Chromosomal aberrations in human lymphocytes induced in vitro by very low doses of X-rays.

This paper presents results of a collaborative experiment between six laboratories which examined the yields of unstable chromosomal aberrations in human lymphocytes induced in vitro by X-rays over the dose range 0-300 mGy. The work included data points of nominal doses of 0, 3, 5, 6, 10, 20, 30, 50 and 300 mGy. Cells from 24 donors were examined and a total of about 300,000 metaphases were scored. The work was undertaken to determine the limits of sensitivity of the system taking into account variations in scoring data due to inter-donor sample and inter-laboratory effects. Despite the existence of these effects, aberration yields significantly in excess of control values were seen at doses greater than 20 mGy and these were consistent with a linear extrapolation from higher doses. Below 20 mGy the observed dicentric yields were generally lower than background, but not significantly so. Excess acentric aberrations, on the other hand, and centric rings, were higher than the controls but the increase was usually not significant. It is concluded that the statistical uncertainties are such that below 20 mGy this technique cannot distinguish between a linear or a threshold model.     

Appendicitis in the era of ultrasound: Are plain radiographs still useful?

We reviewed plain radiographs of 215 pediatric patients with surgically proven appendicitis to study the value of plain radiography for diagnosis.     

Energetics and evolution: An emerging research domain

The study of energetics is important to human biology because the availability and utilization of food energy influence health, survival, and reproduction. Over the last decade, human biologists, biological anthropologists, and other evolutionary scientists have increasingly come to recognize the importance of energy dynamics in shaping evolutionary processes. Thus far, different lines of energetics research have been conducted largely in isolation from one another. This thematic collection examines topics of evolutionary energetics from several different perspectives, drawing together research from human paleontology, comparative primate and mammalian biology, human population biology, and mathematical modeling. It represents a starting point for further integrative research on human evolutionary energetics. Am. J. Hum. Biol. 14: 547–550, 2002. © 2002 Wiley‐Liss, Inc.     

Congenital supratentorial and infratentorial peripheral neurogenic tumor: a clinical, ultrastructural, and immunohistochemical study

Congenital neoplasms of the central nervous system are extremely rare, although they have been well documented since the earliest reports from the mid-19th century. Medulloblastoma, other primitive neuroectodermal tumors, and various types of gliomas have comprised the majority of cases. This report describes a highly unusual infratentorial and supratentorial tumor presenting as a scalp mass in a neonate who experienced in utero distress. The supratentorial mass extended through a defect in the skull to the parietooccipital lobe, and the infratentorial aspect involved the 9th and 10th cranial nerves in the region of the cerebellopontine angle. A complex spindle cell neoplasm incorporating peripheral nerve sheath and vascular characteristics was further characterized by electron microscopy and immunohistochemistry. Based upon these studies, the tumor was interpreted as a congenital schwannoma with divergent vascular differentiation. The child has been tumor-free for approximately 2 years after the initial operative procedure.     

Adjuvant therapy for adenocarcinoma of the rectum

Surgical resection continues to be the primary curative modality for patients with adenocarcinoma of the rectum. However, local tumor recurrence in the pelvis and/or distant metastasis may occur in spite of complete excision of grossly visible malignant disease. Surgical and pathologic staging can identify a subset of surgically treated rectal cancer patients at high risk for tumor relapse and death. Irradiation and chemotherapy have been used as adjuvant therapy in conjunction with surgery as single modalities and in combination for patients with high risk rectal cancer. Evidence from controlled clinical trials indicates a significant decrease in local tumor recurrence, and a significant improvement in disease-free and overall survival with the use of combined postoperative irradiation and chemotherapy in this setting. A current national clinical trial in the United States of America is studying whether irradiation can be combined with new chemotherapy regimens which have shown significant therapeutic benefit as surgical adjuvant therapy for patients with high risk colon cancer (5FU + levamisole) and for patients with metastatic colorectal cancer (5FU + leucovorin) to further improve the efficacy of surgical adjuvant therapy for adenocarcinoma of the rectum.

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Resumen La resección quirúrgica continúa siendo la modalidad curativa primaria en pacientes con adenocarcinoma del recto. Sin embargo, la recurrencia local del tumor en la pelvis y/o las metástasis distantes puede ocurrir a pesar de la resección completa de la enfermedad maligna macroscópicamente visible. La estadificación operatoria y patológica puede indentificar un subgrupo de pacientes tratados quirúrgicamente con alto riesgo de relapso tumoral y meserte. La irradiación y la quimioterapia han sido utlizados como terapia adyuvante en unión con la cirugía como modalidades únicas y en combinación para pacientes con cáncer rectal de alto riesgo. La evidencia surgida de ensayos clínicos controlados señala una disminución significativa en las tasas de recurrencia tumoral local, y una superación significativa en las tasas globales de sobrevida y de sobrevida libre de enfermedad con el uso de la combinación postoperatoria de irradiación y quimioterapia. Un ensayo clínico nacional que se ejecute en el momento actual en los Estados Unidos investiga si la irradiación puede ser combinada con los nuevos regímenes quimioterapéuticos que han demostrado beneficio significantivo como terapia quirúrgica adyuvante en pacientes con cáncer de colon de alto riesgo (5 FU + levamisol) y en pacientes con cáncer colorrectal metastásico (5 FU + leucovorin) con el propósito de mejorar aún más la eficicacia de la terapia quirúrgica adyuvante en el adenocarcinoma del recto.

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Résumé La chirurgie est le principal moyen thérapeutique de l'adénocarcinome du rectum. La récidive tumorale pelvienne et/ou à distance peut cependant se produire malgré une résection apparemment complète. Un bilan d'extension chirurgical et anatomopathologique peut identifier un sous-groupe de patients susceptible de présenter une récidive ou d'en mourir. La radio-et chimiothérapie ont été préconisées comme traitement adjuvant après l'exérèse chirurgicale, soit seule, soit combinée, chez cez patients à risque. Les résultats de plusieurs essais thérapeutiques semblent indiquer que la radio-et la chimiothérapie combinée à la chirurgie diminuent significativement le taux de récidives locales et améliorent significativement la survie globale et la survie sans maladie. Un essai actuellement en cours aux Etats-Unis étudie si la radiothérapie peut être utilement combinée avec les nouveaux régimes chimiothérapeutiques ayant fait preuve de leur efficacité chez les patients à risque (5FU + lévamisole) ou chez les patients ayant des métastases (5FU + leucovin).

     

Effect of compressive follower preload on the flexion-extension response of the human lumbar spine.

Traditional experimental methods are unable to study the kinematics of whole lumbar spine specimens under physiologic compressive preloads because the spine without active musculature buckles under just 120 N of vertical load. However, the lumbar spine can support a compressive load of physiologic magnitude (up to 1200 N) without collapsing if the load is applied along a follower load path. This study tested the hypothesis that the load-displacement response of the lumbar spine in flexion-extension is affected by the magnitude of the follower preload and the follower preload path. Twenty-one fresh human cadaveric lumbar spines were tested in flexion-extension under increasing compressive follower preload applied along two distinctly different optimized preload paths. The first (neutral) preload path was considered optimum if the specimen underwent the least angular change in its lordosis when the full range of preload (0-1200 N) was applied in its neutral posture. The second (flexed) preload path was optimized for an intermediate specimen posture between neutral and full flexion. A twofold increase in flexion stiffness occurred around the neutral posture as the preload was increased from 0 to 1200 N. The preload magnitude (400 N and larger) significantly affected the range of motion (ROM), with a 25% decrease at 1200 N preload applied along the neutral path. When the preload was applied along a path optimized for an intermediate forward-flexed posture, only a 15% decrease in ROM occurred at 1200 N. The results demonstrate that whole lumbar spine specimens can be subjected to compressive follower preloads of in vivo magnitudes while allowing physiologic mobility under flexion-extension moments. The optimized follower preload provides a method to simulate the resultant vector of the muscles that allow the spine to support physiologic compressive loads induced during flexion-extension activities.     

The measurement of carnitine and acyl-carnitines: application to the investigation of patients with suspected inherited disorders of mitochondrial fatty acid oxidation.

We describe an improved radio-enzymatic method for the measurement of carnitine, short-chain acyl-carnitine and long-chain acyl-carnitine in plasma and tissue. An internal standard, hexadecanoyl-[CH3-3H]-carnitine was synthesised and used to improve the determination of long-chain acyl-carnitine. The between and within batch precisions were 10.4 and 7%, respectively. Control data for neonates, infants, children and adults in the fed and fasted state are documented. In addition we confirm the hypocarnitinaemia associated with pregnancy. Patients with medium-chain acyl-CoA dehydrogenase deficiency were studied during episodes of hypoglycaemia. In both fasted controls and patients there were high concentrations of short-chain acyl-carnitine, however in the latter group there were also low concentrations of free carnitine. We suggest that the monitoring of plasma carnitine and its derivatives is a useful adjunct to the investigation of children suspected to suffer from inherited disorders of mitochondrial beta-oxidation. We also describe a sample preparation procedure suitable for high performance liquid chromatographic analysis of specific acyl-carnitines from urine, plasma and tissue homogenates. The recoveries of acetyl-carnitine, octanoyl-carnitine and hexadecanoyl carnitine from urine were 101.5, 95 and 91% and from plasma 99.5, 91.5 and 85.5%, respectively. Acyl-carnitines (C2-C16) were analysed as their p-bromophenacyl derivatives by reverse-phase high performance liquid chromatography using a ternary gradient of acetonitrile/water/triethylamine phosphate. We report ten patients who excreted octanoyl-carnitine, hexanoyl-carnitine and in some cases a small amount of decanoyl-carnitine. In most of these cases suberylglycine and dicarboxylic acids were also detected by GC/MS. We had access to cultured fibroblasts from five of these patients and were able to demonstrate medium-chain acyl-CoA dehydrogenase deficiency by direct enzyme assay.     

Liver transplantation for erythropoietic protoporphyria liver disease.

In erythropoietic protoporphyria (EPP), there is excessive production of protoporphyrin, primarily in the bone marrow, resulting in increased biliary excretion of this heme precursor. Some patients will develop progressive liver disease that may ultimately require liver transplantation. However, excessive production of protoporphyrin by the bone marrow continues after transplantation, which may cause recurrent disease in the allograft. This study was performed to define post-transplant survival, the risk of recurrent disease, and specific management issues in patients transplanted for EPP liver disease. The patients studied consisted of twelve males and eight females, with an average age of 31 (range, 13-56) years at the time of transplantation. The estimated maximum MELD score prior to transplant was 21 (range, 15-29). Unique complications in the perioperative period were light induced tissue damage in four patients and neuropathy in six, requiring prolonged mechanical ventilation in four. Patient and graft survival rates were 85% at 1 year, 69% at 5 years, and 47% at 10 years. Recurrent EPP liver disease occurred in 11 of 17 patients (65%) who survived more than 2 months. Three patients were retransplanted at 1.8, 12.6, and 14.5 years after the initial transplant for recurrent EPP liver disease. In conclusion, the 5-year patient survival rate in patients transplanted for EPP liver disease is good, but the recurrence of EPP liver disease appears to diminish long term graft and patient survival.     

Opiate receptor subtype binding in gerbil hippocampus is altered by forebrain ischemia

A role for endogenous opioids in trauma-induced brain injury has been supported by pharmacological studies. The present series of experiments were initiated to extend these observations by measuring opiate receptor subtype binding in gerbil hippocampus following 7 days recovery from a 10 min ischemic insult. Quantitative in vitro autoradiography was utilized to measure mu [( 3H]DAGO), kappa [( 3H]bremazocine + 10 microM morphiceptin + 100 nM DSLET), delta [( 3H]DSLET + 10 microM morphiceptin) and lambda [( 3H]naloxone + 300 nM diprenorphine) binding. While ischemic tissue samples at the level of the dorsal hippocampus showed complete loss of CA1 pyramidal cells, we observed no significant alterations in mu or delta binding suggesting a non-pyramidal cell localization of these receptors. Kappa binding decreased significantly to 88% of control in the CA1 and CA3 regions while lambda binding in the stratum lucidum (CA3) increased to 165% of control. Our results show that opiate receptor subtypes are differentially affected by an ischemic insult.