Consensus on the Management of Posterior Urethral Valves from Antenatal Period to Puberty.

The need for successful management of posterior urethral valves always captivates the minds of pediatric surgeons. Its success, however, depends on several factors ranging from prenatal preservation of upper tracts to postoperative pharmacological compliance. Regardless of measures available, some cases do not respond and progress to end stage. The management depends on several issues ranging from age and severity at presentation to long-term follow-up and prevention of secondary renal damage and managing valve bladder syndrome. This article is based on a consensus to the set of questionnaires, prepared by research section of Indian Association of Paediatric Surgeons and discussed by experienced pediatric surgeons based in different institutions in the country. Standard operating procedures for conducting a voiding cystourethrogram and cystoscopy were formulated. Age-wise contrast dosage was calculated for ready reference. Current evidence from literature was also reviewed and included to complete the topic.

Serum lipoprotein ratios as markers of insulin resistance: a study among non-diabetic acute coronary syndrome patients with impaired fasting glucose.

BACKGROUND & OBJECTIVES: Recent data suggest that insulin resistance can predict cardiovascular disease independently of the other risk factors, such as hypertension, visceral obesity or dyslipidaemia. However, the majority of available methods to evaluate insulin resistance are complicated to operate, expensive, and time consuming. This study was undertaken to assess whether serum lipoprotein ratios could predict insulin resistance in non-diabetic acute coronary syndrome (ACS) patients. METHODS: Ninety non-diabetic patients with impaired fasting glucose admitted with a diagnosis of ACS were included in the study. At the time of admission fasting glucose and insulin concentrations were measured. The homeostatic model assessment-insulin resistance (HOMA-IR) was used for insulin resistance. The fasting serum total cholesterol (TC), triglycerides (TG) and high density lipoprotein cholesterol (HDL-C) levels were checked, and then TC/HDL-C and TG/HDL-C ratios were calculated. The areas under the curves (AUC) of the receiver operating characteristic (ROC) curves were used to compare the power of these serum lipoprotein ratios as markers. RESULTS: Lipoprotein ratios were significantly higher in patients with HOMA-IR index > 2.5 as compared to patients with index <2.5 (P < 0.05). Both TG/HDL-C and TC/HDL-C ratios were significantly correlated with HOMA-IR (P<0.05). The area under the ROC curve of the TG/HDL-C and TC/HDL-C ratio for predicting insulin resistance was 0.80 (95% CI, 0.67 to 0.93), 0.78 (95% CI, 0.65 to 0.91), respectively. INTERPRETATION & CONCLUSIONS: The findings of this study demonstrate that serum lipoprotein ratios can provide a simple means of identifying insulin resistance and can be used as markers of insulin resistance and cardiovascular diseases risk in adult non-diabetic patients.

Pulmonary coccidiomycosis in New Delhi, India.

Coccidioidomycosis is an endemic disease of the western hemisphere. In cases occurring in non-endemic areas, eliciting a history of exposure as well as a high index of suspicion is imperative for timely and accurate diagnosis. In this case, a 65-year-old male presented to our hospital with fever, dry cough and malaise, and on X-ray chest, was found to have a lower lobe consolidation left lung with nodular lesions in both lungs and necrotic mediastinal lymphadenopathy. He lived in Arizona, USA, for 6 months before admission. Pulmonary coccidioidomycosis was confirmed by the isolation of Coccidioides spp. in pure culture from both broncho-alveolar lavage and lung biopsy specimens. The identity of the isolate was confirmed as C. posadasii by gene sequencing. The patient improved after being treated with fluconazole.

Endobronchial ultrasound for tubercular mediastinal adenopathy and its comparison with traditional tools.

SETTING: Endobronchial ultrasound (EBUS) is now the preferred tool to sample malignant mediastinal lesions. Data on its role in tubercular mediastinal adenopathy are limited.OBJECTIVE: To evaluate the efficacy of EBUS in diagnosing tubercular mediastinal lymphadenopathy and correlate the cytological and microbiological results obtained on aspirate with standard methods (radiology and the tuberculin skin test) suggesting tuberculosis (TB).DESIGN: A prospective study of 125 patients with suspected tubercular mediastinal lymphadenopathy who underwent EBUS-transbronchial needle aspiration. Only patients with a microbiologically confirmed diagnosis or unequivocal clinico-radiological response to anti-TB treatment during follow-up were included.RESULTS: A total of 122 patients showed findings suggesting TB on cytopathology (sensitivity 97.6%), 105 (84%) of whom had microbiological evidence of TB (positive smear/culture or both). Performing staining for acid-fast bacilli on slides prepared during the procedure vs. only on samples submitted in saline significantly improved the yield. Only 92 patients (73.6%) were Mantoux-positive. Cytology was more sensitive than computed tomography in picking up necrosis. Granulomas, with or without necrosis, were equally likely to be microbiologically positive. However, presence of only necrosis in a TB-endemic region invariably points towards TB diagnosis.CONCLUSIONS: EBUS was highly sensitive and specific for diagnosis of mediastinal TB and may be considered the investigation of choice for tubercular mediastinal adenopathy.

Experimental concurrent infection of Afar breed goats with Oestrus ovis (L1) and Haemonchus contortus (L3): interaction between parasite populations, changes in parasitological and basic haematological parameters.

The study was conducted to examine the occurrence and interaction between Oestrus ovis and Haemonchus contortus in experimentally infected Ethiopian Afar breed of goats. Twenty goats were divided into four groups (O, OH, H, and C) of five animals each. Each animal of groups O and OH received weekly infections for 5 weeks with 66 first instar larvae (L1) of O. ovis. Then animals of groups OH and H were infected with a single dose of 5000 third stage larvae (L3) of H. contortus. Goats of group C were kept free of any infection as non-infected control. Faecal egg count (FEC), blood cell count, total serum protein level and body weight were recorded weekly throughout the study period. At necropsy worm burden, female worm length, fecundity and larval burden of O. ovis in the nasal-sinus cavities of infected animals were assessed. The results showed that the presence of H. contortus in the abomasum of goats of group OH had no influence on the development of O. ovis. On the contrary, a significant reduction (P<0.05) in FEC, worm burden, fecundity and female worm length was revealed in group OH animals compared to the mono-infected animals (group H). This was associated with eosinophilia and reduced packed cell volume.

Prevalence of bovine trypanosomosis and trypanocidal drug sensitivity studies on Trypanosoma congolense in Wolyta and Dawero zones of southern Ethiopia.

Cross-sectional studies were conducted in tsetse and non-tsetse-controlled areas of the Southern Nation Nationalities and Peoples Regional State (SNNPRS) of Ethiopia to determine the prevalence of bovine trypanosomosis as well as drug sensitivity tests on Trypanosoma congolense in both naturally and experimentally infected cattle and mice, respectively. A total trypanosome prevalence of 4.8% (95% CI: 1.8-7.5) and 20.4% (95% CI: 14-26.8) were recorded in the tsetse-controlled study area of Humbo district and the non-tsetse-controlled area of Mareka district, respectively, indicated statistically significant difference between the two areas (P<0.001). The mean PCV value for Humbo and Mareka was 26.2 (95%: 25.7-26.7) and 22.7 (95% CI: 22.1-23.3), respectively, which were also statistically significant (P<0.001). The prophylactic activity of isometamidium chloride (ISMM) was observed in Humbo on nine naturally positive zebu cattle. Breakthrough infections were recorded in (6/9) 66.7% of the cases in less than 5 weeks. A qualitative assay on mice was conducted on two T. congolense isolates obtained from the breakthrough cases with ranges of doses of ISMM and diminazene diaceturate (DA). Thereafter the mice were followed for relapse infection. ISMM at doses 0.5-4 mg/kg body weight (bw) and DA at doses of 3.5-28 mg/kg bw failed completely to cure T. congolense infections in any of the mice. A quantitative assay on mice was conducted on four T. congolense isolates obtained from Mareka. The four isolates were pooled into two pools (Pool-1 and Pool-2) for the quantitative assay on mice. The pooled isolates were tested with the same trypanocidal drugs and ranges of doses as it was used for the qualitative assay on mice. The minimum curative dose (MCD) of ISMM that cleared T. congolense infected mice was 4 and 2mg/kg bw for Pool-1 and Pool-2, respectively, whereas MCD of DA was 28 and 14 mg/kg bw, in Pool-1 and Pool-2, respectively. Although cloned populations were not used to prove whether the observed resistance was at the individual level or not, the results show that there is resistance to both ISMM and DA; failure of the "sanative pair".

Gastrointestinal nematodes in dogs from Debre Zeit, Ethiopia.

The study was conducted during the period between January 2005 and June 2006 to determine the frequency of gastrointestinal (GI) nematode infections of dogs in and around Debre Zeit, using qualitative and quantitative coprological (N = 100) and postmortem examinations (N = 20). By coproscopy 51% dogs were positive for different types of nematodal eggs, out of which 23.5% were with mixed infections. On necropsy 95% animals were found positive for adult parasites, of which 31.6% were showing more than one species of adult nematodes. The coproscopical examination revealed 32% infection with Ancylostoma caninum followed by Toxocara canis (21%), Spirocerca lupi (7%) and Trichuris vulpis (3%), while postmortem examination showed 70, 45, 23.5 and 5% infection, respectively. The study further indicated significant difference (P < 0.05) in overall frequency of GI nematode infections among different age groups but no difference (P > 0.05) between sexes.

Site-specifically located 8-amino-2'-deoxyguanosine: thermodynamic stability and mutagenic properties in Escherichia coli.

2-Nitropropane (2-NP), an important industrial solvent and a component of cigarette smoke, is mutagenic in bacteria and carcinogenic in rats. 8-Amino-2'-deoxyguanosine (8-amino-dG) is one of the types of DNA damage found in liver, the target organ in 2-NP-treated rats. To investigate the thermodynamic properties of 8-amino-dG opposite each of the four DNA bases, we have synthesized an 11mer, d(CCATCG*CTACC), in which G* represents the modified base. By annealing a complementary DNA strand to this modified 11mer, four sets of duplexes were generated each containing one of the four DNA bases opposite the lesion. Circular dichroism studies indicated that 8-amino-dG did not alter the global helical properties of natural right-handed B-DNA. The thermal stability of each duplex was examined by UV melting measurements and compared with its unmodified counterpart. For the unmodified 11mer, the relative stability of the complementary DNA bases opposite G was in the order C > T > G > A, as determined from their -DeltaG degrees values. The free energy change of each modified duplex was lower than its unmodified counterpart, except for the G*:G pair that exhibited a higher melting transition and a larger -DeltaG degrees than the G:G duplex. Nevertheless, the stability of the modified 11mer duplex also followed the order C > T > G > A when placed opposite 8-amino-dG. To explore if 8-amino-dG opposite another 8-amino-dG has any advantage in base pairing, a G*:G* duplex was evaluated, which showed that the stability of this duplex was similar to the G*:G duplex. Mutagenesis of 8-amino-dG in this sequence context was studied in Escherichia coli, which showed that the lesion is weakly mutagenic (mutation frequency approximately 10(-3)) but still can induce a variety of targeted and semi-targeted mutations.

Recognition and incision of site-specifically modified C8 guanine adducts formed by 2-aminofluorene, N-acetyl-2-aminofluorene and 1-nitropyrene by UvrABC nuclease.

Nucleotide excision repair plays a crucial role in removing many types of DNA adducts formed by UV light and chemical carcinogens. We have examined the interactions of Escherichia coli UvrABC nuclease proteins with three site-specific C8 guanine adducts formed by the carcinogens 2-aminofluorene (AF), N:-acetyl-2-acetylaminofluorene (AAF) and 1-nitropyrene (1-NP) in a 50mer oligonucleotide. Similar to the AF and AAF adducts, the 1-NP-induced DNA adduct contains an aminopyrene (AP) moiety covalently linked to the C8 position of guanine. The dissociation constants for UvrA binding to AF-, AAF- and AP-DNA adducts, determined by gel mobility shift assay, are 33 +/- 9, 8 +/- 2 and 23 +/- 9 nM, respectively, indicating that the AAF adduct is recognized much more efficiently than the other two. Incision by UvrABC nuclease showed that AAF-DNA was cleaved approximately 2-fold more efficiently than AF- or AP-DNA (AAF > AF approximately AP), even though AP has the largest molecular size in this group. However, an opened DNA structure of six bases around the adduct increased the incision efficiency for AF-DNA (but not for AP-DNA), making it equivalent to that for AAF-DNA. These results are consistent with a model in which DNA damage recognition by the E. coli nucleotide excision repair system consists of two sequential steps. It includes recognition of helical distortion in duplex DNA followed by recognition of the type of nucleotide chemical modification in a single-stranded region. The difference in incision efficiency between AF- and AAF-DNA adducts in normal DNA sequence, therefore, is a consequence of their difference in inducing structural distortions in DNA. The results of this study are discussed in the light of NMR solution structures of these DNA adducts.

Molecular requirements for the mutagenicity of malondialdehyde and related acroleins.

Malondialdehyde, a product of lipid peroxidation and prostaglandin biosynthesis, is mutagenic in Salmonella. To determine the molecular requirements for its mutagenicity, we tested a series of beta-substituted acroleins in Salmonella typhimurium hisD3052 . Mutagenicity is dependent on the steric bulk of the substituent (revertants/mumol) at the beta position: beta- methoxyacrolein , 220; beta- ethoxyacrolein , 110; and beta- isobutoxyacrolein , 40. A good leaving group at the beta position substantially increases the mutagenic activity (revertants/mumol): beta-(p-nitrophenoxy)acrolein, 620; beta- benzoyloxyacrolein , 320; beta- chloroacrolein , 890; and di-gamma- oxopropenyl ether, 870. These data suggest that nucleophilic attack on the beta-carbon followed by elimination of the beta substituent is important for mutagenicity. Substitution of a methyl group at the alpha-carbon abolishes mutagenicity of these compounds. This effect can be explained by the lack of chemical reactivity of the alpha-methyl analogues toward oxygen or nitrogen nucleophiles. Propynal , which can add nucleophiles to generate a substituted acrolein, exhibits the highest mutagenicity (1370 revertants/mumol) in this series. The importance of the aldehyde functionality is suggested by the nonmutagenicity of propiolonitrile , ethyl propiolate , 4-benzoyloxy-3- buten -2-one, and 4-methoxy-3- buten -2-one. Aldehyde addition subsequent to the formation of the Michael adduct is, therefore, important for mutagenesis. An investigation of the toxicity of the present series indicates that toxicity and mutagenicity are independent events based on different chemical reactions.

O6-alkyldeoxyguanosine detection by 32P-postlabeling and nucleotide chromatographic analysis.

The 32P-postlabeling procedure, developed originally by Randerath and coworkers, has been modified for the detection and analytical quantitation of O6-alkyl-2'-deoxyguanosine residues in DNA. Chromatographic techniques were developed to resolve individually the normal deoxyribonucleotide-3'-monophosphates and the O6-alkyldeoxyguanosine-3'-monophosphates by high-pressure liquid chromatography. Selective deoxyribonucleotide-3'-monophosphates (e.g., O6-alkyldeoxyguanosine-3'-monophosphates) were then converted to labeled deoxyribonucleotide-[5'-32P]monophosphates by 32P-postlabeling and nuclease P1 treatment and separated by two-dimensional thin layer chromatography. The O6-methyl- and O6-ethyl-2'-deoxyguanosine-3'-monophosphate nucleotides, and the respective 5'-monophosphates, were chemically synthesized for standardization of these quantitative procedures. The quantitation of O6-methl- and O6-ethyl-2'-deoxyguanosine was observed to be analytically accurate between one O6-alkyl-2'-deoxyguanosine residue per 10(4) and 10(7) 2'-deoxyguanosines. The limit of detection was less than one O6-alkyl-2'-deoxyguanosine in 10(7) 2'-deoxyguanosine residues in a sample size of 100 micrograms of DNA, i.e., approximately 10 pg of adduct. The quantitation of O6-methyl-2'-deoxyguanosine in the liver DNAs of rats treated with [14C-Me]N-nitrosodimethylamine compared well with values obtained by both 14C and high-pressure liquid chromatography coupled with fluorescence detection. Thus, these 32P-postlabeling and nucleotide chromatographic procedures should be useful in monitoring human exposure to methylating and ethylating carcinogens.

Augmented arterial pressure responses to cyclosporine in spontaneously hypertensive rats. Role of cytochrome P-450 3A.

Evidence to support a hypertensinogenic role of family 3A cytochrome P-450 (CYP3A) activity is that troleandomycin, a selective inhibitor of CYP3A, decreases both blood pressure and in vivo corticosterone 6 beta-hydroxylation in spontaneously hypertensive rats (SHR). Renal CYP3A activity is markedly increased in SHR compared with Wistar-Kyoto (WKY) rats. Cyclosporine acutely increases both systolic blood pressure and renal total cytochrome P-450 in SHR. We tested the hypothesis that the augmentation of blood pressure by cyclosporine is mediated by a further increase in renal CYP3A activity. Accordingly, we assessed the effect of troleandomycin administration on cyclosporine-induced systolic blood pressure increase and renal and hepatic microsomal CYP3A activity in SHR. Cyclosporine (5 mg/kg SC) given daily in 11-week-old SHR resulted in substantial augmentation of blood pressure after 6 days. This blood pressure increase was attenuated by troleandomycin (40 mg/kg) given either during or after development of hypertension. Cyclosporine increased renal (60%) but decreased hepatic (25%) microsomal CYP3A activity in SHR. In contrast, cyclosporine failed to produce any detectable increase in either blood pressure or renal CYP3A activity in WKY rats. Troleandomycin completely inhibited renal CYP3A activity measured after cyclosporine treatment of SHR, which correlated with its attenuation of the cyclosporine-induced blood pressure increase. These findings suggest that renal CYP3A could play an important role in acute cyclosporine-induced hypertension.

Technetium-99m-HMPAO SPECT cerebral blood flow study in children with craniosynostosis.

UNLABELLED: Premature closure of cranial sutures (primary craniosynostosis) in children leads to characteristic skull deformities and prevents the constricted brain from growing normally. Although the cause remains unknown, several etiological factors have been cited. Recently, hypovascularity has been reported as a possible cause of craniosynostosis. METHODS: In a prospective study regional cerebral blood flow studies were carried out with 99mTc-HMPAO SPECT in seven children with craniosynostoses. Five preoperative and six postoperative studies were conducted and the results correlated with radiological and surgical findings. RESULTS: Preoperative studies revealed regional hypovascularity in the underlying cerebral hemisphere, corresponding to the fused sutures. Postoperative studies revealed disappearance of these perfusion defects in most cases, indicating normalization of perfusion following surgical decompression. CONCLUSION: This study establishes the presence of cerebral hypovascularity in craniosynostoses and suggests that early surgery and release of craniostenosis is essential to achieve optimum perfusion and brain development.

Renal and hepatic family 3A cytochromes P450 (CYP3A) in spontaneously hypertensive rats.

Troleandomycin (TAO), a selective family 3A cytochromes P450 (CYP3A) inhibitor, decreases enhanced in vivo corticosterone 6 beta-hydroxylation and blood pressure in spontaneously hypertensive rats (SHR). Corticosterone 6 beta-hydroxylation was measured in liver and kidney microsomes, to determine ontogeny and the effect of TAO on CYP3A activity at the organ level. SHR kidney CYP3A activity increased from 4 to 8 weeks, stabilized at 11 and 16 weeks, and was much higher than in control (Wistar-Kyoto, WKY) rats at all ages. Hepatic activity showed less consistency in strain difference. TAO produced a relatively large decrease in renal CYP3A activity compared with liver. Although renal CYP3A mRNA was not present in sufficient quantity for detection by northern blot analysis of total RNA, its presence was demonstrated in SHR by reverse transcriptase-polymerase chain reaction amplification. Correlations between renal CYP3A activity and systolic blood pressure in SHR and WKY rats with variations in age, strain and drug treatment are consistent with the role of the enzyme in the pathogenesis of blood pressure elevation in SHR.

Maternal environment defines blood pressure and its response to troleandomycin in spontaneously hypertensive rats.

Relationship between family-3A cytochrome P-450-dependent (troleandomycin inhibitable) and maternal environmental-dependent systolic blood pressure (SBP) was investigated in spontaneously hypertensive rats (SHR). Adult SHR nursed by foster or natural SHR mothers had indistinguishable SBP. Troleandomycin reduced 50% of Wistar-Kyoto (WKY)-SHR strain difference in SBP. SHR having WKY foster mothers had SBP similar to troleandomycin-reduced SHR levels, which was unaffected by troleandomycin. The two components of SBP elevation appear identical. Because observations of others demonstrated that WKY fostered to SHR show no SBP increase, the maternally dependent/troleandomycin-sensitive component of SBP elevation may reflect epistatic interaction between genes determining maternal differences and offspring sensitivity, respectively.

Synthesis and characterization of oligodeoxynucleotides containing the major DNA adducts formed by 1,6- and 1,8-dinitropyrene.

[reaction: see text] An efficient method for the synthesis of oligonucleotides containing a site-specific DNA adduct formed by the carcinogens 1,6- and 1, 8-dinitropyrene has been developed. Palladium-catalyzed amination provided a straightforward route for the synthesis of aminonitropyrenes which, following separation, were reduced to the nitrosonitropyrenes. The N-hydroxyaminonitropyrene, generated in situ from each nitrosonitropyrene, was used successfully to introduce the dinitropyrene-derived DNA adduct at a defined site in an oligonucleotide.

Graft interposition splenocaval shunt for total or selective decompression of portal hypertension.

A new operation for selective or total decompression of the portal venous system in cases of intrahepatic portal hypertension is described. It involves interposition of a large-caliber Dacron graft between the splenic vein and the inferior vena cava. The graft-interposition splenocaval shunt is performed readily and quickly, satisfying the variable hemodynamic needs of patients with portal hypertension. It can be either selective (S-SCS) or total (T-SCS) from the beginning, or a T-SCS may be converted subsequently to a S-SCS should surgically induced hepatic decompensation supervene. It is less demanding technically than distal splenorenal shunt (D-SRS). The S-SCS conserves portal venous perfusion of the liver, preserves hepatocellular function and architecture at the preoperative levels, avoids precipitation of postshunt portal-systemic encephalopathy, and decompresses gastric-esophageal varices with prevention of further variceal bleeding even better than D-SRS. One hundred percent graft patency has been obtained, and the surgical results have been superior to those following portacaval shunt in patients with large liver blood flow and relative benignity of the liver disease, be it cirrhosis or noncirrhotic portal fibrosis. In patients with advanced cirrhosis, variceal bleeding, and small liver blood flows, T-SCS would be indicated. Patients of this category obtained inferior surgical results and had operative deaths (16.7%) following S-SCS. The concept of the operation has merits and deserves further evaluation.

Direct splenocaval shunt for selective decompression of portal hypertension in children.

A new operation for selective decompression of portal hypertension in children with diminutive splenic veins is desired. The operation, direct splenocaval shunt (S-D-SCS), produces transplenic decompression of gastric-esophageal varices without interfering with the existing portal flow status in any significant measure. The proximal free end of the inferior vena cava (IVC) is joined to the side of the splenic vein, which is ligated on the hepatic side of the anastomosis. Addition of partial gastric devascularization completes the operation. Technically the operation is simple and easily executable. Because the IVC is utilized in creation of the shunt, anastomoses as large as 1.72 +/- 0.45 cm in diameter are obtained with splenic veins of less than 1 cm in diameter. S-D-SCS was performed in 10 children with a mean age of 9.25 +/- 3.36 years and a mean splenic vein size of 8.2 +/- 2.25 mm in diameter. Shunt thrombosis occurred in one patient who died. Nine patients survived the operation and obtained class A surgical results over a follow-up period of 7 to 12 months. None rebled, developed postshunt encephalopathy (PSE), or manifested laboratory evidences of protein intolerance. Insignificant alterations were brought about in liver blood flow (EHBF) and sinusoidal pressure (CSP); portal blood flow to the liver was maintained; and liver function tests were preserved at preoperative levels. The surgical results were superior to those following mesentericocaval and portacaval shunts in our earlier series of children with comparable mean age, body weight, and postoperative interval when studied functionally. About 30% of all of the shunt patients died of liver failure within weeks or months after the operations, and an additional 30% of the patients developed clinically significant PSE over variable periods of follow-up. These high mortality and morbidity rates were preceded by significant reductions in EHBF and CSP and concomitant precipitation of liver function abnormalities.