Changes in protein turnover, IGF-I and IGF binding proteins in children with cancer

Changes in insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding proteins (IGFBPs) were correlated with protein synthesis and breakdown using [1- ¹³C]leucine before chemotherapy and during subsequent febrile neutropenia (FN) in eight children with cancer, aged 6.3–17.5 y. IGF-I levels were similar to age-matched controls before chemotherapy (mean ±SEM: 250 ±28 and 228 ±22 μg l^-1, respectively). During FN, IGF-I fell to 156 ±22 /ng l ^-1(p= 0:02), and rose to 276 ±27 μ g l ^-1 with recovery at 6 months (p = 0:004). Similarly, IGFBP-3 decreased from 4.0 ±0.2mgl^-1 before chemotherapy to 3.0 ±0.3 mgl^-1 during FN (p= 0:01), and returned to 4.1 ±0.2mgl ^-1 at 6 months (p= 0:01). IGF-I correlated with IGFBP-3 (r=+0:7, p <0:001). Scanning densitometry showed a decrease in IGFBP-3 from 94 to 54% during FN, when the presence of IGFBP-3 protease activity was observed. Compared with normal human serum, IGFBP-2 was elevated throughout the study. IGFBP-1 increased from 14.6 ±3.5 to 30.6 ±2.8/ngl^-1 (p = 0:004), whereas serum insulin decreased from 26.5 ±6.8 to 7.8 ±0.8 mUl^-1 (p= 0:03) before and during FN, respectively. Whilst IGF-I and IGFBP-3 fell, daytime growth hormone increased from 3.3 ±0.6 to 6.7±0.8mUl ^-1 (p= 0:01), and cortisol from 197 ±48 to 594±98nmoll ^-1 (p = 0:005). Albumin decreased from 47 ±2 to 38 ±2gl^-1 (p= 0:004) and improved to 47 ±2gl^-1 with recovery (p= 0:003). Protein synthesis increased from 4.5 ±0.4 to 5.0 ±0.6gkg^-1 d^-1 before chemotherapy and during FN, while protein breakdown rose from 5.4 ±0.4 to 6.3 ±0.4kg^-1d^-1. Increasing protein breakdown was related to falling IGF-I and IGFBP-3 levels. Modification of IGFBP-3 by circulating proteolytic activity may alter IGF bioavailability, allowing protein synthesis to increase during periods of severe catabolic stress.     

Interacting effects of Ca2+ and hypoxia in the induction of sarcolemmal damage in mouse diaphragm in vitro

Experiments have been undertaken to investigate the basis for the selective damage of centrally placed fibres in mouse diaphragms exposed to Ca²⁺ loading in vitro. Incubation under hypoxic conditions (non-aerated saline) for 30 min had no discernible effect on the muscle. Incubation for 120 min led to permeabilisation of the sarcolemma (assayed by penetration of Procion Yellow) in 54% of cells. Sarcolemmal permeabilisation was almost completely restricted to centrally placed cells, as has previously been described for the effects of the Ca²⁺ channel agonist Bay K 8644. Ultrastructural damage to the myofibrils and mitochondrial swelling were also widespread amongst centrally placed cells. Permeabilisation was inhibited when hypoxic incubations were carried out in Ca²⁺-free saline. Incubation in hypoxic Ca²⁺-containing saline for 30 min followed by further incubation in Ca²⁺-free, hypoxic saline, up to a total of 120 min, resulted in permeabilisation similar to that seen in muscles incubated for 120 min in Ca²⁺-containing, hypoxic saline. It is suggested that selective damage to central fibres induced by Ca²⁺ loading resulting from treatment with Bay K 8644 is related to increased oxygen demand.     

Risk factors for development of dehydration in children aged under five who have acute watery diarrhoea: a case-control study

Objective: To identify risk factors for development of dehydration in under five year olds with acute watery diarrhoea.Design: Hospital based unmatched case-control study.Setting: Diarrhoea Treatment Unit, Government Medical College Hospital, Nagpur, India.Participants: The study included 387 cases of diarrhoea having severe or moderate dehydration and 387 controls suffering from diarrhoea with mild or no dehydration.Risk factors: The study included infancy, female sex, religion, residing in urban slums or rural area, under nutrition, cessation of breast feeding during diarrhoeal episode, fluid intake decreased/stopped during diarrhoea, ORS not received, home available fluids (HAF) not received, both ORS and HAF not received, non-washing of hands by mother before preparation of food, after defaecation, after disposal of faeces, history of measles in the previous six months, frequency of stools >8/d, frequency of vomiting more than twice per day and temperature more than 99°F, as risk factors for development of dehydration.Statistical analysis: Univariate analysis included OR, 95% CI for OR and Chi-square test. Multivariate analysis was carried out by unconditional multiple logistic regression (MLR).Results: This study identified the significance of infancy, religion, severe undernutrition, non-washing of hands by mother before preparation of food, frequency of stool >8/d, frequency of vomiting >2/d, history of measles in previous six months, withdrawal of breast feeding during diarrhoea, withdrawal of fluids during diarrhoea and not giving ORS, HAF or both during diarrhoea, in the outcome of development of moderate or severe dehydration.Conclusions: Timely intervention in the preventable risk factors included in this study may prevent the development of moderate or severe dehydration in the children suffering form acute watery diarrhoea.     

Comparison of two methods of transporting paramedics to cardiac arrests outside hospital.

OBJECTIVE: To compare the deployment of paramedics in a separate rapid response unit with their deployment in a standard emergency ambulance. DESIGN: A one year period of each deployment. SETTING: Throughout the community in some parts of West Yorkshire. PARTICIPANTS: All patients receiving resuscitation for cardiac arrest by paramedics. INTERVENTIONS: Using the same group of paramedics and central control, 12 months with the paramedics deployed in separate cars in addition to the standard ambulances (period 1) were followed by another 12 months when they were deployed as one crew member of a standard emergency ambulance (period 2). MAIN OUTCOME MEASURES: Number of arrests attended, number of patients in ventricular fibrillation at paramedic arrival, response times, survival to leave hospital. RESULTS: In period 1, 580 arrests were attended with 31 survivors. In period 2, 462 arrests resulted in 25 survivors. The mean response time was shorter in period 1 (6.24 versus 6.60 min, Cl--0.01-0.73 min). In period 1, 217 patients were found in ventricular fibrillation (23 survivors): In period 2, 141 patients were found in ventricular fibrillation (11 survivors). CONCLUSION: Separating paramedics from the standard emergency ambulances increases the number of survivors of cardiac arrest but the difference may not be sufficiently large to justify the additional expenditure.     

Pretibial myxoedema associated with Hashimoto''s thyroiditis

Pretibial myxoedema is a cutaneous mucinosis typically associated with Graves' disease, although it may also develop in subjects with non-thyrotoxic thyroid pathologies. This report presents a rare case of pretibial myxoedema occurring in a 58-year-old woman with biopsy-proven Hashimoto's thyroiditis. The hypothetical pathogenetic link between the two disorders is discussed with particular attention to the role of thyroid stimulating hormone receptor antibodies.