Percutaneous radiologic gastrostomy: results and analysis of factors contributing to complications.
INTENT: Assessment of feasibility of percutaneous radiologic gastrostomy (PRG) for long- or short-term nutritional support and analysis of attendant complications and their underlying causes. A retrospective analysis of outcome, complications, and their underlying causes was carried out in 391 patients who had percutaneous gastrostomies performed in two different university medical centers from January 2005 to April 2010 by interventional radiology. Forty-three were performed under general anesthesia and 348 were under local anesthesia and conscious sedation; in 349, fluoroscopic guidance was used, in 17 ultrasound, and in 22 CT. Three hundred and seventy-six procedures were technically successful (96%). The procedure-related mortality was 2.5%. Fifty-seven gastrostomies were removed after clinical condition of the patients had improved. Only 36 gastrostomies remained functional for a year or longer. Major complications attributable to PRGs occurred in 6.1% (24 of 391) of our patients. On retrospective analysis, faulty technique may have been a major factor in many of these 24 patients. Injuries of abdominal organs and misplaced gastrostomies occasioned by improper localization of T fasteners were the major culprits. Minor complications occurred in 17.6% of patients. Meticulous pre-procedural assessment of the topographic anatomy, preferably by CT, is mandatory to avoid or minimize by injury of colon, spleen, liver etc. Precise placement of T fasteners and confirmation of gastric access under cross-table lateral fluoroscopy is necessary for proper placement of the gastrostomy tube. Percutaneous radiologic gastrostomy has proven an excellent technique for short- and long-term nutritional support.


Langevin dynamics, entropic crowding, and stochastic cloaking.
We consider a pack of independent probes--within a spatially inhomogeneous thermal bath consisting of a vast number of randomly moving particles--which are subjected to an external force. The stochastic dynamics of the probes are governed by Langevin's equation. The probes attain a steady state distribution which, in general, is different than the concentration of the particles in the spatially inhomogeneous thermal bath. In this paper we explore the state of "entropic crowding" in which the probes' distribution and the particles' concentration coincide--thus yielding maximal relative entropies of one with respect to the other. Entropic crowding can be attained by two scenarios which are analyzed in detail: (i) "entropically crowding thermal baths"--in which the particles crowd uniformly around the probes; (ii) "entropically crowding Langevin forces"--in which the probes crowd uniformly amongst the particles. Entropic crowding is equivalent to the optimal stochastic cloaking of the probes within the spatially inhomogeneous thermal bath.


Characterization of defective CD4-CD8- T cells in murine tumors generated independent of antigen specificity.
Immune-based therapy confers limited benefits to hosts bearing late-stage tumors. Mounting evidence points to local suppression of T cell function as the most substantial barrier to effective antitumor immunity in hosts with large tumor burdens. Despite this, events responsible for locally defective T cells and immune suppression in tumors remain unclear. We describe in this study a predominant T cell population localized within two murine tumors that is characterized by expression of apoptotic markers and TCRalphabeta/CD3, but not CD4, CD8, or NK-associated markers. These defective cells resembled double negative (DN) T cells in lpr mice, harbored defects in the expression of T cell signaling molecules, and produced the anti-inflammatory cytokine, IL-10. Conditions known to increase or decrease the accumulation of lpr DN T cells had corresponding effects on local DN tumor infiltrating lymphocyte (TIL) levels and inversely impacted host survival. Adoptive transfer into s.c. tumors demonstrated that naive CD8(+) T cells were highly susceptible to becoming DN TIL, and local supplementation of tumors with nontumor Ag-bearing MHC class I-expressing fibroblasts decreased both this susceptibility and endogenous DN TIL levels. These findings identify a major defective T cell population with suppressive potential within tumors. The data also suggest that local T cell defectiveness is controlled by the tumor environment independent of cognate Ag specificity per se. Decreasing defective DN TIL levels by increasing noncognate peptide MHC class I availability, or modulating TCR or cytokine signaling may facilitate host survival by bolstering endogenous immunity to late-stage tumors, and may help improve therapeutic tumor vaccines.


Three-dimensional arbitrary voxel shapes in spectroscopy with submillisecond TEs.
A novel spectroscopic method for submillisecond TEs and three-dimensional arbitrarily shaped voxels was developed and applied to phantom and in vivo measurements, with additional parallel excitation (PEX) implementation. A segmented spherical shell excitation trajectory was used in combination with appropriate radiofrequency weights for target selection in three dimensions. Measurements in a two-compartment phantom realized a TE of 955 µs, excellent spectral quality and comparable signal-to-noise ratios between accelerated (R = 2) and nonaccelerated modes. The two-compartment model allowed a comparison of the spectral suppression qualities of the method and, although outer volume signals were suppressed by factors of 1434 and 2246 compared with the theoretical unsuppressed case for the clinical and PEX modes, respectively, incomplete suppression of the outer volume (935 cm(3) compared with a target volume of 5.86 cm(3) ) resulted in a spectral contamination of 10.2% and 6.5% compared with the total signal. The method was also demonstrated in vivo in human brain on a clinical system at TE = 935 µs with good signal-to-noise ratio and spatial and spectral selection, and included LCModel relative quantification analysis. Eight metabolites showed significant fitting accuracy, including aspartate, N-acetylaspartylglutamate, glutathione and glutamate.


[Superior protective activity of phenytoin against hypoxia in pharmacological screening test].
In the treatment of cerebral infarction, it is important to select drugs for inhibiting development of the pathology. In order to select markedly effective drugs among many drugs, it is possible to grasp the outline of drug effects by means of an experimental system with simplicity and regularity--a screening test. In the present study, we induced a hypoxic load by exposing mice to a gas mixture consisting of 4% O2 and 96% N2, and investigated the effects of various kinds of drugs with reference to the survival time(ST: mean +/- SE), the time until the respiratory arrest of the mice. In the control group (n = 110), ST was 170 +/- 6 sec, with a normal distribution, and no mice that survived for eight minutes or more after the load were found. In contrast, ST was 1,833 +/- 487 sec in the suloctidil-treated group (12.5 mg/kg, n = 11), 1,160 +/- 342 sec in the vitamin E group (200 mg/kg, n = 15), 602 +/- 74 sec in the pentobarbital group (50 mg/kg, n = 12) and 2667 +/- 452 sec in the phenytoin group (100 mg/kg, n = 10). On the other hand, no prolongation of ST was found in the groups to which vitamin C, coenzyme Q, cytochrome c, betamethasone, mannitol or germanium-132 were administered. The ratio of the mice that survived for one hour or more after the load was 0% in the control group, 45.5% in the suloctidil group (12.5 mg/kg), 23.5% in the vitamin E group (200 mg/kg), 0% in the pentobarbital group (50 mg/kg) and 70% in the phenytoin group (100 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)


[Molecular study of CYP21A2 gene for prenatal diagnosis of congenital adrenal hyperplasia. Report of a family].
Prenatal treatment of pregnancies at risk of congenital adrenal hyperplasia (CAH) may prevent ambiguous genitalia in female fetuses. We present the prenatal treatment performed in an extended family with two mutations. The proband, a boy with CAH-salt losing form, and his relatives were studied. The proband's paternal uncles/aunts were married to the maternal aunts/uncles, respectively. The relatives had normal basal and stimulated 17OHProgesterone levels, which did not clarify their carrier status. The CYP21A2 gene was sequenced. The proband and the paternal relatives harbored a Q318X, R483W mutation in one allele. The maternal relatives and the proband exhibited an R483 frameshift mutation. Early dexamethasone treatment was given during two pregnancies and stopped when male gender was confirmed by early ultrasonography Both newborns were healthy and had normal 17OHProgesterone levels. This family had three mutations which abolish the 21-hydroxylase activity. Two mutations were detected in codon 483 of CYP21A2 gene, exon 10, which have not been reported previously in Latin-America. The molecular study performed in this family allowed us to give an appropriate genetic counseling and prenatal treatment.


Ultrasonography reinvents the originally described technique for ganglion impar neurolysis in perianal cancer pain.
Visceral pain in the perineal area associated with malignancies may be effectively treated with neurolysis of the ganglion impar. Since the first description of the technique of accessing the ganglion impar through anococcygeal ligament, many techniques for ganglion impar block have been described. We present a patient diagnosed with carcinoma of the anal canal who was successfully given ultrasound-guided ganglion impar block using a Chiba needle inserted through the anococcygeal ligament. In summary, ultrasound-guided ganglion impar neurolysis is a fast, safe, and cost-effective method, which can be used as a first-line pain relief intervention for good quality of life in patients with perianal cancers.


Why do lesser toes deviate laterally in hallux valgus? A radiographic study.
Hallux valgus foot with laterally deviated lesser toes is a complex condition to treat. Ignoring the laterally deviated lesser toes in hallux valgus might result in unsatisfactory foot shape. Without lateral support of the lesser toes, it might increase the risk of recurrence of hallux valgus. We sought to identify associated radiographic findings in patients where lesser toes follow the great toe in hallux valgus and deviate laterally. The weight-bearing, anteroposterior foot radiographs of 24 female hallux valgus feet with laterally deviated lesser toes (group L), 34 female hallux valgus feet with normal lesser toes (group H), and 43 normal female feet (group N) were selected for the study. A 2-dimensional coordinated system was used to analyze the shapes and angles of these feet by converting each dot made on the radiographs onto X and Y coordinates. Diagrams of the feet in each group were drawn for comparison. The hallux valgus angle, lateral deviation angle of the second toe, intermetatarsal angles, toe length, metatarsal length, and metatarsus adductus were calculated according to the coordinates of the corresponding points. The mapping showed the bases of the second, third, and fourth toe in group L shifted laterally away from their corresponding metatarsal head (P < .001). The mean 2-3 intermetatarsal angles were: group L, H, N = 7.7 ± 2.6, 4.3 ± 1.9, 4.3 ± 1.3 degrees, respectively (P < .001); mean 3-4 intermetatarsal angles were, for groups L, H, N = 7.3 ± 2.3, 6.1 ± 2.1, 6.3 ± 1.4 degrees, respectively (P < .05). Larger hallux valgus angles (P < .001), more adducted first metatarsal (P < .05), and divergent lateral splaying of the lesser metatarsals (P < .001) were found in group L. Larger 2-3 and 3-4 intermetatarsal angles, larger hallux valgus angle, more adducted first metatarsal, and divergent lateral splaying of the lesser metatarsals were associated with lateral deviation of the lesser toes in hallux valgus. Level III, comparative study.


Large renal aneurysm successfully treated by percutaneous embolization using detachable steel coils.
A 71-year-old man was referred to our hospital because of hematuria. A computed tomography scan showed a huge aneurysm (43 x 32 x 30 mm) in the right kidney. The patient was treated successfully with transcatheter arterial embolization (TAE) using detachable steel coils. At present, 1 year after TAE, the patient has no hematuria and hypertension. To our knowledge, this case is the second largest aneurysm treated successfully by TAE.


GTP-bound human MxA protein interacts with the nucleocapsids of Thogoto virus (Orthomyxoviridae).
Human MxA protein is an interferon-induced member of the dynamin superfamily of large GTPases. MxA inhibits the multiplication of several RNA viruses, including Thogoto virus, an influenza virus-like orthomyxovirus transmitted by ticks. Previous studies have indicated that GTP binding is required for antiviral activity, but the mechanism of action is still unknown. Here, we have used an in vitro cosedimentation assay to demonstrate, for the first time, a GTP-dependent interaction between MxA GTPase and a viral target structure. The assay is based on highly active MxA GTPase as effector molecules, Thogoto virus nucleocapsids as viral targets, and guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) as a stabilizing factor. We show that MxA tightly interacts with viral nucleocapsids by binding to the nucleoprotein component. This interaction requires the presence of GTPgammaS and is mediated by domains in the carboxyl-terminal moiety of MxA. We propose that GTP-bound MxA adopts an antivirally active conformation that allows interaction with viral nucleocapsids, thereby impairing their normal function.


Antimalarial polyamine analogues.
A series of novel tetraamines of the general formula RNH(CH2)xNH(CH2)yNH(CH2)xNHR was synthesized and examined for activity against growth of Plasmodium falciparum in vitro. Within the series, dibenzyl analogues (R = benzyl) were found to be the most effective growth inhibitors, with IC50 values of about 10(-6) M. Further modifications of the tetraamine provided the optimum chain length for antimalarial activity of y = 7, x = 3. Compound 8 (MDL 27,695) with the structure y = 7, x = 3, R = benzyl, in combination with the ornithine decarboxylase inhibitor alpha-(difluoromethyl)ornithine, resulted in radical cures when tested against experimental Plasmodium berghei infections in mice. The structure-activity relationships of the series are discussed.


A polymethoxyflavone mixture extracted from orange peels, mainly containing nobiletin, 3,3',4',5,6,7,8-heptamethoxyflavone and tangeretin, suppresses melanogenesis through the acidification of cell organelles, including melanosomes.
Skin color is determined by melanin contents and its distribution. Melanin is synthesized in melanosomes of melanocytes, catalyzed by tyrosinase, melanogenic enzymes. Regarding the process of melanin synthesis, melanosomal pH is considered to play an important role, because it has been reported to differ between Caucasian and Black melanocytes. Although polymethoxyflavone (PMF) has many beneficial effects, it has not been reported which PMF suppresses melanogenesis. In this study, we identified the mechanism underlying the effect of PMF on melanogenesis METHODS: We determined the effects of a PMF mixture extracted from orange peels on melanogenesis, on tyrosinase expression, on the localization of tyrosinase and on the acidification of organelles, including melanosomes, in HM3KO human melanoma cells. RESULTS TREATMENT: with the PMF mixture elicited the suppression of melanogenesis, the degradation of tyrosinase in lysosomes and the mislocalization of tyrosinase associated with the acidification of intracellular organelles, including melanosomes. The neutralization of cell organelle pH by ammonium chloride restored melanogenesis and the correct localization of tyrosinase to melanosomes, which had been suppressed by the PMF mixture. These results suggest that the PMF mixture suppresses the localization of tyrosinase to melanosomes and consequently inhibits melanogenesis due to the acidification of cell organelles, including melanosomes.


Wrist ganglia. Incidence and recurrence rate after operation.
165 patients operated on for primary wrist ganglia during 1970-71 were followed-up 5 years later in order to study the recurrence rate after a standardized surgical procedure. A questionnaire was used and the overall response rate was 86%. The recurrence rate was 12.7% and the annual incidence rate was 43/100,000 for females and 25/100 000 for males, giving a F/M sex ratio of 1.7 to 1.


Update of familial pancreatic cancer in Germany.
The prevalence of familial pancreatic cancer (FPC) and the characteristics of FPC have not yet been well investigated in the German population. Therefore, a German case collection for FPC was established in July 1999 to collect and evaluate data on FPC families. The prevalence of pancreatic cancer (PC) as well as other tumours and diseases was studied in families with at least 2 first-degree relatives with histologically confirmed PC, and in families of patients with PC and a first-degree relative with malignant melanoma. All participating family members were genetically counselled and evaluated by a standardised questionnaire. In an 18-month period, 73 independent kindreds with potential FPC contacted the national case collection. So far, 20 kindreds have fulfilled the criteria for FPC and have undergone complete workups. Most families revealed an autosomal dominant pattern of inheritance. Twelve families revealed an isolated accumulation of PC. Importantly, in 8 of 20 (35%) families, additional tumour types such as melanoma, breast and prostate cancer occurred. The observed phenotypic heterogeneity indicates an association with predisposing tumour suppressor genes p16 and BRCA2 in up to 30% of FPC families. Mutation analysis of these candidate genes might lead to the identification of the predisposing gene defect in a proportion of FPC families.


Medical management of the diabetic patient with coronary artery disease.
The prevalence of type 2 diabetes is rising at an alarming rate worldwide. Coronary artery disease (CAD) is the leading cause of morbidity and mortality in the diabetic population. Future CAD risk should be routinely assessed in patients with diabetes as specific subgroups might benefit from information derived from cardiac stress testing and other diagnostic procedures. Risk factor control is of paramount importance in all cases and it usually requires sustained lifestyle modifications, coupled with pharmacological interventions. Statins and angiotensin-converting enzyme (ACE) inhibitors are the first-line agents for the treatment of dyslipidaemia and hypertension, respectively. Microvascular, but not macrovascular, complications of diabetes are effectively prevented by good glycaemic control. Metformin is considered the first-choice agent in overweight diabetic subjects, while the role of thiazolidinediones is currently the focus of medical research. The diagnosis of acute coronary events in patients with diabetes is often challenging because of the high prevalence of silent ischaemia in these subjects. All acute cardiac events need to be promptly treated and myocardial reperfusion attempted without delay. Maintaining glucose levels as close to normal as possible, during and shortly after an acute event, improves prognosis in patients with diabetes. Risk factor control remains the cornerstone of secondary prevention; beta-blockers, ACE-inhibitors and antiplatelet agents confer additional symptomatic and survival benefit. Similar therapeutic principles also apply to patients with type 1 diabetes. This article addresses the complex problem of managing patients with diabetes and coronary artery disease.


Improving recruitment of older people to research through good practice.
There is widespread evidence both of the exclusion of older people from clinical research, and of under-recruitment to clinical trials. This review and opinion piece provides practical advice to assist researchers both to adopt realistic, achievable recruitment rates and to increase the number of older people taking part in research. It analyses 14 consecutive recently published trials, providing the number needed to be screened to recruit one older participant (around 3:1), numbers excluded (up to 49%), drop out rates (5-37%) and whether the planned power was achieved. The value of planning and logistics are outlined, and approaches to optimising recruitment in hospital, primary care and care home settings are discussed, together with the challenges of involving older adults with mental incapacity and those from minority groups in research. The increasingly important task of engaging older members of the public and older patients in research is also discussed. Increasing the participation of older people in research will improve the generalisability of research findings and inform best practice in the clinical management of the growing older population.


Effects of a short-term rehabilitation program on airway inflammation in children with cystic fibrosis.
Respiratory therapy in cystic fibrosis (CF) consists of airway clearance, infection control, and reduction of airway inflammation. It is well recognized that physical activity as well as daily chest physiotherapy, enhance airway clearance. We investigated the effects of pulmonary rehabilitation, including physical activity and chest physiotherapy, on airway inflammation in children with CF. Eighteen children with stable CF (six females), aged 8.2-16.2 years, participating in a 3-week multidisciplinary inpatient rehabilitation program were recruited. Assessment at the beginning and the end of the program included clinical score, pulmonary function test, exhaled breath condensate (EBC) and sputum analysis. Sputum supernatant and EBC were analyzed for interleukin (IL)-1b, 6, 8, 10, 12, tumor necrosis factor-alpha (TNF-alpha) and LTB4. Median (IQR) symptom scores decreased from 19 [23] to 16 [21], P = 0.005. Vital capacity and FVC increased significantly (P < 0.05). However no difference was found for the total sputum cells and sputum as well as EBC cytokines between the two visits. Significant correlations were found for sputum IL-1 (+), IL-6 (-), and IL-8 (+) to total sputum cell count and neutrophils and for IL-8 to TNF-alpha. We have shown that a short-term inpatient rehabilitation for children with stable CF with intensive physical activity mainly improve subjective clinical symptoms and measures of lung function such as VC and FVC but does not influence airflow obstruction and airway inflammation as assessed by sputum and EBC analysis.


Propranolol in DOCA hypertensive rats: development of hypertension inhibited and pressor responsiveness enhanced.
D,L-Propranolol given in single doses by gavage or s.c. injection to awake rats, always slowed the heart without affecting blood pressure. Doses of 0.2 mg/100 g injected twice daily lowered systolic pressure after 3 days in DOCA hypertensive but not in normotensive or spontaneously hypertensive rats. When chronic treatment with propranolol preceded the induction of DOCA hypertension, the pressure elevation attained 14 weeks later was less in treated than in untreated rats. Pressor responses to injected norepinephrine and to posterior hypothalamic stimulation were significantly larger in DOCA hypertensive rats that had been treated chronically with propranolol than in those that had not. These results suggest that propranolol's antihypertensive effects are unimpressive because they are simultaneously opposed by an enhanced cardiovascular responsiveness to pressor stimuli.


A safe, simple method for preparing heat-damaged red cells for diagnosing splenic infarct or trauma.
The purpose of this study was to demonstrate a fast, safe and simple method for preparing heat-damaged red blood cells. Patient blood was radiolabeled using the Ultra-Tag RBC kit and then heated to 49.5 degrees C for 20 min. The reaction vial was cooled in ice water for 1 min and the required activity was administered to the patient. The patient was imaged 60 min postinjection. High-quality planar and SPECT images of the spleen were obtained with low background activity noted. Radiolabeling efficiency was greater than 95%. The method was safe and simple to perform. High-quality images of the spleen were obtained.


Surface heterogeneity of bovine sperm revealed by aqueous two-phase partition.
Ejaculated, bovine sperm have been subjected to multiple partition in aqueous two-phase systems. This partition, carried out in a countercurrent fashion, reveals heterogeneity of the sperm population with respect to surface properties. The sperm, when partitioned in phase systems that detect non-change associated surface properties (change-insensitive) are largely distributed as two distinct populations. In charge-sensitive phase systems (which principally detect cell surface molecules carrying charge) the sperm do not show any obvious surface heterogeneity. Considerable heterogeneity is revealed in affinity-ligand phase systems containing palmitic acid coupled to one of the phase components-poly(ethylene glycol). There is a difference in surface heterogeneity between sperm which have been washed in buffer or left unwashed, direct from the ejaculate. This is indicative of weak adsorption of proteins to the sperm surface in seminal fluid. These results show that bovine ejaculated sperm is a heterogeneous cell population having unequal distributions of a number of different surface molecules.


Removal of PCR inhibitors from soil DNA by chemical flocculation.
Extracting high-purity DNA directly from soil has become essential for the study of microorganisms in environmental samples. However, many soils contain compounds that inhibit enzymes involved in manipulating DNA. In this study, chemical flocculation using multivalent cations was investigated as a potential method for eliminating soil-based inhibitors during the extraction process. The addition of AlNH(4)(SO(4))(2) during extraction significantly reduced the co-purification of PCR inhibitors with minimal loss of DNA yield.


Screening human genes for small alterations performing an enzymatic cleavage mismatched analysis (ECMA) protocol.
Many human diseases are caused by small alterations in the genes and in the majority of cases sophisticated protocols are required for their detection. In this study we estimated the efficacy of an enzymatic protocol, which using a new mismatch-specific DNA plant endonuclease from celery (CEL family) recognizes and cleaves mismatched alleles between mutant and normal PCR products. The protocol was standardized on a variety of known mutations, in 11 patients with cystic fibrosis (CF), Fabry's disease (FD), steroid 21-hydroxylase deficiency (21-HD), and Duchenne/Becker muscular dystrophy (DMD/BMD). The method does not require special equipment, labeling or standardization for every PCR product, since conditions of heteroduplex formation and enzyme digestion are universal for all products. The results showed that the method is rapid, effective, safe, reliable, and very simple, as the mutations are visualized on agarose or nusieve/agarose gels. The protocol was furthermore evaluated in three DMD patients with the detection of three alterations, which after sequencing, were characterized as disease causative mutations. The proposed assay, which was applied for the first time in a variety of monogenic disorders, indicates that point mutation identification is feasible in any conventional molecular lab even for cases where other techniques have failed.


New mechanisms of drug resistance in parasitic protozoa.
The main line of defense now available against parasitic protozoa--which are responsible for major diseases of humans and domestic animals--is chemotherapy. This defense is being eroded by drug resistance and, with few new drugs in the pipeline, prevention and circumvention of resistance are medical and veterinary priorities. Although studies of resistance mechanisms in parasites have lagged behind similar studies in bacteria and cancer cells, the tools to tackle this problem are rapidly improving. Transformation with exogenous DNA is now possible with all major parasitic protozoa of humans. Hence, putative resistance genes can be tested in sensitive protozoa, allowing an unambiguous reconstruction of resistance mechanisms. Gene cloning, the polymerase chain reaction, and monoclonal antibodies against resistance-related proteins have made it possible to analyze potential resistance mechanisms in the few parasites that can be obtained from infected people. Hence, the prospect of applying new knowledge about resistance mechanisms to parasites in patients is good, even though today virtually all knowledge pertains to parasites selected for resistance in the laboratory. Resistance mechanisms highlighted in this review include: 1. Decrease of drug uptake because of the loss of a transporter required for uptake. This decrease contributes to resistance to arsenicals and diamidines in African trypanosomes. 2. The export of drugs from the parasite by P-glycoproteins and other traffic ATPases. This export could potentially be an important mechanism of resistance, as these proteins are richly represented in the few protozoa analyzed. There are indications that such transmembrane transporters can be involved in resistance to emetine in Entamoeba spp., to mefloquine in Plasmodium spp., and to antimonials in Leishmania spp. 3. The possible involvement of the P-glycoprotein encoded by the Plasmodium falciparum pfmdr1 gene in chloroquine resistance. We present the available data that lead to the conclusion that overproduction of the wild-type version of this protein results in chloroquine hypersensitivity rather than resistance. 4. The involvement of the PgpA P-glycoprotein of Leishmania spp. in low-level resistance to arsenite and antimonials. We raise the possibility that this protein transports glutathione conjugates of arsenite and antimonials rather than the compounds themselves. 5. Loss of drug activation as the main mechanism of metronidazole resistance in Trichomonas and Giardia spp. Recent evidence indicates that a decrease of the proximal cellular electron donor for metronidazole activation, ferredoxin, is the main cause of resistance in Trichomonas. 6. Resistance arising through alteration of drug targets. The amino acid substitutions in the dihydrofolate reductase-thymidylate synthase of Plasmodium spp. are good examples of this mechanism.(ABSTRACT TRUNCATED AT 400 WORDS)


Collisional statistics of the hard-sphere gas.
We investigate the probability distribution functions of the free flight time and of the number of collisions in a hard-sphere gas at equilibrium. At variance with naive expectation, the latter quantity does not follow Poissonian statistics, even in the dilute limit, which is the focus of the present analysis. The corresponding deviations are addressed both numerically and analytically. In writing an equation for the generating function of the cumulants of the number of collisions, we came across a perfect mapping between our problem and a previously introduced model: the probabilistic ballistic annihilation process [Coppex, Phys. Rev. E 69, 11303 (2004)]. We exploit this analogy to construct a Monte Carlo-like algorithm able to investigate the asymptotically large time behavior of the collisional statistics within a reasonable computational time. In addition, our predictions are compared with the results of molecular dynamics simulations and the direct simulation Monte Carlo technique. An excellent agreement is reported.


Luteolytic potency in a novel prostaglandin analogue.
Estrus induction in cycling sows with exogenous prostaglandin is hindered by the extended refractory period and resistance of swine to the luteolytic action of PG's. The luteolytic potency of a novel PGF2 alpha analogue, Schering ZK 71677, was assessed at four different dosages in chronically cannulated cycling swine. Dosages totalling 1, 1.5, 3 and 10 mg of ZK 71677 were split into two injections given intramuscularly on day 13 of the estrous cycle. Onset of behavioural estrus and serum levels of progesterone and PGF metabolite were monitored. The three lowest doses did not advance estrus but did cause a transitory decline in serum progesterone concentration on day 13. The 10 mg level advanced estrus in three of four sows although the overall mean cycle length did not differ from pretreatment cycles (18.5 +/- 1.3 vs 21.3 +/- 0.6 days). Progesterone values dropped steadily in all four sows in the 10 mg treatment group. No level of ZK 71677 affected serum levels of PGF metabolite. The highest level tested of PGF2 alpha analogue ZK 71677 elicited an uninterrupted decline in serum progesterone concentrations but was inconsistent in its ability to promote early onset of behavioural estrus in swine.


Cognitive decline and education in mild dementia.
Recent studies suggested that education may modify the clinical expression of dementia and Alzheimer's disease through its association with a brain reserve capacity. We studied whether education would be related to degree of cognitive decline in mild dementia. Equations to estimate premorbid cognitive ability were derived from a representative normative sample of 83 community-dwelling African Americans using age, education, and gender as independent variables and Word List Learning (WLL) and Animal Fluency (AF) scores from the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological test battery as dependent variables. These equations were applied to a second sample of 131 African Americans (22 with dementia, 109 healthy) who completed CERAD test batteries as part of an epidemiologic study of dementia in the community. Differences between obtained and estimated premorbid WLL and AF test scores were calculated and then analyzed in a 2 (Education) x 2 (Diagnosis) ANOVA. A significant interaction association between Education and Diagnosis on WLL scores and a borderline significant interaction on AF scores showed that the high-education demented group had a greater cognitive decline from estimated premorbid levels than the low-education demented group. Thus, at comparable levels of clinical dementia severity, greater cognitive decline occurred in highly educated patients than in low-educated patients.


Histologic evaluation of periodontal attachment apparatus following the insertion of a biodegradable copolymer barrier in humans.
The purpose of this study was to histologically evaluate the effectiveness of polylactide:polyglycolide 50:50 (DL-PLGA) as a barrier to prevent epithelial migration and to promote new connective tissue attachment. Mucoperiosteal flaps were performed on 17 human teeth. DL-PLGA membrane was placed over the roots and alveolar bone. DL-PLGA was not placed over control teeth. Ninety days following surgery, block sections were obtained and processed for histologic evaluation. All specimens revealed a mean length of epithelial attachment within physiologic limits and recession of the gingival margin. There was little or no reattachment of the connective tissue. It is concluded that this copolymer barrier did not prevent epithelial migration nor enhance connective tissue attachment to human roots with severe horizontal bone loss and active periodontal disease.


Is the Mediterranean lifestyle still a reality? Evaluation of food consumption and energy expenditure in Italian and Spanish university students.
To evaluate the correspondence of diet and lifestyle to the Mediterranean model in two groups of Italian and Spanish university students. A cross-sectional nutritional survey to determine BMI, dietary habits (FFQ), energy daily expenditure and lifestyle (SenseWear Armband; BodyMedia Inc.), and to define the Mediterranean diet quality index (MDQI) in the different student groups. Bologna (Italy) and León (Spain). The survey was carried out on 210 (105 Italian; 105 Spanish) university students (mean age 27.0 (sd 3.8) years) of two different Mediterranean areas, Bologna (Italy) and León (Spain). The frequency of consumption of some food groups showed differences related to nationality and gender. Some classic Mediterranean foods such as cereals and vegetables were generally consumed more frequently by Italian students; others such as fish and pulses by Spanish students. Percentage of overweight was higher among Spanish students in spite of their higher physical activity level. Young generations seem to give up the traditional Mediterranean dietary pattern, adopting new dietary trends. Overweight appears to be related not only to physical activity level, but also to the poor MDQI.


[Late stent thrombosis in a young patient who had ulcerative colitis].
Arterial and venous thrombosis are well recognized systemic complications of inflammatory bowel disease predominantly in patients with crohn's colitis and in those with ulcerative colitis (UC). Aim : report a new case. We describe the case of a 35 years old man presenting previously an anterior infarct with a tighten stenosis in the middle part of the left anterior descending artery (LAD). The stenosis was treated percutaneously with a bare stent deployment. During an acute exacerbation of UC, the patient developed an acute coronary syndrome with ST elevation secondary to a late stent thrombosis, needing a primary coronary angioplasty. Following course is favorable. Based on this case, we'll discuss the relationship between UC and thrombosis, and therapeutic considerations inherent to thrombotic and bleeding risks.


Regulation of the synthesis of M protein by sugars, Todd Hewitt broth, and horse serum, in growing cells of Streptococcus pyogenes.
Various sugars were tested for their effect on the differential rate of synthesis of M protein during the growth of Streptococcus pyogenes strain 0055 M12T12. In a semisynthetic medium alone, a high rate of M protein synthesis occurred with glucose as a substrate; decreasing rates of synthesis occurred with sucrose and trehalose, in that order, although the rates of growth were approximately equal with all sugars. A period of derepressed synthesis of M protein occurred in the lag phase of growth and in the stationary period as the substrates were being depleted. Although glucose inhibited the utilization of other sugars, diauxie was not apparent from the growth curves. However, synthesis of M protein followed strong diauxie curves with a reduction in rate of synthesis during the utilization of the second sugar. With glucose as a substrate, 2-deoxyglucose showed a strong permanent repression of M protein synthesis, whereas both glucose and 2-deoxyglucose caused temporary repression when sucrose was the substrate. Horse serum increased the rate of synthesis of M protein in a manner very similar to that caused by adding cyclic AMP, although quantitative analyses suggested that cyclic AMP, per se, was not the effector in horse serum. Addition of Todd Hewitt broth permitted the organisms to grow on phosphorylated sugars. Although the rates of growth on phosphorylated sugars were similar to that obtained with glucose, M protein was not synthesized when a phosphorylated sugar was the sole substrate. The addition of phosphorylated sugars with glucose or sucrose as substrates strongly repressed the synthesis of M protein with glucose-1-phosphate and with fructose 1,6-diphosphate repressing M protein synthesis the most. Clearly, M protein synthesis, which was not required for growth, was preferentially induced by glucose as compared to the other sugars and was dependent upon the metabolic route by which glucose was utilized.


Daily stress and the trajectory of mood: spillover, response assimilation, contrast, and chronic negative affectivity.
Experience sampling methodology was used to examine the effects of current and prior problems on negative mood within and across days. Forty male community residents wore signal watches and kept dairy records of problem occurrence and mood 8 times a day for 8 consecutive days. Trait negative affectivity (NA), prior mood, and concurrent stress were related to mood during the day. Mood in response to a current problem was worse if the prior time had been problem free than if the prior time had been stressful. High NA Ss were more reactive to concurrent stressors than were low NAs, but the effect was small. NA and current-day stress were the major influences of mood across days. High NAs were more distressed by current-day problems and recovered more slowly from problems of the preceding day. The benefits of conceptualizing the effects of daily stressors on mood in terms of spillover, response assimilation, habituation, and contrast are discussed.


The effect of atropine and vagal stimulation on the release of neurotensin-like immunoreactivity in man.
This study investigated the food stimulated release of neurotensin-like immunoreactivity (NTLI) in man with and without the administration of atropine, and the influence of vagal stimulation by modified sham feeding and insulin hypoglycaemia. NTLI was measured, after ethanol extraction, by specific C- and N-terminally directed antisera. With both a liquid fat meal and a mixed meal an early peak of NTLI occurred. The mixed meal also produced a second sustained rise in plasma NTLI. An intramuscular injection of 0.6 mg atropine sulphate abolished the early peak, but had no effect on the late peak. Modified sham feeding and insulin hypoglycaemia did not release NTLI. We conclude that it is possible that a cholinergic non-vagal mechanism is responsible for the early phase of food stimulated release of NTLI in man, and that the second sustained rise may be cholinergically independent.


Health Security and Risk Aversion.
Health security has become a popular way of justifying efforts to control catastrophic threats to public health. Unfortunately, there has been little analysis of the concept of health security, nor the relationship between health security and other potential aims of public health policy. In this paper I develop an account of health security as an aversion to risky policy options. I explore three reasons for thinking risk avoidance is a distinctly worthwhile aim of public health policy: (i) that security is intrinsically valuable, (ii) that it is necessary for social planning and (iii) that it is an appropriate response to decision-making in contexts of very limited information. Striking the right balance between securing and maximizing population health thus requires a substantive, and hitherto unrecognized, value judgment. Finally, I critically evaluate the current health security agenda in light of this new account of the concept and its relationship to the other aims of public health policy.


Representing uncertainty: the role of cost-effectiveness acceptability curves.
Decision-making in health care is inevitably undertaken in a context of uncertainty concerning the effectiveness and costs of health care interventions and programmes. One method that has been suggested to represent this uncertainty is the cost-effectiveness acceptability curve. This technique, which directly addresses the decision-making problem, has advantages over confidence interval estimation for incremental cost-effectiveness ratios. However, despite these advantages, cost-effectiveness acceptability curves have yet to be widely adopted within the field of economic evaluation of health care technologies. In this paper we consider the relationship between cost-effectiveness acceptability curves and decision-making in health care, suggest the introduction of a new concept more relevant to decision-making, that of the cost-effectiveness frontier, and clarify the use of these techniques when considering decisions involving multiple interventions. We hope that as a result we can encourage the greater use of these techniques.


Does acute psychological stress increase perception of oesophageal acid?
Gastro-oesophageal reflux disease (GORD) patients often report an increase in their reflux symptoms during stressful situations. The aim of this study was to assess the influence of acute psychological stress on oesophageal acid perception. In 15 healthy volunteers and 10 GORD patients with a positive symptom-reflux association an oesophageal acid perfusion test was performed, once with and once without the presence of an acute psychological stressor (IQ test). The order of the measurements was randomized. The time from onset of the acid infusion to first acid perception, discomfort and pain was noted. Blood pressure was measured to assess the effect of the stress task. In healthy volunteers, the time to first perception (control task: 617 +/- 174 s vs stress task: 561 +/- 162 s), discomfort (control task: 969 +/- 158 s vs stress task: 940 +/- 151 s) or pain (control task: 1393 +/- 122 s vs stress task: 1366 +/- 121 s) did not differ significantly between both measurements. In GORD patients, no significant differences between both measurements were found either in time to first perception (control task: 63 +/- 26 s vs stress task: 43 +/- 15 s), discomfort (control task: 153 +/- 44 s vs stress task: 249 +/- 62 s) or pain (control task: 558 +/- 139 s vs stress task: 633 +/- 118 s). Systolic blood pressure rose significantly during the stress task in both the healthy volunteers (6 +/- 1 mmHg) and the GORD patients (9 +/- 2 mmHg). Neither in the healthy volunteers nor in the GORD patients, the acute psychological stress induced by an IQ test increased oesophageal acid perception. The observed increase in systolic blood pressure shows that the experimental stressors were effective.


Immunocytochemical localization of a urate oxidase immunoreactive protein in the plasma membranes and membranes of the secretory/endocytic compartments of digestive gland cells of the mussel Mytilus galloprovincialis.
The subcellular compartmentalization of urate oxidase (UOX) in the digestive glands of mussels, Mytilus galloprovincialis Lmk, was studied by means of immunoblotting and immunocytochemistry, using an antibody raised in rabbit against rat liver UOX. Western blot analysis of subcellular fractions revealed an immunoreactive polypeptide with a molecular weight similar to the corresponding mammalian hepatic protein. This crossreactive polypeptide of 32 kDa was particle-bound yet not peroxisome-associated. In paraffin sections the antiserum specifically labeled the plasma membrane of the digestive gland epithelial cells and discrete regions within the perinuclear and apical portions of the digestive tubules and duct cells. By electron microscopy gold particles representing antigenic sites were found on the microvilli and the lateral plasma membrane as well as the membranes of the secretory/ endocytic compartments, that is, the Golgi complex, secretory and some endocytic vesicle membranes. Since the peroxisomal UOX-antibody exhibits a comparable immunoreactivity towards a urate-transporter channel protein in rat kidney proximal tubules and has been used for its molecular cloning (Leal-Pinto et al., 1997, J. Biol. Chem. 272, 617-625), we suggest that the membrane protein identified in mussel digestive glands could represent a homologous urate-transporter protein.


Etiology of cerebral vasospasm.
Cerebral vasospasm is a gradual onset and prolonged constriction of the cerebral arteries in the subarachnoid space after subarachnoid hemorrhage. The principal cause is the surrounding blood clot. The significance of vasospasm is that flow through the constricted arteries may be reduced sufficiently to cause cerebral infarction. Subarachnoid blood clot is sufficient to cause vasospasm; it does not require additional arterial injury, intracranial hypertension or brain infarction, although these elements are often coexistent. The blood released at the time of aneurysmal rupture into the alien subarachnoid environment is an extraordinarily complex mix of cellular and extracellular elements that evolves as clotting occurs; cells disintegrate; local inflammation, phagocytosis and repair take place; severe constriction alters the metabolism and structure of the arterial wall as well as the balance of vasoconstrictor and dilator substances produced by its endothelium, neurogenic network and perhaps smooth muscle cells.


Axial and reformatted four-chamber right ventricle-to-left ventricle diameter ratios on pulmonary CT angiography as predictors of death after acute pulmonary embolism.
The purpose of this article is to retrospectively compare right ventricular-to-left ventricular (RV/LV) diameter ratios measured on the standard axial view versus the reformatted four-chamber view as predictors of mortality after acute pulmonary embolism (PE). Six hundred seventy-four consecutive patients (mean age, 58 years; 372 women) with a diagnosis of acute PE on pulmonary CT angiography were considered. The axial and reformatted four-chamber RV/LV diameter ratios were compared as predictors of 30-day all-cause and PE-related mortality. Ninety-seven patients (14%) died within 30 days; 39 deaths were PE related. There was no significant difference in the univariate hazard ratios (HRs) of axial and four-chamber RV/LV diameter ratios greater than 0.9 for both all-cause (HR, 2.13 [95% CI, 1.29-3.51] vs HR, 1.95 [95% CI, 1.22-3.14]; p = 0.74) and PE-related (HR, 19.6 [95% CI, 2.70-143] vs HR, 21.8 [95% CI, 2.99-158]; p = 1.0) mortality. Axial and four-chamber multivariate HRs accounting for potential confounders such as age and cancer were also similar for all-cause (HR, 1.79 [95% CI, 1.07-2.99] vs HR, 1.54 [95% CI, 0.95-2.49]; p = 0.62) and PE-related (HR, 16.3 [95% CI, 2.22-119] vs HR, 17.7 [95% CI, 2.43-130]; p = 1.0) mortality. There was no significant difference in sensitivity, specificity, negative predictive value, or positive predictive value. Axial and four-chamber measurements were well correlated (correlation coefficient, 0.857), and there was no significant difference in overall accuracy for predicting all-cause (area under the curve [AUC], 0.582 vs 0.577; p = 0.72) and PE-related (AUC, 0.743 vs 0.744; p = 1.0) mortality. The axial RV/LV diameter ratio is no less accurate than the reformatted four-chamber RV/LV diameter ratio for predicting 30-day mortality after PE.


The assessment of the risk of fracture in femora with metastatic lesions: comparing case-specific finite element analyses with predictions by clinical experts.
Previously, we showed that case-specific non-linear finite element (FE) models are better at predicting the load to failure of metastatic femora than experienced clinicians. In this study we improved our FE modelling and increased the number of femora and characteristics of the lesions. We retested the robustness of the FE predictions and assessed why clinicians have difficulty in estimating the load to failure of metastatic femora. A total of 20 femora with and without artificial metastases were mechanically loaded until failure. These experiments were simulated using case-specific FE models. Six clinicians ranked the femora on load to failure and reported their ranking strategies. The experimental load to failure for intact and metastatic femora was well predicted by the FE models (R(2) = 0.90 and R(2) = 0.93, respectively). Ranking metastatic femora on load to failure was well performed by the FE models (τ = 0.87), but not by the clinicians (0.11 < τ < 0.42). Both the FE models and the clinicians allowed for the characteristics of the lesions, but only the FE models incorporated the initial bone strength, which is essential for accurately predicting the risk of fracture. Accurate prediction of the risk of fracture should be made possible for clinicians by further developing FE models.


Potential of piperonyl butoxide-synergised pyrethrins against psocids (Psocoptera: Liposcelididae) for stored-grain protection.
Piperonyl butoxide (PB)-synergised natural pyrethrins (pyrethrin:PB ratio 1:4) were evaluated both as a grain protectant and a disinfestant against four Liposcelidid psocids: Liposcelis bostrychophila Badonnel, L. entomophila (Enderlein), L. decolor (Pearman) and L. paeta Pearman. These are key storage pests in Australia that are difficult to control with the registered grain protectants and are increasingly being reported as pests of stored products in other countries. Firstly, mortality and reproduction of adults were determined in wheat freshly treated at 0.0, 0.75, 1.5, 3 and 6 mg kg(-1) of pyrethrins + PB (1:4) at 30 +/- 1 degrees C and 70 +/- 2% RH. Next, wheat treated at 0.0, 1.5, 3 and 6 mg kg(-1) of pyrethrins + PB (1:4) was stored at 30 +/- 1 degrees C and 70 +/- 2% RH and mortality and reproduction of psocids were assessed after 0, 1.5, 3 and 4.5 months of storage. Finally, the potential of synergised pyrethrins as a disinfestant was assessed by establishing time to endpoint mortality for adult psocids exposed to wheat treated at 3 and 6 mg kg(-1) of synergised pyrethrins after 0, 3, 6, 9 and 12 h of exposure. Synergised pyrethrins at 6 mg kg(-1) provided 3 months of protection against all four Liposcelis spp., and at this rate complete adult mortality of these psocids can be achieved within 6 h of exposure. Piperonyl butoxide-synergised pyrethrins have excellent potential both as a grain protectant and as a disinfestant against Liposcelidid psocids.


Characterization of enhanced behavioral responses to L-DOPA following repeated administration in the 6-hydroxydopamine-lesioned rat model of Parkinson's disease.
Long-term treatment of Parkinson's disease with dopamine-replacing agents such as L-3,4-dihydroxyphenylalanine (L-DOPA) is compromised by many side-effects, most notably involuntary movements, L-DOPA-induced dyskinesia. Acute challenge with dopamine-replacing drugs elicits a rotational response in the 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease. This rotation is contraversive to the lesion and is considered to represent an antiparkinsonian effect. More recently, it has become clear that the rotational response shows plasticity and that repeated L-DOPA or apomorphine therapy is accompanied by a marked enhancement in this response. In this study, we demonstrate that the enhanced behavioral response to repeated dopamine-replacement therapy seen in the 6-OHDA-lesioned rat has pharmacological characteristics similar to L-DOPA-induced dyskinesia seen in MPTP-lesioned primates and man. Thus, the magnitude and rate of development of the enhanced response to L-DOPA treatment is related to both the number of doses and the size of the dose of L-DOPA administered. In contrast, de novo administration of dopaminergic drugs that are associated with a lower incidence of dyskinesia, e.g., bromocriptine or lisuride, does not lead to an enhanced behavioral response following repeated treatment. However, following a single "priming" administration of apomorphine, the rotational response elicited by subsequent bromocriptine administrations is enhanced with repeated treatment. Once established, the enhanced behavioral response to repeated L-DOPA-administration (6.5 mg/kg, twice daily) can, like L-DOPA-induced dyskinesia in man and MPTP-treated monkeys, be selectively reduced by coadministration of L-DOPA with the alpha2-adrenergic receptor antagonist yohimbine (10 mg/kg, -95%), the 5-HT uptake inhibitor 5-MDOT (2 mg/kg, -90%), or the beta-adrenergic receptor antagonist propranalol (10 mg/kg, -35%). While these rats do not exhibit symptoms of dyskinesia per se, this rodent model does exhibit behaviors, the underlying mechanism of which is likely to be similar to that underlying L-DOPA-induced dyskinesia and may prove useful in studying the molecular and cellular mechanisms of L-DOPA-induced dyskinesia in Parkinson's disease.


Brugada syndrome complicated with sudden death.
Brugada syndrome is an electrocardiographic diagnosis that is increasingly recognized as a cause of sudden cardiac death. The authors present a clinical case of a patient with a family history of sudden death, in whom a diagnosis of Brugada syndrome had been established, and who died suddenly. They also present a brief review of the main findings of this entity, particularly the diagnostic criteria and treatment of choice, since it is recognized that its prevalence will rise in the coming years.


Perforin is not co-expressed with granzyme A within cytotoxic granules in CD8 T lymphocytes present in lymphoid tissue during chronic HIV infection.
Residual HIV-1-infected cells are poorly eliminated from lymphoid tissue (LT) reservoirs by effector cytotoxic T lymphocytes (eCTL) despite antiretroviral therapy. Perforin and granzyme A (grA) constitute major effector molecules within eCTL granules that induce apoptosis and lysis of virally infected cells. Expression of perforin and grA was studied at the single cell level in LT and blood from 16 patients infected with HIV-1 (stage A1-C) who were not taking antiretroviral therapy. Immunohistochemical analysis by in situ imaging of cells from blood and LT. Quantitative in situ imaging showed that perforin-expressing CD8 T cells comprised 0.3-1.5% of total cells within the LT from recent HIV-1 seroconverters, while grA was found in 2.1-7.2% of total cells. However, despite high-level grA upregulation (1.5-4.5% of total cells) compared with that in non-infected individuals (0.4-0.9%), perforin expression remained low (< 0.1% of total cells) (P < 0.02) in LT from patients with chronic HIV-1 infection (stage A2-C). This contrasted with findings in peripheral blood mononuclear cells (PBMC) from the same HIV-1 infected cohort where perforin was detected in 13-31% of all PBMC, which was 10- to 100-fold higher than in lymphoid tissue (P < 0.001); grA was found in 14-32% of total PBMC. Two-colour staining showed that granular expression of perforin and grA was restricted to CD8 T cells in over 90% of total cells in both LT and blood. These findings indicate that cytotoxic perforin expression is impaired at local sites of HIV replication within lymphoid tissue. Since perforin is required together with grA for granule-mediated cytolysis, the low perforin expression in the LT may limit the ability of eCTL to eliminate HIV-1 infected cells in lymphoid tissue.


Diabetic neuropathy in Mauritius: prevalence and risk factors.
The study of diabetic neuropathy has been primarily in Europids, despite the high prevalence of diabetes in other populations. We set out to ascertain the prevalence of diabetic neuropathy and its risk factors in the island nation of Mauritius. Population surveys were carried out in 1987 and 1992 in Mauritius to establish the prevalence of Type 2 diabetes. In the second survey, vibration perception threshold (VPT) was also measured at the great toe in 847 subjects with diabetes, 204 subjects with impaired glucose tolerance and 127 subjects with normal glucose tolerance. Neuropathy was defined as levels of VPT exceeding the mean plus 2 standard deviations defined separately for three age groups of Mauritian non-diabetic subjects. Risk factors for neuropathy were identified cross sectionally from the 1992 data, and longitudinally from the 1987 data. Neuropathy was detected in 8.3% of the 847 diabetic subjects (12.7%) of those with known diabetes, and 3.6% of those with newly diagnosed diabetes). Logistic regression identified diabetes duration (odds ratio [95% CI]; 1.08 [1.04-1.13] per year, P=0.0002), treatment with insulin or oral hypoglycaemic agents (2.63 [1.36-5.09], P=0.004) and greater height (1.36 [1.19-1.57] per 5 cm, P < 0.001) as risk factors for neuropathy, in the cross sectional analysis. In the longitudinal analysis, diabetes duration (1.11 [1.05-1.18] per year, P=0.001), fasting glucose (1.12 [1.03-1.22] per mmol/l, P=0.01) and height (1.23 [1.03-1.45] per 5 cm, P=0.02) were associated with neuropathy. A lower 2-h plasma insulin was also associated with neuropathy in the longitudinal analysis. The prevalence of diabetic neuropathy in Mauritius is the lowest reported for any population, but the risk factors associated with it are similar to those previously found.


[Clinical and polysomnographyc differences between obese and non obese patients with obstructive sleep apnea-hypopnea syndrome].
To describe the clinical and polysomnographyc differences between obese and non- obese patients with obstructive sleep apnea-hypopnea (OSAH) syndrome. A physical examination, the Epworth Sleepiness Scale (ESS) and a polysomnography were performed to all included patients. Obesity was defined as a body mass index (BMI) of ≥ 30 kg/m(2). 408 patients with OSAH were analyzed, out of these, 119 (47 %) were obese. OSAH was mild in 101 (25 %), moderate in 91 (22 %) and severe in 216 (53 %). There were no age, sex and EES score differences between obese and non-obese patients. Cervical perimeter and sleepiness prevalence according to the ESS were significant higher in obese population. Obese patients had higher comorbidity related to dyslipidemia, high blood pressure and coronary disease. With respect to the polysomnographyc variables, the indexes of respiratory events and the levels of oxygen saturation were worse in obese patients. There were no differences in the other variables. The regression analysis showed association between obesity and OSAH severity. OSAH is a clinical condition not limited to obese population, although this group has a higher comorbidity and OSAH severity.


Definition of the critical interval for Smith-Magenis syndrome.
Smith-Magenis syndrome (SMS) comprises a complex physical and behavioral phenotype that is associated with an interstitial deletion of chromosome 17p11.2. The deletions observed in patients can range from <2 to >9 megabases of DNA and may include more than 100 genes. In order to determine the critical deletion interval responsible for the syndrome phenotype, we have examined several patients with varying deletions involving 17p11.2 by somatic cell hybrid analyses. We have binned 112 markers along 17p11.2, including 27 markers within the critical interval for SMS, which is bound proximally by D17S29 and distally by cCI17-638. In addition, we present two patients who carry deletions involving 17p11.2 but do not exhibit the typical features of SMS. Patients such as these will allow genotype:phenotype correlations to be made and the gene(s) responsible for the SMS phenotype to be determined.


Influence of type of surgery on the occurrence of parasympathetic reinnervation after cardiac transplantation.
Cardiac autonomic reinnervation after human cardiac transplantation has been demonstrated frequently but to date only for sympathetic efferents. Standard surgical techniques leave many parasympathetic branches intact in the original atria and thus with less stimulus to reinnervate the donor atria. We used changes in the RR-interval power spectrum induced by sinusoidal modulation of arterial baroreceptors by neck suction at different frequencies to detect both parasympathetic and sympathetic reinnervation in 79 subjects with "standard" and 10 "bicaval" heart transplants. In 24 subjects (17 standard and 7 bicaval), the protocol was repeated 6 and 11 months after transplantation. Neck suction at 0.20 Hz produced a component at 0.20 Hz in the RR-interval spectrum not due to respiration (fixed at 0.25 Hz), which suggested parasympathetic reinnervation, in 4 of 10 bicaval but in only 2 of 79 standard transplant subjects (whose recipient atria underwent >50% resection to remove scars of previous interventions), P<.001. In only 1 (bicaval) transplant subject was parasympathetic reinnervation present 6 months after transplantation (confirmed 3 months later); in 4 subjects, it was absent at 6 months but appeared after 11 months after transplantation. Atropine (0.04 mg/kg i.v.) abolished the response to fast (0.20 Hz) and reduced that to slow stimulation, confirming the presence of parasympathetic reinnervation (4 subjects). Parasympathetic reinnervation depends on the surgical technique: because bicaval surgery cuts all sympathetic and parasympathetic nerves, regeneration might be stimulated similarly in both branches. Standard surgery cuts only approximately 50% of sympathetic fibers; most recipient parasympathetic axons remain intact, hence their regeneration might not be stimulated.


Danish Education Registers.
Collection of systematic information on education is a long-established practice in Denmark. We describe the education registers available through Statistics Denmark. In particular, we describe the most widely used register: the Population Education Register (PER). In 2008, 96% of the Danish population aged 15-69 have non-missing education information in PER. For the immigrant population born in the same cohorts the coverage is 85-90%, which is a high coverage in an international context. The validity and coverage of the Danish education registers are very high.


Intraspecific variation within populations of Fusarium oxysporum based on RFLP analysis of the intergenic spacer region of the rDNA.
Fifty-six isolates of Fusarium oxysporum, including F. oxysporum f. sp. melonis and nonpathogenic strains, were chosen from a larger collection to represent diversity in vegetative compatibility groups (VCGs), mitochondrial DNA (mtDNA) haplotype, geographic distribution, and virulence. Using PCR, a 2.6-kb fragment including the intergenic spacer (IGS) region of the ribosomal DNA was amplified from each isolate. The enzymes EcoRI, Sau3A, CfoI, and AvaII, cut this fragment differentially, revealing 5, 6, 6, and 7 patterns, respectively. Among the 56 isolates, a total of 13 unique IGS haplotypes was identified. Among most F. o. melonis isolates. IGS haplotype correlated with VCG and mtDNA haplotype, but did not differentiate among races. However, a race 1 isolate found in VCG 0131 shared virulence, mtDNA, and IGS haplotypes characteristic of VCG 0134; this isolate may represent a conversion in VCG from 0134 to 0131. Four nonpathogens shared the pathogen vegetative compatibility phenotypes. One race 1, 2 isolate associated with VCG 0134 shared both IGS haplotype and VCG with a nonpathogen, but these isolates did not share the same mtDNA haplotype. Another nonpathogenic isolate shared mtDNA and IGS haplotypes with pathogen group 0131 and may simply be an avirulent mutant of a pathogenic strain. For the other two nonpathogenic isolates, vegetative compatibility indicated a close relationship to the pathogen, but differences in both mtDNA and IGS haplotype suggest otherwise. Overall, the IGS haplotype was more variable among the nonpathogenic F. oxysporum VCGs among which 12 of the 13 IGS haplotypes were found. Nonpathogenic isolates that shared a common mtDNA haplotype, but were associated with different VCGs, often had different IGS haplotypes.


Presence of S100A8/Gr1-Positive Myeloid-Derived Suppressor Cells in Primary Tumors and Visceral Organs Invaded by Breast Carcinoma Cells.
Increased S100A8/A9 expression in Gr1-positive cells has been shown in myeloid-derived suppressor cells and may play a role in the formation of a metastatic milieu. We aimed to determine S100A8/A9 expression alone and with coexpression of Gr1 (a myeloid marker) in primary tumor and visceral tissues invaded by metastatic breast carcinoma. Female BALB/c mice were injected with 4TLM, 4THM, and 67NR orthotopically. Confluent cells (75%-80%) were used. Primary tumor, lung, liver, and spleen tissue samples were removed 26 days after injection. Peripheral blood smears and metastasis assay were performed, as was immunohistochemistry and staining. S100A8/A9 immunoreactivity alone or coexpressed with Gr1 was found in primary tumors formed by 4TLM and 4THM cells, which was markedly higher than in primary tumors formed by nonmetastatic 67NR cells. Similarly, liver and lung tissues obtained from mice injected with 4TLM or 4THM cells were invaded by S100A8/A9-positive and Gr1-positive cells. Double-positive cells were markedly fewer in liver and lung tissues of animals injected with 67NR cells. S100A8/A9-positive cells were mostly localized in red pulp of spleens. We observed an increased number of neutrophils in the peripheral blood of mice injected with metastatic breast carcinoma cells. Tumor-derived factors may increase S100A8/A9-positive cells locally and systemically, and S100A8/A9-positive cells may provide an appropriate milieu for the formation of metastasis.


In vitro resistance to interferon-alpha of hepatitis B virus with basic core promoter double mutation.
The hepatitis B virus (HBV) genome basic core promoter (BCP) modulates HBeAg secretion at the transcriptional level. In addition to pre-core mutations, variations in the BCP are related to hepatitis B e antigen (HBeAg)-negative chronic hepatitis B. HBeAg-negative chronic hepatitis B patients show a lower sustained response to interferon (IFN). The aim of this study was to determine if there is a relationship between HBV BCP mutation and sensitivity of HBV to IFN-alpha in vitro. BCP mutations were introduced by site-directed mutagenesis and the entire genomes of wild-type and mutant HBV were transiently transferred into Huh7 cells by calcium phosphate transfection. With or without IFN-alpha, viral products in the culture medium and viral replication intermediates in the cytoplasm were detected 3 days after transfection. The amount of hepatitis B surface antigen (HBsAg) secreted by wild-type HBV and the BCP mutant was similar, while HBeAg secreted by the mutant was decreased by 35.4%. HBV particles and replication intermediates of the BCP mutant were increased. After IFN-alpha was added, HBeAg, HBV DNA and HBV replication intermediates decreased for both the wild-type HBV (by 25.7%, 31.8%, 29.8%, respectively) and the BCP mutant (by 8.4%, 27.4%, 10.1%, respectively). These data indicate that HBV harboring the BCP double mutation has stronger replication competence and lower sensitivity to IFN-alpha than wild-type.


Synthesis and preliminary screening of novel indole-3-methanamines as 5-HT4 receptor ligands.
Twenty-three indole-3-methanamines were designed, synthesized and evaluated as ligands for the 5-HT(4) receptor. Compounds I-d, I-j, I-o, I-q and I-u showed good affinity at 100 microM and I-o was found to be only 5-fold less potent than the agonists serotonin (1) and 5-methoxytryptamine (2). Substitution on the 3-methanamine nitrogen clearly influenced activity with docking experiments into a homology model of the 5-HT(4) receptor showing a range of interactions with these side chain substituents. This modelling work together with the SAR determined in this study has provided promising ideas for future synthetic work.


The Use of Mass Spectrometry to Examine IDPs: Unique Insights and Caveats.
A sizeable proportion of active protein sequences lack structural motifs making them irresolvable by NMR and crystallography. Such intrinsically disordered proteins (IDPs) or regions (IDRs) play a major role in biological mechanisms. They are often involved in cell regulation processes, and by extension can be the perpetrator or signifier of disease. In light of their importance and the shortcomings of conventional methods of biophysical analysis to identify them and to describe their conformational variance, IDPs and IDRs have been termed "the dark proteome." In this chapter we describe the use of ion mobility-mass spectrometry (IM-MS) coupled with electrospray ionization to analyze the conformational diversity of IDPs. Using the LEA protein COR15A as an exemplar system and contrasting it with the behavior of myoglobin, we outline the methods for analyzing an IDP using nanoelectrospray ionization coupled with IM-MS, covering sample preparation, purification; optimization of mass spectrometry conditions and tuning parameters; data collection and analysis. Following this, we detail the use of a "toy" model that provides a predictive framework for the study of all proteins with ESI-IM-MS.


A novel microscopic assay for oral malodor-related microorganisms.
Previous research has shown that the production of volatile sulfide compounds (VSC) by oral bacteria is associated with oral malodor. In the present study, we report a novel technique (microscopic sulfide assay (MSA)) for the quantification of VSC-producing oral microorganisms. The MSA was performed by overnight incubation of saliva samples in the presence of ferrous sulfate and sodium thiosulfate, followed by digital analysis of cells stained black due to cell-associated precipitation of ferric sulfide. This method was found to correlate significantly with oral malodor parameters, including mean odor judge scores (two judges, r = 0.48 and p = 0.001) and Halimeter® readings (r = 0.53 and p < 0.001), in a group of 42 subjects. As compared with odor judge scores as the gold standard, the new MSA technique yielded a diagnostic accuracy of 0.7 (ROC, p = 0.023). Results indicate that the MSA may serve as a diagnostic technique for assessing oral malodor levels and aid in identifying the particular bacteria involved in this condition.


Patients With Chronic Total Occlusions Undergoing Percutaneous Coronary Interventions: Characteristics, Success, and Outcomes.
Percutaneous coronary intervention (PCI) for chronic total occlusions (CTO) has been identified as a beneficial treatment, but there is limited information about its use in everyday practice. Data from New York's PCI registry between July 1, 2009, and June 30, 2012, were used to examine the utilization and variation in use of CTO PCI, the success rates across providers, the multivariable correlates of success, and the mortality of successful CTO PCI. A total of 4030 (3.1%) patients undergoing PCI underwent CTO PCI with a success rate of 61.3%. Patients with successful CTO PCIs were younger; had higher ejection fractions; were less likely to have had previous revascularization or carotid/cerebrovascular disease; and were more likely to have the CTO in the left anterior descending artery. Operators with annual CTO PCI volumes of at least 48 per year (the top volume quartile) had odds of achieving success that were more than twice as high as the half of all operators who performed <9 CTO PCIs per year. Patients with unsuccessful CTO PCIs had significantly higher 2.5-year mortality (adjusted hazard ratio, 1.63; 95% confidence interval, 1.28-2.08) than patients who had complete revascularization (CR) for all CTOs and other diseased lesions. The success rate for CTO is low compared with the rate for other lesions. Successful revascularization of CTO is associated with improved survival compared with procedures with unsuccessful CTO, and higher-volume CTO operators are more successful.


A prospective comparison of remote monitoring systems in implantable cardiac defibrillators: potential effects of frequency of transmissions.
Currently, cardiac implantable electronic devices allow remote monitoring (RM) based on periodic (Boston Latitude [LAT], Medtronic Carelink [MCL], St. Jude Merlin [SJM]) or daily transmissions (Biotronik Home Monitoring [BHM]). The aim of this study was to compare all the current RM systems in normal practice and investigate the effect of periodicity of RM transmissions on early detection of clinical and device-related events. Two hundred eleven ICD patients (mean age 69±11 years, 158 males), were remotely followed up for 1 year (61 with BHM, 49 with LAT, 65 with MCL, 36 with SJM). Remote follow-ups were configured quarterly, except for the BHM (daily transmissions). The event-free rates were 49% with BHM, 57% with LAT, 57% with MCL, and 58 % with SJM (long-rank, p=0.23). BHM generated 304 (interquartile range, 184–342) transmissions per patient in a year, LAT 9 (8–11), MCL 7 (5–10), and SJM 8 (7–14) (p<0.000001). Eighty actionable events occurred at 1 year follow-up, 69 (86%) with RM systems: BHM was associated with a higher cumulative rate of actionable events. At a multivariate analysis, daily transmissions were independently associated with an increased probability of event detection as compared to periodic transmission systems. The chance of event detection is reduced by 20% (p=0.036) for a 1-month increase of the between-transmission interval (27 % for actionable events, p=0.004). Although all RM systems effectively detected major events, daily transmission was associated with a higher probability of early event detection.


The total lifetime costs of smoking.
Net costs of smoking in a lifetime perspective and, hence, the economic interests in antismoking policies have been questioned. It has been proposed that the health-related costs of smoking are balanced by smaller expenditure due to shorter life expectancy. A dynamic (life cycle) method taking differences in life expectancy into account. Main outcome measures were direct and indirect lifetime health costs for ever-smokers and never-smokers, and cost ratios (ever-smokers to never-smokers). The estimations were based on annual disease rates of use of the healthcare services, smoking relative risks, smoking prevalences, and costs. Annual direct and indirect costs of ever-smokers were higher than for never-smokers in all age groups of both genders. The direct and indirect cost ratios were highest at age 45 for women, and at age 35 and 40 for men, respectively. Taking life expectancy differences into account, direct and indirect lifetime health costs for men aged 35, discounted by 5% per year were 66% and 83% higher in ever-smokers than in never-smokers. Corresponding results for women were 74% and 79%, respectively. The results are insensitive to a broad range of relative risk-estimates and discount rates including no discounting. Excess costs of ever-smokers disappear if the inclusion of smoking-related diseases is narrowed to that of previous studies. Smoking imposes costs to society even when taking life expectancy into consideration--both in direct and indirect costs.


The Self Test: a screening tool for dementia requiring minimal supervision.
The main purpose of this study was to correlate a newly developed, simple, but comprehensive screening test for dementia called the Self Test (ST) with the Mini-mental State Examination (MMSE), and establish the reliability and validity of the ST. The ST was administered to 42 consecutive new referrals to the memory clinic at the Cole Neuroscience Center, University of Tennessee Medical Center (UTMC), Knoxville, TN, U.S.A. and 41 age-matched control subjects at regular intervals over a 12-month period. The total ST scores correlated well with cognitive severity as measured by the MMSE (r = 0.71, p < 0.01). The area under the receiver-operating characteristic curve (AUROCC) in the group of patients with Alzheimer's disease (AD) with less than a high school education was 0.80, and 0.89 in those with at least a high school education. Reliability analysis showed a mean inter-item correlation of 0.31 for patients with AD, and 0.47 for normal participants. Cronbach's alpha was calculated to be 0.70 for the AD group. Test-retest reliability was determined using intraclass correlation coefficients (ICC = 0.93, p < 0.01). The ST is an internally consistent, reliable and valid screening test for cognitive impairment in persons exhibiting early symptoms of dementia. In addition, the ST requires minimal nonprofessional supervision and may be administered by an untrained person.


Differences of polyunsaturated fatty acid in patients with colorectal cancer and healthy people.
This study aims to compare the difference of polyunsaturated fatty acid (PUFA) between patients with colorectal cancer and healthy people and analyze the effect of PUFA on colorectal cancer by testing serum of PUFA. One hundred and fifty-six healthy people and 79 patients with colorectal cancer were randomly chosen in Beijing, China. PUFA level was measured in two groups. According to different stages, sizes, degree of differentiation, lymph node metastases from patients with colorectal cancer, we compared metabolize situation of PUFA. Total omega-6 PUFA level was higher in healthy people group than that in colorectal cancer group (25.77 ± 3.21 vs. 26.86 ± 1.65, P = 0.0125); moreover, arachidonic acid (AA) level was also higher in healthy people group than that in colorectal cancer group (5.02 ± 1.32 vs. 6.08 ± 1.26, P = 0.0344); total omega-3 PUFA level was lower in colorectal cancer group than that in healthy people group; furthermore, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) was also lower in colorectal cancer group than that in healthy people group. AA and total omega-6 were significant differences between less than 5 cm of tumor size and more than 5 cm of tumor size (13.11 ± 2.91 vs. 14.44 ± 1.81, P < 0.05; 27.02 ± 4.54 vs. 28.76 ± 3.08, P < 0.05). PUFA level was significant difference between healthy people and colorectal cancer patients in the Chinese population. Tumor size probably had influence on the metabolism of PUFA.


Pfeiffer syndrome update, clinical subtypes, and guidelines for differential diagnosis.
Steven Pfeiffer syndrome pedigrees (three 3 generation and four 2 generation) have been recorded to date in addition to at least a dozen sporadic cases. Autosomal dominant inheritance with complete penetrance is characteristic of the 7 familial instances. Variable expressivity has involved mostly the presence or absence of syndactyly and the degree of syndactyly when present. Classic Pfeiffer syndrome is designated type I. Type 2 consists of cloverleaf skull with Pfeiffer hands and feet together with ankylosis of the elbows. Such patients do poorly with an early death. All reported instances to date have been sporadic. Type 3 is similar to type 2 but without cloverleaf skull. Ocular proptosis is severe in degree and the anterior cranial base is markedly short. These patients also do poorly and tend to have an early death. To date all cases have occurred sporadically. Although these 3 clinical subtypes do not have status as separate entities, their diagnostic and prognostic implications are important. Type 1 is commonly associated with normal intelligence, generally good outcome, and can be found dominantly inherited in some families. Types 2 and 3 generally have severe neurological compromise, poor prognosis, early death, and sporadic occurrence. Recognition of type 3 is particularly important because extreme ocular proptosis in the absence of cloverleaf skull but with various visceral anomalies can result in failure to diagnose Pfeiffer syndrome and labeling the patient as an "unknown" or as a "newly recognized entity."(ABSTRACT TRUNCATED AT 250 WORDS)


Sonographic and color Doppler findings of gastrointestinal myogenic tumors with a marked extraluminal growth.
We present five cases with gastro (four cases) and intestinal (one case) myogenic tumors with a marked extraluminal growth. In all cases, incidental discovery of an asymptomatic mass prompted further examination. One of three cases with a pedunculated growth mimicked a gallbladder cancer. The mass of a jejunal leiomyoma case changed markedly in location under probe compression. Color Doppler sonography confirmed not only the hypervascular nature of the mass but also feeding and draining vessels.


Development and validation of a LC-MS/MS method for quantitation of fosfomycin - Application to in vitro antimicrobial resistance study using hollow-fiber infection model.
Extensive use and misuse of antibiotics over the past 50 years has contributed to the emergence and spread of antibiotic-resistant bacterial strains, rendering them as a global health concern. To address this issue, a dynamic in vitro hollow-fiber system, which mimics the in vivo environment more closely than the static model, was used to study the emergence of bacterial resistance of Escherichia coli against fosfomycin (FOS). To aid in this endeavor we developed and validated a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for quantitative analysis of FOS in lysogeny broth. FOS was resolved on a Kinetex HILIC (2.1 × 50 mm, 2.6 μm) column with 2 mm ammonium acetate (pH 4.76) and acetonitrile as mobile phase within 3 min. Multiple reaction monitoring was used to acquire data on a triple quadrupole mass spectrometer. The assay was linear from 1 to 1000 μg/mL. Inter- and intra-assay precision and accuracy were <15% and between ±85 and 115% respectively. No significant matrix effect was observed when corrected with the internal standard. FOS was stable for up to 24 h at room temperature, up to three freeze-thaw cycles and up to 24 h when stored at 4°C in the autosampler. In vitro experimental data were similar to the simulated plasma pharmacokinetic data, further confirming the appropriateness of the experimental design to quantitate antibiotics and study occurrence of antimicrobial resistance in real time. The validated LC-MS/MS assays for quantitative determination of FOS in lysogeny broth will help antimicrobial drug resistance studies.


A test of positional properties of avian wing-bud mesoderm.
Supernumerary wing structures are readily produced by grafting pieces of wing-bud mesoderm into different locations of host wing buds, but the mechanism underlying their formation remains obscure. The major aim of this study was to examine the ability of posterior quail wing-bud mesoderm, cultured in vitro long enough to lose ZPA (zone of polarizing activity) activity, to stimulate or participate in the formation of supernumerary structures when grafted into anterior slits of host chick wing buds. Small pieces of anterior and posterior quail wing-bud mesoderm (HH stages 21-23) were placed in in vitro culture for up to 3 days. After 2 days, ZPA activity of cultured mesoderm was lost. After the grafting of 2- to 3-day cultured anterior quail wing-bud mesoderm into posterior slits of host chick wing-buds, a consistently high percentage (70%-90%) of grafts result in formation of supernumerary cartilage; in this experiment, however, only a low percentage of grafts resulted in supernumerary cartilage when 2- to 3-day cultured posterior mesoderm was grafted into anterior slits. Taken with controls, these results show that positional differences exist between cultured anterior and posterior wing-bud mesoderm. Serial-section analysis of numerous operated wings has shown several patterns of contribution to supernumerary structures by cells of graft and host. Single supernumerary digits induced by grafts of ZPA mesoderm into anterior slits were normally composed entirely of host cells, but graft cells regularly contributed to skeletal elements of more complex supernumerary structures. Cartilage rods produced by anterior-to-posterior grafts were composed mostly of graft cells, but cartilage nodules and the bases of some rods were often mosaics of chick and quail cells. The results support the proposition that mesodermal cells of the quail wing-bud possess a form of anteroposterior positional memory, but its nature and the means by which the memory of grafted cells interacts with host mesoderm are still not clear.


Compassion fatigue, moral distress, and work engagement in surgical intensive care unit trauma nurses: a pilot study.
Preparation for replacing the large proportion of staff nurses reaching retirement age in the next few decades in the United States is essential to continue delivering high-quality nursing care and improving patient outcomes. Retaining experienced critical care nurses is imperative to successfully implementing the orientation of new inexperienced critical care nurses. It is important to understand factors that affect work engagement to develop strategies that enhance nurse retention and improve the quality of patient care. Nurses' experience of moral distress has been measured in medical intensive care units but not in surgical trauma care units, where nurses are exposed to patients and families faced with sudden life-threatening, life-changing patient consequences.This pilot study is a nonexperimental, descriptive, correlational design to examine the effect of compassion satisfaction, compassion fatigue, moral distress, and level of nursing education on critical care nurses' work engagement. This is a partial replication of Lawrence's dissertation. The study also asked nurses to describe sources of moral distress and self-care strategies for coping with stress. This was used to identify qualitative themes about the nurse experiences. Jean Watson's theory of human caring serves as a framework to bring meaning and focus to the nursing-patient caring relationship.A convenience sample of 26 of 34 eligible experienced surgical intensive care unit trauma nurses responded to this survey, indicating a 77% response rate. Twenty-seven percent of the nurses scored high, and 73% scored average on compassion satisfaction. On compassion fatigue, 58% scored average on burnout and 42% scored low. On the secondary traumatic stress subscale, 38% scored average, and 62% scored low. The mean moral distress situations subscale score was 3.4, which is elevated. The mean 9-item Utrecht Work Engagement Scale total score, measuring work engagement, was 3.8, which is considered low.Content analysis was used to identify themes of Role Conflict With Management/Rules, Death and Suffering, Dealing With Violence in the Intensive Care Unit, Dealing With Family, Powerlessness, Physical Distress, and Medical Versus Nursing Values. Additional themes identified were caring, helping families, long-time interdependent relationships of colleagues, and satisfaction in trauma nursing.As work engagement increased, compassion satisfaction significantly increased, and burnout significantly decreased. Results of this study support moral distress as a clinically meaningful issue for surgical intensive care unit nurses. Moral distress scales were elevated, whereas work engagement scales were low. This finding was congruent with Lawrence's study and may reflect ongoing need for greater supports for experienced intensive care unit nurses, from both education and management. Future recommendations for research include examining the interaction of these variables in larger samples to examine additional explanatory factors as well as strategies for self-care, motivation, and behavior change.


Adenosine attenuates the vasoconstrictor response to the cold pressor test in humans.
The forearm vasoconstrictor response to a standardized cold pressor test (CPT) was studied twice in eight healthy subjects, once during local intraarterial infusion of adenosine and once during infusion of equipotent dosages of the control vasodilator sodium nitroprusside (SNP). During local SNP infusion, the forearm vascular resistance (FVR) decreased from 70 +/- 14 to 30 +/- 7 arbitrary units (AU). Adenosine induced a comparable vasodilator response, with a decrease in FVR from 56 +/- 14 to 28 +/- 6 AU. Subsequent cold exposure induced a mean percentage increase in FVR of 62 +/- 17% during SNP, whereas the increase was only 27 +/- 12% during adenosine infusion (p = 0.014). There were no differences in the calculated cold-induced changes in forearm production of norepinephrine (NE) between the SNP and the adenosine tests. We conclude that adenosine attenuates forearm vasoconstrictor response to the CPT, probably by a postjunctional mechanism of action.


[Fragmented fracture due to fibrous lacunae of the lower femur. Apropos of a case].
The authors report a case of partial fracture of the border of a cortical defect of the distal femoral metaphysis after a mild trauma. Periostal apposition did evoke a tumor. Similar cases are very seldom in the literature.


A finite element method for growth in biological development.
We describe finite element simulations of limb growth based on Stokes flow models with a nonzero divergence representing growth due to nutrients in the early stages of limb bud development. We introduce a "tissue pressure" whose spatial derivatives yield the growth velocity in the limb and our explicit time advancing algorithm for such tissue flows is described in de tail. The limb boundary is approached by spline functions to compute the curvature and the unit outward normal vector. At each time step, a mixed hybrid finite element problem is solved, where the condition that the velocity is strictly normal to the limb boundary is treated by a Lagrange multiplier technique. Numerical results are presented.


[Relationship between the expression of matrix metalloproteinase-13 protein and other biomarkers, prognosis in invasive breast cancer].
The study was designed to investigate the expression patterns of metalloproteinase (MMP)-13 protein in invasive breast carcinoma and to determine the clinicopathological and prognostic values of its various localization and relation to the tumor phenotypes. Immunohistochemistry was performed on paraffin-embedded tissue array from 263 invasive breast carcinomas to investigate the protein expressions of MMP-13, estrogen receptor, progesterone receptor, HER2, MMP-2, MMP-9 and tissue inhibitor of matrix metalloproteinases (TIMP)-1, TIMP-2. MMP-13 protein was detected in the cytoplasm of carcinoma cells and peritumoral fibroblasts. High level expression of MMP-13 protein in tumor cells was associated with more lymph node involvement and higher tumor grade (both P < 0.01), and positively correlated with HER2 (P = 0.015) and TIMP-1 protein (P < 0.01) expression in carcinoma cells. Moreover, high expression of MMP-13 was associated with shortened overall survival for the entire patient population and the patient group with positive lymph node. Tumor cell derived MMP-13 had different impact on patients with different HER2 status. Peritumoral fibroblasts derived MMP-13 protein, although correlated with tumor cell derived MMP-13 and associated with lymph node stage and HER2 expression, was found having less prognostic impact. Univariate survival analysis showed that the tumor size, grade, lymph node status, PR status, HER2 expression, tumors TIMP-1 and MMP-13 expression were prognostic factors. However, multivariate survival analysis showed that only tumor size, lymph node status, HER2 expression, tumors TIMP-1 and MMP-13 were independent prognostic factors. MMP-13 protein expressed by tumor cells correlates with the invasion and metastasis of breast carcinoma, and therefore, may serve as a poor prognostic marker for the patient.


Impact of surgeon experience and buttress material on postoperative complications after laparoscopic sleeve gastrectomy.
Sleeve gastrectomy is gaining popularity whether as a primary, staged or revisional operation. The aim of this study is to evaluate the perioperative safety and the learning curve for laparoscopic sleeve gastrectomy (LSG). We performed a retrospective review of the prospectively collected data for all patients who underwent LSG for the treatment of morbid obesity at our institution from January 2003 to December 2008. Data from 230 consecutive patients [male 47%, female 53%; mean age 44.0 ± 10.0 years, mean preoperative body mass index (BMI) 56.7 ± 11.5 kg/m(2)], who were operated upon by three surgeons with different degrees of bariatric experience, were analyzed. There was no 30-day mortality, but there were two cases of late mortality (0.87%). Early complications were noted in 23 cases (10.0%), including 10 cases of leak (4.3%) and 10 cases of hemorrhage (4.3%). In 17 cases (7.4%) reoperations were performed. The rates of overall and major complications did not differ among surgeons or between early and late period of experience for the three surgeons; this trend held true individually and in subgroups. Overall, over the course of the learning curve, a significant decrease in operative time was noted. The only factor that was independently associated with complications was use of buttress material; the likelihood of complications was found to be 72% lower in patients in whom buttress material was used. LSG constitutes a potentially safe anti-obesity procedure with acceptable morbidity. Experience at the beginning can be discouraging, even for surgeons with advanced laparoscopic skills. LSG can be performed safely, with proper mentoring and in appropriate settings, even by less experienced bariatric surgeons. The use of staple-line reinforcement was associated with improved perioperative outcomes, and it should be considered in an attempt to decrease leaks.


Comparison of ataxia-telangiectasia mutated protein expression in diffuse large B-cell lymphomas of primary central nervous system and non-central nervous system origin.
The ataxia-telangiectasia mutated (ATM) gene encodes a nuclear 370-kd phosphoprotein known to be associated with chromosomal regions containing double-strand breaks. The mutations in the ATM gene may be involved in the development of some subtypes of sporadic lymphomas and leukemias. In primary central nervous system diffuse large B-cell lymphomas (PCNS DLBCLs), the pathogenetic role of ATM mutation has not been investigated. To investigate ATM protein expression in PCNS DLBCLs, in comparison with that in non-central nervous system (non-CNS) DLBCLs and to study the relationship of ATM protein loss with several clinicopathologic parameters. This study included 42 cases of PCNS DLBCL and 33 cases of non-CNS DLBCL from immunocompetent patients. The ATM protein loss was analyzed by immunohistochemical staining. For the subclassification of DLBCL and analysis of the relationship between ATM and other prognostic markers, we performed immunohistochemical evaluation to detect the following markers: Bcl-6, CD10, multiple myeloma-1, CD138, Bcl-2, Ki-67, and p53. The loss of ATM expression was statistically more frequent in PCNS DLBCLs (21/42 cases [50.0%]) than in non-CNS DLBCLs (0/33 cases [0.0%]; P < .001). The loss of ATM expression was not a prognostic marker in PCNS DLBCLs (P = .64). The loss of ATM expression had a strong correlation with the germinal center B-cell-like subtype (P = .01), a low Ki-67 labeling index (P = .03), and low Bcl-2 expression (P = .01) among several clinicopathologic parameters. Our results suggest that the ATM protein is more strongly correlated with PCNS DLBCL lymphomagenesis than with non-CNS DLBCLs, especially in germinal center B-cell-like subtypes demonstrating low Ki-67 labeling indexes and low Bcl-2 expression.