Improved Diagnostic Sensitivity of Bowel Disease of Prematurity on Contrast-Enhanced Ultrasound

Bowel diseases of prematurity, including necrotizing enterocolitis, are dreaded ailments of neonates. Early diagnosis is difficult, with clinical and radiographic findings often inconclusive. We present a novel use of contrast-enhanced ultrasound in detection of pediatric bowel disease. Early identification of compromised blood flow or an at-risk bowel can be quantitatively detected and monitored. This ability has implications for guidance of emerging therapies, allowing targeting of inflammation. These findings represent an advancement in detection of bowel disease in neonates.     

Erythropoietin deficiency and relative resistance cause anaemia in post-renal transplant recipients with normal renal function

BACKGROUND: Following successful renal transplantation, blood erythropoietin(Epo) levels peak in two phases during the first 2–3 months,and blood haemoglobin/haematocrit (Hb/Hct) levels are restoredto normal in a period of 2–6 months. However, some transplantrecipients continue to remain anaemic in spite of normal graftfunction and in the absence of recognizable causes. The roleof endogenous Epo production in the causation of anaemia insuch patients is poorly understood and has been investigatedin this study. METHODS: Twenty-three post-renal transplant recipients with stable normalrenal function were studied. Eleven of these patients had normalHb/Hct levels (group 1) and served as control for the rest 12patients with anaemia (group 2). Patients included in group2 had no readily recognizable cause for their anaemia. Otherlaboratory and clinical findings were similar in both groups.Patients with erythrocytosis were excluded. Serum Epo levelswere measured in all patients. Five patients in group 2 weretreated with recombinant human erythropoietin (rHuEpo) and theirerythropoietic response was assessed. rHuEpo was discontinuedwhen the target Hb/Hct levels (lowest normal range) were achievedand the patients were followed up for a further period of 9–12months. RESULTS: Five patients in group 1 had normal expected serum Epo levelswhereas the other six patients had inappropriately high serumEpo levels with respect to their Hb/Hct status suggestive ofrelative ‘Epo resistance’. Serum Epo levels in allpatients except two in group 2 were low indicative of ‘Epodeficiency’. The two exceptional patients in group 2 hadhigher serum Epo levels in the presence of anaemia suggestiveof relative ‘Epo resistance’. All five patients treated with rHuEpo responded adequately byachieving normal Hb/Hct levels. Three of them were originally‘Epo deficient’ and they reached target Hb/Hct levelsin a mean period of 4 weeks, requiring a mean cumulative rHuEpodose of 428.3 units/kg. The other two patients with higher initialserum Epo levels, and considered to be ‘Epo resistant’,required an average of 11 weeks of treatment and a mean cumulativerHuEpo dose of 1582.5 units/ kg, indicating an increased Epodemand. On cessation of therapy the Hb/Hct levels fell in allfive patients to pretreatment values in 6 months. CONCLUSIONS: There are important variations in the endogenous Epo productionin renal transplant patients with normal renal function, thecause of which is not clear. Epo deficiency and relative Eporesistance play a causative role for anaemia in some post-renaltransplant recipients with stable normal renal function. Theyrespond adequately to rHuEpo administration.     

The index manic episode in juvenile-onset bipolar disorder: the pattern of recovery.

OBJECTIVE: Recent studies of patients with juvenile bipolar disorder report low rates of recovery and high rates of chronicity. However, we lack data on the short-term outcome. This study examines the pattern of recovery from the index episode in an aggressively treated juvenile sample. METHOD: We assessed 25 subjects (< 16 years) with a diagnosis of mania, using the Diagnostic Interview for Children and Adolescents-Revised) (DICA-R), Young Mania Rating Scale (YMRS), and Children's Global Assessment Scale (CGAS) at intake and at 3 and 6 months. We studied the time taken to recover from the index episode, the level of functioning, and the factors predicting them. RESULTS: After 6 months, 24 (96%) subjects had recovered from the index manic episode. The median time to recovery was 27 days. Total episode length was significantly longer among those with previous affective episodes. CONCLUSIONS: The findings suggest that juvenile-onset mania has high rates of recovery and low rates of chronicity. These differences from the existing literature need further exploration.     

Pheochromocytoma and pregnancy: a case report and review of anesthetic management

PURPOSE: To describe a patient diagnosed with pheochromocytoma in the third trimester of pregnancy and discuss the perioperative and anesthetic management. CLINICAL FEATURES: A 32-yr-old previously healthy woman (gravida 4, para 2) presented to our tertiary care obstetrical hospital at 34 weeks five days gestation with a history of labile blood pressure and severe hypertension. A week prior to admission she began having episodes of severe headache, dizziness, sweating and nausea. On a routine obstetric visit she was noted to be severely hypertensive with a blood pressure of 200/120 mmHg. Biochemical investigations confirmed the diagnosis of pheochromocytoma and magnetic resonance imaging demonstrated a 3 cm x 3 cm right adrenal mass. The patient was invasively monitored in the intensive care unit and treated with alpha- followed by beta-blockade with phenoxybenzamine and metoprolol. A multidisciplinary conference was organized involving endocrinology, anesthesiology, general surgery and obstetrics to determine the most appropriate management of the patient. An uncomplicated laparoscopic adrenalectomy was performed following a period of recovery after an uneventful elective Cesarean delivery. CONCLUSIONS: The primary goals in the management of pheochromocytoma in pregnancy are early diagnosis, avoidance of a hypertensive crisis during delivery and definitive surgical treatment. Timing of surgical resection will depend on the gestational age at which diagnosis is made. Cesarean section is the preferred mode of delivery when the tumour is still present. This case illustrates that with antenatal diagnosis, advanced methods of tumour localization, adequate preoperative adrenergic blockade and team planning, pheochromocytoma in pregnancy can be treated successfully.     

Effects of mono-, di-, and triamines on the N-methyl-D-aspartate receptor complex: a model of the polyamine recognition site.

Systematic series of monoamines, diamines, and triamines were used to define the structural requirements for interaction at the polyamine recognition site of the N-methyl-D-aspartate receptor complex. Effects of amines on binding of [3H]MK-801 to washed synaptic plasma membranes were measured in the presence of L-glutamate and glycine (100 microM each), in the absence or presence of spermine (10 microM). Linear aliphatic monoamines of methylene chain length up to 12 (dodecylamine) did not interact with the polyamine recognition site. Nonspecific inhibition of binding was observed at high concentrations of the longer monoamines. alpha,omega-Diamines of methylene chain length 2 (1,2-diaminoethane, DA2) through 12 (1,12-diaminododecane, DA12) had varying actions, depending on chain length. The shortest diamines (DA2 and DA3) acted as weak partial agonists, enhancing the binding of [3H[MK-801. Intermediate-length diamines (DA4-DA7) were selective polyamine antagonists, having little or no effect on binding of [3H]MK-801 measured in the absence of spermine but inhibiting binding measured in the presence of spermine. The longest diamines tested (DA8-DA12) acted as inverse agonists; they inhibited binding in the absence or presence of spermine, and this inhibition was blocked by the selective polyamine antagonist diethylenetriamine. Computer modeling of conformations of the diamines quantitatively documented that 1) these molecules are flexible and 2) long diamines may easily adopt conformations with inter-nitrogen distances mimicking those of short diamines. The cis and trans isomers of 1,4-diaminocyclohexane are inflexible, conformationally restricted diamines with markedly different actions. The cis isomer was a partial agonist and the trans isomer was an antagonist at the polyamine recognition site. Triamines of general structure NH2(CH2)3NH(CH2)xNH2 (TRI[3,x]), in which x = 3-12, were synthesized and tested for activity at the polyamine recognition site. Despite the large range of size, TRI[3,3] through TRI[3,9] were all fully polyamine agonists of similar potency. TRI[3,10] was a partial agonist, whereas TRI[3,12] inhibited binding of [3H]MK-801. Diethylenetriamine did not attenuate the effect of TRI[3,12]. Based on the results of the radioligand binding studies and the computer analysis, a model of the polyamine recognition site is proposed.     

Comparative uptake and retention of adriamycin andN-benzyladriamycin-14-valerate in human CEM leukemic lymphocyte cell cultures

Summary N-Benzyladriamycin-14-valerate (AD 198) is a new lipophilic adriamycin (ADR) analogue that shows marked therapeutic superiority to ADR in murine tumor model systems yet differs mechanistically from ADR in a number of ways. Among its other properties, AD 198 produces a delayed but profound effect on cell-cycle progression and a pattern of continuing DNA damage in cultured cells briefly exposed to the drug. Using radiolabeled drug forms and radioassays combined with HPLC separation and fluorimetric detection techniques, aspects of drug accumulation, biotransformation, and retention in cultured human CEM leukemic lymphocytes were studied, in part to determine a possible pharmacologic basis for the latent effects seen with this drug. In addition, the cellular pharmacology of AD 198 and ADR were comparatively examined under identical experimental conditions. When CEM cells were incubated with drug at equi-growth inhibitory/minimally cytotoxic concentrations (AD 198, 1.0 M; ADR, 0.1 M), a number of differences were apparent. Under conditions of continuous 24-h drug exposure, a slow cellular accumulation and equilibration was observed with ADR (cell: medium equilibrium, 1:11 after 4–6 h), whereas the uptake of AD 198 was rapid and extensive (cell: medium equilibrium, 3:1 within 30 min). In drug-retention studies, when cells were pretreated at the same drug concentrations as before (AD 198 for 1 h; ADR for 4 h) and then transferred to drug-free media, both compounds re-equilibrated their intracellular drug content with the fresh media, losing about 50% of their respective anthracycline levels. Liquid chromatographic analysis of ADR-treated cultures under both sets of conditions showed the parent drug to be the only intracellular anthracycline species, whereas analysis of AD 198-treated cultures revealed two fluorescent signals corresponding to the parent drug and its 14-deesterified biotransformation product,N-benzyladriamycin (AD 288). Levels of AD 288 rose from 2% of the total intracellular anthracycline content immediately on drug admixture to 61% following 24 h continuous drug exposure and to 69% at 24 h in cells exposed to drug for 1 h and then continued in drug-free media for 24 h. At all times, the balance of the intracellular anthracycline fluorescence was attributable to the parent drug; no ADR was detectable in AD 198-treated cells by either fluorescence detection or radioassay. Thus, AD 198 is not a prodrug form of ADR, and the in vitro effects of this agent, including the latent effects on cell-cycle inhibition and DNA damage seen in cells following short-term drug exposure, can be explained on the basis of the high levels of active parent drug and biotransformation product that accumulate and persist in the cells.Abbreviations ADR adriamycin (doxorubicin) - AD 198 N-benzyladriamycin-14-valerate - AD 288 N-benzyladriamycin - AD 32 N-trifluoroacetyladriamycin-14-valerate - AD 143 N-trifluoroacetyladriamycin-14-0-hemiadipate - AD 41 N-trifluoroacetyladriamycin - [¹⁴C]-AD 198 [benzyl]--methylene-¹⁴C]-N-benzyladriamycin-14-valerate - [¹⁴C]-ADR [14-¹⁴C]-adriamycin - HPLC high-performance liquid chromatography - TLC thin-layer chromatography - DMSO dimethylsulfoxide - S-MEM Eagle's minimum essential medium for suspension culture - PBS phosphate-buffered saline (pH 7.0)     

High HIV prevalence and risk behaviors in men who have sex with men in Chennai, India

OBJECTIVE: To estimate HIV and sexually transmitted disease (STD) prevalence and behavioral risk characteristics of men who have sex with men (MSM) in Chennai, India. METHODS: A cross-sectional population-based random sample survey was conducted in 2001. Randomly selected residents of 30 slums in Chennai were interviewed for behavioral risk factors through face-to-face interviews. Sera and urine were examined for syphilis, HIV-1, gonorrhea, and chlamydia. Logistic regression analyses were used to assess associations between MSM status and HIV infection and to identify risk characteristics of MSM. RESULTS: Of 774 men, 46 reported (5.9%) sex with other men. MSM were more likely to be seropositive for HIV (odds ratio [OR] = 8.57; 95% confidence interval [CI]: 1.83, 40.23) and were more likely to have a history of STD (OR = 2.66; 95% CI: 1.18, 6.02) than non-MSM. Men who used illicit drugs in past 3 months (adjusted odds ratio [AOR] = 4.01; 95% CI: 1.92, 8.41), ever exchanged money for sex (AOR = 3.93; 95% CI: 1.97, 7.84), or were ever tested for HIV (AOR = 3.72; 95% CI: 1.34, 10.34) were significantly more likely to report sex with men. CONCLUSIONS: MSM in Chennai slums are at high risk for HIV. HIV prevention strategies aimed at changing unsafe drug and sexual practices should target the general population of men, with specific attention to areas with high rates of MSM.