Serum-Starved Apoptotic Fibroblasts Reduce Blastocyst Production but Enable Development to Term after SCNT in Cattle

Cell cycle synchronization by serum starvation (SS) induces apoptosis in somatic cells. This side effect of SS is hypothesized to negatively affect the outcome of somatic cell nuclear transfer (SCNT). We determined whether apoptotic fibroblasts affect SCNT yields. Serum-starved, adult, bovine fibroblasts were stained with annexin V-FITC/propidium iodide to allow apoptosis detection by flow cytometry. Positive and negative cells sorted by fluorescence activated cell sorting (FACS) and an unsorted control group were used as nuclear donors for SCNT. Reconstructed embryos were cultured in vitro and transferred to synchronized recipients. Apoptosis had no effect on fusion and cleavage rates; however, it resulted in reductions in blastocyst production and quality measured by apoptotic index. However, reconstructed embryos with apoptotic cells resulted in pregnancy rates similar to that of the control on day 30, and generated one live female calf. In conclusion, we showed that apoptotic cells present in serum-starved cultures negatively affect embryo production after SCNT without compromising full-term development. Further studies will evaluate the ability of the oocyte to reprogram cells in specific phases of apoptosis.

Negative stress and the outcome of treatment for binge eating

This study investigated the ability of negatively versus positively perceived stress to predict outcome of treatment for binge eating disorder (BED). Participants were 62 obese women satisfying the DSMIV research criteria for BED. Stress was measured using an instrument based on the Recent Life Change Questionnaire (RLCQ). Participants experiencing high negative stress during the study period reported a binge eating frequency three times greater than that reported by subjects experiencing low negative stress (2.14 vs. 0.65 binge-days/week). Negative stress predicted how fast an individual would reduce binge eating and demonstrated more predictive power than positive stress.

Outcome with calcium channel antagonists after myocardial infarction: A community-based study

Objectives. We sought to estimate the risk of death and recurrent myocardial infarction associated with the use of calcium antagonists after myocardial infarction in a population-based cohort study. Background. Calcium antagonists are commonly prescribed after myocardial infarction, but their long-term effects are not well established. Methods. Patients 25 to 69 years old with a suspected myocardial infarction were identified and followed up through a community-based register of myocardial infarction and cardiac death (part of the World Health Organization Monitoring Trends and Determinants in Cardiovascular Disease [MONICA] Project in Newcastle, Australia). Data were collected by review of medical records, in-hospital interview and review of death certificates. Results. From 1989 to 1993, 3,982 patients with a nonfatal suspected myocardial infarction were enrolled in the study. At hospital discharge, 1,001 patients were treated with beta-adrenergic blocking agents, 923 with calcium antagonists, 711 with both beta-blockers and calcium antagonists and 1,346 with neither drug. Compared with patients given beta-blockers, patients given calcium antagonists were more likely to suffer myocardial infarction or cardiac death (adjusted relative risk [RR] 1.4, 95% confidence interval [CI] 1.0 to 1.9), cardiac death (RR 1.6, 95% CI 1.0 to 2.7) and death from all causes (RR 1.7, 95% CI 1.1 to 2.6). Compared with patients given neither beta-blockers nor calcium antagonists, patients given calcium antagonists were not at increased risk of myocardial infarction or cardiac death (RR 1.0, 95% CI 0.8 to 1.3), cardiac death (RR 0.9, 95% CI 0.6 to 1.2) or death from all causes (RR 1.0, 95% CI 0.7 to 1.3). No excess in risk of myocardial infarction or cardiac death was observed among patients taking verapamil (RR 0.9, 95% CI 0.6 to 1.6), diltiazem (RR 1.1, 95% CI 0.8 to 1.4) or nifedipine (RR 1.3, 95% CI 0.7 to 2.2) compared,vith patients taking neither calcium antagonists nor beta-blockers. Conclusions. These results are consistent with randomized trial data showing benefit from beta blockers after myocardial infarction and no effect on the risk of recurrent myocardial infarction and death with the use of calcium antagonists. Comparisons between beta-blockers and calcium antagonists favor beta blockers because of the beneficial effects of beta-blockers and not because of adverse effects of calcium antagonists. (C) 1998 by the American College of Cardiology.

Bioelectrical impedance analysis predicts outcome in patients with suspected bacteremia

Fluid shifts from intracellular to extracellular water (ICW to ECW) are a feature of sepsis, caused by increased vascular permeability and cell catabolism. Changes in ECW and total body water (TBW) were assessed in a prospective observational study of patients with bacteremia by a bedside technique, and its prognostic impact determined; In 78 hospital patients with fever, the resistance ratio (Rinf/RO) and estimated ECW/TBW ratio from multifrequency bioelectrical impedance analysis, and serum albumin concentration were measured. Rinf/RO and ECW/TBW ratios decreased from day 0 to 2 in patients with significant bacteremia (n = 31), but not in patients with doubtful or negative blood cultures (n = 22 and 25), Increased Rinf/RO at baseline, and further increase of ECW/TBW from day 0 to 2, were associated with lower rate of recovery after 1 week and with higher mortality. Baseline Rinf/RO above the median (0.75) had positive and negative predictive values of 0.31 and 0.95 for death. This prognostic effect was independent of underlying disease and blood culture result in a multivariate model. Hypoalbuminemia at baseline was predictive of outcome, but changes in albumin from day 0 to 2 were unrelated to blood culture results or outcome. In patients with bacteremia,fluid shifts from intracellular to extracellular,vater occur early are rapidly reversible by antibiotic treatment but are associated with adverse prognosis. Bioelectrical impedance deserves further study as a tool for bedside monitoring of patients with bacteremia.

Cluster analysis of self-awareness levels in adults with traumatic brain injury and relationship to outcome

The purpose of this study was to investigate the relationship between self-awareness, emotional distress, motivation, and outcome in adults with severe traumatic brain injury. A sample of 55 patients were selected from 120 consecutive patients with severe traumatic brain injury admitted to the rehabilitation unit of a large metropolitan public hospital. Subjects received multidisciplinary inpatient rehabilitation and different types of outpatient rehabilitation and community-based services according to availability and need, Measures used in the cluster analysis were the Patient Competency Rating Scale, Self-Awareness of Deficits Interview, Head Injury Behavior Scale, Change Assessment Questionnaire, the Beck Depression Inventory, and Beck Anxiety Inventory; outcome measures were the Disability Rating Scale, Community Integration Questionnaire, and Sickness Impact Profile. A three-cluster solution was selected, with groups labeled as high self-awareness (n = 23), low self-awareness (n = 23), and good recovery (n = 8). The high self-awareness cluster had significantly higher levels of self-awareness, motivation, and emotional distress than the low self-awareness cluster but did not differ significantly in outcome. Self-awareness after brain injury is associated with greater motivation to change behavior and higher levels of depression and anxiety; however, it was not clear that this heightened motivation actually led to any improvement in outcome. Rehabilitation timing and approach may need to be tailored to match the individual's level of self-awareness, motivation, and emotional distress.

Self-efficacy for refusal mediated by outcome expectancies in the prediction of alcohol-dependence amongst young adults

The present study examined the relative importance of outcome expectancies and self-efficacy [1] in the prediction of alcohol dependence [2] and alcohol consumption in a sample of young adult drinkers drawn from a milieu previously reported as supportive of risky drinking. In predicting alcohol dependence, outcome expectancies were found to mediate self-efficacy and the same pattern was found for both males and females. This suggests that male and female drinkers may become more similar as they progress along the drinking continuum from risky drinking to dependent drinking. However, in women, in comparison to men, a greater array of expectancies and self-efficacy scales were found to predict heavy drinking, as measured by quantity and frequency. These results suggest that heavy drinking women are particularly at risk of developing drinking related complications and that preventative education needs to take into account gender differences.

The functional outcome of children after a burn injury: A pilot study

Assessment of functional outcome can be used as a measure of the effectiveness of intervention during recovery from a burn injury. This pilot study identifies the factors that are likely to be most important for determining standardized functional outcome measures for children after a burn injury; it highlights the contribution of these factors to variations in children's postburn outcomes. A focus group of 8 parents and a self-report questionnaire administered to 12 children and 13 parents were the means of obtaining information for this exploratory study. Itching was found to be one of the primary impairments that contributed to reduced functional outcome during skin healing after a burn injury. The activities of children who had been burned that were most frequently affected by the injury (as reported by parents) were schoolwork and sports; these were closely followed by sleeping, playing with other children, and unliked activities. Least affected activities were enjoying the family, eating, seeing friends, watching television, and bathing or showering. Eighty-five percent of parents reported at least some level of interference with the listed daily activities. Burn injuries are likely to cause interference with several aspects of a patient's daily life. As a result, families require ongoing support and monitoring. Further research should longitudinally compare the performance of children who have been burned with other children and adolescents.

Trends in the incidence, severity, and short-term outcome of stroke in Perth, Western Australia

Background and Purpose-This report describes trends in the key indices of cerebrovascular disease over 6 years from the end of the 1980s in a geographically defined segment of the city of Perth, Western Australia. Methods-Identical methods were used to find and assess all cases of suspected stroke in a population of approximately 134 000 residents in a triangular area of the northern suburbs of Perth. Case fatality was measured as vital status at 28 days after the onset of symptoms. Data for first-ever strokes and for all strokes for equivalent periods of 12 months in 1989-1990 and 1995-1996 were compared by age-standardized rates and proportions and Poisson regression. Results-There were 355 strokes in 328 patients and 251 first-ever strokes (71%) for 1989-1990 and 290 events in 281 patients and 213 first-ever strokes (73%) for 1995-1996. In Poisson models including age and period, overall trends in the incidence of both first-ever strokes (rate ratio = 0.75; 95% confidence limits, 0.63, 0.90) and all strokes (rate ratio = 0.73; 95% confidence limits, 0.62, 0.85) were obviously significant, but only the changes in men were independently significant. Case fatality did not change, and the balance between hemorrhagic and occlusive strokes in 1995-1996 was almost indistinguishable from that observed in 1989-1990. Conclusions-Our results, which are the only longitudinal population-based data available for Australia for key indices of stroke, suggest that it is a change in the frequency of stroke, rather than its outcome, that is chiefly responsible nationally for the fall in mortality from cerebrovascular disease.

Effect of increased lung expansion on lung growth and development near midgestation in fetal sheep

Obstruction of the fetal trachea is a potent stimulus for fetal lung growth and may have therapeutic potential in human fetuses with lung hypoplasia. However, the effects of increased lung expansion on lung development near midgestation, which is the preferred timing for fetal intervention, have not been well studied. Our aim was to determine the effects of increased lung expansion on lung development at 75-90 d of gestation in fetal sheep. In three groups of fetuses (n = 4 for each), the trachea was occluded for either 10 [10-d tracheal occlusion (TO) group] or 15 d (15-d TO group) or left intact (control fetuses). TO for both 10 and 15 d caused fetal hydrops, resulting in significantly increased fetal body weights. Both periods of TO significantly increased total lung DNA contents from 99.8 +/- 10.1 to 246.0 +/- 5.3 and 246.9 +/- 48.7 mg in 10- and 15-d TO fetuses, respectively. TO for 10 and 15 d also increased airspace diameter, although the percentage of lung occupied by airspace was not increased in 10-d TO fetuses due to large increases in interairway distances; this resulted from a large increase in mesenchymal tissue. The interairway distances at 15 d of TO were reduced compared with the 10-d value but were still similar to 30% larger than control values. We conclude that TO at

Placental growth hormone (GH), GH-binding protein, and insulin-like growth factor axis in normal, growth-retarded, and diabetic pregnancies: Correlations with fetal growth

We previously described significant changes in GH-binding protein (GHBP) in pathological human pregnancy. There was a substantial elevation of GHBP in cases of noninsulin-dependent diabetes mellitus and a reduction in insulin-dependent diabetes mellitus. GHBP has the potential to modulate the proportion of free placental GH (PGH) and hence the impact on the maternal GH/insulin-like growth factor I (IGF-I) axis, fetal growth, and maternal glycemic status. The present study was undertaken to investigate the relationship among glycemia, GHBP, and PGH during pregnancy and to assess the impact of GHBP on the concentration of free PGH. We have extended the analysis of specimens to include measurements of GHBP, PGH, IGF-I, IGF-II, IGF-binding protein-1 (IGFBP-1), IGFSP-2, and IGFBP-3 and have related these to maternal characteristics, fetal growth, and glycemia. The simultaneous measurement of GHBP and PGH has for the first time allowed calculation of the free component of PGH and correlation of the free component to indexes of fetal growth and other endocrine markers. PGH, free PGH, IGF-I, and IGF-II were substantially decreased in IUGR at 28-30 weeks gestation (K28) and 36-38 weeks gestation (K36). The mean concentration (+/-SEM) of total PGH increased significantly from K28 to K36 (30.0 +/- 2.2 to 50.7 +/- 6.2 ng/mL; n = 40), as did the concentration of free PGH (23.4 +/- 2.3 to 43.7 +/- 6.0 ng/mL; n = 38). The mean percentage of free PGH was significantly less in IUGR than in normal subjects (67% vs. 79%; P < 0.01). Macrosomia was associated with an increase in these parameters that did not reach statistical significance. Multiple regression analysis revealed that PGH/IGF-I and IGFBP-5 account for 40% of the variance in birth weight. IGFBP-3 showed a significant correlation with IGF-I, IGF-II, and free and total PGK at K28 and K36. Noninsulin-dependent diabetes mellitus patients had a lower mean percentage of free PGH (65%; P < 0.01), and insulin-dependent diabetics had a higher mean percentage of free PGH (87%; P < 0.01) than normal subjects. Mean postprandial glucose at K28 correlated positively with PGH and free PGH (consistent with the hyperglycemic action of GH). GHBP correlated negatively with both postprandial and fasting glucose. Although GHBP correlated negatively with PGH (r = -0.52; P

Epidural anaesthesia and analgesia and outcome of major surgery: a randomised trial

Background Epidural block is widely used to manage major abdominal surgery and postoperative analgesia, but its risks. and benefits are uncertain. We compared adverse outcomes in high-risk patients managed for major surgery with epidural block or alternative analgesic regimens with general anaesthesia in a multicentre randomised trial. Methods 915 patients undergoing major abdominal surgery with one of nine defined comorbid states to identify high-risk status were randomly assigned intraoperative epidural anaesthesia and postoperative epidural analgesia for 72 h with general anaesthesia (site of epidural selected to provide optimum block) or control. The primary endpoint was death at 30 days or major postsurgical morbidity. Analysis by intention to treat involved 447 patients assigned epidural and 441 control. Findings 255 patients (57.1%) in the epidural group and 268 (60.7%) in the control group had at least one morbidity endpoint or died (p=0.29). Mortality at 30 days was low in both groups (epidural 23 [5.1%], control 19 [4.3%], p=0.67). Only one of eight categories of morbid endpoints in individual systems (respiratory failure) occurred less frequently in patients managed with epidural techniques (23% vs 30%, p=0.02). Postoperative epidural analgesia was associated with lower pain scores during the first 3 postoperative days. There were no major adverse consequences of epidural-catheter insertion. Interpretation Most adverse morbid outcomes in high-risk patients undergoing major abdominal surgery are not reduced by use of combined epidural and general anaesthesia and postoperative epidural analgesia. However, the improvement in analgesia, reduction in respiratory failure, and the low risk of serious adverse consequences suggest that many high-risk patients undergoing major intra-abdominal surgery will receive substantial benefit from combined general and epidural anaesthesia intraoperatively with continuing postoperative epidural analgesia.

Outcome research in psychodynamic psychotherapy: Psychological, social and neuropsychological factors

While many studies have demonstrated positive outcomes from psychotherapy when it is practiced in a controlled research environment with carefully selected (or excluded) patient groups and rigid manualised therapy sessions there is a paucity of research regarding effective outcomes from psychotherapy as it is practiced in actual clinical conditions. The aim of this series of studies was to investigate outcomes, using an effectiveness approach, from psychodynamic psychotherapy as it is practiced by private psychiatrists. Three studies were planned. The aim of Study 1 was to provide standardized baseline measures on the following dimensions • Personal Demographic Information (PDI), • Target Symptoms and Disorders (TSD) including a neuropsychological profile • Inter and Intra Personal (IIP) factors, and, • General Functioning and Quality of Life (GFQoL) factors. Study 2 aimed to examine changes in patient characteristics during the course of treatment. Thus, baseline assessments were repeated at sixmonthly intervals to determine if therapy had been effective for individual patients. A third study was planned to assess the extent to which the results of significant outcome predictors could be replicated in different patient samples. Twenty-nine psychiatrists consented to refer patients with 20 patients having completed pre therapy assessments and six and 18-month follow-up questionnaires. The presentation of this research will focus on the interesting research methodology utilized, patient demographic characteristics and on the patient changes occurring over time on the dimensions of Defence Style (DSQ), Quality of Life (WHOQOL- Bref) and the severity of depression (BDI). The patient sample included 10 male and 10 female patients, whose ages ranged from 19 years to 66 years (mean = 43 years). While seven of the patients did not meet SCID-IV criteria for a current DSM-IV Axis 1 disorder, six patients met criteria for a current mood disorder, three for panic disorder, one patient each for PTSD, alcohol abuse and dependence, and 2 patients met current criteria for multiple Axis 1 disorders. The research is ongoing.

Perioperative epidural analgesia and outcome after major abdominal surgery in high-risk patients

In a primary analysis of a large recently completed randomized trial in 915 high-risk patients undergoing major abdominal surgery, we found no difference in outcome between patients receiving perioperative epidural analgesia and those receiving IV opioids, apart from the incidence of respiratory failure. Therefore, we performed a selected number of predetermined subgroup analyses to identify specific types of patients who may have derived benefit from epidural analgesia. We found no difference in outcome between epidural and control groups in subgroups at increased risk of respiratory or cardiac complications or undergoing aortic surgery, nor in a subgroup with failed epidural block (all P > 0.05). There was a small reduction in the duration of postoperative ventilation (geometric mean [SD]: control group, 0.3 [6.5] h, versus epidural group, 0.2 [4.8] h, P = 0.048). No differences were found in length of stay in intensive care or in the hospital. There was no relationship between frequency of use of epidural analgesia in routine practice outside the trial and benefit from epidural analgesia in the trial. We found no evidence that perioperative epidural analgesia significantly influences major morbidity or mortality after major abdominal surgery.

Response to The quality of epidural Anesthesia is crucial in the assessment of periciperative outcome

In their letter, Gogarten et al. question the effectiveness of the epidural regimens across the trial centers. In our original publication (1), we clearly demonstrated that patients in the epidural group had a working epidural block intraoperatively (evidenced by significantly more hypotension) and postoperatively (evidenced by significantly improved pain scores for 3 days).