Prolonged infusion of suxamethonium in infants and children.
The neuromuscular blockade produced by a prolonged (greater than 90 min) continuous infusion of suxamethonium and measured with train-of-four stimulation was studied in 20 infants and 20 children during nitrous oxide and halothane in oxygen anaesthesia. The results were compared with a previous study in adults. Suxamethonium requirement was increased in infants and children. Mean peak infusion rates were 297 and 284 micrograms kg-1 min-1 in infants and children, compared with 134 micrograms kg-1 min-1 in adults. An initial tachyphylaxis was followed by bradyphylaxis, and the peak requirement occurred earlier in infants than in children and adults (40 v. 80-100 min). Phase II block developed during the tachyphylaxis. Recovery of neuromuscular activity commenced after stopping the infusion and was accelerated with neostigmine.


Hemodynamic effects of antagonists of the vasoconstrictor action of vasopressin in conscious dogs.
Two antagonists of the pressor action of arginine-vasopressin (AVP) were studied in conscious, normally hydrated dogs: 1-deaminopenicillamine-4-valine-8-D-arginine-vasopressin, or dPVDAVP, and 1-(beta-mercapto-beta, beta-cyclopentamethylene propionic acid)2-(O-methyl)tyrosine arginine-vasopressin, or d(CH2)5Tyr(Me)AVP. We first examined the hemodynamic effects of these antagonists when given alone. The infusion of dPVDAVP, 200 ng/kg/min, increased cardiac output (measured with an aortic electromagnetic flowmeter) by 23% and heart rate by 27%, leaving arterial pressure unchanged. Most of the change in cardiac output reflected a large increase in skeletal muscle blood flow, as determined by radioactive microspheres. The injection of d(CH2)5Tyr(Me)AVP, 10 micrograms/kg, had little effect on cardiac output, arterial pressure, and heart rate. We then examined the ability of the two antagonists to block the hemodynamic responses to injections of AVP. In the absence of the antagonists, AVP induced dose-related increases in mean arterial pressure and total peripheral resistance, as well as decreases in heart rate and cardiac output. The antagonist dPVDAVP shifted the dose-response curves to the right without changing their slope. On the contrary, the hemodynamic response to AVP was strikingly modified following blockade with d(CH2)5Tyr(Me)AVP. Cardiac output and heart rate increased, whereas total peripheral resistance decreased, for doses of AVP between 25 and 400 ng/kg. It is concluded that some antagonists of the pressor action of vasopressin may influence hemodynamics of conscious dogs by effects other than competitive antagonism at the level of vascular receptors.


Synapsin III is a key component of α-synuclein fibrils in Lewy bodies of PD brains.
Lewy bodies (LB) and Lewy neurites (LN), which are primarily composed of α-synuclein (α-syn), are neuropathological hallmarks of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). We recently found that the neuronal phosphoprotein synapsin III (syn III) controls dopamine release via cooperation with α-syn and modulates α-syn aggregation. Here, we observed that LB and LN, in the substantia nigra of PD patients and hippocampus of one subject with DLB, displayed a marked immunopositivity for syn III. The in situ proximity ligation assay revealed the accumulation of numerous proteinase K-resistant neuropathological inclusions that contained both α-syn and syn III in tight association in the brain of affected subjects. Most strikingly, syn III was identified as a component of α-syn-positive fibrils in LB-enriched protein extracts from PD brains. Finally, a positive correlation between syn III and α-syn levels was detected in the caudate putamen of PD subjects. Collectively, these findings indicate that syn III is a crucial α-syn interactant and a key component of LB fibrils in the brain of patients affected by PD.


Effects of early postnatal environment on phenotype and survival of a lizard.
Nutritional and thermal regimes experienced early in life can strongly influence offspring quality and ultimately adult life histories, especially in ectotherms. However, the importance of the interaction between diet and temperature during postnatal development and the effect on offspring quality are unknown. We compared offspring quality (size, shape, speed, behavior, and survival) of juvenile McCann's skinks (Oligosoma maccanni) housed outdoors under variable thermal conditions (under shelter, but exposed to daily and seasonal variations in light and temperature) with those housed indoors under more stable thermal conditions (controlled temperatures providing 30-40% more basking opportunity) and with a control group (open field conditions). For those caged in captivity (indoors and outdoors), we also compared outcomes between those fed a restricted diet and those fed ad libitum. By comparing individuals raised under different environmental regimes, we aimed to determine whether direct effects of temperature or indirect effects of food supply are more important for offspring quality. Individuals provided with food ad libitum grew faster, and attained larger sizes than those raised on a restricted diet or in the field. Activity rates were higher in individuals exposed to stable rather than variable thermal conditions. Survival post release in the field was highest for larger neonates, and lowest in individuals raised under stable thermal conditions and a restricted diet. We found little evidence for effects of an interaction between feeding and thermal regimes on most factors measured. However, the conditions experienced by young animals (especially diet) do influence important traits for population persistence, such as survival, and may influence key reproductive parameters (e.g., age and size at maturity), which could have implications for conservation management. Further research, including the ultimate influence of early environmental conditions on fecundity and life expectancy, is urgently needed.


A cytokeratin immunohistochemical study of alcoholic liver disease: evidence that hepatocytes can express 'bile duct-type' cytokeratins.
A cytokeratin immunohistochemical study was performed on 40 liver biopsies diagnosed as alcoholic liver disease to further investigate the cytoskeletal changes occurring in this disease. On paraffin sections of 29 cases, a variable number of hepatocytes were reactive with a polyclonal antiserum that normally stains only bile ducts. Using monoclonal antibodies specific for a single cytokeratin polypeptide on cryostat sections, a variable number of hepatocytes were immunoreactive for cytokeratin no. 7 in 23 cases and also for cytokeratin no. 19 in seven cases. Both these polypeptides are restricted to bile duct cells in the normal liver. The number of hepatocytes positive for bile duct-type cytokeratins increased and their location changed with the severity of the disease. Mallory bodies were reactive with monoclonal antibodies CAM 5.2 and anti-cytokeratin no. 18 but unreactive with anti-cytokeratin no. 8. except in one case. In two cases, Mallory bodies reactive with both monoclonal antibodies anti-cytokeratin no. 7 and anti-cytokeratin no. 19 were found. These results clearly indicate that hepatocytes in alcoholic liver disease can express immunoreactivity for bile duct-type cytokeratins. Our data also demonstrate heterogeneity in the composition of Mallory bodies. Whether hepatocytes expressing bile duct-type cytokeratins are the precursors of Mallory body-containing cells is not clear at present.


The antrum in duodenal ulcer patients. Relationship between antrum size, nerve of Latarjet, gastrin cell quantity, and gastric acid secretion.
Estimates of the border between antral and fundic mucosa, antral size, antral G-cell density, G-cell population, and total G-cell volume were made from multiple biopsies taken from the gastric curves during parietal cell vagotomy for duodenal ulcer in 33 patients. No relation was found between the landmarks of Latarjet's nerve and the border. The fundic mucosa was underdenervated in 20% of the patients, and the postoperative acid response to sham feeding in these was higher than in patients with an overdenervated or optimally denervated border. No relation was found between antral size, defined as antral mucosal volume containing G-cells, and preoperative acid secretion. However, an inverse relation was found between antral size, defined as antral mucosal volume containing no parietal cells, and preoperative maximum acid secretion, suggesting an inverse relation between areas with and without parietal cells. No relation was found between acid secretion and G-cell densities, G-cell population, or total G-cell volume.


Some heavy metals, essential elements, and chlorinated hydrocarbons in polar bear (Ursus maritimus) at Svalbard.
During the period 1978-1989, samples of liver, kidney and subcutaneous fat from 24 polar bears, Ursus maritimus, from Svalbard were analysed for mercury, cadmium, lead, copper, zinc, selenium, arsenic, HCB, DDE, PCBs (as Aroclor 1260 or Phenoclor DP6). In a selected number of liver (seven) and fat (three) samples, the composition of individual PCB congeners was studied by comparison with 23 individual PCB congeners (IUPAC nos 28, 52, 74, 101, 99, 110, 149, 118, 114, 105, 153, 141, 138, 187, 128, 183, 156, 157, 180, 170, 194, 206 and 209). In the seven liver samples, the concentrations of o,p'- and p,p'-isomers of DDT, TDE, DDE, alpha-, beta- and gamma-HCH, oxychlordane, heptachlor, heptachlorepoxide, aldrin and dieldrin were also determined. The hepatic concentrations of mercury, cadmium and lead in animals of all ages were 0.4-6.0, <0.1-1.2, and <0.5-1.6 microg g(-1), respectively. This indicates a moderate exposure. Concentrations of mercury and selenium were correlated (r=0.80). The levels of copper and zinc represented normal physiological concentrations. The concentrations of HCB, DDE and PCBs in fat were <0.05-1.5, <0.1-3.4 and 2.9-90 microg g(-1), respectively. The corresponding results for liver were <0.01-0.11, <0.1-0.5 and 0.1-78 microg g(-1), respectively. Six PCB congeners, PCB-99, -153, -138, -180, -170, and, -194 accounted for about 99 and 87% of the total PCB content (sum of the 12 congeners, nos. 28, 99, 153, 138, 128 + 187, 156, 157, 180, 170, 194, 206 and 209) in liver and fat, respectively. PCB-153 represented 37+/-3 30+/-16% of the sum PCB (sum of 12 congeners) in liver and fat, respectively. The range of the hepatic concentration of oxychlordane was 5-19 microg g(-1). Quantifiable concentrations of heptachlor, heptachlorepoxide, beta-HCH and dieldrin were also found in all the liver samples analysed. Low concentrations of p,p'- and o,p'-DDT were found in two of seven liver and two of two fat samples. Comparisons are made with investigations from Canada and Greenland. Possible effects of PCBs, especially on reproduction, cannot be excluded. Ringed seal, Foca hispida, and to some extent bearded seal, Erignathus barbatus, are the main food of the polar bear. It is therefore likely that the exposure to environmental pollutants occurs via the consumption of these two species.


The significance of paired MEFV mutations in individuals without symptoms of familial Mediterranean fever.
The majority of patients with familial Mediterranean fever (FMF) have identifiable mutations in both alleles of the MEFV gene, while some individuals with paired MEFV mutations do not have clinical symptoms of the disease. During family studies we identified nine such individuals from six kindreds, most of whom either subsequently developed FMF or had other clinically significant inflammatory disease; one case benefiting substantially from colchicine therapy. Four individuals remained asymptomatic. Two further asymptomatic subjects with paired MEFV mutations were identified among 49 healthy controls from western Turkey, of whom a further 18.4 per cent were simple heterozygotes. This carrier rate was higher than would be expected from prevalence of FMF in this region, suggesting that penetrance of paired recognised pathogenic MEFV mutations may frequently be incomplete. MEFV genotyping results must be interpreted with due caution, and follow-up of apparently asymptomatic subjects with paired mutations is advisable.


[Effect of oxyhydromassage therapy on some physiological parameters].
The oxygen uptake of the living organism through the cardiorespiratory system is one of the most basic physiological procedures, and the capacity for the oxygen uptake is an important parameter of both the health and the performance of the living organism. During the past decade several experiments have been performed in order to elaborate a hyperoxygenisation method which avoids the respiratory system. The consumption of oxygen-rich mineral water and its application in hydromassage are also such methods. The combination of the two methods was applied on 57 overweight volunteers during a 3-week treatment period. Their average values were the following: body mass index 29.5+/-5.5; body fat rate 35.2+/-8.6%. The treatment was called oxyhydromassage. Before and after the treatment certain somatic parameters were determined, and also parameters which verify the fact of hyperoxygenisation. Data show that the average loss of body weight was 2.3+/-1.9 kg, and that the body fat rate and the body mass index also decreased. The average decrease of the body fat rate was 3.2+/-2.7%, while that of the body mass index was 0.7+/-0.5. Hyperoxygenisation occurred in 68-75% of the participants, while somatic changes in 79-83%. These results are significant at a 5% level. One can presume that due to the hyperoxygenisation effect the oxidative (aerobic) energy supply accelerated in the mitochondria of the muscular fibres, and this process contributed to the oxidation of fats, too. The authors found that hyperoxygenisation achieved by the oxyhydromassage treatment had several beneficial effects on most of the participants. Further therapeutic applications of the oxyhydromassage, especially if it is combined with other vasodilatation methods, e.g. biomagnetic method, can be of even greater importance.


Novel r(2)(p25q31) cytogenetic abnormality in a pediatric patient with acute leukemia of ambiguous lineage.
We describe a case of acute leukemia of ambiguous lineage with a novel cytogenetic abnormality. A 1-year-old boy presented with abnormal complete blood count findings, and was found to have blasts and mild dysgranulopoiesis. The blasts showed immunophenotypic evidence of myeloid and T-lineage differentiation. Subsequent cytogenetic analysis showed r(2)(p25q31) as the sole stem line cytogenetic defect with clonal evolution. While cytogenetic abnormalities can have a critical role in the classification and prognostication of acute lymphoblastic and acute myeloid leukemia, the significance of cytogenetic abnormalities in acute leukemia of ambiguous lineage remains unclear. This finding has not been reported previously to the best of our knowledge.


Azithromycin versus ceftriaxone for the treatment of uncomplicated typhoid fever in children.
A total of 108 children aged 4-17 years were randomized to receive 7 days of azithromycin (10 mg/kg/day; maximum, 500 mg/day) or ceftriaxone (75 mg/kg/day; maximum, 2.5 g/day), to assess the efficacy of the agents for the treatment of uncomplicated typhoid fever. Salmonella typhi was isolated from the initial cultures of blood samples from 64 patients. A total of 31 (91%) of the 34 patients treated with azithromycin and 29 (97%) of the 30 patients treated with ceftriaxone were cured (P>.05). All 64 isolates were susceptible to azithromycin and ceftriaxone. Of the patients treated with ceftriaxone, 4 subsequently had relapse of their infection. No serious side effects occurred in any study subject. Oral azithromycin administered once daily appears to be effective for the treatment of uncomplicated typhoid fever in children. If these results are confirmed, the agent could be a convenient alternative for the treatment of typhoid fever, especially in individuals in developing countries where medical resources are scarce.


Chemoprevention of colorectal cancer with ursodeoxycholic acid: pro.
Colorectal cancer is the third and second most common cancer among men and women, respectively, in France. Interest in the chemoprevention of colorectal cancer has increased over the last two decades. Experimental data strongly suggest that ursodeoxycholic acid (UDCA) may have chemopreventative actions in colorectal cancer. UDCA is able to inhibit tumor development in azoxymethane and in dextran-related colitis models. In high-risk populations such as subjects with previous colorectal adenoma removal or inflammatory bowel disease, five out of 10 published studies suggested beneficial effects with UDCA on colonic carcinogenesis. In the azoxymethane model, UDCA inhibited tumor development by counteracting the tumor-promoting effects of secondary bile acids such as deoxycholic acid (DCA). The opposing effects of UDCA and DCA on lipid raft composition may be central to their effects on colonic tumorigenesis. Differential effects of DCA and UDCA on growth factor and inflammatory signals involved in colorectal carcinogenesis, such as epidermal growth factor receptor (EGFR) signaling and COX-2 expression, very likely mediate their opposing effects on colonic tumor promotion and tumor inhibition, respectively.


Synchronous hepatocellular carcinoma and cholangiocarcinoma arising in two different dysplastic nodules.
We present the first reported case of explant cirrhotic liver that had synchronous cholangiocarcinoma and hepatocellular carcinoma arising in two different high-grade dysplastic nodules. The patient was a 55-year-old woman who had hepatitis B virus-associated liver cirrhosis for 3 years. The moderately differentiated cholangiocarcinoma occurred in high-grade dysplastic nodule with a 1.7-fold cell density compared with that of cirrhotic nodule. The hepatocellular carcinoma arose in a nodule-in-nodule pattern within a peripherally low-grade and centrally high-grade dysplastic nodule and had a 2.7-fold cell density compared with that of cirrhotic nodule. By immunohistochemistry, the tumor cells of the cholangiocarcinoma as well as bile ductular cells in dysplastic nodule were diffusely positive for cytokeratin 7, whereas hepatocellular carcinoma cells and dysplastic hepatocytes were negative for cytokeratin 7. The c-kit-positive hepatic progenitor cells were singly scattered between hepatocytes, and their number was highest in cirrhotic nodule and decreased in dysplastic nodule, whereas they were absent in cholangiocarcinoma and hepatocellular carcinoma arising in dysplastic nodules. Proliferation indices were progressively increased in cirrhotic nodule, dysplastic nodule, and cholangiocarcinoma or hepatocellular carcinoma, sequentially. These observations indicate that cholangiocarcinoma as well as hepatocellular carcinoma can develop in dysplastic nodule and that hepatic progenitor cells might play a role in the early stage of cholangiocarcinogenesis and hepatocarcinogenesis.


Reversed-phase high-performance liquid chromatographic determination of tetracyclines in urine and plasma.
The high-performance liquid chromatographic separation and quantitative analysis of oxytetracycline, tetracycline, and chlortetracycline from urine and plasma were effected on an octadecylsilane reversed-phase packing. The calcium complexes of the tetracyclines were extracted from urine and plasma with ethylacetate and then reextracted into hydrochloric acid. Following the injection of the hydrochloric acid extracts onto the column, the individual tetracyclines were eluted isocratically and quantitated spectrophotometrically. Concentrations of less than 1 microng/ml in urine and 1.5 microng/ml in plasms were quantitatively determined with a relative standard deviation of less than 5%.


Effects of dietary supplementation with marine lipid concentrate on the plasma lipoprotein composition of hypercholesterolemic patients.
Although the triglyceride-lowering actions of n-3 fatty acids of marine lipids are now well-recognized, their effects on plasma lipoproteins have not been studied systematically in patients with hypercholesterolemia. To address this question, we supplemented the Phase 1 American Heart Association diets of 14 hypercholesterolemic ambulatory outpatients with a commercially available preparation of marine lipid concentrate (SuperEPA) containing 7.5 g n-3 fatty acids per day and studied their plasma lipids and lipoproteins before and after 30 days of treatment. Both plasma triglyceride and cholesterol levels fell uniformly in all patients while the mean VLDL- and LDL-cholesterol decreased by 58% (P less than 0.005) and 13% (P less than 0.025) respectively. The decrease in whole plasma cholesterol was significantly correlated with the fall in LDL-cholesterol (r = 0.85, P less than 0.01), and not VLDL-cholesterol (r = 0.39, NS). Among the other potentially beneficial actions observed was an increase in HDL2 in all patients (mean increment 41%, P less than 0.005), and an increase in the HDL2/HDL3 ratio (+46%, P less than 0.001) and decreases in the LDL/HDL ratio (-14%, P less than 0.005) and in the unesterified cholesterol/lecithin ratio (-17%; P less than 0.001) in plasma. The increase in the unesterified cholesterol/esterified cholesterol ratio in VLDL and HDL3 suggested that marine lipid therapy resulted in a reduction in the size of lipoprotein particles in these fractions. Since these changes may reduce cardiovascular risk, these findings suggest that marine lipids may prove useful in the treatment of certain patients with hypercholesterolemia.


EEG Brain Wave Activity at Rest and during Evoked Attention in Children with Attention-Deficit/Hyperactivity Disorder and Effects of Methylphenidate.
The aim of this study was to assess baseline EEG brain wave activity in children with attention-deficit/hyperactivity disorder (ADHD) and to examine the effects of evoked attention and methylphenidate on this activity. Children with ADHD (n = 19) were tested while they were stimulant free and during a period in which they were on stimulant (methylphenidate) medication. Control subjects (n = 18) were tested once. EEG brain wave activity was tested both at baseline and during focussed attention. Attention was evoked and EEG brain wave activity was determined by means of the BioGraph Infiniti biofeedback apparatus. The main finding of this study was that control subjects and stimulant-free children with ADHD exhibited the expected reactivity in high alpha-wave activity (11-12 Hz) from baseline to focussed attention; however, methylphenidate appeared to abolish this reactivity. Methylphenidate attenuates the normal cortical response to a cognitive challenge.


[Progress on the biosynthesis of medium-chain-length polyhydroxyalkanoates by microorganisms].
Polyhydroxylkanoates(PHAs) are a class of polyesters produced as reserve materials by a large number of microorganisms under metabolic stress. The most fascinating feature of PHAs is its degradability, and which is supposed to take place of the traditional plastics made from petroleum in the future. PHAs are divided into two classes: short-chain-length PHAs(scl-PHAs) and medium-chain-length PHAs. mcl-PHAs is more welcome owing to its more wide crystallinity and higher extension to break than scl-PHAs, especially when some kind of new functional groups were incorporated into the side chain of the polyester. Since Psedumonas oleovorans is the most typical microorganism to produce mcl-PHAs, here the author summarized how P. oleovorans synthesize the mcl-PHAs and the production of mcl-PHAs by fermentation and give some of the idea about the future research of this field.


Physiological determinants of Ficus fruit temperature and implications for survival of pollinator wasp species: comparative physiology through an energy budget approach.
Figs are completely dependent for pollen dispersal on species-specific fig-pollinating wasps that develop within developing fig fruits. These wasps are very sensitive to heat and die at temperatures only a few degrees above ambient. Such temperatures are expected and observed in objects exposed to full sunlight, as fig fruits frequently are. In detailed field and experimental studies of 11 species of Panamanian figs with fruit ranging in size from 5 mm to 50 mm in diameter, we found that both the relative and absolute contribution of transpiration to maintaining non-lethal fruit temperatures increased with fruit size. Small and large fruits reached temperatures of 3 and 8°C, respectively, above air temperature in full sunlight when transpiration was prevented by grease. The temperature reached by large, nontranspiring fruits was sufficient to kill their pollinators. Control fruits which transpired reached temperatures of 2-3°C above air temperature in sunlight, regardless of size. An analysis of the solar energy budget of fruit revealed that large fruits must transpire to maintain tolerable temperatures for the wasps because heat diffusion from fruit to air was too low to balance net radiation in sunlight. By contrast, small fruits do not need to transpire to maintain tolerable temperatures for the pollinators.


Expressing qualitative biomedical knowledge exactly using the language LESK.
A language (LESK) is described which allows one to make mainly qualitative declarations of the essential terminology and facts in some technical subject. LESK is essentially first order predicate calculus, made to look like natural language. A LESK system, now partially implemented in PROLOG, allows one to enter declarations and assertions, check consistency, and deductively answer predominately generic, universally quantified questions. An extensive example is presented in which LESK is used to describe neurophysiological knowledge about the stretch reflex.


Radiologic evaluation of the trachea.
Multidetector computed tomography (CT) allows for an accurate, noninvasive means of evaluating tracheal anatomy and pathology. The integration of information obtained from axial images, multiplanar reformats and 3-D rendering enables precise anatomical localization of tracheal pathology, provides detailed information on surrounding structures, aids in surgical planning, and allows for assessment of posttreatment response. Although bronchoscopy remains the gold standard in the diagnosis of tracheal pathology, the proper utilization of radiologic imaging can allow for improved patient care.


Radionuclide parathyroid imaging: a concise, updated review.
The hypercalcemia of hyperparathyroidism (HPT) can cause devastating effects to the patient and only surgical removal of the hyperfunctioning parathyroid tissue can definitely cure the disease. Radionuclide parathyroid imaging has no role in the diagnosis of hyperparathyroidism or in the selection of the type of treatment. However, once surgery is decided (99m)Tc-sestamibi scanning can localize abnormal parathyroid glands preoperatively. In primary HPT radionuclide assessment may occasionally be helpful before bilateral neck exploration, it can identify patients suitable for focused surgery and is a prerequisite of the minimally invasive radioguided parathyroidectomy. In secondary and tertiary HPT the clinical value of parathyroid scintigraphy remains debatable, but in persistent or recurrent disease this modality is a first line examination before reoperation. In conclusion, (99m)Tc-sestamibi assessment has a well defined clinical role in the surgical management of patients with primary hyperparathyroidism and in recurrent disease, but its usefulness in cases of secondary hyperparathyroidism is not clearly established.


[Radionuclide techniques in early diagnosis of pulmonary artery thromboembolism].
A combined procedure of indirect radionuclide phlebography and emission tomography of the lung with human serum albumin microspheres was employed to diagnose thromboembolism of pulmonary arterial branches (TPAB) and thrombosis in the inferior cava system. Four hundred and forty nine patients suspected for TPAB were examined. The data characteristic of pulmonary thromboembolism were obtained in 21.6% of cases. In 75 (17.6%) of 432 patients, indirect radionuclide phlebography revealed signs of thrombosis in the inferior cava at various sites. The radionuclide study of pulmonary perfusion is the only technique that assesses the degree of recovery of pulmonary perfusion after TPAB.


Medical confidentiality and patient privacy: the Jewish perspective.
This article presents the approach of Jewish law to the major issue of medical confidentiality and patient privacy. For an extensive discussion of Jewish medical ethics and an in-depth presentation of the Jewish view of 39 major issues in medical ethics, the reader is referred elsewhere [15]. Briefly, the Jewish view toward medical ethical subjects is predicated on the general principle of the supreme value of human life. In Judaism, all biblical and rabbinic laws are temporarily waived in order to save a human life. Physicians are obligated to heal patients from their illness, to induce remission and cure of disease whenever possible. Similarly, patients are obligated to lead healthy lifestyles, to consult physicians when they are sick and to be compliant with the physician's therapeutic recommendations. The Jewish view on medical confidentiality and patient privacy as presented in this essay flows from these general principles of Jewish medical ethics.


Recovery of time on limits of stability from functional fatigue in Division II collegiate athletes.
Health and fitness professionals working with athletes could establish effective and safe practice and training programs if recovery time on dynamic balance from exertion was available. Research investigating the time needed to recover dynamic limits of stability (LOS) from exertion has not been reported. The purpose of this study was to determine the recovery timeline on LOS from functional fatigue in collegiate athletes. Eighteen athletes (11 men, 7 women) from Division II collegiate soccer team who passed prescreening tests to identify their fitness levels were randomly tested on 2 different days by condition (fatigue or nonfatigue). Functional fatigue was determined by using the Borg 15-point rating of perceived exertion (RPE) scale. Subjects were tested on LOS on the Biodex Balance System pre, post, 10, 15, and 20 minutes for each condition. The main effect for condition was not significant (F() = 0.004, p = 0.948), whereas the main effect for time was significant (F(4,64) = 6.167, p < 0.001). The RPE scoring revealed the significant main effect in FATIGUE (F(2.69, 45.73) = 234.8, p < 0.001). In conclusion, 20 minutes of functional activity will likely have a negative influence on dynamic balance, with balance recovery occurring within 10 minutes after the cessation of exercise in Division II collegiate soccer athletes. Moreover, the level of exertion measured by RPE would correspond to athletes' ability to control their center of mass.


Best Clinical Practice Guidance for clinicians dealing with children presenting with Molar-Incisor-Hypomineralisation (MIH): An EAPD Policy Document.
The European Academy of Paediatric Dentistry (EAPD) has long recognised the necessity of promoting further research and knowledge regarding the dental defect described as molar-incisor-hypomineralisation (MIH). Following the establishment by EAPD of the defect diagnostic criteria in 2003, the publication of various papers and a whole issue assigned to the defect in the European Archives of Paediatric Dentistry (2008), an Interim Seminar and Workshop on MIH was organized in Helsinki in 2009. The outcome of this event is the present consensus paper on the prevalence, diagnosis, aetiology and treatment for children and adolescents presenting with MIH. A clear diagnostic proposal and a treatment decision-making guide are presented together with suggestions on aetiology and guidance for future research. MIH is an important clinical problem that often concerns both the general dental and specialist paediatric dentists; the present 'best clinical practice guidance' aims to further help clinicians dealing with the condition.


Chain conformation in polymer nanocomposites with uniformly dispersed nanoparticles.
The effect of nanoparticles (NP) on chain dimensions in polymer melts has been the source of considerable theoretical and experimental controversy. We exploit our ability to ensure a spatially uniform dispersion of 13 nm silica NPs miscible in polystyrene melts, together with neutron scattering, x-ray scattering, and transmission electron microscopy, to show that there is no measurable change in the polymer size in miscible mixtures, regardless of the relative sizes of the chains and the nanoparticles, and for NP loadings as high as 32.7 vol%. Our results provide a firm basis from which to understand the properties of polymer nanocomposites.


Clinical AV nodal reentrant tachycardia in a patient with left sided accessory pathway and immediate occurrence of antidromic AV reentrant tachycardia after slow pathway ablation.
The only inducible arrhythmia in a patient with exclusive antegrade conducting left anterolateral accessory pathway, consists of slow/fast atrioventricular nodal reentrant tachycardia. After radiofrequency catheter ablation of the slow pathway, true antidromic AV reentrant tachycardia was easily induced by atrial pacing. Following ablation of the accessory pathway no arrhythmia could be induced.


Role of lipoprotein-associated phospholipase A2 in leukocyte activation and inflammatory responses.
Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an emerging cardiovascular risk marker. To explore the biologic role of Lp-PLA2 in atherosclerosis, we examined its expression and contribution to leukocyte activation under proatherogenic conditions. Following the induction of diabetes and hypercholesterolemia in a porcine model, a rapid increase in plasma Lp-PLA2 activity was observed at 1 month. This was accompanied by upregulated Lp-PLA2 mRNA expression by peripheral blood mononuclear cells (PBMC) at 3 months, and elevated Lp-PLA2 mRNA expression in coronary arteries at 6 months. These changes were paralleled by increased inflammatory responses by circulating PBMC (ICAM-1, IL-6), in coronary tissues (ICAM-1, VCAM-1), and the subsequent accumulation of inflammatory cells. In human PBMC, proinflammatory mediators augmented the synthesis and release of functional Lp-PLA2. Furthermore, lysophosphatidylcholine (lysoPC), a product of Lp-PLA2 activity, induced an increase in several inflammatory cytokines (IL-1beta, IL-6, TNF-alpha) in a concentration-dependent manner. In contrast, Lp-PLA2 inhibition (SB677116; 1 microM) abrogated the inflammatory response elicited by oxidized LDL. In an experimental model of diabetes and hypercholesterolemia, leukocyte activation was associated with augmented Lp-PLA2 expression. In vitro, Lp-PLA2 activity mediated leukocyte activation and inflammatory responses, whereas Lp-PLA2 inhibition abolished inflammatory responses induced by oxidized LDL. Collectively, these observations support a proatherogenic role for Lp-PLA2.


Exploring the binding profiles of ConA, boronic acid and WGA by MALDI-TOF/TOF MS and magnetic particles.
Concanavalin A, boronic acid and Wheat germ agglutinin functionalized magnetic micro-particles were developed to enrich glycosylated peptides and proteins. The bead functionalities were validated according to their specificity by analyses of model proteins. Validated beads were employed for the enrichment of glycosylated human serum proteins. Eluted glycoproteins were digested by trypsin and the resulting peptides were purified by magnetic MB-HIC C8 beads. Each fraction was analyzed by MALDI-TOF MS and single peaks were subjected to MALDI-TOF/TOF MS with the objective to identify the respective proteins by database search. Search results revealed overlapping profiles of known serum glycoproteins.


Prognostic value of PET/CT with (18)F-fluoroazomycin arabinoside for patients with head and neck squamous cell carcinomas receiving chemoradiotherapy.
The prognostic value of positron emission tomography/computed tomography (PET/CT) with (18)F-fluoroazomycin arabinoside (FAZA) was evaluated in patients with head and neck squamous cell carcinoma (HNSCC) who underwent chemoradiotherapy (CRT). Twenty-nine patients with head and neck cancer underwent FAZA PET/CT before treatment. Data acquisition started 2 h after FAZA administration. In 26 patients with squamous cell carcinoma, FAZA uptakes by the primary lesions (tumor-muscle ratio in primary lesion: Pr T/M) and by the lymph node metastases (tumor-muscle ratio in lymph node metastasis) were compared with various clinical parameters. For the HNSCC patients who completed CRT protocol (n = 23), those who experienced disease progression were compared with those who did not experience disease progression with respect to the clinical and PET parameters. The prognostic values of the clinical and PET parameters were then evaluated with regard to progression-free survival (PFS). Pr T/M positively correlated with the lesion's maximum diameter, and it was significantly higher in stage IV lesions compared with stage I-III lesions. No significant differences were observed between the patients who experienced disease progression and those who did not, with respect to the clinical parameters. The average Pr T/M tended to be higher in patients with disease progression, although the differences were not statistically significant (p = 0.086). Kaplan-Meier analysis with log-rank tests indicated that Pr T/M was an only significant predictor of PFS among PET and clinical parameters evaluated (p = 0.010). FAZA uptake by the primary lesion was a significant prognostic indicator in HNSCC patients undergoing CRT. Hence, FAZA PET/CT may provide useful information in the management of HNSCC patients treated with CRT. Registration number of clinical trial's registry: UMIN000003440.


Short-term growth hormone administration at the time of opportunistic infections in HIV-positive patients.
A 12-week course of recombinant human growth hormone is an effective but expensive therapy for established HIV-related wasting. Wasting in HIV disease is often episodic, coinciding with bouts of acute opportunistic infection. We hypothesized that a short course of growth hormone, targeted at the time of opportunistic infection, might improve protein metabolism thereby reducing lean tissue loss. HIV-infected men with acute opportunistic infections, who received standard antimicrobial treatment for their infection as well as intensive nutritional counselling and oral energy supplements, were randomized to receive growth hormone or placebo for 14 days. Principal assessments were protein metabolism (measured by 13C-leucine infusion), body composition (measured by DEXA) and safety. There were no significant changes in outcome parameters in the placebo group (n = 11). In the growth hormone group (n = 9), protein catabolic rate decreased by 60% in the fasted state (P = 0.02 versus placebo), lean body mass increased by 2.2 kg (P = 0.03 versus baseline) and fat mass decreased by 0.7 kg (P = 0.002 versus baseline). There was no increase in adverse or serious adverse events in the growth hormone as compared with the placebo group. A two-week course of growth hormone at the time of acute opportunistic infection in HIV-infected patients improves protein metabolism and body composition during therapy and appears to be safe. This may represent a rational and economical approach to the use of growth hormone therapy.


Calpain is a mediator of myocardial injury in experimental uremia: is it activated by endogenous ouabain?
Incidence of cardiovascular disease is more than 20-fold higher in patients with chronic renal failure than in aged-matched individuals with normal renal function. Little is understood about the causes or the mechanism of uremia-induced cardiovascular injury, but the involvement of calpain as a possible mediator has recently been under investigation. Mean calpain activity was found to be 3.4-fold higher in the hearts of uremic rats than in control or spontaneously hypertensive (SHR) rats. In addition, calpain activity was found to be stimulated in myoblasts (Girardi) treated with media enriched with uremic serum compared with cells treated with serum from healthy volunteers. In this study, we assessed the impact of calpain activation in uremia and explored the possibility that calpain might be activated in uremia by endogenous ouabain. Ouabain is known to be elevated in uremia and is strongly associated with left ventricular hypertrophy in essential hypertension. Calpain activity was measured in situ in human-derived myoblasts treated with low doses of ouabain similar to those concentrations found in uremic patients. Low concentrations of ouabain (10 nmol/L) caused a highly significant increase in calpain activity, which could be completely inhibited by the simultaneous chelation of intracellular and extracellular Ca2+, and by the chelation of extracellular Ca2+ alone. Calpain activity can be stimulated by nanomolar concentrations of ouabain due to an influx of extracellular Ca2+. As circulating ouabain is known to be elevated in uremia and strongly associated with LVH remodeling, we hypothesize that endogenous ouabain might be one of the factors that facilitates the remodeling of the left ventricle in patients with renal failure.


Lymphocyte subsets in normal human bone marrow harvested for routine clinical transplantation.
Bone marrow and peripheral blood of 25 healthy bone marrow donors from our allogeneic bone marrow transplantation program were assessed for cell subsets bearing T11(CD2), T4(CD4), T8(CD8), B1(CD20) J5(CALLA, CD10), Mo1(CD11b), MY7(CD13). Mo2(CD14), MY9(CD33) and NKH-1 antigens. Bone marrow cell samples were taken for analysis at the start or at the end of the harvesting procedure of aspiration from the iliac crest. All samples were analysed on a flow cytometer at the lymphocyte window as obtained on the two-parameter (L90oLSxFALS) scatter diagram. There were no differences in the lymphocyte subset composition of bone marrow samples taken at the start or at the end of the harvesting procedure. In contrast to the majority of literature data, a high CD4/CD8 ratio was detected in bone marrow samples: it did not differ from that in the peripheral blood. The proportions of CD2 and CD4 T cell markers in the bone marrow correlated with those in the peripheral blood, thus further documenting a substantial bone marrow contamination with peripheral blood cells. A relatively large aspirate volume (4-5 ml) obtained from individual aspiration sites was identified as the only factor possibly accounting for the high-level contamination of bone marrow samples with peripheral blood. This conclusion was corroborated by low T cell proportions and low CD4/CD8 ratios found in the bone marrow washed from bone fragments and in bone marrow samples aspirated at first bone puncture in a volume of 1.0 ml. Taken together, these findings imply that less vigorous suction may decrease the number of T lymphocytes in bone marrow harvested for transplantation purposes.


TLR7/8 agonists trigger immunostimulatory properties of human 6-sulfo LacNAc dendritic cells.
Imiquimod and resiquimod represent Toll-like receptor (TLR) 7 and 8 agonists, which emerged as attractive candidates for tumor therapy. To elucidate immune cells, which mainly contribute to TLR7/8-mediated antitumoral activity, we investigated the impact of imiquimod and resiquimod on native human 6-sulfo LacNAc (slan) dendritic cells (DCs). We found that both TLR7/8 agonists significantly improve the release of various proinflammatory cytokines by slanDCs and promote their tumor-directed cytotoxic activity. Furthermore, resiquimod efficiently augmented the ability of slanDCs to stimulate T cells and natural killer cells. These results indicate that imiquimod and resiquimod trigger various immunostimulatory properties of slanDCs, which may contribute to their antitumor effects.


Implementation of a Voice Messaging System is Associated With Improved Time-to-Treatment and Overall Survival in Patients With Hepatocellular Carcinoma.
The diagnosis and treatment of cancer is a continuum, with multiple steps and interfaces between patients and providers allowing for potential delays in cancer recognition and subsequent treatment. The diagnosis and treatment of hepatocellular carcinoma (HCC) is especially prone to missteps along the continuum, leading to treatment delays due to non-tissue-based diagnosis and multiprovider treatments. The aim of this study was to evaluate outcome measures after implementation of a voice messaging system (VMS) designed to streamline patient referrals to downstream treatment physicians and ultimately reduce delays in HCC treatment, thereby improving outcome measures. A retrospective study of outpatients with HCC was conducted in a safety net hospital between February 2008 and January 2012. In February 2010, VMS notification of HCC to the ordering physician and downstream treating physicians was implemented. Patients were divided into 2 groups: (1) preintervention: diagnosis 2 years before implementation or failure of notification following implementation, and (2) postintervention: diagnosis 2 years after implementation. Demographics, tumor characteristics, treatment, and survival were compared. This study included 96 patients diagnosed with HCC: 51 in the preintervention group and 45 in the postintervention group. The main cause of chronic liver disease was HCV infection, and no differences in symptoms, liver dysfunction, tumor characteristics, or treatment were observed between groups. The time from diagnosis to clinic contact (0.5 vs 2.9 months; P=.003) and time from detection to treatment (2.2 vs 5.5 months; P=.005) was significantly shorter after implementation of the VMS. Barcelona Clinic Liver Cancer stage A status (hazard ratio [HR], 3.1; 95% CI, 2, 6), treatment (HR, 1.9; 95% CI, 1, 4), and VMS (HR, 1.8; 95% CI, 1, 3) were independently associated with overall survival. Patients diagnosed after implementation of the VMS had a median survival of 28.5 versus 15.7 months (P=.02). Implementation of VMS reduces time to treatment and time to clinic visit. Reduction in time to treatment is associated with improved outcome independent of tumor stage, underlying liver function, and treatment.


Bladder recurrence after radical nephroureterectomy: predictors and impact on oncological outcomes.
To identify predictive factors of bladder recurrence after radical nephroureterectomy and to evaluate the impact of this event on oncological outcomes. We carried out a retrospective analysis of 237 patients treated with radical nephroureterectomy for urothelial carcinoma of the upper tract at our institution from 1998 to 2011. Univariable and multivariable models evaluated the prognostic factors of bladder recurrence, and its impact on recurrence-free survival and cancer-specific survival. The median age was 69.3 years (interquartile range 60-76). With a median follow up of 44 months (interquartile range 24-79), bladder recurrence occurred in 85 patients (35.9%). A previous history of bladder cancer (P = 0.01) and the presence of concomitant carcinoma in situ (P = 0.005) remained independent predictors of bladder recurrence. The presence of bladder recurrence was not correlated with worse oncological outcomes in terms of disease recurrence (P = 0.075) and cancer-specific mortality (P = 0.06). However, the patients who experienced muscle-invasive bladder cancer recurrence had worse outcomes in terms of cancer-specific mortality (P = 0.01). Standard pathological features of aggressiveness, such as higher tumor stage (P = 0.05), higher grade (P = 0.01) and carcinoma in situ (P = 0.03), were independent predictors of muscle-invasive bladder cancer recurrence. Previous history of bladder cancer, tumor location and concomitant carcinoma in situ are independent predictors of bladder recurrence in patients undergoing radical nephroureterectomy. Bladder recurrence overall does not impact the oncological outcomes, but a muscle-invasive bladder recurrence is associated with a worse cancer-specific mortality. Standard pathological features of urothelial carcinoma of the upper tract aggressiveness (pT-stage, grade) are independent predictors of muscle-invasive bladder cancer recurrence.


The effect of rigid cervical collar height on full, active, and functional range of motion during fifteen activities of daily living.
Laboratory biomechanical experiment. To evaluate how different anterior cervical collar heights restrict full, active range of motion (ROM), and functional ROM during 15 activities of daily living. Hard cervical collars are commonly used in the clinical setting. Collar fit is presumed to affect immobilization, making neck height an important variable. No prior study has evaluated how different collar heights affect full, active and functional ROM. A previously validated electrogoniometer device was employed to quantify both full, active, and functional ROM. For each of 10 subjects, these ROM measurements were repeated without a collar and with an adjustable, hard collar (Aspen Vista) at each of 6 collar neck height settings. For each increase in collar height, there was a corresponding decrease in mean full, active ROM of 3.7% (3°) in the sagittal plane (R2 = 0.91, P = 0.003), 3.9% (3°) in the coronal plane (R2 = 0.88, P = 0.005), and 2.8% (4°) in the rotational plane (R2 = 0.86, P = 0.006). For each increase in collar height, there was a corresponding decrease in mean functional ROM across all of the tested activities of daily living of 1.1% (1°) in the sagittal plane (R2 = 0.90, P = 0.004), 0.4% (0.4°) in the coronal plane (R2 = 0.86, P = 0.007), and 0.6% (0.5°) in the rotational plane (R2 = 0.81, P = 0.014). For each increase in collar height, there was a 1.7° increase in mean neck extension while in the neutral position (R2 = 0.99, P < 0.001). This study suggests that greater cervical collar height for hard cervical collars will better restrict full, active, and functional cervical ROM. However, the change in functional ROM was only about one quarter to that of full active ROM and the clinical significance of this may be questioned. This must be balanced by the fact that this increased collar height forces the neck into greater extension which may not be the most clinical desired or functional position and may cause skin-related issues at the jaw or chest.


Generation of intense single-order harmonic pulse in the vacuum ultraviolet region using a deep ultraviolet driving laser.
A 90 nm single-order harmonic pulse with a 200 nJ on-target pulse energy at 1 kHz was realized through a harmonic generation process with a 35 fs Ti:Sa third harmonic in a Kr gas cell.


[Mucoepidermoid carcinoma of the epibulbar connective tissue with diffuse intraocular epithelial invasion].
A 55-year-old man was treated twice with local excision and crycoagulation for a recurrent limbal mass of the left eye. The original histologic diagnosis was squamous cell carcinoma. Three months after the last recurrence the globe was enucleated because of a spontaneous perforation at the corneoscleral limbus with iris prolapse. Histologic examination, including PAS and mucicarmine stains, revealed a mucoepidermoid carcinoma of the epibulbar conjunctiva with infiltration of the cornea, sclera, iris and ciliary body. Examination of specially stained sections (e.g. with mucicarmine) should be routinely performed for those conjuctival neoplasms that contain a squamous component. Aggressive surgical management, such as early enucleation including normal appearing tissue next to the globe, should be considered for treatment of primary mucoepidermoid carcinoma to avoid later exenteration or metastasis.


Impact of rufloxacin and ciprofloxacin on the intestinal microflora in a germ-free mice model.
The impact of rufloxacin and ciprofloxacin on faecal microflora was investigated in an experimental germ-free mice model into which human gastrointestinal flora was introduced and stabilized. Animals received oral doses of 10, 40 or 80 mg rufloxacin/kg, 30 or 60 mg ciprofloxacin/kg once daily for 10 days, or no treatment. Microflora was studied before, during and 1 week after treatment. No significant effect ( < 2 log reduction, p > 0.05) on aerobic microflora was observed after rufloxacin as compared to controls, except for a marked decrease in enterobacteria and a slight decrease in enterococci, staphylococci and anaerobes at the highest dose. Both doses of ciprofloxacin significantly reduced enterobacteria and clostridia, while the lower dose slightly reduced peptococci, bifidobacteria and eubacteria. The depression of the intestinal ecosystem was reversible, except for enterobacteria at the higher ciprofloxacin dose. No bacterial resistance was detected after either treatment.


Role of trauma on acute haematogenic osteomyelitis aetiology.
In this study we attempted to assess the role of trauma in acute haematogenic osteomyelitis (AHO). Twenty-four 6-8 week-old white New Zealand rabbits were divided into three groups. Group 1 received an injury to the proximal tibias; group II received a standardized bacteraemia with Staphylococcus aureus; group III received both the trauma and the bacteraemia. Scintigraphy was done by Gallium-67 citrate and, histopathologic examination was used for the diagnosis of osteomyelitis. In contrast to group I, AHO was seen in one case in group II and in all cases of group III.


Improving the copy numbers of antibody fragments expressed on the major coat protein of bacteriophage M13.
Antibody fragments have been expressed on the major coat protein of filamentous phage using a gene VIII expression system, but with low copy numbers (averaging 0.2 Fab/phage). As a general strategy to increase copy number, the phage vector was optimized by site directed mutagenesis. One mutation was the introduction of a random six amino acid tether between the heavy chain and pseudo gene VIII to form a phage library. The other mutation was the removal of two cysteine residues which form a disulfide bond between the heavy and light chains. An assay was developed to measure Fab concentrations and used to calculate the average number of copies displayed on phage. Phage libraries containing random tethers were panned, and clones containing a proline rich motif were extracted. Removing the interchain disulfide had a greater effect on copy number and soluble Fab concentrations in the periplasmic space of the bacterial cultures. A tenfold increase in the copy number was achieved using the optimized vector. Incorporation of these vector mutations may be a general strategy for optimizing Fab display on the major coat protein of bacteriophage M13.


Lumbosacral radiculopathy screen. Optimizing the number of muscles studies.
The literature is unclear as to which muscles and how many are required for a sensitive lumbosacral radiculopathy (LSR) screen. A retrospective study of 247 electrodiagnostically confirmed LSRs in 201 patients over a 3-yr period was conducted to determine how many muscles were required to identify a LSR. All LSRs showed abnormal spontaneous activity (positive waves or fibrillation potentials) in two or more muscles innervated by the same nerve root level but different peripheral nerves. All cases were categorized by radiculopathy level, and the most frequently abnormal individual muscles were combined into different muscle screens. The frequency with which each muscle screen identified a radiculopathy was the frequency with which one or more muscles in the screen displayed abnormal spontaneous activity divided by the total number of radiculopathies. The paraspinal muscles (PM) alone identified 88% of LSRs. Without PM, two muscle screens identified only 14-68%, three muscle screens identified 37-89% and four muscle screens identified 45-92%. Including PM, three muscle screens identified 86-94% of LSRs, four muscle screens identified 91-97% and five muscle screens yielded 94-98% identification. Seven to ten muscle screens resulted in minimal improvements in identifying a LSR with 98-99% identification. We conclude that five muscle LSR screens, including PM, are sufficient to identify LSRs while minimizing patient discomfort and examiner time.


Cytogenetics and outcome of allogeneic transplantation in first remission of acute myeloid leukemia: the French pediatric experience.
We analyzed the impact of cytogenetics on 193 children enrolled in two successive French trials (LAME89/91 and ELAM02), who received hematopoietic stem cell transplantation during CR1. Detailed karyotype was available for 66/74 (89%) in LAME89/91 and 118/119 (99%) in ELAM02. Several karyotype and transplant characteristics differed according to therapeutic protocol: unfavorable karyotypes were more frequent in ELAM02 (36% vs 18%), pretransplant chemotherapy included high-dose cytarabine in ELAM02 and not in LAME89/91, IV replaced oral busulfan in the conditioning regimen, methotrexate was removed from post-transplant immunosuppression, and matched unrelated donor and cord blood transplantation were introduced. Five-year overall survival (OS) was 78.2% in LAME89 and 81.4% in ELAM02. OS was significantly lower for the unfavorable cytogenetic risk group in LAME89/91 when compared with intermediate and favorable groups (50% vs 90.6 and 86.4%, P=0.001). This difference was no longer apparent in ELAM02 (80.9% vs 71.3% and 5/5, respectively). Survival improvement for children with unfavorable karyotype was statistically significant (P=0.026) and was due to decrease in relapse risk. Five-year transplantation-related mortality was 6.75% in LAME89/91. In ELAM02, it was 3.2% for patients with a sibling donor and 10.9% with an unrelated donor or cord blood. We conclude that the outcome of children with unfavorable karyotype transplanted in CR1 has improved.


Joint salvage using sandwich technique for giant cell tumors around knee.
The most common site for giant cell tumors (GCT) is knee, where the tumor characteristically extends right up to the subarticular bone plate. Extensive curettage with preservation of the joint should be done wherever possible. The alternatives for filling the void left after curettage are either bone graft or bone cement. Sandwich technique uses the advantages of both, taking care to prevent damage to articular cartilage. This study was done to evaluate the results of sandwich technique in tumors around the knee joint. It was a prospective study of 26 consecutive patients (15 females and 11 males) with Campanacci grade II and grade III GCT around the knee, which qualified the inclusion criterion and underwent knee reconstruction with sandwich technique, after extended curettage of the tumor. The mean age of the patients at the time of surgery was 32.73 ± 11.30 years (range, 18-62 years), and the mean follow-up was 3.87 ± 1.26 years (range, 6.5-2 years). At final follow-up, the functional evaluation was done using Musculoskeletal Tumor Society (MSTS) score and measuring range of motion around the knee. Three patients had recurrence of tumor; in one case, we were able to salvage the joint and repeat sandwich surgery was performed, and in the other two cases, the joint was breached; therefore, we resorted to resection arthrodesis. At final follow-up, the mean functional arc of motion around the knee and the mean MSTS score in patients without arthrodesis was 123.52 ± 10.21 degrees (range, 100-130 degrees) and 27.04/30, respectively; all patients were able to do their activities of daily living with ease. Sandwich technique is a good reconstruction procedure in GCT around knee joint with good survival rate, minimal complications, and good functional outcome.


Incidence and significance of chromosome mosaicism involving an autosomal structural abnormality diagnosed prenatally through amniocentesis: a collaborative study.
Among 179,663 prenatal diagnosis cases collected from ten institutions and two publications, 555 (0.3 per cent) were diagnosed as having chromosome mosaicism. Of these, 57 (10.3 per cent) were mosaic for an autosomal structural abnormality, 28 (5 per cent) for a sex chromosome structural abnormality, and 85 (15.3 per cent) were mosaic for a marker chromosome. Ninety-five cases of prenatally diagnosed mosaicism with a structural abnormality in an autosome and a normal cell line, and with a known phenotypic outcome, were collected for karyotype-phenotype correlations through our collaboration (40 cases), a prior survey (26 cases), and published reports (29 cases). They included 13 balanced reciprocal translocations, one unbalanced reciprocal translocation, four balanced Robertsonian translocations, four unbalanced Robertsonian translocations, four inversions, 17 deletions, three ring chromosomes, 19 i(20q), seven +i(12p), six other isochromosomes, and 17 partial trisomies resulting from a duplication or other rearrangement. All cases mosaic for a balanced structural rearrangement resulted in a normal phenotype. All cases of 46/46,i(20q) resulted in normal liveborns. Five of seven cases with 46/47,+i(12p) had an abnormal phenotype compatible with Killian-Pallister syndrome. The overall risk for an abnormal outcome for a mosaic case with an unbalanced structural abnormality, excluding 46/46,i(20q) and 46/47,+i(12p), is 40.4 per cent. In the same category, the study also suggested a correlation between the percentage of abnormal cells and an abnormal phenotype. For mosaicism involving a terminal deletion, the possibility of a familial fragile site should be considered.


Outcome in prostate cancer: association with endothelial nitric oxide synthase Glu-Asp298 polymorphism at exon 7.
The endothelial cell-specific form of nitric oxide synthases (ecNOS) was mapped at 7q35-q36 and plays an important role in vascular development and tumor growth in human prostate cancer. Bone metastasis, clinical T-stage, tumor grade, and serum prostate-specific antigen (PSA) have been shown to have prognostic importance in the outcome of prostate cancer. The purpose of this study was to evaluate ecNOS polymorphism as a genetic indicator of the outcome of the disease. In this study, we characterized the Glu-Asp298 ecNOS polymorphism in a series of 161 prostate cancer cases. Logistic regression models were used to assess the contribution of these genotypes to prostate cancer progression. For Glu-Asp298 polymorphism, we found that GG genotype was associated to advanced disease [P = 0.020; odds ratio (OR), 2.12; 95% confidence interval (CI), 1.12-4.03] and bone metastasis (P = 0.038; OR, 2.23; 95% CI, 1.03-4.84). Furthermore, after logistic regression analysis with step-wise routine to identify predictive parameters of metastasis, which included age at diagnosis, advanced stage, GG genotype, high grade, and high serum PSA, we observed that Glu-Asp298-GG genotype (P = 0.004; OR, 7.4; 95% CI, 1.87-29.26), high grade tumor (P = 0.009; OR, 6.15; 95% CI, 1.56-24.17), and high serum PSA (P < 0.001; OR, 245.12; 95% CI, 19.93-3013.90) were significantly associated with bone metastasis. This study demonstrates a strong association between Glu-Asp298-GG genotype as a nitric oxide-related genetic factor and advanced disease and bone metastasization. The establishment of a genetic profile for each patient may be useful in the prediction of the outcome of prostate cancer patients.


Effect of pH on complex formation between debranched waxy rice starch and fatty acids.
Complex formations between debranched waxy rice starch (DBS) and fatty acids (FA) of different hydrocarbon chain lengths (8:0, 10:0, 12:0, 14:0, 16:0, and 18:0) were studied in an aqueous solution by measuring the blue colour stained with iodine. The objective of this study was to understand the effects of the solubility and hydrophobicity of guest molecules (FA) on the complex formation with DBS. Lauric acid (12:0) displayed the greatest complex forming ability with DBS by showing the least blue colour developed with iodine. The effect of pH (3-7) on the DBS/FA complex formation was evaluated by measuring the iodine-scanning spectra of the mixture. Short-chain FA (8:0) displayed less complex formation at pH>or=5, above the pK(a) of fatty acid (approximately 4.8), which suggested that the charge formation of the short-chain FA caused a lower partitioning of the FA into the hydrophobic cavity of the DBS single helix. On the contrary, FA of 10:0-18:0 displayed an increased complex formation at pH>5, which could be attributed to increased solubility of these longer-chain FA at a dissociated and ionized form. The hydrocarbon chain length of the FA had an important impact on the extent of the complex formation. A FA that had a shorter hydrocarbon chain was more soluble in an aqueous solution and more readily formed a complex with DBS. At pH 6 and 7 (above the pK(a)), 10:0 formed less inclusion complexes with DBS than did 12:0. Iodine-scanning spectra showed that the absorbances of all iodine-stained DBS/FA solutions at higher wavelength were substantially lower than that of the iodine-stained DBS alone, suggesting that FA preferentially formed inclusion complexes with DBS of longer chains.


Fluid therapy in the neonate: not your mother's fluid space.
Fluid therapy is a universally used therapeutic modality in critical care patients. To effectively deliver fluids to neonates., an understanding of their fluid physiology is necessary. Neonates, as they make the transition from fetal physiology, have increased capillary filtration and a compliant interstitium producing a large ISF reserve. This reserve helps the neonate to adapt to fluid challenges, serving as a ready source of fluids in times of need, but it also frustrates therapeutic fluid administration by damping the effect of intravenous fluid therapy when treating hypovolemia. Additionally,it explains the difficulty neonates have in handling fluid overload. Successful treatment of hypovolemia requires aggressive volume repletion using 20-mL/kg fluid boluses. Once euvolemia is restored and ongoing losses are replaced, maintenance fluid rates should be conservative so as to avoid fluid overload. The neonate's unique sodium handling must also be recognized. Many critical neonates benefit from sodium restriction, whereas others may have high ongoing losses and require careful sodium replacement therapy. Careful attention to fluid therapy formulation ensures positive fluid support without adding to the physiologic stress of the critical neonate.


Studies on malaria during pregnancy in a tribal area of central India (Madhya Pradesh).
In tribal villages of central India where malaria is highly prevalent (mesoendemic), this preliminary study was undertaken to determine the effects of malaria infection in a group of 456 pregnant women with or without fever. Only 96 women were found infected with malaria, of which Plasmodium falciparum accounted for 64% of the detected parasites, while P. vivax for the remaining 36%. There were no instances of cerebral malaria or death however, one abortion and four still births were recorded among 38 primigravid women. Only one neonate was found infected with P. falciparum on day 21 though parasitemia was not high. Anemia was commonly present in most of the women (80%). Failure to clear P. falciparum parasitemia after a chloroquine regimen (25 mg/kg of body weight) was commonly observed. Persistent P. falciparum parasitemia was recorded in 8% cases. Poor response to chloroquine suggests the need to change the drug policy.


Phase II trial of menogaril in patients with previously treated multiple myeloma or chronic lymphocytic leukemia.
Menogaril is a semisynthetic anthracycline with relative lack of cardiotoxicity. Ten patients with multiple myeloma (MM), seven patients with chronic lymphocytic leukemia (CLL), and one patient with diffuse well-differentiated lymphocytic lymphoma (DWDL) were treated with menogaril, 160 mg/m2 (for MM) or 200 mg/m2 (for CLL/DWDL), given as a 2-hour intravenous infusion, repeated every 28 days. All patients except one with CLL had been previously treated with one chemotherapy regimen and had either not responded or had relapsed after a response to prior treatment. There were no objective responses to treatment. Among the six evaluable patients with MM, two had stable disease with subjective improvement in symptoms for five to 25 cycles, and among the eight patients with CLL/DWDL, five patients remained stable for two to eight cycles on treatment. The remainder of the patients had progressive disease after one to two cycles of chemotherapy. Five grade 4 hematologic toxicities were observed. There was one fatal neutropenic sepsis. Menogaril, as administered in this study, does not appear to have significant activity in patients with previously treated MM or CLL.


Carrier-mediated transport of thyroid hormones into rat glial cells in primary culture.
The uptake of 3,3',5-[3'-125I]triiodo-L-thyronine ([125I]L-T3) and of L-[3',5'-125I]thyroxine ([125I]L-T4) by cultured rat glial cells was studied under initial velocity (Vi) conditions. Uptake of both hormones was carrier mediated and obeyed simple Michaelis-Menten kinetics. The following respective values of Km (microM) and Vmax (fmol/min/microgram of DNA) were obtained at 25 degrees C: 0.52 +/- 0.09 and 727 +/- 55 for L-T3 and 1.02 +/- 0.21 and 690 +/- 85 for L-T4. Ki values (microM) for the inhibition of [125I]L-T3 uptake by unlabeled analogues were as follows: L-T4, 0.88; 3,3',5'-triiodo-L-thyronine, 1.4; 3,3'-diiodo-L-thyronine, 2.9; 3,3',5-triiodo-D-thyronine, 4.8; and triiodothyroacetic acid, 5.3. These values indicate that the uptake system is stereospecific. Unlabeled L-T3 was a better competitor than unlabeled L-T4 for the uptake of [125I]L-T4, an observation suggesting that both hormones were taken up by a common carrier system. L-T3, and L-T4 uptake was pH dependent, a finding suggesting that the phenolic unionized form of the hormones was preferentially taken up. L-T3 uptake was studied in the presence of various inhibitors; the results suggest that uptake was independent of the transmembrane Na+ gradient and of the cellular energy. Compounds that inhibited cellular uptake but were without effect on L-T3 binding to isolated nuclei also inhibited L-T3 nuclear binding in intact cells, an observation suggesting that uptake could be rate limiting for the access of L-T3 to nuclear receptors when transport is severely inhibited.


Localizing the rostrolateral prefrontal cortex at the individual level.
The functions of the rostrolateral prefrontal cortex (RLPFC) have recently become the target of multiple theories and empirical investigations. This region can be loosely defined as the lateral portion of Brodmann area (BA) 10. One of the challenges in testing theories about RLPFC functions is the difficulty in defining its boundaries when formulating predictions for its recruitment. Here we present a procedure that goes beyond the currently available anatomical definitions to attempt a functional localization of RLPFC. A combination of functional and anatomical criteria was employed, consistent with other localizer procedures. Functional localization was performed by comparing a relational condition involving relational matching to a control condition involving feature matching. It was expected that within an anatomically defined BA10 region, this procedure would produce functional activations in the lateral but not the medial subregions. The task was administered in the course of a single 13-min fMRI session. Results showed remarkable consistency, with all subjects activating RLPFC and activations consistently localized in the lateral part of BA10. These results demonstrate the practical feasibility of localizing RLPFC using a short procedure and a combination of functional and anatomical criteria. Such localization presents with a number of potential advantages for testing theories of RLPFC functions, including improved anatomical precision of experimental predictions, as well as the possibility of reduction in the rate of false-negative findings across studies. In addition, the results provide further support for the previously proposed functional dissociation between lateral and medial BA10.


Carotid artery intima-media thickness, but not coronary artery calcium, predicts coronary vascular resistance in patients evaluated for coronary artery disease.
There is growing evidence that coronary artery disease (CAD) affects not only the conduit epicardial coronary arteries, but also the microvascular coronary bed. Moreover, coronary microvascular dysfunction (CMVD) often precedes the stage of clinically overt epicardial CAD. Coronary artery calcium (CAC) and carotid intima-media thickness (C-IMT) measured with computed tomography (CT) and ultrasound, respectively, are among the available techniques to non-invasively assess atherosclerotic burden. An increased CAC score and C-IMT have also been associated with CMVD. It is therefore of interest to explore and compare the potential of CAC against C-IMT to predict minimal coronary vascular resistance (CVR). We evaluated 120 patients (mean age 56 ± 9 years, 58 men) without a documented history of CAD in whom obstructive CAD was excluded. All patients underwent C-IMT measurements, CAC scoring, and vasodilator stress (15)O-water positron emission tomography (PET)/CT, during which the coronary flow reserve (CFR) and minimal CVR were analysed. Minimal CVR increased significantly with increasing tertiles of C-IMT (22 ± 6, 27 ± 11, and 28 ± 9 mmHg mL(-1)min(-1) g(-1), P < 0.01), whereas the CFR was comparable across all C-IMT groups (P = 0.50). Minimal CVR increased significantly with an increase in CAC score (23 ± 9, 27 ± 8, 32 ± 10, and 32 ± 7 mmHg mL(-1) min(-1) g(-1), P < 0.01), whereas the CFR did not show a significant decrease with higher CAC scores (P = 0.18). Multivariable regression analysis revealed that C-IMT (P = 0.03), but not CAC, was independently associated with minimal CVR. C-IMT, but not CAC score, independently predicts minimal CVR in patients with multiple cardiovascular risk factors and suspected of CAD.


Mechanotransduction in endothelial responses to shear stress: review of work in Dr. Chien's laboratory.
Shear stresses play an important role in vascular biology in health and disease. While disturbed flows with low shear stresses in the bends and bifurcations of the arterial tree are atherogenic, laminar flows with high shear stresses in the straight part of the vessel is atheroresistant. Thus, elucidation of the mechanotransduction mechanism in vascular endothelial cells in response to shear stress has become an important research topic among bioengineers and vascular biologists. Here is a summary of studies performed in Dr. Shu Chien's laboratory on shear stress-induced signal transduction and gene expression during the period from 1992-1999. These studies, together with efforts from other research groups, demonstrate that integrins, which are transmembrane molecules that interact with both extracellular matrices and intracellular cytoskeleton and kinases in the focal adhesions, are important in mechanotransduction. This hypothesis is mainly supported by the similarity between cellular and molecular events elicited by shear stress and those activated during the integrin-mediated cell attachment to extracellular matrices. Evidence is also provided to show that the dynamic and specific interaction between integrin and extracellular matrices is essential for mechanotransduction.


Analysis of factors involved in determining urinary bladder voiding cycle in urethan-anesthetized rats.
The mechanism(s) involved in determining the voiding cycle of the rat urinary bladder have been investigated in urethan-anesthetized animals. Fluid emission is almost confined to that phase of the voiding cycle which is characterized by the presence of a series of high-frequency oscillations in intraluminal pressure (IPHFO). During this phase the mean urethral flow rate reached a maximum and fluid was expelled in a stream-like fashion. The index obtained by multiplying the amplitude of IPHFO by their duration was significantly related to the maximal value of urethral flow rate. The IPHFO were selectively abolished by administration of d-tubocurarine at a dose that barely affects detrusor contractility. Moreover, d-tubocurarine reduced mean urethral flow rate and increased residual volume. The reflex (hexamethonium sensitive) mechanism(s) responsible for the generation of IPHFO is more developed in male than female rats. This mechanism, which involves activation of skeletal muscle, plays a significant role in determining bladder voiding in this species.


Electron microscopic detection of calcium binding to the duodenal absorptive cell plasma membranes.
Electron dense structures (EDS) were observed on the plasma membranes of duodenal absorptive cells of chicks of various physiological states regarding the calcium binding protein (CaBP). EDS were seen only when calcium was added to formal-glutaraldehyde fixative in cacodylate buffer and the material was post-osmicated in phosphate buffer. Microvillar, lateral and basal plasma membranes showed the EDS and these were seen always in the inner dark layer of the three-layered unit membrane. No EDS were seen in the embryonic material and some were present in material from chicks two days after hatching. There were more in that of 6-week-old normal and vitamin D replete animals. The absorptive cells from chicks, fed on a diet supplemented with cestrum powder, known to mimic the effects of 1,25-dihydroxycholecalciferol, showed the highest number of EDS. On the basis of this distinct correlation of EDS frequency with amounts of CaBP known to be present in chick duodenum, it seems that EDS, precipitated calcium phosphate, strongly suggest the sites of CaBP.


The cochlear nuclei in two patients with Usher syndrome type I.
Does long-term sound deprivation lead to degeneration of the cochlear nuclei in two Usher type I patients? The cochlear nuclei of these patients were morphometrically analyzed and compared with two age-matched controls. Routine autopsy of the brainstems was performed before the design of this study was known. During this procedure, the ventral cochlear nucleus (VCN) can easily be damaged. Five partially damaged VCN could nevertheless be analyzed for this study, including the right VCN of Usher patient 1 and both VCN of Usher patient 2. Using 15 microm thick serial paraffine sections of the cochlear nuclei, estimates of volume, neuronal densities, number of cells and mean cell diameter of the dorsal cochlear nucleus (DCN) and VCN were obtained. This study presents unique material of the cochlear nuclei in two patients with Usher syndrome type I. Data regarding volume and total cell number of the VCN are influenced by the absence of a part of the VCN. Results suggest a decrease in mean cell diameter of the VCN in Usher patients. Other parameters of the VCN and DCN, however, showed no major differences between Usher type I patients and controls. Only minor degenerative changes are apparent in the cochlear nuclei of two patients with Usher type I, who were deprived of acoustic stimuli since birth.


Rate of DNA synthesis in mammalian cells irradiated with ultraviolet light: a model based on the variations in the rate of movement of the replication fork and in the number of active replicons.
A model is proposed to describe the rate of DNA synthesis observed under certain conditions in UV irradiated mammalian cells. It is assumed that shortly after irradiation the rate of DNA synthesis drops mainly as a consequence of the drop in the rate of movement of the replication fork. This in turn, is due to a pause at the dimer for a limited length of time. Later on, a recovery in the rate of DNA synthesis occurs, and it is proposed that one of the parameters contributing to that is an increase in the number of active replicons. This simple model enables one to predict variations in the rate of DNA synthesis as a function both of UV dose and of time after irradiation.


The precision and accuracy of symphysis--fundus distance measurements during pregnancy.
We studied the precision and accuracy of SF measurements. Five trained obstetricians made three measurements of SF on each of 33 patients in the third trimester. The intraobserver variation varied from 0 cm to 8 cm, and comprised on average 1.5 to 2 cm (95th centiles 2.5 to 4 cm). The interobserver variation varied from 1 to 13 cm, and comprised on average 4 cm (95th centile 8 cm). The accuracy of SF measurements was estimated by comparison with ultrasound-guided measurements, which showed a very high precision. Two of the investigators differed significantly, by -1.56 cm and -1.97 cm, from the other 3.


Electrochemical and pulse radiolysis study of misonidazole and its azo and azoxy derivatives.
Pulse radiolysis experiments were carried out on methanolic solutions of misonidazole and its azo and azoxy derivatives in order to obtain the spectra of their radical anions. The rate constants for the reaction of these compounds with es- were 2.5 X 10(10), 2.3 X 10(10) and 1.9 X 10(10) M-1 s-1 respectively. The electrochemical properties of the compounds were studied with the aim of producing their radical anions by electrolysis in aprotic medium (DMF, 0.1 M TEAP ). The potentials at cathodic peaks were -1.05, -1.10 and -1.18 V for misonidazole, azo and azoxy derivatives, respectively. The decay of the radical anion of misonidazole, which produces nitrite ions, was studied in particular, the corresponding rate constant being 2.8 X 10(-4) s-1. The possibility of using electrochemistry in the study of these transient species is discussed.


Soluble CD30 and CD23 in cord blood are not related to atopy in early childhood.
Atopic disease, including atopic dermatitis (AD), is associated with a T-helper 2 (Th2)-dependent immune response. The cytokine receptor CD30 appears to be preferentially expressed on, and its soluble form (sCD30) released by, Th2 cells. Therefore, sCD30 may be a potential marker for atopic disorders. The aim of this study was to test the hypothesis that the sCD30 level in cord blood could be used to predict the development of atopy or AD in early childhood. In a case-control study, levels of sCD30, as well as soluble low-affinity immunoglobulin E (IgE) receptor (sCD23), interleukin-4 (IL-4) and IgE, were measured in cord blood in 35 children who subsequently developed allergic sensitization and AD before the age of three, and the results were compared to those of 35 matched children without a history of atopy. There was no difference in cord blood levels of sCD30 between controls (32.5 U/ml; 19.7-80.1) and children with subsequent atopy and AD (32.2 U/ml; 22-75.9) (median; quartiles). The concentration of sCD30 showed no relation to the levels of total IgE, sCD23 or IL-4. Levels of sCD23 were similar in children with subsequent atopy (60.2 U/ml; 44.5-76.8) and controls (55.2 U/ml; 38.3-72.5), whereas IL-4 was detectable in 10 of the atopic children and in only two of the controls (p <0.05). In conclusion, cord blood levels of sCD30 or sCD23 do not seem to be related to the subsequent development of atopy or AD at the age of three.


An advanced algorithm for dispersion encoded full range frequency domain optical coherence tomography.
Dispersion encoded full range (DEFR) optical coherence tomography (OCT) has become highly attractive as it is a simple way to increase the measurement range of OCT systems. Full range OCT is especially favorable as it does not only increase the measurement range but also shifts the highest sensitivity into the center of the measurement range. While the early versions of DEFR were highly computational expensive, new versions reduce the number of necessary Fourier transforms. Recently it has been shown that a GPU based algorithm can perform DEFR with more than 20,000 A-lines per second. We present a new version of the DEFR algorithm that requires only one Fourier transform per A-scan and uses convolution in z-space instead of multiplication in k-space, therefore reducing the computational effort considerably. While dispersion encoding has so far only been used to suppress mirror artifacts, we show that, with dispersion encoding and only one more Fourier transform, autocorrelation terms can be removed likewise. Since very high values of dispersion reduce the effective measurement range in dispersion encoded OCT, we present an estimate for a sufficient amount of dispersion for a successful image recovery, which is depending on the thickness of the scattering layers. Furthermore, we demonstrate the usability of ZnSe as a new dispersive material with a very high dispersion and describe a simple method to extract the dispersive phase from the measurement of a single reflex of a glass surface. Using a standard consumer PC, an artifact-free recovery of 1000 - 2000 A-scans per second with 2048 depth values including autocorrelation removal was achieved. The dynamic range (sensitivity) is not reduced and the suppression ratio of mirror artifacts and autocorrelation signals is more than 50dB using ZnSe.


Human beta-defensin-1, a potential chromosome 8p tumor suppressor: control of transcription and induction of apoptosis in renal cell carcinoma.
Human beta-defensin-1 (hBD-1) is a candidate tumor suppressor gene located on chromosome 8p23. Previously, we showed that cancer-specific loss of hBD-1 was found in 90% of renal clear cell carcinomas and in 82% of prostate cancers. To investigate the possible mechanisms of decreased gene expression and determine the function of hBD-1 protein in urological cancers, we sequenced hBD-1 gene coding regions in prostatic and renal cancer samples. We then analyzed the frequency distribution of promoter polymorphisms and determined the effect of these base changes on transcriptional activity of the hBD-1 promoter. A polymorphism at -688 bases upstream of the ATG start codon affects hBD-1 promoter activity, leading to a rate of reporter gene transcription that is 40% to 50% lower than the wild-type sequence when tested in either DU145 or TSU-Pr1 cell lines. In addition, a polymorphism at -44 bases was shown to enhance transcription up to 2.3 times more than the wild-type sequence in the same cell lines. In addition, three novel hBD-1 promoter mutations were found in renal and prostate cancer clinical samples. An iso-5-aza-2'-deoxycytidine treatment was effective in transcription up-regulation in DU145, suggesting a possible upstream methylation-dependent effect. Synthetic hBD-1 peptide inhibited bladder cancer cell TSU-Pr1 proliferation. Overexpression of the hBD-1 gene in renal cancer cells SW156 resulted in caspase-3-mediated apoptosis. These data support the hypothesis that hBD-1 is a potential tumor suppressor gene for urological cancers. Promoter point mutations may be responsible for cancer-specific loss of hDB-1 expression.


Adsorption thermodynamics of acidic proline-rich human salivary proteins onto calcium apatites.
The thermodynamics of adsorption of four acidic proline-rich salivary proteins from their aqueous solutions onto hydroxyapatite (HA) and fluorapatite (FA) have been analyzed. Enthalpies and entropies of adsorption were derived from isotherms at 37 degrees C and 4 degrees C and led to the unexpected conclusion that adsorption of the macromolecules studied is an endothermic process. Consequently, adsorption is driven by an increase in entropy. Most of this increase originates in the adsorbate molecules, probably through disruption of internal ion pairs, hydrogen bonds, and displacement of water molecules. Integral free energies of adsorption (delta G) and the partial contributions of adsorbent and adsorbate were both calculated as a function of the adsorption coverages. For equal coverages (of each adsorbate), delta G is lower with FA than with HA. Most of the contribution to delta G originates from the adsorbate, although the adsorbent contribution becomes significant as adsorption saturation is approached. The differences in the various thermodynamic quantities are qualitatively related to the known structural features of the four proteins. The results are important in understanding the role played by the proline-rich proteins in the oral environment.


[Cognitive impairments as a universal clinical syndrome in a therapist's practice].
The problem of cognitive dysfunctions in patients with somatic diseases occupies a prominent place now since they are one of the most common manifestations of organic brain lesions. The early detection of potentially cured cognitive impairments is one of the important tasks of a present-day therapist, cardiologist, endocrinologist, and family doctor as the patients with early-stage cognitive impairments constitute the majority of those who have sought medical advice. In the modern world, primary health care physicians' actions are decisive in predicting the development of dementia since the detection of early non-dementia forms of cognitive impairments and neuroprotective therapy with mexidol in particular are frequently quite sufficient to considerably reduce the degree of the impairments and to improve the prognosis of dementia.


The effects of reduced glutathione and cysteine on prostaglandin synthesis in rabbit kidney medulla slices.
The effects of GSH and cysteine on the generation of medullary prostaglandins E2 and F2 alpha were examined. The formation of prostaglandin E2 was enhanced by GSH, but was reduced by cysteine in a dose-related manner. GSH inhibited prostaglandin F2 alpha production, while cysteine stimulated it. These results suggest that GSH and cysteine have contrary effects on prostaglandins E2 and F2 alpha synthesis by affecting endoperoxide E2 isomerase or endoperoxide reductase.


Sevelamer is cost-saving vs. calcium carbonate in non-dialysis-dependent CKD patients in italy: a patient-level cost-effectiveness analysis of the INDEPENDENT study.
To conduct a cost-effectiveness analysis of sevelamer versus calcium carbonate in patients with non-dialysis-dependent CKD (NDD-CKD) from the Italian NHS perspective using patient-level data from the INDEPENDENT-CKD study. Patient-level data on all-cause mortality, dialysis inception and phosphate binder dose were obtained for all 107 sevelamer and 105 calcium carbonate patients from the INDEPENDENT-CKD study. Hospitalization and frequency of dialysis data were collected post hoc for all patients via a retrospective chart review. Phosphate binder, hospitalization, and dialysis costs were expressed in 2012 euros using hospital pharmacy, Italian diagnosis-related group and ambulatory tariffs, respectively. Total life years (LYs) and costs per treatment group were calculated for the 3-year period of the study. Bootstrapping was used to estimate confidence intervals around outcomes, costs, and cost-effectiveness and to calculate the cost-effectiveness acceptability curve. A subgroup analysis of patients who did not initiate dialysis during the INDEPENDENT-CKD study was also conducted. Sevelamer was associated with 0.06 additional LYs (95% CI -0.04 to 0.16) and cost savings of EUR -5,615 (95% CI -10,066 to -1,164) per patient compared with calcium carbonate. On the basis of the bootstrap analysis, sevelamer was dominant compared to calcium carbonate in 87.1% of 10,000 bootstrap replicates. Similar results were observed in the subgroup analysis. RESULTS were driven by a significant reduction in all-cause mortality and significantly fewer hospitalizations in the sevelamer group, which offset the higher acquisition cost for sevelamer. Sevelamer provides more LYs and is less costly than calcium carbonate in patients with NDD-CKD in Italy.


The two Bernard Berenson cousins: The interplay among immigration, culture, and narcissism.
The lives of two 19th century cousins, both of whom changed their names to Bernard Berenson, are considered from historical and psychodynamic perspectives, using a psychobiographical method. The Jewish cousins immigrated separately to Boston from Lithuania in 1875 and 1882. One cousin, later calling himself simply B.B., became a world-renowned art historian. The other Bernard became a misanthrope after feeling deeply humiliated by his cousin's family in Boston. Many biographies were written about the famous B.B. The only histories of his cousin Bernard were family stories, as he was the author's great-grandfather. The intersecting lives of these cousins are discussed. Both men faced the challenges of immigration as well as intense anti-Semitism and prejudice in each country in which they lived. These cultural and historical conditions interacted with the cousins' narcissistic vulnerabilities. Their lives demonstrate different manifestations of narcissistic suffering, with B.B's being more consistent with the construct of a "grandiose narcissist" and Bernard's being more consistent with that of a "closet narcissist." The life stories of these two cousins with the same name offers an intriguing instance of a complicated relationship among immigration, prejudice, and narcissism and case examples of the manifestation of how narcissistic suffering can influence lives.


Effects of selective cholecystokinin antagonists L364,718 and L365,260 on food intake in rats.
The selective type A and B cholecystokinin (CCK) receptor antagonists L364,718 and L365,260 were used to identify the receptor subtype that mediates the satiety effect of endogenous CCK. Male rats (n = 12-13/group), fed ground rat chow ad lib, received L364,718 (0, 1, 10, 100, or 1000 micrograms/kg IP) or L365,260 (0, 0.1, 1, 10, 100, 1000, or 10,000 micrograms/kg IP) 2 h after lights off, and food intake was measured 1.5, 3.5, and 5.5 h later. L364,718 significantly stimulated 1.5-h food intake by more than 40% at 10 micrograms/kg and higher doses; cumulative intake at 3.5 and 5.5 h remained elevated by about 20% at 1000 and 100 micrograms/kg of L364,718, respectively. In contrast, L365,260 had no significant stimulatory effect on feeding at any dose. The potency of L365,260 for antagonizing gastrin-stimulated gastric acid secretion was examined in unanesthetized rats. Male rats (n = 14), prepared with gastric and jugular vein cannulas, received doubling doses of gastrin (G-171) (0.16-5 nmol/kg/h IV), each dose for 30 min, and gastric juice was collected for each 30-min period. G-171 stimulated gastric acid output dose dependently; the minimal effective dose was 0.16 nmol/kg/h, while maximal output (5-fold above basal) occurred at 5 nmol/kg/h. L365,260 (0, 1, 10, 100, 1000, or 10,000 micrograms/kg IV), administered 30 min before continuous infusion of G-171 (1.25 or 5 nmol/kg/h), significantly inhibited acid output only at 10,000 micrograms/kg; cumulative 60-min output was decreased by 60%. These results suggest that CCK acts at CCK-A receptors to produce satiety during the dark period in ad lib-feeding rats.


"Turn-on" fluorescent sensor for Hg2+ based on single-stranded DNA functionalized Mn:CdS/ZnS quantum dots and gold nanoparticles by time-gated mode.
An ultrasensitive "turn-on" fluorescent sensor was presented for determination of Hg(2+). This method is mainly based on Hg(2+)-induced conformational change of a thymine-rich single-stranded DNA. The water-soluble long-lifetime fluorescence quantum dot (Mn:CdS/ZnS) acted as the fluorophore, which was labeled on a 33-mer thymine-rich single-stranded DNA (strand A). The gold nanoparticles (GNPs) functionalized 10-mer single-stranded DNA (strand B) is selected as the quencher to quench the fluorescence of Mn:CdS/ZnS. Without Hg(2+) in the sample solution, strands A and B could form hybrid structures, resulting in the fluorescence of Mn:CdS/ZnS being decreased sharply. When Hg(2+) is present in the sample solution, Hg(2+)-mediated base pairs induced the folding of strand A into a hairpin structure, leading to the release of GNPs-tagged strand B from the hybrid structures. The fluorescence signal is then increased obviously compared with that without Hg(2+). The sensor exhibits two linear response ranges between fluorescence intensity and Hg(2+) concentration. Meanwhile, a detection limit of 0.18 nM is estimated based on 3α/slope. Selectivity experiments reveal that the fluorescent sensor is specific for Hg(2+) even with interference by high concentrations of other metal ions. This sensor is successfully applied to determination of Hg(2+) in tap water and lake water samples. This sensor offers additional advantage to efficiently reduce background noise using long-lifetime fluorescence quantum dots by a time-gated mode. With excellent sensitivity and selectivity, this sensor is potentially suitable for monitoring of Hg(2+) in environmental applications.


Generation of capsule-deficient Neisseria meningitidis strains by homologous recombination.
Capsule-deficient mutants of Neisseria meningitidis serogroup B strain B1940 were constructed by allelic replacement using the plasmids pMF120 and pMF121, which contain the flanking regions of the gene locus for the biosynthesis pathway of the group B meningococcal capsular polysaccharide. Southern blot analysis of chromosomal DNA of the capsule-deficient meningococcal strains confirmed the generation of large deletions in the chromosomal cps gene complex. The same strategy proved useful in constructing meningococcal strains with capsular types A, C, W135, Y and Z.


Serum levels of platelet endothelial cell adhesion molecule-1 (PECAM-1) and soluble vascular endothelial growth factor receptor (sVEGFR)-1 and -2 in HIV associated preeclampsia.
The angiogenic-antiangiogenic imbalance evident in preeclampsia (PE) may be used as a predictive tool to identify women likely to develop the clinical features in early pregnancy. This retrospective study examined normotensive pregnant (n = 38) and preeclamptic (n = 38) HIV-infected and uninfected women to quantify sVEGFR-1 and -2 and PECAM-1 levels. In contrast to PECAM-1, sVEGFR-1 and -2 differed according to pregnancy type (p = 0.07; p = 0.001; p = 0.002) but not by HIV status (p = 0.68; p = 0.13; p = 0.43). Irrespective of the HIV status, we report an upregulation of sVEGFR-1 with concomitant decline of PECAM-1 and sVEGFR-2 levels in PE compared to normotensive pregnancies.


[The diagnosis of myocardial fatty dystrophy in putrefaction-altered cadaveric material (biochemical and histological studies)].
The biochemical method of lipid level assessment by their hexane extraction permits a judgement on the presence of obesity (fatty dystrophy) in the myocardium in drastic putrefactive changes in the corpse, when other methods are useless. Use of this method in cases with putrefactive changes will help in many cases to decide the problem on the possible 'cardiac' mechanism of death.