The effect of artificial feeding on cholestasis, gallbladder sludge and lithiasis in infants: correlation with plasma cholecystokinin levels

The occurrence of hepatic cholestatis (judged by fasting serum bile acid levels), gallbladder sludge formation and lithiasis (ultrasonography) and their correlation with plasma cholecystokinin (CCK) levels was studied in a group of children on continuous total parenteral nutrition (TPN) (n = 95), and later in 40 of these children on cyclic TPN (cTPN). After resumption of oral feeding, 75 were studied on partial oral feeding (2-4 meals) and 40 on constant rate enteral nutrition (CREN) then 45 on total oral feeding (4-6 meals). Gallbladder sludge occurred in 23% of the children on TPN for 1 month and 32% of those on cTPN for 3 months. On CREN, the sludge rate was unchanged, but dropped significantly (17%) on partial oral feeding, and disappeared in children on total oral feeding. Serum bile acids were abnormal in 80% of children on TPN or cTPN and diminished significantly on total oral feeding only. Plasma CCK levels on TPN, cTPN and CREN were identical to fasting levels of children on total oral feeding. Plasma CCK levels increased significantly 1 h post-prandially during both partial (p < 0.02) and total oral feeding (p < 0.001). There was a significant negative correlation between the gallbladder sludge rate and CCK levels for all methods of feeding. This study demonstrates the frequent occurrence of hepatic cholestasis in infants, and the much lower frequency of gallbladder sludge in children compared to adults on TPN. Plasma CCK levels obtained during the different methods of feeding could explain the reduction and eventual disappearance of sludge following stimulation of CCK secretion by discontinuous feeding.     

Therapy of visceral leishmaniasis in renal transplant recipients intolerant to pentavalent antimonials

Visceral leishmaniasis should be suspected in renal transplant recipients in whom a fever develops of unknown origin. A 53-year-old renal transplant recipient developed pyrexia, hepatosplenomegaly, and pancytopenia 4 years after transplantation. Antileishmaniasis serology was negative, and the diagnosis was confirmed through bone marrow examination. Treatment with glucantine (N-methylglucamine antimoniate) led to acute pancreatitis, and treatment with ketoconazole plus allopurinol for 21 days was effective to eradicate Leishmania donovani.     

Ataque de Nervios and History of Childhood Trauma

Objective: Ataque de nervios is a common, self-labeled Hispanic folk diagnosis. It typically describes episodic, dramatic outbursts of negative emotion in response to a stressor, sometimes involving destructive behavior. Dissociation and affective dysregulation during such episodes suggested a link to childhood trauma. We therefore assessed psychiatric diagnoses, history of ataque, and childhood trauma in treatment-seeking Hispanic outpatients (N = 70). Significantly more subjects with an anxiety or affective disorder plus ataque reported a history of physical abuse, sexual abuse, and/or or a substance-abusing caretaker than those with psychiatric disorder but no ataque. In some Hispanic individuals, ataque may represent a culturally sanctioned expression of extreme affect dysregulation associated with childhood trauma. Patients with ataque de nervios should receive a thorough traumatic history assessment.     

Treatment of oesophageal cancer with preoperative chemoradiotherapy may increase operative mortality

AIMS: This phase II multicentric study evaluates a modified preoperative chemoradiotherapy schedule. METHODS: Patients <75 years with potentially resectable neoplasm were eligible. Treatment included an initial course of CDDP 100 mg/m2 (Day 1) and 5-FU CI 5000 mg/m2 (Days 1-5) followed by 45 Gy (Days 28-63) and 5-FU CI 5000 mg/m2 (Days 28-33), CDDP 75 mg/m2 (Day 56) and 5-FU CI 3750 mg/m2 (Days 56-61). Regional lymph nodes were irradiated. RESULTS: Nineteen patients were studied. Oesophagectomy was performed in 17. Clear margins were achieved in 16 of these. Eight patients showed a pathologic complete response (pCR). One patient died of infection during the preoperative treatment and four died due to acute surgical complications. The study was closed prematurely because of excessive mortality. Median follow-up was 19 months. Local and regional relapse occurred in one and three patients, respectively. Median time and actuarial 3-year of overall survival and progression free rates were 18.6 months and 28%, and 12.7 months and 10.4%, respectively. CONCLUSIONS: This schedule showed a high pCR, resectability and local control rate. Treatment-related mortality limits its clinical applicability, but further investigations are warranted.     

Tamoxifen aziridine binding to cytosolic proteins from human breast specimens is negatively associated with estrogen receptors, progesterone receptors, pS2, and cathepsin-D

[³H]Tamoxifen Aziridine ([³H]TAZ) is a derivative of the antiestrogen tamoxifen that covalently labels the Estrogen Receptor (ER), and perhaps other uncharacterized proteins. In a previous article we described that [³H]TAZ binds to a cytosolic protein from human uterine tissues that shares some, but not all, the ER properties. Here we have extended these studies to [³H]TAZ binding to cytosol proteins from human breast cancer specimens, and studied its quantitative association with other molecular markers and clinico-pathological variables. Cytosols were obtained in hypotonic buffer containing 20 mM molybdate and protease inhibitors, incubated with [³H]TAZ, and subjected to Sucrose Gradient Analysis (SGA). A [³H]TAZ labeled peak that consistently migrated with the 4S fractions was found in most of the assayed cytosols (range of 0 to 1278 fmol/mg p.). The 4S peak of [³H]TAZ was partially inhibited by both estrogens and antiestrogens. When [³H]E₂ was used instead of [³H]TAZ, only an 8S peak was detected. [³H]TAZ was covalently bound to a protein with an apparent MW of 65 kDa, as determined by SDS-PAGE and fluorography. The mean of [³H]TAZ binding was significantly higher in the subgroups of samples classified as ER-, PR-, pS2- or cathepsin D-, than in the respective positive subgroups (P < 0.01 in all the cases). [³H]TAZ binding was not associated with clinico-pathological variables, except that its mean was significantly larger in tumors larger than 5 cm than in smaller tumors. These results, and those previously reported, suggest that: 1) [³H]TAZ labels a cytosolic protein present in human breast cancers and uterine tissues that does not share all the ER properties, and 2) the [³H]TAZ binding by breast cancer cytosols is negatively associated with markers of estrogenic dependency, and its quantification may provide valuable information on antiestrogen responsiveness of a given tumor.