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Biomedical subjects

S P Sahoo

Publications and source records attributed to S P Sahoo.

16 recordsLinked to original sources

Enteric perforation--single-layer closure.

A hundred cases of enteric perforation, treated surgically by single- or double-layer closure, were studied prospectively. Mortality and morbidity rates were 10-18 and 37-42% and comparable in the two groups. The presence of preoperative shock was the single most important prognostic indicator observed in this study. Hence it is good closure of the perforation rather than single- or double-layer closure that determines the outcome in patients with enteric perforation.

Adolescent↗

Hydatid disease in children may have an atypical presentation.

Although there is voluminous literature describing various aspects of hydatid disease in children, little attention has been paid to the small group of patients whose symptoms result in atypical presentation. This article addresses this problem, describing the features in ten children aged from 2 to 12 years. The sites of involvement were within a choledochal cyst (1). the pelvic cavity (1), the spleen (1), and transverse mesocolon. Albendazole was efficacious in the treatment of one recurrent case, as well as in preventing recurrence.

Adolescent↗

Evidence for peroxisome proliferator-activated receptor (PPAR)alpha-independent peroxisome proliferation: effects of PPARgamma/delta-specific agonists in PPARalpha-null mice.

Peroxisome proliferators are a diverse group of compounds that cause hepatic hypertrophy and hyperplasia, increase peroxisome number, and on chronic high-dose administration, lead to rodent liver tumorigenesis. Various lines of evidence have led to the conclusion that these agents induce their pleiotropic effects exclusively via agonism of peroxisome proliferator-activated receptor (PPAR)alpha, a member of the steroid receptor superfamily involved in the regulation of fatty acid metabolism. Recently, agonists of two other members of this receptor family have been identified. PPARgamma is predominantly expressed in adipocytes where it mediates differentiation; PPARdelta is a widely expressed orphan receptor with yet unresolved physiologic functions. In the course of characterizing newer PPAR ligands, we noted that highly selective PPARgamma agonists or dual PPARgamma/PPARdelta agonists, lacking apparent murine PPARalpha agonist activity, cause peroxisome proliferation in CD-1 mice. We therefore made use of PPARalpha knockout mice to investigate whether these effects resulted from agonism of PPARalpha by these agents at very high dose levels or whether PPARgamma (or PPARdelta) agonism alone can result in peroxisome proliferation. We report here that several parameters linked to the hepatic peroxisome proliferation response in mice that were seen with these agents resulted from PPARalpha-independent effects.

Animals↗

Novel peroxisome proliferator-activated receptor (PPAR) gamma and PPARdelta ligands produce distinct biological effects.

The peroxisome proliferator-activated receptors (PPARs) include three receptor subtypes encoded by separate genes: PPARalpha, PPARdelta, and PPARgamma. PPARgamma has been implicated as a mediator of adipocyte differentiation and the mechanism by which thiazolidinedione drugs exert in vivo insulin sensitization. Here we characterized novel, non-thiazolidinedione agonists for PPARgamma and PPARdelta that were identified by radioligand binding assays. In transient transactivation assays these ligands were agonists of the receptors to which they bind. Protease protection studies showed that ligand binding produced specific alterations in receptor conformation. Both PPARgamma and PPARdelta directly interacted with a nuclear receptor co-activator (CREB-binding protein) in an agonist-dependent manner. Only the PPARgamma agonists were able to promote differentiation of 3T3-L1 preadipocytes. In diabetic db/db mice all PPARgamma agonists were orally active insulin-sensitizing agents producing reductions of elevated plasma glucose and triglyceride concentrations. In contrast, selective in vivo activation of PPARdelta did not significantly affect these parameters. In vivo PPARalpha activation with WY-14653 resulted in reductions in elevated triglyceride levels with minimal effect on hyperglycemia. We conclude that: 1) synthetic non-thiazolidinediones can serve as ligands of PPARgamma and PPARdelta; 2) ligand-dependent activation of PPARdelta involves an apparent conformational change and association of the receptor ligand binding domain with CREB-binding protein; 3) PPARgamma activation (but not PPARdelta or PPARalpha activation) is sufficient to potentiate preadipocyte differentiation; 4) non-thiazolidinedione PPARgamma agonists improve hyperglycemia and hypertriglyceridemia in vivo; 5) although PPARalpha activation is sufficient to affect triglyceride metabolism, PPARdelta activation does not appear to modulate glucose or triglyceride levels.

Adipocytes↗

Appendicostomy as a venting enterostomy for colonic atresia.

Colonic atresia is usually managed surgically by resection and end-to-end anastomosis but preferably with a venting enterostomy, if presentation is delayed. A new technique of appendicostomy was performed as a venting enterostomy in eight cases of colonic atresia with good results in our children's hospital during the period 1990-1995.

Appendix↗

An unusual variant of rectal atresia with rectovestibular fistula.

Isolated rectal atresia in the girl with a normal anal canal is extremely rare, and its association with a fistula has not been reported in the literature. A 6-year-old girl who had a unique combination of rectal atresia and rectovestibular fistula was treated successfully by a posterior sagittal approach.

Anastomosis, Surgical↗

4-Methyl-3-oxo-4-aza-5alpha-androst-1-ene-17beta-N-aryl-carboxamides: an approach to combined androgen blockade [5alpha-reductase inhibition with androgen receptor binding in vitro].

4-Aza-5alpha-androstan-3-one 17beta-(N-substituted carboxamides) are potent human type 2 5alpha-reductase (5aR) inhibitors with generally poor binding to the human androgen receptor (hAR). When the 17-amide N-substituent included an aromatic residue, potent dual inhibitors of both type 1 and 2 5aR are produced, but hAR binding remained poor. Tertiary-substituted-17-amides have reduced inhibition of both 5aR isozymes. The addition of an N4-methyl substitutent to the A-ring profoundly increased hAR affinity and the addition of unsaturation to the A-ring (delta1) modestly augmented hAR binding. The unsubstituted carbanilides in the delta1-N4-methyl series show some selectivity for type 1 5aR over the type 2 isozyme, whereas addition of aryl substituents, particularly at the 2-position, increased type 2 5aR binding to provide dual inhibitors with excellent hAR binding, e.g. N-(2-chlorophenyl)-3-oxo-4-methyl-4-aza-5alpha-androst-1-ene-17bet a-carboxamide (9c). Compounds of this type exhibit low nanomolar IC50s for both human 5aR isozymes as well as the human androgen receptor. Kinetic analysis confirms that the prototype 9c displays reversible, competitive inhibition of both human isozymes of 5aR with K(i) values of less than 10 nM. Furthermore, this compound binds to the androgen receptor with an IC50 equal to 8 nM. Compounds in this series are projected to be powerful antagonists of testosterone and dihydrotestosterone action in vivo, with potential utility in the treatment of prostatic carcinoma (PC).

5-alpha Reductase Inhibitors↗

Covered exstrophy: a rare variant of classical bladder exstrophy.

Covered exstrophy is an extremely rare variant of exstrophy-epispadias complex. It is less distressing and easier to manage than classical exstrophy of the bladder. We report three cases of this entity, two associated with anorectal malformation and one with unilateral renal agenesis, along with a review of the literature.

Abnormalities, Multiple↗

A new variant of esophageal atresia with tracheoesophageal fistula and duodenal atresia: a diagnostic dilemma.

A new variant of esophageal atresia (EA) with tracheoesophageal fistula (TEF) associated with duodenal atresia is reported. The TEF was between the lower pouch and the trachea, with a cystic dilatation in the midportion. The tracheal end of the fistula was obstructed by a membranous septum at both ends of a cystic dilatation, leading to a diagnosis of pure EA (gasless abdomen). After the lower pouch was opened beyond the cystic dilatation, 100 ml nonbilious fluid was obtained. A laparotomy revealed a type III atresia of the first part of the duodenum.

Duodenal Obstruction↗

Abdominal cocoon in children: a report of four cases.

Abdominal cocoon is a rare cause of intestinal obstruction. The authors report four cases (3 boys, 1 girl; age range, 6 to 8 years) that presented with features of intestinal obstruction. There was no history of previous surgery, peritonitis, or prolonged drug intake in any of these cases. One patient presented with acute intestinal obstruction and gangrene of bowel. The etiology, preoperative diagnosis, and management of this condition are discussed.

Acute Disease↗

MK 287: a potent, specific, and orally active receptor antagonist of platelet-activating factor.

MK 287 (L-680,573), a tetrahydrofuran analog, potently inhibited [3H]C18-PAF binding to human platelet, polymorphonuclear leukocyte (PMN) and lung membranes with K1 values of 6.1 +/- 1.5, 3.2 +/- 0.7, and 5.49 +/- 2.3 nM, respectively. The inhibitory effects are stereospecific and competitive. The racemate, L-668,750 is less potent and the enantiomer, L-680,574 is 20-fold less potent than MK 287. Inhibition of the binding of [3H]C18-PAF to human PMN membranes by MK 287 was associated with the reduction of the affinity of the radioligand but not the number of the receptor sites. Binding of other radioligands (e.g., LTB4, LTC4, C5a, FMLP) to their specific receptors was unaltered at 1-10 microM MK 287. [3H]MK 287 bound to membranes from human platelets and PMNs: KD = 2.1 +/- 0.6 and 2.9 +/- 1.2 nM, respectively. When examined on isolated human cells, MK 287 potently and selectively inhibited PAF-induced aggregation of platelets in plasma (ED50 = 56 +/- 38 nM) or gel-filtered platelets (ED50 = 1.5 +/- 0.5 nM) and elastase release from PMNs (ED50 = 4.4 +/- 2.6 nM). In studies in vivo, MK 287 inhibited PAF-induced lethality in mice (ED50 = 0.8 mg/kg orally) and PAF-induced bronchoconstriction in guinea pigs (ED50 = 0.18 mg/kg intraduodenally and 0.19 mg/kg intravenously). Inhibition of PAF-induced bronchoconstriction was accompanied by parallel rightward shifts in concentration-response curves for PAF-induced platelet aggregation measured ex vivo.

Administration, Oral↗

Role of steroid in childhood haemangioma: a 10 years review.

1195 cases of various type of haemangioma were treated with various steroid modalities. The response to intralesional steroids was excellent in strawberry and mixed haemangiomas. The response to oral steroids was also good in these two types. The response of cavernous variety was poor with either modality used alone but with combined modality, a moderate response can be obtained.

Antineoplastic Agents, Hormonal↗