients who sustained injury at our center (type A [N = 9], D [N = 5], and E1 [N = 2]), in 14, the injury was detected during LC, and two patients manifested with postoperative bile leak. All patients had an excellent outcome at a median follow-up of 5.5 (range 1.9-8.0) years. Of the 18 patients who sustained injury elsewhere (type C [N = 1], D [N = 2], E [N = 14; 6 with external biliary fistula (EBF) and 8 with benign biliary stricture (BBS)], and not known [1]), 9 had EBF, 1 had biliary peritonitis, and 8 had BBS at the time of presentation. Of these 18 patients, 4 underwent early repair of the BDI before referral (repair over a T-tube [N = 2] and Roux-Y hepaticojejunostomy [N = 2]). Three of them developed restricture. One patient was referred to us within 12 hours of injury and had a successful repair over a T-tube. Two patients with early repair for lateral injury had an excellent outcome. Eleven patients with BBS underwent repair with an excellent (N = 10) or fair (N = 1) outcome at a median follow-up of 5.0 (2.0-6.2) years. Three patients were lost to follow-up. CONCLUSION: The spectrum of injuries sustained at LC at a tertiary-care center is different from that in the community hospitals. Missed injuries and attempts at repair in inexperienced hands result in serious sequelae of stricture formation and long-term morbidity.
Immunohistochemical analysis of brains of patients with Alzheimer disease (AD) revealed that the cysteine proteinase inhibitor cystatin C colocalizes with amyloid beta-protein (Abeta) in parenchymal and vascular amyloid deposits. No evidence of cerebral hemorrhage was observed in any of the brains studied. Immunoelectron microscopy demonstrated dual staining of amyloid fibrils with anti-Abeta and anti-cystatin C antibodies. Cystatin C immunoreactivity was also observed in amyloid deposits in the brain of transgenic mice overexpressing human beta amyloid precursor protein. Massive deposition of the variant cystatin C in the cerebral vessels of patients with the Icelandic form of hereditary cerebral hemorrhage with amyloidosis is thought to be responsible for the pathological processes leading to stroke. Anti-cystatin C antibodies strongly labeled pyramidal neurons within cortical layers most prone to amyloid deposition in the brains of AD patients. Immunohistochemistry with antibodies against the carboxyl-terminus of Abeta(x-42) showed intracellular immunoreactivity in the same neuronal subpopulation. It remains to be established whether the association of cystatin C to Abeta plays a primary role in amyloidogenesis of AD or is a late event in which the protein is bound to the previously formed Abeta amyloid fibrils.
Explore the source record for details and available documents.