Perceptions of success of a local UK public health collaborative†.

Summary: Successful public health initiatives require multi-sector collaboration. AVONet was a UK collaborative developed to provide evidence-based strategies for active ageing. This study explored the success of AVONet in the achievement of its objectives as perceived by all partners. A convergent parallel mixed-methods design was employed, utilizing a quantitative survey and qualitative semi-structured interviews. Data collection was undertaken in September 2010, 18 months after establishing the collaborative and 6 months after funding had ceased. AVONet partners (n = 24) completed a 27-item survey. A sub-sample of four academics and four practitioners participated in semi-structured interviews. Quantitative and qualitative comparisons were made between academics' and practitioners' perceptions of success, potential for sustainability and satisfaction with structure and relationships. Participants perceived the AVONet collaborative positively. Significant between-group (academic v practitioner) differences in survey responses were observed for success (U = 19.5; p = 0.003) and structure (U = 125.5; p = 0.001). Strong positive correlations were observed between success and structure and balance between information transfer and exchange (r = 0.756; p < 0.001). Interviews confirmed positive perceptions and perceived importance of the collaborative and highlighted the need for further integration and tangible outcomes for practitioners. Suggestions to enhance sustainability were provided, such as smaller working groups and local council-led governance. Perceived success in building a multi-sectoral collaborative can be achieved during a 10-month period, despite differing needs of contributors. For collaboratives developed as a result of external funding aimed primarily at facilitating research, involvement of practitioners at an early stage may help set more comprehensive goals, supportive communication strategies, and increase potential for sustainability.

Long-term cognitive impairment after critical illness.

BACKGROUND: Survivors of critical illness often have a prolonged and disabling form of cognitive impairment that remains inadequately characterized. METHODS: We enrolled adults with respiratory failure or shock in the medical or surgical intensive care unit (ICU), evaluated them for in-hospital delirium, and assessed global cognition and executive function 3 and 12 months after discharge with the use of the Repeatable Battery for the Assessment of Neuropsychological Status (population age-adjusted mean [±SD] score, 100±15, with lower values indicating worse global cognition) and the Trail Making Test, Part B (population age-, sex-, and education-adjusted mean score, 50±10, with lower scores indicating worse executive function). Associations of the duration of delirium and the use of sedative or analgesic agents with the outcomes were assessed with the use of linear regression, with adjustment for potential confounders. RESULTS: Of the 821 patients enrolled, 6% had cognitive impairment at baseline, and delirium developed in 74% during the hospital stay. At 3 months, 40% of the patients had global cognition scores that were 1.5 SD below the population means (similar to scores for patients with moderate traumatic brain injury), and 26% had scores 2 SD below the population means (similar to scores for patients with mild Alzheimer's disease). Deficits occurred in both older and younger patients and persisted, with 34% and 24% of all patients with assessments at 12 months that were similar to scores for patients with moderate traumatic brain injury and scores for patients with mild Alzheimer's disease, respectively. A longer duration of delirium was independently associated with worse global cognition at 3 and 12 months (P=0.001 and P=0.04, respectively) and worse executive function at 3 and 12 months (P=0.004 and P=0.007, respectively). Use of sedative or analgesic medications was not consistently associated with cognitive impairment at 3 and 12 months. CONCLUSIONS: Patients in medical and surgical ICUs are at high risk for long-term cognitive impairment. A longer duration of delirium in the hospital was associated with worse global cognition and executive function scores at 3 and 12 months. (Funded by the National Institutes of Health and others; BRAIN-ICU ClinicalTrials.gov number, NCT00392795.).

Striatal dopamine release in schizophrenia comorbid with substance dependence.

Dopamine (DA) has a role in the pathophysiology of schizophrenia and addiction. Imaging studies have indicated that striatal DA release is increased in schizophrenia, predominantly in the precommissural caudate (preDCA), and blunted in addiction, mostly in the ventral striatum (VST). Therefore, we aimed to measure striatal DA release in patients with comorbid schizophrenia and substance dependence. We used [(11)C]raclopride positron emission tomography and an amphetamine challenge to measure baseline DA D2-receptor availability (BPND) and its percent change post-amphetamine (ΔBPND, to index amphetamine-induced DA release) in striatal subregions in 11 unmedicated, drug-free patients with both schizophrenia and substance dependence, and 15 healthy controls. There were no significant group differences in baseline BPND. Linear mixed modeling using ΔBPND as the dependent variable and striatal region of interest as a repeated measure indicated a significant main effect of diagnosis, F(1,24)=8.38, P=0.008, with significantly smaller ΔBPND in patients in all striatal subregions (all P ≤ 0.04) except VST. Among patients, change in positive symptoms after amphetamine was significantly associated with ΔBPND in the preDCA (rs=0.69, P=0.03) and VST (rs=0.64, P=0.05). In conclusion, patients with comorbid schizophrenia and substance dependence showed significant blunting of striatal DA release, in contrast to what has been found in schizophrenia without substance dependence. Despite this blunting, DA release was associated with the transient amphetamine-induced positive-symptom change, as observed in schizophrenia. This is the first description of a group of patients with schizophrenia who display low presynaptic DA release, yet show a psychotic reaction to increases in D2 stimulation, suggesting abnormal postsynaptic D2 function.

Changes in reported food intake in adults with type 2 diabetes in response to a nonprescriptive dietary intervention.

OBJECTIVES: There is a lack of published data about the food intake of patients with type 2 diabetes and the changes that they make in response to patient-centred dietary advice. The present study describes the changes reported in response to a nonprescriptive dietary intervention based upon UK dietary guidelines. METHODS: Two hundred and sixty-two patients (87 women and 175 men) from the Early ACTivity in Diabetes (ACTID) trial who received the dietary intervention returned 4 days food diaries at baseline and 6 months. Nonparametric tests were used to examine changes in meal patterns, total energy intake and energy from food groups between baseline and 6 months. RESULTS: Mean (SD) number of reported meals day(-1) was 3.0 (0.3) and mean (SD) number of snacks was 1.1 (0.6) at both baseline and 6 months for men and women. Men reported decreasing energy intake by a mean (SD) of 912 (1389) KJ/day [218 (332) kcal day(-1) ] (P < 0.001) and women by 515 (1130) KJ/day [123 (270) kcal day(-1) ] (P < 0.001). Men reported reducing energy from alcoholic drinks [-234 (527) KJ day(-1) ; P < 0.001], white bread [-113 (402) KJ day(-1) ; P = 0.001], biscuits [i.e. cookies -67 (205) KJ day(-1) ; P < 0.001] and cakes [-50 (410) KJ day(-1) ; P = 0.0012]. Women reported reducing energy from mixed main meals [-134 (456) KJ day(-1) ; P = 0.036], pasta and rice [-79 (326) KJ day(-1) ; P = 0.019], high-energy drinks [-59 (159) KJ day(-1) ; P = 0.001] and white bread [-59 (368) KJ day(-1) ; P = 0.042]. CONCLUSIONS: Men and women in the Early ACTID study reported small changes in higher-energy and lower-fibre foods and drinks in response to patient-centred dietary advice.

Histopathological diagnosis and surgical complications following bilateral anal sacculectomy for the treatment of unilateral canine apocrine gland anal sac adenocarcinoma: 35 cases (2019-2023).

OBJECTIVES: To report the histopathological diagnosis of both anal sacs in dogs undergoing bilateral anal sacculectomy for the treatment of unilateral apocrine gland anal sac adenocarcinoma and to compare the surgical complication rate associated with this procedure in this population with previously published literature. MATERIALS AND METHODS: Records were retrospectively reviewed for dogs that underwent bilateral anal sacculectomy for the treatment of apparently unilateral apocrine gland anal sac adenocarcinoma, at a single institute between 2019 and 2023. Clinical staging, surgical treatment, histological findings, intra- and postoperative complications were evaluated. RESULTS: Thirty-five dogs were included. Only five of 35 (14%) dogs were found to have histologically normal contralateral anal sacs. Non-neoplastic anal sac disease was found in 23 of 35 (66%) dogs and bilateral apocrine gland anal sac adenocarcinoma was seen in seven of 35 (20%) dogs. None of the dogs diagnosed with bilateral neoplasia had evidence of bilateral neoplasia before surgery despite a thorough work-up. Complications attributable to the primary tumour removal were seen in 9% of dogs intraoperatively and 14% of dogs postoperatively, commonly tumour capsule disruption and surgical site infection, respectively. CLINICAL SIGNIFICANCE: Bilateral anal sac disease was diagnosed histologically in the majority of presumed normal anal sacs, with 20% of cases being found to have bilateral apocrine gland anal sac adenocarcinoma. The surgical complication rates of this cohort were comparable to those reported for unilateral anal sacculectomy alone. These findings promote and encourage the use of bilateral anal sacculectomy in cases of suspected unilateral anal sac neoplasia.

Insulin-like growth factor-1 and delirium in critically ill mechanically ventilated patients: a preliminary investigation.

BACKGROUND: Delirium occurs frequently in the intensive care unit (ICU), but its pathophysiology is still unclear. Low levels of insulin-like growth factor 1 (IGF-1), a hormone with neuroprotective properties, have been associated with delirium in some non-ICU studies, but this relationship has not been examined in the ICU. We sought to test the hypothesis that low IGF-1 concentrations are associated with delirium during critical illness. METHODS: Mechanically ventilated medical ICU patients were prospectively enrolled, and blood was collected after enrollment for measurement of IGF-1 using radioimmunometric assay. Delirium and coma were identified daily using the Confusion Assessment Method for the ICU and the Richmond Agitation-Sedation Scale, respectively. The association between IGF-1 and delirium was evaluated with logistic regression. In addition, the association between IGF-1 and duration of normal mental state, measured as days alive without delirium or coma, was assessed using multiple linear regression. RESULTS: Among 110 patients, the median age was 65 years (IQR, 52-75) and APACHE II was 27 (IQR, 22 -32). IGF-1 levels were not a risk factor for delirium on the day after IGF-1 measurement (p = 0.97), at which time 65% of the assessable patients were delirious. No significant association was found between IGF-1 levels and duration of normal mental state (p = 0.23). CONCLUSIONS: This pilot study, the first to investigate IGF-1 and delirium in critically ill patients, found no association between IGF-1 and delirium. Future studies including serial measurements of IGF-1 and IGF-1 binding proteins are needed to determine whether this hormone has a role in delirium during critical illness.

Peptide gels of fully-defined composition and mechanics for probing cell-cell and cell-matrix interactions in vitro.

Current materials used for in vitro 3D cell culture are often limited by their poor similarity to human tissue, batch-to-batch variability and complexity of composition and manufacture. Here, we present a "blank slate" culture environment based on a self-assembling peptide gel free from matrix motifs. The gel can be customised by incorporating matrix components selected to match the target tissue, with independent control of mechanical properties. Therefore the matrix components are restricted to those specifically added, or those synthesised by encapsulated cells. The flexible 3D culture platform provides full control over biochemical and physical properties, allowing the impact of biochemical composition and tissue mechanics to be separately evaluated in vitro. Here, we demonstrate that the peptide gels support the growth of a range of cells including human induced pluripotent stem cells and human cancer cell lines. Furthermore, we present proof-of-concept that the peptide gels can be used to build disease-relevant models. Controlling the peptide gelator concentration allows peptide gel stiffness to be matched to normal breast (<1 kPa) or breast tumour tissue (>1 kPa), with higher stiffness favouring the viability of breast cancer cells over normal breast cells. In parallel, the peptide gels may be modified with matrix components relevant to human breast, such as collagen I and hyaluronan. The choice and concentration of these additions affect the size, shape and organisation of breast epithelial cell structures formed in co-culture with fibroblasts. This system therefore provides a means of unravelling the individual influences of matrix, mechanical properties and cell-cell interactions in cancer and other diseases.

Patent foramen ovale, cardiac valve thickening, and antiphospholipid antibodies as risk factors for subsequent vascular events: the PICSS-APASS study.

BACKGROUND AND PURPOSE: We sought to estimate risk of recurrent stroke/TIA/death in the subgroup of the Patent Foramen Ovale in the Cryptogenic Stroke Study (PICSS) cohort with patent foramen ovale (PFO) and antiphospholipid antibodies (aPL) and to estimate risk of recurrent stroke/TIA/death in aPL-positive patients who have thickened left-side heart valves (VaT). PFO is associated with cryptogenic ischemic stroke. Also, the presence of aPL is associated with ischemic cerebrovascular disease. METHODS: Combined data from 2 major substudies of the Warfarin Aspirin Recurrent Stroke Trial (WARSS) were evaluated. PICSS subjects were included if they were enrolled in the Antiphospholipid Antibodies and Stroke Study (APASS) and underwent a baseline aPL test (lupus anticoagulant, anticardiolipin antibodies, or both) within 1 month of the stroke. All patients in PICSS underwent transesophageal echocardiography for PFO as well as VaT, which was performed blinded to aPL status and treatment arm (325 mg/day aspirin or adjusted dose warfarin; target international normalized ratio, 1.4-2.8). The primary outcome event was the 2-year risk of recurrent stroke/TIA/death and was evaluated using Cox proportional hazards model. Because there was no treatment effect, warfarin and aspirin groups were combined to increase power. For the combined end point, power to detect HR of 2 was 47.8% for the PFO and aPL-positive group, and 75.3% for the valve thickening and aPL-positive group, assuming 2-sided type I error of 0.05. RESULTS: Five hundred twenty-five subjects were tested for the combined presence of PFO and aPL and were available for evaluation. The primary outcome event rate was 23.9% (HR, 1.39; 95% CI, 0.75-2.59) in the PFO-positive/aPL-positive group, compared to 13.9% (HR, 0.83; 95% CI, 0.44-1.56) in the PFO-positive/aPL-negative group, and 19.9% (HR, 1.16; 95% CI, 0.68-1.90) in the PFO-negative/aPL-positive group. Five hundred forty-five subjects tested for combined presence of aPL and left-side cardiac VaT were available for evaluation. The primary event rate was 22.6% (HR, 1.65; 95% CI, 0.88-3.09) in the VaT-positive/aPL-positive group, compared to 19.4% (HR, 1.50; 95% CI, 0.82-2.75) in the VaT-positive/aPL-negative group, and 20.2% (HR, 1.63; 95% CI, 0.81-3.25) in the VaT-negative/aPL-positive group. CONCLUSIONS: The combined presence of aPL either with a PFO or with left-side cardiac VaT did not significantly increase risk of subsequent cerebrovascular events in this PICCS/APASS cohort of patients.

Oral anticoagulation in patients with cardiomyopathy or heart failure in sinus rhythm.

BACKGROUND: Despite many prospective randomized studies defining the benefits of anticoagulation in atrial fibrillation (AF), there have been no adequate studies in cardiomyopathy (CM) in sinus rhythm. METHODS: We review the current knowledge of the risk of stroke in CM, left ventricular systolic dysfunction and heart failure as well as the indications for antithrombotic agents and compare this with AF. RESULTS: The current knowledge of risk factors for stroke and indications for antithrombotic agents in CM is similar to that of AF prior to the treatment studies of the 1980s-1990s. CONCLUSION: Prospective randomized trial data are urgently needed to determine the role of antithrombotic drugs in CM.

Preferences for commercial strawberry drinkable yogurts among African American, Caucasian, and Hispanic consumers in the United States.

The drinkable yogurt marketplace is a competitive and growing category in the dairy industry. Understanding sensory differences is critical for understanding the product, and ultimately, consumer preference. The objective of this study was to identify and define the sensory characteristics of commercial drinkable yogurts and link these specific sensory attributes to consumer preferences among Caucasian, African American, and Hispanic consumers in the United States. Focus groups with each ethnic group (n = 10 for each group) were conducted to gain insights into perceptions of drinkable yogurts. A descriptive sensory language was identified to document the sensory properties (visual, flavor, and mouthfeel) of drinkable yogurts. Thirteen commercial drinkable yogurts (strawberry flavor) were subsequently evaluated by a trained sensory panel using the developed sensory language. Five representative yogurts were chosen for consumer testing by each ethnic group (minimum of 75 consumers per group). Both internal and external preference mapping was conducted to identify key drivers of liking. Drinkable yogurts were differentiated by descriptive analysis in visual, flavor, and mouthfeel attributes. Variability was observed in consumer acceptability across the 3 ethnic groups, but these differences were small compared with differences observed among 3 identified consumer preference clusters regardless of ethnicity. Key drivers for all 3 clusters were natural strawberry flavor/aroma and sweet taste. The influence of intensity changes in these 3 drivers along with the presence or absence of other attributes differentiated the 3 clusters. Acceptability varies widely among consumers, and drinkable yogurts with specific flavor and physical properties could be marketed to specific target market segments. The results indicate that these consumer clusters are not defined solely by ethnicity.

Managing the screen-viewing behaviours of children aged 5-6 years: a qualitative analysis of parental strategies.

OBJECTIVES: The present study used qualitative methods to: (1) examine the strategies that were used by parents of children aged 5-6 years to manage screen viewing; (2) identify key factors that affect the implementation of the strategies and (3) develop suggestions for future intervention content. DESIGN: Telephone interviews were conducted with parents of children aged 5-6 years participating in a larger study. Interviews were transcribed verbatim and analysed using an inductive and deductive content analysis. Coding and theme generation was iterative and refined throughout. SETTING: Parents were recruited through 57 primary schools located in the greater Bristol area (UK). PARTICIPANTS: 53 parents of children aged 5-6 years. RESULTS: Parents reported that for many children, screen viewing was a highly desirable behaviour that was difficult to manage, and that parents used the provision of screen viewing as a tool for reward and/or punishment. Parents managed screen viewing by setting limits in relation to daily events such as meals, before and after school, and bedtime. Screen-viewing rules were often altered depending on parental preferences and tasks. Inconsistent messaging within and between parents represented a source of conflict at times. Potential strategies to facilitate reducing screen viewing were identified, including setting screen-viewing limits in relation to specific events, collaborative rule setting, monitoring that involves mothers, fathers and the child, developing a family-specific set of alternative activities to screen viewing and developing a child's ability to self-monitor their own screen viewing. CONCLUSIONS: Managing screen viewing is a challenge for many parents and can often cause tension in the home. The data presented in this paper provide key suggestions of new approaches that could be incorporated into behaviour change programmes to reduce child screen viewing.

Characterization of ferritin in murine erythroleukaemia cells.

Murine erythroleukaemic cells were studied to determine whether different isoferritins have different functions. The cells were labelled with radioactive iron and the pattern of isoferritins was analysed by chromatofocussing. No change was found after iron-loading the cells but after inducing erythroid differentiation with dimethyl sulphoxide (DMSO), iron was incorporated into both more basic and more acidic isoferritins. This was compared to ferritin subunit synthesis; DMSO induced the synthesis of a third, minor subunit whereas iron-loading had no effect. The fate of murine erythroleukaemic cell ferritin iron was followed after incubations in iron-deficient medium containing DMSO; some, but not all, of the ferritin iron was mobilized and used for haem synthesis, and the remaining iron was found amongst the more basic isoferritins. Finally, sequential radioactive iron labels were used to demonstrate that the movement of iron from ferritin to haem was compatible with the 'last-in-first-out' principle, but this could not be related to different isoferritins. These results show firstly that DMSO changes the pattern of isoferritins and ferritin subunits in murine erythroleukaemic cells. Secondly, iron associated with more basic isoferritins seems to be less easily mobilized for haem synthesis. These results support the concept that different isoferritins have different functions.

A systematic review of brief dietary questionnaires suitable for clinical use in the prevention and management of obesity, cardiovascular disease and type 2 diabetes.

The aim of this systematic review was to identify and describe brief dietary assessment tools suitable for use in clinical practice in the management of obesity, cardiovascular disease and type 2 diabetes. Papers describing development of brief (<35 items) dietary assessment questionnaires, that were accessible, simple to score and assessed aspects of the diet of relevance to the conditions of interest were identified from electronic databases. The development of 35 tools was described in 47 papers. Ten tools assessed healthy eating or healthy dietary patterns, 2 assessed adherence to the Mediterranean diet, 18 assessed dietary fat intake, and 5 assessed vegetable and/or fruit intake. Twenty tools were developed in North America. Test-retest reliability was conducted on 18 tools; correlation coefficients for total scores ranged from 0.59 to 0.95. Relative validation was conducted on 34 tools. The most common reference variable was percentage energy from fat (15 tools) and correlation coefficients ranged from 0.24, P<0.001 to 0.79, P<0.002. Tools that have been evaluated for reliability and/or relative validity are suitable for guiding clinicians when providing dietary advice. Variation in study design, settings and populations makes it difficult to recommend one tool over another, although future developers can enhance the understanding and use of tools by giving clear guidance as to the strengths and limitations of the study design. When selecting a tool, clinicians should consider whether their patient population is similar in characteristics to the evaluation sample.

The influence of friends and siblings on the physical activity and screen viewing behaviours of children aged 5-6 years: a qualitative analysis of parent interviews.

OBJECTIVES: The present study uses qualitative data to explore parental perceptions of how their young child's screen viewing and physical activity behaviours are influenced by their child's friends and siblings. DESIGN: Telephone interviews were conducted with parents of year 1 children (age 5-6 years). Interviews considered parental views on a variety of issues related to their child's screen viewing and physical activity behaviours, including the influence that their child's friends and siblings have over such behaviours. Interviews were transcribed verbatim and analysed using deductive content analysis. Data were organised using a categorisation matrix developed by the research team. Coding and theme generation was iterative and refined throughout. Data were entered into and coded within N-Vivo. SETTING: Parents were recruited through 57 primary schools located in Bristol and the surrounding area that took part in the B-ProAct1v study. PARTICIPANTS: Fifty-three parents of children aged 5-6 years. RESULTS: Parents believe that their child's screen viewing and physical activity behaviours are influenced by their child's siblings and friends. Friends are considered to have a greater influence over the structured physical activities a child asks to participate in, whereas the influence of siblings is more strongly perceived over informal and spontaneous physical activities. In terms of screen viewing, parents suggest that their child's friends can heavily influence the content their child wishes to consume, however, siblings have a more direct and tangible influence over what a child watches. CONCLUSIONS: Friends and siblings influence young children's physical activity and screen viewing behaviours. Child-focused physical activity and screen viewing interventions should consider the important influence that siblings and friends have over these behaviours.

Effects of recombinant insulin-like growth factor-I and growth hormone on bone turnover in elderly women.

We evaluated the effects of recombinant insulin-like growth factor-I (IGF-I) and growth hormone (GH) on calciotropic hormones and bone turnover markers in 16 healthy elderly women 71.9 +/- 1.3 years of age (mean +/- SEM). Subjects consumed a fixed diet providing 1000 mg of calcium and 0.9 g/kg of protein for 10 days before starting baseline 24-h urine and blood collections. Specimens were collected for 6 consecutive days before initiating subcutaneous injections of GH (25 micrograms/kg/day, n = 5) and IGF-I at 60 micrograms/kg b.i.d. (high-dose, n = 5) or at 15 micrograms/kg b.i.d. (low-dose, n = 6) for 28 days. Resorption markers included urine hydroxyproline (OHP), total pyridinolines (PYD), and N-telopeptide; formation markers include osteocalcin, skeletal alkaline phosphatase (sALP), and type I procollagen carboxy-terminal extension peptide (CICP). For each subject, baseline daily turnover markers varied substantially (DV = 16-22%). With GH and high-dose IGF-I, resorption and formation markers increased progressively to maximum levels at day 21. For GH, the increase in day 21 PYD, N-telopeptide, osteocalcin, and CICP was 143, 111, 53, and 81%, respectively (p < 0.96-0.02). For high-dose IGF-I, these increases were 108, 81, 77, and 111% (p < 0.02-0.002). However, with low-dose IGF-I no change was observed in resorption markers while osteocalcin and CICP increased progressively (day 21, % increases = 88 +/- 51, 36 +/- 14). Twenty-four hour urine collections during the last days of baseline and of study drug were taken as six 4 h aliquots. When deoxyPYD was measured on these samples in the low-dose IGF-I group, a significant increase was observed only on the 0800-1200 h aliquot. Serum phosphorus concentrations increased with GH (21.2 +/- 3.3%) and high-dose IGF-I (8.8 +/- 3.6%) by day 21 but actually decreased by day 28 (-9.7 +/- 2.7, p < 0.02) with low-dose IGF-I. Urinary phosphorus excretion decreased with high-dose IGF-I only. Twenty-four hour calcium excretion increased with all treatments. These results indicate that both GH and high-dose IGF-I activate remodeling osteons. By contrast, low-dose IGF-I may directly increase osteoblastic function with only a minimal increase in bone resorption and may therefore provide a useful means to increase bone mass. The results also suggest some of the GH action on renal phosphorus handling represents a direct action of GH on the nephron which does not involve the intermediacy of IGF-I. Finally, even under controlled conditions bone turnover markers exhibit substantial daily variation so that a very large treatment effect will be required for these markers to have clinical utility.

Modulation of inositol(1,4,5)trisphosphate-sensitive calcium store content during continuous receptor activation and its effects on calcium entry.

Changes in intracellular Ca2+ concentration ([Ca2+]i) following the activation of muscarinic receptors with carbachol were studied in cells from the exocrine avian nasal gland that had been maintained in culture for 40-48 h. In these cells, the carbachol-induced sustained increase in [Ca2+]i could be further increased by the subsequent addition of thapsigargin. This increase was due to an additional release of intracellular Ca2+ and a corresponding further enhancement of Ca2+ entry. However, thapsigargin-sensitive and Ins(1,4,5)P3-sensitive stores appeared to be coincident and the initial carbachol stimulus was sufficient to completely empty these stores. It was concluded that the subsequent effect of thapsigargin was due to a partial refilling of the Ins(1,4,5)P3-sensitive stores despite the continued presence of agonist, an effect that was not the result of any decline in levels of cellular Ins(1,4,5)P3 or changes in the generation of Ins(1,3,4,5)P4, which were sustained throughout. Possible explanations for this refilling response include compartmentalization of intracellular Ins(1,4,5)P3, or a desensitization of the Ins(1,4,5)P3 receptor/Ca(2+)-release channel. Alternatively, the data are also compatible with a recently proposed kinetic separation of Ca2+ uptake and release sites. An important implication of this particular interpretation of our findings would be an apparent dependence of Ca2+ entry specifically on the status of the Ca(2+)-uptake component of the agonist-sensitive store, rather than the Ca(2+)-release component.

The effects of recombinant human insulin-like growth factor-I and growth hormone on body composition in elderly women.

The purpose of this study was to determine the effects of recombinant human GH (rhGH; 0.025 mg/kg.day) and one of two doses of recombinant human insulin-like growth factor-I (rhIGF-I; 0.015 and 0.060 mg/kg, twice daily) on body composition in elderly women. Sixteen healthy elderly women (mean age +/- SEM, 71.9 +/- 1.3 yr) were randomly assigned to receive either rhGH (GH; n = 5), low dose rhIGF-I (n = 6), or high dose rhIGF-I (n = 5). A 2-week predrug baseline period was followed by 4 weeks of hormone treatment, with a standardized diet fed throughout. All groups experienced a significant increase in serum IGF-I and IGFBP-3 levels over the treatment period, accompanied by significant decreases in IGF-II (P < 0.05). Fat mass decreased in all groups, with significant increases in lean body mass and nitrogen retention occurring in the high dose IGF and GH groups. Total body water did not change, whereas increases observed in intracellular fluid approached significance (P = 0.06). These anabolic changes were accompanied by numerous negative side-effects in the GH and high dose IGF groups, including headaches, lethargy, joint swelling/pain, and bloatedness. The low IGF dose was well tolerated. These results demonstrate that the administration of rhGH and rhIGF-I for 4 weeks results in anabolic changes in body composition in elderly women.

Effects of human growth hormone, insulin-like growth factor I, and diet and exercise on body composition of obese postmenopausal women.

To determine the effects of GH and insulin-like growth factor I (IGF-I) administration, diet, and exercise on weight loss, body composition, basal metabolic rate (BMR), muscle strength, and psychological status, 33 moderately obese postmenopausal women (67.1 +/- 5.2 yr) participated in a 12-week randomized, double blind study. Participants were placed on a diet that provided 500 Cal/day less than that needed for weight maintenance, and they walked 3 days and strength trained 2 days each week. Subjects also self-injected GH (0.025 mg/kg BW.day), IGF-I (0.015 mg/kg BW.day), a combination of these doses of GH and IGF-I, or placebo (P). Twenty-eight women completed the study, as five subjects dropped out due to intolerable side-effects (e.g. edema). Weight loss occurred in all groups, with the largest decrease occurring in the GH plus IGF-I group (5.6 +/- 1.4 kg). Fat mass significantly decreased in all groups, with the largest losses observed in GH and GH plus IGF-I groups (6.3 +/- 1.8 and 8.4 +/- 2.8 kg, respectively). Despite weight loss, BMR was maintained in all groups. Muscle strength increased with training for all groups, and depression and anxiety scores decreased in groups receiving IGF-I. These data show that obese postmenopausal women can lose weight and fat without compromising fat free mass, BMR, or gains in muscle strength, and that GH and IGF-I given together may enhance fat loss over either given alone.

Effects of diet and exercise on energy expenditure in postmenopausal women.

The purpose of this study was to determine the effect of a 24-wk diet + exercise (DE) or diet-only program on basal metabolic rate (BMR), bone mineral density (BMD), energy expended during daily activities, muscle strength, and maximal oxygen consumption (VO2max) in 40 postmenopausal women. Daily energy need was determined by measuring BMR and assessing physical activity with 8-d self-reported activity records. The DE group consumed 2092 kJ/d less than the daily energy need and walked and performed strength-training exercises during which they expended an additional 837 kJ/d. The two diet-only groups consumed either 2092 kJ/d (D-2092) or 2929 kJ/d (D-2929) less than the daily energy need. BMD, BMR, muscle strength, VO2max, and energy expended during lying, sitting, standing, and walking were measured at baseline and after 12 and 24 wk of treatment. A significant decrease in BMR and energy expended during sitting and walking occurred in all groups, with no significant differences observed among groups. Although the declines in BMR were significant, they were small and may not have been physiologically relevant. No changes in BMD or VO2max occurred, whereas strength increased significantly in the DE group. The results showed that postmenopausal women significantly improved their body composition over a period of 6 mo without experiencing a large decline in BMR, BMD, or select components of energy expenditure.

Effects of diet and exercise on common cardiovascular disease risk factors in moderately obese older women.

Diet and exercise studies of premenopausal women have shown reductions in obesity and other cardiovascular disease (CVD) risk factors. Forty-one healthy, moderately obese (120-140% of ideal body weight, LBW), postmenopausal women (65.6 +/- 3.3 y) participating in 24-wk diet or diet + exercise programs were studied to determine whether similar CVD risk reduction would occur. Daily energy need (DEN) was estimated from basal energy expenditure and self-reported activity. The diet + exercise group (n = 16) reduced their daily energy intake (DEI) by 2092 kJ from their DEN and expended 837 kJ/d in walking and resistance exercise. The two diet-only groups (n = 13 and n = 12) reduced their DEI by 2092 and 2929 kJ from their DEN, respectively. Body weight, waist-to-hip and subscapula-to-triceps ratios, blood lipids (total, low-density-lipoprotein, and high-density-lipoprotein cholesterol, and triacylglycerols), glucose, and insulin concentrations were measured at baseline and after 12 and 24 wk of diet and diet + exercise. Data were analyzed by using analysis of variance with repeated measures (P < or = 0.05) and Tukey's post hoc test. Loss of body weight was significant for all groups between baseline and 12 and 24 wk (baseline: 79.3 +/- 7.6 kg; 12 wk; 75.1 +/- 7.7 kg; 24 wk; 72.8 +/- 8.0 kg) but did not differ among groups. No significant time or treatment effects were observed between baseline and 24 wk for changes in mean blood lipid, glucose, and fasting insulin concentrations or measures of body fat distribution. Although 24 wk of diet or diet+exercise significantly reduced body weight in this group, this loss in body weight was not accompanied by a reduction of other commonly accepted CVD risks.