Oxytocin levels in individuals with schizophrenia are high in cerebrospinal fluid but low in serum: A systematic review and meta-analysis

Metabolic Brain Disease - Schizophrenia is a debilitating mental illness. Levels of oxytocin have been proposed as a biomarker of schizophrenia; however, the observed levels of oxytocin in...     

Concurrent use of transgenic plants expressing a single and two Bacillus thuringiensis genes speeds insect adaptation to pyramided plants

Transgenic plants expressing insecticidal proteins from the bacterium Bacillus thuringiensis (Bt) were grown on over 13 million ha in the United States and 22.4 million ha worldwide in 2004. Preventing or slowing the evolution of resistance by insects ("resistance management") is critical for the sustainable use of Bt crops. Plants containing two dissimilar Bt toxin genes in the same plant ("pyramided") have the potential to delay insect resistance. However, the advantage of pyramided Bt plants for resistance management may be compromised if they share similar toxins with single-gene plants that are deployed simultaneously. We tested this hypothesis using a unique model system composed of broccoli plants transformed to express different Cry toxins (Cry1Ac, Cry1C, or both) and a synthetic population of the diamondback moth (Plutella xylostella) carrying genes for resistance to Cry1Ac and Cry1C at frequencies of approximately 0.10 and 0.34, respectively. After 24-26 generations of selection in the greenhouse, the concurrent use of one- and two-gene plants resulted in control failure of both types of Bt plants. When only two-gene plants were used in the selection, no or few insects survived on one- or two-gene Bt plants, indicating that concurrent use of transgenic plants expressing a single and two Bt genes will select for resistance to two-gene plants more rapidly than the use of two-gene plants alone. The results of this experiment agree with the predictions of a Mendelian deterministic simulation model and have important implications for the regulation and deployment of pyramided Bt plants.     

A randomized placebo-controlled trial of combined early intravenous captopril and recombinant tissue-type plasminogen activator therapy in acute myocardial infarction.

The adjunctive use of intravenous captopril with tissue plasminogen activator early during acute myocardial infarction offers theoretic advantages of diminishing left ventricular volume, preventing ventricular dilation and improving patient survival. To test the safety and efficacy of combined early administration of intravenous captopril and recombinant tissue-type plasminogen activator (rt-PA), 38 patients treated with rt-PA 3 +/- 0.3 h (mean +/- SE) after the onset of myocardial infarction were randomized to intravenous followed by oral captopril or placebo therapy. They underwent cardiac catheterization with measurement of hemodynamic variables and left ventricular function and determination of serum renin, angiotensin and aldosterone levels on days 1 and 7. Oral administration of the selected agent was continued for 3 months along with other antianginal medications, including nonangiotensin-converting enzyme inhibitor vasodilators. Repeat measurements of left ventricular function were obtained before hospital discharge and at 3 months. There were no significant differences in baseline clinical characteristics between groups. One patient in the captopril-treated group became hypotensive during intravenous therapy, requiring discontinuation of treatment. Compared with the placebo-treated group, the captopril-treated group had significant reductions at day 7 in left ventricular end-diastolic pressure (22.5 +/- 1.5 versus 16.3 +/- 1.6 mm Hg, p less than 0.01) and mean systemic arterial pressure (93.6 +/- 3.3 versus 86.2 +/- 2.7 mm Hg, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Outcomes of care and resource utilization among patients with knee or shoulder disorders treated by general internists, rheumatologists, or orthopedic surgeons

PURPOSE: Previous studies have suggested that specialists may achieve better clinical outcomes for patients, albeit often at greater cost. We sought to compare outcomes of care and resource utilization among patients with shoulder or knee problems who were treated by general internists, rheumatologists, and orthopedic surgeons. SUBJECTS AND METHODS: Outpatients with knee or shoulder complaints who were seen by general internists, rheumatologists, or orthopedic surgeons at an academic medical center were administered questionnaires at enrollment in the study and again 3 months later. The questionnaires included validated measures of satisfaction, functional status, and pain severity, as well as resource utilization. We compared baseline clinical characteristics, satisfaction with care, resource utilization, and changes in function and symptoms during 3 months of follow-up among patients who were cared for by the three different types of providers. RESULTS: A total of 534 patients responded to the baseline survey and 436 (82%) to the 3-month follow-up survey. About 60% (n = 323) had knee pain. Orthopedists cared for 40% (n = 211) of the patients, with the remainder treated in approximately equal numbers by general internists or rheumatologists. At baseline, patients of internists had less severe pain (differences of 0.3 to 0.6 points on a 1 to 5 scale, P <0.05) and functional limitations (differences of 0.4 to 0.6 points on a 1 to 5 scale, P <0.0006) than patients of rheumatologists and orthopedic surgeons. Adjusting for baseline differences, there were no significant differences among provider groups in pain relief or functional improvement during follow-up. However, in adjusted analyses, patients with shoulder pain who were cared for by orthopedic surgeons were least satisfied with the office environment [adjusted mean (+/- SD) satisfaction score of 1.6 +/- 0.8 on a 1 to 4 scale for orthopedic surgeons vs 1.3 +/- 0.8 for rheumatologists and 1.4 +/- 0.8 for internists, P = 0.004]. Among patients with knee pain, those treated by rheumatologists and orthopedic surgeons were more satisfied with the doctor-patient interaction (adjusted mean satisfaction scores of 1.1 +/- 0.9 for rheumatologists and 1.2 +/- 0.7 for orthopedic surgeons on a 1 to 4 scale vs 1.4 +/- 0.8 for general internists, P = 0.003). Orthopedic surgeons obtained significantly more radiographs of the knee or shoulder and more magnetic resonance imaging scans of the knee. Rheumatologists performed significantly more aspirations or injection procedures. Among all patients, those treated by rheumatologists were most satisfied with the physician interaction, and those treated by orthopedic surgeons were most satisfied with treatment results. CONCLUSION: The relative benefits of specialist compared with generalist care for patients with knee or shoulder pain depend on the importance attached to resource utilization, patient satisfaction, and health outcomes.     

Predictors of cardiogenic shock after thrombolytic therapy for acute myocardial infarction

OBJECTIVES: This study characterized clinical factors predictive of cardiogenic shock developing after thrombolytic therapy for acute myocardial infarction (AMI). BACKGROUND: Cardiogenic shock remains a common and ominous complication of AMI. By identifying patients at risk of developing shock, preventive measures may be implemented to avert its development. METHODS: We analyzed baseline variables associated with the development of shock after thrombolytic therapy in the Global Utilization of Streptikonase and Tissue-Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) trial. Using a Cox proportional hazards model, we devised a scoring system predicting the risk of shock. This model was then validated in the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO-III) cohort. RESULTS: Shock developed in 1,889 patients a median of 11.6 h after enrollment. The major factors associated with increased adjusted risk of shock were age (chi2 = 285, hazard ratio [95% confidence interval] 1.47 [1.40, 1.53]), systolic blood pressure (chi2 = 280), heart rate (chi2 = 225) and Killip class (chi2 = 161, hazard ratio 1.70 [1.52, 1.90] and 2.95 [2.39, 3.63] for Killip II versus I and Killip III versus I, respectively) upon presentation. Together, these four variables accounted for >85% of the predictive information. These findings were transformed into an algorithm with a validated concordance index of 0.758. Applied to the GUSTO-III cohort, the four variables accounted for > 95% of the predictive information, and the validated concordance index was 0.796. CONCLUSIONS: A scoring system accurately predicts the risk of shock after thrombolytic therapy for AMI based primarily on the patient's age and physical examination on presentation.     

Growth hormone and pituitary radiotherapy, but not serum insulin-like growth factor-I concentrations, predict excess mortality in patients with acromegaly

Increased mortality in patients with acromegaly has been confirmed in a number of retrospective studies, but causative factors and relationship to serum IGF-I remain uncertain. The West Midlands Pituitary database contains details of 419 patients (241 female) with acromegaly. Serum IGF-I data from the Regional Endocrine Laboratory were available for 360 patients (86%). At diagnosis, mean age was 47 yr (range, 12-84) and mean duration of follow-up was 13 yr (0.5-48). Sixty-one percent were treated by surgery and 39% by nonsurgical means. Radiotherapy was used alone or as adjuvant therapy in 50%. All patients were registered with the Office of National Statistics to obtain information on deaths. At the date of analysis (31 December 2001), 95 of the 419 patients had died (43 males), giving a standardized mortality ratio of 1.26 [confidence interval (CI), 1.03-1.54; P = 0.046]. After controlling for age and sex, data indicated that mortality was increased in subjects with posttreatment GH levels more than 2 micro g/liter, compared with those with levels less than 2 micro g/liter [ratio of mortality rates (RR), 1.55 (range, 0.97-2.50); P = 0.068]. By contrast, a much smaller increase was observed for subjects with elevated posttreatment IGF-I levels compared with those with normal levels [RR, 1.20 (range, 0.71-2.03); P = 0.50]. Treatment with radiotherapy was associated with increased mortality [RR, 1.67 (range, 1.09-2.56); P = 0.018], with cerebrovascular disease the predominant cause of death [standardized mortality ratio, 4.42 (range, 2.71-7.22); P = 0.005]. These results confirm the increased mortality in acromegaly and suggest that reduction of GH levels to less than 2 micro g/liter is beneficial in terms of improving long-term outcome. The sole use of IGF-I as a marker for effective treatment of acromegaly is not justified by this data. This study also highlights the potential deleterious effect of radiotherapy.     

The effect of acute exercise on high density lipoprotein-cholesterol and the subfractions in females

The effect of an acute exercise session on high density lipoprotein-cholesterol (HDL-C) and the subfractions HDL2-C and HDL3-C was determined for 9 healthy females (VO2max = 46.62 +/- 4.82 ml X kg-1 min-1). Each subject underwent a continuous 40-min run on a treadmill at a workload corresponding to 70% of VO2max. A venous blood sample was obtained immediately prior to exercise and 5 min, 24, 48 and 96 h after the exercise. Pre-exercise values were: HDL-C (61.7 +/- 3.7 mg X dl-1); HDL2-C (22.4 +/- 2.1 mg X dl-1); HDL3-C (39.3 +/- 2.0 mg X dl-1). At 5 min after exercise, HDL-C (66.2 +/- 4.4 mg X dl-1) and HDL3-C (44.5 +/- 2.8 mg X dl-1) were significantly elevated (P less than 0.01) when compared to pre-exercise values. HDL-C and HDL3-C were not significantly different from pre-exercise at the remaining time points. In comparison with pre-exercise, HDL2-C showed no significant change at any of the post-exercise time points. Results indicated that the rise in HDL-C following acute exercise was due to an increase in the subfraction HDL3-C. The change in total HDL-C and HDL3-C was transient in that pre-exercise values were re-attained within 24 h following acute submaximal exercise.     

Diabetic retinopathy is associated with a switch in splicing from anti- to pro-angiogenic isoforms of vascular endothelial growth factor

Aims/hypothesis Proliferative diabetic retinopathy results from excess blood vessel growth into the vitreous fluid of the eye. Retinal angiogenesis is regulated by expression of vascular endothelial growth factor (VEGF), and many studies have shown that VEGF is critically involved in proliferative diabetic retinopathy. VEGF is alternatively spliced to form the angiogenic (VEGF_xxx) and potentially anti-angiogenic (VEGF_xxxb) family of isoforms. The VEGF_xxxb family is found in normal tissues, but down-regulated in renal and prostate cancer. Previous studies on endogenous expression of VEGF in the eye have not distinguished between the two families of isoforms.Methods We measured VEGF_xxxb isoform expression in normal human eye tissue (lens, sclera, retina and iris) and vitreous fluid using enzyme-linked immunosorbent assay and Western blotting with a VEGF_xxxb-specific antibody.Results VEGF_xxxb protein was expressed in lens, sclera, retina, iris and vitreous fluid. Multiple isoforms were seen, including VEGF₁₆₅b, VEGF₁₂₁b, VEGF₁₄₅b, VEGF₁₈₃b and VEGF₁₈₉b. In non-diabetic patients, 64±7% of the VEGF in the vitreous was VEGF_xxxb (n=18), whereas in diabetic patients only 12.5±3.6% of total VEGF was VEGF_xxxb.Conclusions/interpretation Since VEGF_xxxb inhibits VEGF_xxx-induced angiogenesis in a one-to-one stoichiometric manner, these results show that in the eye of diabetic patients VEGF splicing was switched from an anti-angiogenic to a pro-angiogenic environment. This occurred through changes to the ratio of VEGF_xxx : VEGF_xxxb. Alterations to splicing, and through that to the balance of VEGF isoforms, could therefore be a potential therapeutic strategy for diabetic retinopathy.Konopatskaya and Perrin are joint first authors.