The principle of regulation in biology--from bone to eating behavior.

Cell physiology and molecular biology typically follow a reductionistic approach in science. In the last decade, molecular principles and pathogenetic factors involved in the development of many diseases have been successfully discovered. Therefore, early biological concepts based on systemic and cybernetic thoughts have been largely overshadowed by these more recent molecular and pathogenetic factors. This review highlights discoveries on bone development and hypothalamic controlled feeding and eating behavior with a cybernetic and systemic perspective. Interestingly, ancient ideas on bone development and hypothalamic function are still reasonable considerations to embed new molecular discoveries into a systemic concept of principles organizing nature.     

The impact of poverty on educational outcomes for children

Over the past decade, the unfortunate reality is that the income gap has widened between Canadian families. Educational outcomes are one of the key areas influenced by family incomes. Children from low-income families often start school already behind their peers who come from more affluent families, as shown in measures of school readiness. The incidence, depth, duration and timing of poverty all influence a child’s educational attainment, along with community characteristics and social networks. However, both Canadian and international interventions have shown that the effects of poverty can be reduced using sustainable interventions. Paediatricians and family doctors have many opportunities to influence readiness for school and educational success in primary care settings.     

Heart Rate Variability Predicts Severe Hypotension after Spinal Anesthesia for Elective Cesarean Delivery

Background: Hypotension due to vasodilation during subarachnoid block (SAB) for elective cesarean delivery may be harmful. Heart rate variability (HRV), reflecting autonomic control, may identify patients at risk of hypotension.

Methods: Retrospectively, HRV was analyzed in 41 patients who were classified into one of three groups depending on the decrease in systolic blood pressure (SBP): mild (SBP > 100 mmHg), moderate (100 > SBP > 80 mmHg), or severe (SBP < 80 mmHg). Prospectively, HRV and hemodynamic data of 19 patients were studied. Relative low frequency (LF), relative high frequency (HF), and LF/HF ratio were analyzed.

Results: Retrospective analysis of HRV showed a significantly higher sympathetic and lower parasympathetic drive in the groups with moderate and severe compared with mild hypotension before SAB (median, 25th/75th percentiles): LF/HF: mild: 1.2 (0.9/1.8), moderate: 2.8 (1.8/4.6), P < 0.05 versus mild; severe: 2.7 (2.0/3.5), P < 0.05 versus mild. Results were confirmed by findings of LF and HF. Prospectively, patients were grouped according to LF/HF before SAB: low-LF/HF: 1.5 (1.1/2.0) versus high-LF/HF: 4.0 (2.8/4.7), P < 0.05; low-LF: 58 +/- 9% versus high-LF: 75 +/- 10%, P < 0.05; low-HF: 41 +/- 10% versus high-HF: 25 +/- 10%, P < 0.05. High-risk patients had a significantly lower SBP after SAB (76 +/- 21 vs. 111 +/- 12 mmHg; P < 0.05).     

Coronary atherosclerosis of the donor heart--impact on early graft failure.

OBJECTIVE: Due to the shortage of donor hearts, the criteria for organ acceptability have been considerably extended and donor grafts with coronary atherosclerosis are among those offered. This study evaluated whether and to what degree pre-existing coronary atherosclerosis may be acceptable. METHODS: A total of 1253 consecutive HTx recipients were investigated retrospectively for donor-transmitted coronary atherosclerosis (DCAS). Donor-transmitted coronary atherosclerosis was defined as focal atherosclerosis with stenosis of at least 50%. Inclusion criteria were absence of pre-HTx angiogram but performance of angiogram or autopsy within 6 months after heart transplantation. Kaplan-Meier analysis and log-rank test were used. RESULTS: Eighty-five out of 1253 (6.8%) cases were excluded, since coronary evaluation was not performed within 6 months (n=45) or hearts had undergone pre-transplant angiography (n=40). In 1086 patients no donor-transmitted coronary atherosclerosis was found (NDCAS group) and in 82 patients (7%) donor-transmitted coronary atherosclerosis was diagnosed by angiography (n=49) or autopsy (n=33). Single-vessel donor-transmitted coronary atherosclerosis was found in 53/82 patients (DCAS1 group) and double- or triple-vessel donor-transmitted coronary atherosclerosis in 26/82 patients (DCAS2/3 group). Three of the 82 patients with donor-transmitted coronary atherosclerosis were excluded since the autopsy report was unclear regarding degree of atherosclerosis. Early after heart transplantation the 30-day mortality in the NDCAS and DCAS1 groups was 12.2% versus 13.2% whereas in the DCAS2/3 group it was 61.5%. Beyond the first year the annual decrease with and without donor-transmitted coronary atherosclerosis (single-vessel disease) is comparable. CONCLUSIONS: Donor screening without coronary angiogram overlooks significant atherosclerotic lesions in a considerable number of cases (7.0%). Therefore, angiographic donor screening should be performed. Donor grafts with single-vessel coronary atherosclerosis may be accepted as marginal hearts; however, in our opinion, revascularisation (CABG, PTCA) should be considered. Grafts with two- or even three-vessel coronary atherosclerosis seem to have a serious risk for early graft failure. Beyond the first year the outcome of healthy grafts and grafts with donor-transmitted coronary atherosclerosis seems to be comparable.     

Contraceptive potential of a mifepristone-nomegestrol acetate sequential regimen in women

The effectiveness of a sequential regimen consisting of mifepristone, 10 mg/day for 15 days, followed by nomegestrol acetate (NOMA), 5 mg/day for the next 13 days, for inhibiting ovulation and maintaining regular bleeding cycles was assessed in 10 surgically sterilized volunteers who were followed for one pretreatment and three treated cycles. Hormonal determinations in blood and urine, ovarian ultrasonography, bleeding records in all cycles and an endometrial biopsy taken on day 22-25 of the third treatment cycle were used to monitor the effects of treatment. During treatment, 24 monophasic (no sustained progesterone rise above 12 nmol/l) and six biphasic cycles were recorded. Nine follicular ruptures were detected echographically in these 30 treated cycles, five of which occurred in monophasic cycles. All follicular ruptures occurred on days 1-7 of NOMA treatment. Echographic and endocrine features of ovulatory cycles were both present in only four treated cycles (13.3%). Development of a secretory endometrium was achieved in all cases, but it was always irregular. Regular withdrawal bleeding occurred in all subjects and no adverse reactions were recorded. The ovarian and endometrial effects of this regimen justify testing its contraceptive effectiveness in phase 2 clinical trials.      

Immunogenicity of Corynebacterium pseudotuberculosis and the effect of adjuvants in mice

Intraperitoneal inoculation of CF1 mice with 100 micrograms, 200 micrograms, or 300 micrograms whole cell (WC) or 250 micrograms, 500 micrograms, or 1000 micrograms cell wall (CW) of Corynebacterium pseudotuberculosis induced varying degrees of protection after intravenous challenge of immunity with 7.2 X 10(4) CFU of C. pseudotuberculosis. Generally, the degree of protection increased with the dose of WC or CW. However, intraperitoneal inoculation of mice with 100 micrograms, 200 micrograms, or 300 micrograms heat-killed Mycobacterium bovis BCG; 50 micrograms, 150 micrograms, or 300 micrograms of either muramyl dipeptide (MDP) or trehalose dimycolate (TDM); or 350 micrograms, 700 micrograms or 1400 micrograms Corynebacterium parvum did not induce resistance to intravenous inoculation of 7.4 X 10(4) CFU of C. pseudotuberculosis. The protection induced by 500 micrograms CW was enhanced by adding 100 micrograms BCG, 150 micrograms MDP, or 350 micrograms C. parvum but protection induced in mice by 300 micrograms of WC was not enhanced by adding any adjuvants.