The deletion variant of nicotinamide nucleotide transhydrogenase (Nnt) does not affect insulin secretion or glucose tolerance.
The C57BL/6J (B6J) strain is the most widely used mouse strain in metabolic research. B6J mice produce a truncated form of nicotinamide nucleotide transhydrogenase (NNT), an enzyme that pumps protons across the inner mitochondrial membrane. It has been proposed that this results in B6J mice having reduced insulin secretion and glucose intolerance compared with other strains of mice (e.g. C3H/HeH and DBA/2) that have a full-length NNT. The aim of this study was to determine whether truncated NNT was associated with reduced insulin secretion and glucose intolerance, comparing B6 substrains that differ in having a truncated NNT. C57BL/6N (B6N) mice have wild-type Nnt. We compared Nnt expression and activity levels as well as in vivo insulin secretion and glucose tolerance between these mice and B6J. Body weights and specific fat-pad depot masses were alike and Nnt expression and activity levels were similar between B6N and B6J mice. Glucose-mediated insulin secretion and insulin sensitivity were comparable between the two groups of mice, as were plasma glucose and insulin levels during the oral glucose tolerance test. The presence of a truncated Nnt did not affect insulin secretion or glucose tolerance on the C57BL/6 background. We suggest that low or normal levels of NNT (regardless of truncation) have little effect on insulin secretion. Rather, it is the increase in expression of Nnt that regulates and enhances insulin secretion. Our data confirm that B6J is a reasonable control strain for diabetes research; this is especially important considering that it is the strain commonly used to generate genetically modified animals.


Endothelial cell heterogeneity and organ specificity.
Endothelial cells consist of a heterogeneous population covering the entire inner surface of blood vessels. This review will focus on the factors influencing this heterogeneity including: (1) morphological and functional differences between large and small vessels and between cells derived from various microvascular endothelial beds; (2) the microenvironment and extracellular matrix modulating the phenotype; (3) different response to growth factors; (4) organ specificity reflecting the cumulative expression of post-translation modifications and also the expression of unique genes under the control of organ-specific regulatory elements; and (5) pathological conditions, such as tumor growth, which is accompanied by the development of a characteristic tumor vasculature and tumors formed by endothelial cells.


Neurological and neuroradiological examination of chronic cannabis smokers.
Twelve subjects, eight male and four female, who had smoked on average more than 1 gm of cannabis daily for 10 years, were investigated with a clinical neurological examination and computed tomography (CT) of the brain. No subject had a history of major head trauma or cerebral infection, and just one abused alcohol. Only the subject with a history of alcoholism showed any abnormal cerebral function on clinical tests or any abnormality in the CT scan, compared with normal controls.


Variation in specialty care hospitalization for children with chronic conditions in California.
Despite the documented utility of regionalized systems of pediatric specialty care, little is known about the actual use of such systems in total populations of chronically ill children. The objective of this study was to evaluate variations and trends in regional patterns of specialty care hospitalization for children with chronic illness in California. Using California's Office of Statewide Health Planning and Development unmasked discharge data set between 1999 and 2007, we performed a retrospective, total-population analysis of variations in specialty care hospitalization for children with chronic illness in California. The main outcome measure was the use of pediatric specialty care centers for hospitalization of children with a chronic condition in California. Analysis of 2 170 102 pediatric discharges revealed that 41% had a chronic condition, and 44% of these were discharged from specialty care centers. Specialty care hospitalization varied by county and type of condition. Multivariate analyses associated increased specialty care center use with public insurance and high pediatric specialty care bed supply. Decreased use of regionalized care was seen for adolescent patients, black, non-Hispanic children, and children who resided in zip codes of low income or were located farther from a regional center of care. Significant variation exists in specialty care hospitalization among chronically ill children in California. These findings suggest a need for greater scrutiny of clinical practices and child health policies that shape patterns of hospitalization of children with serious chronic disease.


Volunteer bias in research employing vaginal measures of sexual arousal.
Demographic, sexual, and personality characteristics of volunteers and nonvolunteers for a laboratory study of sexual arousal were compared. Subjects were 296 female students from an introductory psychology course who had volunteered for a study on sexuality and personality. After completing several questionnaires, subjects were presented with a written description of an experiment that involved viewing sexually explicit videotapes and measurement of sexual arousal with a vaginal photoplethysmograph and indicated in writing whether or not they would be interested in participating in the experiment. Chi-square analyses revealed that a greater percentage of volunteers had experienced sexual trauma and that fewer women in this group reported objections to viewing sexually explicit films than nonvolunteers. A discriminant function analysis revealed that the volunteers masturbated more frequently, had more exposure to commercialized erotica materials, were exposed to these materials at an earlier age, and reported less sexual fear than nonvolunteers. Other personality, demographic, and sexual characteristics did not differ across the groups. This study demonstrates that the external validity of studies employing vaginal measures of sexual arousal is limited. Researchers must use caution when discussing the generality of findings based on genital measurement of sexual arousal.


Relationship between external anal sphincter atrophy at endoanal magnetic resonance imaging and clinical, functional, and anatomic characteristics in patients with fecal incontinence.
External anal sphincter atrophy at endoanal magnetic resonance imaging has been associated with poor outcome of anal sphincter repair. We studied the relationship between external anal sphincter atrophy on endoanal magnetic resonance imaging and clinical, functional, and anatomic characteristics in patients with fecal incontinence. In 200 patients (mean Vaizey score, 18 (+/-2.9 standard deviation)) magnetic resonance images were evaluated for external anal sphincter atrophy (none, mild, or severe) by radiologists blinded to anorectal functional test results and details from medical history. Subgroups of patients with and without atrophy were compared for medical history, anal manometry, pudendal nerve latency testing, anal sensitivity testing, external anal sphincter thickness, and external anal sphincter defects. Whenever significant differences were detected, we tested for differences between patients with mild and severe atrophy. External anal sphincter atrophy was demonstrated in 123 patients (62 percent): graded as mild in 79 (40 percent), and severe in 44 patients (22 percent). Patients with atrophy were more often female (P < 0.001) and older (P = 0.003). They had a lower maximal squeeze (P = 0.01) and squeeze increment pressure (P < 0.001). Patients with severe atrophy had a lower maximal squeeze (P = 0.003) and squeeze increment pressure (P < 0.001) than patients with mild atrophy. These effects were not attenuated by potential confounding variables. Patients with atrophy could not be identified a priori by other characteristics. External anal sphincter atrophy at endoanal magnetic resonance imaging was depicted in 62 percent of patients, varying from mild to severe. Because increasing levels of atrophy were associated with impaired squeeze function, further studies are needed to evaluate whether grading atrophy is clinically valuable in selecting patients for anal sphincter repair.


DNA methylation alterations in urothelial carcinoma.
In urothelial cancer, hypermethylation of specific genes and genome-wide hypomethylation, reflected in decreased methylation of LINE-1 retrotransposons, have both been reported, but were never investigated in the same specimens. We analyzed hypermethylation of six genes by methylation-specific PCR and LINE-1 hypomethylation by Southern blotting in 96 carcinoma tissues. Hypermethylation frequencies were: SFRP1 (55%), APC (45%), RASSF1A (35%), DAPK1 (29%), RARB2 (19%), and CDKN2A (2%). Three groups of cancers could be discerned, with escalating hypermethylation. Hypermethylation increased with tumor stage, particularly at the transition to invasive cancers, and RARB2 hypermethylation was indicative of lymph node involvement. A comparison to a previous study on prostate cancer using the same techniques suggests that hypermethylation in urothelial carcinoma occurs in a random rather than coordinated manner. LINE-1 hypomethylation was present in 90% of specimens, largely independent of hypermethylation. Lack of hypomethylation indicated a significantly better clinical prognosis. Bisulfite sequencing of SFRP1 demonstrated dense or patchy hypermethylation in tumor tissues that likely accounts for discrepant reported frequencies. In urothelial carcinoma cell lines, the same genes as in tissues were frequently hypermethylated. SFRP1 hypermethylation was concordant with lack of expression. 5-Aza-deoxycytidine induced its reexpression in some lines, whereas additional treatment with a histone deacetylase inhibitor was required in others. Thus, epigenetic SFRP1 inactivation occurs in a graduated manner. In conclusion, markers of genome-wide hypomethylation seem optimally suited for urothelial carcinoma detection, whereas combinations of hypermethylation and hypomethylation assays hold promise for classification.


Inhibitory effect of tumor necrosis factor α on gluconeogenesis in perfused rat liver.
Tumor necrosis factor α (TNFα) is a cytokine involved in many metabolic responses in both normal and pathological states. Considering that the effects of TNFα on hepatic gluconeogenesis are inconclusive, we investigated the influence of this cytokine in gluconeogenesis from various glucose precursors. TNFα (10 μg/kg) was intravenously injected in rats; 6 h later, gluconeogenesis from alanine, lactate, glutamine, glycerol, and several related metabolic parameters were evaluated in situ perfused liver. TNFα reduced the hepatic glucose production (p < 0.001), increased the pyruvate production (p < 0.01), and had no effect on the lactate and urea production from alanine. TNFα also reduced the glucose production (p < 0.01), but had no effect on the pyruvate production from lactate. In addition, TNFα did not alter the hepatic glucose production from glutamine nor from glycerol. It can be concluded that the TNFα inhibited hepatic gluconeogenesis from alanine and lactate, which enter in gluconeogenic pathway before the pyruvate carboxylase step, but not from glutamine and glycerol, which enter in this pathway after the pyruvate carboxylase step, suggesting an important role of this metabolic step in the changes mediated by TNFα.


Validity of the Hospital Anxiety and Depression Scale and Patient Health Questionnaire-9 to screen for depression in patients with coronary artery disease.
Depression is common but frequently undetected in patients with coronary artery disease (CAD). Self-report screening instruments for assessing depression such as the Hospital Anxiety and Depression Scale (HADS) and the Patient Health Questionnaire-9 (PHQ-9) are available but their validity is typically determined in depressed patients without comorbid somatic illness. We investigated the validity of these instruments relative to a referent diagnostic standard in recently hospitalized patients with CAD. Three months post-discharge for a cardiac admission, 193 CAD patients completed the HADS and PHQ-9. The Mini International Neuropsychiatric Interview (MINI) was the criterion standard. Scale reliability was calculated using Cronbach's alpha. Convergent validity was computed using Pearson's intercorrelations. Sensitivity and specificity for various cut-off scores for both measures and for the PHQ-9 categorical algorithm were calculated using receiver operating characteristics (ROC). For analyses, participants were assigned to two groups, 'major depressive disorder' or 'any depressive disorder'. For all calculations, alpha was 0.05 and tests were two-tailed. Internal consistencies for the two measures were excellent. Criterion validity for the PHQ-9 and HADS was good. We found no statistical differences between the PHQ-9 and HADS for detecting either group; however, the categorical algorithm of the PHQ-9 for diagnosing major depression had a superior LR+ when compared with the summed HADS or PHQ-9. The operating characteristics of the screening instruments for 'any depressive disorder' were slightly lower than for 'major depressive disorder'. Some optimum cut-off scores were lower than the generally recommended cut-off scores, particularly when screening for major depression (e.g., > or = 5/6 vs. > or = 10 and > or = 8 for PHQ-9 and HADS, respectively). Lowering the cut off scores substantially improved the sensitivity of these instruments while retaining specificity, thereby improving their usefulness to screen for CAD patients with depression. Both instruments have acceptable properties for detecting depression in recently hospitalized cardiac patients, and neither scale is statistically superior when summed scores are used. The categorical algorithm of the PHQ-9 for diagnosing major depression has a superior LR+ compared to the summed PHQ-9 and HADS scores. Use of the generally recommended cut-off scores should be cautious. In light of the aversive outcomes associated with depression in CAD, screening for depression is a clinical priority.


Human papillomavirus genotype distribution in low-grade squamous intraepithelial lesions in France and comparison with CIN2/3 and invasive cervical cancer: the EDiTH III study.
In the present study (EDiTH III study), the genotype-specific prevalence of HPV in low-grade squamous intraepithelial lesions (LSIL) was estimated to predict the potential benefit of HPV vaccination in France. This prevalence was compared to that previously reported in France in high-grade cervical intraepithelial neoplasia (CIN2/3, EDiTH II study) and squamous cell carcinoma (SCC, EDiTH I study) to identify the genotypes preferentially associated with a progression to malignancy. 397 smears with LSIL diagnosis (Preservcyt) were retrospectively collected in different centres in France and genotyped using the INNO-LiPA assay allowing the detection of 24 HPV genotypes. HPV was found in 98% of cases. The most prevalent genotypes in LSIL in France were HPV 66 (25%), HPV 16 (21%), HPV 53 (18%), 51 (17%) and 52 (14%). HPV 16 and/or 18 were present in 28% and HPV 6, 11, 16 and/or 18 in 33% of LSIL. The highest SCC/LSIL prevalence ratios were shown for HPV 16, 33 and 18. With a 95% vaccine efficacy on CIN1 and theoretical vaccine coverage of 100%, HPV vaccination might prevent 27% (with a 16, 18 bivalent vaccine) and up to 32% (with a 6, 11, 16, 18 quadrivalent vaccine) of LSIL cases in France. In this study, LSIL related to HPV 16, 18 or 33 are at highest risk of progression to malignancy and thus could require a stringent surveillance. Conversely, anxiety and over-treatment could be avoided in women with low risk of progression.


Starnes procedure in a neonate with pulmonary atresia and intact ventricular septum.
We describe the case of 7-day-old neonate with pulmonary atresia, intact ventricular septum, and severe tricuspid valve (TV) dysplasia who underwent a Starnes right ventricular exclusion procedure (RVEP). The patient had severe tricuspid stenosis and regurgitation and right ventricular dysfunction after perforation and balloon dilation of the pulmonary valve.


Calcium-independent inhibition of GABA(A) current by caffeine in hippocampal slices.
Although inhibitory postsynaptic currents (IPSCs) mediated by GABA(A) receptor is thought to be affected by intracellular calcium ion concentration ([Ca2+]i), origin or route of [Ca2+]i increment has not been well elucidated. Reports on the effect of [Ca2+]i elevation on GABA(A)ergic IPSCs per se are also controversial. In this study, effects of caffeine and several other [Ca2+]i-mobilizing drugs were examined on the IPSCs in acute slices of rat hippocampus. Using the patch clamp recording method, spontaneous and evoked currents were recorded from CA3 neurons. Caffeine strongly inhibited both extra-synaptic and synaptic GABAergic IPSCs, regardless of the presence or absence of extracellular Ca2+. This inhibition was not relieved by the intracellular application of EGTA or 1,2-bis(2-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (BAPTA). This inhibition by caffeine was not prevented by preequilibration with caffeine. Ca2+ store depletion caused by thapsigargin or repetitive stimulation by caffeine could not prevent the inhibition. Moreover, ruthenium red and ryanodine could not overcome the inhibition. On the contrary, GABA(A)ergic currents were not inhibited by stimulation with several Ca2+-mobilizing agonists. Forskolin could not mimic the effect of caffeine on the IPSC, and caffeine inhibited the IPSC in the presence of adenosine. These results suggest that intracellular Ca2+ mobilization through ryanodine-sensitive store stimulation does not significantly affect GABAergic IPSCs, and most of the inhibitory effect of caffeine is independent of [Ca2+]i elevation under the present experimental conditions.


pH-dependent bilayer destabilization and fusion of phospholipidic large unilamellar vesicles induced by diphtheria toxin and its fragments A and B.
The passage by the low endosomal pH is believed to be an essential step of the diphtheria toxin (DT) intoxication process in vivo. Several studies have suggested that this low pH triggers the insertion of DT into the membrane. We demonstrate here that its insertion into large unilamellar vesicles (LUV) is accompanied by a strong destabilization of the vesicles at low pH. The destabilization has been studied by following the release of a fluorescent dye (calcein) encapsulated in the liposomes. The influence of the lipid composition upon this process has been examined. At a given pH, the calcein release is always faster for a negatively charged (asolectin) than for a zwitterionic (egg PC) system. Moreover, the transition pH, which is the pH at which the toxin-induced release becomes significant, is shifted upward for the asolectin LUV as compared to the egg PC LUV. No calcein release is observed for rigid phospholipid vesicles (DPPC and DPPC/DPPA 9/1 mol/mol) below their transition temperature whereas DT induces an important release of the dye in the temperature range corresponding to the phase transition. The transition pH associated to the calcein release from egg PC vesicles is identical with that corresponding to the exposure of the DT hydrophobic domains, as revealed here by the binding of a hydrophobic probe (ANS) to the toxin. This suggests the involvement of these domains in the destabilization process. Both A and B fragments destabilize asolectin and PC vesicles in a pH-dependent manner but to a lesser extent than the entire toxin.(ABSTRACT TRUNCATED AT 250 WORDS)


Clinical course in insulin-dependent diabetics undergoing hemodialysis.
Nephropathy continues to be the most serious complication in type I-diabetics. When we started chronic hemodialysis in these patients 15 years ago survival figures were poor. Later on the survival rate for diabetics undergoing hemodialysis has improved progressively. The aim of this report was to present our own experience in hemodialysis treatment of insulin-dependent diabetics. The cumulative survival rate of 46 insulin-dependent diabetics undergoing hemodialysis has increased progressively and now amounts to 70% after one year, and 50% after two years of treatment. At the same time we could attain a certain improvement of metabolic control. Nutrition has also been improved, as indicated by increased transferrin (p less than 0.05) and stable serum protein levels. Systolic blood pressure control became better (p less than 0.05) but, a fluid overload was still present. Here, further improvements are necessary to increase the survival rate. Therefore, the survival of diabetic patients with hemodialysis may be approaching that of non-diabetics. In some patients retinopathy was improved after one year of treatment. Despite a better prognosis for survival in diabetics treated by chronic hemodialysis we suggest that the successful renal transplantation should be the treatment of choice in patients suffering from diabetic nephropathy. In general, hemodialysis and renal transplantation should be started earlier than hitherto, i.e. already at creatinine levels of about 600 mumol/l, and at urea levels of 30 mmol/l. Strict metabolic and blood pressure control, as well as early laser coagulation therapy of retinopathy should be instituted for patients with creatine levels above 200 mumol/l, in close cooperation of a diabetologist, nephrologist, and ophthalmologist. This will be our future therapeutic strategy for these patients.


The Femtochemistry of a Ferracyclobutadiene.
The eminent role of metallacyclobutadienes as catalytic intermediates in organic synthesis and polymer chemistry is widely acknowledged. In contrast, their photochemistry is as yet entirely unexplored. Herein, the photo-induced primary processes of a ferracyclobutadiene tricarbonyl complex in solution are revealed by femtosecond mid-infrared spectroscopy. The time-resolved vibrational spectra expose an ultrafast substitution of a basal CO ligand by a solvent molecule in a consecutive dissociation-association mechanism. Following optical excitation, the system relaxes non-radiatively to the triplet ground state from which a CO is expelled. Since the triplet state is bound with respect to Fe-CO cleavage, the dissociation can only occur from vibrationally excited states. The excitation energy, vibrational relaxation, and intersystem crossing to the singlet ground state control the primary quantum yield for formation of the ferracyclic dicarbonyl-solvent product complex.


Safety stitch: a modification to postoperatively adjustable suture strabismus surgery of the inferior rectus muscle.
To introduce a variation of adjustable suture recession surgery of the inferior rectus muscle by adding a non- absorbable "safety stitch" to reduce post surgery overcorrection. Eleven patients with vertical strabismus who needed inferior rectus recession were the subjects of this study. The vertical deviation was measured preoperatively, 24 hours after the adjustment, and after a minimum of a year followup. An adjustable suture technique through a limbal incision with a silicon sheet was used. We added a non-absorbable suture in the medial edge of the tendon of the inferior rectus muscle and fixed it at the scleral insertion of the muscle. This area of the inferior rectus tendon was exposed for the adjustment, which was performed 24-48 hours after the surgery. The safety suture was then fastened with a knot and 4-6 prism diopters (pd) of undercorrection in down gaze was intentionally left. The average preoperative vertical deviation was 17 prism diopters (pd) in primary position, and 21.6 pd in down gaze. Six of the eleven patients were adjusted postop' leaving an average residual vertical deviation of 2 pd in primary position and 4.7 pd in down gaze. After a year of followup, the average vertical deviation was 0.4 pd in primary position and 2 pd in down gaze. Ten of the eleven patients were considered to have "successful" primary surgery using this technique. The eleventh required a second operation for an undercorrection which resulted from inadequate original placement of the safety stitch. The non-absorbable safety stitch technique provided satisfactory results, superior to previously reported techniques for postop' adjustable recession strabismus surgery of the inferior rectus muscle.


[Cancer chemotherapy and apoptosis].
Tumor cells undergo apoptotic cell death when treated with several chemotherapeutic agents. Since these agents, acting on different cellular targets, induce a similar pattern of cell death (apoptosis), it is suggested that a common signaling pathway of apoptosis could exist and that apoptosis resistance could cause a new form of multi-drug resistance in tumor cells. Although the mechanisms of apoptosis are not fully understood, the involvement of ICE/ced-3 family proteases in chemotherapy-induced apoptosis is strongly suggested. Identification of factors directly acting on these apoptosis pathway will offer new strategies in cancer chemotherapy.


Artesunate suppresses inflammation and oxidative stress in a rat model of colorectal cancer.
Anti-inflammatory drugs are well known to reduce the risk of colon cancer and prophylactic use of such agents is gaining acceptance as a cancer prevention therapy. As artesunate, an antimalarial drug, has been shown to exhibit chemopreventive properties, the present study was carried out to evaluate its inhibitory effect on oxidative stress and inflammation in a rat model of colon carcinogenesis. A chemical carcinogen, 1,2-dimethylhydrazine was injected twice at an interval of 1 week to induce preneoplastic lesions in the colon and the parameters indicating oxidative stress and inflammation were evaluated after 8 weeks. Artesunate (50 and 150 mg/kg) and aspirin (60 mg/kg) were administered orally throughout the study. Analysis of colon tissue revealed that both the drugs preserved histoarchitecture, inhibited cellular influx, decreased the levels of oxidative stress and inflammatory markers, downregulated cyclooxygenase-2, inducible nitric oxide synthase, nuclear factor κB, and interleukin 1β in comparison to the experimental control. Suppression of oxidative stress and pro-inflammatory signaling by both the drugs were found to contribute to inhibition of colon carcinogenesis. The protection afforded by these drugs was found to be comparable. Our study shows that like aspirin, use of artesunate could also reduce the risk of colon cancer and it has a potential for further evaluation for the treatment purpose.


Serotonin increases L-type Ca2+ current and SR Ca2+ content through 5-HT4 receptors in failing rat ventricular cardiomyocytes.
Rats with congestive heart failure (CHF) develop ventricular inotropic responsiveness to serotonin (5-HT), mediated through 5-HT(2A) and 5-HT(4) receptors. Human ventricle is similarly responsive to 5-HT through 5-HT(4) receptors. We studied isolated ventricular cardiomyocytes to clarify the effects of 5-HT on intracellular Ca(2+) handling. Left-ventricular cardiomyocytes were isolated from male Wistar rats 6 wk after induction of postinfarction CHF. Contractile function and Ca(2+) transients were measured in field-stimulated cardiomyocytes, and L-type Ca(2+) current (I(Ca,L)) and sarcoplasmic reticulum (SR) Ca(2+) content were measured in voltage-clamped cells. Protein phosphorylation was measured by Western blotting or phosphoprotein gel staining. 5-HT(4)- and 5-HT(2A)-receptor stimulation induced a positive inotropic response of 33 and 18% (both P < 0.05) and also increased the Ca(2+) transient (44 and 6%, respectively; both P < 0.05). I(Ca,L) and SR Ca(2+) content increased only after 5-HT(4)-receptor stimulation (57 and 65%; both P < 0.05). Phospholamban serine(16) (PLB-Ser(16)) and troponin I phosphorylation increased by 26 and 13% after 5-HT(4)-receptor stimulation (P < 0.05). 5-HT(2A)-receptor stimulation increased the action potential duration and did not significantly change the phosphorylation of PLB-Ser(16) or troponin I, but it increased myosin light chain 2 (MLC2) phosphorylation. In conclusion, the positive inotropic response to 5-HT(4) stimulation results from increased I(Ca,L) and increased phosphorylation of PLB-Ser(16), which increases the SR Ca(2+) content. 5-HT(4) stimulation is thus, like beta-adrenoceptor stimulation, possibly energetically unfavorable in CHF. 5-HT(2A)-receptor stimulation, previously studied in acute CHF, induces a positive inotropic response also in chronic CHF, probably mediated by MLC2 phosphorylation.


Synthetic 2',5'-dimethoxychalcones as G(2)/M arrest-mediated apoptosis-inducing agents and inhibitors of nitric oxide production in rat macrophages.
In an effort to develop novel antitumor or chemopreventive agents, a series of 2',5'-dimethoxychalcone derivatives were prepared by Claisen-Schmidt condensation of appropriate acetophenones with suitable aromatic aldehyde. In vitro screening revealed low micromolar activity (IC(50)) against several human cancer lines. Activity in MCF-7 cells correlated with the ability to induce G(2)/M arrest-mediated apoptosis following drug treatment by the most potent agent, 8, an observation further reinforced by fluorescence microscopy. Compounds 3, 8, and 10 showed potent inhibitory effect on NO production in lipopolysaccharide (LPS)-activated RAW 264.7 macrophage-like cells. The present results demonstrated that 3, 8, and 10 are potential anti-inflammatory and cancer chemopreventive agents.


Half-life of oxazaphosphorines in biological fluids.
Plasma AUC and half-life values for cyclophosphamide were determined in rats manipulated to hydroxylate cyclophosphamide at different rates; plasma AUC and apparent half-life values for two pharmacologically important metabolites of cyclophosphamide, viz. 4-hydroxycyclophosphamide/aldophosphamide and phosphoramide mustard, were also determined in these animals. Apparent plasma half-life values for 4-hydroxycyclophosphamide/aldophosphamide and phosphoramide mustard increased with an increase in plasma half-life values for cyclophosphamide. AUC values for cyclophosphamide increased approximately linearly with an increase in its plasma half-life but AUC values for 4-hydroxycyclophosphamide/aldophosphamide and phosphoramide mustard remained approximately constant with an increase in their respective apparent plasma half-life values. Given that the cytotoxic effects of cyclophosphamide are directly proportional to AUC values for 4-hydroxycyclophosphamide/aldophosphamide and/or phosphoramide mustard, we conclude that changes in the rate of cyclophosphamide hydroxylation will not alter the systemic toxic and therapeutic responses to a given dose of cyclophosphamide. Actual half-life values for 4-hydroxycyclophosphamide/aldophosphamide and phosphoramide mustard after the iv infusion of these agents were also determined. A comparison of the actual plasma half-life values for cyclophosphamide (29 min), 4-hydroxycyclophosphamide/aldophosphamide (14 min), and phosphoramide mustard (14 min) with the apparent plasma half-life values obtained for 4-hydroxycyclophosphamide/aldophosphamide (34 min) and phosphoramide mustard (55 min) following cyclophosphamide administration suggests that the major determinant with regard to the apparent plasma half-life of 4-hydroxycyclophosphamide/aldophosphamide is its rate of formation whereas in the case of phosphoramide mustard, an additional determinant, perhaps efflux from the cell, is operative.(ABSTRACT TRUNCATED AT 250 WORDS)


[Rectal cancer in clinical material. Effect of advanced clinical staging, tumor location and type of surgical treatment on long term results].
The aim of the research is presentation of patients' material, operated on in The Clinic in the years 1965-1993 because of rectal cancer. The material makes 1363 patients, where group of 214 patients was separated from, treated in the years 1989-1993, basing on modern system of medical examinations qualifying for the surgical intervention and included by intensive prospecting monitoring. At investigative periods 1965-1989 and 1989-1993 the transition of rectal Dukes' stages on A and B interest was noticed, this admitted to increase the whole number of local excision et anterior rectum resection and improve distant treatment results, five years' survival measured. Percentage of patients with inoperable clinical staging, at periods: 1965-1989 and 1989-1993, is similar, in spite of considerable development of diagnostic methods.


Lennard-Jones Potentials for the Interaction of CO2 with Five-Membered Aromatic Heterocycles.
We used M06-2X/Def2-TZVPP to calculate a broad set of rigid interaction profiles between CO2 and 30 different aromatic heterocycles, based on pyrrole, furan, and thiophene with ring positions subsituted with up to four nitrogens. For each system, several orientations of the fragments were explored to both find the preferred interaction mode and have information about other interaction modes that can contribute to the binding energy when CO2 is captured by complex systems. From these data, Lennard-Jones potentials were obtained, which can be used for the parametrization of force fields that correctly describe the multipolar and dispersion interactions at play between these kinds of fragments. These results are expected to contribute to the development of new force fields for the study of chemical systems for the capture and sequestration of CO2 and also directly for the design of such systems.


An evaluation of tribromoethanol (TBE) as an anaesthetic agent in the Mongolian gerbil (Meriones unguiculatus).
Mongolian gerbils injected i.p. with a 1.25% solution of tribromoethanol (TBE) quickly lost the righting reflex and showed good surgical anaesthesia, the duration of which was positively related to the dose administered. All levels (225-450 mg/kg bodyweight) of TBE injected s.c. resulted in loss of the righting reflex, though surgical anaesthesia was not attained. Following recovery from anaesthesia induced with 2.25% TBE i.p., or high doses of 1.25% TBE i.p., visceral adhesions and deaths occurred. To avoid these TBE-induced fatalities such extreme care must be taken during the preparation, storage and administration of the agent that it is not recommended as a suitable anaesthetic for general use in the gerbil.


An approach to objective assessment of caries prophylactic measures in a dental health program.
In a retrospective survey the mean number of intact proximal surfaces on the first molars of 13-year-old children was found to increase from 2.6 to 4.8 following 7 years of a preventive program with fortnightly fluoride mouthrinsings (0.2% NaF). This improvement was significant and corresponded to a reduction of the totally filled surfaces from 30.0 to 16.6. Caries on the proximal surfaces on the first molars was assessed from bite-wing radiographs. Judged from interexaminer comparisons, the number of filled surfaces was a reliable parameter of the caries prevalence in 13-year-old children. In a group of 54 children aged 13 who participated in the preventive program, the caries experience on the proximal surfaces of the first molars was significantly associated with the total DMFS.


Hydrogen peroxide and nitric oxide mediated cold- and dehydration-induced myo-inositol phosphate synthase that confers multiple resistances to abiotic stresses.
myo-Inositol phosphate synthase (MIPS) is the key enzyme of myo-inositol synthesis, which is a central molecule required for cell metabolism and plant growth as a precursor to a large variety of compounds. A full-length fragment of MfMIPS1 cDNA was cloned from Medicago falcata that is more cold-tolerant than Medicago sativa. While MfMIPS1 transcript was induced in response to cold, dehydration and salt stress, MIPS transcript and myo-inositol were maintained longer and at a higher level in M. falcata than in M. sativa during cold acclimation at 5 °C. MfMIPS1 transcript was induced by hydrogen peroxide (H(2) O(2)) and nitric oxide (NO), but was not responsive to abscisic acid (ABA). Pharmacological experiments revealed that H(2) O(2) and NO are involved in the regulation of MfMIPS1 expression by cold and dehydration, but not by salt. Overexpression of MfMIPS1 in tobacco increased the MIPS activity and levels of myo-inositol, galactinol and raffinose, resulting in enhanced resistance to chilling, drought and salt stresses in transgenic tobacco plants. It is suggested that MfMIPS1 is induced by diverse environmental factors and confers resistance to various abiotic stresses.


Single and multiple dose pharmacokinetics of ciprofloxacin.
Penetration of ciprofloxacin into nasal secretion was studied in 20 healty volunteers to whom 500 mg oral ciprofloxacin was administered twice daily for eight days. Nasal secretion and blood samples were collected following the 1st and 15th dose and samples assayed microbiologically. Absolute concentrations of ciprofloxacin in serum and nasal secretion as well as kinetic parameters indicate that repeated administration did not result in significantly increased serum or nasal secretions levels although there was a tendency towards slight drug accumulation. The rate of penetration of ciprofloxacin into nasal secretion was 73% following the first oral dose and 90% following the 15th oral dose.


Establishing a Hybrid Wound and Ostomy Continuing Education Program.
Wound and ostomy nurses receive specialty training and certification to provide care in abdominal stomas, ostomies, wounds, fistulas, and pressure injuries. The eight existing nationwide programs in 2011 were inadequate to meet increasing patient population demands. We developed an innovative nondegree, postbaccalaureate continuing wound and ostomy education program using a hybrid design. The program integrated interactive online classes with intensive onsite classes and skills training. The program has been granted seven-year accreditation; student evaluations have been positive.


Hernsubanine E, a new hasubanan alkaloid from Stephania hernandifolia.
A new hasubanan alkaloid, hernsubanine E (1), as well as two known compounds p-hydroxybenzaldehyde (2) and (-)-syringaresinol (3) have been isolated from the whole plants of Stephania hernandifolia by various column chromatographic methods. Their structures were identified by physicochemical properties and spectral analyses. Compounds 2 and 3 were isolated from the genus of Stephania for the first time.


Risk factors for early wound complications after orthopedic surgery for rheumatoid arthritis.
To identify risk factors for the occurrence of early wound complications following orthopedic surgery in patients with rheumatoid arthritis (RA). We reviewed records of patients with RA undergoing joint surgery to identify predictors of the following early postoperative surgical outcomes: (1) prolonged drainage; (2) wound cellulitis; (3) wound dehiscence; (4) suture abscess; and (5) superficial or deep wound infection. During the study, 204 patients with RA underwent 119 total knee replacements, 105 total hip replacements and 143 procedures of other joints, for a total of 367 orthopedic surgeries. A total of 57 complications were observed (15.9%) of which 26 were considered major (7%). Of the 230 total arthroplasties of the hip, knee, shoulder or elbow, 3 were followed by early deep wound infections (1.3%). In univariate analysis, factors significantly related to the occurrence of complications included Hispanic ethnicity [relative risk (RR) 1.43, 95% confidence interval (CI) 1.16 to 1.78]. and preoperative use of azathioprine (RR 2.13, 95% CI 1.04 to 4.37). Complications were less frequent among patients given methotrexate, but the differences was not significant. Operative blood loss was inversely related to the occurrence of complications. In the multivariate model, the only significant predictors of complications were Hispanic ethnicity (RR 2.86, 95% CI 1.43 to 5.56) and operative blood loss (RR 0.50/liter lost, 95% CI 0.29 to 0.86). We were unable to demonstrate an independent effect of antirheumatic therapy at the time of surgery on the occurrence of postoperative wound complications. Our study suggests that patients with RA of Hispanic ethnicity may be at increased risk of developing postoperative wound complications following orthopedic surgery. Further study is necessary to explain the mechanism of increased complications in this population.


Re-inoculation strategies enhance the degradation of emerging pollutants in fungal bioaugmentation of sewage sludge.
The use of Trametes versicolor has been partially successful in the removal of some pharmaceuticals from sewage sludge in laboratory-scale biopile systems. The application of two strategies for the re-inoculation of biomass was assessed during the fungal bioaugmentation of non-sterile sludge (42-d treatment) as an approach to improve the elimination of pharmaceuticals and other groups of emerging pollutants. Globally, the re-inoculation of biopiles with blended mycelium exerted a major effect on the removal of pharmaceuticals (86%), brominated-flame-retardants (81%) and UV filters (80%) with respect to the re-inoculation with additional lignocellulosic substrate colonized by the fungus (69-67-22%). The performance was better than that of the analogous non-re-inoculated systems that were assayed previously for the removal of pharmaceuticals. The results demonstrate the ability of T. versicolor to remove a wide spectrum of emerging micropollutants under non-sterile conditions, while re-inoculation appears to be a useful step to improve the fungal treatment of sludge.


Multiple loci affect genetic predisposition to hepatocarcinogenesis in mice.
The C3H/He mouse represents a good experimental model of genetic predisposition to hepatocellular tumor development. We analyzed an interspecific test-cross population of 106 urethane-treated male (C3H/He x Mus spretus) x C57BL/6J mice, typed with 222 genetic markers to locate precisely the hepatocellular tumor susceptibility (Hcs) loci. Three regions, on chromosomes 2, 5, and 19, showed a significant linkage with hepatocellular tumor development, as indicated by different quantitative indexes estimating liver tumor size. Liver tumor frequency was not genetically controlled. These loci are different from three other Hcs loci that we have previously mapped in an F2 progeny of the C3H/He mouse crossed with the resistant laboratory strain A/J. The present result indicates a multigenic model of inheritance for hepatocellular tumor susceptibility.


Failure to confirm cyclic AMP as second messenger for norepinephrine in rat cerebellum.
Microiontophoretic applications of adenosine 3',5'-monophosphate (cyclic AMP) to spontaneously active, electrophysiologically identified Purkinje cells of the rat cerebellum failed to mimic the strong depressant action of norepinephrine on the same cells. These findings, in combination with a reevaluation of other studies, cast doubt on the hypothesis that cyclic AMP mediates the depressant actions of norepinephrine in the cerebellum.


Contemporary Management of Ulcerative Colitis.
We discuss the newest evidence-based data on management of ulcerative colitis (UC). We emphasize risk-stratification, optimizing medical therapies, and surgical outcomes of UC. Recent medical advances include introduction of novel agents for UC. Vedolizumab, an anti-adhesion molecule, has demonstrated efficacy in moderate to severe UC. Tofacitinib, a small molecule, has also demonstrated efficacy. Data on optimization of infliximab show the superiority of combination therapy with azathioprine over monotherapy with infliximab or azathioprine alone. Data on anti-tumor necrosis factor-alpha (anti-TNF) therapeutic drug monitoring also hold promise, as do preliminary data on the dose escalation of infliximab in severe hospitalized UC. Surgical outcome data are reassuring, with new fertility data showing the effectiveness of in vitro fertilization. UC management is multi-disciplinary and changing. While novel therapies hold promise, better optimization of our current arsenal will also improve outcomes.


Muscularis mucosae - the forgotten sibling.
Lamina muscularis mucosae sitting beneath mucosal surface of the digestive tract has received little attention to date compared with external smooth muscle layers. Motor activity of the muscularis mucosae shows a great regional and species difference. Autonomic innervation profile is also different from esophagus to colon or between animal species. Intracellular transduction mechanisms for motor activity of the muscularis mucosae are also different from those of external longitudinal and circular muscles or from vascular and airway smooth muscles. Since the submucosal area is a major source for eicosanoid production, abnormality of muscularis mucosae motor activity may link with abnormality of mucosal absorption and secretion functions. Inflammatory bowel diseases such as diarrhea, irritable bowel syndrome and Crohn's disease accompanied with altered motor activity of the muscularis mucosae. Much attention should be attracted to the human muscularis mucosae as a new therapeutic target for inflammatory bowel diseases.


Modeling of separations by closed-loop steady-state recycling chromatography of a racemic pharmaceutical intermediate.
Closed-loop steady-state recycling (SSR) is a cyclic, one-column process that is similar to simulated moving bed (SMB) chromatography in several respects. Both processes are cyclic. In both SMB and SSR, fractions are collected from the leading and trailing portions of the circulating chromatographic profile, and fresh sample is injected into the interior of the profile. However, SMB is a continuous process whereas SSR is a discontinuous, repetitive process. This paper presents a model for the closed-loop SSR process and its experimental validation in a case of practical importance. For this last purpose, we used the closed-loop SSR separation of the enantiomers of a racemic pharmaceutical intermediate. The experimental determination of the competitive adsorption equilibria was performed by frontal analysis in a system composed of a chiral HPLC column as the stationary phase and pure acetonitrile as the mobile phase. All the adsorption data were well correlated by the Langmuir model. The Langmuir model was used to calculate overloaded band profiles corresponding to the separation of racemic mixtures at both analytical and preparative scales. Theoretical band profiles were calculated using the equilibrium-dispersive model. With proper corrections for the contributions of the sources of extra-column band broadening, the model properly predicts the experimental band profiles obtained in the closed-loop SSR setup and demonstrates that a cyclic steady-state develops after the completion of a finite number of cycles. The results also show that the extra-column effects must be accounted for in order to model the closed-loop SSR process accurately.


Isolation of Glomeruli and In Vivo Labeling of Glomerular Cell Surface Proteins.
Proteinuria results from the disruption of the glomerular filter that is composed of the fenestrated endothelium, glomerular basement membrane, and podocytes with their slit diaphragms. The delicate structure of the glomerular filter, especially the slit diaphragm, relies on the interplay of diverse cell surface proteins. Studying these cell surface proteins has so far been limited to in vitro studies or histologic analysis. Here, we present a murine in vivo biotinylation labeling method, which enables the study of glomerular cell surface proteins under physiologic and pathophysiologic conditions. This protocol contains information on how to perfuse mouse kidneys, isolate glomeruli, and perform endogenous immunoprecipitation of a protein of interest. Semi-quantitation of glomerular cell surface abundance is readily available with this novel method, and all proteins accessible to biotin perfusion and immunoprecipitation can be studied. In addition, isolation of glomeruli with or without biotinylation enables further analysis of glomerular RNA and protein as well as primary glomerular cell culture (i.e., primary podocyte cell culture).


Pulmonary artery constriction produces a greater right ventricular dynamic afterload than lung microvascular injury in the open chest dog.
Investigators model noncardiogenic pulmonary hypertension by constricting the pulmonary artery to increase right ventricular afterload. To investigate this model's validity, we compared the right ventricular afterload, quantified as pulmonary input impedance, created by constricting the pulmonary artery and by inducing a pulmonary microvascular injury (with glass beads infused into the pulmonary circulation). The pulmonary injury constriction produced a different right ventricular afterload than the microvascular injury. The constriction increased both the input resistance and the characteristic impedance. Microvascular injury increased only input resistance. Physiological levels of lung inflation did not influence pulmonary impedance, but lung hyperinflation increased input resistance both before and while constricting the pulmonary artery or after producing microvascular injury. Total right ventricular power output and stroke work were unchanged during each vascular intervention. Pulmonary artery constriction did not affect power output distribution, whereas microvascular injury decreased oscillatory power and its relative contribution to total power. Lung hyperinflation dramatically reduced right ventricular power and left ventricular stroke work. These effects appeared mediated by right ventricular afterload increase uncompensated for by right ventricular preload increase. These observations help explain the hemodynamic consequences of acute pulmonary hypertension and the effects of lung hyperinflation with positive end-expiratory pressure respiration in such patients.


Confocal Raman spectrocopy for the analysis of nail polish evidence.
Nail polishes are cosmetic paints that may be susceptible of forensic analysis offering useful information to assist in a crime reconstruction. Although the nail polish appearance could allow a quick visual identification of the sample, this analysis is subjected to the perception and subjective interpretation of the forensic examiner. The chemical analysis of the nail polishes offers great deal of information not subjected to analyst interpretation. Confocal Raman spectroscopy is a well-suited technique for the analysis of paints due to its non-invasive and non-destructive nature and its ability to supply information about the organic and inorganic components of the sample. In this work, 77 regular and gel nail polishes were analyzed with confocal Raman spectroscopy using two laser wavelengths (532 and 780 nm). The sample behavior under the two laser wavelengths and the differences in the spectra taken at different points of the sample were studied for each nail polish. Additionally, the spectra obtained for all the nail polishes were visually compared. The results concluded that the longer laser wavelength prevents sample burning and fluorescence effects; the similarity among the spectra collected within the sample is not directly related with the presence of glitter particles; and 64% of the samples analyzed showed a characteristic spectrum. Additionally, the use of confocal Raman spectroscopy for the forensic analysis of nail polishes evidence in the form of flakes or smudges on different surfaces were studied. The results showed that both types of evidence can be analyzed by the technique. Also, two non-invasive sampling methods for the collection of the evidence from the nails of the suspect or the victim were proposed: (i) to use acetone-soaked cotton swabs to remove the nail varnishes and (ii) to scrape the nail polish from the nail with a blade. Both approaches, each exhibiting advantages and drawbacks in terms of transport and handling were appropriate for a further chemical analysis of the samples.


Leiomyoma of the male urethra: a case report and review of the literature.
We describe the case of a 48-year-old quadriplegic black man with history of C4-C5 cervical spine and cord injury secondary to a fall, who presented to the University of Cincinnati Medical Center Urology Service with obstructive symptoms at urination. A bulbous urethral stricture was diagnosed and subsequently resected with primary urethral reanastomosis. On pathologic examination, the surgical specimen contained an epithelioid leiomyoma at the site of the urethral stricture. Although leiomyomas of the female urethra are relatively common, we identified only 2 previously reported cases of leiomyomas of the male urethra in the English-language medical literature. To the best of our knowledge, we describe the third case of leiomyoma of the male urethra, the first of the epithelioid type.


Uptake and release of [3H]-serotonin in photophores of the midshipman fish, Porichthys notatus.
A kinetic analysis of [3H]-5-HT uptake in the photocytes of the photophores of Porichthys notatus revealed a high affinity (Km: 1.71 X 10(-7] and low affinity component (Km: 1.10 X 10(-5) M). The high affinity uptake was sodium- and potassium-dependent but largely insensitive to temperatures between 0 and 20 C. Ouabain (5 X 10(-3) M) and dinitrophenol (10(-3) M) reduced uptake significantly. DMI, imipramine and fluoxetine, in that order of potency, greatly inhibited [3H]-5-HT uptake. Noradrenaline and adrenaline reduced uptake in a non-competitive manner, while dopamine, tryptophan, 5-hydroxytryptophan and Cypridina luciferin had little or not effect on uptake. Non-facilitated luminescent responses to electrical stimulation were accompanied by release of [3H]-5-HT accumulated in the photocytes. Facilitatory luminescence excitation consistently failed to induce the release of [3H]-5-HT. Electrical and adrenaline (10(-5) M) stimulation of photophores after [3H]-5-HT release has occurred, failed to elicit any additional luminescent response. The photophores were responsive to KCN (10(-3) M) under these conditions. The results indicate that a specific carrier-mediated transport system is responsible for photocytic [3H]-5-HT uptake, and that release of photocytic [3H]-5-HT is stringently regulated and followed by inhibition of luminescence excitability.


Ex vivo magnifying endoscopic observation of bile duct mucosa using narrowband imaging.
Detailed endoscopic findings of the bile duct mucosa have not been fully established. This fundamental ex vivo study assesses the relationship between magnified endoscopic findings and pathological findings of the bile duct mucosa. Forty-one surgically resected common bile duct mucosae were investigated. Each common bile duct was cut open longitudinally for ex vivo endoscopic observation. A magnifying endoscope commonly used for the gastrointestinal tract was used, using both white light imaging and narrowband imaging. After pathological diagnosis, the association between the magnifying endoscopic findings and histopathology was evaluated. Totally, 39 non-neoplastic mucosae and 13 neoplastic mucosae were evaluated. In 13 non-neoplastic mucosae without inflammation, an oval-shaped depressed area and a fine, regular network of microvessels were observed. These findings were not clearly seen or not seen at all in the non-neoplastic mucosae with inflammation. Although vessels with loop-like structure were observed on all eight papillary tumors of 13 neoplastic mucosae, no characteristic vessels were seen on the other five. Ishida and colleagues assessed the association between magnifying endoscopic findings and histopathological findings of the bile duct mucosa ex vivo. Oval-shaped, depressed areas and a fine, regular network of microvessels are characteristic features of normal bile duct mucosa, while loop structures may be indicative of a type of tumor vessel.


Enhancement of Pool Boiling Heat Transfer Using Aligned Silicon Nanowire Arrays.
Enhancing the critical heat flux (CHF), which is the capacity of heat dissipation, is important to secure high stability in two-phase cooling systems. Coolant supply to a dry hot spot is a major mechanism to prevent surface burn-out for enhancing the CHF. Here, we demonstrate a more ready supply of coolant using aligned silicon nanowires (A-SiNWs), with a high aspect ratio (>10) compared to that of conventional random silicon nanowires (R-SiNWs), which have a disordered arrangement, for additional CHF improvement. We propose the volumetric wicking rate, which represents the coolant supply properties by considering both the liquid supply velocity and the amount of coolant (i.e., wicking coefficient and wetted volume, respectively). Through experimental approaches, we confirm that the CHF is enhanced as the volumetric wicking rate is increased. In good agreement with the fabrication hypothesis, A-SiNWs demonstrate higher coolant supply abilities than those of R-SiNWs. The longest (7 μm) A-SiNWs have the highest volumetric wicking rate (25.11 × 10-3 mm3/s) and increase the CHF to 245.6 W/cm2, which is the highest value obtained using nanowires among reported data (178 and 26% enhanced vs unmodulated plain surface and R-SiNWs, respectively). These well-aligned SiNWs can increase the CHF significantly with efficient coolant supply, and it can ensure high stability in extremely high thermal load systems. Moreover, our study provides nanoscale interfacial design strategies for further improvement of heat dissipation.


A new simplified sonographic approach for pararadicular injections in the lumbar spine: a CT-controlled cadaver study.
Injection therapies play a major role in the treatment of lower back pain and are to date performed mainly under CT or fluoroscopic guidance. The benefits of US-guided instillation procedures have been shown in many studies. We conducted this study to simplify an US-guided approach to the lumbar spinal nerves and to assess the feasibility and preliminary accuracy by means of CT and anatomic dissection. Ten US-guided injections at 5 different levels (L1-L5) were performed on 1 embalmed cadaver. Images in 3 sagittal/parasagittal scanning planes were obtained at each lumbar level: 1) the plane of the spinous processes, 2) the plane of the lumbar arches/zygapophyseal-joints, and 3) the plane of the transverse processes. The PAP was then defined by positioning the transducer perpendicularly over the medial part of the respective transverse processes, depicting the hyperechoic intertransverse ligament. In the "in-plane technique," spinal needles were advanced through the respective segmental intertransverse ligament. A solution consisting of a contrast agent and a pigmented dispersion was subsequently injected into the pararadicular compartment. An anatomic dissection of the specimen and CT scans were performed to verify the exact placement of the needle tips and to evaluate fluid dispersion in the punctured compartment. CT examination confirmed that each needle tip was correctly placed within the intended compartment with sufficient contrast accumulation around the respective proximal segment of the spinal nerve. On each anatomic section, dye was identified in the correct compartment and directly around each targeted spinal nerve with needles shown in the correct position. This modified US approach for therapeutic root injections in the lumbar spine by using the intertransverse ligament as a new anatomic landmark allows an easy and correct needle placement within the pararadicular compartment.


Structure and function of fibrinogen: insights from dysfibrinogens.
The structure-function relationships of dysfibrinogens and their clinical implications are discussed on the basis of the data provided from representative molecules.


An unusual variant of Cushing syndrome.
To discuss the initial clinical manifestations of primary pigmented nodular adrenocortical disease. We present a case report of a 4-year-old boy who had the classic clinical features of Cushing syndrome. Results of hormonal investigations are reviewed, and histopathologic findings are illustrated. Investigations revealed adrenocorticotropic hormone (corticotropin)-independent Cushing syndrome. Findings on magnetic resonance imaging of the pituitary gland and abdomen were within normal limits. The patient underwent bilateral adrenalectomy. The histopathologic features were consistent with primary pigmented nodular adrenocortical disease. Primary pigmented nodular adrenocortical disease should be suspected in patients with corticotropin-independent Cushing syndrome who have normal findings on adrenal imaging.


[Incidence and mortality of laryngeal neoplasms. Soria, 1950-1989].
Age-adjusted mortality and incidence rates for larynx cancer were calculated in Soria (urban and rural areas), for the 1950-89 and 1981-89 periods respectively. Both mortality and incidence rates were higher in urban area (p less than 0.01), and in males (p less than 0.01). There has been no increase in the mortality trend for the 1950-89 period. Age-adjusted incidence rates for men in Soria are higher respect to those reported in other countries. Soria and Murcia rates are the lowest in Spain larynx cancer records, being Asturias rates the highest in the world (20.6 per 100,000 population).


Special features of gram-positive bacterial eradication by photosensitizers.
Antibiotic resistance of pathogenic bacteria is a major concern and presents a special challenge for development of alternative antibacterial modalities. One of these alternative approaches is based on using the photodynamic therapy (PDT) for eradicating bacteria. Photosensitizer-induced PDT exhibits unique properties and demonstrates efficient microbe-killing effects. The efficient and irreversible antimicrobial effects of PDT are not dependent on the antibiotic susceptibility of the pathogenic bacteria to antibiotics. Gram-positive bacteria exhibit efficient binding of the photosensitizer to the bacterial barriers, leading to immediate photoinactivation of the bacteria. Photoinactivation of Gram-positive bacteria by various photosensitizers has become a high priority, since these bacteria are responsible for life-threatening infections in humans, especially in the elderly and in compromised hosts in whom they cause hospital-acquired infections. The present review concentrates on the photoinactivation of Staphylococi, Streptococci, Propionibacterium acnes, Deinococcus radiodurans, aerobic spore-forming Bacilli by various photosensitizers and by various methods described in numerous works and patents.


Diagnosis and management of aggressive, acquired cholesteatoma with skull base and calvarial involvement: a report of 3 cases.
A prospective case review of 3 patients treated at a tertiary referral center from 1997 to 2002 are presented. Three men, age 30 to 68 (mean, 45) years, were treated for acquired cholesteatoma with skull base invasion. Two patients had no prior otological surgery, and 1 was detected after 4 prior mastoid procedures. One presented with progressive unilateral facial palsy, 1 with otorrhea, and 1 with temporal mass above a modified radical mastoidectomy cavity. All 3 patients were treated with single-staged canal wall-down mastoidectomy. Patients were followed up with otoscopy and neuroimaging from 40 to 61 months. Two patients had no recurrence of cholesteatoma, and 1 had squamous debris in the mastoid cavity removed in the outpatient clinic. One had complete ipsilateral facial nerve paralysis preoperatively and recovered to House-Brackmann grade III within 1 year of surgery. Patient 1 had labyrinthine involvement before surgery and had ipsilateral anacusis after resection and repair. No other complications occurred. Initial presentation, workup, surgical challenges, disease follow-up, facial nerve function, hearing results, and complications are reported.


An in vitro assessment of the effect of load and pH on wear between opposing enamel and dentine surfaces.
Previous in vitro studies have described the wear characteristics of specimens in which enamel has been opposed to enamel and dentine opposed to dentine. The aim of this study was to assess the characteristics of wear between specimens in which enamel was opposed to dentine at loads simulating attrition and at pH values simulating different erosive environments. It was hypothesized that enamel would wear more slowly than dentine under all conditions. Opposing enamel and dentine specimens from 57 human third molar teeth were worn in electromechanical machines with various loads (32, 62 and 100 N) and lubricants (pH 1.2, 3.0 and 6.1). Tooth wear was quantified by measuring reduction in dentine volume over time using a 3D profilometer. Qualitative assessment was also carried out using scanning electron microscopy. Dentine wear increased with increasing load, and dentine wear was faster at pH 1.2 than at pH 3.0 or 6.1 for all loads tested. Interestingly, enamel wore more rapidly than dentine at pH 1.2 under all loads. At pH values of 3.0 and 6.1, enamel wear rates were not measurably different from zero and they were less than wear rates for opposing dentine specimens at all loads. Micrographic assessment showed extensive surface destruction of dentine wear facets due to erosion at pH 1.2. Dentine wear facets were smoother at pH 3.0 that at pH 6.1. When enamel wears against dentine in an acidic environment enamel will wear more rapidly at very low pH, while under less acid conditions dentine will wear faster than enamel.


Molecular recognition and binding of a GC site-avoiding thiazole-lexitropsin to the decadeoxyribonucleotide d-[CGCAATTGCG]2: 1H-NMR evidence for thiazole intercalation.
The structural and dynamic aspects of the interaction of the thiazole containing lexitropsin (1) with an oligodeoxyribonucleotide were studied by high field 1H-NMR spectroscopy. Complete assignment of the 1H-NMR resonances of lexitropsin 1 was accomplished by 2D-NMR techniques. The complexation-induced chemical shifts and NOE cross peaks in the NOESY map of the 1:1 complex of lexitropsin (1) and d-[CGCAATTGCG]2 reveal that the thiazole ring of the lexitropsin (1) intercalates between dA4.A5 bases and the rest of the ligand resides in the minor groove of the AT rich core of decamer, thus occupying the 5'-AATT sequence on the DNA. Intercalation of the thiazole moiety of the drug has been detected by the presence of intermolecular NOEs both in the major and the minor groove of the decamer helix. The absence of intranucleotide NOEs between base protons and H1'/H2' protons suggested local unwinding of the binding site on the DNA. From COSY and NOESY methods of 2D-NMR, it was established that the N-formyl (amino) terminus of the thiazole lexitropsin (1) is projecting into the major groove towards A5H8 while the amidinium terminus lies in the minor groove towards the T7G8 base pairs of the opposite strand. The expected intranucleotide NOEs confirmed that the decadeoxyribonucleotide in the 1:1 complex exists in a right handed B-conformation. The presence of exchange signals along the binding site 5'-AATT indicated an exchange of the bound drug process wherein the rate of exchange between the two equivalent sites was estimated to be congruent to 130 s-1 at 30 degrees C and with delta G degrees of 62.4 kJ mol-1. Force field and Pi calculations permitted a rationalization of the experimentally observed binding mode in terms of preferred conformation of the ligand and repeat length in lexitropsins compared with the DNA receptor.


Should all melanoma patients undergo sentinel lymph node biopsy?
It is now well established that sentinel lymph node biopsy is a powerful test to predict prognosis for melanoma patients. Controversy exists, however, regarding the appropriate selection of patients for sentinel lymph node biopsy, especially among patients with thin melanomas (< 1 mm Breslow thickness), thick melanomas (> 4 mm Breslow thickness), or locally recurrent melanoma. The majority of the studies in the past 2 years regarding sentinel lymph node biopsy have been concerned with identifying factors that can better predict regional nodal metastasis and survival. Other studies have proposed a better risk stratification model, which includes these factors, to best select those patients at increased risk of nodal positivity. Although much research has been done to select appropriate patients for sentinel lymph node biopsy based on multiple prognostic factors, further studies are necessary to completely define the indications for this procedure in patients with thin, thick and locally recurrent melanomas.


Perinuclear-antineutrophil cytoplasmic antibodies are associated with vasculitis.
We describe a 62-year-old man with perinuclear-antineutrophil cytoplasmic antibodies-associated vasculitis, which involved the heart, lung, and kidneys. The patient's care was complicated by total occlusions of the brachiocephalic and right renal arteries and a stenosis of the left renal artery. Involvement of large-sized vessels has not been reported in patients with perinuclear-antineutrophil cytoplasmic antibodies-associated vasculitis.


Cd(ii)-MOF-IM: post-synthesis functionalization of a Cd(ii)-MOF as a triphase transfer catalyst.
A robust and porous Cd(ii)-MOF based on a bent imidazole-bridged ligand was synthesized and post-synthetically functionalized with linear alkyl chains to afford imidazolium salt (IM)-type triphase transfer catalysts for organic transformations. The imidazolium salt decorated Cd(ii)-MOF-IM exhibits typical solid phase transfer catalytic behavior for the azidation and thiolation of bromoalkane between aqueous/organic phases. Moreover, they can be easily recovered and reused under the PTC conditions. Cd(ii)-MOF-IM herein created a versatile family of solid phase transfer catalysts for promoting a broad scope of reactions carried out in a biphasic mixture of two immiscible solvents.


[Complexity of therapeutic regimens prescribed for elderly retirees, Belo Horizonte/MG, Brazil].
To examine factors associated with therapeutic regimen complexity of drug prescriptions for elderly people in Belo Horizonte, Minas Gerais, Brazil. A household survey of elderly people selected by simple random sampling from Brazil's social security register. The medication complexity index (MCI), a direct measurement of actions required to administer medication, was derived from information in the latest prescription. Univariate and bivariate analyses were performed to identify factors associated with the MCI. Of the 667 interviewees, 56.5% had prescriptions meeting the inclusion criteria; most (69.2%) were females aged 72.4 years (mean); 35.5% self-rated their health good or very good; and 37.4% reported five or more diseases. In the 15 days prior to interview, 1873 drugs were used (mean=5.1), of which 942 appeared on the prescriptions examined (mean=2.5). Over the same period, 22.3% of interviewees failed to use some prescribed drug. The MCI ranged from 1 to 24 (mean=6.1). Number of drugs prescribed (>2), less schooling, worse perception of health and a lower benefit payment associated positively with greater complexity (p<0.05). An association was observed between regimen complexity and failure to use some drug in the preceding 15 days (p=0.034). Elderly people in worse socio-economic and health conditions seem more likely to receive more complex therapeutic regimens, which are associated with non-compliance to the proposed treatment. This is an important consideration in the healthcare of elderly. Simplification of therapy could aid self-care among the elderly.


The multiple facets of multiple sclerosis.
Multiple sclerosis (MS) is an inflammatory and degenerative entity that may involve the brain, optic nerve, and/or the spinal cord. We reviewed 137 patients, aged 4-54 years old at the time of the diagnosis and will report on the vision, different motility disorders found, visual fields, optic neuritis and RAPD, return of vision following the neuritis, visual evoked potential, nerve fiber layer analysis, and systemic problems such as Uhthoff phenomenon, L'Hermitte sign, urinary urgency, and constipation. One hundred thirty-seven patients were given full ophthalmologic and orthoptic evaluations. Particular attention was given to subtle relative afferent pupillary defects (RAPD), oscillopsia, pain with eye movement, and other specialty testing including visual evoked potentials and nerve fiber layer assessment. The immunology, pediatric MS, clinical courses, and treatment are also discussed. Treatment included medication, orthoptic modalities, strabismus procedures, and cooling devices. Motiltiy disorders included exophoria, unilateral Internuclear Ophthalmoplegia (INO), esophoria, and various types of nystagmus. The majority of nonmotility ophthalmic entities included optic neuritis, RAPD, and abnormal nerve fiber layer studies. Most patients were diagnosed based on white matter lesions on the MRI and oligoclonal bands in the spinal fluid after lumbar puncture. The majority of systemic signs were numbness, Uhthoff sign, and balance difficulties. Thirty-four percent of the patients were helped with either convergence therapy, prisms for all kinds of diplopia, and field manipulation. MS is a multi-factorial entity. It is important to emphasize how important a few extra history questions are, including: any pain with eye movement, any bouncing of the images, and is vision or balance any worse in the heat? The Visual Evoked Potential (VEP) and nerve fiber layer studies are important in the diagnosis of MS. Seventy percent of patients with had eye complaints as their initial symptom. Finally, one-third of all patients were helped with some form of orthoptic therapy.


Complexation of risperidone with a taste-masking resin: novel application of near infra-red and chemical imaging to evaluate complexes.
The purpose of the study was to investigate the complexation between a weakly basic drug (risperidone) and an ion exchange resin (amberlite IRP-64) used as a taste-masking agent via two preparation methods: physical mixture and solvent evaporation. Both methods were prepared in different drug-to-resin ratios by weight (1:1, 1:2, 1:4, 1:6). Physicochemical characterizations were performed using differential scanning calorimetry, x-ray diffraction, infra-red spectroscopy, Raman spectroscopy, near infra-red spectroscopy, chemical imaging and drug release studies. These physicochemical techniques revealed that risperidone formed complex with the resin via the solvent evaporation method where enhanced dissolution occurred but not with the physical mixtures.


Dislodged caval stent in right pulmonary artery.
Percutaneous intervention for central vein occlusion is getting popular. Self-expandable stent is user-friendly in this field, however, jump-out displacement may happen. An 82-year-old woman with end-stage renal disease and central vein occlusion underwent central vein stenting. Dislodgement of the self-expandable stent was encountered. Migration into right ventricle and subsequently right pulmonary artery was noted. Chest films of this rare condition were reported.


Distinguishing between High- and Low-Spin States for Divalent Mn in Mn-Based Prussian Blue Analogue by High-Resolution Soft X-ray Emission Spectroscopy.
We combine Mn L2,3-edge X-ray absorption, high resolution Mn 2p-3d-2p resonant X-ray emission, and configuration-interaction full-multiplet (CIFM) calculation to analyze the electronic structure of Mn-based Prussian blue analogue. We clarified the Mn 3d energy diagram for the Mn(2+) low-spin state separately from that of the Mn(2+) high-spin state by tuning the excitation energy for the X-ray emission measurement. The obtained X-ray emission spectra are generally reproduced by the CIFM calculation for the Mn(2+) low spin state having a stronger ligand-to-metal charge-transfer effect between Mn t2g and CN π orbitals than the Mn(2+) high spin state. The d-d-excitation peak nearest to the elastic scattering was ascribed to the Mn(2+) LS state by the CIFM calculation, indicating that the Mn(2+) LS state with a hole on the t2g orbital locates near the Fermi level.


Recent clinical issues related to the use of depot medroxyprogesterone acetate (Depo-Provera).
This report critically reviews recent original research articles concerning patient use of depot medroxyprogesterone acetate. Specifically, recent studies have been conducted on the following clinical issues: depression, galactorrhea, weight gain, bone mineral density, epithelial and mucus changes in the lower genital tract, and the acceptability of and continuation rates with the use of depot medroxyprogesterone acetate.


Sudden death in a pediatric heart transplant recipient with peripheral eosinophilia and eosinophilic myocardial infiltrates.
Eosinophilia has been rarely reported in pediatric heart transplant recipients and has been suggested to play a role in graft rejection. We report a case of a young female patient with peripheral blood eosinophilia who died suddenly 2 years following ABO-incompatible heart transplantation. She was found at autopsy to have myocardial infiltration of not only T-lymphocytes and macrophages expected in acute cellular rejection but also of eosinophils, B-lymphocytes, and plasma cells indicating myocarditis.


How are HCV-infected patients being identified in Brazil: a multicenter study.
Hepatitis C is an important health problem. In Brazil, 1-2 million people are infected. Despite this expressive number, and the availability of very successful treatment, many patients remained undiagnosed mainly because of the asymptomatic nature of the infection. To describe epidemiological characteristics of HCV-infected patients seen at referral centers in Brazil, the source of referral, and the time spanned to reach a reference center, in order to improve the identification of undiagnosed patients. Multicenter observational, cross-sectional study carried out in 15 centers of Brazil, between January/2016 and June/2017. Data of patients with a confirmed diagnosis (anti-HCV and HCV-RNA) were collected by interview using standard questionnaires and by review of charts. Two thousand patients were included; 55.1% were male, mean age 58±11 years. Only 14.9% had higher education and 84.2% received up to five monthly minimum Brazilian wages (approximately US$260.00/month). The time between diagnosis and beginning of follow-up was 22.9 months. The most common reasons for testing were check-up (33.2%) and blood donation (19%). General practitioners diagnosed most of the patients (30.1%). Fibrosis stage was mainly evaluated by liver biopsy (61.5%) and 31.3% of the patients were cirrhotic at diagnosis. This multicenter Brazilian study showed that the mean time to reach a referral center for treatment was almost two years. Primary care physicians diagnoses most hepatitis C cases in the country. Population campaigns and medical education should be encouraged to intensify screening of asymptomatic individuals, considering the efficiency of check-ups in identifying new patients.


Signal transduction in red blood cells of the lizards Ameiva ameiva and Tupinambis merianae (Squamata, Teiidae).
The fluorescent calcium probe, Fluo-3, AM was used to measure the intracellular calcium concentration in red blood cells (RBCs) of the teiid lizards Ameiva ameiva and Tupinambis merianae. The cytosolic [Ca2+] is maintained around 20 nM and the cells contain membrane-bound Ca2+ pools. One pool appears to be identifiable with the endoplasmic reticulum (ER) inasmuch as addition of the sarco-endoplasmic reticulum Ca2+ ATPase, SERCA, inhibitor thapsigargin induces an increase in cytosolic [Ca2+ both in the presence and in the absence of extracellular Ca2+. In addition to the ER, an acidic compartment appears to be involved in Ca2+ storage, as collapse of intracellular pHgradients by monensin, a Na+ -H+ exchanger, and nigericin, a K+ -H+ exchanger, induce the release of Ca2+ from internal pools. A vacuolar H+ pump, sensitive to NBD-Cl and bafilomycin appears to be necessary to load the acidic Ca2+ pools. Finally, the purinergic agonist ATP triggers a rapid and transient increase of [Ca2+]c in the cells from both lizard species, mostly by mobilization of the cation from internal stores.


Simultaneous evaluation of basal FSH and oestradiol response to GnRH analogue (F-G-test) allows effective drug regimen selection for IVF.
To determine whether preliminary assessment of ovarian reserve by simultaneous evaluation of basal follicle-stimulating hormone (FSH) and oestradiol response to gonadotrophin releasing hormone (GnRH) analogue (F-G-test) can be used to tailor individually the drug regimen for ovarian stimulation, the in-vitro fertilization (IVF) results of 238 patients were retrospectively analysed. Sixty-two women with abnormal response to the test (DeltaE2 <180 pmol/l and/or FSH >9.5 mIU/ml) had commenced buserelin nasal spray in the mid-luteal phase and discontinued it on cycle day 1. Ovarian stimulation was started on cycle day 3 with 375 IU/day of gonadotrophin. Fifty-three patients completed the treatment cycle (group A). A total of 176 women with normal response to the test (DeltaE2 >180 pmol/l and FSH <9.5 mIU/ml) had continued the GnRH analogue throughout the stimulation cycle and a starting dose of 225 IU/day of gonadotrophin was used from cycle day 3. A total of 158 patients completed the treatment cycle (group B). Group A had significantly higher age (34.9 +/- 4.2 versus 33.2 +/- 4.2) (P < 0.05) and basal FSH (9.2 +/- 3.8 versus 7.0 +/- 2.2) (P < 0.05) and required a higher total dose of gonadotrophin. The numbers of oocytes retrieved and embryos transferred were significantly lower. However, fertilization, clinical pregnancies, and implantation rates were similar in both groups. It was concluded that simultaneous evaluation of basal FSH and oestradiol response to GnRH analogue can be useful in identifying subcategories of women with reduced ovarian reserve who may benefit from reduced GnRH analogue administration and a higher starting dose of gonadotrophin.


Plasticity in action of intrathecal clonidine to mechanical but not thermal nociception after peripheral nerve injury.
Intrathecal clonidine reduces tactile allodynia in animal models of neuropathic pain, and this effect is blocked by atropine. However, the role of tonic spinal cholinergic activity and its interaction with alpha2-adrenergic systems in normal and neuropathic conditions and to different sensory methods has not been systematically examined. The authors examined cholinergic receptor involvement in thermal and mechanical sensitivity in normal and neuropathic animals and its interaction with intrathecal clonidine. Normal rats and rats that received L5/L6 spinal nerve ligation were tested with acute radiant heat, paw pressure, and punctate mechanical stimulation before and after the intrathecal administration of saline, the muscarinic receptor antagonist, atropine, or a toxin to destroy cholinergic neurons, and then after intrathecal clonidine. Atropine, the cholinergic neuronal toxin, and saline did not alter baseline withdrawal thresholds. In nerve-injured rats, neither saline nor atropine altered antinociception from clonidine to a thermal stimulus, but atropine reduced the effect of clonidine to von Frey filament withdrawal threshold (34 +/- 5.6 vs. 14 +/- 5.8 g [mean +/- SEM], saline vs. atropine; P < 0.05) and to withdrawal threshold to paw pressure after clonidine (174 +/- 18 g vs. 137 +/- 16 g, saline vs. atropine; P < 0.05). These data suggest that after nerve injury, mechanical but not thermal antinociception from intrathecal clonidine relies on a muscarinic interaction, because only mechanical antinociception was antagonized by atropine. These results do not favor a regulation of nociceptive transmission by a tonic release of acetylcholine in nerve-injured rats.


Electric stimulation regulates the level of Ca-channels in chick muscle culture.
To examine the role of muscle activity in the expression of 1,4-dihydropyridine (DHP)-sensitive Ca-channels, we electrically stimulated chick skeletal muscle cells growing in culture. The number of Ca-channels was determined by a radioligand binding technique using [3H]PN200-110. The function of these channels was measured by depolarization-induced 45Ca uptake. We found that both the amount and the function of these channels were higher as a result of the increased muscle activity caused by electrical stimulation (ES).


Tumor-initiating activity of the dihydrodiols of 8-methylbenz[a]anthracene and 8-hydroxymethylbenz[a]anthracene.
The tumor-initiating activity of the 3,4-dihydrodiols (diols) as well as other metabolites of 8-methylbenz[a]anthracene (8-MBA) and 8-hydroxymethylbenz[a]anthracene (8-OHMBA) were examined in the classical 2-stage initiation-promotion model on mouse skin. The 3,4-diol of 8-MBA caused 2.2 times as many papillomas/mouse as did 8-MBA. The 3,4-diol of 8-OHMBA was not more tumorigenic than either 8-MBA or 8-OHMBA. None of the other diols tested, including the 5,6- and 8,9-diol of 8-MBA and the 5,6 and 10,11-diol of 8-OHMBA were remarkably tumorigenic. These data indicate that the 3,4-diol of 8-MBA is a good candidate as a proximate carcinogen of 8-MBA and further suggest that the bay region 3,4-diol-1,2-epoxide is a likely ultimate carcinogen of this compound on mouse skin.


Methodological issues in the use of administrative claims data to study surveillance after cancer treatment.
Administrative claims databases linked to tumor registry data provide an excellent opportunity for studying the follow-up care of cancer patients. Methodological principles of study design are reviewed, using examples drawn from the recently published literature. Most follow-up care is outpatient-based. Therefore, in studies using Medicare claims, the patient should be eligible for Medicare Part B and should not be enrolled in a Medicare HMO. In studies of surveillance testing, it may be appropriate to exclude subjects who are near death, in a hospice, or in whom a new or recurrent cancer develops. The definition of the period for measurements of surveillance testing requires consideration, as does periodicity in patterns of testing. Several analytic methods can be employed, from proportions undergoing testing to survival analysis methods. Measurement of 'surveillance tests' among control subjects (those without cancer) may be useful for comparison with cancer patients. To date, administrative claims data have been most useful in studies investigating the quality of, and disparities in, cancer care. With appropriate attention to methodological issues, linked tumor registry and administrative databases can provide important insights into the quality of survivorship care for cancer.


Tissue-specific expression of ALA synthase-1 and heme oxygenase-1 and their expression in livers of rats chronically exposed to ethanol.
5-Aminolevulinic acid synthase-1 (ALAS1) and heme oxygenase-1 (HO-1) are the rate-controlling enzymes for heme biosynthesis and degradation, respectively. Expression of these two genes showed tissue-specific expression pattern at both mRNA and protein levels in selected non-treated rat tissues. In the livers of rats receiving oral ethanol for 10 weeks, ALAS1 mRNA levels were increased by 65%, and the precursor and mature ALAS1 protein levels were increased by 1.8- and 2.3-fold, respectively, while no changes were observed in HO-1 mRNA and protein levels, compared with pair-fed controls. These results provide novel insights into the effects of chronic ethanol consumption on hepatic heme biosynthesis and porphyrias.


Brain ultrasound features in multiple births due to spontaneous conception compared with assisted reproductive techniques: a cross-sectional, population-based study.
Multiple pregnancies from spontaneous conception and obtained by assisted reproductive techniques (ART) are associated with a disproportionate share of complications compared with natural singleton pregnancies. The outcome of multiple pregnancies obtained by ART is still the subject of controversial opinions in the medical literature as they are associated with increased rates of perinatal complications, and perinatal mortality, as well as maternal complications. Aim of this study was to determine whether there are differences between these two groups of infants. We examined the imaging findings by means of brain ultrasound (performed at birth and sequentially up to their 6th month of age) in a cohort of 296 twins and triplets born following different techniques of assisted fertilization (63 pregnancies; 119 neonates) vs. spontaneous conception (94 pregnancies; 177 neonates). We did record, by means of X square corrected test, statistically significant differences (P=0.002) between the two populations at birth in the number of normal ultrasound scans (ART<spontaneous neonates); transient hyperechogenecity (spontaneous<ART neonates) and persistent hyperechogenecity (ART<spontaneous neonates). No differences in brain ultrasound findings between the two groups of ART and between spontaneous vs. assisted conceptions (P=0.959) at long-term follow-up have been noticed.


Australian infection control in endoscopy consensus statements on carbapenemase-producing Enterobacteriaceae.
Outbreaks of carbapenemase-producing Enterobacteriaceae clinical infections related to endoscopic transmission are well documented. The high morbidity and mortality associated with these infections emphasizes the need to reassess endoscopic reprocessing protocols. The Gastroenterological Society of Australia established a multi-society committee to formulate evidence-based consensus statements on the prevention and management of endoscopic transmission of carbapenemase-producing Enterobacteriaceae. A literature search was undertaken utilizing the MEDLINE database. Further references were sourced from published paper bibliographies. Nine statements were formulated. Using the Delphi methodology, the statements were initially reviewed electronically by the committee members and subsequently at a face-to-face meeting in Melbourne, Australia. After further discussion, four additional sub-statements were added resulting in a total of 13 statements. Each statement was assessed for level of evidence, recommendation grade and the voting on recommendation was recorded. For a statement to be accepted, five out of six committee members had to "accept completely" or "accept with some reservation." All 13 statements achieved consensus agreement. Eleven statements achieved 100% "accepted completely." Two statements were 83% "accepted completely" and 17% "accepted with some reservation." Of particular significance, automated flexible endoscope reprocessors were mandated for high-level disinfection, and the use of forced-air drying cabinets was mandated for endoscope storage. These evidence-based statements encourage preventative strategies with the aim of ensuring the highest possible standards in flexible endoscope reprocessing thereby optimizing patient safety. They must be considered in addition to the broader published guidelines on infection control in endoscopy.


[Contribution of PET using FDG in the diagnosis of lung cancer--first results].
Positron emission tomography (PET), when used with F-18 fluoro-deoxyglucose (FDG), contributes to the evaluation of patients with lung cancer. This technique of imaging detects active tumor tissue by showing increased radiopharmaceutical uptake by metabolically active cells. Thus, PET assists in the early diagnosis of pulmonary malignancies that appear only as non-specific findings on CT-scan or chest X-ray. In addition, it is helpful in staging lung cancer before and after resection, chemotherapy or radiotherapy, or their combined use. We performed 135 FDG-PET studies between July '97-April '99 and present our preliminary results with examples of the main indications for PET in lung cancer.


[Cytochromes c and P-450 as terminal acceptors in a reconstituted system of mitochondrial hydroxylation].
Both cytochromes c and P-450 can be reduced in vitro by a mitochondrial hydroxylation chain consisting of flavoprotein, adrenodoxin and NADPH as electron donors. The effects of pH, ionic strength, content and stoichiometry of intermediate electron carriers on the reduction rate of cytochromes c and P-450 have been compared. The data obtained demonstrate that the reduction of these cytochromes proceeds by different ways. It has been found that cytochrome c has an inhibitory effect on cytochrome P-450 reduction. On the other hand, cytochrome P-450 remarkably activates the process of cytochrome c reduction.


Quantitative three-dimensional sonographic assessment of pelvic blood after transvaginal ultrasound-guided oocyte aspiration: factors predicting risk.
To evaluate the fluid volume in the pelvis immediately and 3-5 days after transvaginal ultrasound-guided oocyte aspiration (TOAS) and to identify predictive factors for intraperitoneal bleeding. This was a prospective study of 83 infertile women undergoing controlled ovarian hyperstimulation followed by TOAS and embryo transfer (ET). Pelvic blood volume was measured by three-dimensional (3D) ultrasound examination 3-5 h after TOAS (post-TOAS), and prior to ET (2-3 days after TOAS; pre-ET). Pelvic blood volume was then correlated with the following procedure-related variables: day of hCG administration: number and diameter of ovarian follicles, endometrial thickness, serum estradiol levels; day of TOAS: number of retrieved oocytes, patient's perceived pain (Likert scale), duration of TOAS, diameters (using two-dimensional (2D) ultrasound) and 3D volume of pelvic fluid; day of ET: 2D diameters and 3D volume of pelvic fluid, perceived pain; pregnancy rate. The mean +/- SD volume of blood measured by 3D ultrasound after TOAS and before ET was 12.94 +/- 16.88 (range, 0-98.00) mL and 19.13 +/- 17.84 (range, 0-70.20) mL, respectively. Blood volume in the pelvis correlated most strongly with number of oocytes retrieved (post-TOAS: P < 0.01; pre-ET: P < 0.05), followed by pain level (post-TOAS: P < 0.01), number of follicles (post-TOAS: P < 0.05) and endometrial thickness (post-TOAS: P < 0.05). When all study variables were held constant, the number of oocytes and serum estradiol level proved to be significant predictors of the amount of fluid in the pelvis (post-TOAS/pre-ET: P < 0.01). If 2D ultrasound was used, the best predictor of fluid volume after TOAS was the width of the fluid scanned in the pelvis (P < 0.001). The amount of blood in the pelvis following TOAS in the present series was within acceptable clinical limits. The number of retrieved oocytes and pain after TOAS were found to be indicators of patients at risk of excessive bleeding. These findings have important implications for the improvement of postprocedural care.


[Evoked otoacoustic emissions and their modification by contralateral acoustic stimulation].
The active vibration of the basilar membrane as well as evoked otoacoustic emissions (EOAE) are probably based on the motile properties of cochlear outer hair cells (OHC). In the present study we examined the effects of contralateral acoustic stimulation on ipsilateral EOAE and thereby the active cochlear micromechanics. Contralateral white noise with intensities below 30 dB HL enhanced the EOAE amplitude, whereas higher sound levels reduced the evoked acoustic emissions. Similar effects of contralateral acoustic stimuli on ipsilateral EOAE were observed in patients with a conductive hearing loss. However, the required sound levels were higher compared to probands with normal hearing. In controls with unilateral deaf patients white noise up to 60 dB HL did not alter the EOAE amplitude. We concluded, that in patients with normal hearing or unilateral conductive hearing loss, effects of contralateral acoustic stimulation on evoked ipsilateral sound emissions may be due to the activation of crossed olivo-cochlear efferents reaching the OHCs.


Genomics and Ecology of Novel N2O-Reducing Microorganisms.
Microorganisms with the capacity to reduce the greenhouse gas nitrous oxide (N2O) to harmless dinitrogen gas are receiving increased attention due to increasing N2O emissions (and our need to mitigate climate change) and to recent discoveries of novel N2O-reducing bacteria and archaea. The diversity of denitrifying and nondenitrifying microorganisms with capacity for N2O reduction was recently shown to be greater than previously expected. A formerly overlooked group (clade II) in the environment include a large fraction of nondenitrifying N2O reducers, which could be N2O sinks without major contribution to N2O formation. We review the recent advances about fundamental understanding of the genomics, physiology, and ecology of N2O reducers and the importance of these findings for curbing N2O emissions.


The realness of risk: gene technology in Germany.
This paper examines the material relations of risk within a dispute about the hazards of manufacturing human insulin using gene technology, and the rôle played by the referent 'real risk' in the technical performance of risk in that dispute. It draws on recent work in science and technology studies that extends actor-network theory to examine the performance of reality in scientific practice. The multiplicity of risks in the dispute, and the links made and unmade between them, are examined. I argue that in the dispute, risks were contingently linked and separated around a referent 'real risk' that emerged within the recombinant DNA debate of the late 1970s. I contrast my account of risk with realist and relativist accounts, each of which values risk as an abstract entity. In my account, risk's value is contingent upon sets of material relations that link hazards and procedures for their minimization. Risk's realness emerges as some risks are linked and others separated, working a multiple/singular relation in an ontological politics of risk.