Perthes' disease treated by prolonged recumbency and femoral head containment: a long-term appraisal

The results of a long-term review of 102 hips in eighty-seven patients with Perthes' disease are described, the mean follow-up interval being seventeen years. All had been treated by an extremely rigorous conservative regime in which the patients were kept in hospital for an average period of twenty-six months, during which time they were confined to bed with the legs in wide abduction, first in traction and later in "broomstick" plasters to ensure "containment" of the femoral head. The patients were assessed by the joint clincial and radiological method described by Ratliff (1956). The results were very satisfactory, with only 2 per cent poor results and 10 per cent fair. The remaining 88 per cent were good. The radiological results at the end of treatment have also been compared with control series described by Catterall (1972) and with the osteotomy series of Lloyd-Roberts, Catterall and Salamon (1976). From this it appears that the described regime offers no benefit compared with the natural history in Catterall's Groups I and II, and in Group III the results were only marginally better than those following osteotomy. In Group IV cases, however, where the femoral head was totally involved, the benefit was important, and since these are the cases which carry the worst natural prognosis it is suggested that the use of the method described in such instances must be seriously considered in spite of its social disadvantages. The theoretical implications of the findings are considered, and it is concluded that the benefits of the method cannot be ascribed wholly to the application of the "containment" principle.     

Complete physical map of the common deletion region in Williams syndrome and identification and characterization of three novel genes

Williams syndrome (WS) is a contiguous gene deletion disorder caused by haploinsufficiency of genes at 7q11.23. We have shown that hemizygosity of elastin is responsible for one feature of WS, supravalvular aortic stenosis (SVAS). We have also implicated LIM-kinase 1 hemizygosity as a contributing factor to impaired visual-spatial constructive cognition in WS. However, the common WS deletion region has not been completely characterized, and genes for additional features of WS, including mental retardation, infantile hypercalcemia, and unique personality profile, are yet to be discovered. Here, we present a physical map encompassing 1.5 Mb DNA that is commonly deleted in individuals with WS. Fluorescence in situ hybridization analysis of 200 WS individuals shows that WS individuals have the consistent deletion interval. In addition, we identify three novel genes from the common deletion region: WS-betaTRP, WS-bHLH, and BCL7B. WS-betaTRP has four putative beta-transducin (WD40) repeats, and WS-bHLH is a novel basic helix-loop-helix leucine zipper (bHLHZip) gene. BCL7B belongs to a novel family of highly conserved genes. We describe the expression profile and genomic structure for each of these genes. Hemizygous deletion of one or more of these genes may contribute to developmental defects in WS.     

Localization and dynamic regulation of biogenic amine transporters in the mammalian central nervous system

The monoamines, serotonin, dopamine, norepinephrine, epinephrine and histamine, play a critical role in the function of the hypothalamic-pituitary-adrenal axis and in the integration of information in sensory, limbic, and motor systems. The primary mechanism for termination of monoaminergic neurotransmission is through reuptake of released neurotransmitter by Na+, CI-dependent plasma membrane transporters. A second family of transporters packages monoamines into synaptic and secretory vesicles by exchange of protons. Identification of those cells which express these two families of neurotransmitter transporters is an initial step in understanding what adaptive strategies cells expressing monoamine transporters use to establish the appropriate level of transport activity and thus attain the appropriate efficiency of monoamine storage and clearance. The most recent advances in this field have yielded several surprises about their function, cellular and subcellular localization, and regulation, suggesting that these molecules are not static and most likely are the most important determinants of extracellular levels of monoamines. Here, information on the localization of mRNAs for these transporters in rodent and human brain is summarized along with immunohistochemical information at the light and electron microscopic levels. Regulation of transporters at the mRNA level by manipulation in rodents and differences in transporter site densities by tomographic techniques as an index of regulation in human disease and addictive states are also reviewed. These studies have highlighted the presence of monoamine neurotransmitter transporters in neurons but not in glia in situ. The norepinephrine transporter is present in all cells which are both tyrosine hydroxylase (TH)- and dopamine beta-hydroxylase-positive but not in those cells which are TH- and phenyl-N-methyltransferase-positive, suggesting that epinephrine cells may have their own, unique transporter. In most dopaminergic cells, dopamine transporter mRNA completely overlaps with TH mRNA-positive neurons. However, there are areas in which there is a lack of one to one correspondence. The serotonin transporter (5-HTT) mRNA is found in all raphe nuclei and in the hypothalamic dorsomedial nucleus where the 5-HTT mRNA is dramatically reduced following immobilization stress. The vesicular monoamine transporter 2 (VMAT2) is present in all monoaminergic neurons including epinephrine- and histamine-synthesizing cells. Immunohistochemistry demonstrates that the plasma membrane transporters are present along axons, soma, and dendrites. Subcellular localization of DAT by electron microscopy suggests that these transporters are not at the synaptic density but are confined to perisynaptic areas, implying that dopamine diffuses away from the synapse and that contribution of diffusion to dopamine signalling may vary between brain regions. Interestingly, the presence of VMAT2 in vesicles underlying dendrites, axons, and soma suggests that monoamines may be released at these cellular domains. An understanding of the regulation of transporter function may have important therapeutic consequences for neuroendocrine function in stress and psychiatric disorders.     

Phase 1B ventricular arrhythmia in the dog: localized reentry within the mid-myocardium

Our aim was to investigate the relationships between defensiveness and repression, on the one hand, and self-reported stressor exposure and resting blood pressure, on the other hand. In addition, different operationalizations of defensiveness and repression were compared. Participants were 310 male and 90 female employees representing a wide range of occupations. Before a medical examination, all subjects completed questionnaires measuring defensiveness, anxiety, repression, daily hassles, and life events. After controlling for potentially confounding variables, multiple regression analyses revealed an inverse association between defensiveness and self-reported number of daily hassles and a positive link between defensiveness and resting systolic blood pressure. In general, the interaction between defensiveness and anxiety (representing repression) did not add to the predictive power of defensiveness and anxiety alone. The results support the notion that defensive individuals tend to underreport problems, while exhibiting elevated resting blood pressures.