Observations on the development of stunting in children of the Khon Kaen region of Thailand.

A cohort of children in North-East Thailand was followed from birth to 2 years of age in an attempt to throw light on factors determining the development of stunting in linear growth. By 2 years the group as a whole had an average deficit in height of nearly -2 standard deviations. Those index children whose sibs were stunted had larger deficits than those with normal sibs. Their mothers were also shorter and lighter. These findings suggest that it is possible to think in terms of stunted families. No differences were identified in socio-economic factors and the prevalence of infection was in general low. Dietary intakes estimated by 24-hour recall, supplemented at 1 and 2 years by 24 h weighing, were satisfactory for most nutrients except iron, calcium and niacin. Intakes of Ca and P were lower in the more stunted children. A number of variables were measured in urine and blood at 1 and 2 years but few relationships could be established with the degree of stunting. Excretions of calcium and phosphorus showed weak negative correlations with height. On average the serum concentration of calcium was satisfactory but that of phosphorus was somewhat low. Concentrations of somatomedin C, thyroxin and vitamin D were within reported normal ranges, with no relation to the degree of stunting. From a comparison of the linear growth of these children with the results of other reports from Thailand it is suggested that environmental factors have produced stunting in the cohort as a whole, but the cohort is essentially homogeneous, showing within it a normal range of genetic variation. If that is so, major differences in intake or biochemistry between the taller and shorter children would not be expected. The problem remains of why the group as a whole is stunted. This is the first systematic attempt to assess biochemical factors that may be related to stunting in Third World children; these results are essentially negative, although there are hints that point at a possible deficiency of calcium.     

Molecular diagnosis of exocrine pancreatic cancer using a percutaneous technique

Background: The K-ras oncogene is activated by point mutations at codon 12 in most patients with exocrine pancreatic cancer. Mutant-enriched polymerase chain reaction (PCR) amplification can enhance the detection of mutated K-ras. This technique was applied to patients undergoing percutaneous fine-needle aspiration (FNA) biopsy of suspect pancreatic lesions. Methods: Twenty-five patients underwent percutaneous FNA of the pancreas for cytologic and molecular analysis. After preparing cytologic smears, the 22-gauge needle and syringe used for FNA were rinsed in RPMI-1640. The specimen was centrifuged, and DNA was extracted from the supernatant and subjected to mutant-enriched PCR using appropriate mismatched primers that introduce a BstNI restriction endonuclease cleavage site at codon 12 of wild-type, but not mutant, K-ras. After digestion with BstNI, the DNA was reamplified. To increase assay sensitivity, the final five PCR cycles were completed incorporating 5 μCi of (α-32P)dCTP. The DNA was then redigested and subjected to gel electrophoresis and autoradiography. Results: The median amount of DNA retrieved per specimen was 3.33 μg. Mutant K-ras was detected as a band of 143 bps; residual wild-type DNA was seen as a 114-bp fragment. Twenty-one of 25 specimens demonstrated mutated K-ras DNA. Two patients with nondiagnostic cytology results had mutated K-ras DNA; adenocarcinoma of pancreatic origin was confirmed in both cases after pancreatectomy. Conclusion: The molecular diagnosis of pancreatic cancer through identification of mutations in K-ras can be readily performed on specimens obtained by percutaneous FNA. As aggressive multimodality management of this disease becomes more common, pretreatment analysis of molecular determinants may have greater clinical significance. Presented at the 48th Cancer Symposium of The Society of Surgical Oncology, Boston, Massachusetts, March 23–26, 1995.     

Human breast milk exosomes attenuate intestinal damage

Pediatric Surgery International - Human breast milk (HBM), which contains an abundant supply of exosomes, is known to prevent necrotizing enterocolitis (NEC). Preterm infants are commonly given...     

Early Hepatocellular Carcinoma: Pathology, Imaging, and Therapy

Background In 1987, Japanese researchers proposed to define the pathological concept of early hepatocellular carcinoma (HCC). However, there are some conceptual differences between the East and the West in the diagnosis and treatment of early HCC. Methods To provide up-to-date data for making a worldwide consensus, this article has collected six papers focused on the management of early HCC, which were presented in the Fifth International Meeting of “Hepatocellular Carcinoma: Eastern and Western Experiences” in Houston in January 2007. Results In the pathological perspective, the common criteria to discriminate early HCC from dysplastic nodule included hepatocytic invasion of portal triads and septa (stromal invasion). The current imaging modalities such as contrast-enhanced ultrasound (CEUS), computed tomography (CT), and magnetic resonance imaging (MRI) with the use of intravenous contrast material with multiphasic imaging could enhance their ability to accurately characterize early HCC. From the treatment perspective, a single early HCC had a high chance for cure by resection, ablation, or transplantation, which proved to be the earliest clinical entity (Stage 0 HCC). Conclusions Early HCC is characterized by its incipient malignant nature and by an extremely favorable clinical outcome, thereby justifying its definition. Proceedings of the Fifth International Meeting Hepatocellular Carcinoma: Eastern and Western Experiences held in Houston, TX, January 11–13, 2007.     

Biodistribution of paclitaxel and poly(l-glutamic acid)-paclitaxel conjugate in mice with ovarian OCa-1 tumor

Purpose: Poly(l-glutamic acid)-paclitaxel (PG-TXL) is a water-soluble paclitaxel (TXL) conjugate made by conjugating TXL to poly(l-glutamic acid) via ester bonds. In preclinical studies, PG-TXL has shown significant antitumor activity against a variety of solid tumors. To elucidate the relationship between tissue distribution and antitumor efficacy of PG-TXL, we studied and compared the biodistribution of PG-TXL and TXL. Methods: Female C3Hf/Kam mice bearing syngeneic ovarian OCa-1 tumors were injected with either [³H]TXL or PG-[³H]TXL at an equivalent TXL dose of 20 mg/kg. Mice were killed at various times after drug injection, and samples of blood, spleen, liver, kidney, lung, heart, muscle, brain, fat, and tumor were removed and the radioactivity counted. In addition, concentrations of free [³H]TXL released from PG-[³H]TXL in the spleen, liver, kidney, and tumor were analyzed by using high-performance liquid chromatography (HPLC). Whole-body autoradiographs of mice killed 1 day and 6 days after administration of PG-[³H]TXL were obtained to study the intratumoral distribution of PG-TXL. Results: When [³H]TXL was conjugated to polymer, the biodistribution pattern of PG-[³H]TXL differed from that of [³H]TXL. Based on area under the tissue concentration-time curve (AUC) values, tumor exposure to [³H]TXL was five times greater when administered as PG-TXL than as TXL formulated in Cremophor EL/alcohol vehicle. Furthermore, concentrations of free paclitaxel released from PG-[³H]TXL remained relatively constant in tumor tissue, being 489, 949 and 552 ng/g tumor tissue at 5, 48 and 144 h after dosing, respectively. Autoradiographic images of mice injected with PG-[³H]TXL revealed that radioactivity was primarily located in the periphery of the tumor on day 1 after drug administration and was homogeneously diffused into the center of the tumor by day 6. Over the 144-h study period, [³H]TXL concentrations, predominantly as the inactive conjugate, were higher in tissues with a more abundant reticular endothelial system (i.e. liver, kidney, spleen, lung) than in tissues with less abundant or lacking RE systems (i.e. muscle, fat, brain). Both [³H]TXL and PG-[³H]TXL were excreted primarily through the hepatobiliary route, with a small fraction of each drug (5% and 8.7%, respectively) excreted into the urine within 48 h. Conclusions: This study indicates that the distribution to tumor tissue was enhanced when [³H]TXL was administered as a macromolecular conjugate, and that free TXL was released and maintained within the tumor for a prolonged period. Thus, the antitumor activity of PG-TXL observed in preclinical studies may be attributed in part to enhanced tumor uptake of PG-TXL. Received: 22 December 1999 / Accepted: 24 May 2000     

Hemodynamic and morphologic changes after portal vein embolization: differential effects in central and peripheral zones in the liver on multiphasic computed tomography

OBJECTIVE: To evaluate hemodynamic and morphologic effects in the liver after portal vein embolization (PVE). METHODS: Hepatic computed tomography scans of 7 patients who had undergone preoperative PVE were retrospectively reviewed. Pre- and post-PVE computed tomography densities were evaluated for the unenhanced, late arterial, and portal venous phases in peripheral and central hepatic regions and in the 3 main hepatic veins. Relative changes in areas in these regions were assessed in 5 evaluable patients with serial post-PVE scans. RESULTS: During the late arterial phase, enhancement was significantly higher after PVE than it was before PVE in the peripheral hepatic regions, and it was higher in the peripheral regions than in the central regions. Enhancement was also significantly higher in the right main hepatic vein than in the middle and left hepatic veins during the late arterial phase. The ratio of areas of the peripheral/central regions decreased significantly after PVE. CONCLUSIONS: Zonal enhancement in the late arterial phase changed after PVE and seemed to be associated with differential parenchymal atrophy. We speculate that the hepatic arterial supply increases peripherally and that peribiliary/periportal plexuses maintain the portal supply centrally.