Papillary thyroid carcinoma after recombinant GH therapy for Turner syndrome

Turner syndrome (TS) has been included for several years among the indications for GH treatment, generally with satisfactory outcomes. Nevertheless, the long-term effects of this treatment in non-GH deficient patients are not fully known. The incidence of thyroid carcinoma is rare in patients during childhood, it is unusual to find this neoplasia in children under sixteen years old. This article reports the cases of two Spanish patients with papillary thyroid carcinoma after GH treatment for TS. Recent studies have indicated a possible relationship between the GH-IGF axis and the pathogenesis of neoplasias, questioning the chance association of these two pathologies. In line with this, we detected GH receptor expression in the papillary carcinoma cells. Long-term prospective studies are required to clarify the possible effects of GH treatment on the risk of neoplasia.     

Prevention of fall-related injuries in long-term care: a randomized controlled trial of staff education

BACKGROUND: Fall-related injuries, a major public health problem in long-term care, may be reduced by interventions that improve safety practices. Previous studies have shown that safety practice interventions can reduce falls; however, in long-term care these have relied heavily on external funding and staff. The aim of this study was to test whether a training program in safety practices for staff could reduce fall-related injuries in long-term care facilities. METHODS: A cluster randomization clinical trial with 112 qualifying facilities and 10,558 study residents 65 years or older and not bedridden. The intervention was an intensive 2-day safety training program with 12-month follow-up. The training program targeted living space and personal safety; wheelchairs, canes, and walkers; psychotropic medication use; and transferring and ambulation. The main outcome measure was serious fall-related injuries during the follow-up period. RESULTS: There was no difference in injury occurrence between the intervention and control facilities (adjusted rate ratio, 0.98; 95% confidence interval, 0.83-1.16). For residents with a prior fall in facilities with the best program compliance, there was a nonsignificant trend toward fewer injuries in the intervention group (adjusted rate ratio, 0.79; 95% confidence interval, 0.57-1.10). CONCLUSION: More intensive interventions are required to prevent fall-related injuries in long-term care facilities.     

A nationwide study of mortality associated with hospital admission due to severe gastrointestinal events and those associated with nonsteroidal antiinflammatory drug use

BACKGROUND:  The worst outcome of gastrointestinal complications is death. Data regarding those associated with nonsteroidal antiinflammatory drug (NSAID) or aspirin use are scarce.
AIM:  To determine mortality associated with hospital admission due to major gastrointestinal (GI) events and NSAID/aspirin use.
METHODS:  The study was based on actual count of deaths from two different data sets from 2001. Study 1 was carried out in 26 general hospitals serving 7,901,198 people. Study 2 used a database from 197 general hospitals, representative of the 269 hospitals in the Spanish National Health System. Information regarding gastrointestinal complications and deaths was obtained throughout the Minimum Basic Data Set (CIE-9-MC) provided by participating hospitals. Deaths attributed to NSAID/aspirin use were estimated on the basis of prospectively collected data from hospitals of study 1.
RESULTS:  The incidence of hospital admission due to major GI events of the entire (upper and lower) gastrointestinal tract was 121.9 events/100,000 persons/year, but those related to the upper GI tract were six times more frequent. Mortality rate was 5.57% (95% CI = 4.9–6.7), and 5.62% (95% CI = 4.8–6.8) in study 1 and study 2, respectively. Death rate attributed to NSAID/aspirin use was between 21.0 and 24.8 cases/million people, respectively, or 15.3 deaths/100,000 NSAID/aspirin users. Up to one-third of all NSAID/aspirin deaths can be attributed to low-dose aspirin use.
CONCLUSION:  Mortality rates associated with either major upper or lower GI events are similar but upper GI events were more frequent. Deaths attributed to NSAID/ASA use were high but previous reports may have provided an overestimate and one-third of them can be due to low-dose aspirin use.     

Endoplasmic reticulum stress is a target for therapy in Waldenstrom macroglobulinemia

Waldenstrom macroglobulinemia (WM) is an incurable low-grade lymphoma characterized by bone marrow (BM) involvement of IgM secreting lymphoplasmacytic cells. The induction of unfolded protein response (UPR) genes ("physiologic" UPR) enables cells to differentiate into professional secretory cells capable of production of high amounts of endoplasmic reticulum (ER)-processed proteins, such as immunoglobulins. Ultimately, the initially cytoprotective UPR triggers an apoptotic cascade if ER stress is not corrected, called proapoptotic/terminal UPR. We show that WM cells inherently express the physiologic UPR machinery compared with normal BM cells, and that increased ER stress leads to proapoptotic/terminal UPR in WM cells. We therefore examined tunicamycin, ER stress inducer, for potential antitumor effects in WM. Tunicamycin induced significant cytotoxicity, apoptosis and cell-cycle arrest, and inhibited DNA synthesis in WM cell lines and primary BM CD19(+) cells from patients with WM with an inhibitory concentration (IC(50)) of 0.5 microg/mL to 1 microg/mL, but not in healthy donor cells. Importantly, coculture of WM cells in the context of the BM microenvironment did not inhibit tunicamycin-induced cytotoxicity. Finally, we demonstrate that ER stress inducer synergizes with other agents used in the treatment of WM. These preclinical studies provide a framework for further evaluation of ER stress inducing agents as therapeutic agents in WM.     

The Plasmodium falciparum eIK1 kinase (PfeIK1) is central for melatonin synchronization in the human malaria parasite. Melatotosil blocks melatonin action on parasite cell cycle

Melatonin and its indoles derivatives are central in the synchronization of malaria parasites. In this research, we discovered that melatonin is unable to increase the parasitemia in the human malaria Plasmodium falciparum that lacks the kinase PfeIK1. The PfeIK1 knockout strain is a valuable tool in the screening of indol-related compound that blocks the melatonin effect in wild-type (WT) parasite development. The assays were performed by using flow cytometry with simultaneous labeling for mitochondria viability with MitoTracker Deep Red and nucleus staining with SYBR Green. We found that Melatotosil leads to an increase in parasitemia in P. falciparum and blocks melatonin effect in the WT parasite. Using microscopy imaging system, we found that Melatotosil at 500 nM is able to induce cytosolic calcium rise in transgenic PfGCaMP3 parasites. On the contrary, the compound Triptiofen blocks P. falciparum cell cycle with IC₅₀ 9.76 µM ± 0.6, inhibits melatonin action, and does not lead to a cytosolic calcium rise in PfGCaMP3 parasites. We also found that the synthetic indol-related compounds arrested parasite cycle for PfeIK1 knockout and (WT) P. falciparum (3D7) in 72 hours culture assays with the IC₅₀ values slighting lower for the WT strain. We concluded that the kinase PfeIK1 is central for melatonin downstream signaling pathways involved in parasite cell cycle progression. More importantly, the indol-related compounds block its cycle as an upstream essential mechanism for parasite survival. Our data clearly show that this class of compounds emerge as an alternative for the problem of resistance with the classical antimalarials.     

Duplex Doppler sonography of transplant renal artery stenosis

PURPOSE: The aim of this study was to evaluate the accuracy of duplex Doppler sonography in diagnosing transplant renal artery stenosis (TRAS) and to determine which parameter is the most reliable for making that diagnosis. METHODS: Over a 3-year period, we sonographically evaluated patients who were referred for investigation of possible TRAS. We investigated the following parameters: peak systolic velocity (PSV) in the external iliac and renal arteries, acceleration time and acceleration in the intrarenal arteries, acceleration time in the renal artery, resistance index, and the ratio of the PSVs in the renal and external iliac arteries. We also used MR angiography and digital subtraction arteriography to verify the degree of stenosis. After the evaluations, the patients were classified into 2 groups, 1 with and the other without significant stenosis (> 50% narrowing of the lumen) on digital subtraction arteriography. We also included a control group of patients who had undergone renal transplantation at least 6 months before, had had a good course after transplantation, had a diastolic blood pressure of 90 mm Hg or less, and were taking a maximum of 1 antihypertensive drug. RESULTS: Our study population consisted of 22 patients suspected to have TRAS (10 without and 12 with confirmed significant stenosis) and 19 control patients. We found statistically significant differences between the mean values of these 3 groups except for the PSV in the iliac artery and the resistance index in the intrarenal arteries. The most accurate parameters to use in diagnosing TRAS were an acceleration time of 0.1 second or higher in the renal and intrarenal arteries, a PSV of greater than 200 cm/second in the renal artery, and a ratio of PSVs in the renal and external iliac arteries of greater than 1.8. CONCLUSIONS: Duplex Doppler sonography is an excellent method for screening patients suspected to have TRAS and can help select which of those patients should undergo digital subtraction arteriography.     

Effects of Ni and Cu Residuals on the Magnetic Properties and Microstructure of SmCo5 Magnets

The effect of Ni/Cu-coating residuals on the magnetic properties and microstructures of samarium–cobalt (SmCo₅) magnets was studied. SmCo₅ magnets with 0.0, 0.5, 1.0, 2.0, 3.0 and 4.0 wt.% of added Ni/Cu (85 wt.% Ni/15 wt.% Cu) were prepared using a conventional sintering route. The magnetic properties of the magnets were found to be consistent up to 2 wt.% Ni/Cu. Any further increase in the Ni/Cu content resulted in a significant reduction in the magnetic properties, to lower than values that would be commercially acceptable. SEM/EDS studies showed that two major phases, i.e., the SmCo₅ matrix phase and Sm₂O₃ were present in all the sintered SmCo₅ magnets. The presence of Sm₂Co₇ as a minor phase fraction was detected in the sintered SmCo₅ magnets containing up to 2 wt.% Ni/Cu. A 2 wt.% Ni/Cu addition to magnets resulted in the presence of two new phases with compositions close to SmCo and Sm₂Co₁₇ in addition to SmCo₅ and Sm₂O₃ as major phases in the SEM-observed microstructure. These newly formed phases are present in small fractions and are presumably homogenously distributed at the grain boundaries of the magnets. As they are known to act as nucleation sites for reverse magnetic domains, they effectively reduce the intrinsic grain boundary magnetic strength, leading to a drop in the coercivity. We concluded that the sintered SmCo₅ magnets could be recycled with up to 2 wt.% Ni/Cu as a residual from the coating under our sintering and heat treatment conditions.     

Detection of a recurring mutation in the human growth hormone-releasing hormone receptor gene

OBJECTIVE: Mutations in the gene encoding for the GH-releasing hormone receptor (GHRHR) have been recently described in patients with familial isolated GH deficiency (IGHD) type IB. To date, all reported mutations have been found in kindreds sharing common ancestors. The only exception is a T to A transversion which causes a substitution of histidine for leucine in codon 144 (L144H) and creates a DraIII restriction site. This mutation was described in two families with different ethnic background residing in two different continents (Europe and North America). DESIGN: We searched for GHRHR mutations in a new family with IGHD from a third continent (South America) and found the affected individuals to be homozygous for the same L144H change. We performed linkage analysis with intra- and para-genic polymorphisms to determine if the three families carrying the L144H allele are related. RESULTS: Linkage analysis studies demonstrated that one of the three families does not share the same para- and intragenic GHRHR polymorphisms with the other two. CONCLUSIONS: The L144H mutation has arisen at least twice and should be considered for initial genetic analysis in patients with familial IGHD in whom the a GHRHR mutation is suspected.     

The impact of diabetic retinopathy on long-term outcome following coronary artery bypass graft surgery

OBJECTIVES: We sought to assess the impact of diabetic retinopathy on long-term outcome among patients with diabetes and multivessel coronary artery disease (MVD) following coronary artery bypass graft surgery (CABG). BACKGROUND: For diabetics, CABG is the preferred revascularization strategy. Diabetic retinopathy is a major microvascular complication of diabetes, and its severity is directly related to total glycemic exposure. METHODS: We identified 223 consecutive diabetics with MVD whose retinae were evaluated within one year prior to CABG. The most recent ophthalmologic records up until the time of CABG were used to evaluate the severity of retinopathy. The median follow-up after CABG was 11.6 years. RESULTS: Diabetic retinopathy was a strong independent predictor of overall mortality (relative risk [RR], 4.0), and repeat revascularization (RR, 3.0). In separate analyses of diabetics with retinopathy and without retinopathy, predictors of mortality differed significantly between the two groups. Among diabetics with retinopathy, the presence of either preoperative renal (RR, 2.5) or ventricular (RR, 2.0) dysfunction had unfavorable effects on mortality, but the survival curves did not differ significantly according to the presence or absence of internal thoracic artery (ITA) grafting. In comparison, among diabetics without retinopathy, ITA grafting (RR, 0.34) had a beneficial effect on mortality, and the survival curves varied somewhat according to the presence or absence of renal or ventricular dysfunction. CONCLUSIONS: Diabetics with retinopathy had a distinct post-CABG course with a worse long-term prognosis, as compared with diabetics without retinopathy. Retina evaluation is useful for prediction of long-term prognosis and management of diabetics who need CABG.     

Tissue Doppler imaging and long axis left ventricular function: hypertrophic cardiomyopathy versus athlete's heart.

BACKGROUND: The different diagnosis between hypertrophic cardiomyopathy and athlete's heart has important clinical implications. The assessment of long axis left ventricular function with tissue Doppler imaging in hypertrophic cardiomyopathy (showing systolic and diastolic dysfunction with heterogeneity and asynchrony), may be useful in the differentiation of these situations. AIM: To study, with tissue Doppler imaging, long axis left ventricular function in a population of athletes (rowers) and to compare it with a population of non-obstructive hypertrophic cardiomyopathy patients. METHODS: In 24 patients with non-obstructive hypertrophic cardiomyopathy and in 20 competitive rowers with similar age, blood pressure and heart rate, we analyzed mitral annulus motion with pulsed tissue Doppler imaging in the 4 sides of the annulus (septal, lateral, inferior, anterior), in apical views. In each wave (systolic, rapid filling and atrial contraction) we measured velocities, time intervals and velocity-time integrals, and calculated heterogeneity and asynchrony indices. Data were compared between the groups, between the different sides in each group ("parallel analysis") and with conventional indices of global function. RESULTS: Hypertrophic cardiomyopathy patients showed: systolic function: lower velocities and integrals, shorter ejection time and shorter systolic time. These abnormalities occurred even in annular sites contiguous to walls without hypertrophy. DIASTOLIC FUNCTION: Much lower rapid filling velocities and integrals, lower atrial contraction velocities and integrals, lower e/a, longer isovolumic relaxation time and time to peak rapid filling wave. These abnormalities occurred even in annular sites adjacent to walls without hypertrophy. In the athletes group, the e/a ratio was never < 1, in any annular site. In hypertrophic cardiomyopathy patients this ratio was < 1 in 27% of the sites. CONCLUSIONS: 1--Systolic and diastolic long axis left ventricular function is different in hypertrophic cardiomyopathy and in athletes, in all mitral annulus sides. 2--The presence of these abnormalities in annular sites contiguous to walls without hypertrophy suggests that this technique may be useful in the differential diagnosis between these groups, particularly in the "gray zone" of Maron.