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71.
Aim: To determine whether homocysteine concentrations in umbilical cord plasma of neonates born to mothers with pre-eclampsia are elevated compared to concentrations in neonates born to normotensive women.
Method: Maternal blood from eight women with pre-eclampsia and ten women without pre-eclampsia was collected on admission for labour. Cord blood was collected from these same pregnancies at delivery. Plasma was extracted and stored at −70°C. Samples were batch-analysed for homocysteine.
Result: Maternal plasma homocysteine levels were observed to be significantly higher in the pregnancies complicated by pre-eclampsia compared to the control pregnancies ( P  = 0.043) with median levels of 5.4 µmol/L (interquartile range (IQR) 4.6–7.9; range 3.6–16.7) versus 4.1 µmol/L (IQR 3.4–5.1, range 3.1–6.7). Homocysteine concentrations in umbilical cord plasma in pregnancies complicated by pre-eclampsia were also significantly higher compared to those in normotensive pregnancies ( P  = 0.016) with median concentration levels of 5.3 µmol/L (IQR 4.8–7.2, range 2.5–16.6) versus 3.8 µmol/L (IQR 2.8–4.4, range 0.8–1.6).
Conclusion: Both maternal and umbilical cord plasma homocysteine concentrations were elevated in pregnancies complicated by pre-eclampsia compared to normotensive controls.  相似文献   
72.
A variety of disturbances in thermoregulatory processes have been identified in patients with anorexia nervosa (AN). Malnutrition, loss of thermal insulation, and hypoglycemia are generally accepted as the principal underlying mechanisms. Many of these thermoregulatory aberrations, however, may persist beyond the period of malnutrition and after substantial gains in body weight (in particular, hypothermia and an absence of shivering). It is proposed that during the course of the illness a physiologic state similar to that of cold-adapted mammals may occur in AN patients. As a consequence of this aberrant physiologic state we postulate that an increase in functional nonshivering thermogenesis (NST) interferes with normal shivering responses to cold. An increase in functional brown adipose tissue is proposed to underlie the development of NST in AN patients.  相似文献   
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The pneumococcal pilus has been shown to be an important determinant of adhesion and virulence in mouse models of colonization, pneumonia, and bacteremia. A pilus is capable of inducing protective immunity, supporting its inclusion in next-generation pneumococcal protein vaccine formulations. Whether this vaccine target is common among pneumococci in sub-Saharan Africa is uncertain. To define the prevalence and genetic diversity of type I and II pili among invasive pneumococci in Malawi prior to the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) into routine childhood immunization, we examined 188 Streptococcus pneumoniae isolates collected between 2002 and 2008 (17% serotype 1). In this region of high disease burden, we found a low frequency of invasive piliated pneumococci (14%) and pilus gene sequence diversity similar to that seen previously in multiple global pneumococcal lineages. All common serotypes with pilus were covered by PCV13 and so we predict that pilus prevalence will be reduced in the Malawian pneumococcal population after PCV13 introduction.  相似文献   
79.

Background

Inflammation contributes to chronic kidney disease (CKD), in part mediated through activation of interleukin (IL)-1β by the NLRP3 inflammasome within the kidney. This process also likely contributes to the accelerated atherosclerosis associated with nephropathy.

Objectives

The authors hypothesized that canakinumab, a human monoclonal antibody targeting IL-1β, might reduce cardiovascular event rates and improve renal function among post-myocardial infarction patients with CKD.

Methods

Stable post-myocardial infarction patients with high-sensitivity C-reactive protein (hsCRP) ≥ 2mg/l were randomly allocated to placebo or to 1 of 3 doses of canakinumab (50, 150, or 300 mg) given subcutaneously once every 3 months. Participants were followed for incident myocardial infarction, stroke, hospitalization for unstable angina requiring urgent revascularization, cardiovascular death, or death from any cause over a median follow-up period of 3.7 years (maximum 5 years). All patients additionally had serial monitoring of estimated glomerular filtration rate (eGFR), creatinine, the urine albumin to creatinine ratio (uACR), and were monitored for adverse renal and urinary events.

Results

Of 10,061 participants, 1,875 (18.6%) had baseline eGFR <60 ml/min/1.73 m2. These moderate CKD patients had higher incidence rates for major adverse vascular events compared with those with eGFR ≥60 ml/min/1.73 m2 (6.92 vs. 4.13 per 100 person-years; p < 0.0001). Random allocation to canakinumab reduced the risk of major adverse cardiovascular events among those with CKD (hazard ratio: 0.82; 95% confidence interval: 0.68 to 1.00; p = 0.05) with the largest cardiovascular benefits accruing among those who achieved on-treatment hsCRP levels below 2 mg/l measured after taking the first dose (hazard ratio: 0.68; 95% confidence interval: 0.53 to 0.86; p = 0.0015). Comparable effects were observed among those with baseline albuminuria or diabetes. Canakinumab had neither clinically meaningful benefits nor substantive harms with respect to serial measures of eGFR, creatinine, the uACR, or reported adverse renal events during trial follow-up.

Conclusions

IL-1β inhibition with canakinumab reduces major adverse cardiovascular event rates among high-risk atherosclerosis patients with CKD, particularly among those with a robust anti-inflammatory response to initial treatment. These cardiovascular benefits accrued with no adverse clinical renal events. (Canakinumab Anti-inflammatory Thrombosis Outcomes Study [CANTOS]; NCT01327846)  相似文献   
80.
Fludarabine was used to treat 68 patients with previously treated chronic lymphocytic leukemia (CLL). Nine (13%) patients achieved a complete remission and 30 (44%) a partial remission. The response rates for Rai stages 0 to 2, 3, and 4 were 64%, 58%, and 50% respectively. Seventeen (43%) of the 40 Rai stage 1 to 3 patients and four (19%) of the Rai stage 4 patients returned to Rai stage 0. Survival was strongly correlated with the final Rai stage achieved. The survival of the 11 partial responders with residual disease consisting only of residual bone-marrow nodules was similar to the complete responders (36+ months) and superior to the other partial response patients (16 months). The response to fludarabine was rapid, with 36 (92%) of the 39 responders having achieved at least a partial response following the first three courses. Complete responses occurred in the blood, liver, spleen, and lymph nodes in 48% to 69% of the patients. Eradication of all disease in the bone marrow occurred in only 13% of the cases. Neutropenia and thrombocytopenia occurred in 56% and 25% of evaluable courses. Major infections occurred in 9% of evaluable courses and fevers of unknown origin or minor infections in 12% of courses respectively. Myelosuppression and infection were more common in patients with initial Rai stages 3 and 4 and in nonresponding patients. Other toxicity was mild. No CNS toxicity was noted.  相似文献   
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