Could associations between breastfeeding and insulin‐like growth factors underlie associations of breastfeeding with adult chronic disease? The Avon Longitudinal Study of Parents and Children

Objective The influence of infant feeding method (breast/formula) on growth factor levels could underlie associations of breastfeeding with childhood growth and risk factors for cardiovascular disease. We investigated associations of having been breastfed with serum IGF‐I and IGFBP‐3 in childhood. Methods Prospective birth cohort study (subsample of the Avon Longitudinal Study of Parents and Children, UK) based on 871 children born in 1991/1992 who underwent clinical follow‐up and blood tests at age 7–8 years. A total of 488 (56%) children had complete data. Results In children with complete data, the age‐ and sex‐standardized IGF‐I levels of those who were partially or exclusively breastfed were 6·1 and 13·8 ng/ml higher, respectively, than those who were never breastfed (increase in IGF‐I levels per category of breastfeeding exclusivity: 7·1 ng/ml; 95% CI: 0·3–13·9; P = 0·04). In models also controlling for birthweight, gestational age, mother's age, and socioeconomic and dietary factors, the breastfeeding–IGF‐I association was attenuated (regression coefficient: 3·3 ng/ml; ?4·2–10·7; P = 0·4); further adjustment for IGFBP‐3 made little difference (regression coefficient: 4·1 ng/ml; ?2·8–10·9; P = 0·2). There was little evidence for an association between breastfeeding and IGFBP‐3 or the molar ratio IGF‐I/IGFBP‐3. Conclusions The positive association between breastfeeding and IGF‐I could be due to residual confounding or to chance. Nevertheless, the magnitude of the fully adjusted effect estimate and the novelty of the association suggest that larger studies should now be conducted to confirm or refute the hypothesis that variations in IGF‐I by infant feeding mode explain associations of breastfeeding with health in later life.     

Bromocriptine for Cocaine Dependence

On the basis of the dopamine depletion theory, bromocriptine has been tested to treat cocaine withdrawal and dependence. The authors conducted a 6-week study with 1 week of pretreatment observation and 5 weeks of a randomized, double-blind, placebo-controlled clinical trial of bromocriptine for DSM-III-R-defined cocaine dependence in methadone-maintained male patients. The bromocriptine group (n = 24) did not differ from the placebo group (n = 26) in self-reported cocaine use, proportion of positive urine toxicology samples, craving for cocaine, resistance to cocaine use, or mood symptoms between the pretreatment baseline and the last week of the clinical trial. Both groups showed significant reduction in self-reported frequency of cocaine use, resistance to craving, and mood symptoms during participation in the protocol. The results of this study are consistent with recent clinical and laboratory findings in primary cocaine users. Despite initially promising pilot studies, recent evidence does not support the efficacy of bromocriptine to reduce cocaine use or craving.     

Is serial determination of inspiratory muscle strength a useful prognostic marker in chronic heart failure?

BACKGROUND: Little data exists on the prognostic role of inspiratory muscle strength (PImax) in chronic heart failure (CHF). Training studies, however, frequently use it as a therapeutic target and surrogate marker for prognosis. The prognostic value of changes of PImax that allow this extrapolation is unknown. DESIGN: Patients with stable CHF were prospectively included and 1-year and all-time event rates recorded for endpoint analysis. METHODS: In 158 patients (85% men; New York Heart Association functional class: 2.4+/-0.6), PImax was measured along with clinical evaluations at two visits, the initial visit and the second visit, 6.4+/-1.4 months apart. The mean follow-up was 59+/-34 months. RESULTS: Overall, 59 patients (37%) reached the primary endpoint of death or hospitalization (endpoint positive), and overall mortality rate (secondary endpoint) was 26% (42 patients). PImax did not differ between endpoint-negative and endpoint-positive patients, both at the initial and at the second visit (8.3+/-5.6 vs. 7.3+/-3.4 kPa and 8.8+/-6.0 vs. 7.9+/-3.6 kPa, respectively; P=NS), and both groups showed increased PImax (0.6+/-2.6 vs. 0.6+/-2.8 kPa; P=NS). Cox analyses found neither the absolute nor the relative change of PImax to be significant predictors for the primary and secondary endpoints (P=NS for both), both for the 1-year and for the all-time event rates. Endpoint rates did not differ between patients showing increasing or decreasing PImax (P=NS; relative risk (RR): 0.77; 95% confidence interval: 0.47-1.27). CONCLUSION: Trials focusing on inspiratory muscle function should use the actual levels of PImax as a surrogate marker to represent prognostic information, rather than relative or absolute changes. This is the first study to investigate the prognostic information of the changes of PImax over time, regarding both short-term and long-term morbidity and mortality in patients with stable CHF.     

Essential role of p21/waf1 in the mediation of the anti-proliferative effects of GHRH antagonist JMR-132

GHRH, besides its neuroendocrine action in controlling the release of GH from the pituitary, stimulates the growth of various cancers in vivo and in vitro by direct mechanism(s). However, the molecular mechanism that mediates these proliferative effects of GHRH in extrapituitary tissues remains poorly characterized. In the present study, we investigated whether the tumor suppressor p21/waf1 is involved in the mediation of the proliferative effects of GHRH in A549 human lung cancer epithelial cells. Exposure of A549 cells to the GHRH antagonist JMR-132 caused a significant inhibition in the rate of cell proliferation. In A549 cells, GHRH suppressed while JMR-132 increased the levels of p21 expression in a dose-dependent manner. This suggests that GHRH could regulate p21 levels. We then evaluated whether p21 is required in A549 cells for the regulation of cell proliferation by GHRH. To this end, we knocked-down p21 expression in A549 cells by siRNA and assessed the effects of antagonist JMR-132 on cell proliferation. We found that the loss of p21 expression abolished the anti-proliferative effects of JMR-132. Suppression of p21 expression by siRNA in human HT29 colon cancer cells and non-transformed mouse osteoblasts KS483 also blocked the anti-proliferative effects of JMR-132 suggesting that the regulation of cell proliferation by GHRH is p21 dependent. These results shed light on the molecular mechanism of action of GHRH antagonists in tumor tissues and suggest that the antineoplastic activity of GHRH antagonists could be considered for the treatment of cancers expressing p21.     

Complete mesocolic excision and extended (D3) lymphadenectomy for colonic cancer: is it worth that extra effort? A review of the literature

Purpose

Recent interest in complete mesocolic excision (CME) with central vascular ligation (CVL) or extended (D3) lymphadenectomy (EL) for curative resection of colon cancer has been driven by published series from experienced practitioners showing excellent survival outcomes and low recurrence rates. In this article, we attempt to clarify the role of CME or EL in modern colorectal surgery.

Methods

A narrative review of the evidence for CME and EL in the curative treatment of colon cancer.

Results

The principal of CME surgery, similar to total mesorectal excision (TME) for rectal cancer, is the removal of all lymphatic, vascular, and neural tissue in the drainage area of the tumour in a complete mesocolic envelope with intact mesentery, peritoneum and encasing fascia. Extended (D3) lymphadenectomy (EL) is based on similar principles. Sound anatomical and oncological arguments are made to support the principles of removing the tumor contained within an intact mesocolic facial envelope together with an extended lymph node harvest. Excellent oncological outcomes with minimal morbidity and mortality have been reported. This has led to calls for the standardisation of surgery for colon cancer using CME. However, there is conflicting evidence regarding the prognostic benefit of greater lymph node harvests and the evidence for an oncological benefit of CME is limited by methodology flaws and several potential confounding factors.

Conclusions

Although there is a reasonable anatomical and oncological basis for these techniques, there are no randomised controlled trials from which to draw confident conclusions and there is insufficient consistent high quality evidence to recommend widespread adoption of CME.

     

Germinal center B (GCB) and non-GCB cell-like diffuse large B cell lymphomas have similar outcomes following autologous haematopoietic stem cell transplantation

Patients with germinal center B cell-like (GCB) and non-GCB diffuse large B cell lymphomas (DLBCL) receiving first line therapy have distinct prognosis. We explored the differences in outcome following salvage autologous hematopoietic stem cell (HSC) transplantation between patients with GCB and non-GCB DLBCL. Forty-four patients with relapsed and 15 patients with primary refractory chemosensitive disease undergoing BEAM (BCNU [carmustine], etoposide, cytarabine, melphalan) conditioning and autologous HSC were included. Immunohistochemical analysis was performed for CD10, BCL-6, MUM1 (allowing classification into GCB and non-GCB-like DLBCL) and BCL-2. Median follow-up of survivors was 25 months; median age at the time of transplantation was 60 years (range 17–77). Thirty-two patients (54%) were classified as having GCB and 27 (46%) as having non-GCB-like DLBCL. Patients with GCB and non-GCB DLBCL did not differ in the risk of progression after HSC transplant ( P  = 0·78) or overall survival ( P  = 0·48). In multivariate analysis, only time to progression after initial treatment impacted overall survival. We conclude that patients with relapsed or primary refractory chemosensitive GCB and non-GCB-like DLBCL derive similar benefit from autologous HSC transplant.     

Fetal lamb coagulation system during birth asphyxia

Levels of many coagulation factors are low in the healthy infant and even lower in the asphyxiated premature infant. We investigated whether a brief exposure to asphyxia at the time of birth causes the activation and consumption of coagulation factors. Following delivery by caesarean section, premature lambs were asphyxiated by occluding the endotracheal tube for 10 min and then resuscitated. Blood was obtained prior to and following birth for measurement of blood gases and the coagulation system. Birth asphyxia in the premature lamb resulted in thrombin generation and rapid consumption of specific coagulation factors.     

Abnormalities of pulmonary artery wedge pressures in sleep-induced apnea

Six patients with sleep apnea syndrome were studied with continuous hemodynamic monitoring during sleep. Sleep apnea had been previously documented with an average number of apneas per hour of sleep ranging from 23 to 93 (mean 63). There was a significant decrease in heart rate during sleep (82 ± 5 to 69 ± 6, P < 0.01). There was a significant rise in systemic blood pressure (103 ± 2 mm Hg to 116 ± 6 mm Hg, P < 0.05) and pulmonary artery pressure (20 ± 1 mm Hg to 32 ± 5 mm Hg) during sleep. In addition, pulmonary artery wedge pressure increased (12 ± 2 mm Hg to 20 ± 3 mm Hg, P < 0.05) during sleep and 5 of the 6 patients developed an abnormal pulmonary wedge pressure. There was a significant decrease in P_O2 during sleep (71 ± 3 mm Hg to 49 ± 2 mm Hg, P < 0.005). These findings suggest that increases in pulmonary wedge pressures may be contributing to increase in pulmonary artery pressures in these patients during sleep.     

A randomized,double-blind,placebo-controlled trial of dexamethasone in severe respiratory syncytial virus (RSV) infection: effects on RSV quantity and clinical outcome

Forty-one previously healthy children <2 years of age who required mechanical ventilation for respiratory syncytial virus (RSV) infection were randomized to receive dexamethasone (0.5 mg/kg; n=22) or saline placebo (n=19) intravenously every 12 h for 4 days. RSV quantity was measured by quantitative plaque assay in fresh tracheal and nasal aspirates obtained at intervals of 24+/-3 h on days 0, 1, 2, 5, and 7 following entry. Analysis by linear mixed-effects modeling demonstrated a significantly greater decline in mean tracheal RSV quantity in the placebo group than in the dexamethasone group from day 0 to day 1 (0.82 vs. 0.21 log pfu/mL; P=.01) and from day 0 to day 2 (1.45 vs. 0.53 log pfu/mL; P=.03). No differences were found between groups in nasal RSV quantity, white blood cell counts in tracheal or nasal aspirates, serum neutralizing antibody titers during convalescence, or duration of mechanical ventilation, intensive care unit stay, or hospital stay.     

Acute pancreatitis in patients on chronic peritoneal dialysis: an increased risk?

OBJECTIVES: The primary aim of this study is to determine if patients with end-stage renal disease (ESRD) on peritoneal dialysis (PD) have a higher risk of developing acute pancreatitis (AP) than patients on hemodialysis (HD). The secondary aim is to compare the outcomes of AP between the two groups. METHOD: This is a retrospective case-control study. The study groups consisted of all patients initiated on HD and PD between January 1, 1998 and August 1, 2003. AP was identified using ICD-9 codes. Statistical analysis was carried out using Poisson regression, Kaplan-Meier curve, log-rank test, and Cox regression. RESULTS: One thousand two hundred and thirty-three and 160 eligible patients were identified in the HD and PD groups, respectively. Twenty-eight patients had AP. Eight patients were excluded as they had identifiable etiologies for AP. Of the remaining 20 patients with AP, 14 were in the HD group and 6 were in the PD group (p= 0.009). Incidence of AP was 18.4 per 1,000 person-years in the PD group and 6.5 per 1,000 person-years in the HD group (p= 0.033). Kaplan-Meier curves showed a significant difference in AP-free survival between the two groups (log-rank p= 0.026). Using time-dependent analysis, the hazard ratio for AP in PD patients after adjustment for age and sex was 3.94 (p= 0.006). There was no observed difference in length of hospital stay and ICU stay. All cases of AP were interstitial. There were no complications or deaths related to AP. CONCLUSION: PD is a risk factor for AP. There is no statistical difference in AP-related mortality and morbidity between HD and PD.