Prevalence and trends in the antimicrobial susceptibility pattern of Salmonella enterica serovars Typhi and Paratyphi A among children in a pediatric tertiary care hospital in South India over a period of ten years: a retrospective study.

The aim of this study was to determine the prevalence and trends in the antimicrobial resistance of typhoidal salmonellae in children and adolescents at a pediatric tertiary care hospital in South India. Typhoidal salmonellae were isolated from 483 of the 77,713 blood cultures received during the ten-year study period (2007-2016). Isolates were speciated by conventional biochemical reactions and serotyping. Antimicrobial susceptibility testing was performed and interpreted according to the British Society for Antimicrobial Chemotherapy (BSAC)/European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. The overall blood culture isolation rates of Salmonella enterica serovars Typhi and Paratyphi A in children were 0.5% (408 cases) and 0.1% (73 cases), respectively, with the highest isolation rates in school [299 (61.9%)] and preschool children [113 (23.4%)]. A decreasing prevalence of enteric fever was seen from 2012 to 2015, with a sudden surge in 2016. From 2011 onwards, a high fluoroquinolone resistance (90-100%) was observed. Multidrug resistance was observed in only four (0.9%) S. Typhi isolates. 100% susceptibility to third-generation cephalosporins and azithromycin was noted. Enteric fever as seen in a pediatric tertiary care hospital in India affects children and adolescents of all age groups, with greater isolation rates in school children, followed by those in preschool years, calling for targeted interventions against these age groups. The study findings support the use of third-generation cephalosporins and azithromycin as first-line therapy and ampicillin and co-trimoxazole as step-down therapy in pediatric enteric fever. However, continued local surveillance should be done to detect antimicrobial resistance trends to optimize treatment.

Evaluation of different culture methods for the diagnosis of peritonitis in patients on continuous ambulatory peritoneal dialysis.

A total of 170 continuous ambulatory peritoneal dialysis (CAPD) fluids were processed by various culture methods, including direct inoculation of the centrifuged sediment, inoculation into automated blood culture bottles, water lysis, Tween-80 incorporated blood agar, and Triton-X treatment of the specimen. Of 170 CAPD fluids, 127 showed the growth of bacteria/fungi. Sixty-three fluids showed growth by all methods, the water lysis alone detected 24 additional positive cultures, while Tween-80 blood agar and Triton-X yielded 30 additional positive cultures. A combination of water lysis, Tween-80 blood agar and Triton-X treatment of the CAPD fluid is recommended for diagnosis of CAPD peritonitis in resource-limited settings.

Diagnosis of spontaneous bacterial peritonitis: Role of tween 80 and triton X in ascitic fluid cultures.

A patient with alcoholic cirrhosis of the liver, portal hypertension with hepatic encephalopathy and spontaneous bacterial peritonitis (SBP) was admitted in an obtunded condition. Attempts at delineating the aetiology of the SBP using conventional cultures as well as automated systems were not successful. The use of non-anionic surfactant agents such as Tween 80-incorporated blood agar and Triton X treatment of the specimens facilitated the growth of Klebsiella pneumoniae from the ascitic fluid, which otherwise would have been concluded to represent culture-negative neutrocytic ascites. Thus, the use of the aforementioned agents could be explored in elucidating the aetiology of body cavity infections when conventional methods fail.

Modified PAP method to detect heteroresistance to vancomycin among methicillin resistant Staphylococcus aureus isolates at a tertiary care hospital.

This study was an attempt at developing, establishing, validating and comparing the modified PAP method for detection of hetero-vancomycin resistant Staphylococcus aureus (h-VRSA) with the routine antimicrobial susceptibility testing (using the BSAC standardized disc diffusion method), minimum inhibitory concentrations of vancomycin using standard E-test methodology and the Hiramatsu's screening method. A total of 50 methicillin resistant Staphylococcus aureus obtained from various clinical specimens, along with the Mu 3 and Mu 50 strains as controls, were studied. No VRSA isolates were obtained. However, four of the test strains were positive by the Hiramatsu's screening method, of which only one isolate could be confirmed by the modified PAP analysis method. This isolate was a coloniser from the drain fluid of a liver transplant recipient. The sensitivity, specificity, positive predictive value and the overall efficiency of the Hiramatsu's screening method with the modified PAP analysis as the gold standard were found to be 100, 93.8, 25 and 94%, respectively. It is very essential for clinical laboratories to screen for h-VRSA, given the increasing use of glycopeptide antibiotics in therapy and the potential for failed therapy in patients infected with these strains.

Cyclosporiasis in an infant.

This report describes cyclosporiasis in a seven month old infant who presented with incessant crying and refusal of feeds. The routine modified ZN stained smears showed the oocysts of Cyclospora when all other tests failed to reveal enteric pathogens. The need for the clinical laboratory to screen faeces samples for all possible pathogens in a given clinical situation needs to be emphasized.

L-carnitine moderately improves the exercise tolerance in chronic stable angina.

OBJECTIVES: To study the safety and efficacy (with reference to exercise ECG testing) of oral L-carnitine in chronic stable angina. METHODS: Forty-seven patients, 30 men and 17 women, aged 56 +/- 8 years, were randomized to receive L-carnitine (n = 28) or placebo (n = 19) in the dose of 2 g/day for 3 months. The adjuvant treatment was not changed during the study. Patients were evaluated by computerized stress test (CST) done at the beginning and end of the trial. The parameters assessed were exercise duration, time to onset of ST changes, total ST score at peak exercise, rate-pressure product at peak exercise, and time needed for the ST changes to recover to baseline. RESULTS: The two groups were comparable at the beginning of the study. There was no change in the CST parameters in the placebo group at the end of 3 months. In the L-carnitine group there was a statistically significant improvement in the exercise duration from 7.8 +/- 2.2 min to 8.6 +/- 1.8 min (p = 0.006) and in the time needed for the ST changes to revert to baseline from 7.2 +/- 3.9 min to 5.7 +/- 3.8 min (p = 0.019). No change was noted in the time to onset for ST depression, ST score and double product. There were no systemic adverse effects or coronary events in either group. CONCLUSION: Oral L-carnitine is safe and moderately improves the duration of exercise and time to recovery of ST changes in patients with chronic stable angina.

Brain extracellular levels of the putative antipsychotic CI-1007 and its effects on striatal and nucleus accumbens dopamine overflow in the awake rat.

The compound CI-1007 (R-(+)-1,2,3,6-tetrahydro-4-phenyl-1 [(3-phenyl-3-cyclohexen-1-yl)methyl]pyridine maleate) has been identified as a partial dopamine agonist and putative antipsychotic in in-vitro and in-vivo neurochemical, neurophysiological and behavioural tests. By use of microdialysis in conjunction with high-performance liquid chromatography (HPLC) with electrochemical detection, the effects of the drug on brain dopamine release, previously observed in anaesthetized animals, were shown to occur in awake animals also. Detection of peripherally administered CI-1007 in the brain, i.e. evidence of the drug's ability to penetrate the blood-brain barrier, was achieved by use of in-vivo brain microdialysis in awake, freely moving rats and capillary HPLC in combination with tandem mass spectrometry (HPLC/MS/MS). Intravenous administration of CI-1007 (40 mg kg-1) significantly inhibits dopamine release in the nucleus accumbens, a region associated with dopamine hyperactivity in schizophrenia, while having a non-significant impact on the striatal dopamine neurotransmission which is critical to regular motor function. The differential neurochemical profile of the drug indicates its potential usefulness in treating positive disease symptoms and implies that its extrapyramidal side effects are lower than those of typical antipsychotics.

Microdialysis and SPECT measurements of amphetamine-induced dopamine release in nonhuman primates.

The competition between endogenous transmitters and radiolabeled ligands for in vivo binding to neuroreceptors might provide a method to measure endogenous transmitter release in the living human brain with noninvasive techniques such as positron emission tomography (PET) or single photon emission computerized tomography (SPECT). In this study, we validated the measure of amphetamine-induced dopamine release with SPECT in nonhuman primates. Microdialysis experiments were conducted to establish the dose-response curve of amphetamine-induced dopamine release and to document how pretreatment with the dopamine depleter alpha-methyl-para-tyrosine (alpha MPT) affects this response. SPECT experiments were performed with two iodinated benzamides, [123I]IBZM and [123I]IBF, under sustained equilibrium condition. Both radio-tracers are specific D2 antagonists, but the affinity of [123I]IBZM (KD-0.4 nM) is lower than that of [123I]IBF (KD 0.1 nM). With both tracers, we observed a prolonged reduction in binding to D2 receptors following amphetamine injection. [123I]IBZM binding to D2 receptors was more affected than [123I]IBF by high doses of amphetamine, indicating that a lower affinity increases the vulnerability of a tracer to endogenous competition. With [123I]IBZM, we observed an excellent correlation between reduction of D2 receptor binding measured with SPECT and peak dopamine release measured with microdialysis after various doses of amphetamine. Pretreatment with alpha MPT significantly reduced the effect of amphetamine on [123I]IBZM binding to D2 receptors, confirming that this effect was mediated by intrasynaptic dopamine release. Together, these results validate the use of this SPECT paradigm as a noninvasive measurement of intrasynaptic dopamine release in the living brain.

Prospective angiographic study of the abnormalities of systemic venous connections in congenital and acquired heart disease.

UNLABELLED: Angiographic definition of systemic venous connections was obtained prospectively in 780 consecutive patients with congenital heart disease and 102 patients with acquired valvular heart disease undergoing cardiac catheterization. Attempts were made to enter the innominate vein and perform a balloon occlusion angiogram in each patient. In patients with congenital heart disease, bilateral superior vena cava were present in 32/771 patients (approximately 4%) with levocardia and 3/9 patients with dextrocardia. Among patients with bilateral superior vena cava (n = 35), an innominate vein of variable size that could be entered was present in six patients. Small tributaries connecting the right and left superior vena cava were found and entered in six patients. The superior vena cava was entered via its connection to morphologic left atrium in five patients and via the coronary sinus in 17 patients. Abnormalities of the inferior vena cava were seen in 7/780 patients. The following abnormalities of the inferior vena cava were noted: azygous continuation of rightsided inferior vena cava in levocardia -- 3 patients, hemiazygos continuation of the leftsided inferior vena cava in levocardia -- 1 patient, azygos continuation of the leftsided inferior vena cava in dextrocardia -- 1 patient, interruption of inferior vena cava below the liver with a plexus of veins joining the azygos vein -- 1 patient, and an inferior vena cava draining into the leftward aspect of the common atrium -- 1 patient. Abnormalities of the systemic venous connections were seen in 2/102 patients with acquired heart disease: bilateral superior vena cava in 1 patient and bilateral inferior vena cava in 1 patient. CONCLUSIONS: Abnormalities of systemic venous connections were seen in approximately 5% patients with congenital heart disease and approximately 2% patients with acquired heart disease. Small tributaries or an innominate vein of variable size often connect left and right superior vena. Contrast material can be injected into these connections to document the presence of bilateral superior vena cava.

Serotonin-mediated increase in prefrontal cortex dopamine release: pharmacological characterization.

Interactions between serotonin (5-HT) and dopamine (DA) neuronal systems in the prefrontal cortex (PFC) may be important in the pathophysiology of cognitive disorders such as schizophrenia. We have examined the effect of 5-HT, applied locally through a microdialysis probe, on extracellular DA in the PFC, and compared the response to that observed in the striatum. 5-HT in concentrations of 1 to 10 microM increased extracellular DA dose-dependently to a greater extent in the PFC than in the striatum. The PFC response was pharmacologically characterized to determine the 5-HT receptor subtype mediating the increase in DA levels. The coperfusion of selective 5-HT2A and 5-HT3 antagonists MDL 100,907 ((R-(+)-(2,3-dimethoxyphenyl)-1-[2(4-flourophenylethyl)]-4- piperidine-methanol) and MDL 72222 (3-tropanyl-3,5-dichlorobenzoate), respectively, with 5-HT failed to significantly attenuate the 5-HT induced increase of extracellular DA. Furthermore, the local application of the 5-HT2A/2C agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl aminopropane did not yield an increase in extracellular DA. On the other hand, coperfusion of the selective 5-HT1B/1D antagonist GR 127935 (N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2'-methyl-4'-(5-methyl-1 ,2,4-oxadiazol-3-yl)-[1,1-biphenyl]-4-carboxamide)) with 5-HT completely blocked the effect of 5-HT alone. Infusion of the selective 5-HT1B agonists CP 93,129 (3-(1,2,5,6-tetrahydro-4-pyridyl)pyrrolo[3,2-b]pyrid-5-one) and CP 94,253 (3-(1,2,5,6-tetrahydro-4-pyridyl)-5-propoxypyrolo[3,2-b]pyridine) resulted in a significant increase in extracellular DA and the effect of CP 93,129 was attenuated by coperfusion of GR 127935. The results obtained demonstrate a functional interaction between DA and 5-HT pathways in the PFC, with evidence of potential mediation by the 5-HT1B receptor subtype.

Cocaine and cocaethylene: effects on extracellular dopamine in the primate.

Cocaine and cocaethylene (a psychoactive metabolite of concurrent cocaine and ethanol consumption) were studied in the anesthetized vervet monkey. The ability of each to elevate extracellular DA in the caudate nucleus was assessed using microdialysis probes acutely lowered through chronic guide cannulae. Blood samples were also collected to determine plasma levels of the two drugs. Doses of 1.5 mumol/kg cocaine (equivalent to 0.5 mg/kg cocaine-HCl) and cocaethylene were administered intravenously. Microdialysis and blood samples were collected at 5-min intervals immediately following drug administration. Both drugs caused a maximal four-fold increase in extracellular DA during the 5- to 10-min period following drug administration. This is the first report of cocaine (and cocaethylene) induced alterations in extracellular DA in primates. The abilities of cocaine and cocaethylene to produce euphoria are being compared in ongoing clinical research studies. The potential use of these results for interpreting the neurochemical basis of any differences in those studies is discussed.

Tryptophan pretreatment augmentation of p-chloroamphetamine-induced serotonin and dopamine release and reduction of long-term neurotoxicity.

The impact of tryptophan (TRP) pretreatment on the neurochemical effects of p-chloroamphetamine (PCA) was investigated. The neurotoxic effects of PCA on serotonin (5-HT) neurons, the acute effects of PCA on extracellular 5-HT and dopamine (DA), and the displacement by PCA of whole blood 5-HT were examined. TRP pretreatment (400 mg/kg of the methyl ester) significantly reduced the long-term (1 week) decrease in tissue 5-HT resulting from PCA (2 mg/kg, i.p., of the hydrochloride salt) in the prefrontal cortex and striatum, but not in the dorsal hippocampus. Microdialysis studies in awake animals showed that this pretreatment regimen resulted in augmented PCA-induced increases in extracellular 5-HT (4-fold) and DA (2-fold). TRP pretreatment also resulted in increased displacement of 5-HT from whole blood. The implications of these results toward possible mechanisms of action of PCA-induced neurotoxicity are discussed.

Effect of new diamidines against Leishmania donovani infection.

The impact of interamidine distance on antileishmanial activity of new aryldiamidines have been evaluated against amastigotes of L. donovani in hamster. Of the 20 compounds tested, only four (2,8-diamidino-9,10-dihydrodibenzoxepin; 2,7-diamidinoxanthone; 2,7-diamidinothioxanthone and 2,7-diamidinoxanthene) showed significant inhibition (more than 80%) of multiplication of amastigotes in spleen. The interamidine distance in the structure appears to have bearing on antileishmanial activity. The observations made are likely to evoke new understanding on the structure activity relationship of diarylamidines.

Synthesis of substituted 1-hydroxy-2-naphthanilides as potential cestodicidal agents.

A series of substituted 1-hydroxy-2-naphthanilides 4--14 has been synthesized by treating 1-hydroxy-2-naphthoic acids 2 with substituted anilines 3. The nitronaphthanilides, on reduction and subsequent treatment with thiophosgene, gave the corresponding substituted 2-naphthanilide isothiocyanates 30--33. Substitution of the chlorine of 8 by various cyclic amines gave 3'-nitro-4'-substituted 1-hydroxy-2-naphthanilides 15--21. Various 3-aryl-4-oxo-2,3-dihydro-1,3-naphthoxazine-2-thiones 34-43 and 3 aryl-2,4-dioxo-2,3-dihydro-1,3-naphthoxazines 44--51 have been prepared by reacting the corresonding naphthanilides with thiophosgene and ethyl chloroformate, respectively. All the compounds were tested for their cestodicidal activity against Hymenolepis nana infection in rats; 30 was found to be the most active compound of the series, showing 100% clearance of infection at a single oral dose of 7.5 mg/kg.