Familial hypophosphatemic rickets caused by a large deletion in PHEX gene.
X-linked hypophosphatemic rickets/osteomalacia (XLH), autosomal dominant and recessive hypophosphatemic rickets/osteomalacia (ADHR and ARHR) share common clinical features including high fibroblast growth factor 23 (FGF23) levels. These diseases are caused by mutations in phosphate regulating endopeptidase homolog, X-linked (PHEX), FGF23, and dentin matrix acidic phosphoprotein 1 (DMP1) gene respectively. It remains unclear whether these diseases can be clinically discriminated. To clarify the underlying mechanism of patients with hypophosphatemic rickets whose parents showed no physical findings suggesting rickets. The proband is a 39-year-old woman. She and her 37-year-old brother show the same clinical features such as bowing of legs together with hypophosphatemia (sister: P 1.8 mg/dl, brother: P 1.6 mg/dl) and high FGF23 levels (sister: 542 pg/ml, brother: 96 pg/ml). Physical findings of their parents are normal and ARHR was suspected. Sequencing of all coding exons and exon-intron junctions of DMP1 and FGF23 genes showed no mutation. Subsequent analysis revealed that there is a deletion of 52 143 bp including exons 1-3 in PHEX gene in the brother. His sister was found to be a heterozygote for the same deletion indicating that they are suffering from XLH. The same deletion was detected in the mother. However, the amount of the wild-type allele was more and that of the mutant one was less in genomic DNA from the mother compared with those from the sister. Single nucleotide polymorphism (SNP) analysis indicated that the mother has three kinds of PHEX alleles suggesting a somatic mosaicism. Careful genetic analysis is mandatory for correct differential diagnosis of hypophosphatemic rickets with high FGF23 levels.


Intensive upper limb therapy including a robotic device after surgically repaired brachial plexus injury: a case study.


Shortage of full-time faculty in dermatology.
A persistent shortage of full-time faculty exists in dermatology. Despite the addition of 124 new full-time faculty since 1971 through 1972, 136 training programs in 1974 through 1975 were actively seeking 88 new full-time faculty and believed they needed 243. With a net gain of 30 new faculty a year, it will take 2.93 years to add 88 new faculty that are being actively sought and 5.16 years to add 155 more that are urgently needed. During this eight years, demand for new faculty will increase, so that figures of need may remain essentially unchanged in 1982 through 1983 and between 1971 through 1972 and 1974 through 1975. Expertise that was most needed was in immunology, electron microscopy, histopathology, microbiology, and biochemistry; many accept faculty in any area or with no special training. Measures should be taken to attract and retain more dermatologists in full-time academic positions.


Genome-wide linkage scan and association study of PARL to the expression of LHON families in Thailand.
Leber hereditary optic neuropathy (LHON) is the most common mitochondrially inherited disease causing blindness, preferentially in young adult males. Most of the patients carry the G11778A mitochondrial DNA (mtDNA) mutation. However, the marked incomplete penetrance and the gender bias indicate some additional genetic and/or environmental factors to disease expression. Herein, we first conducted a genome-wide linkage scan with 400 microsatellite markers in 9 large Thai LHON G11778A pedigrees. Using an affecteds-only nonparametric linkage analysis, 4 regions on chromosomes 3, 12, 13 and 18 showed Zlr scores greater than 2 (P < 0.025), which is consistently significant across several linkage statistics. The most suggestive marker D3S1565 (Zlr > 2 in 10 of 16 allele sharing models tested) was then expanded to include the region 3q26.2-3q28 covering SLC7A14 (3q26.2), MFN1 (3q26.32), MRPL47 (3q26.33), MCCC1 (3q27.1), PARL (3q27.1) and OPA1 (3q28-q29). All of these candidate genes were selected from the Maestro database and had known to be localized in mitochondria. Sixty tag SNPs were genotyped in 86 cases, 211 of their relatives and 32 unrelated Thai controls, by multiplex-PCR-based Invader assay. Analyses using a powerful association testing tool that adjusts for relatedness (the M(QLS) statistic) showed the most evidence of association between two SNPs, rs3749446 and rs1402000 (located in PARL presenilins-associated rhomboid-like) and LHON expression (both P = 8.8 x 10(-5)). The mitochondrial PARL protease has been recently known to play a role with a dynamin-related OPA1 protein in preventing apoptotic events by slowing down the release of cytochrome c out of mitochondrial cristae junctions. Moreover, PARL is required to activate the intramembranous proteolyses resulting in the degradation of an accumulated pro-apoptotic protein in the outer mitochondrial membrane. Under these circumstances, variants of PARL are suggested to influence cell death by apoptosis which has long been believed to intrigue the neurodegeneration of LHON.


[Autoimmunity factor in chronic gastritis: incidence of antiparietal cell antibodies and their relation to antral histology and basal blood gastrins].
In 118 patients with histological proven chronic gastritis, was performed a study of seric antibodies against parietal cells (ACCP), following the indirect inmuno-fluorescence method. The results were positives in 36 cases (30%). Four positives cases were found in 40 normal controls (10%), two of them were compensated diabetics, one have the thyrohyoid Hashimoto's disease, and the remainder, brother of a patient with chronic gastritis, was a positive ACCP. A major positiveness (44.4%) was obtained in 9 cases of gastric atrophy than in 65 cases with atrophic gastritis (32%) and in 44 cases of superficial gastritis (25%); although due to the few cases of gastric atrophy regarding other histological types, conclusions cannot be obtained about the incidence of ACCP and histological variety of chronic gastritis. If we do group the patients according to their acid secretory debit, 53 achlorhydric patients had a positiveness of ACCP of 45%, while over 63 with decreased secretory capability, only 18.4%, was positive. The distribution by age groups, shows a major incidence of ACCP about the 4th and 5th decade of life. Thirty seven patients with chronic atrophic gastritis and achlorhydria, and seven with chronic superficial gastritis and hypochlorhydria, besides the antibodies study were on a basal dosage of gastrinemia and antral endoscopic biopsy, finding out that, achlorhydric patients (15 on 19) with normal or slightly altered antrus, have gastrinemia (222 +/- 123 Pgo/oo) and the majority of patients with normal gastrinemia (32 +/- 16 pgo/oo) have more important antral lesions. The ratio between antral histology and ACCP in auto--immune gastritis (Type A), conciliates only partially with the observation by Strickland et al., as only 52.4% of achlorhydric patients and ACCP have a normal antrus or al least with mild lesions. Our results suggest the possibility of that on auto--immune gastritis could act other pathogenic factors of antral lesion.


Treatment options to intensify hemodialysis.
At present, three methods are practiced to intensify hemodialysis (HD): 3 times weekly, 8-hour HD, short daily HD and slow daily nocturnal HD. Three times weekly 8-hour dialysis increase both the dialysis dose and time. The longest experiences are in Tassin. Five-year survival in Tassin was better in all age groups compared with the major registries - Japan, EDTA and US Medicare and more obvious for older age groups. The data of Tassin show that increasing the dialysis time provides better blood pressure control, need for no or less antihypertensive drugs, less intradialytic complications, better middle molecule and phosphate clearance, better nutritional status, less requirement for erythropoietin and increased survival. These data of Tassin could be mainly confirmed in our dialysis center. The main difference to Tassin was that in our center most of the patients still need few antihypertensive drugs. The reasons for the difference are that in Tassin the patients are on very low sodium diet (<5 g/day) and in Tassin extracellular volume (ECV) is reduced as far as possible independent of residual renal function. The concept of our center was to preserve residual renal function and accept slightly higher ECV and few antihypertensive drugs. Another concept to intensify HD is short daily HD (6 times/week for 90-180 min). This form of dialysis is offered as in-center and home HD with and without dialysis partner. All studies demonstrated significant improvement of nutritional status, quality of life, control of blood pressure, phosphate and anemia. Survival of AV fistula even with daily double punctures was excellent. The most extensive form of dialysis is slow daily nocturnal dialysis (6 times/week for 8-10 h). This form of dialysis provides excellent urea, phosphate clearance and fourfold increase of beta(2)-microglobulin clearance. Patients discontinue phosphate binders and several patients need phosphate addition to dialysis. Blood pressure control is excellent, all patients are off antihypertensive drugs. Improvement of nutrition, anemia, blood pressure and quality of life is even more pronounced compared to short daily HD or 3 times weekly 8-hour HD. Nocturnal dialysis was able to improve sleep apnea. Nocturnal dialysis is offered only as home HD with and without dialysis partner. Any patient who could be trained for home HD was eligible. Presence of co-morbidities was not a contraindication.


Porothramycin, a new antibiotic of the anthramycin group: production, isolation, structure and biological activity.
A new antitumor antibiotic porothramycin was produced by a new strain of Streptomyces albus. The antibiotic was isolated in two active forms, the natural free hydroxyl form (porothramycin A) or the crystalline methyl ether form (porothramycin B) depending upon the isolation process used. Structural studies established that porothramycin is a new member of the pyrrolo[1,4]benzodiazepine group antibiotics having only one substituent on the benzene ring. The antibiotic exhibited antimicrobial activity against Gram-positive bacteria and anaerobes and significantly prolonged the survival times of mice implanted with experimental tumors.


Brain infarction correlates more closely with acrolein than with reactive oxygen species.
Although it is thought that the major factor responsible for cell damage is reactive oxygen species (ROS), our recent studies have shown that acrolein is more toxic than ROS. Thus, the relative importance of acrolein and ROS in cell damage during brain infarction was compared using photochemically induced thrombosis model mice. The levels of acrolein-conjugated albumin, and of 4-hydroxynonenal (HNE)-conjugated albumin and 8-OHdG were evaluated as indicators of damage produced by acrolein and ROS, respectively. The increase in acrolein-conjugated albumin was much greater than the increase in HNE-conjugated albumin or 8-OHdG, suggesting that acrolein is more strongly involved in cell damage than ROS during brain infarction. It was also shown that infarction led more readily to RNA damage than to DNA or phospholipid damage. As a consequence, polyamines were released from RNA, and acrolein was produced from polyamines, especially from spermine by spermine oxidase. Production of acrolein from spermine by spermine oxidase was clarified using spermine synthase-deficient Gy mice and transglutaminase 2-knockout mice, in which spermine content is negligible or spermidine/spermine N(1)-acetyltransferase activity is elevated.


Radiation dose and risk from fluoroscopically guided percutaneous transluminal angioplasty and stenting in the abdominal region.
The objective of this study was to estimate the radiation dose and associated risks resulting from fluoroscopically guided percutaneous transluminal angioplasty with or without stent placement in the abdominal region. Average examination parameters for renal and aortoiliac procedures were derived using data from 80 consecutive procedures performed in our institute. Organ and effective doses were estimated for endovascular procedures with the use of a Monte Carlo (MC) transport code and an adult mathematical phantom. Thermoluminescent dosimeters were used in an anthropomorphic phantom to verify MC calculations. Radiation-induced risks were estimated. Results are presented as doses normalized to dose area product, so that the patient dose from any technique and X-ray unit can be easily calculated for iliac and renal PTA/stenting sessions. The average effective dose varied from 75 to 371 microSv per Gycm(2) depending on the beam quality, procedure scheme and sex of the patient. Differences up to 17% were observed between MC-calculated data and data derived from thermoluminescent dosimetry. The radiation-induced cancer risk may be considerable for younger individuals undergoing transluminal angioplasty with stent placement.


Nest predation and the species diversity of birds.
In a recent series of papers, Thomas E. Martin has suggested that selective, density-dependent predation on nests may promote ecological diversification of birds and constrain the number of coexisting species in a community. In an experimental study, Martin has demonstrated density-dependent predation on artificial nests constructed and placed so as to mimic natural ones. Comparisons between habitats indicate that availability of suitable nest sites may influence community diversity more strongly than does diversity of foraging niches. Although his case is circumstantial at this point, Martin argues compellingly for considering predation more seriously in studies of community ecology. Indeed, many patterns attributed to competition for food resources may arise, instead, from the partitioning of predator-escape space.


Bilateral chylothoraces without chyle leakage after left-sided neck dissection for thyroid cancer: report of two cases.
Bilateral chylothorax is a rare complication of neck dissection, but it is potentially serious and sometimes life threatening. Because of the rarity of chylothorax, surgeons are unfamiliar with its early signs, which allow a prompt diagnosis and effective management. Most cases reported in the literature were associated with a concurrent external chyle leakage, which occurred either during or after surgery. We report two cases of bilateral chylothoraces without concurrent external chyle leakage, which occurred after left-sided neck dissections for thyroid cancer. We treated both patients successfully with conservative management.


Efficiency of solar PV panel by the application of coconut fibres saturated by earthen clay pot water.
Performance of the solar cell is hindered at higher operating temperature. Although higher irradiation increases the yield annually, the higher temperature would do a disservice. As temperature increases, the solar cell undergoes a thermal stress owing a way to carrier recombination. It becomes imperative to ease of the thermal stress, thereby running the PV system effectively and achieving the higher yield. An alternative cooling method is applied by cooling both the sides of the PV panel simultaneously. It includes cooling of the panel top surface by allowing a thin film of water to flow. The rear surface is packed with a biomaterial, which is saturated with the constant supply of water. This makes up a cooling unit. Here, the experimental study is carried out on comparison between a conventional PV panel and PVT panel packed with coir pith at the rear surface. The latter is cooled at two different modes, one among the panel by normal water and the other by earthen pot water. The results show that cooling the coir pith using earthen pot water has increased the overall efficiency up to 64%. It is higher than the other two panels, as the temperature of the pot water is 5°-8°C lower than the ambient air.


Epilepsy in the Renaissance: a survey of remedies from 16th and 17th century German herbals.
Before modern anticonvulsive drugs were developed people in central Europe used herbal remedies to treat epilepsy. Hundreds of different plants for this indication can be found in German herbals of the 16th and 17th centuries. Here we compile these plants and discuss their use from a pharmacological perspective. Nine of the most important European herbals of the 16th and 17th century including Bock (1577), Fuchs (1543), Mattioli (1590), Lonicerus (1660, 1770), Brunfels (1532), Zwinger (1696), and Tabernaemontanus (1591, 1678) were searched for terms related to epilepsy, and plants and recipes described for its treatment were documented. We then searched scientific literature for pharmacological evidence of their effectiveness. Additionally the overlapping of these remedies with those in De Materia Medica by the Greek physician Dioscorides was studied. Two hundred twenty one plants were identified in the herbals to be used in the context of epilepsy. In vitro and/or in vivo pharmacological data somehow related to the indication epilepsy was found for less than 5% of these plants. Less than 7% of epilepsy remedies are in common with De Materia Medica. Numerous plants were used to treat epilepsy in the 16th and 17th centuries. However, few of these plants have been investigated with respect to pharmacological activity on epilepsy related targets.


Variability levels, population size and structure of American and European Drosophila montana populations.
The level and patterns of nucleotide diversity have been characterized for two X-linked loci, fused (fu; a region of 2362 bp) and suppressor of sable (su(s); a region of 413 bp), in one European and one American D. montana population. Sequence variation at these loci shows that the two populations are divergent, although they may not be completely isolated. Data on the level of silent site variability at su(s) (1.1% and 0.5% for the European and American populations, respectively) suggest that the effective population sizes of the two populations may be similar. At the fused locus, one European sequence was highly divergent and may have resulted from gene conversion, and was excluded from the analysis. With this sequence removed, the level of silent site variability was significantly lower in the European population (0.28%) than in the American population (2.3%), which suggests a selective sweep at or near fu in the former population.


Visual evoked potentials in two forms of hereditary spastic paraplegia.
Visual evoked potentials (VEPs) were used to study two forms of hereditary spastic paraplegia. We recorded the VEP in 6 homozygotes and 5 obligate heterozygotes in one family with recessively transmitted disease and in 5 persons with dominantly transmitted hereditary spastic paraplegia. The VEPs in the affected persons from both families were similar; both had delayed conduction times and changes in the wave form. The VEPs of the obligate heterozygotes were indistinguishable from those of the unaffected control subjects. Comparison of our findings with those of other disease processes that affect the VEPs suggest that the conduction delays in our patients' VEPs may be associated with changes in myelin.


Oral treatment of erectile dysfunction with apomorphine SL.
Apomorphine SL (Ixense, Uprima) is a new oral medication shown to be effective in the treatment of erectile dysfunction. This compound is a dopaminergic agonist with affinity for dopamine receptor sites - mostly D(2) - within the brain known to be involved in sexual function. Apomorphine induces selective activation in the nucleus paraventricularis leading to erectogenic signals. More than 5,000 men with erectile dysfunction participated in phase II/III clinical trials assessing the safety and efficacy of doses ranging from 2 to 6 mg. The most favorable risk/benefit ratio is seen with a dose-optimization regimen of 2-3 mg: the 3-mg dose provides efficacy comparable to that of 4 mg but with fewer side effects. Consequently, review of clinical studies focuses on data with the 2- to 3-mg dose, the registered dose for use in clinical practice. The primary efficacy endpoint in most clinical trials with apomorphine SL was the percentage of attempts resulting in erections firm enough for intercourse - one of the most rigorous endpoints used in ED trials to date. These data were collected from both patients and their partners by reviewing entries in patient diaries and partner BSFI questionnaires. Secondary endpoints included percentage of attempts resulting in intercourse and improvement in ED severity based on the International Index of Erectile Function (IIEF). The proportion of attempts resulting in erections firm enough for intercourse was 49.4% with 3 mg compared with the baseline value of 24.3%. Partner evaluations corresponded with those of the patients. Erections occurred between 18 and 19 min after taking apomorphine SL 2 or 3 mg. The most common side effect was nausea which declined with continued use. Vasovagal syncope was reported in <0.2% of men, and was preceded by clear prodromal symptoms. Thus, apomorphine SL is an effective, well-tolerated drug for erectile dysfunction.


Comparison of conventional CTA and volume perfusion CTA in evaluation of cerebral arterial vasculature in acute stroke.
CTA-like datasets can be reconstructed from whole-brain VPCTA. The aim of our study was to compare VPCTA with CTA for detection of intracranial stenosis and occlusion in stroke patients. Omitting CTA from stroke CT could reduce radiation dose. One hundred sixty-three patients were included in this retrospective analysis. Inclusion criterion was suspected stroke within 4.5 hours after onset of symptoms. All examinations were performed on a 128-section multidetector CT scanner. Axial, coronal, and sagittal maximum intensity projections were reconstructed from CTA and from peak arterial phase of VPCTA. Images were scored for quality and presence of intracranial stenosis >50% or occlusion. For statistical analysis, the Wilcoxon signed-rank test and Fisher exact test were used, with a 2-tailed P value of .05 or less for statistical significance. Average image quality was superior in CTA (P < .05). However, image quality dichotomized for diagnostic significance was without difference between CTA and VPCTA (P > .05). Comparative statistical analysis revealed no significant difference for detection of intracranial stenosis and occlusion between CTA and VPCTA (P > .05). Substitution of intracranial CTA by VPCTA would lower radiation dose by 0.5 mSv. VPCTA is suited to assess the intracranial vasculature in patients with stroke and might have the potential to decrease radiation dose by substituting for intracranial CTA in stroke CT. Additional studies are necessary to further evaluate potential benefits of the dynamic nature of VPCTA.


[Neonatal pseudohypoaldosteronism: when a denied truth can delay a diagnosis].
A child with neonatal pseudohypoaldosteronism is referred. The diagnosis was delayed and complicated as her parents didn't tell us that her sister had been affected by the same illness. The child was born after premature rupture of membranes at 34 weeks. At birth, her conditions were satisfactory. The general conditions of the child gradually worsened and, though she regularly ate human pastorized bank milk, she didn't gain any weight. After 13 days she appeared dehydrated with marbled dry skin and haloed eyes, hypotonic and hyporeflexic. Her suction became more and more weaker, with frequent regurgitations and vomiting. Laboratory tests pointed out hyponatremia (110 mEq/l) and hyperkalemia (6.8 mEq/l). We were able to establish diagnosis of primary pseudohypoaldosteronism measuring plasma concentrations of aldosterone (> 5000 pg/ml), 17 hydroxyprogesterone (normal) and corticosteroids (normal). The child was then supplemented with sodium chlorure. A gradual improvement of general conditions took place. We assumed that both childrens and mother were affected by a milder form of primary pseudohypoaldosteronism, characterized by an autosomal dominant way of transmission. We found high levels of aldosterone with normal levels of blood salts also in the sister and mother patient's. After the neonatal period, pseudohypoaldosteronism can be only suspected in case of positive family history.


Anal canal pressure in anal fissure before and after internal sphincterotomy.
To assess whether the anal canal pressure is increased in patients with a chronic anal fissure and to examine the effects of internal anal sphincterotomy (IASy) on this pressure. Anorectal manometry was performed in 28 patients in whom an anal fissure had been diagnosed by means of physical examination and anuscopy. After IASy the manometric measurement was repeated on the 15th postoperative day and compared with the value obtained in twelve healthy volunteers. In patients with chronic anal fissure, the mean maximal resting pressure (MRP) was found to be 112.38 +/- 8.35 cm H2O pre-operatively and 66.23 +/- 8.44 cm H2O postoperatively, with a significant drop after IASy (p < 0.001). The MRP value was found as 75.16 +/- 10.22 cm H2O in the control group. The pre-operative MRP values in patient group was found to be higher than in the control group (p < 0.001). In patients with chronic anal fissure, the anal canal MRP pressures decreased significantly following IASy and complete clinical recovery was attained.


Lack of endothelium-derived hyperpolarizing factor (EDHF) up-regulation in endothelial dysfunction in aorta in diabetic rats.
It is not known whether the impairment of nitric oxide (NO)-dependent vasodilation of the aorta of diabetic rats is associated with any changes in the endothelial production of vasoactive prostanoids and endothelium-derived hyperpolarizing factor (EDHF). Therefore, we analyzed the contribution of NO, vasoactive prostanoids and EDHF to the decreased endothelium-dependent vasorelaxation in Sprague-Dawley rats at 4 and 8 weeks after diabetes mellitus induced by streptozotocin (STZ). The acetylcholine-induced (Ach) endothelium-dependent relaxation was significantly decreased in the thoracic aorta 8 weeks after the STZ-injection (Ach 10(-6) M: 73.1 +/- 7.4% and 56.7 +/- 7.9% for control and diabetic rats, respectively). The sodium nitroprusside-induced (NaNP) endothelium-independent vasodilation was also impaired in the diabetic rats (8 weeks after STZ) (NaNP 10(-8) M: 74.2 +/- 11.4% and 35.9 +/- 9.4% for control and diabetic rats, respectively). In contrast, the basal NO production, as assessed by the N omega-nitro-L-arginine methyl ester (L-NAME)-induced vasoconstriction was not modified in diabetes. Moreover, the amount of 6-keto-PGF(1 alpha) (stable metabolite of prostacyclin / prostaglandin I2 / PGI2 ), 12-L-hydroxy-5,8,10-heptadecatrienoic acid (12-HHT) and thromboxane B2 (TxB2 ) (stable metabolite of thromboxane A2 - TxA2) were significantly increased in the 8 weeks diabetic rat aorta. The EDHF-pathway did not change in the aortic endothelium during the development of STZ-induced diabetes. Our results indicate that STZ-induced diabetes mellitus did not modify the basal NO production, but induced the impairment of acetylcholine- and sodium nitroprusside-induced vasodilation in the thoracic aorta. In parallel with the impairment of NO-dependent vasodilation, the basal PGI2, 12-HHT and TxA2 synthesis were increased. The EDHF-pathway did not contribute to the endothelium-dependent relaxation either in control or diabetic aorta. The above alterations in the endothelial function may play an important role in the development of endothelial dysfunction and vascular complications of diabetes.


Coronary microvascular dysfunction in chronic inflammatory rheumatoid diseases.
Chronic inflammatory rheumatoid diseases (CIRD) such as rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis are an important risk factor for the development of ischaemic heart disease and a source of high cardiovascular morbidity and mortality. In patients affected by CIRD, inflammation can affect coronary microvascular function and contribute to the development of myocardial ischemia and cardiovascular events, even in the absence of obstructive epicardial coronary artery disease. Understanding the molecular aspects that underlie the development of coronary microvascular dysfunction (CMD) in CIRD is of fundamental importance to identify specific therapeutic targets. In this article, we review the pathogenic mechanisms leading to CMD in CIRD, including the controversial results obtained with the use of different therapeutic strategies. We also propose that a practical diagnostic algorithm as the identification of CMD in patients with CIRD may lead to effective measures to prevent the development of angina pectoris and reduce the risk of rapid disease progression.


Effect of gamma irradiation on the efficacy of beta-glucan against acetaminophen induced toxicity in mice.
The present study was conducted to compare the efficacy of unirradiated beta-glucan (UBG) and gamma irradiated beta-glucan (GIBG) against acetaminophen (APAP) induced hepatotoxicity in mice. Mice of BALB/c strain were pretreated with UBG and GIBG (50mg/kg, p.o.) for 7 days and on the 8th day they received an overdose of APAP (500 mg/kg, i.p.). Eight hours after the APAP injection, the levels of serum aminotransferase (AST) and alanine aminotransferase (ALT) were measured and liver, kidney and lung tissue were examined for morphological changes. A significant elevation (p<0.001) of the levels of AST and ALT was observed in mice toxicated with APAP. Histology data revealed severe liver centrilobular necrosis, portal vein damage with apparent toxicity in renal glomerulus and lung inflammation associated with edema. However, a significant inhibition (p<0.05) in the elevation of AST and ALT was observed in mice that received UBG and GIBG compared with APAP-treated mice. Histology examination revealed the non-statistical difference between the protective effects of GIBG and UBG against acetaminophen challenge. In conclusion, it was demonstrated that gamma irradiation induced no severe alteration in the protective activity of beta-glucan against APAP-induced hepatotoxicity.


In-hospital mortality in non-variceal upper gastrointestinal bleeding Forrest 1 patients.
Non-variceal upper gastrointestinal bleeding (NVUGIB) is recognized world-wide as a common cause of emergency hospitalization, and it often represents a life-threatening event. The purpose of this prospective study was to assess in-hospital mortality in NVUGIB Forrest 1 patients admitted to the emergency unit owing to active bleeding. We enrolled all patients consecutively admitted to the emergency unit for NVUGIB, acutely bleeding at endoscopy (spurting or oozing). Demographic characteristics, clinical and biochemical parameters, endoscopic findings and treatments were evaluated. Of a total of 142 patients (98 M (69%), mean age+/-SD=66+/-14 years), spurting (16 (11.3%)) and oozing (126 (88.7%)) were identified. All patients received endoscopic treatment within 6 h of admission and were managed according to the guidelines. Seventeen (12%) patients suffered rebleeding, 4 patients (2.8%) required surgery to stop the bleeding, and 8 (5.6%) died during hospitalization (4 within 5 days and the remainder within 24 days of admission) - 3 as a consequence of bleeding (2.1%) and 5 of non-surgical complications (3.5%). Cox regression analysis showed that the lesions in more than one segment of the esophagogastroduodenal tract (p=0.008, hazard ratio (95% CI)=7.623 (1.680-34.600)) and the number of blood units transfused during the first 48 h of hospitalization (p=0.038, 2.075 (1.041-4.135)) were predictive of in-hospital death. In Forrest 1 patients given rapid endoscopic treatment, in-hospital mortality seems to be related to the contemporaneous presence of bleeding and non-bleeding lesions in more than one segment of the esophagogastroduodenal tract and the number of blood units transfused during the first 48 h of hospitalization.


Prediction of Dissolution Data Integrated in Tablet Database Using Four-Layered Artificial Neural Networks.
A large number of dissolution data were measured and integrated into a previously constructed tablet database composed of 14 kinds of compounds as model active pharmaceutical ingredients (APIs) with contents ranging from 10 to 80%. The database has contained physicochemical and powder properties of APIs, together with basic physical attributes of tablets such as the tensile strength and the disintegration time. In order to enhance the value of this database, drug dissolution data are essential to improving key information for designing tablet formulations. A four-layered artificial neural network (4LNN), newly implemented in commercially available software, was employed to predict dissolution data from physicochemical and powder properties of APIs. Our results showed that an excellent model for the prediction of dissolution data was achieved with 4LNN method. The function of 4LNN was appreciably better than that of conventional three-layered model, despite both models adopting the same number of nodes and algorithms for activation functions. Furthermore, linear regression models resulted in poor prediction of dissolution data.


Elevated levels of FVIII:C within families are associated with an increased risk for venous and arterial thrombosis.
Elevated levels of coagulation factor VIII:C (FVIII:C) are associated with an increased risk for venous and arterial thromboembolism. Whether relatives of patients with elevated levels of FVIII:C are also at increased risk for thrombotic disease is unknown. The objective was to determine the annual incidences of both venous and arterial thrombotic events in first-degree relatives of patients with elevated levels of FVIII:C and venous thromboembolism (VTE) or premature atherosclerosis. A retrospective study with 584 first-degree relatives of 177 patients with elevated levels of FVIII:C was performed. The level of FVIII:C was determined and relatives with elevated and normal levels of FVIII:C were compared. Of the participants, 40% had elevated levels of FVIII:C. The annual incidence of a first episode of VTE was 0.34% and 0.13% in relatives with elevated levels of FVIII:C and those with normal levels, respectively [OR 3.7 (95% CI 1.9-7.5)]. The absolute annual incidence in the youngest age group with elevated levels of FVIII:C was 0.16% (0.05-0.37) and gradually increased to 0.99% (0.40-2.04) in those older than 60 years of age, although the odds ratios were not statistically significant. The annual incidences of a first arterial thrombotic event were 0.29% and 0.14% in relatives with and without elevated levels of FVIII:C, respectively [OR 3.1 (1.4-6.6)]. In particular the risks for a first myocardial infarction [OR 4.3 (1.0-18.1); P =0.046] and a first peripheral arterial thrombosis [OR 8.6 (1.6-47.6)] were increased. Within families of patients with elevated levels of FVIII:C and VTE or premature atherosclerosis, 40% of their first-degree relatives has elevated levels of FVIII:C as well, and they are at increased risk for both VTE and arterial thrombosis as compared with their relatives with normal levels.


Superior survival in treatment of primary nonmetastatic pediatric osteosarcoma of the extremity.
A protocol to treat osteosarcoma of the extremity was developed at two local institutions. The study involved a dose-intensified neoadjuvant protocol of intravenous doxorubicin and intra-arterial cisplatin administered repetitively until maximum angiographic response was noted. Definitive surgery was delayed until > or =90% reduction in tumor neovascularity was documented. Prospective assessment of serial arteriograms was highly accurate (94%) in predicting histological response and assisted in surgical planning. After resection, if patients were determined to be good responders (> or =90% tumor necrosis), they underwent a 4-month postoperative course with the same agents. Poor responders (<90% necrosis) were treated with alternative agents for 12 months from diagnosis. Forty-seven assessable patients with primary, high-grade, nonmetastatic osteosarcoma of the extremity were included in this analysis. The median age was 15 years (range, 7-21 years). Patients underwent an average of four preoperative intra-arterial courses. Forty-three patients underwent limb-preservation procedures, and 41 had >90% tumor necrosis. With an average follow-up of 92 months (range, 20-178 months), 39 patients were continuously disease free, 3 died of disease, 1 died of other causes, and 4 have no evidence of disease 11 to 51 months after relapse (all pulmonary metastases). There were no local recurrences. Kaplan-Meier analysis demonstrated a 10-year overall survival of 92% and an event-free survival of 84%. This study demonstrates excellent survival with a dose-intensified neoadjuvant protocol. Future endeavors should involve a multi-institutional randomized study comparing this approach with another multiagent intravenous neoadjuvant protocol.


Single cell study of adipose tissue mediated lipid droplet formation and biochemical alterations in breast cancer cells.
Obesity is a known risk factor for breast cancer and a negative prognostic factor for cancer recurrence and survival. Several studies demonstrated that aggressive breast tumor cells contain higher numbers of intracellular lipid droplets (LDs). Here we applied simultaneous visualization, identification and quantification of the lipid accumulation in lipid droplets (LDs) of aggressive, human triple-negative MDA-MB-231 breast cancer cells treated with adipose tissue-conditioned medium (ACM) derived from overweight and obese patients. In addition to Oil Red O and AdipoRed fluorescent staining, label-free confocal Raman microspectroscopy (CRM) has been applied. CRM enables imaging of cell compartments as well as quantification and monitoring of specific biomolecules and metabolic processes on a single cell level. Interestingly, breast cancer cells incubated with ACM showed a significantly higher number of intracellular LDs. Cultivation of breast tumor cells with ACM of obese patients induced the formation of LDs with a 20-fold higher lipid concentration than cultivation with basal medium. This is in line with the significantly higher levels of NEFAs (non-esterified fatty acids) detected in the ACM obtained from obese patient compared to ACM obtained from overweight patients or basal medium. Further, by principal component analysis, we identified a significant increase in unsaturation, esterification and lipid to protein ratio in LDs in breast cancer cells incubated with ACM. CRM analyses might function as a valuable diagnostic tool to identify metabolic alterations in biological samples which in turn could provide more detailed insights in the pathogenesis of breast cancer in association with obesity.


"Early" carcinoma of the breast: evaluation of regional therapy and features influencing prognosis.
Between 1944 and 1969, 192 women with carcinoma of the breast were treated at The University of Texas System Cancer Center M. D. Anderson Hospital and Tumor Institute by standard radical mastectomy for small outer quadrant lesions and pathologically negative axillary lymph nodes. Twenty percent of these patients with "localized disease" eventually had disseminated breast cancer. Various patient, hormonal, genetic, and pathologic factors were found to have little influence on the prognosis. Patterns of metastatic disease revealed that these patients did not have a unique form of breast cancer, but apparently an earlier stage in the spectrum of advancing disease. The results of this study appear to represent the best that can be obtained with regional therapy for carcinoma of the breast and emphasize the need for reliable adjuvant therapy.


Modeling the magnetic disturbance of pulsatile blood flow in a static magnetic field.
Non-invasive continuous monitoring of blood flow may be particularly valuable for early detection of different anomalies such as hypovolemia and internal bleeding. Recent studies have demonstrated the potential clinical benefits of photo-plethysmography in detecting hypovolemia before the onset of cardiovascular decompensation. The magnetic sensing method bears advantages of size, weight, and cost along with less stringent body placement rules. In this work, a detailed three-dimensional mathematical model for the acquisition of the ventricular response using the disturbance created by magnetized blood undergoing a stationary permanent magnet is presented. The proposed model accounts for the different magnetic properties of the blood such as the relaxation time and the magnetic saturation. The blood flow is simulated by means of Navier-Stocks equations with pulsatile inlet pressure. The blood is assumed to be in the deoxygenated state and has a diamagnetic properties. Moreover, a moving mesh technique is implemented in the Finite-Element model to represent the idle and the moving states of the blood which provides the capability to model the magnetized blood as a moving magnet. The simulated magnetic field at different sensor locations is found to be in good agreement with experimental observations from the literature. The presented model can provide basis for understanding the magnetic modulated blood signal as well as the practical constraints that might be encountered in the design of such devices.


Molecular basis of downregulation of G-protein-coupled inward rectifying K(+) current (I(K,ACh) in chronic human atrial fibrillation: decrease in GIRK4 mRNA correlates with reduced I(K,ACh) and muscarinic receptor-mediated shortening of action potentials.
Clinical and experimental evidence suggest that the parasympathetic nervous system is involved in the pathogenesis of atrial fibrillation (AF). However, it is unclear whether changes in G-protein-coupled inward rectifying K(+) current (I(K,ACh)) contribute to chronic AF. In the present study, we used electrophysiological recordings and competitive reverse-transcription polymerase chain reaction to study changes in I(K,ACh) and the level of the I(K,ACh) GIRK4 subunit in isolated human atrial myocytes and the atrial tissue of 39 patients with sinus rhythm and 24 patients with chronic AF. The density of I(K,ACh) was approximately 50% smaller in myocytes from patients with AF compared with those in sinus rhythm, and this was accompanied by decreased levels of GIRK4 mRNA. The current density of the inward rectifying K(+) current (I(K1)) was 2-fold larger during AF than in sinus rhythm, in correspondence with an increase in Kir2.1 mRNA. The larger I(K1) in AF is consistent with more negative membrane potentials in right atrial trabeculae from AF patients. Moreover, action potential duration was reduced in AF, and the action potential shortening produced by muscarinic receptor stimulation was attenuated, indicating that the changes of I(K1) and I(K,ACh) were functionally relevant. Chronic human AF induces transcriptionally mediated upregulation of I(K1) but downregulation of I(K,ACh) and attenuates the muscarinic receptor-mediated shortening of atrial action potentials. This suggests that atrial myocytes adapt to a chronically high rate by downregulating I(K,ACh) to counteract the shortening of the atrial effective refractory period due to electrical remodeling.


Rare types of rotaviruses isolated from children with acute gastroenteritis in Patras, Greece.
Acute diarrhea remains a major public health issue worldwide, with gastroenteritis agents associated with a high morbidity, especially in infants and young children. A 1-year study (2009-2010) of rotavirus (RV)-caused pediatric diarrhea was performed on hospitalized children admitted with symptoms of acute diarrhea to the University Hospital of Patras, Greece. Twenty-nine fecal samples were investigated for RVs, adenoviruses (AdVs), and enteroviruses (EVs) in an attempt to characterize these enteric viruses, which have been implicated in hospitalized diarrhea. A 44.8% (13/29) incidence of viral infection was reported for the viral targets. Monoinfections accounted for 31% (9/29), while bi-infections accounted for 13.4% (4/29). Sequencing of positive samples allowed identification of RVs G4P[8] (2/29), G9P[8] (1/29), and interestingly of the rare type G12P[8] (2/29). AdV types 1, 2, and 6 were also identified in 4/29, 1/29, and 1/29 of the samples, respectively. Regarding the EVs, EV71 (2/29), coxsackievirus A4 (1/29), echovirus 11 (1/29), and EV96 (1/29) were typed. The results of the present study, and specifically the detection of rare RV G12 and EV71 strains, address the need for continuous epidemiological surveys to provide epidemiological pictures of pediatric viral infections circulating in the community.


A pharmacoeconomic analysis of atypical antipsychotics and haloperidol in first-episode schizophrenic patients in taiwan.
The study prospectively examined the economic outcomes and co-medications among first-episode schizophrenic patients treated with monotherapy of second-generation antipsychotic agents (SGAs) continuously as compared with each other and with haloperidol. The sample included 3047 out of Taiwan's national sample of 29,341 first-episode schizophrenic patients, who were selected, based on International Classification of Disease, Ninth Revision code 295, from the National Health Insurance original claims data from 1999 to 2004. They were treated with only 1 of the following antipsychotic agents: haloperidol (n = 526), clozapine (n = 224), risperidone (n = 827), olanzapine (n = 824), zotepine (n = 286), or quetiapine (n = 360), without changing antipsychotics during the observation for at least 1 year (mean, 1.80 years; SD, 0.93 years) for each subject. Economic outcomes included clinic visits, prescription days, frequencies and duration of hospitalizations, and total and separate treatment costs (outpatient department- and hospital-related costs). Co-medications included use of anticholinergic, anxiolytic, hypnotic/sedative, and antidepressant agents. Patients treated with SGAs had lower number and shorter durations of hospitalizations than did haloperidol-treated patients, except for the clozapine group. Olanzapine was associated with the lowest hospitalization rates per year (mean, 1.63 vs 2.83). In terms of cost, haloperidol was more expensive in total hospitalization expenses (mean, US $3215 per year) and total treatment cost (mean, $3769 per year) than olanzapine, zotepine, or quetiapine. In general, there was no difference among the haloperidol and SGA groups in terms of rates of co-medications. The reduced number of hospitalizations and then lower total hospitalization costs seem to be more than the offset of high medication acquisition costs of SGAs.


Inhibitory mechanisms of flavonoids on insulin-stimulated glucose uptake in MC3T3-G2/PA6 adipose cells.
We assessed the effects of different classes of flavonoids on insulin-stimulated 2-deoxy-D-[1-(3)H]glucose uptake by mouse MC3T3-G2/PA6 cells differentiated into mature adipose cells. Among the flavonoids examined, the flavones, apigenin and luteolin, the flavonols, kaempferol, quercetin and fisetin, an isoflavone, genistein, a flavanonol, silybin, and the flavanols, (-)-epigallocatechin gallate (EGCG) and theaflavins, significantly inhibited insulin-stimulated glucose uptake. Key structural features of flavonoids for inhibition of insulin-stimulated glucose uptake are the B-ring 4'- or 3',4'-OH group and the C-ring C2-C3 double bond of the flavones and flavonols, the A-ring 5-OH of isoflavones, and the galloyl group of EGCG and theaflavins. Luteolin significantly inhibits insulin-stimulated phosphorylation of insulin receptor-beta subunit (IR-beta), and apigenin, kaempferol, quercetin and fisetin, also tended to inhibit the IR-beta phosphorylation. On the other hand, isoflavones, flavanols or flavanonols did not affect insulin-stimulated IR-beta phosphorylation. Apigenin, luteolin, kaempferol, quercetin and fisetin also appeared to inhibit insulin-stimulated activation of Akt, a pivotal downstream effector of phosphatidylinositol 3-kinase (PI3K), and suppressed insulin-dependent translocation of a glucose transporter, (GLUT)4, into the plasma membrane. Although genistein, silybin, EGCG and theaflavins had no effect on the insulin-stimulated activation of Akt, they blocked insulin-dependent GLUT4 translocation. These results provide novel insights into the modulation by flavonoids of insulin's actions, including glucose uptake in adipocytes.


Pharmacokinetics of dalbavancin in plasma and skin blister fluid.
Dalbavancin is a novel lipoglycopeptide antibiotic in development for the treatment of complicated skin and skin structure infections (cSSSIs) caused by Gram-positive bacteria. The aim of the present study was to assess the penetration of dalbavancin into skin blister fluid. Nine healthy subjects (five males; ranging in age from 26 to 57 years) were administered a single 30 min intravenous infusion of dalbavancin at a dose of 1000 mg. Skin blisters were induced by application of cantharidin ointment. Plasma and blister fluid samples were collected over 7 days post-dose, and concentrations of dalbavancin were assessed by a validated LC/MS/MS assay. Pharmacokinetics were determined by non-compartmental methods, and drug penetration was assessed based on the ratio of area under the curve (AUC) in the blister fluid versus plasma for each subject. The mean (SD) peak concentration of dalbavancin in plasma and blister fluid was 285 (31.1) and 67.3 (18.2) mg/L, respectively; the corresponding AUC(Day 7) values were 10 806 (1926) and 6438 (1238) mg . h/L, respectively. The mean (SD) penetration of dalbavancin into blister fluid was 59.6% (6.3%). By Day 7, the mean concentration of dalbavancin in plasma and blister fluid was 46.5 and 30.3 mg/L, respectively. Dalbavancin concentrations in blister fluid remained well above the MIC90 values for pathogens commonly implicated in cSSSIs such as Staphylococcus aureus, including methicillin-resistant S. aureus (MIC90 = 0.06 mg/L) and beta-haemolytic streptococci (MIC90 = 0.03 mg/L) through Day 7. These pharmacokinetic data support the use of dalbavancin in the treatment of cSSSIs caused by susceptible Gram-positive pathogens.


Leptin receptor activation increases Sam68 tyrosine phosphorylation and expression in human trophoblastic cells.
Leptin is produced in placenta where it has been found to be an important autocrine signal for trophoblastic growth during pregnancy, promoting antiapoptotic and trophic effects. Leptin receptor is present in trophoblastic cells and leptin may fully activate signaling. We have previously implicated the RNA-binding protein Sam68 in leptin signal transduction in immune cells. In the present work, we have studied the possible role of Sam68 in leptin receptor signaling in trophoblastic cells (JEG-3 cells). Leptin dose-dependently stimulated Sam68 phosphorylation in JEG-3 cells, as assessed by immunoprecipitation and immunoblot with anti-phosphotyrosine antibodies. As previously observed in other systems, tyrosine phosphorylation of Sam68 in response to leptin inhibits its RNA binding capacity. Besides, leptin stimulation dose-dependently increases Sam68 expression in JEG-3 cells, as assessed by quantitative PCR. Consistently, the amount of Sam68 protein is increased after 24h of leptin stimulation of trophoblastic cells. In order to study the possible role of Sam68 on leptin receptor synthesis, we employed antisense strategy to knockdown the expression of Sam68. We have found that a decrease in Sam68 expression leads to a decrease in leptin receptor amount in JEG-3 cells, as assessed both by quantitative PCR and immunoblot. These results strongly suggest the participation of Sam68 in leptin receptor signaling in human trophoblastic cells, and therefore, Sam68 may mediate some of the leptin effects in placenta.


Amino acid sequence of bacterial microbe-associated molecular pattern flg22 is required for virulence.
Flagellin proteins derived from Pseudomonas syringae pv. tabaci 6605 and flg22Pa (QRLSTGSRINSAKDDAAGLQIA), one of the microbe-associated molecular patterns (MAMP) in bacterial flagellin, induce cell death and growth inhibition in Arabidopsis thaliana. To examine the importance of aspartic acid (D) at position 43 from the N-terminus of a flagellin in its elicitor activity, D43 was replaced with valine (V) and alanine (A) in P. syringae pv. tabaci flagellin and flg22Pta. The abilities of flagellins from P. syringae pv. tabaci D43V and D43A to induce cell death and growth inhibition were reduced, whereas the abilities of flg22PtaD43V and flg22PtaD43A were abolished. These results indicate that D43 is important for elicitor activity in P. syringae pv. tabaci. When tobacco plants were inoculated with each bacterium by the spray method, both P. syringae pv. tabaci D43V and D43A mutants had remarkably reduced ability to cause disease symptoms. Both mutants had reduced or no swimming and swarming motilities and adhesion ability. In P. syringae pv. tabaci D43V, little flagellin protein was detected and few flagella were observed by electron microscopy. These results indicate that mutant flagella are unstable and that flagellar motility is impaired. Thus, the amino acid residue required for MAMP activity is important for the intrinsic flagellar function.


Evolutionary origins of the obesity epidemic: natural selection of thrifty genes or genetic drift following predation release?
This article challenges Speakman's hypothesis that the modern genetic predisposition to obesity has arisen through random genetic drift in the two million years following predation release. We present evidence in support of the hypothesis that a mixture of famines and seasonal food shortages in the post-agricultural era have exerted natural selection in favour of fat storage; an effect most likely mediated through fertility, rather than viability, selection. We conclude that, far from being time to call off the search, recently developed genetic and bioinformatic methods will soon provide a definitive resolution to this long-standing 'thrifty gene' controversy.


Bone remodeling and osteophyte formation after remission of rheumatoid arthritis.
Bone remodeling and osteophyte formation rarely take place in active rheumatoid arthritis (RA). To determine if disease inactivation leads to their occurrence, we studied 38 patients with RA whose disease had gone into drug induced remission. We looked for osteophytes at the metacarpophalangeal (MCP) joints in roentgenograms taken before and after remission, and correlated their presence to that of osteoarthritis of the distal interphalangeal (DIP) joints. There were 21 patients with RA who had a median of 3 (range 1-8) osteophytes in their "remission" films which were rarely present in their "activity" films (p less than 0.0001). The osteophytes were frequently symmetrical and most often located (41%) at the third MCP joint. In addition, we observed a peculiar remodeling of the styloid process in 13 patients, 9 of whom had developed MCP joint osteophytes. There were no other detectable differences between patients who had MCP joint osteophytes and those who did not. Presence of osteoarthritis at the DIP joints did not correlate with development of osteophytes. We were able to classify the MCP osteophytes into 3 types on the basis of their shape: hook-like that were most frequently bilateral and situated on the radial aspect of the metacarpal side of the joint, beak-like that were most often found at the ulnar aspect of the phalangeal side, and nipple-like which occurred equally on either sites. These differences in distribution indicate that they are not stages of the same process. Our findings indicate that paraarticular bone remodeling occurs upon remission of RA, even in joints where osteoarthritis is unusual. Its shape and location may depend on both their site and the mechanism of joint damage.


Comparison of the steroidogenic and melanotropic activities of corticotropin, alpha-melanotropin and analogs with their lipolytic activities in rat and rabbit adipocytes.
The ability of alpha-melanotropin and a series of synthetic peptides related to adrenocorticotropin (ACTH) to stimulate steroidogenesis in isolated rat adrenal cells, melanin dispersion in frog melanophores and lipolysis in rat and rabbit fat cells have been studied. It was found that the steroidogenic activity closely paralleled the lipolytic activity of these peptides in rat fat cells, whereas the melanocyte stimulating activity paralleled the lipolytic activity in rabbit fat cells. These results indicate that the structural requirements for stimulating steroidogenesis in isolated rat adrenal cells and lipolysis in isolated rat fat cells are quite similar. The structural features required for eliciting lipolysis in rabbit fat cells appear to be very similar to those necessary for stimulating frog melanophores. The possibility that regulation of lipid metabolism in the rabbit may be a new function acquired by melanotropin is discussed.


Characterization of a novel C-type lectin-like gene, LSECtin: demonstration of carbohydrate binding and expression in sinusoidal endothelial cells of liver and lymph node.
A new C-type lectin-like gene encodes 293 amino acids and maps to chromosome 19p13.3 adjacent to the previously described C-type lectin genes, CD23, dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN), and DC-SIGN-related protein (DC-SIGNR). The four genes form a tight cluster in an insert size of 105 kb and have analogous genomic structures. The new C-type lectin-like molecule, designated liver and lymph node sinusoidal endothelial cell C-type lectin (LSECtin), is a type II integral membrane protein of approximately 40 kDa in size with a single C-type lectin-like domain at the COOH terminus, closest in homology to DC-SIGNR, DC-SIGN, and CD23. LSECtin mRNA was only expressed in liver and lymph node among 15 human tissues tested, intriguingly neither expressed on hematopoietic cell lines nor on monocyte-derived dendritic cells (DCs). Moreover, LSECtin is expressed predominantly by sinusoidal endothelial cells of human liver and lymph node and co-expressed with DC-SIGNR. LSECtin binds to mannose, GlcNAc, and fucose in a Ca(2+)-dependent manner but not to galactose. Our results indicate that LSECtin is a novel member of a family of proteins comprising CD23, DC-SIGN, and DC-SIGNR and might function in vivo as a lectin receptor.


A technique for three-dimensional microleakage assessment using tooth sections.
Microleakage is commonly assessed using restored teeth, sectioned through the midline of the restoration. It is impossible to determine if this is representative of the leakage throughout the whole tooth. This pilot study examined the feasibility of calculating areas and volumes of leakage using serial sections of restored teeth which had been subjected to dye immersion and image analysis. Using the sections, perspex models of the teeth were constructed to present the pattern of the dye leakage into dentine. This appears to be a viable technique for the three-dimensional assessment of microleakage.


Congenital tumours involving the head, neck and central nervous system.
Congenital intracranial tumours are uncommon and differ from those occurring in older children in clinical presentation, imaging characteristics and prognosis. These tumours are often detected incidentally on routine prenatal US and/or fetal MRI. Hence, the paediatric radiologist should be familiar with the features of those lesions that should be included in the differential diagnosis. In general, the prognosis of these conditions is poor owing to large tumour size and the limitations of adjuvant therapy at such a young age. Congenital lesions involving the head and neck region require a meticulous imaging approach using both US and MRI techniques to better guide prenatal planning and fetal or neonatal surgical procedures.


Effect of various polybrominated biphenyls on cell-cell communication in cultured human teratocarcinoma cells.
Firemaster BP-6 (FM), a mixture of polybrominated biphenyls (PBB), and the congeners 2,2',4,4',5,5'-hexabromobiphenyl (245-HBB), 3,3',4,4',5,5'-hexabromobiphenyl (345-HBB), and 3,3',4,4'-tetrabromobiphenyl (34-TBB) were tested for their ability to inhibit cell-cell communication between human teratocarcinoma cells in culture. Both FM and 245-HBB were capable of inhibiting cell-cell communication in these cells, with only slight effects on cell survival. 345-HBB was highly cytotoxic, but did not show the ability to interrupt cell-cell communication. 34-TBB was moderately cytotoxic and was also ineffective at blocking cell-cell communication. The results agree with previously published findings in Chinese hamster V79 cells, and are in accordance with proposed structure-activity relationships for these compounds. Inhibition of cell-cell communication, either directly (FM and 245-HBB) or indirectly through necrosis-induced compensatory hyperplasia (345-HBB), may be involved in the promotion of hepatocellular neoplasms by these compounds.


Bioremediation of soil contaminated with pentachlorophenol by Anthracophyllum discolor and its effect on soil microbial community.
Bioaugmentation is a promising technology to clean up sites contaminated with recalcitrant chemicals. White-rot fungi have proven to be effective in the degradation of pentachlorophenol. Here, we report the bioremediation of soil contaminated with pentachlorophenol (PCP) by Anthracophyllum discolor and its impact on the soil microbial community. In this study three types of microcosms were established: fresh soil (C(0)), fresh soil plus wheat straw (WS(0)) and, fresh soil plus wheat straw inoculated with A. discolor (WSAD(0)). Additionally, similar treatments and a control of sterile soil spiked with PCP (C(250), WS(250) and WSAD(250)) were used to evaluate the remediation and adsorption of PCP. The PCP removal, total microbial activity, and enzymatic activities were evaluated. This study also investigated the structure of soil microbial community by denaturing gradient gel electrophoresis (DGGE), identifying some of the dominant bacterial and fungal species. The results showed that PCP was effectively degraded in soils by A. discolor and by indigenous soil microorganisms. The addition of wheat straw increased the PCP degradation and enzymatic activities. Only laccase activity was negatively affected by PCP contamination. The PCP degradation was associated with changes in microbial communities, mainly stimulation of members of bacterial phylum Proteobacteria (Xanthomonadaceae, Burkholderiaceae and Enterobacteriaceae), and fungal phylum Ascomycota and Basidiomycota. This study shows the ability of A. discolor to degrade PCP from contaminated soil, and demonstrates that agricultural residues, such as wheat straw, can be used as growth substrate by microorganisms in PCP-contaminated soil, demonstrating a great potential of autochthonous microorganisms for soil remediation.


Antegrade left heart catheterization.
Retograde arterial catheterization has been the standard approach to hemodynamic and angiographic evaluation of the left ventricle and systemic arterial system. An alternative approach--antegrade left heart catheterization--is reported that circumvents arterial puncture. During cardiac catheterization from the femoral vein in 18 children with normally related great arteries who had interatrial communications, a balloon-tipped catheter was looped in a "clockwise" fashion through the left atrium and left ventricle and into the ascending aorta. In 17 children the maneuver was rapidly accomplished without complications; it proved possible to perform in an infant with a hypoplastic left ventricular cavity, and was employed to perform a renal arteriogram. The major advantage of antegrade left heart catheterization is avoidance of complications related to arterial puncture. The antegrade approach also avoids right arm cut-down in children with coarctation of the aorta.


A murC gene in Porphyromonas gingivalis 381.
The gene encoding a 51 kDa polypeptide of Porphyromonas gingivalis 381 was isolated by immunoblotting using an antiserum raised against P. gingivalis alkaline phosphatase. DNA sequence analysis of a 2.5 kb DNA fragment containing a gene encoding the 51 kDa protein revealed one complete and two incomplete ORFs. Database searches using the FASTA program revealed significant homology between the P. gingivalis 51 kDa protein and the MurC protein of Escherichia coli, which functions in peptidoglycan synthesis. The cloned 51 kDa protein encoded a functional product that complemented an E. coli murC mutant. Moreover, the ORF just upstream of murC coded for a protein that was 31% homologous with the E. coli MurG protein. The ORF just downstream of murC coded for a protein that was 17% homologous with the Streptococcus pneumoniae penicillin-binding protein 2B (PBP2B), which functions in peptidoglycan synthesis and is responsible for antibiotic resistance. These results suggest that P. gingivalis contains a homologue of the E. coli peptidoglycan synthesis gene murC and indicate the possibility of a cluster of genes responsible for cell division and cell growth, as in the E. coli mra region.


Intercalative poly(carbazole) precursor electropolymerization within hybrid nanostructured titanium oxide ultrathin films.
A protocol for nanostructuring and electropolymerization of a hybrid semiconductor polycarbazole-titanium oxide ultrathin film is described. Ultrathin (<100 nm) films based on polycarbazole precursor polyelectrolytes and titanium oxide (TiOx) have been fabricated by combining the layer-by-layer (LbL) and surface sol-gel layering techniques. Film growth was followed and confirmed through UV-vis spectroscopy, ellipsometry and quartz crystal microbalance with dissipation (QCM-D). Subsequent anodic electrochemical oxidation of the carbazole pendant units afforded a conjugated polymer network (CPN) film within intercalating TiOx layers of cross-linked and π-conjugated carbazole units. Cyclic voltammetry (CV), UV-vis, and fluorescence spectroscopy measurements confirmed this process. The LbL-driven polyelectrolyte deposition process resulted in a quantified electrochemical response, proportional to the number of layers, while the TiOx acted as a dielectric spacer limiting electron transfer kinetics and attenuating energy transfer in fluorescence. Electro-optical properties were compared with other polycarbazole thin film materials with respect to bandgap energy (Eg). The straightforward protocol in film nanostructuring and barrier/dielectric properties of the inorganic oxide slab (denoted here as, TiOx) should enable applications in organic light-emitting diodes (OLEDs), dielectric mirrors, planar waveguides, and photovoltaic devices for these hybrid ultrathin films.


Microstructure and physical properties of two charge density wave states in NbSe3 nanowires.
The whisker-like niobium triselenide (NbSe3) nanowires were synthesized using the traditional solid state reaction. X-ray diffraction experiment suggested the monoclinic structure (P2(1)/m), and crystal morphology analysis indicated that the band-like shape is the stable morphology. Two charge density wave (CDW) states were observed at around 140 K and 50 K, respectively, and the nonlinear effect was detected in the CDW states from the R-T and I-V measurements. The doped Fe atoms, as pinning centers, play an important role in the nonlinear properties of the CDW state. Electron diffraction and HRTEM experiments were carried out at different temperatures in order to investigate the structural features and their evolution. The sets of incommensurate modulation spots with modulation vector q1 - (h, k +/- 0.243, l) appeared below 145 K, and other sets of complex superstructure spots with modulation vector q2 - (h, k + 0.3, l + 1.3424), q3 - (h, k - 0.3137, 1.5685), q4 = (1/3, k, 1) and q5 = (0.5, 0.25, 0.5) were observed at [1 0 0] and [3 0 1] zone axis at about 20 K, respectively, suggesting the complex incommensurately modulated structures in this material.


Ergonomic principles in patient handling: Knowledge and practice of physiotherapists in Nigeria.
Physiotherapists are advocates of workplace health and safety. Despite the high prevalence of work-related musculoskeletal disorders (WMSDs), there is limited knowledge of ergonomic principles have been successfully applied in the workplace by Nigerian physiotherapists. This study evaluates the knowledge and practice of ergonomic principles in patient handling among physiotherapists in Nigeria. A cross-sectional survey design was used to sample 360 physiotherapists practicing in Nigeria. Participants responded to a three-part structured questionnaire that had a reliability coefficient of 0.77. Data was analyzed using descriptive statistics and Chi-Square. The majority (95.9% ) of the participants had good knowledge of the ergonomic principles in patient handling while only 48.6% reported practicing them. Poor practice was mainly due to a lack of patient handling equipment. There was no significant association between knowledge and practice of ergonomic principles among study participants. Specific areas of physiotherapy practice showed a significant association with ergonomic knowledge and practice. Years of physiotherapy practice and highest educational qualifications showed a significant association with the levels of practice and knowledge respectively. Physiotherapists in Nigeria reported a good level of knowledge of ergonomic principles, but a poor practice level. Perhaps this non-adherence contributed to the high prevalence of WMSDs among physiotherapists in Nigeria.


Lipoxene: a new group of trihydroxy pentaenes of eicosapentaenoic acid derived from porcine leukocytes.
Incubation of porcine leukocytes with [1-14C]-15-hydroperoxyeicosapentaenoic acid (15-HPEPE) results in the formation of a group of polar metabolites which after separation and purification by RP-HPLC and SP-HPLC were found to be a series of new compounds containing three hydroxy groups and four conjugated double bonds. The structures of these new metabolites were established by U. V. spectrophotometry and GC/MS to be trihydroxy pentaenes of EPA, i.e., 5,6,15-trihydroxy-7,9,11,13,17-eicosapentaenoic acid and 5,14,15-trihydroxy-6,8,10,12,17-eicosapentaenoic acid. Because of the additional double bond at C17-18, these two new metabolites of EPA were proposed to be lipoxene A and lipoxene B, respectively.


Campylobacter strains from Swedish patients with diarrhoea. Distribution of serotypes over a five year period.
Serotyping, HS antigen and HL antigen, was performed on 105 Campylobacter jejuni/coli isolates from the same number of consequtive patients seeking medical attention for diarrhoea. The results were compared to a similar study performed five years earlier. It was found that there were only minor differences in frequency of the serotypes commonly isolated during the two different periods.


Pump dysfunction after myocardial infarction: importance of location, extent and pattern of abnormal left ventricular segmental contraction.
To delineate the relative effects on left ventricular function of the site, extent and nature of the abnormal left ventricular segmental contraction (dyssynergy) and thereby determine the mechanism by which anterior myocardial infarction results in greater depression of left ventricular performance than does inferior infarction, 43 patients with remote myocardial infarction of similar extent (average 38 percent of left ventricular systolic perimeter) and associated hypokinesia or dyskinesia confined to either the anterior or inferior wall were compared; 10 additional patients were evaluated who exhibited generalized dyssynergy (72 percent of left ventricular perimeter). When the pattern of dyssynergy and extent of infarction were similar, the location alone of dyssynergy did not influence variables of left ventricular function. However paradoxical outward systolic movement (dyskinesia) of the anterior or inferior wall resulted in greater depression (P less than 0.05) of measures of left ventricular performance than did diminished inward systolic motion (hypokinesia) associated with infarction of similar extent and location. All measures of left ventricular performance were considerably more depressed (P less than 0.05) in the 10 patients with generalized dyssynergy than in the 43 patients with localized dyssynergy. Thus, the location of infarction is not a unique determinant of left ventricular performance. Instead, the size of infarction is the principal characteristic of dyssynergy that impairs left ventricular function; the severity of the pattern of dyssynergy is significant but of lesser importance. It is therefore concluded that the greater reduction of left ventricular function in anterior than in inferior myocardial is largely the result of the more extensive area of necrosis rather than of the location of the infarction.


Intracellular magnesium deficiency in acute myocardial infarction.
It has been hypothesized that intracellular magnesium deficiency is a pathogenetic factor in acute myocardial infarction. This study examined the time course of changes in the erythrocyte magnesium concentration and the correlation between the erythrocyte magnesium concentration and the severity of acute myocardial infarction in 49 consecutive patients with transmural acute myocardial infarction. The data were compared with results from 20 control patients without ischemic heart disease. The erythrocyte magnesium concentration (mg/dl) decreased significantly during the acute phase of the infarction (4.86 +/- 0.09 on day 1, 4.89 +/- 0.10 on day 2 and 4.86 +/- 0.10 on day 3 versus 5.26 +/- 0.19 for controls, all P < 0.05) and then normalized gradually to 5.25 +/- 0.10 on day 28. The serum magnesium concentration (mg/dl) also decreased significantly during the acute phase of the infarction (1.93 +/- 0.04 on day 1 and 2.11 +/- 0.03 on day 2 versus 2.26 +/- 0.08 for controls, all P < 0.05), before recovering to 2.28 +/- 0.06 on day 28. There were significant correlations between the erythrocyte magnesium concentration on day 1 and maximal values of serum cardiac enzymes (r = -0.30 for creatine kinase, r = -0.34 for glutamic oxaloacetic transaminase and r = -0.57 for lactate dehydrogenase, all P < 0.05). Moreover, the erythrocyte magnesium concentration was significantly lower in patients with (4.32 +/- 0.08 mg/dl, n = 13) than in those without (5.06 +/- 0.09 mg/dl, n = 36, P < 0.0001) serious arrhythmias. These data indicate that intracellular magnesium deficiency is involved in the acute phase of myocardial infarction.


Feasibility and acceptance of a nonpharmacological cognitive remediation intervention for patients with Parkinson disease.
Many patients with idiopathic Parkinson disease (PD) experience deficits in executive skills (ES; eg, attentional control, self-monitoring), which are associated with a range of impairing symptoms such as visual hallucinations, decreased motor control, and increased apathy. Pharmacological methods for improving ES in PD have shown to be somewhat unreliable. The goal of this study was to evaluate the feasibility and patient acceptance of a nonpharmacological cognitive remediation program that aimed to improve sustained, selective, alternating, and divided attentional abilities in a sample of 16 nondemented PD patients. Based on ratings of 4 feasibility dimensions (fatigue, effort, progress, enjoyment), patients with PD demonstrated a high degree of acceptance and successfully engaged in the program. As predicted, ratings of progress differed significantly across tasks according to difficulty level and were positively related to posttraining improvement in ES. Fatigue ratings showed negative associations with other indices across task types, suggesting that monitoring fatigue during cognitive remediation is essential. Patients' ratings of enjoyment did not correspond to task difficulty, indicating that tasks could be simultaneously challenging and rewarding. Males reported exerting greater effort during the training than females. It was concluded that the intervention is appropriate for testing in a randomized controlled trial.


Comprehensive review of rasagiline, a second-generation monoamine oxidase inhibitor, for the treatment of Parkinson's disease.
Inhibitors of monoamine oxidase (MAO) with selectivity and specificity for MAO type B (MAO-B) prolong the duration of action of both endogenously and exogenously derived dopamine. Rasagiline [N-propargyl-l(R)-aminoindan] is a second-generation propargylamine pharmacophore that selectively and irreversibly inhibits brain MAO-B and is specifically designed for the treatment of Parkinson's disease (PD). The aim of this study was to review the pharmacology, tolerability, and clinical efficacy of rasagiline in the treatment of PD. MEDLINE (1966-April 2007), the Cochrane Database of Systematic Reviews, and International Pharmaceutical Abstracts (1970-April 2007) were searched for original research and review articles published in English. The search terms were monoamine oxidase, neuroprotection, Parkinson disease, propargylamine, rasagiline, and selegiline. The reference lists of articles were also consulted, as was information provided by the manufacturer of rasagiline. Data from 63 clinical and laboratory studies were analyzed. Based on the results from those studies, we concluded that rasagiline PO QD, at the therapeutic dosage range of 0.5 to 1 rag/d, is effective and well tolerated and completely, selectively, and specifically inhibited MAO-B. Pharmacologically, rasagiline was found to be < or =10-fold more potent than selegiline and was not metabolized to amphetamine derivatives. Rasagiline was effective both as monotherapy in early PD and as adjunctive treatment in patients with advancing PD and motor fluctuations. As monotherapy, rasagiline provided modest yet clinically meaningful benefit. A randomized, double-blind, placebo-controlled study found that, after 26 weeks of treatment, the adjusted effect size for total Unified Parkinson's Disease Rating Scale score was -4.20 (95% CI, -5.66 to -2.73) for rasagiline 1 mg/d versus placebo (P < 0.001). Preliminary long-term data from an open-label study suggest a sustained therapeutic advantage when rasagiline is initiated early (before the need for dopaminergic agents) rather than later. In patients with more advanced disease who received treatment with dopaminergic agents, rasagiline and entacapone were associated with reductions of "off" time significantly greater than placebo (-1.18 and -1.2 vs 0.4 hour; both, P < or = 0.001). Rasagiline was well tolerated in younger (aged <;70 years) and older (aged > or =70 years) patients with early or advanced PD. Pharmacologically, rasagiline has the potential to augment the vasopressor effects of diet-derived tyramine (ie, the "cheese reaction"). However, clinical challenge studies of tyramine have found this unlikely to occur even with ingestion of supraphysiologic amounts of tyramine. In experimental models, rasagiline has been found to have neuroprotective properties that may be independent of MAO-B inhibition. Based on this review, rasagiline has been found to be well tolerated and effective in the treatment of early PD and as adjunctive treatment in motor fluctuations. Whether rasagiline is associated with clinically significant neuroprotection (ie, disease modification) in PD is the subject of ongoing clinical trials.


Experimental and numerical study on effects of airflow and aqueous ammonium solution temperature on ammonia mass transfer coefficient.
This paper reports the results of an investigation, based on fundamental fluid dynamics and mass transfer theory, carried out to obtain a general understanding of ammonia mass transfer from an emission surface. The effects of airflow and aqueous ammonium solution temperature on ammonia mass transfer are investigated by using computational fluid dynamics (CFD) modeling and by a mechanism modeling using dissociation constant and Henry's constant models based on the parameters measured in the experiments performed in a wind tunnel. The validated CFD model by experimental data is used to investigate the surface concentration distribution and mass transfer coefficient at different temperatures and velocities for which the Reynolds number is from 1.36 x 10(4) to 5.43 x 10(4) (based on wind tunnel length). The surface concentration increases as velocity decreases and varies greatly along the airflow direction on the emission surface. The average mass transfer coefficient increases with higher velocity and turbulence intensity. However, the mass transfer coefficient estimated by CFD simulation is consistently larger than the calculated one by the method using dissociation constant and Henry's constant models. In addition, the results show that the liquid-air temperature difference has little impact on the simulated mass transfer coefficient by CFD modeling, whereas the mass transfer coefficient increases with higher liquid temperature using the other method under the conditions that the liquid temperature is lower than the air temperature. Although there are differences of mass transfer coefficients between these two methods, the mass transfer coefficients determined by these two methods are significantly related.


Exercise and newer insulins: how much glucose supplement to avoid hypoglycemia?
To determine the glucose supplement required to prevent hypoglycemia during moderate-intensity exercise in Type 1 diabetic patients using newer analog insulins. Nine subjects performed 60 min of ergocycle exercise (50% VO2max), 3 h after a standard breakfast in three different conditions. Subjects were randomly assigned to preexercise liquid glucose supplement of 0 g of glucose (0G), 15 g of glucose (15G), and 30 g of glucose (30G). Blood glucose (BG) was measured before, during, and following the exercise. All subjects used Humulin N (N) and analog insulin Humalog (Lispro). A dextrose infusion was initiated when BG fell below 5 mmol x L(-1). There was no significant difference in the magnitude of the decrease in BG exercise-induced when comparing the three experimental conditions. However, the quantity of dextrose infused was significantly higher in the 0G (10.5 +/- 3.2 g) than in the 15G (3.5 +/- 1.8 g) or the 30G conditions (1.6 +/- 1.0 g). The addition of a glucose supplement (15G or 30G) significantly prolonged the delay before the need for dextrose infusion (31.7 +/- 7.5, 51.3 +/- 4.2, and 55.6 +/- 2.6 min; 0G, 15G, and 30G, respectively). The quantity of dextrose infusion was plotted against the three preexercise glucose supplements and a regression equation obtained. Solving this equation, a glucose supplement of 40 g was estimated in order to maintain BG levels within the normal range during and after exercise. For 60 min of late postprandial exercise followed by 60 min of recovery, an estimated 40 g of a liquid glucose supplement, ingested 15 min prior exercise, would seem likely to help maintain safe BG levels in subjects using N-Lispro.


Comparison of tandem and conventional mass spectrometry using electron capture negative ionization in the detection of chemically oxidized dexamethasone in human plasma.
Chemistry and Biochemistry, Michigan State University, East Lansing, Michigan, USA Dexamethasone, a synthetic steroid, can be oxidized chemically to a ketonic steroid structure that is readily detected by electron capture negative ionization mass spectrometry (ECNI/MS). Previous work from this laboratory has demonstrated that the chemical oxidation procedure provides advantages of low detection limits and high selectivity for detection of oxidized dexamethasone against chemical background that would otherwise interfere with detection of this steroidal drug in biological samples using more conventional methodology. This report describes the extent to which tandem mass spectrometry (MS/MS) can further enhance the selectivity of the oxidation/ECNI methodology for the detection of dexamethasone during the analysis of human plasma and presents evidence that sample introduction by direct inlet probe (DIP) can be used successfully under ECNI conditions. For purposes of comparing the methodologies, the same human plasma samples are analyzed by ECNI, first with detection by conventional mass spectrometry using selected ion monitoring (SIM) and then by MSIMS using selected reaction monitoring (SRM) with sample introduction by the gas chromatographic (GC) inlet and by the DIP. The results indicate that use of the DIP is a viable means of sample introduction for ECNI when sample processing involves the specialized oxidation procedure described herein because the sample matrix does not compete significantly for the thermal electrons in the ion source. Whereas SIM and SRM provide comparable results when sample introduction is achieved by the GC inlet, the MS/MS approach offers the possibility for sample introduction using the DIP, which significantly simplifies and shortens the analysis.


Oxygen delivery and consumption in patients with hyperdynamic septic shock.
We analyzed the relationship of increases in oxygen delivery to changes in oxygen consumption in ten patients with hyperdynamic septic shock. Increases in oxygen delivery from 413 +/- 14 (SEM) to 535 +/- 19 ml/min X m2 (p less than .01) were associated with increases in oxygen consumption from 136 +/- 10 to 161 +/- 5 ml/min X m2 (p less than .05). Arterial lactate decreased from 4.6 +/- 1.6 to 2.1 +/- 0.3 mmol/L (p less than .05). These observations suggest that oxygen utilization is perfusion-limited in hyperdynamic septic shock.


Congenital absence of superior vena cava: unusual anomaly of superior systemic veins complicating pacemaker placement.
Congenital anomalies of the superior systemic veins can complicate placement of transvenous pacemaker electrode leads. Persistent left superior vena cava is the most common congenital anomaly; in this paper, we describe the case of a patient who had congenital absence of both superior venae cavae, which has not been reported previously. The superior systemic veins drained into persistent double azygos veins subdiaphragmatically. The anomaly was verified by venography. Temporary cardiac pacing was established by passing the electrode lead through the femoral vein, and a permanent epicardial pacemaker lead was placed thereafter. This appears to be the first recorded case of such an anomaly.


Nosocomial outbreak of hepatitis B virus infection involving two hospitals in the Republic of Ireland.
The routes of nosocomial hepatitis B virus (HBV) transmission have changed over the years. Initiatives to prevent transfusion-associated HBV and healthcare worker-to-patient transmission have had a positive impact on these transmission routes. Recent reports of outbreaks of nosocomial HBV have implicated breaches in standard precautions as important causes of HBV transmission. This report describes a nosocomial outbreak of HBV infection in the Republic of Ireland, which occurred between January 2005 and March 2006. The outbreak was detected following identification of a case of acute HBV infection in a patient whose only risk factor was a recent surgical procedure. The extensive multi-agency investigation that followed revealed that the patient was one of five cases of acute HBV infection and that four separate transmission events between infectious cases had occurred in two different hospitals over a 15-month period. A definitive cause for each transmission event was not identified, although lapses in adherence to standard precautions, safe injection and phlebotomy practices could not be ruled out. Two secondary cases of acute HBV infection in community contacts of two of the nosocomial cases were identified. Phylogenetic analysis proved a useful tool in confirming infection with a pre-core HBV mutant and viral transmission between the seven patients. A patient notification exercise involving 1028 potentially exposed patients found no evidence of additional cases of nosocomial HBV infection. These findings highlight the importance of consistent application of standard precautions.


Influence of oral contraceptives on coagulation tests in native blood and plasma.
Routine coagulation laboratory tests, clotting times in native (not anticoagulated) whole blood, platelet-rich and platelet-poor plasma, and recalcification times in citrated whole blood, platelet-rich and platelet-poor plasma were performed in 14 healthy premenopausal women. Blood was taken before and after one or two cycles of low-dose oral contraceptives. After oral contraceptives a reduction in clotting time in native platelet-rich plasma and activated partial thromboplastin time were observed. Recalcification times in whole blood and platelet-rich plasma were shorter than clotting times in their native counterparts. The observed changes are compatible with a procoagulant effect seen soon after the start of oral contraceptive use. The absence of these changes in the recalcification times in citrate systems suggests a masking effect of citrate. The reduction in clotting times in native platelet-rich but not in platelet-poor plasma indicates that the hypercoagulability in oral contraceptives users is mainly related to platelets.


Gout and hyperuricaemia in systemic lupus erythematosus.
Coexistent gout and systemic lupus erythematosus (SLE) have received increasing attention. An additional case is reported and published cases reviewed. Common clinical features of this group include nephritis, diuretic and corticosteroid therapy and a tendency to be older and more frequently male. Prevalence of hyperuricaemia (HU) was assessed in 38 patients with SLE. HU was found in 29% and was closely associated with renal involvement particularly proteinuria and diuretic therapy. The presentation of gout in SLE may be modified or suppressed by anti-inflammatory therapy and may be misinterpreted as SLE arthritis.


Differential interaction of the C3b/C4b receptor and MHC class I with the cytoskeleton of human neutrophils.
As measured by fluorescence microscopy and radioligand binding, C3b/C4b receptors (CR1) became attached to the detergent-insoluble cytoskeleton of human neutrophils when receptors were cross-linked by affinity-purified polyclonal F(ab')2 anti-CR1, dimeric C3b, or Fab monoclonal anti-CR1 followed by F(ab')2 goat anti-mouse F(ab')2. CR1 on neutrophils bearing monovalent anti-CR1 was not attached to the cytoskeleton. In contrast, cross-linked CR1 on erythrocytes and cross-linked MHC Class I on neutrophils were not cytoskeleton associated. A possible role for filamentous actin (F-actin) in the binding of cross-linked CR1 to neutrophil cytoskeleton was suggested by three observations. When neutrophils were differentially extracted with either Low Salt-detergent buffer or High Salt-detergent buffer, stained with FITC-phalloidin, and examined by fluorescent flow cytometry, the residual cytoskeletons generated with the former buffer were shown to contain polymerized F-actin, whereas cytoskeletons generated with the latter buffer were found to be depleted of F-actin. In parallel experiments, High Salt-detergent buffer was also found to release cross-linked CR1 from neutrophils. Second, depolymerization of F-actin by DNAse I released half of the cytoskeletal-associated cross-linked CR1. Third, immunoadsorbed neutrophil CR1, but not MHC Class I or erythrocyte CR1, specifically bound soluble 125I-actin. In addition, Fc receptor and CR3, other phagocytic membrane proteins of neutrophils, specifically bound 125I-actin. These data demonstrate that CR1 cross-linked on neutrophils becomes associated with detergent-insoluble cytoskeleton and that this interaction is mediated either directly or indirectly by actin.


A methodology for the development of software agent based interoperable telemedicine systems: a tele-electrocardiography perspective.
Telemedicine involves the integration of information, human-machine, and healthcare technologies. Because different modalities of patient care require applications running on heterogeneous computing environment, software interoperability is a major issue in telemedicine. Software agent technology provides a range of promising techniques to solve this problem. This article discusses the development of a methodology for the design of interoperable telemedicine systems (illustrated with a tele-electrocardiography application). Software interoperability between different applications can be modeled at different levels of abstraction such as physical interoperability, data-type interoperability, specification-level interoperability, and semantic interoperability. Software agents address the issue of software interoperability at semantic level. A popular object-oriented software development methodology - unified modeling language (UML) - has been used for this development. This research has demonstrated the feasibility of the development of agent-based interoperable telemedicine systems. More research is needed before widespread deployment of such systems can take place.


[The effects of teacher stimulation on student learning motivation].
The purpose of this study was to compare the effects of two types of teacher stimulation on 1) learning motivation of students who were poor in mathematics and 2) the students' impression of the teachers. One type of teacher stimulation was the encouragement of students who were poor in mathematics to make more effort because they had good ability but their ability was not yet realized. The other type of teacher stimulation was the encouragement of the students to exert themselves because of their previous lack of effort. A questionnaire, including the scenario describing the two types of teacher stimulation and several questions about the students' motivation and impression of the teachers, was administered to 378 elementary school, junior high school, and college students. The former type of teacher stimulation was partially more effective in the motivation of students and also fully more effective in the students' impression of the teachers than the latter type of teacher stimulation.


Do beta-blockers really increase peripheral vascular resistance? Review of the literature and new observations under basal conditions.
Most antihypertensive drugs act by counteracting vasoconstrictor mechanisms and lower blood pressure by lowering vascular resistance. The beta-blockers, which have the unique feature of counteracting cardiac sympathetic drive, seem to be a major exception to this generalization. Moreover, their degree of cardiodepression is not only directly correlated with the initial sympathetic tone, but also with their degree of intrinsic sympathicomimetic activity (ISA). Cardiodepression initially evokes a proportional rise in vascular resistance. As indicated by review of the literature, the antihypertensive effect of beta-blockers always parallels a decline in vascular resistance. Minimizing cardiac sympathetic drive by strict bedrest and studying beta-blockers with different degrees of ISA in 50 hypertensive patients showed that initially the effect of the drugs is offset by a rise in vascular resistance proportional to the fall in cardiac output. After that, blood pressure always fell parallel with the decline in vascular resistance. In the long run blood pressure and vascular resistance were always positively correlated, whatever the level of cardiac output. Thus, like all other antihypertensive agents, beta-blockers also lower blood pressure through interference with a vasoconstrictor mechanism.


On Eigen's Quasispecies Model, Two-Valued Fitness Landscapes, and Isometry Groups Acting on Finite Metric Spaces.
A two-valued fitness landscape is introduced for the classical Eigen's quasispecies model. This fitness landscape can be considered as a direct generalization of the so-called single- or sharply peaked landscape. A general, non-permutation invariant quasispecies model is studied, and therefore the dimension of the problem is [Formula: see text], where N is the sequence length. It is shown that if the fitness function is equal to [Formula: see text] on a G-orbit A and is equal to w elsewhere, then the mean population fitness can be found as the largest root of an algebraic equation of degree at most [Formula: see text]. Here G is an arbitrary isometry group acting on the metric space of sequences of zeroes and ones of the length N with the Hamming distance. An explicit form of this exact algebraic equation is given in terms of the spherical growth function of the G-orbit A. Motivated by the analysis of the two-valued fitness landscapes, an abstract generalization of Eigen's model is introduced such that the sequences are identified with the points of a finite metric space X together with a group of isometries acting transitively on X. In particular, a simplicial analog of the original quasispecies model is discussed, which can be considered as a mathematical model of the switching of the antigenic variants for some bacteria.


Is there a role for selective decontamination of the digestive tract in primarily infected patients in the ICU?
The role of selective decontamination of the digestive tract (SDD) for the prevention of nosocomial infection in critically ill patients remains controversial, and the efficacy of this technique in patients who are already infected on presentation to the intensive care unit has not previously been assessed. We performed a double-blind randomized placebo controlled trial of SDD (parenteral cefotaxime, six-hourly oral and enteral polymyxin E, tobramycin, and amphotericin B vs placebo) for all infected patients presenting to the ICU requiring mechanical ventilation for more than 48 hours and ICU stay of more than 5 days. Daily clinical and microbiological monitoring for secondary infection was undertaken until hospital discharge. In all, 59 selective decontamination and 76 placebo fully comparable patients fulfilled criteria for enrollment and analysis (APACHE II 15.2 vs 15.1). The number of patients receiving SDD who developed nosocomial infections was significantly reduced (P = 0.048), and there were no infections caused by the enterobacteriaceae or Candida spp in this group. No difference in ICU (17.5 vs 18.8 days) or hospital stay (32.7 vs 34.2 days) or mortality (17% vs 22.3%) was shown. Critically ill, primarily infected patients are protected from nosocomial infection by the use of SDD.