A Competency-based Model of Child Depression: A Longitudinal Study of Peer, Parent, Teacher, and Self-evaluations

In a two-wave longitudinal study of third and sixth graders ( N = 617), we obtained self-reports of depression and peer, teacher, parent, and self-reports of competence in five domains: academic, social, attractiveness, conduct, and athletic. Competency evaluations by others predicted change in self-perceived competence over time for girls, but not for boys. Depression predicted change in self-perceived competence over time for boys but not for girls. Among girls, the relative importance of parent, teacher, and peer appraisals shifted from third to sixth grade. For both boys and girls, self-perceptions of competence predicted change in depression scores over time. Furthermore, self-perceived competencies mediated the relation between competency appraisals by others and children's self-reported depression. Results are interpreted in light of a competency-based model of child depression.     

Adenoid Cystic Carcinoma of the Salivary Glands: A Review of 10 Years

A retrospective analysis was performed of 50 patients with adenoid cystic carcinoma who were seen in the Department of Radiation Oncology, University of Witwatersrand, Johannesburg, South Africa, in the past 10 years. There were 25 men and 25 women with a mean age of 52 years (age range, 21 to 88 years). Five patients had metastatic disease, and 17 had neural invasion. Thirty-four patients had surgery (11, complete; 23, microscopic residual). Sixteen patients had radiotherapy as initial management. The disease-free survival was 26%, overall survival was 29%, and local control was 30% at 10 years. Most recurrences occurred in the first 3 years. Nine patients had metastasis following treatment. The mean survival after metastasis was 15 months. Seven prognostic variables were analyzed using the log-rank test. There was no impact of age, site, type of salivary gland (major vs. minor), tumor stage, node positivity, or neural invasion on disease-free survival, overall survival, or local control. Extent of surgical resection (complete vs. microscopic residual) had a significant impact on disease-free survival and local control (P < 0.05) but no impact on overall survival (P > 0.05) because of the slow-growing nature of these tumors. Similarly, patients who had microscopic residual after surgery and were treated with radiotherapy did better than those who had biopsy and radiotherapy, although this was not significant statistically (P > 0.05). Thus, whenever possible, every attempt must be made to remove all microscopic tumor by surgery. Addition of postoperative radiotherapy with high-energy photons did not improve the locoregional control or survival in our series. There is a place for neutrons in the treatment of adenoid cystic carcinomas in advanced cases of inoperable or recurrent tumors, as a review of literature shows.     

Nutritional origins of insulin resistance: a rat model for diabetes-prone human populations

While there has been little success identifying the genetic bases of noninsulin-dependent (type-2) diabetes, current epidemiological data and animal models implicate fetal undernutrition in the development of type-2 diabetes. We examined the effects of fetal undernutrition on insulin responses and glucose tolerance in adulthood in genetically normal rats. Control rats were adequately nourished in utero and consumed nutritionally adequate (N) diets throughout life. Experimental rats (F1 generation) were undernourished in utero and consumed either N or high-energy, high-fat (HF) diets postweaning. The offspring of the experimental rats (F2 generation) received the respective diets of their parent. Body weights of experimental F1 rats at d 4 were 40% less than that of control pups, and they remained significantly smaller than controls throughout adulthood. The experimental F1 rats consuming N diets postweaning had a reduced insulin response (-30%) at 30-min postglucose challenge in adulthood (P > 0.05). However, their offspring (F2 generation) displayed a markedly elevated insulin response [+80% at 30 min (P < 0.05) and + 230% at 120 min (P < 0.001) postglucose challenge]. The insulin response of the F2 generation rats fed the high-energy, HF diet was even more pronounced [+130% at 30 min (P < 0.003) and + 250% at 120 min (P < 0.001) postglucose challenge]. Thus, undernourishment in utero produces striking insulin resistance in genetically normal, well-nourished second-generation rats.     

Phase II trial of edatrexate plus carboplatin in metastatic non-small-cell lung cancer: a Southwest Oncology Group study

Background: Edatrexate and carboplatin are each active single agents in the treatment of non-small-cell lung cancer (NSCLC). Preclinical studies in NSCLC lines have demonstrated schedule-dependent synergy of edatrexate followed by carboplatin. In a phase I trial, we demonstrated the tolerability of this combination, the ability of ice-chip cryotherapy to ameliorate dose-limiting mucositis, and promising activity in NSCLC. This phase II trial (SWOG 9207) was undertaken to investigate the efficacy of this regimen in stage IV NSCLC. Methods: A total of 24 patients with stage IV disease were accrued to this Southwest Oncology Group (SWOG) multicenter study. Treatment consisted of edatrexate 80 mg/m² (50% dose on day 8) intravenously weekly for 5 weeks, then every other week, and carboplatin 350 mg/m² every 28 days. Results: Of the 24 patients, 23 were assessable for toxicity and response; one was ineligible for study entry. Myelosuppression was the most significant toxicity; grade 3–4 neutropenia was seen in 8/23 patients. Two patients died of neutropenic sepsis during the first cycle of therapy, in both instances associated with the presence of pleural effusions. Although mild mucositis was common, it was dose-limiting (grade 3) in only three patients. Objective response was observed in 3/23 patients (13%). The median survival time was 7 months, and 30% of patients remained alive at one year. Conclusions: This study suggests that ice-chip cryotherapy is effective in reducing the severity of mucositis typically associated with this edatrexate schedule of administration. However, unexpectedly severe myelosuppression resulted in death from neutropenic sepsis in two patients with third space fluid collections, leading to a protocol amendment to exclude such patients from study entry. Furthermore, response and median survival with this dose schedule of edatrexate and carboplatin do not appear to be improved compared to other chemotherapeutic regimens tested by SWOG in this patient population. Received: 12 August 1996 / Accepted: 8 May 1997     

Antibody-directed enzyme prodrug therapy: pharmacokinetics and plasma levels of prodrug and drug in a phase I clinical trial

Antibody-directed enzyme prodrug therapy (ADEPT) was administered to ten patients in a phase I clinical trial. The aim was to measure plasma levels of the prodrug 4-[(2-chloroethyl)(2-mesyloxyethyl) amino] benzoyl-l-glutamic acid (CMDA) and the bifunctional alkylating drug (CJS11) released from it by the action of tumour-localised carboxypeptidase G2 (CPG2) enzyme. New techniques were developed to extract the prodrug and drug from plasma by solid-phase adsorbtion and elution and to measure CPG2 activity in plasma and tissue. All extracts were analysed by high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS). CPG2 activity was found in metastatic tumour biopsies but not in normal tissue, indicating that localisation had been successful. The clearing agent SB43-gal, given at 46.5 mg/m², achieved the aim of clearing non-tumour-localised enzyme in the circulation, indicating that conversion of prodrug to drug could take place only at the site of localised conjugate. Plasma prodrug did not always remain above its required threshold of 3 μM for the “therapeutic window” of 120 min after dosing, but the presence of residual prodrug after the first administration of each day indicated that this could be achieved during the remaining four doses over the following 8 h. Despite considerable inter-patient prodrug plasma concentration variability, the elimination half-life of the prodrug was remarkably reproducible at 18 ± 8 min. Rapid appearance of the drug in plasma indicated that successful conversion from the prodrug had taken place, but also undesirable leakback from the site of localisation into the bloodstream. However, drug plasma levels fell rapidly by at least 50% at between 10 and 60 min with a half-life of 36 ± 14 min. Analysis of the plasma extracts by LC/MS indicated that this technique might be used to confirm qualitatively the presence of prodrug, drug and their metabolites. Received: 21 July 1996 / Accepted: 20 January 1997     

Effect of composition of ruminally-infused short-chain fatty acids on net fluxes of nutrients across portal-drained viscera in underfed ewes

Four ewes, each fitted with a rumen cannula and with catheters in the mesenteric artery and portal and mesenteric veins, received continuous intrarumen infusions of water or of short-chain fatty acids (SCFA). SCFA infusions were isoenergetic (83 kJ/h) and provided rumen molar proportions (acetate:propionate:butyrate) of 70:20:10, 50:40:10 or 50:20:30. The rumen SCFA production rate with the basal diet was 90.0, 23.1 and 8.8 mmol/h for acetate, propionate and butyrate respectively. Portal net fluxes indicated that 74, 67 and 22-30% of infused acetate, propionate and butyrate respectively, reached the portal vein. Portal net release of beta-hydroxybutyrate increased with SCFA infusions, irrespective of the amount of butyrate infused. Portal net release of lactate decreased with high-butyrate infusion. Portal net uptake of glucose increased with the SCFA infusions. In ewes infused with water, a portal net uptake of total amino acids (AA) was observed. SCFA infusions decreased the uptake of nonessential AA (glutamate, glycine, but not glutamine) and increased the net release of tyrosine and essential AA (isoleucine, leucine). Portal net fluxes of AA were similar with both high-acetate and high-propionate infusions. Lower net uptake of glutamine and net release of most essential AA and some nonessential AA were observed with the high-butyrate infusion. Energetic summation of portal net release was not significantly different between the three SCFA infusions, although it tended to be lower with high-butyrate infusion. This may be related to the higher trophic effect of butyrate on the digestive mucosa.     

Hypoglycémie hyperinsulinémique persistante du nouveau-né et du nourrisson

Persistent hyperinsulinemic hypoglycaemia of infancy (PHHI) is the most frequent cause of hypoglycaemia in infancy. Clinical presentation is heterogeneous, with variable onset of hypoglycaemia and response to diazoxide, and presence of sporadic or familial forms. Underlying histopathological lesions can be focal or diffuse. Focal lesions are characterised by focal hyperplasia of pancreatic islet-like cells, whereas diffuse lesions implicate the whole pancreas. The distinction between the two forms is important because surgical treatment and genetic counselling are radically different. Focal lesions correspond to somatic defects which are totally cured by limited pancreatic resection, whereas diffuse lesions require a subtotal pancreatectomy exposing to high risk of diabetes mellitus. Diffuse lesions are due to functional abnormalities involving several genes and different transmission forms. Recessively inherited PHHI have been attributed to homozygote mutations for the beta-cell sulfonylurea receptor (SUR1) or the inward-rectifying potassium-channel (Kir6.2) genes. Dominantly inherited PHHI can implicate the glucokinase gene, particularly when PHHI is associated with diabetes, the glutamate dehydrogenase gene when hyperammonaemia is associated, or another locus.     

Tuberous sclerosis complex and Wolff-Parkinson-White syndrome

This report highlights the association between tuberous sclerosis and Wolff-Parkinson-White syndrome. Ten patients with concurrent diagnoses of Wolff-Parkinson-White syndrome and tuberous sclerosis were identified. Wolff-Parkinson-White syndrome presented early in life, nine cases being diagnosed in the first year. Eight of the 10 cases were male. In eight cases, the syndrome was associated with supraventricular tachycardias, and in nine with cardiac rhabdomyomata. One child died from cardiac failure secondary to obstruction of the left ventricular outflow tract by a rhabdomyoma. Five of nine survivors showed resolution of Wolff-Parkinson-White syndrome on follow up. The accessory pathway was localised in nine patients from surface electrocardiograms: six children had left sided pathways and three had right sided pathways.