Spontaneous coronary dissection associated with sleep deprivation presenting with acute myocardial infarction

Spontaneous coronary dissection is a rare cause of myocardial ischemia, myocardial infarction and sudden cardiac death. Idiopathic spontaneous coronary artery dissection (SCAD) occurs in patient without risk factors for coronary artery disease and without underlying pregnancy. We describe a case of idiopathic spontaneous coronary dissection after sleep deprivation presenting with acute myocardial infarction. A 40 year old woman presented to an emergency department with squeezing substernal chest pain lasting 1 hour following 72 h sleep deprivation due to overtime work. On admission, ECG showed no significant ST change. But the level of CK-MB and Troponin T were increased up to 77.54 ng/ml and 1.62 ng/ml, respectively. Emergent coronary angiography demonstrated a longitudinal dissection of the middle portion in the diagonal artery with TIMI III flow to the distal part of the vessel. Because the dissected vessel was too small to pass the intravascular ultrasound (IVUS) and deploy the stent, angioplasty was not performed. Under medical treatment with aspirin, clopidogrel and unfractionated heparin, conservative management was proposed; she remained free of symptom and discharged free of chest pain and in good condition.     

Influence of abdominal circumference on the inappropriateness of left ventricular mass and diastolic function in non-obese patients

BACKGROUND AND OBJECTIVE: Adipose tissue may be one of the sources of the humoral factors increasing left ventricular mass (LVM) via non-hemodynamic mechanisms. The involvement of visceral obesity in excessive or inappropriate LVM has not been established. We investigated the effect of abdominal circumference on the inappropriateness of LVM in non-obese patients. METHODS: Echocardiographic parameters for LVM and the indices for diastolic function were analyzed in 312 non-obese patients. Inappropriate LVM was defined as observed/predicted ratio (OPR) of LVM > 130%. Predicted LVM was calculated by the equation of 54.9 + 7.62 x height (m(2.7)) + 0.67 x stroke work--13.2 x sex (male = 1, female = 2). Abdominal obesity was defined by abdominal circumference > 80 cm in females and > 90 cm in males. RESULTS: Multiple regression analysis showed abdominal circumference was a significant factor for OPR of LVM (beta = 0.256) which was independent of age (beta = 0.215), sex, systolic blood pressure (beta = -0.232), body mass index (beta = 0.232), and fasting blood glucose (beta = 0.146). Odds ratio (OR) of abdominal obesity for inappropriate LVM was 3.28 (1.72-6.28), which was independent of age > or = 55 [OR: 2.17(1.11-4.25)], body mass index > or = 22.5 kg/m2 [OR: 2.24(1.13-4.41)], and diabetes mellitus [OR: 2.27 (1.06-4.85)]. Age and sex adjusted abdominal circumference (86.4 +/- 0.9 vs 82.1 +/- 0.5), abdominal obesity (28.1% vs 54.1%), and metabolic syndrome (19.4% vs 51.6%) were higher in the inappropriate LVM group than the appropriate LVM group (p < 0.001). CONCLUSIONS: Abdominal obesity or the presence of metabolic syndrome is an important factor to predict the inappropriateness of LVM even in non-obese patients.     

Akt1 in murine chondrocytes controls cartilage calcification during endochondral ossification under physiologic and pathologic conditions

Objective

To examine the role of the phosphoinositide‐dependent serine/threonine protein kinase Akt1 in chondrocytes during endochondral ossification.

Methods

Skeletal phenotypes of homozygous Akt1‐deficient (Akt1^−/−) mice and their wild‐type littermates were compared in radiologic and histologic analyses. An experimental osteoarthritis (OA) model was created by surgically inducing instability in the knee joints of mice. For functional analyses, we used primary costal and articular chondrocytes from neonatal mice and mouse chondrogenic ATDC5 cells with retroviral overexpression of constitutively active Akt1 or small interfering RNA (siRNA) for Akt1.

Results

Among the Akt isoforms (Akt1, Akt2, and Akt3), Akt1 was the most highly expressed in chondrocytes, and the total level of Akt protein was decreased in Akt1^−/− chondrocytes, indicating a dominant role of Akt1. Akt1^−/− mice exhibited dwarfism with normal proliferative and hypertrophic zones but suppressed cartilage calcification in the growth plate compared with their wild‐type littermates. In mice with surgically induced OA, calcified osteophyte formation, but not cartilage degradation, was prevented in the Akt1^−/− joints. Calcification was significantly suppressed in cultures of Akt1^−/− chondrocytes or ATDC5 cells overexpressing siRNA for Akt1 and was enhanced in ATDC5 cells overexpressing constitutively active Akt1. Neither proliferation nor hypertrophic differentiation was affected by the gain or loss of function of Akt1. The expression of ANK and nucleotide pyrophosphatase/phosphodiesterase 1, which accumulate pyrophosphate, a crucial calcification inhibitor, was enhanced by Akt1 deficiency or siRNA for Akt1 and was suppressed by constitutively active Akt1.

Conclusion

Our findings indicate that Akt1 in chondrocytes controls cartilage calcification by inhibiting pyrophosphate during endochondral ossification in skeletal growth and during osteophyte formation in OA.

     

Variable sulfation of dietary polyphenols by recombinant human sulfotransferase (SULT) 1A1 genetic variants and SULT1E1.

Human cytosolic sulfotransferases (SULTs) catalyze the sulfate conjugation of several important endo- and xenobiotics. Among the superfamily of SULT enzymes, SULT1A1 catalyzes the sulfation of small planar phenolic compounds, whereas SULT1E1 has a major role in estrogen conjugation. The human SULT1A1 gene has common single nucleotide polymorphisms that define three allozymes, SULT1A1*1, *2, and *3. The enzyme kinetics of SULT1A1 allozymes and SULT1E1 were characterized for the polyphenolic substrates apigenin, chrysin, epicatechin, quercetin, and resveratrol. Purified recombinant SULT proteins were generated in a baculoviral-insect cell system, and incubated in vitro with each substrate to determine catalytic activity. The effect of polyphenol sulfation was examined in mammalian cell lines stably expressing SULT1E1. For all polyphenols investigated, "normal-activity" SULT1A1*1 allozyme had significantly greater Vmax estimates than SULT1E1, and allele-specific differences in SULT1A1-mediated sulfation were observed. The polymorphic SULT1A1*2 allozyme exhibited low activity toward apigenin, epicatechin, and resveratrol. SULT1A1*1 and *3 acted as normal-activity allozymes for these substrates. Altered cellular proliferation was observed in MCF-7 cells stably expressing SULT1E1 upon treatment with chrysin, quercetin, or resveratrol, thus suggesting inactivation of these compounds by SULT1E1. These results suggest an important role for SULT isozymes and their pharmacogenetics in polyphenol disposition.     

18Fluorodeoxyglucose positron emission tomography in the diagnosis and staging of lung cancer: a systematic review

Lung cancer is the leading cause of cancer-related death in industrialized countries. The overall mortality rate for lung cancer is high, and early diagnosis provides the best chance for survival. Diagnostic tests guide lung cancer management decisions, and clinicians increasingly use diagnostic imaging in an effort to improve the management of patients with lung cancer. This systematic review, an expansion of a health technology assessment conducted in 2001 by the Institute for Clinical and Evaluative Sciences, evaluates the accuracy and utility of 18fluorodeoxyglucose positron emission tomography (PET) in the diagnosis and staging of lung cancer. Through a systematic search of the literature, we identified relevant health technology assessments, randomized trials, and meta-analyses published since the earlier review, including 12 evidence summary reports and 15 prospective studies of the diagnostic accuracy of PET. PET appears to have high sensitivity and reasonable specificity for differentiating benign from malignant lesions as small as 1 cm. PET appears superior to computed tomography imaging for mediastinal staging in non-small cell lung cancer (NSCLC). Randomized trials evaluating the utility of PET in potentially resectable NSCLC report conflicting results in terms of the relative reduction in the number of noncurative thoracotomies. PET has not been studied as extensively in patients with small-cell lung cancer, but the available data show that it has good accuracy in staging extensive- versus limited-stage disease. Although the current evidence is conflicting, PET may improve results of early-stage lung cancer by identifying patients who have evidence of metastatic disease that is beyond the scope of surgical resection and that is not evident by standard preoperative staging procedures. Further trials are necessary to establish the clinical utility of PET as part of the standard preoperative assessment of early-stage lung cancer.     

Treatment of sialorrhoea with repeated ultrasound-guided injections of botulinum toxin A into the parotid and submandibular glands

Botulinum toxin injections are useful in patients with refractory sialorrhoea although the optimum treatment protocol and its efficacy over a long period of follow up are controversial. The aim of our prospective study was to examine the efficacy and complications of a protocol of repeated ultrasound-guided botulinum toxin injections of fixed doses at a tertiary children’s hospital. A total of 79 procedures were done in 34 patients who were followed up for two years. The overall complication rate was 3%. The outcome measures considered included the Drooling Frequency Severity Scale (DFSS), visual analogue scale (VAS), and carers’ assessments of the reduction in drooling. Our study highlighted two types on non-responders (primary and secondary) of which 3/34 required definitive surgical management. In summary, this study shows that a protocol of repeated injections of fixed doses of botulinum toxin A, while not beneficial in all cases, is a potentially valuable option for the safe and effective treatment of sialorrhoea in children.     

Colonic mucosal tears in collagenous colitis

In general, the colonic mucosa is macroscopically normal in collagenous colitis, although minor, non-specific abnormalities may be found. Significant endoscopic abnormalities, "mucosal tears" representing longitudinal mucosal lacerations, have been reported in a few patients with collagenous colitis. We report the cases of three women with collagenous colitis and mucosal tears detected at the index colonoscopy in order to illustrate the endoscopic characteristics and review the literature. Including the present cases, a total of 12 patients with mucosal tears and collagenous colitis have been reported. In 10 patients, the mucosal lacerations involved the ascending or the transverse colon. Three of the 12 patients had a colonic perforation immediately after the colonoscopy. The colonoscopist should be aware that the risk of perforation is likely to be increased when mucosal tears are present.     

Prevalence of seropositivity to spotted fever group rickettsiae and Anaplasma phagocytophilum in a large, demographically diverse US sample.

BACKGROUND: Most epidemiologic studies of tick-borne rickettsial diseases in the United States are small and have limited demographic scope, making broader risk assessment difficult. METHODS: We conducted a seroprevalence study of spotted fever group rickettsiae and Anaplasma phagocytophilum, the agent of human granulocytic anaplasmosis. Specimens were selected randomly from the Department of Defense Serum Repository for 10,000 diverse military personnel at various stages in their careers who were serving with active duty status in 1997. Antibody testing included enzyme-linked immunosorbent assay for Rickettsia rickettsii and A. phagocytophilum, and Western blot confirmation for A. phagocytophilum. Risk factors were assessed using logistic regression. RESULTS: Subjects were mostly male and young and were diverse ethnically and geographically. Spotted fever group rickettsiae seropositivity was 6.0% (95% confidence interval, 5.5%-6.4%). In univariable logistic regression, seroprevalence was significantly higher among older subjects, men (6.5%, compared with 3.3% among women), black individuals (8.7%, compared with 5.6% among white individuals), subjects from states with above-average Rocky Mountain spotted fever incidence, and subjects in ground combat specialties. Associations remained significant in multivariable analysis for age, sex, black versus white race, home state with high incidence, and ground combat specialty. Among 696 subjects with serum samples obtained within 7 days after entering the military, the rate of seropositivity was 3.4% (95% confidence interval, 2.1%-4.8%). Seroprevalence was nonsignificantly lower in men (3.4%, compared with 3.7% in women ) and in black individuals (3.4%, compared with 4.1% in white individuals). A. phagocytophilum seropositivity, as determined by by enzyme-linked immunosorbent assay and Western blot, was 2.6% and 0.11% (95% confidence interval, 0.05%-0.18%), respectively. Western blot seropositivity was not significantly associated with subject characteristics in univariable analysis. CONCLUSIONS: Spotted fever group rickettsiae exposure was common and A. phagocytophilum exposure was rare in a US population with broad demographic diversity.     

A novel adenoviral gutless vector encoding sphingosine kinase promotes arteriogenesis and improves perfusion in a rabbit hindlimb ischemia model

OBJECTIVES: We previously demonstrated that sphingosine kinase (SPK) increases the level of extracellular sphingosine-1-phosphate and promotes neovascularization in a mouse matrigel model. In this study, we tested the hypothesis that SPK gene transfer using a novel adenoviral 'gutless' vector (AGV) can enhance arteriogenesis in a rabbit hindlimb ischemia model. METHODS: Thirty-five male New Zealand white rabbits were randomized to the AGV-SPK group (n=13), AGV-null group (n=13), and control group (n=9). On day 10, after the induction of unilateral hindlimb ischemia, gene vectors or buffer were introduced and the effect examined on day 30, using calf blood pressure, quantitative angiographic analysis, and histology. RESULTS: Calf systolic blood pressure ratios of the ischemic limb to the normal limb on day 30 were 0.77+/-0.13 in control groups, including the AGV-null group, and 0.91+/-0.14 in the AGV-SPK group (P<0.05). Angiographic vessel counts were significantly increased (8.0+/-2.1 at baseline and 11.8+/-3.2 on day 30, P<0.001) in the AGV-SPK group. Histologic analysis showed that microscopic total vessel counts on day 30 were 3.5+/-1.8/field in the control and AGV-null group and 5.4+/-1.0/field in the AGV-SPK group. Arterioles (AGV-SPK; 3.0+/-0.8 versus control and AGV-null; 2.1+/-1.1, P<0.05) were significantly increased in the AGV-SPK group. CONCLUSIONS: This study shows that SPK promotes arteriogenesis, as evidenced by the maximal improvement in the blood pressure restoration and collateral vessel counts. SPK may be an important angiogenic target to improve perfusion in ischemic tissues.