Congenital diaphragmatic hernia: new models,new ideas

An animal model for congenital diaphragmatic hernia following interference with the development of the primary lung bud by 2,4-dinitro-p-diphenylether (nitrofen) is described. It has been used for pathogenetic studies to evaluate the presence of pulmonary hypoplasia and a closing defect of the diaphragm. Functional studies revealed abnormal surfactant levels and differences in pressure/volume curves following birth and during artificial ventilation for 6 h together with a disturbed antioxidant enzyme response. This animal model opens up new ways of studying the effects of prenatal hormonal modulation (corticosteroids, thyrotrophin-releasing hormone) on lung development as a novel therapeutic modality.     

Angiolymphoid hyperplasia with eosinophilia or Kimura's disease

A rare affection of unknown etiology that is benign but frequently recurrent, Kimura's disease involves infiltration of the dermis and hypodermis usually of the face. Documented data exists describing clinical findings and results of histopathology that are analogous but are grouped under other names: angiolymphoid hyperplasia with eosinophilia, pyogenic pseudogranuloma, atypical pyogenic granuloma. A case followed up for 13 years is reported.     

A Korean kindred with autosomal dominant nocturnal frontal lobe epilepsy and mental retardation

BACKGROUND: A Korean family had distinctive clinical and neuroimaging features and carried the same genetic mutation that was found in a previously described Japanese kindred with autosomal dominant nocturnal frontal lobe epilepsy. OBJECTIVE: To describe the first Korean family with autosomal dominant nocturnal frontal lobe epilepsy. METHODS: Members of a large family, including 9 affected individuals from 3 generations, underwent a comprehensive genetic, clinical, electroencephalographic, neuropsychological, and neuroimaging evaluation. Affected members were tested for possible mutations in transmembrane regions 1 through 3 of the neuronal nicotinic acetylcholine receptor alpha4 subunit (CHRNA4) by direct sequencing and subsequent restriction analysis. RESULTS: Seizures began in childhood, presenting as nocturnal episodes of staring, confusion, shouting, perioral movements, unintelligible speech, and hand waving. Some patients had ictal or interictal epileptiform activity in the temporal and/or frontocentral areas. Neurological examination and brain magnetic resonance imaging results showed no abnormalities, except that all patients available for testing had mild to moderate mental retardation. Fluorodeoxyglucose F 18 with positron emission tomography showed mild decreased glucose uptake in the superior and middle frontal regions, more so on the left than on the right. Patient response to carbamazepine was poor. All affected members were heterozygous for the CHRNA4 Ser252Leu mutation. CONCLUSIONS: Disorders associated with mutations in the transmembrane region 2 of CHRNA4 are genetically and phenotypically heterogeneous. Distinctive features of this kindred include (1) mental retardation in all affected members available for testing, (2) abnormal brain findings on fluorodeoxyglucose F 18 with positron emission tomography, (3) poor response to carbamazepine, and (4) full penetrance.     

Alzheimer's disease patients display gender dimorphism in circulating anorectic adipokines

Among neurodegenerative diseases, Alzheimer's disease (AD) is a leading cause of death in elderly individuals. AD is characterized, among other clinical findings, by unexplained weight loss, cachexia and altered immune function. To explore whether any relationship between gender and circulating levels of several eating-controlling metabolites exist, we evaluated leptin, tumor necrosis factor (TNF)-alpha, triiodothyronine (T(3)), free (F) thyroxine (T(4)), TSH, PRL, insulin (INS), and cortisol in 15 AD-treated patients (age range 55-82 years): 9 postmenopausal females (without hormone replacement therapy) and 6 males. The results (mean +/- SEM) indicated that circulating leptin levels were significantly (p < 0.05) higher in female AD (40.34 +/- 11.1 ng/ml) than in male AD (6.07 +/- 1.39 ng/ml) patients. The difference found in circulating leptin levels was noticed regardless of BMI (26.75 +/- 1.77 and 24.55 +/- 1.93 kg/m(2), in females and males, respectively) and waist:hip ratios (0.91 +/- 0.03 and 0.94 +/- 0.02, in females and males, respectively). Moreover, serum TNF-alpha concentrations were also significantly (p < 0.02) higher in AD females (12.24 +/- 1.47 pg/ml) than in AD males (6.62 +/- 1.44 pg/ml), regardless of TNF-alpha:BMI ratios (0.50 +/- 0.09 and 0.28 +/- 0.08, in females and males, respectively; p > 0.05). Finally, no differences were observed between gender (in female and male AD patients, respectively) in circulating levels of T(3) (151.33 +/- 9.91 vs. 116 +/- 17.04 ng/dl), FT(4) (1.26 +/- 0.08 vs. 1.24 +/- 0.06 ng/dl), TSH (1.28 +/- 0.16 vs. 2.46 +/- 0.67 microIU/ml), PRL (10.53 +/- 2.47 vs. 12.61 +/- 2.37 ng/ml), INS (11.76 +/- 1.95 vs. 8.59 +/- 1.34 microIU/ml) and cortisol (15.71 +/- 1.23 vs. 12.63 +/- 1.47 microg/dl). These results indicate that our AD group of patients, with normal corticoadrenal and thyroid functions and normoprolactinemia, displayed a gender-related characteristic in the circulating levels of two very important anorectic signals, leptin and TNF-alpha, being both higher in female than in male AD patients, regardless of BMI. Our study suggests that increased circulating levels of both anorexigenic adipokines may contribute to the metabolic changes observed in AD females.     

Attraction exerted in vivo by grafts of embryonic neocortex on developing thalamic axons

In a previous study we provided evidence that embryonic (E) day 16 frontal cortical cells grafted into the occipital cortex of newborn rats receive inputs from the ventrolateral (VL) and ventromedial (VM) thalamic nuclei which, normally, project to the frontal cortex (25). The present study was designed to examine further the conditions of development of the thalamic innervation of heterotopic neocortical grafts. We demonstrate that VL/VM axons do not provide transitory aberrant input to the occipital cortex either in intact newborn animals or in rats having received neonatal occipital lesion and subsequent graft of E16 occipital cells. These findings indicate, therefore, that the VL/VM projection to the graft does not result from the stabilization of an initial widespread cortical projection from these thalamic nuclei occurring either spontaneously or in response to the lesion and homotopic transplantation procedures. We also show that the VL/VM projection to frontal-to-occipital grafts develops within a few days posttransplantation and is maintained in adulthood. Finally, this study establishes that most VL/VM axons which enter the grafts are not collaterals of thalamofrontal axons. After having reached the cortex, they proceed caudally primarily within the infragranular layers. The findings of this and previous (25) in vivo studies for the first time provide evidence that developing thalamic axons have the capacity to respond to signals from grafts of E16 cortical cells and are capable of deviating their trajectory to establish contact with the grafts. Only those axons arising from thalamic nuclei appropriate for the cortical locus of origin of the grafted cells respond to the guidance signals. The mechanisms by which the thalamic axons find their way to the graft probably rely on cell-contact signaling and/or long-range attraction exerted by diffusible molecules.