C-reactive protein gene variants: independent association with late-life depression and circulating protein levels

C-reactive protein (CRP) is a heritable biomarker of systemic inflammation that is commonly elevated in depressed patients. Variants in the CRP gene that influence protein levels could thus be associated with depression but this has seldom been examined, especially in the elderly. Depression was assessed in 990 people aged at least 65 years as part of the ESPRIT study. A clinical level of depression (DEP) was defined as having a score of ⩾16 on The Center for Epidemiologic Studies Depression scale or a diagnosis of current major depression based on the Mini-International Neuropsychiatric Interview and according to Diagnostic and Statistical Manual of Mental Disorders-IV criteria. Five single-nucleotide polymorphisms spanning the CRP gene were genotyped, and circulating levels of high-sensitivity CRP were determined. Multivariable analyses adjusted for socio-demographic characteristics, smoking, ischemic pathologies, cognitive impairment and inflammation-related chronic pathologies. The minor alleles of rs1130864 and rs1417938 were associated with a decreased risk of depression in women at Bonferroni-corrected significance levels (P=0.002). CRP gene variants were associated with serum levels in a gender-specific manner, but only rs1205 was found to be nominally associated with both an increased risk of DEP and lower circulating CRP levels in women. Variants of the CRP gene thus influence circulating CRP levels and appear as independent susceptibility factors for late-life depression.     

Noninvasive assessment of coronary stenoses by myocardial imaging during pharmacologic coronary vasodilatation. III. Clinical trial

Thallium-201 myocardial imaging was performed at rest, after maximal treadmill exercise and during coronary vasodilatation induced by the intravenous administration of dipyridamole in 62 patients undergoing coronary angiography. Myocardial images after dipyridamole infusion were compared with rest and exercise thallium-201 images to determine the utility of pharmacologic stress for detecting coronary artery disease. Dipyridamole, 0.142 mg/min, was infused for 4 minutes with electrocardiographic and blood pressure monitoring, and thallium-201 was injected intravenously 4 minutes after infusion.Myocardial/background count ratios of 2.3 ± 0.5 (mean ± 1 standard deviation) after the administration of dipyridamole were higher than similar ratios for exercise images (2.1 ± 0.5; P < 0.001). The sensitivity of thallium-201 imaging for detecting significant coronary artery disease was equal for dipyridamole and exercise stress. In 51 patients with a 50 percent or greater stenosis of one or more coronary arteries, image defects were identified in 34 of 51 (67 percent) exercise and dipyridamole images. Twenty of 51 patients (39 percent) had abnormal rest images; in 17 of 20 patients, new or increased image defects were present after exercise and the infusion of dipyridamole. One of 11 patients (9 percent) with no stenosis of 50 percent or greater had a defect on exercise and dipyridamole images. Six of seven patients with new or enlarged image defects after the intravenous administration of dipyridamole also had new or enlarged defects after the oral administration of dipyridamole.After the infusion of dipyridamole, the heart rate increased from 64 ±10 beats/min supine to 88 ± 13 beats/min standing (P < 0.001), and blood pressure decreased from $\text{129 ±}\text{16}\text{80}\text{± 9}\text{to}\text{120 ±}\text{17}\text{75}\text{± 9}\text{mm Hg}\text{(P < 0.001)}$. Angina and S-T depression occurred more frequently with exercise than with dipyridamole. S-T depression occurred in only two patients (3 percent) with dipyridamole, suggesting that diagnostic images were often obtained without significant ischemia. This study demonstrates that pharmacologic coronary vasodilatation is as effective as maximal treadmill exercise in creating myocardial perfusion abnormalities detectable with thallium-201 imaging in man.     

Clinical features and outcome of T-cell acute lymphoblastic leukemia in childhood with respect to alterations at the TAL1 locus: a Pediatric Oncology Group study

Alteration of the TAL1 locus is the most common nonrandom genetic defect in childhood T-cell acute lymphoblastic leukemia (T-ALL). To determine if rearrangements of the TAL1 proto-oncogene confer a distinct leukemic phenotype, we studied leukemic peripheral blood or bone marrow samples from 182 children with newly diagnosed T-ALL enrolled on Pediatric Oncology Group treatment protocols. Forty-eight (26%) of the samples had a local rearrangement of the TAL1 locus. Demographic and clinical features were compared for patient subgroups with and without TAL1 rearrangements. The only clinical correlates that were significantly associated with TAL1 gene rearrangements were higher white blood cell count (P = .017) and higher hemoglobin (P = .007) at diagnosis. Immunophenotypically, samples with altered TAL1 were more likely to be CD2+ (P = .001) and lack CD10 (cALLa) expression (P = .007) than those without the rearrangement. There was a trend toward improved event-free survival (EFS) in patients with TAL1 rearrangements (4-year EFS was 44% +/- 7% for patients without the rearrangements v 59% +/- 11% for those with rearrangements), but the difference was not significant (P = .34). The role of TAL1 in leukemogenesis has yet to be clearly defined, and the prognostic significance of TAL1 gene rearrangements in T-ALL deserves further study.     

Surgery for ulcerative colitis in the era of the pouch: the St Mark's Hospital experience.

The choice of operation for ulcerative colitis among 422 patients having all their surgery at one hospital between 1976 (the year of the first restorative proctocolectomy) and 1990, was reviewed. The 15 year period was divided into three quinquennia (1976-80, 1981-85, 1986-90). Elective surgery was performed in 316 patients with one operative death. The proportions of conventional proctocolectomy, colectomy with ileorectal anastomosis, and restorative proctocolectomy for the three quinquennia were 36/60, 17/60, 4/60; 29/111, 30/111, 35/111; 30/145, 17/145, 75/145. Of 106 urgent operations with three postoperative deaths, 12 had a conventional proctocolectomy and 86 a colectomy with ileostomy and preservation of the rectum. Of 85 survivors of the latter there were two late deaths and in 13 no further surgery had been done at the time of this assessment. In the remaining 70 having subsequent surgery the proportion of conventional proctocolectomy, colectomy with ileorectal anastomosis, and restorative proctocolectomy for the three quinquennia respectively were 19/27, 4/27, 14/27; 11/21, 2/21, 8/21; 5/22, 4/22, 13/22. Of the 76 patients having colectomy with ileorectal anastomosis 12 (16%) no longer had a functioning rectum at the end of 1990. Of the 153 patients having an ileoanal pouch procedure, 11 (7%) no longer had, a functioning anus. The study showed an increase in the numbers of patients having elective surgery for ulcerative colitis during the three quinquennia. It also showed a rise of restorative over conventional proctocolectomy with diminution in elective colectomy with ileorectal anastomosis in the last five year period.     

Passive donor-to-recipient transfer of antiphospholipid syndrome following allogeneic stem-cell transplantation

Autoantibody production following allogeneic stem-cell transplantation is common and is often ascribed to the immune dysregulation associated with graft-versus-host disease. Recent data suggests that donor-memory B cells can be reactivated on exposure to antigen and result in antibody production in the recipient identical to that seen in the donor. Here we describe the production of autoantibodies in a recipient of bone marrow from a donor with systemic lupus erythematosus and antiphospholipid syndrome. Autoantibody appearance was precipitated by the onset of graft-versus-host disease, was identical to that of the donor, and ultimately lead to cerebrovascular thrombosis, which was successfully treated with antiplatelet and anticoagulant therapy.     

Coenzyme Q10 attenuates diastolic dysfunction, cardiomyocyte hypertrophy and cardiac fibrosis in the db/db mouse model of type 2 diabetes

Aims/hypothesis  

An increase in the production of reactive oxygen species is commonly thought to contribute to the development of diabetic cardiomyopathy. This study aimed to assess whether administration of the antioxidant coenzyme Q₁₀ would protect the diabetic heart against dysfunction and remodelling, using the db/db mouse model of type 2 diabetes. Furthermore, we aimed to compare the efficacy of coenzyme Q₁₀ to that of the ACE inhibitor ramipril.     

Effects of Beauveria bassiana on survival, blood-feeding success, and fecundity of Aedes aegypti in laboratory and semi-field conditions

The fungus Beauveria bassiana reduces Aedes aegypti longevity in laboratory conditions, but effects on survival, blood-feeding behavior, and fecundity in realistic environmental conditions have not been tested. Adult, female Ae. aegypti infected with B. bassiana (FI-277) were monitored for blood-feeding success and fecundity in the laboratory. Fungal infection reduced mosquito-human contact by 30%. Fecundity was reduced by (mean ± SD) 29.3 ± 8.6 eggs per female per lifetime in the laboratory; egg batch size and viability were unaffected. Mosquito survival, blood-feeding behavior, and fecundity were also tested in 5 meter × 7 meter × 4 meter semi-field cages in northern Queensland, Australia. Fungal infection reduced mosquito survival in semi-field conditions by 59-95% in large cages compared with 61-69% in small cages. One semi-field cage trial demonstrated 80% reduction in blood-feeding; a second trial showed no significant effect. Infection did not affect fecundity in large cages. Beauveria bassiana can kill and may reduce biting of Ae. aegypti in semi-field conditions and in the laboratory. These results further support the use of B. bassiana as a potential biocontrol agent against Ae. aegypti.