Homozygous LIPE mutation in siblings with multiple symmetric lipomatosis, partial lipodystrophy, and myopathy.

Despite considerable progress in identifying causal genes for lipodystrophy syndromes, the molecular basis of some peculiar adipose tissue disorders remains obscure. In an Israeli-Arab pedigree with a novel autosomal recessive, multiple symmetric lipomatosis (MSL), partial lipodystrophy and myopathy, we conducted exome sequencing of two affected siblings to identify the disease-causing mutation. The 41-year-old female proband and her 36-year-old brother reported marked accumulation of subcutaneous fat in the face, neck, axillae, and trunk but loss of subcutaneous fat from the lower extremities and progressive distal symmetric myopathy during adulthood. They had increased serum creatine kinase levels, hypertriglyceridemia and low levels of high-density lipoprotein cholesterol. Exome sequencing identified a novel homozygous NC_000019.9:g.42906092C>A variant on chromosome 19, leading to a NM_005357.3:c.3103G>T nucleotide change in coding DNA and corresponding p.(Glu1035*) protein change in hormone sensitive lipase (LIPE) gene as the disease-causing variant. Sanger sequencing further confirmed the segregation of the mutation in the family. Hormone sensitive lipase is the predominant regulator of lipolysis from adipocytes, releasing free fatty acids from stored triglycerides. The homozygous null LIPE mutation could result in marked inhibition of lipolysis from some adipose tissue depots and thus may induce an extremely rare phenotype of MSL and partial lipodystrophy in adulthood associated with complications of insulin resistance, such as diabetes, hypertriglyceridemia and hepatic steatosis. © 2016 Wiley Periodicals, Inc.

Chest pain unit in an internal medicine department: comparison of a year with the facility to a year without.

BACKGROUND: Chest pain is one of the most common reasons for emergency department visits and hospital admissions. Chest pain units (CPU) are being incorporated in tertiary hospitals for rapid and effective management of patients with chest pain. In Israel prior to 2010, only one chest pain unit existed in a tertiary hospital. OBJECTIVES: To report our first year experience with a CPU located in an internal medicine department as compared to the year before establishment of the CPU. METHODS: We retrospectively evaluated the medical records of consecutive patients who were admitted to our internal medicine department for the investigation of chest pain for 2 different years: a year before and a year after the establishment of the CPU in the department. We focused on the patients' characteristics and the impact of the CPU regarding the investigational modalities used and the length of in-hospital stay. RESULTS: In the year before establishment of the CPU, 258 patients were admitted to our department with chest pain, compared to 417 patients admitted to the CPU in the first year of its operation. All patients were followed for serial electrocardiographic and cardiac enzyme testing. All CPU patients (100%) underwent investigation compared to only 171 patients (66%) in the pre-CPU year. During the year pre-CPU, 164 non-invasive tests were performed (0.64 tests per patient) compared to 506 tests (1.2 tests/patient) in the CPU population. Coronary arteriography was performed in 35 patients (14%) during the pre-CPU year, mostly as the first test performed, compared to 61 patients (15%) during the CPU year, mostly as a second test, with only 5 procedures (1.1%) being the first test performed. The length of hospitalization was significantly shorter during the CPU year, 37.8 +/- 29.4 hours compared to 66.8 +/- 46 hours in the pre-CPU year. CONCLUSIONS: Establishment of a CPU in an internal medicine department significantly decreased the need for invasive coronary arteriography as the first modality for investigating patients admitted with chest pain, significantly decreased the need for invasive procedures (especially where no intervention was performed), and significantly shortened the hospitalization period. CPU is an effective facility for rapid and effective investigation of patients admitted with chest pain.

Consumption of polyphenolic-rich beverages (mostly pomegranate and black currant juices) by healthy subjects for a short term increased serum antioxidant status, and the serum's ability to attenuate macrophage cholesterol accumulation.

The present study analyzed the antioxidative effects of various beverages, in vitro, and also the effect of short term consumption of beverages richest in polyphenols by healthy subjects on serum anti-atherogenic properties. Healthy subjects consumed 250 mL of the selected beverages for 2 h, or daily, for up to 1 week.We hypothesized that differences in the anti-atherogenic properties of the studied beverages could be related, not only to the quantity of polyphenols, but also to their quality. Furthermore, we hypothesized that consumption of these juices by healthy subjects for just a short-term, will increase their serum anti-atherogenic properties, as was demonstrated previously in long-term consumption studies.Of 35 beverages studied, both 100% Wonderful-variety pomegranate and 100% black currant juices were the most potent antioxidants in vitro, as they inhibited copper ion-induced LDL oxidation by up to 94% and AAPH-induced serum lipid peroxidation by up to 38%. Furthermore, they increased in vitro serum paraoxonase 1 (PON1) lactonase activity by up to 51%. Consumption of five selected polyphenol rich beverages by healthy subjects increased serum sulfhydryl group (SH) levels and serum PON1 activities after 2 h, and more so after 1 week of drinking these beverages. These effects were most pronounced after the consumption of 100% Wonderful-variety pomegranate and 100% black currant juices. In conclusion, polyphenolic-rich juices with impressive in vitro antioxidant properties, also demonstrate antioxidant effects in vivo when analyzed for short term consumption. In this respect, 100% Wonderful-variety pomegranate and 100% black currant juices were most the potent.

Early inflammation and risk of long-term development of heart failure and mortality in survivors of acute myocardial infarction predictive role of C-reactive protein.

OBJECTIVES: We aimed to study the relationship between C-reactive-protein (CRP), obtained within 12 to 24 h of symptoms onset, and long-term risk of death and heart failure (HF) in survivors of acute myocardial infarction (MI). BACKGROUND: A robust inflammatory response is an integral component of the response to tissue injury during MI. The magnitude of the early inflammatory response to ischemic injury might be an important determinant of long-term outcome. METHODS: We prospectively studied 1,044 patients admitted with acute MI and discharged from hospital in stable condition. RESULTS: During a median follow-up of 23 months (range, 6 to 42 months), 113 patients died and 112 developed HF. In a multivariable Cox regression model adjusting for clinical variables and predischarge ejection fraction, compared with patients in the first CRP quartile, the adjusted hazard ratios (HRs) for death progressively increased with higher quartiles of CRP (second quartile 1.4 [95% confidence interval (CI) 0.6 to 2.9]; third quartile 2.3 [95% CI 1.2 to 4.6]; fourth quartile 3.0 [95% CI 1.5 to 5.7]; for trend, p = 0.0002). Compared with patients in the first CRP quartile, the adjusted HRs for HF were: second quartile, 1.1 (95% CI 0.5 to 2.3); third quartile, 1.9 (95% CI 1.0 to 3.6); and fourth quartile, 2.1 (95% CI 1.2 to 3.9) (for trend, p = 0.005). CONCLUSIONS: C-reactive-protein is a marker of long-term development of HF and mortality in patients with acute MI and provides prognostic information beyond that provided by conventional risk factors and the degree of left ventricular systolic dysfunction.

Undertreatment of acute pain in the emergency department: a challenge.

OBJECTIVE: Evaluation and improvement of pain management in our emergency department (ED). DESIGN: This was a "before-after" study. For each subject, the nurse, the physician, and the patient were asked to rate the initial intensity of the pain on a Visual Analogue Score (VAS). The timing and the type of analgesics administered were then recorded and follow-up VAS was performed. SETTING: A teaching, community-based, 400-bed hospital. STUDY PARTICIPANTS: 140 patients admitted for acute pain related to orthopedic injuries. MAIN OUTCOME MEASURES: The gap between the VAS expressed by the patient and estimated by the staff, the proportion of patients receiving analgesics, and the length of time delays between admission and analgesic administration. INTERVENTION: The intervention included education of medical and nursing staffs, insertion of a VAS template in the patient's chart, initiation of routine VAS assessment and re-assessment, and implementation of a protocol for pain management with standing orders for nurses. RESULTS: The VAS gap between the patient and the nurse decreased significantly from 1.91 2.04 to 1.03 1.97 after the intervention (P = 0.01). The percentage of patients receiving analgesics rose from 70 to 82% following the intervention. Time from admission to analgesia decreased from 80 +/- 68 min (mean +/- SD) before the intervention, to 58 +/- 37 min after the intervention (P = 0.05). CONCLUSION: Inadequate pain management in the ED appears related to poor staff assessment of pain and may be improved by routine VAS recording and by a nurse-based pain protocol.