Is there a diurnal pattern in the clinical symptoms of HELLP syndrome?

OBJECTIVE: To determine if there is a diurnal pattern in the clinical symptoms of HELLP (Hemolysis, Elevated Liver enzymes, Low Platelets) syndrome. STUDY DESIGN: A retrospective study was performed in 134 pregnancies complicated by HELLP syndrome. The medical records were reviewed to describe each HELLP episode. Time of day was divided into three periods, day, evening, and night. The following parameters were categorized according to the time of day: onset of symptoms, consultation by the doctor, initial blood sampling, diagnosis and decrease of symptoms. Biochemical parameters at clinical presentation and consecutive changes within 24 h were recorded. RESULTS: In 65 pregnancies 77 HELLP episodes were well documented. Times of onset of symptoms and consultation by the doctor were significantly higher during the evening and night (p < 0.001), whereas times of diagnosis and decrease of symptoms occurred significantly more during the day (p < 0.001). In only 49.3% of the cases were diagnostic laboratory criteria met at clinical presentation. This was mainly due to platelet values in excess of 100 x 10(9)/l. Several hours later (median 8 h, range 2-23) the decrease in platelets occurred. CONCLUSIONS: A diurnal pattern exists in the clinical symptoms of HELLP syndrome that is characterized by an exacerbation during the night and recovery during the day. There is a considerable delay between the onset of symptoms and the fulfillment of diagnostic laboratory criteria.     

Utility of exhaled nitric oxide as a noninvasive biomarker of lung inflammation in a disease model.

There is a great deal of interest in developing less invasive markers for monitoring airway inflammation and the effect of possible novel anti-inflammatory therapies that may take time to impact on disease pathology. Exhaled nitric oxide (eNO) has been shown to be a reproducible, noninvasive indicator of the inflammatory status of the airway in the clinic. The aim of the present study was to determine the usefulness of measuring eNO as a marker of the anti-inflammatory impact of glucocorticoid and an inhibitor of kappaB kinase-2 (IKK-2) inhibitor 2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide (TPCA-1), in a pre-clinical model of airway inflammation. Rats were given vehicle, budesonide or TPCA-1 prior to exposure to lipopolysaccharide, previously shown to induce an increase in eNO and airway neutrophilia/eosinophilia. Comparison of the effect of the two compounds on inflammatory components demonstrated a significant correlation between the impact on eNO and inflammatory cell burden in the airway. The current study demonstrates the usefulness of profiling potential disease-modifying therapies on exhaled nitric oxide levels and the way in which an effect on this noninvasive biomarker relates to effects on pathological parameters such as lung cellularity. Information from studies such as the current one would suggest that the measurement of exhaled nitric oxide has potential for monitoring inflammatory status in lung tissue.     

Role of tumour necrosis factor-alpha receptor p75 in cigarette smoke-induced pulmonary inflammation and emphysema.

Chronic obstructive pulmonary disease (COPD) is characterised by a local pulmonary inflammatory response to respiratory pollutants and by systemic inflammation. Tumour necrosis factor (TNF)-alpha has been implicated in systemic effects of COPD and operates by binding the p55 (R1) and p75 (R2) TNF-alpha receptors. To investigate the contribution of each TNF-alpha receptor in the pathogenesis of COPD, the present study examined the effects of chronic air or cigarette smoke (CS) exposure in TNF-alpha R1 knockout (KO) mice, TNF-alpha R2 KO mice and wild type (WT) mice. CS was found to significantly increase the protein levels of soluble TNF-alpha R1 (by four-fold) and TNF-alpha R2 (by 10-fold) in the bronchoalveolar lavage of WT mice. After 3 months, CS induced a prominent pulmonary inflammatory cell influx in WT and TNF-alpha R1 KO mice. In TNF-alpha R2 KO mice, CS-induced pulmonary inflammation was clearly attenuated. After 6 months, no emphysema was observed in CS-exposed TNF-alpha R2 KO mice in contrast to WT and TNF-alpha R1 KO mice. CS-exposed WT and TNF-alpha R1 KO mice failed to gain weight, whereas the body mass of TNF-alpha R2 KO mice was not affected. These current findings suggest that both tumour necrosis factor-alpha receptors contribute to the pathogenesis of chronic obstructive pulmonary disease, but tumour necrosis factor-alpha receptor-2 is the most active receptor in the development of inflammation, emphysema and systemic weight loss in this murine model of chronic obstructive pulmonary disease.     

Characteristics and outcome of patients with active pulmonary tuberculosis requiring intensive care.

Severe tuberculosis (TB) requiring intensive care unit (ICU) care is rare but commonly known to be of markedly bad prognosis. The present study aimed to describe this condition and to determine the mortality rate and risk factors associated with mortality. Patients with confirmed TB admitted to ICU between 1990 and 2001 were retrospectively identified and enrolled. Clinical, radiological and bacteriological data at admission and during hospital stay were recorded. A multivariate analysis was performed to identify the predictive factors for mortality. A total of 58 TB patients (12 females, mean age 48 yrs) admitted to ICU were included. Mean Acute Physiology and Chronic Health Evaluation (APACHE) II score at admission was 13.1+/-5.6 and 22 of 58 (37.9%) patients required mechanical ventilation. The in-hospital mortality was 15 of 58 (25.9%); 13 (22.4%) patients died in the ICU. The mean survival of patients who died was 53.6 days (range 1-229), with 50% of the patients dying within the first 32 days. The factors independently associated with mortality were: acute renal failure, need for mechanical ventilation, chronic pancreatitis, sepsis, acute respiratory distress syndrome, and nosocomial pneumonia. These data indicate a high mortality of patients with tuberculosis requiring intensive care unit care and identifies new independently associated risk factors.     

Energy cost of activity and exercise in children and adolescents with cystic fibrosis.

In cystic fibrosis (CF), perturbations of total daily energy expenditure (TDEE) may be a major determinant of altered nutrition and growth. Measurement of TDEE is problematic, though the flex-heart rate method (FHRM) provides a close estimation of TDEE, as compared to the cost-prohibitive, gold standard, the double-labeled water method, and permits estimates of the energy cost of daily activities (ECA) above resting energy expenditure (REE). We hypothesize that alterations in ECA affects TDEE in CF. PURPOSE: To measure components of TDEE in adolescents with CF and normal lung function compared with controls, and to determine whether ECA can be improved by diet and exercise. METHODS: Clinically stable CF subjects (aged 9-13, n=12) and age- and gender-matched controls (n=13) had repeated measurements of TDEE by FHRM, REE, and maximal cardiopulmonary exercise testing (CPET) during a 6-week exercise and diet program. RESULTS: While the mean REE was similar in both groups, ECA was significantly lower in CF adolescents as compared to controls (p=0.02). During CPET, maximal exercise in CF was characterized by hyperventilation, which was unrelated to ventilation-perfusion mismatching. There were no changes in REE after dietary intervention. CONCLUSION: ECA in CF adolescents with normal lung function is lower when compared to healthy controls. These findings support the hypothesis that clinically stable patients with CF have inefficient energy metabolism or alternatively conserve energy during activities of daily living.     

复合杂合parkin基因突变家族的不同表型

背景：Parkin基因（PRKN）突变可导致常染色体隐性遗传性早发帕金森病（EOPD）。目的：探讨EOPD白人家族PRKN突变的表现和基因型-表型关系。设计：对EOPD家族的3代20例成员进行基因分析，该家族有4例患者。应用直接基因组DNA测序、半定量聚合酶链反应、实时定量聚合酶链反应以及逆转录酶聚合酶链反应分析以确定PRKN突变。结果：4例早发患者（年龄30—38岁）被确定有PRKN复合杂合突变（T240M和EX5_6缺失），虽然PRKN的杂合T240M和纯合EX5_6缺失突变已有描述，但是据悉，本文为上述复合杂合突变的首次报道。患者的表型为典型常染色体隐性遗传性EOPD的表现，其特征是对左旋多巴治疗有效、相对缓慢的进展和运动障碍。所有杂合突变的基因携带者（T240M或EX5_6缺失）和1例56岁的复合杂合突变女性携带者（T240M和EX5_6缺失）无任何神经系统症状。结论：研究发现，PRKN基因复合杂合突变（T240M和EX5_6缺失）导致一个大的白人家族中4例成员发生常染色体隐性遗传性EOPD。另外1例成员具有相同的突变，比4例患者的平均发病年龄大10岁，并且无本病的临床表现。不完全的外显率对遗传咨询具有暗示作用，并且提示复杂的基因一环境交互作用在PRKN相关EOPD的发病机制中发挥作用。     

The role of vessel wall physiology in predicting coronary bypass graft patency

Pulmonary hamartomas are usually an incidental finding and range in size from 1 cm to 8 cm in diameter in various series. We report a case of a massive pulmonary hamartoma (size 25.5 × 17.5 × 6.5 cm and weighing 1134 g) in a 61 year old male who presented with a short history of breathlessness. The tumour was arising from the medial border of the right lung and occupying most of the right chest extending in to the anterior mediastinum. The tumour was compressing the right lung and there was no evidence of infiltration into the surrounding structures. It was successfully treated by surgical resection and final histology was pulmonary hamartoma with predominantly adipose and leiomyomatous differentiation.     

Oral beta2-agonist use by preschool children with asthma in East and Central Harlem, New York.

Although studies have documented underuse of controller medications and overuse of short-acting inhaled ss(2)-agonist among children with persistent asthma in disadvantaged communities, the persistence of oral ss(2)-agonist use in pediatric practice has not been studied since inhaled short-acting ss(2)-agonists became widespread. We describe medications used to treat asthma among children 3 to 5 years of age at 10 Head Start and other subsidized preschool centers in East and Central Harlem, New York City. We interviewed 149 parents/guardians of children who were identified as having probable asthma based on physician's diagnosis, persistent symptoms, hospitalization, and medication use. We classified 86 of the 149 children (58%) as having current persistent asthma. Only 15 of them (17%) were reported to have used controller medications at least 5 days/week in the last 4 weeks-only 2 of whom used inhaled corticosteroids. By contrast, 53 children (62%) used oral ss(2)-agonist in the last 4 weeks, often (72%) in conjunction with nebulized or inhaled short-acting ss(2)-agonist. Use of oral ss(2)-agonist was associated with more severe symptoms. This study documents the continued widespread use of oral ss(2)-agonist for treatment of children in a low-income community with high prevalence of asthma.