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.     

Complete obstruction of the sigmoid colon treated by primary resection and anastomosis—An improved technique (preliminary report)

Three patients with complete colonic obstruction treated by primary resection and anastomosis with intraoperative colon tube decompression and bowel lumen sterilization without a protective colostomy are presented. An improved colonic decompressor was used. It is postulated that this procedure is an alternative safe technique in patients with colonic obstruction in whom an end-colostomy, mucous fistula, or Hartmann pouch would be necessary.     

Healthcare worker competencies for disaster training

Background  

Although training and education have long been accepted as integral to disaster preparedness, many currently taught practices are neither evidence-based nor standardized. The need for effective evidence-based disaster training of healthcare staff at all levels, including the development of standards and guidelines for training in the multi-disciplinary health response to major events, has been designated by the disaster response community as a high priority. We describe the application of systematic evidence-based consensus building methods to derive educational competencies and objectives in criteria-based preparedness and response relevant to all hospital healthcare workers.     

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.     

Surgery and Chemotherapy for Small Cell Lung Cancer in Stages I–II with or without Radiotherapy

PURPOSE: To analyze the effectiveness of surgery and chemotherapy with or without radiotherapy in the management of limited small cell lung cancer (LSCLC) in stages I and II. PATIENTS AND METHODS: 39 patients (median age 62 years) with LSCLC in stages pT1 or pT2 and pN0 or pN1 (stages IA-IIB) who had a tumor resection and systematic lymph node dissection were reviewed retrospectively. The median follow-up period was 29 months. 35 patients (90%) received a median of four cycles of a platinum-containing chemotherapy postoperatively. 16 patients (41%) received an adjuvant thoracic radiotherapy (TRT, median 50 Gy); 21 patients (54%) received a prophylactic cranial irradiation (PCI, median 30 Gy). RESULTS: The median overall survival for all patients was 47 months, resulting in actuarial 1-, 3-, and 5-year survival rates of 97%, 58%, and 49%, respectively. Distant metastases were found in 13 patients (33%) after a median of 16 months. Patients who received an adjuvant TRT showed a trend toward improved thoracic recurrence-free survival (p = 0.06) and improved overall survival (p = 0.07) compared to those treated with surgery and chemotherapy only. Brain metastasis-free survival (p = 0.01) and overall survival (p = 0.01) were improved significantly in patients who received a PCI. CONCLUSION: Surgical tumor resection may be considered for carefully selected patients. Adjuvant chemotherapy and PCI are recommended for all patients. Adjuvant TRT is currently used in patients with positive lymph nodes (pN1), because the probability of a subclinical involvement of the mediastinal lymphatic system appears to be increased in these patients.     

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.