Preventing progression to first-episode psychosis in early initial prodromal states.

BACKGROUND: Young people with self-experienced cognitive thought and perception deficits (basic symptoms) may present with an early initial prodromal state (EIPS) of psychosis in which most of the disability and neurobiological deficits of schizophrenia have not yet occurred. AIMS: To investigate the effects of an integrated psychological intervention (IPI), combining individual cognitive-behavioural therapy, group skills training, cognitive remediation and multifamily psychoeducation, on the prevention of psychosis in the EIPS. METHOD: A randomised controlled, multicentre, parallel group trial of 12 months of IPI v. supportive counselling (trial registration number: NCT00204087). Primary outcome was progression to psychosis at 12- and 24-month follow-up. RESULTS: A total of 128 help-seeking out-patients in an EIPS were randomised. Integrated psychological intervention was superior to supportive counselling in preventing progression to psychosis at 12-month follow-up (3.2% v. 16.9%; P = 0.008) and at 24-month follow-up (6.3% v. 20.0%; P = 0.019). CONCLUSIONS: Integrated psychological intervention appears effective in delaying the onset of psychosis over a 24-month time period in people in an EIPS.

Reduced subjective quality of life in persons at risk for psychosis.

OBJECTIVE: Subjective quality of life (sQoL) and potentially contributing factors were investigated in individuals putatively in an early (EIPS) or late initial prodromal state (LIPS) and healthy controls (HC). METHOD: Participants comprised 58 EIPS individuals, 157 LIPS individuals and 87 HC individuals. sQoL was assessed together with locus of control (LoC), coping, demography and psychopathology. RESULTS: Putatively prodromal groups exhibited markedly lower sQoL than HC (all domains P < 0.00001). EIPS and LIPS individuals did not differ significantly. Depression was the most consistent explaining variable of sQoL in EIPS and LIPS individuals. In EIPS individuals, LoC emerged as an additional predictor. CONCLUSION: Individuals at risk for psychosis experienced a marked impairment of sQoL across all domains. This was evident even in the early state, showed no significant further deterioration during the late state and was predominantly explained by non-specific symptoms.

Mechanomyographic and electromyographic amplitude and frequency responses from the superficial quadriceps femoris muscles during maximal, eccentric isokinetic muscle actions.

The purposes of this study were to examine the effects of gender and muscle (vastus lateralis = VL, rectus femoris = RF, and vastus medialis = VM) on the velocity-related patterns for peak torque (PT), mean power output (MP), mechanomyographic (MMG) amplitude, electromyographic (EMG) amplitude, MMG mean power frequency (MPF), and EMG MPF during maximal, eccentric isokinetic muscle actions. Thirteen females (mean +/- SD age = 21 +/- 1 years) and eleven males (mean +/- SD age = 21 +/- 2 years) volunteered for this investigation. PT and MP were measured on a calibrated Cybex 6000 dynamometer at randomly ordered velocities of 60, 120, and 180 degrees.s-1, while MMG and EMG signals were recorded simultaneously from the VL, RF, and VM muscles. The results indicated no gender-related differences for the patterns of PT, MP, MMG amplitude, EMG amplitude, MMG MPF, or EMG MPF. Furthermore, no muscle-related differences were found for the patterns of MMG amplitude, EMG amplitude, or MMG MPF. The normalized values for MP and MMG amplitude increased from 60 to 180 degrees.s-1 (60 degrees.s-1 < 120 degrees.s-1 < 180 degrees.s-1). PT and EMG MPF remained unchanged across velocity, while EMG amplitude remained unchanged from 60 to 120 degrees.s-1, but decreased (approximately 10%) from 120 to 180 degrees.s-1. The findings indicated a close association between the patterns for MP and MMG amplitude, and a similarity between the patterns for PT, EMG amplitude, and EMG MPF across velocity. Therefore, the present findings suggested that motor unit recruitment (EMG amplitude), firing rate (MMG MPF), and muscle fiber action potential conduction velocity (EMG MPF) exhibited velocity-related patterns that were similar to PT production, while MMG amplitude was more closely associated with MP.

Development of a branching submaximal treadmill test for predicting VO2max.

This study determined the reliability and validity of a branching treadmill protocol in predicting VO2max. Thirty-seven, apparently healthy individuals (19 women and 18 men); volunteered to participate. On 2 separate testing days, each subject underwent maximal exercise testing using the protocol developed. Stepwise regression analysis indicated that the percentage of age-predicted maximum heart rate (APMHR) achieved at stage 3, speed and grade at stage 3, and APMHR accounted for 89% of the variance in VO2max. The 4 predictor variables were statistically significant (p < 0.01), and the standard error of the estimate was 4.56 ml x kg(-1) min(-1). Results indicate that health and fitness professionals can incorporate this protocol into their practices for the purpose of predicting VO2max for their clients outside the laboratory environment. Furthermore, our results indicate that using the proposed regression model is reliable and has received preliminary construct validity support.

Treatment with the humanized CD154-specific monoclonal antibody, hu5C8, prevents acute rejection of primary skin allografts in nonhuman primates.

BACKGROUND: Allogeneic skin transplantation remains a rigorous test of any immune intervention designed to prevent allograft rejection. To date, no single, clinically available immunosuppressant has been reported to induce long-term primary skin allograft survival in primates. We have previously shown that treatment with the humanized CD154-specific monoclonal antibody, humanized 5C8 (hu5C8), induces long-term renal allograft survival in nonhuman primates. In this study, we evaluated the efficacy of hu5C8 in preventing primary skin allograft rejection in rhesus monkeys. METHODS: Ten rhesus monkeys were transplanted with full-thickness skin allografts mismatched at both class I and class II major histocompatibility loci. Of these, two were given no treatment, five were treated with hu5C8 alone, and three received hu5C8 combined with whole blood donor-specific transfusion (DST). All recipients also received skin autografts for comparison. Animals were followed by inspection, serial biopsy, mixed lymphocyte culture, and alloantibody determination. RESULTS: Treatment with hu5C8 alone or hu5C8 plus DST greatly prolonged allograft survival. Rejection occurred in the untreated group within 7 days. Mean allograft survival in the monotherapy hu5C8 group was >236 days and in the DST group was >202 days; these differences were not significant. Rejection eventually occurred in most animals. Allograft survival was not correlated with the development of T cell hyporesponsiveness in mixed lymphocyte culture. Rejection was not predicted by the development of donor-specific alloantibody. CONCLUSION: These results show that treatment with the CD154-specific monoclonal antibody, hu5C8, greatly delays the onset of acute skin allograft rejection.

Impact of coronary artery disease on left ventricular systolic function and geometry in hypertensive patients with left ventricular hypertrophy (the LIFE study).

Hypertensive patients with left ventricular (LV) hypertrophy have a higher incidence of cardiovascular events than those without it. We hypothesized that a close relation exists between clinical evidence of coronary artery disease (CAD) and alterations in LV structure and function that contribute to their higher risk. Echocardiograms were recorded in 963 hypertensive patients (mean age 66 +/- 7 years, 41% women) with electrocardiographic LV hypertrophy, and divided into 149 with and 814 without clinical (prior myocardial infarction or angina pectoris) or electrocardiographic (Minnesota codes 1.1, 1.2) evidence of CAD. Patients with CAD had larger LV internal dimensions (5.5 +/- 0.6 vs 5.2 +/- 0.5 cm), increased LV mass (136 +/- 31 vs 122 +/- 24 g/m(2), and 62.4 +/- 19.4 vs 55.5 +/- 12.1 g/m(2.7)), lower ejection fraction (58 +/- 10% vs 62 +/- 8%), higher circumferential end-systolic wall stress (cESS) (198 +/- 59 vs 181 +/- 47 kdynes/cm(2), all p <0.001), and higher total peripheral resistances (2,088 +/- 628 vs 1,963 +/- 553 dynes x s x m(2)/cm(3), p = 0.02). Although eccentric LV hypertrophy predominated, the CAD group had a greater prevalence of this geometric pattern than the non-CAD group (56% vs 47%, p <0.02). An index of myocardial oxygen demand per beat--the LV mass x cESS x ejection time--was 20% higher in patients with CAD. In conclusion, clinical evidence of CAD in hypertensive patients with electrocardiographic evidence of LV hypertrophy identifies subjects with structural and functional abnormalities at high risk for cardiovascular events. LV mass. cESS. ejection time, a noninvasive index that parallels myocardial oxygen demand per beat, is especially high in hypertensive patients with CAD.

Progressive strength training in sedentary, older African American women.

PURPOSE: This study investigated effects of an 8-wk, low-frequency and low-volume, supervised, progressive strength training program emphasizing free weight, multijoint movements on the muscular power, strength, endurance, and flexibility of African American women 44 to 68 yr of age. METHODS: Nineteen sedentary African American women were randomly assigned to a strength training (ST) only group (N = 12; mean age, 51 yr) or a nonexercise control (C) group (N = 7; mean age, 52 yr). Maximal power, strength, absolute endurance, and flexibility were assessed before and after training. Subjects trained 2 d x wk(-1) using free weight (barbells and dumbbells) and machine (plate loaded) exercises for two to three sets of 8 to 10 repetitions on both primary and assistance exercises. RESULTS: Upper body power (medicine ball put distance) significantly increased statistically (P = 0.002), but gains possibly lacked practical significance because of measurement variation. Lower body power (peak watts on bicycle) experienced a small, nonsignificant increase in the ST group. Significant increases (P = 0.000) in 1RM muscle strength occurred in the ST group (leg press, +99.8%; bench press, +34.4%). Absolute endurance significantly increased (P = 0.000) in the ST group (leg press repetitions to failure at 70% pretest 1RM, +221%; bench press repetitions to failure at 50% pretest 1RM, +112%). Significant flexibility gains occurred in the ST group (sit-and-reach test, +8.2%; P = 0.017). No significant changes occurred in power, strength, absolute endurance, or flexibility in the C group. CONCLUSION: This study demonstrates that 8 wk of low-frequency, supervised, progressive strength training emphasizing free weight, multijoint movements can safely cause significant gains in muscle strength, absolute endurance, and flexibility in older African American women.

Induction therapy with monoclonal antibodies specific for CD80 and CD86 delays the onset of acute renal allograft rejection in non-human primates.

CD80 and CD86 (also known as B7-1 and B7-2, respectively) are both ligands for the T cell costimulatory receptors CD28 and CD152. Both CD80 and CD86 mediate T cell costimulation, and as such, have been studied for their role in promoting allograft rejection. In this study we demonstrate that administering monoclonal antibodies specific for these B7 ligands can delay the onset of acute renal allograft rejection in rhesus monkeys. The most durable effect results from simultaneous administration of both anti-B7 antibodies. The mechanism of action does not involve global depletion of T or B cells. Despite in vitro and in vivo evidence demonstrating the effectiveness of the anti-B7 antibodies in suppressing T cell responsiveness to alloantigen, their use does not result in durable tolerance. Prolonged therapy with murine anti-B7 antibodies is limited by the development of neutralizing antibodies, but that problem was avoided when humanized anti-B7 reagents are used. Most animals develop rejection and an alloantibody response although still on antibody therapy and before the development of a neutralizing antibody response. Anti-B7 antibody therapy may have use as an adjunctive agent for clinical allotransplantation, but using the dosing regimens we used, is not a tolerizing therapy in this non-human primate model.

Cardiopulmonary responses, muscle soreness, and injury during the one repetition maximum assessment in pulmonary rehabilitation patients.

PURPOSE: The safety of one repetition maximum (1RM) testing for patients with chronic obstructive pulmonary disease (COPD) has not been determined. Therefore, this study was conducted to determine the prevalence of abnormal cardiopulmonary responses, muscle soreness, and muscle injury of patients with moderate to severe COPD in response to 1RM testing. METHODS: Twenty pulmonary rehabilitation patients (11 women and 9 men) with moderate or severe COPD participated in this investigation. The 1RM testing was performed using the parallel squat and incline press. Blood pressure, heart rate dyspnea ratings, and oxygen saturation responses were measured immediately following the 1RM procedure. Ratings of muscle soreness and injury were measured immediately after 1RM testing and on days 2 and 7. RESULTS: No injury, significant muscle soreness, or abnormal cardiopulmonary responses occurred as a result of 1RM testing. No gender differences were found for any variable measured in response to 1RM testing. CONCLUSIONS: A properly supervised and screened pulmonary rehabilitation population can be 1RM tested without significant muscle soreness, injury, or abnormal cardiopulmonary responses.

Treatment with humanized monoclonal antibody against CD154 prevents acute renal allograft rejection in nonhuman primates.

CD154 is the ligand for the receptor CD40. This ligand-receptor pair mediates endothelial and antigen-presenting cell activation, and facilitates the interaction of these cells with T cells and platelets. We demonstrate here that administration of a CD154-specific monoclonal antibody (hu5C8) allows for renal allotransplantation in outbred, MHC-mismatched rhesus monkeys without acute rejection. The effect persisted for more than 10 months after therapy termination, and no additional drug was required to achieve extended graft survival. Indeed, the use of tacrolimus or chronic steroids seemed to antagonize the anti-rejection effect. Monkeys treated with antibody against CD154 remained healthy during and after therapy. The mechanism of action does not require global depletion of T or B cells. Long-term survivors lost their mixed lymphocyte reactivity in a donor-specific manner, but still formed donor-specific antibody and generated T cells that infiltrated the grafted organ without any obvious effect on graft function. Thus, therapy with antibody against CD154 is a promising agent for clinical use in human allotransplantation.

Long-term effects on cardiac output and peripheral resistance in patients treated with enalapril after acute myocardial infarction. CONSENSUS II Multi-Echo Study Group. Cooperative New Scandinavian Enalapril Survival Study.

In the Cooperative New Scandinavian Enalapril Survival Study (CONSENSUS II), in which enalapril treatment was initiated intravenously within 24 h after acute myocardial infarction, there was a neutral effect on 6-month mortality, whereas a beneficial effect on the progression of congestive heart failure was noted. We studied the effect of enalapril on left ventricular systolic function in terms of cardiac output and mean acceleration time measured by pulsed-wave Doppler in the left ventricular outflow tract and peripheral resistance. Early angiotensin-converting enzyme inhibition after acute myocardial infarction did not result in a general improvement of cardiac output. However, a small increase in cardiac output was observed in a subgroup of enalapril-treated patients with ejection fraction > or = 45%, probably due to a reduction in peripheral resistance in these patients.

Serial Holter ST-segment monitoring after first acute myocardial infarction. Prevalence, variability, and long-term prognostic importance of transient myocardial ischemia.

Based on serial Holter monitoring performed 7 times within 3 years after a first acute myocardial infarction, we assessed the prevalence, variability and long-term clinical importance of transient myocardial ischemia (TMI) defined as episodes of ambulatory ST-segment depression. In all, 121 consecutive male patients <70 years old were studied. The prevalence of TMI on different Holter recordings varied around 20% ranging between 18 and 27%. Fifty-five of the patients (46%) had TMI on at least 1 of the 7 Holter recordings. Considerable variability was found within and between patients for the presence of TMI. No high-risk group for cardiac death, nonfatal reinfarction or coronary revascularization during up to 10 years of follow-up could be identified by the detection of TMI. From these results we conclude that a routine search for TMI on serial Holter monitoring cannot be recommended in male survivors of an uncomplicated first acute myocardial infarction.

Comparison of degrees of left ventricular dilation within three hours and up to six days after onset of first acute myocardial infarction.

Following an acute myocardial infarction (AMI) there is immediate deterioration of contractility in the infarcted left ventricular (LV) wall. This can be followed by regional dilation (expansion) as well as global remodeling. We examined 35 consecutive patients--with no history of myocardial ischemia--who were admitted to hospital within 3 hours after initial symptoms and with ST-segment changes on an electrocardiogram consistent with transmural ischemia. Echocardiography was performed at admission, and at 6 hours, 12 hours, 24 hours, 3 days, and 6 days after onset of the AMI. Within 3 hours after onset of symptoms an increase in both end-diastolic volume index (EDVI) and end-systolic volume index (ESVI) was found in both anterior and inferior infarcts when compared with healthy controls (mean +/- SD EDVI: 99 +/- 13 ml/m2 [anterior], 69 +/- 17 ml/m2 [inferior], 51 +/- 15 ml/m2 [controls], p < or = 0.00001; ESVI: 62 +/- 12 ml/m2 [anterior], 38 +/- 11 ml/m2 [inferior], 17 +/- 6 ml/m2 [controls], p < or = 0.00001). At all points in time, volumes were larger in anterior infarcts than in inferior infarcts (p < 0.05). The volumes did not change during the 6 days (p > 0.1). Thus, major LV dilation is present within 3 hours after onset of symptoms of first AMI. The dilation is more pronounced in anterior versus inferior infarcts. From 3 hours until day 6 no further changes in LV volumes occurred.

Effect of enalapril initiated early after acute myocardial infarction on heart failure parameters, with reference to clinical class and echocardiographic determinants. CONSENSUS II Multi-Echo Study Group.

BACKGROUND AND HYPOTHESIS: Although the angiotensin-converting enzyme inhibitor enalapril has recently been shown to reduce mortality and the need for hospitalization in patients with left ventricular dysfunction and congestive heart failure, this drug was found to have no significant impact on short-term mortality after acute myocardial infarction (AMI) in the CONSENSUS II trial. The effect of enalapril initiated early after AMI on clinical and echocardiographic determinants of left ventricular (LV) function was studied in a subset of patients from CONSENSUS II. METHODS: Symptoms and signs of heart failure were classified as NYHA and dyspnea classes. Echocardiography included LV end-systolic volumes (ESV) and end-diastolic volumes (EDV), as well as ejection fraction (EF), wall motion index (WMI), and mitral flow indices. In all, 428 patients were included and followed for an average of 5.1 months by serial examinations, starting 2-5 days after myocardial infarction (MI) and repeated after 1 month and at the completion of the study. RESULTS: There was no beneficial effect of enalapril on clinically determined function. Changes (i.e., changes in NYHA class) in the functional status remained correlated with changes in echocardiographic determinants throughout the study in patients belonging to the placebo group: EDV index (r = 0.36, p = 0.002, ESV index (r = 0.49, p < 0.001), EF (r = -0.41, p < 0.001), and WMI (r = 0.29, p = 0.008). In a stepwise logistic regression model, the best baseline parameters to predict NYHA class at final visit in all patients were age (p = 0.014) and ESV index (p = 0.001). CONCLUSION: Enalapril treatment for an average period of 5.1 months following MI resulted in no clinically significant beneficial effects on NYHA and dyspnea class. Changes in clinical function class were correlated with changes in echocardiographic determinants in placebo-treated patients, but not in patients given enalapril.

Benefit of converting enzyme inhibition on left ventricular volumes and ejection fraction in patients receiving beta-blockade after myocardial infarction. CONSENSUS II multiecho study group.

Beta-blockers reduce infarct size and improve survival after acute myocardial infarction (MI). Post-MI angiotensin-converting enzyme inhibition also improves survival and may attenuate left ventricular (LV) dilatation. We evaluated the effect of early enalapril treatment on LV volumes and ejection fraction (EF) in patients on concomitant beta-blockade after MI. Intravenous enalaprilat or placebo was administered <24 hours after MI and was continued orally for 6 months. LV volumes were assessed by echocardiography 3 +/- 2 days, 1 and 6 months after MI. Change in LV diastolic volume during the first month was attenuated with enalapril (2.7 vs placebo 6.5 ml/m2 change; p < 0.05), and significantly lower LV diastolic and systolic volumes were observed with enalapril treatment compared with placebo at 1 month (enalapril 47.21 23.9 vs placebo 53.1/29.2 ml/m2; p < 0.05) and at 6 months (enalapril 47.9/24.8 vs placebo 53.8/29.6 ml/m2; p < 0.05). EF was also significantly higher 1 month after MI in these patients (enalapril 50.4% vs placebo 46.4%; p < 0.05). Our date demonstrate that early enalapril treatment attenuates LV volume expansion and maintains lower LV volumes and higher EF in patients receiving concurrent beta-blockade after MI. A possible additive effect of combined therapy should be evaluated prospectively.

The role of medium-chain triglycerides in exercise.

Studies investigating fat as a fuel for exercise have found that increasing free fatty acids during exercise tends to spare muscle glycogen due to increased utilization of free fatty acids for energy, which in turn can enhance the capacity for endurance exercise. Medium-chain triglycerides do not delay gastric emptying or absorption. They are broken down by lipase in the stomach and duodenum to glycerol and medium-chain fatty acids (MCFA). Since MCFAs are metabolized as quickly as glucose, it has been speculated that they might provide an alternative carbon source for the muscle during prolonged exercise. While the majority of studies investigating the role of medium-chain triglycerides and exercise have found no sparing effect of muscle glycogen after consumption of medium-chain triglycerides, two recent studies have presented conflicting results. This review will investigate the speculated role of medium-chain triglycerides as an alternative fuel source for exercising muscles and will discuss the possibility that medium-chain triglycerides preserve muscle glycogen during exercise.

Characteristics and prognostic importance of ST-segment elevation on Holter monitoring early after acute myocardial infarction.

The correlation between episodes of ST-segment elevation on Holter monitoring, clinical characteristics, left ventricular function, exercise testing, and long-term prognosis was determined in 123 consecutive patients 55 +/- 8 years old (mean +/- SD) with a first acute myocardial infarction (AMI). During 36 hours of Holter recording 11 +/- 5 days after AMI, 11 patients (9%) had 91 episodes of ST-segment elevation (group 1), whereas 112 patients had no such episodes (group 2). Most episodes of ST-segment elevation occurred in leads with pathologic Q waves or small, indistinct R waves. Large, anterior Q-wave AMIs were more prevalent in group 1 than in group 2, and in-hospital heart failure also occurred more frequently in group 1 patients (82% vs 23%; p < 0.0005). Regional and global left ventricular function was reduced in group 1 compared with group 2: ejection fraction 33 +/- 11% vs 50 +/- 11% (p = 0.0001). All episodes of ST-segment elevation were asymptomatic and did not correlate with different indicators of myocardial ischemia. Indeed, exercise-induced ST-segment depression was more prevalent in group 2 than in group 1: 57 vs 18% (p < 0.035). Over a mean of 5 years (range 4 to 6) of follow-up, an association between episodes of ST-segment elevation on Holter monitoring and (1) cardiac death (Kaplan-Meier analysis; p < 0.005), and (2) cardiac death and nonfatal reinfarction (Kaplan-Meier analysis; p < 0.025) was found.(ABSTRACT TRUNCATED AT 250 WORDS)