ERCC polymorphisms and risk of osteosarcoma: a meta-analysis.

OBJECTIVE: The association between excision repair cross-complementation (ERCC) gene family (ERCC1 and ERCC2) and osteosarcoma risk was controversial. The aim of this study was to evaluate the association between ERCC1 or ERCC2 and osteosarcoma risk by systematic meta-analysis. MATERIALS AND METHODS: Relative studies were retrieved from electronic databases without language restriction. The last search was updated on March 2017. Quality assessment was analyzed by the Newcastle-Ottawa Scale (NOS) score, which was recommended by the Agency for Healthcare Research and Quality (AHRQ). Meta-analysis was conducted by R language package (R 3.12). RESULTS: This meta-analysis was performed based on 4 case-control studies that included 1208 cases and 2448 controls. The ERCC2-rs1799793 AA+AC > CC (OR=1.3428, 95% CI=1.0201; 1.7674) had an effect on the risk of osteosarcoma development, whereas, there were no significant associations among the other ERCC SNPs (ERCC1 rs3212986, ERCC1 rs11615, and ERCC2 rs13181) and osteosarcoma. CONCLUSIONS: The ERCC2 rs1799793 polymorphism is related to the high risk of osteosarcoma development.

Factors associated with osteoporosis in patients with chronic obstructive pulmonary disease-a nationwide retrospective study.

The present study aimed to identify the factors associated with osteoporosis in patients with chronic obstructive pulmonary disease in Taiwan. The study found that female sex, old age, and use of a high dose of oral corticosteroids were significantly associated with osteoporosis in these patients. INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is becoming an increasingly serious and prevalent issue worldwide. The treatment of COPD with long-term steroid use may cause osteoporosis and have significant influences on disability and mortality. However, few studies have evaluated the association between steroid use and osteoporosis in patients with COPD. The present study aimed to identify the factors, including demographic characteristics and steroid use (oral corticosteroids [OCSs], inhaled corticosteroids, and injected steroids), associated with osteoporosis in patients with COPD in Taiwan. METHODS: This was a retrospective case-control study. Data were obtained from the National Health Insurance Research Database from 1997 to 2009. Cox proportional hazard regression models were used to identify the factors associated with osteoporosis. RESULTS: The incidence of osteoporosis in the patients with COPD was 1343.0 per 100,000 person-years, the majority of patients were women (63.6 %), and the mean age of the patients was 72.5 years. In multivariate regression analysis, female sex, old age, and use of a high OCS dose with a defined daily dose (DDD) >56 (hazard ratio 1.85, 95 % confidence interval 1.52-2.26, P < .0001) exhibited significant independent associations with osteoporosis. CONCLUSIONS: Female sex, old age, and use of a high OCS dose with a cumulative DDD >56 are associated with osteoporosis in patients with COPD. Additionally, female patients >50 years old and male patients >70 years old have a higher risk of osteoporosis. Medical personnel should actively provide health education for the prevention of osteoporosis in these patients.

Assessing the chronic neuropsychologic sequelae of human immunodeficiency virus-negative cryptococcal meningitis by using diffusion tensor imaging.

BACKGROUND AND PURPOSE: The high rate of neuropsychologic sequelae in CM survivors indicates that initial antifungal therapy is far from being satisfactory. This prospective cross-sectional study applied DTI on HIV-negative CM patients to determine whether microstructural changes in brain tissue are associated with subsequent cognitive symptoms. MATERIALS AND METHODS: Fifteen patients with HIV-negative CM and 15 sex- and age-matched healthy volunteers were evaluated and compared. All underwent complete medical and neurologic examinations and neuropsychologic testing. Brain DTI was obtained to derive the FA and ADC of several brain regions. Correlations among DTI parameters, neuropsychologic rating scores, and cryptococcal-antigen titer in CSF were analyzed. RESULTS: Significant ADC values increased and FA values decreased in HIV-negative CM patients in multiple selected regions of interest, including the genus of the corpus callosum and the frontal, parietal, orbito-frontal, and periventricular white matter and lentiform nucleus. Higher CSF cryptococcal-antigen titer on admission was associated with poorer DTI parameters (r = -0.666, P = .018), which were linearly related to worse cognitive performance during follow-up. CONCLUSIONS: The decline in brain DTI parameters in the associated brain areas indicates an HIV-negative CM microstructural pathology that is related to neuropsychologic consequences.

Chronic IL-1beta signaling potentiates voltage-dependent sodium currents in trigeminal nociceptive neurons.

The proinflammatory cytokine interleukin-1beta (IL-1beta) mediates inflammation and hyperalgesia, although the underlying mechanisms remain elusive. To better understand such molecular and cellular mechanisms, we investigated how IL-1beta modulates the total voltage-dependent sodium currents (INa) and its tetrodotoxin-resistant (TTX-R) component in capsaicin-sensitive trigeminal nociceptive neurons, both after a brief (5-min) and after a chronic exposure (24-h) of 20 ng/ml IL-1beta. A brief exposure led to a 28% specific (receptor-mediated) reduction of INa in these neurons, which were found to contain type I IL-1 receptors (IL-1RI+) on both their soma and nerve endings. In marked contrast, after a 24-h exposure, the total sodium current was specifically increased by 67%, without significantly affecting the TTX-R component. This potentiation of INa was suppressed in the presence of selective inhibitors of protein kinase C and G-protein-coupled signaling pathways, thereby suggesting that INa can be modulated through multiple pathways. In summary, the potentiation of INa through chronic IL-1beta signaling in nociceptive sensory neurons may be a critical component of inflammatory-associated hyperalgesia.

Cones of skin occur where hypertrophic scar occurs.

Hypertrophic scarring is devastating for the patient, however the pathophysiology and treatment remain unknown after decades of research. The process follows deep dermal injury, occurs only on certain body parts, does not occur in the early fetus or in animals, and is a localized event. This suggests that an anatomic structure in human, deep dermis may be involved. The dermis is a matrix perforated by cones containing many structures including skin appendages and fat domes. We hypothesized that studying the cones might reveal a structure related to scarring. We examined tangential wounds from various body parts on human cadavers along with skin histology from various human body parts, the early fetus, partial thickness burns, hypertrophic scars, and two other species-rats and rabbits. We found that the cones may in fact be the structure. They exist where hypertrophic scar occurs-cheek, neck, chest, abdomen, back, buttock, arm, forearm, dorsal hand, thigh, leg, dorsal foot, helix and ear lobe. They do not exist where hypertrophic scar does not occur-scalp, forehead, concha, eyelid, palm, early fetus, and in rat, or rabbit. It also became apparent that the cones have been omitted from most considerations of skin histology. We suggest that the cones need to be studied in relation to hypertrophic scarring and restored to skin diagrams.

Arterial hemodynamics in human hypertension. Effects of angiotensin converting enzyme inhibition.

Previous studies have shown some distinct hemodynamic alterations in essential hypertension, including increased resistance, wave reflections, and pulse wave velocity and decreased systemic compliance. These abnormalities are completely normalized by nonspecific smooth muscle dilation with nitroprusside but not by combined alpha- and beta-adrenergic blockade. The renin-angiotensin system, acting possibly via both circulating and local tissue effects, is thought to play an important role in essential hypertension, so its role in the altered hemodynamics deserves careful investigation. A hypertensive patient group was compared with a normotensive group similar in age, body size, and proportion of men and women. During diagnostic cardiac catheterization, ascending aortic micromanometer pressures and electromagnetic flows were measured in the baseline state. Intravenous captopril of a sufficient dosage (11 mg) to normalize blood pressure then was given to the hypertensive patients while measurements were repeated. From the pressures and flows, aortic input impedance, wave reflection magnitude, and compliance were computed. In the hypertensive group, the important hemodynamic alterations consisted of increased peripheral resistance, first zero crossing of aortic impedance phase angle, and wave reflections and decreased systemic compliance. Captopril had a pronounced hemodynamic effect. It normalized blood pressure, resistance, and impedance phase angle zero crossing. Compliance, although increased substantially by captopril, was still slightly lower than normotensive levels. The magnitude of wave reflections, although substantially lowered by angiotensin converting enzyme inhibition, was still persistently greater than normal. The present results, together with those previously reported, demonstrate that a complex interplay of factors underlies the increased smooth muscle tone in essential hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Effective renal plasma flow response and atrial natriuretic peptide in patients with uncomplicated acute myocardial infarction.

Effective renal plasma flow was determined by using I-131 labeled iodo-ortho-hippurate in 17 Chinese patients admitted to the coronary care unit with uncomplicated acute myocardial infarction. The first determination, immediately after admission, was significantly higher than the second determination done a week later, 444.5 +/- 153.9 vs. 371.1 +/- 124.9 ml/min (p < 0.02). The initial rise of effective renal plasma flow (ERPF) after acute myocardial infarction seemed to be correlated to the initial elevation of atrial natriuretic peptide (ANP), which was determined sequentially 6 times in each patient (91.3 +/- 39.4, 25.6 +/- 9.7, 37.4 +/- 12.3, 51.8 +/- 18.2, 65.6 +/- 20.8, 57.4 +/- 19.2 pg/ml, respectively). It was concluded that, in the presence of uncomplicated acute myocardial infarction, patients may show renal vasodilatation, and that the elevation of ANP may play some role in this.

Effective arterial elastance as index of arterial vascular load in humans.

BACKGROUND: This study tested whether the simple ratio of ventricular end-systolic pressure to stroke volume, known as the effective arterial elastance (Ea), provides a valid measure of arterial load in humans with normal and aged hypertensive vasculatures. METHODS AND RESULTS: Ventricular pressure-volume and invasive aortic pressure and flow were simultaneously determined in 10 subjects (four young normotensive and six older hypertensive). Measurements were obtained at rest, during mechanically reduced preload, and after pharmacological interventions. Two measures of arterial load were compared: One was derived from aortic input impedance and arterial compliance data using an algebraic expression based on a three-element Windkessel model of the arterial system [Ea(Z)], and the other was more simply measured as the ratio of ventricular end-systolic pressure to stroke volume [Ea(PV)]. Although derived from completely different data sources and despite the simplifying assumptions of Ea(PV), both Ea(Z) and Ea(PV) were virtually identical over a broad range of altered conditions: Ea(PV) = 0.97.Ea(Z) + 0.17; n = 33, r2 = 0.98, SEE = 0.09, p less than 0.0001. Whereas Ea(PV) also correlated with mean arterial resistance, it exceeded resistance by as much as 25% in older hypertensive subjects (because of reduced compliance and wave reflections), which better indexed the arterial load effects on the ventricle. Simple methods to estimate Ea (PV) from routine arterial pressures were tested and validated. CONCLUSIONS: Ea(PV) provides a convenient, useful method to assess arterial load and its impact on the human ventricle. These results highlight effects of increased pulsatile load caused by aging or hypertension on the pressure-volume loop and indicate that this load and its effects on cardiac performance are often underestimated by mean arterial resistance but are better accounted for by Ea.

Reduced left ventricular compliance in human mitral stenosis. Role of reversible internal constraint.

BACKGROUND: The mechanisms of depressed left ventricular (LV) pump performance in human mitral stenosis (MS) remain poorly understood, because reduced filling alone affects many hemodynamic measurements. Therefore, pressure-volume relations were examined in nine subjects with MS and compared with eight age-matched normal controls. METHODS AND RESULTS: Data were obtained by conductance catheter/micromanometer technique with transient inferior vena cava occlusion used to alter load and generate pressure-volume relations. In a subset of patients (n = 5), data were obtained both acutely and at 3 months (n = 4) after balloon valvuloplasty. MS patients had reduced cardiac output (3.3 +/- 0.9 versus 5.6 +/- 1.7 l/min) and end-diastolic volume (68.0 +/- 6.9 versus 115 +/- 31 ml) versus controls (p less than 0.001), with a mean transvalvular gradient of 14 +/- 6 mm Hg and estimated valve area of 0.6 +/- 0.2 cm2. Systolic function as assessed by the end-systolic pressure-volume relation was virtually the same in MS and control subjects. In contrast, end-diastolic pressure-volume relations in MS were consistently shifted leftward and had an increased slope (lower compliance) at matched pressure ranges (6.5 +/- 3.0 versus 2.2 +/- 0.53 ml/mm Hg at a mean diastolic pressure of 8 mm Hg, p less than 0.001). This change was not a result of reduced LV filling or probably of increased right heart loading. Valvuloplasty acutely returned chamber compliance to near normal, a change that was sustained at 3-month follow-up. Systolic function was little altered at this time. CONCLUSIONS: These data indicate an impairment of diastolic function in human MS that can be acutely reversed by balloon valvuloplasty. Lowered LV compliance probably results from a functional restriction caused by ventricular attachment to a thickened and immobile valve apparatus.

The mechanism of symptomatic postural hypotension in the elderly.

To study the mechanism of symptomatic postural hypotension in the elderly, we collected 11 such patients to further divide them into group 1 with central nervous system (CNS) involvement and group 2 without CNS involvement. Group 1 was the so-called Shy-Drager syndrome, and group 2 was the elderly postural hypotension not secondary to the medications or other systemic diseases. All patients had various degree of autonomic dysfunction and heterogenous defects in the reflex arc of autonomic nervous system (ANS). Both groups also had normal plasma volume but reduced blood volume. Patients in group 1 had normal level of plasma norepinephrine in recumbent posture, but failed to increase normally after standing (p less than 0.05, as compared the percentage rising with that of the controls). Patients in group 2 had near normal level of plasma norepinephrine in recumbent posture and could rise normally after standing. They also had normal level of plasma epinephrine in recumbent posture, but failed to rise normally after standing (p less than 0.05 as compared with the controls). These findings suggested that impaired responsiveness of end organs as blood vessels and adrenal medulla is one of the major causes responsible for the symptomatic postural hypotension in the elderly without CNS involvement.