Prevalence and characteristics of moderate to severe pulmonary hypertension in systemic sclerosis with and without interstitial lung disease

OBJECTIVE: To determine the prevalence and characteristics of moderate to severe pulmonary hypertension (PH) in patients with systemic sclerosis (SSc) with and without interstitial lung disease (ILD). METHODS: We retrospectively studied clinical and functional characteristics of 197 consecutive patients with SSc who had undergone a screening echocardiography to detect PH. RESULTS: Moderate to severe PH was suspected in 36 patients (18.3%) and confirmed in 32 who underwent right heart catheterization. The prevalence of PH did not differ between patients with limited and patients with diffuse cutaneous SSc. PH was detected in 12/67 (17.9%) patients without ILD vs 24/110 (21.8%) patients with ILD (p not significant). In patients with ILD, a lower PaO2 appeared as the unique independent factor significantly associated with PH, regardless of the extent of fibrosis. In 3 patients out of 9 (33.3%) with ILD and significantly restrictive disease, PH was out of proportion to the degree of fibrosis. In patients with no ILD, a higher grade of dyspnea appeared as the unique independent factor associated with PH. In patients with no ILD, altered DLCO was the sole indicator of the pulmonary function tests associated with PH (best cutoff value 72%). DLCO correlated with systolic pulmonary arterial pressure only in patients with no ILD. CONCLUSION: Prevalence of moderate to severe PH was similar in SSc patients with and those without ILD. In patients with ILD, a lower PaO2 was the unique independent indicator associated with PH. In some patients with severe ILD, PH was out of proportion to the degree of fibrosis. A linear correlation between DLCO and systolic pulmonary arterial pressure was observed only in patients without ILD. All these indicators should assist identification of patients with or without ILD requiring diagnostic procedures for PH before annual screening.     

Consumption of solutions containing sodium chloride is enhanced in female oxytocin-deficient mice

Intact and ovariectomized oxytocin (OT)-deficient (OT-/-) and wild-type (OT+/+) mice were tested for consumption of 0.5 M NaCl solution or tap water in a 2-bottle choice test. During 3 days of acclimation, voluntary ingestion of NaCl was equal between genotypes. After overnight fluid deprivation, intact OT-/- mice ingested 2 times more NaCl solution than OT+/+ mice in the 6th hr, but not the 1st hr, after reintroduction of fluid. Ovariectomized mice consumed less than intact mice after overnight fluid deprivation. When a 0.2 M NaCl solution was administered for 6 days in ovariectomized mice, OT-/- mice voluntarily consumed greater amounts than OT+/+ mice. After overnight fluid deprivation, consumption by OT-/- mice was 3 times that of OT+/+ mice at 1 hr and 2-fold greater after 6 hr. Enhanced intake of NaCl-containing solutions in female OT-/- mice suggests that central OT may be an important inhibitor of sodium consumption.     

The health of students in institutes of higher education: an important and neglected public health problem?

BACKGROUND: A survey of students in three UK higher education establishments was undertaken to obtain information about students' physical and emotional well-being, their attitudes to, and beliefs about health, and the prevalence of risk factors for future ill health. METHODS: Health was measured by the prevalence of longstanding illness and by the SF-36 health status measurement tool. Survey results were compared with equivalent data for 18- to 34-year-olds in the local population. The prevalence of long-standing illness was also compared with two national surveys. RESULTS: The survey achieved a 49 per cent response rate. More than one-third of respondents reported a long-standing illness, a higher prevalence than in all comparison surveys. Students scored significantly worse than their peers in the local population on all eight SF-36 dimensions. The greatest difference was for role limitations as a result of emotional problems. The main sources of emotional distress were study or work problems and money. CONCLUSION: The poor response rate in this survey dictates the need for caution in interpretation of the results. However, they suggest that the health of students is poor relative to that of their peers, and that their emotional health is more of a problem than their physical health. Public health practitioners might want to pay more attention to the health of this important and relatively neglected group. Worries about studies and money appear to be affecting students' academic work, and this should be of concern to higher education establishments.     

Synthesis and antimicrobial activities of N-substituted imides

In the field of our research programs concerning novel antimicrobial agents, a series of N-substituted imides was synthesized. These compounds were obtained by cyclization of amido-acids in acetic anhydride/sodium acetate or hexamethyldisilazane/zinc bromide for the hydroxy-aromatic derivatives. The hydroxy-alkyl maleimides were directly prepared by condensation of the corresponding amino-alcohol with maleic anhydride in boiling toluene. Most of N-substituted maleimides showed an interesting antimicrobial activity towards bacteria from the ATCC collection (Staphylococcus aureus ATCC 25923, Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853) but the MIC values for P. aeruginosa were always high (128 microg/ml). The imides with alkyl substituents showed higher activities than aromatic analogues with MIC values in the range of 8-32 microg/ml. Comparatively, succinimides were practically inactive.     

Reversible skeletal abnormalities in gamma-glutamyl transpeptidase-deficient mice

Gamma-glutamyl transpeptidase (GGT) is a widely distributed ectopeptidase responsible for the degradation of glutathione in the gamma-glutamyl cycle. This cycle is implicated in the metabolism of cysteine, and absence of GGT causes a severe intracellular decrease in this amino acid. GGT-deficient (GGT-/-) mice have multiple metabolic abnormalities and are dwarf. We show here that this latter phenotype is due to a decreased of the growth plate cartilage total height resulting from a proliferative defect of chondrocytes. In addition, analysis of vertebrae and tibiae of GGT-/- mice revealed a severe osteopenia. Histomorphometric studies showed that this low bone mass phenotype results from an increased osteoclast number and activity as well as from a marked decrease in osteoblast activity. Interestingly, neither osteoblasts, osteoclasts, nor chondrocytes express GGT, suggesting that the observed defects are secondary to other abnormalities. N-acetylcysteine supplementation has been shown to reverse the metabolic abnormalities of the GGT-/- mice and in particular to restore the level of IGF-1 and sex steroids in these mice. Consistent with these previous observations, N-acetylcysteine treatment of GGT-/- mice ameliorates their skeletal abnormalities by normalizing chondrocytes proliferation and osteoblastic function. In contrast, resorbtion parameters are only partially normalized in GGT-/- N-acetylcysteine-treated mice, suggesting that GGT regulates osteoclast biology at least partly independently of these hormones. These results establish the importance of cysteine metabolism for the regulation of bone remodeling and longitudinal growth.     

Intravesical morphine analgesia is not effective after bladder surgery in children: results of a randomied double-blind study

PURPOSE: Intravesical morphine was recently recommended to reduce postoperative pain after reimplantation surgery for vesicoureteral reflux in children. The efficacy of such treatment, so far solely evaluated by open study, needed to be confirmed. MATERIALS AND METHODS: After parental informed consent was obtained, 80 children requiring Cohen cross-trigonal reimplantation were considered for inclusion in a double-blind study. On the day of surgery patients were randomly assigned to receive either 0.04 mg./kg. morphine per hour or placebo (normal saline) at a constant intravesical infusion rate of 0.08 ml./kg. per hour. Postoperative pain was assessed every 3 hours using a pain score adapted to patient age. If the score was above a predefined limit, patients received intravenous acetaminophen and nalbuphine alternately every 3 hours. Bladder infusion was discontinued after 48 hours. RESULTS: Mean and maximum pain scores as well as the number of scores above the limit were not statistically different when comparing the morphine and placebo groups. There was no difference in the number of doses of analgesics administered. Urine output, voiding frequency and the number of painful voiding episodes were not significantly different between the 2 groups. Plasma morphine concentrations were 3.0 +/- 2.7 and 1.9 +/- 1.9 ng./ml. at 24 and 48 hours in the morphine group and undetectable in the placebo group. CONCLUSIONS: Intravesical administration of morphine is not effective for relieving postoperative pain during the first 48 hours after intravesical ureteral reimplantation. This study emphasizes the importance of controlled studies in evaluating the effectiveness of a new drug or procedure before recommending its use for all patients.     

Increased vaccination efficiency with apoptotic cells by silica-induced, dendritic-like cells

We have demonstrated previously the ability of apoptotic cells to prime a functional immune response using an i.p. vaccination protocol with apoptotic cells and interleukin 2, before injecting a lethal dose of tumor cells into syngeneic rats. This protocol resulted in a survival rate of 33%. To elucidate the nature and the activity of the phagocytes involved in the clearance of apoptotic cells in vivo, we modulated the peritoneal cavity environment by administrating either thioglycollate or silica i.p. before injecting the apoptotic cells. Our results showed that thioglycollate abrogated vaccination efficiency, because none of the rats survived under these conditions. In fact, thioglycollate treatment induced a massive recruitment and activation of inflammatory macrophages that efficiently engulfed apoptotic cells, bypassing induction of specific immune responses. In contrast, silica treatment enhanced the vaccination efficiency of apoptotic cells plus interleukin 2 up to 66%. We distinguished a population of dendrite-like cells among the cells derived from the silica-treated peritoneal cavity both by their phenotype (MHC II(+)/CD80(+)/CD86(+)) and by their ability to induce the proliferation of allogeneic T cells in a mixed leukocyte reaction. Our results demonstrate the different roles of macrophages and dendritic-like cells in the physiological clearance of dead tumor cells and their implication in the design of immunomodulating vaccines.     

NextStitch: double-stranded suture chain,a tool to optimize approximation of sutures in valve surgery with echocardiographic correlation

Suture technique for valve replacement surgery has often focused on decreasing the soft tissue injury that leads to pseudoaneurysm formation and associated latent infection. There is universal recognition that precise suture placement is essential for avoiding adverse sequelae while allowing flexibility during the implantation of the prosthesis. The use of a continuous chain of linked horizontal mattress sutures (NextStitch) has allowed maximal precision in the approximation of sutures within the valve annulus. The product was used in a series of consecutive mitral and aortic valve replacements, and typical echocardiographic images from each type of implantation are presented. Postoperative echocardiography images revealed that no perivalvular leaks occurred and that NextStitch did not obscure detailed interrogation or assessment of the valve prosthesis.