Familial bilateral renal agenesis and hereditary renal adysplasia

This paper reports three kindreds (A, B, C) with familial bilateral renal agenesis (BRA). Etiologically, BRA is considered a multifactorially determined disorder; pathogenetically it is viewed as a developmental field defect involving absence of both kidneys and ureters in all cases, and in other cases an associated spectrum of related field defects which range from absence of the uterus and vagina to sirenomelia. In BRA, Potter's syndrome represents a symptomatic deformity complex due to oligohydramnios.Two additional kindreds (D and E) in this paper show that unilateral absence of a kidney may occur in relatives of a propositus with severe bilateral renal adysplasia. The former defect is designated unilateral renal aplasia and is presumed to be a less severe form of bilateral renal adysplasia. In these two families, and in two others from the literature, autosomal dominant inheritance seems responsible for the presence of unilateral aplasia and bilateral adysplasia in different family members; this newly recognized genetic trait, is being designated hereditary renal adysplasia (HRA). In women with unilateral renal aplasia the associated tubal and uterine malformation may be responsible for prematurity plus an increased risk of spontaneous abortion.The opinions or assertions in this paper are those of the authors and are not to be construed as official or reflecting the views of the Navy Department or the Naval Service at large.Supported, in part, by NIH Grants GM 15422, 5 K04-HD 18982, and by a Grant from the National Foundation — March of Dimes. Contributed, in part, as paper No. 1609 from the University of Wisconsin Genetics Laboratory.     

Dextrorphan and levorphanol selectively block N-methyl-D-aspartate receptor-mediated neurotoxicity on cortical neurons

Neocortical neurons in cell cultures prepared from fetal mice were impaled for intracellular recording. Dextrorphan (DX), a clinically tested dextrorotatory morphinan lacking opioid action, did not alter neuronal membrane potential or conductance, but produced a selective attenuation of N-methyl-D-aspartate (NMDA) responses; kainate and quisqualate responses were not affected. DX also antagonized morphological and chemical (lactate dehydrogenase efflux) evidence of cortical neuronal cell injury produced by toxic bath exposure to NMDA, quinolinate or glutamate, but did not affect toxic exposure to quisqualate or kainate. This selective antagonism of neurotoxicity was apparent at micromolar concentrations of DX with an ED50 of 13 to 17 microM. A similar, but less potent neuron-protective effect, was seen with the opioid levorotatory enantiomer of DX, levorphanol (ED50, 40 microM). The O-methyl derivative of DX, dextromethorphan, also antagonized NMDA and glutamate neurotoxicity, but with possibly lower efficacy than DX. The higher potency of DX over levorphanol suggests that this novel neuron-protective action is not mediated by classic opiate receptors; it may be mediated at the "sigma opiate"/phencyclidine site. If further studies establish that DX and related compounds retain neuron-protective efficacy in appropriate animal models, the established clinical safety record of DX and dextromethorphan may allow prompt investigation of the NMDA receptor-blockade strategy in certain neurological disease states.     

Readiness for self‐directed learning among nursing students in Thailand

This study took place in Thailand where didactic and lecture‐driven teaching styles are beginning to transform into student‐centered methods. At Chiang Mai University Faculty of Nursing in Thailand, the readiness of 272 undergraduate students to undertake self‐directed learning was investigated using two instruments: a demographic data questionnaire and Guglielmino's Self Directed Learning Readiness Scale. The study found that the overall self‐directed learning readiness of participants was at a high level in the categories of openness to learning opportunities, self‐concept as an effective learner, initiative and independence in learning, informed acceptance of responsibility for one's own learning, creativity, and the ability to use basic study and problem‐solving skills. The findings provide encouragement to nurse educators to further apply self‐directed learning in nursing courses, to improve teaching and learning methods, and promote life‐long learning for nurses within Thailand and elsewhere.     

Studies of malformation syndromes in man XXXVI: the Pfeiffer syndrome,association with Kleeblattschädel and multiple visceral anomalies

This paper reports sporadic occurrence of the Pfeiffer syndrome with Kleeblattschädel (KS) in a male infant who died at 6 months of pneumonia with signs of increased intracranial pressure and who was found to have hydrocephalus, polymicrogyria, cerebellar herniation, bicuspid aortic valve, a common mesentery, absence of lesser omentum, hypplasia of gallbladder, a single umbilical artery, and multiple eye defects. This case is presumed to represent a new mutation: in other families the Pfeiffer syndrome has been dominantly inherited. The Pfeiffer syndrome is a form of acrocephalosyndactyly and impresses clinically as a mild form of the Apert syndrome. The Kleeblattschädel is an etiologically non-specific developmental field defect (DFC); about two fifths of 51 known cases have apparent thanatophoric dwarfism and about one fifth are probable or possible examples of the Pfeiffer syndrome. The KS-DFC has also been seen in the syndromes of Carpenter, Apert and Crouzon.     

Minamata disease

Summary A case of suspected mercury poisoning (Minamata disease) was studied. Microscopic and ultrastructural changes in the nervous system were compared with those of a confirmed case of mercury poisoning from Minamata Bay, Japan, and those from exprimental animals intoxicated with methyl mercury. Disintegration of the granular layer, disappearance of the Purkinje cells with Bergmann's fiber proliferation and demyelination of the fiber tracts were observed in the cerebellum. Ultrastructural examination also revelad extensive proliferation of astrocytic fibers and characteristic focal demyelination and loosening of the myelin sheaths in many nerve fibers. Such pathological changes were consistent with those observed in both human cases and experimental animals poisoned by methyl mercury.     

Aspartate neurotoxicity on cultured cortical neurons

L-aspartate neurotoxicity was quantitatively characterized in murine cortical cell cultures. Five-minute exposure to 30 microM-3 mM L-aspartate resulted in concentration-dependent (ED50 about 190 microM) neuronal destruction over the next 10 hr; glia were not injured. D-aspartate and L-aspartate were roughly equipotent neurotoxins. Ion substitution experiments suggested that L-aspartate neurotoxicity is comprised of both acute, sodium-dependent "excitotoxicity" and delayed, calcium-dependent degeneration, with the latter predominant under conditions of brief exposure. Aspartate neurotoxicity could be attenuated by D-2-amino-5-phosphonovalerate (D-APV), dextrorphan, ketamine, and kynurenate, but not by L-glutamate diethyl ester or gamma-D-glutamylaminomethyl sulfonate, consistent with principal involvement of N-methyl-D-aspartate receptors. D-APV and dextrorphan produced different effects on the aspartate concentration-toxicity relation; the former drug was consistent with a competitive and the latter with a noncompetitive mechanism of antagonism.     

Generalized gangliosidosis type II (Juvenile GM1 gangliosidosis)

Pathological, histochemical and ultrastructural studies on 3 siblings with GM₁ gangliosidosis type II are reported. These studies support a biochemical defect with profound deficiency of β-galactosidase which results in widespread accumulation of the GM₁ ganglioside and its asialo derivative in brain and to a lesser extent in viscera, as well as in storage of a keratan sulphate-like mucopolysaccharide. Striking valvular changes in the heart without myocardial involvement were seen in all cases. The histochemical and ultrastructural changes are similar to those seen in GM₁ gangliosidosis type I, though less severe. Autosomal recessive inheritance without apparent ethnic predilection seems likely.     

Studies of malformation syndromes of man XXXXI B: Nosologic studies in the Hanhart and the Möbius syndrome

We reviewed etiologic and phenotypic aspects of those orofacial and limb anomalies usually diagnosed as Hanhart syndrome and Möbius syndrome, but also those described, among others, under names such as aglossia-adactylia syndrome, glosso-palatine ankylosis, ankyloglossia superior, peromelia and micrognathia, cleft palate/lateral synechiae syndrome, and the Charlie M. syndrome. By coding the degree of severity of the limb defects it was possible to compare these cases quantitatively and to determine the nosologic significance of associated cranial nerve palsies and chest abnormalities. We analyzed 7 personal and 62 previously reported cases and found: 1. that the severity in the upper limbs and particularly, malformations of the feet, but not the presence or absence of cranial nerve palsies, is a significant feature in the differentiation of cases, and 2. that the group of patients with cranial nerve palsies includes some with limb defects similar to those in the Hanhart syndrome and others with features which overlap the manifestations of the Poland syndrome. Still other cases had cranial nerve palsy as an isolated trait or as a component manifestation of several different syndromes.These findings permit re-definition and nosologic delimitation of the various syndromes as follows: 1. The Hanhart syndrome: usually severe limb defect of at least one hand or foot, frequently associated with severe oral abnormalities and sometimes also with cranial nerve palsy. Most cases reported as aglossia-adactylia syndrome, aglossia-hypomelia syndrome, and some cases reported as glossopalatine ankylosis, ankyloglossia superior and Möbius syndrome describe instances of the Hanhart syndrome. 2. The Poland-Möbius syndrome: we suggest this term to refer to those cases of Möbius syndrome which have a chest defect and/or symbrachydactyly of the type seen in the Poland syndrome. We suspect that these cases of the Möbius syndrome, and most of the cases which are usually diagnosed as Poland syndrome represent a different spectrum of the same condition, hence the term Poland-Möbius syndrome. 3. The autosomal dominant cleft palate/lateral synechiae syndrome delineated by Fuhrmann et al. and other apparently less frequent conditions are mentioned in the discussion.Cranial nerve palsy obviously occurs in several etiologically distinct conditions. An analogous situation is present, although less obvious, in the Hanhart and the Poland-Möbius syndrome. Both of these conditions are formal genesis malformation syndromes which implies that they are etiologically non-specific developmental field complexes. In the Hanhart syndrome Bersu et al. postulate a common pathogenetic disturbance for oral and limb defects, thus suggesting that the manifestations represent a single anomaly rather a syndrome. This anomaly, for which we suggest the term Kettner anomaly, may occur not only in the Hanhart syndrome but also in other conditions. Similarly, the Poland anomaly, i.e. symbrachydactyly and ipsilateral pectoralis muscle hypoplasia, may occur in the Poland-Möbius syndrome as well as in other conditions.Supported by USPHS/NIH Grant GM 20 130, Paper No. 1893 from the University of Wisconsin Genetics Laboratory.     

The pathologic anatomy of the G syndrome

A detailed anatomic study of the organs of a stillborn male infant with the G syndrome was made.The malformations consisted of a subtle physiognostic appearance with severe micrognathia, penoscrotal hypospadias with descended testes, and failure of closure of the laryngotracheal groove. In addition, respiratory tract defects included lack of lung fissures, short trachea with a high carina and a symmetrical bronchial tree. Minor cardiac malformations of systemic and cardiac venous drainage, and urinary tract anomalies were also present. Developmental, clinical and genetical aspects of the G syndrome were discussed.Contributed in part as Paper No. 1509 from the University of Wisconsin Genetics Laboratory, and contribution VIC: Studies of Human Malformation Syndromes from the Birth Defects Research Center, Department of Pediatrics, University of Wisconsin Medical School.Supported in part by NIH Grants GM 15422, GM 08217, 5 KO 4 HD 18982, and by a Grant from the National Foundation-March of Dimes.