Mechanics and function in heart morphogenesis.

For years, biomechanical engineers have studied the physical forces involved in morphogenesis of the heart. In a parallel stream of research, molecular and developmental biologists have sought to identify the molecular pathways responsible for embryonic heart development. Recently, several studies have shown that these two avenues of research should be integrated to explain how genes expressed in the heart regulate early heart function and affect physical morphogenetic steps, as well as to conversely show how early heart function affects the expression of genes required for morphogenesis. This review combines the perspectives of biomechanical engineering and developmental biology to lay out an integrated view of the role of mechanical forces in heart development.     

Radiation dosimetry of iodine-123 HEAT, an alpha-1 receptor imaging agent

Biologic distribution data in the rat were obtained for the alpha-1 adrenoceptor imaging agent (+/-) 2-[beta-(iodo-4-hydroxyphenyl)ethylaminomethyl]tetralone (HEAT) labeled with [125I]. The major excretory routes were through the liver (67%) and the kidney (33%). Internal radiation absorbed dose estimates to nine source organs, total body, the GI tract, gonads, and red bone marrow were calculated for the human using the physical decay data for [123I]. The critical organ was found to be the lower large intestine, receiving 1.1 rad per mCi of [123I]HEAT administered. The total-body dose was found to be 58 mrad per mCi.     

Inhibin and renin in follicular fluids of patients with one or two ovaries stimulated with a GnRH agonist and gonadotrophins

Follicular fluids from eight patients with one ovary and from ten patients with two ovaries were investigated for bioactive inhibin, total renin, oestradiol (E2) and progesterone (P4) concentrations. Four follicular fluids were pooled per patient before assessment. All women had been stimulated similarly using a protocol including a GnRH agonist, HMG and HCG. Renin levels were significantly lower and P4 significantly higher in pools of follicular fluid from patients with one ovary, whereas inhibin and E2 concentrations were similar in both patient groups. A significant negative correlation was found in the pools of follicular fluid between inhibin and E2 in both groups. These results suggest a role for inhibin and renin in the paracrine and autocrine control of stimulated follicular development.     

Limb-salvage treatment versus amputation for osteosarcoma of the distal end of the femur

A retrospective multi-institutional study of 227 patients with osteosarcoma of the distal end of the femur was done to compare rates of local recurrence, metastasis, and survival. Three cohorts of patients who had had either a limb-sparing procedure, an above-the-knee amputation, or disarticulation of the hip were compared. The results revealed prevalences of eight of seventy-three, nine of 115, and zero of thirty-nine as to local recurrence; forty-three of seventy-three, sixty-five of 115, and twenty-one of thirty-nine as to metastasis; and thirty-three of seventy-three, forty-eight of 115, and eighteen of thirty-nine as to death. Of the seventeen patients who had a local recurrence, sixteen died. In the limb-salvage group, eighteen patients required amputation, because of local recurrence in eight and other local complications in ten. The Kaplan-Meier estimates of the percentage of patients who survived and the percentage of patients without recurrent disease showed no difference among the three surgical groups (Mantel-Cox test statistic: p = 0.8) after a median length of follow-up of five and one-half years. Various covariant adjusted estimates yielded similar results. For the entire group of patients, the rate of continuously disease-free survival was 42 per cent, and the over-all rate of survival was 55 per cent at five years. It appears that, compared with above-the-knee amputation or disarticulation of the hip, the use of a limb-salvage procedure for osteosarcoma of the distal end of the femur did not shorten the disease-free interval or compromise long-term survival.     

Working memory after severe traumatic brain injury.

The aim of the present study was to assess the functioning of the different subsystems of working memory after severe traumatic brain injury (TBI). A total of 30 patients with severe chronic TBI and 28 controls received a comprehensive assessment of working memory addressing the phonological loop (forward and backward digit span; word length and phonological similarity effects), the visuospatial sketchpad (forward and backward visual spans), and the central executive (tasks requiring simultaneous storage and processing of information, dual-task processing, working memory updating). Results showed that there were only marginal group differences regarding the functioning of the two slave systems, whereas patients with severe TBI performed significantly poorer than controls on most central executive tasks, particularly on those requiring a high level of controlled processing. These results suggest that severe TBI is associated with an impairment of executive aspects of working memory. The anatomic substrate of this impairment remains to be elucidated. It might be related to a defective activation of a distributed network, including the dorsolateral prefrontal cortex.     

Intracellular messengers and the control of protein synthesis

The molecular events responsible for controlling cell growth and development, as well as their coordinate interaction is only beginning to be revealed. At the basis of these controlling events are hormones, growth factors and mitogens which, through transmembrane signalling trigger an array of cellular responses, initiated by receptor-associated tyrosine kinases, which in turn either directly or indirectly mediate their effects through serine/threonine protein kinases. Utilizing the obligatory response of activation of protein synthesis in cell growth and development, we describe efforts to work backwards along the regulatory pathway to the receptor, identifying those molecular components involved in modulating the rate of translation. We begin by describing the components and steps of protein synthesis and then discuss in detail the regulatory pathways involved in the mitogenic response of eukaryotic cells and during meiotic maturation of oocytes. Finally we discuss possible future work which will further our understanding of these systems.     

A study of the use of intravenous cannulas for medical emergencies in Newham--implications for financial savings

A study of intravenous (i.v.) cannula usage for medical emergencies admitted to hospitals in the Newham Health District was undertaken during two defined periods (24 and 35 days). Almost half the cannulas inserted (47%) were not flushed following an initial bolus injection of heparinized saline. The duration that cannulas remained in a vein ranged from 24 hours to 8 days (median 2 days) and inflammation around the cannula site was related to the length of time since insertion but unrelated to whether the cannula was flushed regularly or to the type of fluid used. Our findings indicate a substantial wastage of i.v. cannulas due to difficulties with insertion and suggest that isotonic saline, without heparin, is effective in maintaining cannula patency for 48 hours. It is concluded that these findings are not unique to the Newham Health District and worthwhile financial savings should be achieved throughout the NHS if clinicians reconsider the indications and use of i.v. cannulas for their patients.     

Hirschsprung's disease in young adults

Hirschsprung's disease is rarely seen in the young adult, and presents unique problems in management because of the massive dilatation and hypertrophy that occur proximal to the aganglionic rectum or the rectosigmoid colon. The diagnosis, which may be suspected by barium enema, is confirmed by suction or full-thickness biopsy of the rectum that may be complemented by anal manometry. Based on our experience with eight patients, a two-stage surgical reconstruction is recommended, with a preliminary sigmoid colostomy through the normally innervated colon and an associated defunctionalized stoma constituting the initial operation. The distal colonic stoma permits cleansing of the caudal colon while the normally innervated proximal colon reverts to near normal caliber, usually within 2 to 6 months. This approach is in accord with the recommendation of Fairgrieve. Reconstruction using a Duhamel or Soave procedure has given good results. The Duhamel procedure seems preferable when a considerable discrepancy remains between the ganglionic and aganglionic segments of rectum.