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Biomedical subjects

R Lal

Publications and source records attributed to R Lal.

At least 55 records · Page 3Linked to original sources

Bladder-neck repair in urinary bladder exstrophy.

A simple modification of an existing technique for bladder-neck reconstruction in exstrophy of the urinary bladder is reported. The technique involves tubularization of the posterior urethra up to just below the ureteric orifices. It differs from other techniques in that no part of the bladder tissue is used for buttressing the repair, but all is utilized for enhancing the bladder volume. Only 2 of 20 patients remained incontinent after bladder-neck reconstruction; the remaining 18 have achieved socially acceptable continence.

Bladder Exstrophy↗

Primary reconstruction of a congenital anterior urethral diverticulum.

A new technique for primary reconstruction of a congenital anterior urethral diverticulum is described. This operation eliminates the obstruction caused by the distal lip of the diverticulum and at the same time strengthens the unsupported urethral wall using tissue from the walls of the diverticulum. It has been used very effectively in two boys.

Child, Preschool↗

Urodynamic evaluation in boys treated for posterior urethral valves.

This study describes the urodynamic findings in 22 patients with posterior urethral valves and discusses their association with urinary incontinence, age, mode of primary treatment, renal function, and changes in the upper tracts. The patients' ages ranged from 3 to 26 years and 27% were either adolescents or older. The urodynamic findings were categorized into 5 main patterns, although mixed patterns were also observed; (1) normal capacity and compliance with normal detrusor contractility (2/22 patients, 9.1%); (2) small-capacity, hypocompliant bladder (8/22 patients, 36.4%); (3) unstable bladder (2/22 patients, 9.1%); (4) large-capacity, hypotonic bladder with decreased detrusor contractility (2/22 patients, 9.1%); and (5) normal capacity and compliance but with decreased detrusor contractility (8/22 patients, 36.4%). More than one-half of the patients (57.1%) evacuated their bladders incompletely, and this seemed to be associated with post-treatment episodes of urinary-tract infection. The commonest symptom was daytime frequency, urgency, and leak with nocturnal enuresis, which urodynamically correlated with a small-capacity, hypocompliant or unstable bladder or to incomplete evacuation of the bladder, leading to significant post-void residue. Significant detrusor dysfunction was identified in 2 asymptomatic patients as well, emphasizing the need to perform a routine urodynamic work-up on all valve patients. Urodynamic properties seemed to be associated with age. Small, hypocompliant, and unstable bladders were almost always seen in prepubertal boys and in the first 5 years following undiversion, whereas large, hypotonic bladders with impaired contractility were seen in post-pubertal boys. While the current policy is to avoid high diversion, data in this study suggest that disorders of detrusor capacity, compliance, and contractility exist in children treated by primary valve ablation and vesicostomy and that abnormal detrusor dynamics seem to be a reflection of inherent developmental detrusor dysfunction consequent to congenital infravesical obstruction.

Adolescent↗

Expectant management of haemoperitoneum.

Nonoperative management was successful in 81 of the 90 patients including two patients with penetrating injury. Nine patients were operated on after an initial period of observation, eight because of continued bleeding and one because of features of peritonitis. There were four deaths. These were due to multisystem injuries and not directly related to haemoperitoneum alone. Nonoperative management is a relatively safe and effective method in management of selected cases of haemoperitoneum.

Abdominal Injuries↗

Endoscopic treatment of tracheoesophageal fistula using electrocautery and the Nd:YAG laser.

BACKGROUND: Endoscopy is a well-established means of diagnosis in recurrent and congenital H-type tracheoesophageal fistulas. There is only limited knowledge of its role in the treatment using either electrocautery or laser. Laser application has not yet been reported in the treatment of recurrent tracheoesophageal fistula. METHODS: From 1993 to 1997 five patients with tracheoesophageal fistula (two congenital H-type and three recurrent) were treated endoscopically using a rigid ventilating bronchoscope. The final diagnosis was made on bronchoscopic examination. In two of the patients with recurrent fistulas and one with congenital fistula, the mucosal lining was fulgurated with electrocautery via an insulated wire. In one patient each with recurrent and congenital fistula, the mucosal lining was vaporized with the Nd:YAG laser via a 600 microm bare quartz fiber. RESULTS: Obliteration of the fistula was achieved in both the patients in whom laser was used, but it was unsuccessful in two of the three children in whom electrocautery was used. The obliquity of the congenital H-type fistula renders it more amenable to obliteration compared with the short and direct recurrent fistula. There was significant respiratory distress in the postoperative period after use of electrocautery. However, it was uneventful with the use of laser. CONCLUSIONS: Endoscopic treatment of recurrent and congenital H-type tracheoesophageal fistula is technically easier than open surgical procedures and helps avoid the risks associated with the latter. The Nd:YAG laser is qualitatively better than electrocautery for the obliteration of the fistula.

Adolescent↗

Long-term prognosis of renal function in boys treated for posterior urethral valves.

This paper discusses the long-term prognosis of renal function in 84 boys treated for posterior urethral valves and followed up for a period ranging from 1-21 years. Thirty-one of the 84 patients (39.3%) were either adolescents or had crossed adolescence and this study highlights the changes through adolescence and puberty. Serum creatinine was found to be raised in 53% patients at presentation and 22.5% patients eventually progressed to chronic renal failure. Serum creatinine value 1 year after appropriate decompression of the urinary tract was a more accurate predictor of the eventual renal outcome rather than serum creatinine at presentation. Decompensation at puberty was detected in 3 patients in this study. The predisposing factors identified were the persistence of gross hydroureteronephrosis with voiding dysfunction after treatment in one patient and renal parenchymal disease in the other 2 patients. The "risk factors" for predicting a poor eventual renal function were persistently raised serum creatinine 1 year after decompression by diversion or fulguration, bilateral high grade vesicoureteral reflux, persistent severe upper tract dilatation after treatment, voiding dysfunction and delayed presentation. This study emphasizes the need to diagnose and intervene early, to investigate post-treatment persistent upper tract dilatation for vesicoureteral junction obstruction and for detrusor dysfunction by a complete urodynamic evaluation and to follow up these patients carefully through adolescence and adulthood.

Adolescent↗

Congenital lung cyst.

This case report describes a congenital lung cyst presenting as a brilliantly transilluminant mass in the left supraclavicular region. Clinically, it was mistakenly thought to be a cervical cystic hygroma with intrathoracic extension. X-ray and CT scan of the neck and chest confirmed the diagnosis. The lung cyst was treated by surgical excision with excellent results.

Child, Preschool↗

Amyloid beta protein-(1-42) forms calcium-permeable, Zn2+-sensitive channel.

Amyloid beta protein (AbetaP) forms senile plaques in the brain of the patients with Alzheimer's disease. The early-onset AD has been correlated with an increased level of 42-residue AbetaP (AbetaP1-42). However, very little is known about the role of AbetaP1-42 in such pathology. We have examined the activity of AbetaP1-42 reconstituted in phospholipid vesicles. Vesicles reconstituted with AbetaP show strong immunofluorescence labeling with an antibody raised against an extracellular domain of AbetaP suggesting the incorporation of AbetaP peptide in the vesicular membrane. Vesicles reconstituted with AbetaP showed a significant level of 45Ca2+ uptake. The 45Ca2+ uptake was inhibited by (i) a monoclonal antibody raised against the N-terminal region of AbetaP, (ii) Tris, and (iii) Zn2+. However, reducing agents Trolox and dithiothreitol did not inhibit the 45Ca2+ uptake, indicating that the oxidation of AbetaP or its surrounding lipid molecules is not directly involved in the AbetaP-mediated Ca2+ uptake. An atomic force microscope was used to image the structure and physical properties of these vesicles. Vesicles ranged from 0.5 to 1 microm in diameter. The stiffness of the AbetaP-containing vesicles was significantly higher in the presence of calcium. The stiffness change was prevented in the presence of zinc, Tris, and anti-AbetaP antibody but not in the presence of Trolox and dithiothreitol. Thus the stiffness change is consistent with the vesicular uptake of Ca2+. These findings provide biochemical and structural evidence that AbetaP1-42 forms calcium-permeable channels and thus may induce cellular toxicity by regulating the calcium homeostasis in Alzheimer's disease.

Amyloid beta-Peptides↗

Upper-tract changes after treatment of posterior urethral valves.

This paper discusses the long-term sequelae in the upper urinary tract with respect to hydroureteronephrosis (HUN), vesicoureteral reflux (VUR), renal parenchymal disease, and their correlation with renal function in 84 boys with posterior urethral valves followed for 1 to 21 years. Thirty-one boys (39.3%) were adolescents or older at the time of review. The incidence of high-grade VUR (grade III or more) was 47.6% at presentation, and resolution following decompression of the lower urinary tract occurred in 38.7% of refluxing units. VUR was associated with a high incidence of chronic renal failure (CRF) (30%) on long-term follow up; however, 16% of non-refluxing patients also progressed to CRF. The incidences of renal parenchymal disease and persistent upper-tract dilatation in the non-refluxing group were 25% and 50% of renal units respectively. Gross HUN persisted in 12.3% of patients despite decompression and reconstructive surgery, with vesicoureteral junction (VUJ) obstruction being documented in 1 patient only. Moderate and mild upper-tract dilatation persisted in 31.6% and 43.9% of patients, respectively. Persistent gross HUN was associated with a very high incidence of CRF (92.3%), while 88.4% of those with persistent mild/moderate dilatation maintained normal renal function over a follow-up period ranging from 1 to 21 years. This study emphasizes the need for systematic evaluation to exclude VUJ obstruction and abnormal urodynamics as a cause of persistent HUN so that effective therapy can be instituted early to relieve back-pressure and to provide a low-pressure reservoir with effective emptying. In the absence of either of these causes, persistent ureterectasis after treatment is presumably due to secondary peristaltic failure as a consequence of ureteral fibrosis, ureteral tortuosity, or developmental dysplasia.

Adolescent↗

Multiple urethral calculi in children: report of two cases.

Multiple urethral calculi are rarely found in children. We report herein two unusual cases of children found to have multiple urethral calculi. In one, the calculi formed proximal to a stricture and in the other they formed within a diverticulum. Both patients required urethrotomy for removal of the calculi. A unique cause of urethral stricture is also described in case 1.

Child↗

Urethral strictures after fulguration of posterior urethral valves.

This report discusses the incidence and predisposing factors for postfulguration urethral strictures in 82 boys with posterior urethral valves treated over 20 years and followed up for a period ranging from 1 to 21 years. A urethral stricture developed in three of the 82 patients (3.6%). All newborns and infants with small urethral caliber at presentation were treated on a temporary tubeless diversion, and fulguration of the valves was deferred until 9 to 12 months of age. A 9F resectoscope with a loop electrode was used to fulgurate at 5, 7, and 12 o'clock positions. A definite technical factor leading to a stricture could be identified in one of these three patients. Comparison of the "stricture" group with the "no stricture" group suggested that although dry fulguration did not have a definite correlation with stricture formation, it is best avoided. Refulguration and properly managed preoperative catheterization did not predispose to stricture formation. Meticulous surgical technique and avoiding oversized instrumentation were the most important factors for preventing this complication.

Adolescent↗

Endoscopic treatment of tracheal diverticulum after primary repair of esophageal atresia and tracheoesophageal fistula.

Two cases of recurrent and persistent respiratory symptoms after primary repair of esophageal atresia and tracheoesophageal fistula are described. The diagnostic workup included barium swallow examination, radionuclide study for gastroesophageal reflux, and bronchoscopy. The tracheal diverticulum was detected on bronchoscopy. Treatment consisted of endoscopic cauterization of the mucosa of the diverticulum and its orifice using electrocoagulation in case 1 and the Nd:YAG laser in case 2. Electrocoagulation produced tracheal edema, which caused severe respiratory distress necessitating temporary tracheostomy. Cauterization with the Nd:YAG laser was safe, effective, and uncomplicated.

Bronchoscopy↗

Selection of suitable marker genes for the development of cloning vectors and electroporation in different strains of Amycolatopsis mediterranei.

To select suitable genetic markers for optimizing electroporation efficiency in Amycolatopsis mediterranei, thiostrepton (tsr), erythromycin (ermE) and apramycin (am) resistance genes were used. Although tsr could not be suitably expressed in A. mediterranei, the cloning of ermE in pRL1 or its derivative (containing am) resulted in the development of cloning vectors pRLM20, pRLM30 and pRL90. In contrast to tsr and km (kanamycin resistance gene), ermE and am were suitably expressed in A. mediterranei strains and no spontaneous mutants were observed among transformants. Under optimum conditions, maximum electroporation efficiency of 1.2 x 10(4) transformants/micrograms DNA was achieved for A. mediterranei DSM 40,773. These plasmids could also be effectively transferred in other strains of A. mediterranei including F1/24 and T-195. With the cloning of ermE and am and their expression in different strains of Amycolatopsis, we have overcome the problem of the choice of suitable selectable markers for A. mediterranei and related species.

Actinomycetaceae↗

ABT-378, a highly potent inhibitor of the human immunodeficiency virus protease.

The valine at position 82 (Val 82) in the active site of the human immunodeficiency virus (HIV) protease mutates in response to therapy with the protease inhibitor ritonavir. By using the X-ray crystal structure of the complex of HIV protease and ritonavir, the potent protease inhibitor ABT-378, which has a diminished interaction with Val 82, was designed. ABT-378 potently inhibited wild-type and mutant HIV protease (Ki = 1.3 to 3.6 pM), blocked the replication of laboratory and clinical strains of HIV type 1 (50% effective concentration [EC50], 0.006 to 0.017 microM), and maintained high potency against mutant HIV selected by ritonavir in vivo (EC50, </=0. 06 microM). The metabolism of ABT-378 was strongly inhibited by ritonavir in vitro. Consequently, following concomitant oral administration of ABT-378 and ritonavir, the concentrations of ABT-378 in rat, dog, and monkey plasma exceeded the in vitro antiviral EC50 in the presence of human serum by >50-fold after 8 h. In healthy human volunteers, coadministration of a single 400-mg dose of ABT-378 with 50 mg of ritonavir enhanced the area under the concentration curve of ABT-378 in plasma by 77-fold over that observed after dosing with ABT-378 alone, and mean concentrations of ABT-378 exceeded the EC50 for >24 h. These results demonstrate the potential utility of ABT-378 as a therapeutic intervention against AIDS.

Animals↗

Development of an improved cloning vector and transformation system in Amycolatopsis mediterranei (Nocardia mediterranei).

A versatile plasmid cloning vector pRL60 carrying kanamycin/neomycin resistance (km/neo), erythromycin resistance (ermE) and alpha-amylase (alpha-amy) marker genes that replicates in various Amycolatopsis mediterranei strains and Escherichia coli has been constructed. This cloning vector has been derived from a hybrid plasmid pRL50, which was developed by cloning ermE from pIJ4026 into a pRL1 derivative pULAM2. While cloning ermE into the BamHI site of pULAM2, only a hybrid plasmid pRL50 with an additional copy of pULAM2 was selected. Thus pRL50 (18.7 kb) contained two copies each of the km/neo, alpha-amy, and one copy of ermE. When pRL50 was transformed into A. mediterranei DSM 40773 through electroporation and selected under erythromycin resistance, the plasmid underwent a spontaneous deletion of 8.5 kb fragment resulting in the formation of plasmid pRL60. pRL60 (10.2 kb) is a shuttle vector between A. mediterranei and E. coli with three marker genes: km/neo, ermE and alpha-amy. ermE is expressed in A. mediterranei thus allowing good selection of transformants. The alpha-amy gene of pRL60 is also expressed in A. mediterranei DSM 40773 and its activity can be easily detected on starch containing medium after iodine staining. Most critical parameters evaluated for electrotransformation using pRL60 in A. mediterranei were growth phase, electrical field strength, pulse length, pretreatment of mycelia with lysozyme and use of salt free water. At optimized parameters, a transformation efficiency of 4.0 x 10(4) transformants/microg DNA was reproducibly achieved for A. mediterranei DSM 40773. pRL60 could also be transformed into A. mediterranei DSM 43304, DSM 46095, MTCC-17 and in mutants F1/24 and T-195, (derived from an industrial strain of A. mediterranei N813). The alpha-amy of pRL60 conferred an amylolytic phenotype to all these strains. With the development of pRL60 and a reproducible transformation protocol, the application of recombinant DNA techniques to these industrial microorganisms has now become feasible.

Actinobacteria↗

Atomic force microscopy of arthropod gap junctions.

Atomic force microscopy has been used to characterize gap junctions isolated from the hepatopancreas of Nephrops norvegicus. The major polypeptide of these gap junctions is ductin, a highly conserved 16- to 18-kDa protein. The hydrated gap junctions, imaged in phosphate-buffered saline, appeared as membrane plaques with a thickness of 14 nm, consistent with their being a pair of apposing membranes. The upper membrane was removed by force dissection using an increased imaging force. The thickness of the lower membrane was 6 nm, giving a separation or gap between the two membranes of 2 nm. High-resolution images show fine details of the force-dissected extracellular surfaces, as previously reported for vertebrate and heart gap junctions. In addition high-resolution AFM images show for the first time detailed substructure on the cytoplasmic face of hydrated gap junctions of either vertebrate or invertebrate. The plaques had particles on their exposed and force-dissected faces. These particles were packed in a hexagonal lattice (a = b = 8.9 nm on both faces) and had a diameter of approximately 6.5 nm, with a central, pore-like depression. Fourier maps calculated from the AFM data suggested that each particle was composed of six subunits. These images show a marked similarity to the widely accepted structure of the connexon channel of vertebrate gap junctions.

Animals↗