Heterogeneity of myosin antigenic expression in vascular smooth muscle in vivo.
Rabbit antisera elicited against purified human nonmuscle (platelet) and smooth muscle (uterine myometrium) myosins identified distinct species of myosin when frozen sections of a variety of mammalian tissues were examined by immunofluorescence microscopy. Antiplatelet myosin antiserum specifically stained several nonmuscle cell types including epithelial, some connective tissue, and all vascular endothelial (arterial, venous, capillary) cells. Antismooth muscle myosin antiserum stained only smooth muscle and no other cell types. Neither antiserum reacted with rat cardiac (ventricular) or skeletal muscle cells. Antismooth muscle myosin antiserum staining was detectable in medial vascular smooth muscle in all vessels examined from rat, bovine, human, and guinea pig sources (including elastic and muscular arteries, arterioles, venules, and veins). Although antiplatelet myosin antiserum did not stain nonvascular smooth muscle or vascular smooth muscle in muscular arteries, arterioles, venules, or veins, it did uniformly and specifically stain medial vascular smooth muscle in elastic arteries. This staining of elastic arteries was abolished by absorption of antiplatelet myosin antiserum with purified platelet myosin but not uterine myosin. Similarly, the reactivity of antismooth muscle myosin antiserum was abolished by incubation with uterine but not platelet myosin. The differences in staining patterns observed with antiplatelet myosin antiserum and antismooth muscle myosin antiserum in elastic arteries versus other blood vessels suggests a heterogeneity of antigenic expression in vascular smooth muscle myosin. The most likely explanations for this heterogeneity are the presence of different gene products (myosin isozymes) or a posttranslational alteration (possibly conformational) of a single myosin species. Heterogeneity in this important component of the contractile apparatus of vascular smooth muscle may have significant implications for the physiology and pathophysiology of the vessel wall.


Excimer laser photorefractive keratectomy for high myopia: four-year experience with a multiple zone technique.
The purpose of the study is to evaluate the results of the authors' 4-year experience with excimer laser photorefractive keratectomy (PRK) and multiple optical zone corneal ablation in highly myopic eyes. The authors retrospectively evaluated 56 eyes of 44 patients (mean refraction, -11.3 diopters [D]; range, -5.75 to -24.5 D) who underwent PRK with a Visx Model 20/20 laser (Visx, Santa Clara, CA). Preoperative visual acuity of 20/40 or better was present in 46 eyes. Corneal ablation was divided into concentric optical zones (4, 5, and 6 mm), allowing corrections of up to 18 D, with a refractive goal of within -1 D from emmetropia in 49 eyes. A hand-held fixation system was always used, and a nitrogen-blowing system (NBS) was used in the first 21 eyes only. Before retreatment, the range of final cycloplegic refraction from emmetropia in eyes treated with NBS versus not was within +/-1 D in 6 (28.6%) and 15 eyes (44.1%), between -1.25 and -3 D in 5 (23.8%) and 14 eyes (41.1%), and more than -3 D in 10 (47.6%) and 5 eyes (14.7%), respectively. No lines of visual acuity were lost in 37 eyes (80.4%) with 20/40 or better visual acuity before surgery. Three eyes showed vision loss due to worsening of myopic maculopathy and one due to corneal haze. Correction stabilized within 9 months, and at a mean time of 25.6 months, the correction attained was of -8.5 +/- 3.6 D, achieving 90.3% of attempted correction. Eyes with preoperative myopia less than -10 D (n = 27) showed regression less than -1 D in 8 eyes (29.6%), between -1.25 and -3.00 D in 5 eyes (18.5%), and greater than -3.00 D in 1 eye (3.7%); eyes with more than -10 D (n = 29) regressed in 3 (10.3%), 6 (20.7%), and 1 eye (3.4%), respectively. Severe haze was observed in 11 eyes (19.6%) 3 months after surgery. Two eyes showed decentration greater than 1.5 mm. At last examination, night driving problems were reported by 12 (41.4%) of 29 patients evaluated who drive. After the NBS was eliminated, the multiple-zone technique achieved a long-term, stable 83.1% reduction of preoperative myopia. Patients with severe myopia appreciated reduction of most of the refractive defect, although perception of halos was noted by 16 patients.


Amelioration of Early Markers of Diabetic Nephropathy by Linagliptin in Fructose-Streptozotocin-Induced Type 2 Diabetic Rats.
Early prediction and clinical intervention are extremely important in order to delay or hinder diabetic nephropathy (DN) progression. This study aimed to detect early signs of DN and study the potential ameliorating effect of the dipeptidyl peptidase-4 inhibitor, linagliptin, on some early markers for DN in fructose-streptozotocin (Fr-STZ)-induced diabetic rats. Fr-STZ rats were treated with either linagliptin (3 mg/kg p.o. daily), metformin (350 mg/kg p.o. daily), or their combination for 6 weeks. Fr-STZ DN rats exhibited obvious tubular renal damage and glomerular podocyte injury as confirmed by renal kidney -injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and vanin-1 mRNA, as well as urinary N-acetyl-β-D-glucosaminidase elevation and nephrin mRNA suppression, associated with the appearance of marked renal interstitial fibrosis and glomerulosclerosis despite the absence of microalbuminuria. Initiation of oxidative, inflammatory, fibrotic, and apoptotic reactions was evident in the settings of renal hyperglycemia. Linagliptin significantly modulated the aforementioned renal tubular injury makers and restored glomerular nephrin expression as well as reversed renal histopathological alterations. Oxidative, inflammatory, fibrotic and apoptotic processes were also alleviated. This study suggests that linagliptin exerts renoprotection against early features of DN in rats probably by inhibition of high glucose-induced renal tubular and glomerular injury thereby hampering KIM-1 and NGAL as well as vanin-1 associated with renal inflammation, fibrosis and oxidative stress.


Long-term results of digital arthrodesis with the Harrison-Nicolle peg.
This study determined the long-term success of digital arthrodesis with the Harrison-Nicolle peg. We reviewed 90 digital joints in 60 patients fused with the peg between 1986 and 1998 at a mean follow-up of 6 (range 2-11) years. The prime indication for surgery was rheumatoid arthritis. The early complication rate was 8%. At 1 month 89% of joints were pain-free and stable. In the long-term follow up, 96% of the joints were pain-free and stable, with the original angle of fusion. 85% achieved bony fusion, with no clinical difference between bony and fibrous fusion. Overall there was a significantly higher complication rate in the distal interphalangeal joint. We conclude that, with the exception of the distal interphalangeal joint, the Harrison-Nicolle peg is extremely effective for digital arthrodesis in the rheumatoid patient.


Self-assembly of anionic gemini surfactant: fluorescence resonance energy transfer and simulation study.
The interaction of dyes with a sulfonated Gemini surfactant was investigated in aqueous solution using Förster resonance energy transfer with acridine orange (AO) as a donor and rhodamine B (RhB) as an acceptor. Surface tension results showed that AO and RhB have different effects on the self-assembly of the Gemini surfactant, with AO giving a higher critical micelle concentration (cmc) and lower surface tension, while the opposite was observed for RhB. Energy transfer from AO to RhB was observed in the presence of the surfactant, and the energy transfer efficiency initially improved with increased surfactant concentration but then decreased significantly when the surfactant reached a higher concentration due to the formation of larger aggregates, which increased the average distance between AO and RhB. Dynamic light scattering demonstrated the existence of these large aggregates. Moreover, simulations using dissipative particle dynamics supported the experimental results.


Quantitative, three-dimensional diagnostics of multiphase drop fragmentation via digital in-line holography.
Quantitative application of digital in-line holography (DIH) to characterize multiphase fragmentation is demonstrated. DIH is applied to record sequential holograms of the breakup of an ethanol droplet in an aerodynamic flow field. Various stages of the breakup process are recorded, including deformation, bag growth, bag breakup, and rim breakup. A recently proposed hybrid method is applied to extract the three-dimensional (3D) location and size of secondary droplets as well as the 3D morphology of the rim. Particle matching between sequential frames is used to determine the velocity. Coincidence with the results obtained from phase Doppler anemometry measurement demonstrates the accuracy of measurement by DIH and the hybrid method.


[Structural typology of Brazilian primary healthcare units: the 5 Rs].
The structural typology of Brazil's 38,812 primary healthcare units (UBS) was elaborated on the basis of the results from a survey in cycle 1 of the National Program for Improvement in Access and Quality of Primary Care. Type of team, range of professionals, shifts open to the public, available services, and installations and inputs were the sub-dimensions used. For each sub-dimension, a reference standard was defined and a standardized score was calculated, with 1 as the best. The final score was calculated by factor analysis. The final mean score of Brazilian UBS was 0.732. The sub-dimension with the worst score was "installations and inputs" and the best was "shifts open to the public". The primary healthcare units were classified according to their final score in five groups, from best to worst: A, B, C, D, and E. Only 4.8% of the Brazilian UBS attained the maximum score. The typology showed specific characteristics and a regional distribution pattern: units D and/or E accounted for nearly one-third of the units in the North, and two-thirds of units A were situated in the South and Southeast of Brazil. Based on the typology, primary healthcare units were classified according to their infrastructure conditions and possible strategies for intervention, as follows: failed, rudimentary, limited, fair, and reference (benchmark). The lack of equipment and inputs in all the units except for type A limits their scope of action and case-resolution capacity, thus restricting their ability to respond to health problems. The typology presented here can be a useful tool for temporal and spatial monitoring of the quality of infrastructure in UBS in Brazil.


Experimental therapy of systemic lupus erythematosus: the treatment of NZB/W mice with mouse soluble interferon-gamma receptor inhibits the onset of glomerulonephritis.
Female NZB/W F1 mice develop an autoimmune disease similar to human systemic lupus erythematosus (SLE), and ultimately die of glomerulonephritis. Starting at the age of 16 weeks NZB/W F1 mice were treated for a period of 19 weeks with soluble interferon-gamma receptor (sIFN-gamma R), anti-IFN-gamma monoclonal antibody (mAb) or IFN-gamma. All mice treated with sIFN-gamma R or anti-IFN-gamma mAb were alive 4 weeks after the treatment was discontinued, whereas 50% of mice died in the placebo groups and 78% of the mice died in the IFN-gamma-treated group. Histologically, there was severe membrano-proliferative glomerulonephritis in IFN-gamma- and placebo-treated mice, and minimal or no mesangioproliferative disease in mice receiving sIFN-gamma R or anti-IFN-gamma mAb. The renal mononuclear infiltrate (T lymphocytes and monocytes), expression of major histocompatibility complex class II antigen and glomerular immunoglobulin and complement deposition were reduced in those mice. These data suggest that an IFN-gamma inhibitor, such as the soluble IFN-gamma R, can be used for SLE therapy in the early stages of the disease.


Oxidative ring expansion of spirocyclic oxindole derivatives.
Oxidation of the spirocyclic oxindole derivative, isamic acid 1, led to decarboxylation and ring expansion to quinazolino[4,5-b]quinazoline-6,8-dione 7 rather than, as previously believed, its isomer 6. The structure of 7 was confirmed by X-ray crystallography. Condensation of isatin (indole-2,3-dione) and 2-aminobenzamide led to the spirocyclic molecule, spiro[3H-indole-3,2'(1H)quinazoline]-2,4'(1H,3H)dione 8, which was also identified as an intermediate in the oxidation of isamic acid. Mild hydrolysis of 7 gave the 10-membered molecule 22. Isamic acid could easily be converted to N-nitrosoisamic acid, which when heated in ethanol underwent a ring expansion to a hydroximino derivative, 38, of compound 6. The structure of 38 was confirmed by X-ray crystallography.


Can idiopathic tinnitus be caused by hyperuricemia?
It is hypothesized that heretofore medically untreatable idiopathic tinnitus of intermittent intensity may be related to hyperuricemia. A number of pathogenic features common to both are given. Hyperuricemia is treatable.


Inguinal sweat gland carcinoma with choriocarcinomatous differentiation.
An inguinal sweat gland carcinoma is described including the unusual occurrence of alpha hCG. The alpha hCG was demonstrated in the tumor presenting choriocarcinomatous differentiation and undifferentiated polygonal cells in ordinary tumor nests. beta hCG and SP-1 were weakly and sporadically demonstrated in a small area of the tumor presenting choriocarcinomatous differentiation. On the other hand, hPL and histochemical reaction of placental type alkaline phosphatase were not observed in the choriocarcinomatous and undifferentiated tumor cells. CEA was observed in both ordinary sweat gland carcinoma nests and choriocarcinomatous differentiated regions. In the ordinary tumor nests, enzyme histochemical reactions of phosphorylase and SDH were positive. And S 100 protein was sporadically demonstrated. In spite of chemotherapy and radiotherapy, the patient died after a short duration of the disease.


Strengths and limitations of meta-analysis: larger studies may be more reliable.
Meta-analysis of randomized controlled trials combines information from independent studies that address a similar question to provide more reliable estimates of treatment effects. At the present time, the methodology and usefulness of meta-analysis is under scrutiny. In the first part of this paper, we summarize the limitations of meta-analysis and make suggestions for improvements. In the second part, we illustrate strengths and limitations using examples of meta-analyses and subsequent large trials that address the same question. We develop the hypothesis that the size of the meta-analysis may be a useful measure of reliability. Small meta-analyses (i.e., those with less than 200 outcome events) may only be useful for summarizing the available information and generating hypotheses for future research. The results of small meta-analyses should be regarded with caution, even if the p value shows extreme statistical significance. Larger meta-analyses (i.e., those with several hundred events) are likely to be more reliable and may be clinically useful. Well-conducted meta-analyses of large trials using individual patient data may provide the best estimates of treatment effects in the cohort overall and in clinically important subgroups.


Establishment of three human liver carcinoma cell lines and some of their biological characteristics in vitro.
Three cell lines derived from liver carcinoma specimens of two male and one female operated patients have been successfully established in vitro and designated by the names of BEL-7402, BEL-7404 and BEL-7405. In the course of the establishment (from the 2nd transfer onwards) studies were made to characterize them. The doubling time of cell population was found to be 20--26 hr. They formed tumor nodules upon heterologous transplantation. They appeared as epithelial-like cells in morphology and showed, in addition to desmosomes, the presence of cytoplasmic tonofibrills which were typical of epithelial cells by electron microscopy. The ultrastructural features were different from normal human liver cells, but similar to clinical hepatoma cells. They had hypotriploid chromosone number with one abnormally long acrocentric chromosome present in all 3 cell lines and additional small acrocentric chromosome and chromosome fragment in BEL-7405 line of cells. AFP were detected intracellularly by the indirect immunofluorescent method. LDH isoenzyme showed a pattern different from that of human adult liver, but similar to those of embryonic liver and clinical hepatoma with the increase of the percentage of LDH-1 (H-type) at the expanse of LDH-5 (M-type), i.e. with a higher H/M ratio. The results suggest the 3 lines of liver carcinoma cells as rapidly growing and not well differentiated epithelial-like malignant cells.


Court strikes out latest action in contaminated blood litigation.
On 24 June 2003, the Federal Court of Canada--Trial Division struck out an action by three hemophiliacs infected with HIV through contaminated blood products. The case arose out of the destruction of records by members of Canadian Blood Committee (CBC) in 1989. The defendants were the government of Canada and three government of Canada employees who worked at the CBC in 1989 and were alleged to have been involved in the destruction of records.


Level of HER-2/neu protein expression in breast cancer may affect the development of endogenous HER-2/neu-specific immunity.
We questioned whether the incidence or magnitude of the humoral or cellular immune response to the self-tumor antigen HER-2/neu is influenced by the level of HER-2/neu protein overexpression as defined by immunohistochemical staining of tumors in breast cancer patients. We obtained peripheral blood from 104 women with stage II, III, and IV pathologically confirmed HER-2/neu-overexpressing breast cancer. Patients were categorized with +1 (n = 14), +2 (n = 20), or +3 (n = 70) HER-2/neu overexpression by institutional pathologic report. Circulating antibodies to HER-2/neu were evaluated using ELISA. T-cell responses to HER-2/neu were measured using an antigen-specific tritiated thymidine incorporation assay. Eighty-two percent of subjects with HER-2/neu antibodies were +3 overexpressors compared with 18% +2 overexpressors and 0% +1 overexpressors, a highly significant difference (P < 0.001), and there were significant differences in the magnitude of the HER-2/neu-specific antibodies between groups with varying HER-2/neu protein expression (P = 0.022). In addition, 65% of subjects with HER-2/neu-specific T cells were +3 overexpressors compared with 16% +2 overexpressors and 19% +1 overexpressors (P = 0.001). Data presented here indicate that endogenous HER-2/neu-specific humoral and T-cell immunity is greater in patients with +3 protein overexpression in their tumors than in patients with lower levels of HER-2/neu expression. Overexpression of a self-tumor-associated protein is a potential mechanism by which immunogenicity is enhanced and may aid in the identification of biologically relevant proteins to target for immune-based molecular cancer therapies.


Lamb serum recognition of infective larvae and adult Haemonchus contortus antigens.
Sixteen- to eighteen-week-old lambs were infected with 2500 3rd stage larvae (L-3) of Haemonchus contortus or kept as uninfected controls. Two months later all animals were challenged with 5000 L-3 of this parasite. Soluble antigens of H. contortus L-3 and adult worms were analyzed by SDS-PAGE and Western blotting during experimental infection and challenge. Antigens from both sources, particularly of low molecular weight under reducing conditions, were recognised by the pooled sera of infected lambs. No single L-3 antigen was recognised by all infected lambs, whereas two peptides having around 25 and 26 kDa from adults were recognised by infected animals during the patency and could be of potential use in the diagnosis of lamb haemonchosis.


Noise reduction in solid-state lasers using a SHG-based buffer reservoir.
The cancellation of resonant intensity noise, from a few kHz up to several GHz, is reported using a second-harmonic generation (SHG) buffer reservoir in a Nd:YAG solid-state laser. This approach is shown to be well suited and easily optimizable for reducing the excess noise lying at the laser relaxation oscillations as well as that originating from the beating between the lasing mode and nonlasing adjacent longitudinal modes. A thorough analysis of noise spectra of both laser and SHG signals confirms definitely that noise reduction is a consequence of a deep laser dynamics modification rather than noise evacuation mechanism.


Peripheral arterial disease and bypass surgery in the diabetic lower limb.
PAD is very common in people with diabetes and is one of the strongest predictors of developing nonhealing foot ulcers and suffering amputation. There is strong evidence to show that early detection of PAD and revascularization will reduce amputations. Despite this, many patients have no vascular assessment even when they present with a foot ulcer or before amputation. Even when identified, patients are referred late, which worsens their outcome. Currently there is no evidence to support surgical revascularization over endovascular treatments, but in reality the techniques are complementary and the choice of revascularization procedure should be determined by an experienced multidisciplinary vascular team. Surgical revascularization can achieve good results but careful patient selection, operative planning, and the use of autologous vein are necessary. What is clearly apparent is that at present not enough patients are being offered revascularization to prevent amputation.


Molecular mechanisms controlling the fibrotic repair phenotype in cornea: implications for surgical outcomes.
Incisional or ablation injury to the corneal stroma is repaired by deposition of a fibrotic tissue produced by activated keratocytes, whereas cells lost from the underlying stroma after epithelial abrasion are simply replaced by keratocyte replication without expression of fibrotic markers. The purpose of this study was to investigate mechanisms that determine this differential keratocyte response. A penetrating keratectomy rabbit model was adapted for mice to study the fibrotic repair response. A mouse epithelial abrasion model was applied to study the stromal cell replacement response. A primary rabbit corneal cell culture model and an organotypic culture model were also used. When the epithelium was prevented from resurfacing the cornea after penetrating keratectomy, expression of fibrotic markers was considerably reduced. TGF-beta2 was determined to be a major substance produced by corneal epithelial cells capable of inducing the fibrotic phenotype. In the intact mouse cornea, TGF-beta2 was confined to the uninjured epithelium, but was released into the stroma during fibrotic repair. By contrast, TGF-beta1 was never found in the epithelium. When epithelial cells were cultured on a basement-membrane-like gel or allowed to deposit their own basement membrane in organotypic culture, TGF-beta2 production was reduced. Return of a basement membrane after wounding in vivo correlated with loss of the fibrotic phenotype. In the epithelial debridement injury model in which the basement membrane was left intact, TGF-beta2 remained confined to the corneal epithelium, consistent with the absence of a fibrotic phenotype. These data suggest that integrity of the basement membrane is a deciding factor in determining the regenerative character of corneal repair.


Gradient of pressure and time between proximal anal canal and high-pressure zone during internal anal sphincter relaxation. Its role in the fecal continence mechanism.
The normal response to rectal distention is a relaxation of the proximal anal canal (PAC). We hypothesized that this mechanism would require a gradient of pressure and time to preserve continence. Sixteen volunteers (10 male), mean age, 41.5 (range, 24-60) years, were studied using an eight port axial catheter with a compliant balloon at its tip. Relaxation was induced by a small volume of rectal distention (15-30 ml of air) and was recorded until recovery of resting anal pressure (RAP). Duration of relaxation was measured until recovery of RAP. Amplitude of relaxation was determined between RAP before rectal distention (RAP-BR) and pressure at the point of maximum relaxation (RAP-PMR). Gradient of pressure was determined by comparing RAP-PMR in the high-pressure zone (HPZ) and PAC. Contraction in the distal anal canal was interpreted as external anal sphincter contraction (EASC) and was compared with RAP-PMR in the HPZ. Relaxation was significantly greater in PAC than in HPZ (50 vs. 36 percent; P = 0.001). RAP-PMR was significantly higher in HPZ than in PAC (30.7 vs. 12.6 mmHg; P = 0.001). EASC was observed in six patients and did not show significant difference with RAP-PMR in HPZ (39.7 vs. 36.3 mmHg; not significant). Relaxation began at the same time in all levels but lasted significantly longer in PAC compared with HPZ (13.5 vs. 9.4 sec; P = 0.003). Anal relaxation induced by small volume rectal distention involves a gradient in the pressure and time of relaxation between PAC and the HPZ.


Relations of alcoholic beverage use to subsequent coronary artery disease hospitalization.
Unresolved questions about the inverse relation between alcohol consumption and coronary artery disease (CAD) include; Dose past drinking have a role in the apparently higher CAD risk of abstainers? Is the lower CAD risk found only among lighter drinkers? Does type of alcoholic beverage matter? Are abstainers at higher risk of CAD because symptoms or illness cause many to quit drinking? In a prospective study among 85,001 health examinees giving an alcohol history at a health examination from 1978 through 1982, 756 persons were later hospitalized for CAD in the same years. Using lifelong abstainers as the reference group and controlling for age, sex, race, smoking, coffee drinking and education, analysis showed that past drinkers and very infrequent drinkers had CAD risk similar to that of lifelong abstainers. A significantly and progressively lower CAD risk was found at higher drinking levels. Preference for wine, liquor or beer had no major independent effect. A subset of persons apparently free of CAD and other recent major illnesses showed a similar alcohol-CAD relation. Thus, this study suggests a negative answer to the 4 questions above and supports the view that alcohol protects against CAD. As most of the apparent protection was present at a daily intake of 1 to 2 drinks/day, an amount generally regarded as safe for most persons, the findings should not be used to justify heavier drinking.


Does consciousness exist?--In what sense?
This commentary on Barutta et al. (IPBS: Integrative Psychological & Behavioral Science 44:2, 2010) elaborates the authors' ideas from a new angle. The following positions of the authors are presented and analyzed: emergetism, two different languages of the description of the phenomena, and the notion of "efficient causality". A different approach to the issue of mind-brain interaction is suggested. The key idea of the approach is based not on posing select characteristics which the mind, the brain, or the human consciousness is supposed to have, but on the description of the logic of the activity of this global system, and of the structures that make this characteristics possible to exist.


Outcome After Surgery for Extremity Soft Tissue Sarcoma in Patients Presenting With Metastasis at Diagnosis.
About 10% of patients present with metastasis at diagnosis in extremity soft tissue sarcoma (STS). Although the prognoses of these patients is generally poor, prolonged survival has been demonstrated in some patients. Thus, better prognostication is needed to guide decisions regarding adjuvant therapy and surveillance. This study sought to analyze the survival and to identify clinicopathologic factors associated with survival in extremity STS patients presenting with metastasis at diagnosis. Review of 43 patients presenting with metastasis at diagnosis who underwent resection of the primary tumor was performed. Patient, tumor, and treatment-related factors were analyzed for possible prognostic effect on survival. The median survival of all patients was 22±4.1 months. The 2- and 5-year survival rates were 45.6% and 18.0%, respectively. In univariate analysis, tumor location in lower extremity (P=0.041) and the performance of metastasectomy (P=0.001) were significantly associated with better survival. In multivariate analysis, only the performance of metastasectomy remained significant (hazard ratio=3.8, P=0.012). The median survival of patients who underwent metastasectomy was significantly longer than that of patients who did not undergo metastasectomy (41±8.4 vs. 11±3.8 mo, P=0.001). Extremity STS patients who present with metastasis at diagnosis have a poor prognosis. Patients who undergo metastasectomy have a better chance for prolonged survival.


Tumors after renal and cardiac transplantation.
Organ transplant recipients treated with immunosuppressive therapy are prone to develop malignancies particularly squamous cell carcinomas of the skin, non-Hodgkin's lymphomas, Kaposi's sarcomas, carcinomas of the vulva and perineum, in situ carcinomas of the uterine cervix, renal carcinomas, hepatomas, and various sarcomas. The earliest tumors to appear are the Kaposi's sarcoma at an average of 21 months after transplantation, and the latest are carcinomas of the vulva and perineum, at an average of 112 months after transplantation. The tumors that develop in cardiac allograft recipients compared with renal transplant recipients are predominantly non-Hodgkin's lymphomas and more rarely, skin, uterine cervical and vulvar tumors. Major factors accounting for these differences are the intensity of immunosuppressive therapy given to the cardiac patients and the much longer follow-up of the renal allograft recipients.


Syndrome of inappropriate antidiuretic hormone in association with amiodarone therapy: a case report and review of literature.
Amiodarone is a class III antiarrhythmic agent that is widely used in the treatment of a variety of arrhythmias. Several different systemic side effects are reported after use of this medication. In this article, we report a case that had developed syndrome of inappropriate antidiuretic hormone (SIADH) after starting treatment with this agent. The patient is a 66-year-old male with past medical history of hypertension, hyperlipidemia, coronary artery disease, and class III New York Heart Association congestive heart failure who presented with monomorphic nonsustained ventricular tachycardia. A loading dose of amiodarone followed by maintenance dose was started. Baseline serum sodium of 138 mmol/L on admission decreased to 119 mmol/L by day 7, and a diagnosis of SIADH was made. The patient was not taking any other medication known to cause SIADH, nor had any such comorbidity to explain it. Serum sodium increased to 133 and 138 mmol/L, respectively, after 16 and 33 days from discontinuation of amiodarone. SIADH is a rare but serious side effect of amiodarone and practicing physicians should be aware of this complication, particularly after loading dose of the medication.


Hematopoietic stem cell transplantation for acute myeloid leukemia: to whom, when, and how.
Allogeneic hematopoietic stem cell transplant (HSCT) is an established treatment modality with curative potential for acute myeloid leukemia (AML). There has been a significant rise in the number of HSCT procedures performed over the past decade due in part to improved supportive care and innovative techniques such as reduced-intensity conditioning. Expanding alternative donor options such as umbilical cord blood and haploidentical HSCT, taken together with improved outcomes of matched unrelated donors, has resulted in a suitable donor for most patients with an HSCT indication. Recent advances in molecular diagnostics that incorporate genetic mutational analysis into existing cytogenetic-based models should improve selection of patients at high risk of relapse most likely to benefit from HSCT. Improvements in minimal residual disease monitoring hold promise for adding prognostic information, and informing the clinician of impending relapse. The choice of the conditioning regimen involves weighing a patient's unique toxicity and relapse risks. Despite improvements, relapse remains the primary source of treatment failure after HSCT for treatment of AML. The introduction of novel therapies into the clinic, together with improved patient selection, offers hope for decreasing relapse and improving outcomes for AML patients.


Transgenic Hypericum perforatum.
Plant transformation is an important tool with many applications in modern plant biology. Although this technique is primarily used to produce superior crop varieties, it is also being utilized to answer basic questions concerning gene function and regulation in contemporary functional genomics research. In our laboratory, we have established a transformation system for Hypericum perforatum. This protocol involves the transfer of foreign DNA into H. perforatum organogenic nodule explants via particle-bombardment and the regeneration of shoots from the explants under selection pressure. We have successfully used this method to express ss-glucuronidase and hygromycin phosphotransferase genes in H. perforatum. Molecular analyses of putative phenotypically normal transgenic plants show stable integration of the transgenes into the plant nuclear genome. Here we describe the procedure for the transformation of H. perforatum.


[Minimum residual leukemic cells in genetically marked brown Norway rat myelocytic leukemia model].
Different methods were used to detect minimal residual leukemic cells (LT 12 nl), which had been genetically marked with E. coli 1 acZ and neo-gene by retrovirus vector mediated gene transfer. The detection levels of flow cytometry based FDG staining and fluorophotometric method based MUG staining were 10(-3) to 10(-4) and 10(-2) to 10(-3), respectively. The method of G 418 selective agar culture was demonstrated as a 10(-4) to 10(-5) levels for the detection of LT 12 nl residual leukemic cells in bone marrow. The results indicated that the selective agar culture can be used as a sensitive method for the study of minimum residual disease in the BNML leukemia model. We have used the selective agar culture to study the distribution of clonal LT 12 nl cells in BNML during minimum residual disease (MRD). A heterogenous distribution pattern of the clonal leukemic cells was found in the genetically marked BNML leukemia model during the MRD phase.


Anterosuperior dislocation of the shoulder joint in an older patient with Parkinson's disease.
An 83-year-old woman, subsequently diagnosed with Parkinson's disease, fell on her right shoulder. Radiographs showed the humeral head dislocated anterosuperiorly. The supraspinatus tendon was massively disrupted and judged irreparable. The subscapularis tendon was repaired, however re-dislocation of the humeral head was confirmed after the surgery but further treatment was rejected as she was almost pain free and had a low activity level. The patient was followed up for one year after surgery and her shoulder became almost pain-free, but range of motion with active elevation was limited. In such cases a goal of absence or reduction of pain rather than real repair might be considered appropriate.


[Agoraphobia: combined treatment and virtual reality. Preliminary results].
Several validation studies have identified the use of certain psychodrugs, cognitive-behavioral therapy (CBT) and combined treatment as effective procedures for the treatment of agoraphobia. Recent findings suggest that agoraphobia can also be treated with virtual reality techniques (VRET) as an alternative exposure technique to virtual reality stimuli. Twenty-seven patients with agoraphobia were distributed into two groups of psychoactive drugs (paroxetine and venlafaxine) and into two cognitive- behavioral procedures (with or without exposure to VRET). Seven virtual situations were used. Preliminary results show significant improvements in all the experimental groups. Regarding the psychodrugs (paroxetine and venlafaxine) both significantly improved the symptoms and in regards to the CBT, patients treated with VRET, especially the chronic patients, seem to obtain the best results. Agoraphobia combined treatments including paroxetine, venlafaxine and cognitive-behavioral therapy (with or without VRET) seem to have clear benefits for the patients. VRET seem to be a possible and effective treatment for agoraphobic patients, especially for those with chronic agoraphobia.


Concurrent and Predictive Associations Between Infants' and Toddlers' Fearful Temperament, Coparenting, and Parental Anxiety Disorders.
This study investigated the bidirectional relations between two dimensions of coparenting (the way parental figures cooperate in parenting), undermining and support, and child fearful temperament longitudinally from infancy to toddlerhood, while inspecting the moderating role of parents' anxiety disorders. Questionnaire data on coparenting and child fearful temperament were obtained from 135 mothers, fathers, and their firstborns at 4 months, 12 months, and 30 months. Parental anxiety disorder severity was assessed with a semistructured interview before the birth of the child. Multilevel analysis revealed that, across measurement moments, undermining coparenting, but not supportive coparenting, was concurrently related to higher child fearful temperament. Parental anxiety disorder severity was related to more undermining coparenting but not to supportive coparenting. No moderation effects for parental anxiety disorder or for parent gender were found in the relations between coparenting and child fearful temperament. We conclude that more parental anxiety is related to a lower quality of the coparenting relationship, which in turn is associated to more child fearful temperament. More specifically, it appears that undermining coparenting, and not supportive coparenting, is related to child fearful temperament and parental anxiety disorder severity. Our results suggest that undermining coparenting, by both father and mother, is one of the mechanisms that may contribute to the intergenerational transmission of anxiety from parent to child. The coparenting relationship may be a useful target in the prevention and treatment of child anxiety.


The effect of loss of gallbladder function on biliary lipid composition in subjects with cholesterol gallstones.
The effect on biliary lipid and bile acid composition was assessed during the development of gallbladder nonfunction in 5 subjects with asymptomatic cholesterol cholelithiasis. There was a significant increase in the relative proportion of bile salt but a decrease in that of cholesterol in bile after development of gallbladder nonfunction which persisted after recovery from cholecystectomy. These findings were associated with a decrease in cholesterol crystals in bile sediment and an increase in the proportion of secondary bile acids after cholangiographic evidence of gallbladder nonfunction. Percentage cholesterol saturation of bile reverted to normal after development of gallbladder nonfunction which persisted after recovery from cholecystectomy.


[Regional variations in homicide mortality in Jalisco, Mexico].
The present study describes regional variations in homicide rates in Jalisco State, Mexico, in 1989-1991, 1994-1996, and 1999-2000, analyzing the trends by gender and socioeconomic stratum. Using mortality data generated by the National Institute for Statistics, Geography, and Information Technology, homicide rates adjusted by age and gender were calculated, along with rate/female rate ratios; rate ratios by socioeconomic stratum and 95% confidence intervals were also calculated. According to the results, the homicide rate showed: a downward trend in the 1990s; a regional homicide mortality pattern, with the highest rates in peripheral regions, considered among the poorest areas in the State; municipalities with the lowest socioeconomic conditions also presenting a statistically significant excess homicide mortality; and an evident over-mortality from homicide among males. The results point to tasks and challenges for public health and law enforcement institutions, including the need to implement different inter-institutional policies that take into consideration the characteristics of homicide and violent crime in Jalisco.


Prospective evaluation of a logistic model based on sonographic morphologic and color Doppler findings developed to predict adnexal malignancy.
To assess prospectively a logistic model based on sonographic morphologic and color Doppler findings, which had been developed to predict adnexal malignancy, 167 consecutive and unselected patients (mean age, 45.7 yr; range, 17 to 81 yr; 113 [67.7%] premenopausal and 54 [32.3%] postmenopausal) diagnosed as having an adnexal mass and scheduled for surgery were prospectively included in this study. All patients were evaluated by transvaginal color Doppler ultrasonography. The probability of adnexal malignancy was estimated prior to surgery, applying a logistic model developed previously. A probability of malignancy greater than 75% was considered to assess model performance. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated for the model. In all cases definitive histopathologic diagnosis was obtained. One hundred and twenty-five (74.9%) benign and 42 (25.1%) malignant tumors were found. The sensitivity, specificity, positive predictive value, and negative predictive value of the model were 85.7% (95% confidence intervals, 71.4% to 94.6%), 100% (95% confidence intervals, 97.1% to 100%), 100% (95% confidence intervals, 90.3% to 100%), and 95.4% (95% confidence intervals, 90.3% to 98.3%), respectively. Overall accuracy was 96.4% (95% confidence intervals, 91.3% to 98.7%). Our results confirm the validity of the proposed logistic model in predicting adnexal malignancy.


[Nose and lungs--two of a kind].
Diseases in the upper and lower airways often occur concomitantly, and evidence indicates a close relationship between them. Optimal treatment of airway disease requires knowledge about this relationship; the article presents an updated overview of the field. This paper is based on extensive clinical experience with airway disease, own research and literature studies. It is well documented that patients suffering from asthma have rhinitis more often than those without. Likewise, those suffering from nose and sinus disease, e.g. allergic rhinitis, sinusitis and nasal polyposis, have an increased incidence of asthma. Treatment of disorders in one airway compartment often has a positive impact on the airways in general. Disorders in the upper and lower airways should be considered as the same disease to a larger extent than they are today. Patients with disease in one airway compartment should be considered for pathology elsewhere in the airways. Therapeutically, the airways should be regarded as one entity.


Obstetrical concerns of epidermolysis bullosa.
Epidermolysis bullosa is a group of autosomally inherited diseases involving skin breakdown of varying degrees and severity. Prenatal diagnosis and evaluation of these diseases is reviewed although pregnancy is not generally adversely affected by these diseases. Labor and delivery practices must be altered for the management of these patients. The obstetrical team must pay careful attention to adhesive dressings and anesthetic devices. Minor trauma may lead to severe lesions.


Respiratory effects of sulfur dioxide in heavily exercising asthmatics. A dose-response study.
Twenty-three asthmatic volunteers 19 to 31 yr of age were exposed to 0 (control), 0.2, 0.4, and 0.6 ppm sulfur dioxide (SO2) in random order at 1-wk intervals. Exposures took place in a controlled-environment chamber at 23 degrees C and 85% relative humidity; they included 5 min heavy exercise (mean minute volume, 48 L) plus time for postexercise physiologic testing. Body plethysmography (preexposure and end-exposure), spirometry (end-exposure only), and symptom questionnaires (covering the exposure period and the following week) all showed highly significant trends toward increased response with increasing SO2 concentration. Pairwise statistical comparisons showed substantial, highly significant, changes at 0.6 ppm, relative to control. Fewer and smaller significant changes were found at 0.4 ppm. At 0.2 ppm, no significant physiologic changes were found, but increases in symptoms during exposure were possibly significant. Symptom reports 1 day and 1 wk postexposure showed no significant variation related to SO2 level, i.e., exposure-related symptoms apparently reversed in less than 1 day.


Achilles tendon lengthening, the panacea for plantar forefoot ulceration?
Recent reports on Achilles tendon lengthening (ATL) have documented rapid healing of chronic plantar neuropathic forefoot ulcers. Sixty-eight patients with 75 ulcerated neuropathic feet (63 patients with diabetes with 69 ulcerated feet) underwent ATL and were retrospectively studied for chronic plantar ulceration in the forefoot and reduced dorsiflexion range of motion at the ankle. Median duration of ulcers was 48 months (range 11-84 months) in 16 forefoot amputation stumps and 11 months (range 3-84 months) for the rest of the patients. Healing of the ulcers was obtained in 68/75 feet (91%). At a median follow-up of 12 months (3-26 months), 4 had never healed, 5/10 recurrent ulcers and 6/11 transfer ulcers (localized to the heel) had not healed, that is, a healing rate of 60/75 (80%). Acute transfer ulcers to the heel occurred in 47% of patients with complete anaesthesia of the heel pad. Late heel ulceration occurred in 14% of those with extreme ankle dorsiflexion (>15 degrees). Failure to heal or ulcer recurrence occurred more frequently at dorsiflexion <10 degrees (33%). Rupture of the Achilles tendon occurred in 7 feet (10%). Charcot event was experienced in 3 (4%). Lengthening of the Achilles tendon is effective in healing plantar neuropathic ulceration. Patients with complete anaesthesia of the heel pad should not undergo this procedure and extreme dorsiflexion should be avoided because of the risk of heel ulceration. Moreover, the procedure should be performed only in a multidisciplinary setting for immediate dealing with complications and for surveillance and treatment of future ulceration.


The effect of non-nutritive sucking on plasma insulin, gastrin, and somatostatin levels in infants.
The aim of the present investigation was to study the effect of non-nutritive sucking on plasma levels of insulin, gastrin, and somatostatin in infants. These hormones were measured with radioimmunoassay in plasma collected from fullterm and preterm infants sucking a pacifier. In fullterm infants, sucking caused a significant increase of insulin levels from 13 +/- 10 microU/ml to 40 +/- 36 microU/ml and 21 +/- 17 microU/ml after 45 sec and 5 min respectively, from when the infants started sucking. A similar pattern was seen in preterm infants. In contrast, gastrin and somatostatin levels were not significantly affected. We suggest that sucking causes an activation of the vagal nerve, which results in the release of insulin. We also suggest that in infants, oral feeding is superior to bolus feeding, since in the latter case no vagal activation and consequently no release of hormones with anabolic properties occurs.


Distribution and mobility of mercury in soils from an old mining area in Mieres, Asturias (Spain).
Mercury content in soils near abandoned mine wastes in the mercury mining area of Mieres (Asturias, Spain) is highly elevated as a result of the long period of mining and abundant Hg production. In this work, an evaluation of Hg concentration, distribution, and mobility in three soil samples from the immediate vicinity of a chimney used for vapour evacuation during pyrometallurgical treatment of the ore was carried out. For that purpose, total Hg contents were determined for the original samples and their grain-size subsamples. The study of mercury mobility in the original samples and in the different particle-size subsamples was made by the application of a sequential extraction method. Results showed that Hg concentration in soils decreases directly with the distance from the chimney and the dispersion of Hg is not influenced by the topographic height of the site tested. The sample collected in the base of the chimney exhibited appreciable amounts of mobile Hg. In general, a higher Hg concentration was found for the finest particle-size subsamples. Hg mobility was found to be higher for quite developed soils. The sample collected downstream from the chimney showed a significant Hg mobile content as a result of a more intensive weathering. An increase of Hg mobility at decreasing particle size was found in all three analysed samples.


Serum sex hormone-binding globulin levels in healthy children and girls with precocious puberty before and during gonadotropin-releasing hormone agonist treatment.
The regulation of SHBG is complex and influenced by sex steroids and insulin. Our objective was to describe serum levels and evaluate determinants of SHBG levels in healthy children and in girls with central precocious puberty (CPP) before and during GnRH analog (GnRHa) treatment. We conducted a cross-sectional study on healthy subjects and a 2-yr longitudinal study in girls with CPP. The study took place at a tertiary referral center for pediatric endocrinology. A total of 903 healthy schoolchildren served as healthy subjects, and 25 girls with precocious/early puberty participated. Girls with CPP were treated with the long-acting GnRHa triptorelin. SHBG levels declined with increasing age in both sexes until adulthood. In healthy children, SHBG was significantly negatively correlated with testosterone, estradiol, dehydroepiandrosterone sulfate, and body mass index (BMI) in boys (total model R(2) = 0.71) but only with dehydroepiandrosterone sulfate and BMI in girls (total model R(2) = 0.26). Body fat percentage was significantly negatively correlated with SHBG levels (P < 0.001) in both boys (R(2) = 0.18) and girls (R(2) = 0.23). Girls with CPP had significantly lower pretreatment SHBG levels compared with age-matched controls [SHBG sd score, -1.29 (-4.48; 0.01)], which declined even further during GnRHa treatment [-2.75 (-5.9; 0.53); P < 0.001]. Even after adjustment for BMI and pubertal stage, girls with CPP had lower SHBG levels (P < 0.001) compared with healthy controls. SHBG levels were strongly dependent on body composition and sex steroid levels in children with normal and precocious puberty. Studies on insulin sensitivity and SHBG in puberty are needed to better understand the interaction between body composition and gonadal maturation.


The development of ambiguous federal policy: early and periodic screening, diagnosis, and treatment (EPSDT).
This paper examines why Congress's first major program for comprehensive health care to needy children took five years to begin even partial operation. An examination of the 1967 program's legislative history reveals that Congress paid little attention to EPSDT's implications: it was left ambiguous whether health (Title V) or welfare (Title XIX) would administer; costs were never clearly stated; eligibility and scope of services to be provided were left vague. Despite pressure from welfare rights interest groups, these ambiguities delayed the preparation of regulation and guidelines which never did succeed in resolving the question of overlapping jurisdiction and costs. In addition, many states' resistance to paying for the program further held up implementation. The paper concluded that: (1) Congress's and HEW's unwillingness to face up to the real costs of health programs threatens long-term public and state support for such programs; (2) division of responsibility between health and welfare lessens the impact of a program; (3) grant-in-aid programs give states the power to distort the intent of federal health policies; and (4) where states fail to implement such policies, initiatives may pass to consumer advocacy groups.


Aminoethylation in model peptides reveals conditions for maximizing thiol specificity.
Control of pH in aminoethylation reactions is critical for maintaining high selectivity towards cysteine modification. Measurement of aminoethylation rate constants by liquid chromatography mass spectrometry demonstrates reaction selectivity of cysteine>>amino-terminus>>histidine. Lysine and methionine were not reactive at the conditions used. For thiol modification, the acid/base property of the gamma-thialysine residue measured by NMR results in a 1.15 decrease in pK(a) (relative to a lysine residue). NMR confirms ethylene imine is the reactive intermediate for alkylation of peptide nucleophiles with bromoethylamine. Conversion of bromoethylamine into ethylene imine prior to exposure to the target thiol, provides a reagent that promotes selectivity by allowing precise control of reaction pH. Reaction selectivity plots of relative aminoethylation rates for cysteine, histidine, and N-terminus imine demonstrate increasing alkaline conditions favors thiol modification. When applied to protein modification, the conversion of bromoethylamine into ethylene imine and buffering at alkaline pH will allow optimal cysteine residue aminoethylation.


Biotherapeutic first-in-human dose selection: making use of preclinical markers.
First-in-human dose-selection criteria for biotherapeutics are changing, primarily based on severe adverse events in a single monoclonal antibody trial in healthy volunteers. Spurred by new EMA guidance, the minimum anticipated biological-effect level (MABEL) for estimating a starting human dose from exposure-response preclinical data have been introduced and should help to create long overdue target mechanism-based models focused on exposure-response relationships. Even though clarity of its application is still developing, this has the potential to become the model for most biotherapeutics in the future. However, maximizing benefit from MABEL will require increased efforts to define and create assays for relevant biomarkers of biological activity and safety as pharmacodynamic end points. Currently, this has not been realized sufficiently to make the model applicable to a majority of biotherapeutics; however, this review suggests how it can be applied universally with monoclonal antibodies.


Time, Resident Involvement, and Supply Drive Cost Variability in Septoplasty with Turbinate Reduction.
Objective To determine factors that influence cost variability in septoplasty with inferior turbinate reduction. Study Design Case series with chart review. Setting Tertiary care hospital and affiliated ambulatory surgical center. Subjects and Methods Surgical costs were reviewed for adult patients undergoing septoplasty with inferior turbinate reduction between December 2014 and September 2017. Cases where additional procedures were performed were excluded. Operative supply costs, operative time, room time, and resident involvement were determined. Contribution of these factors to total costs and variability were analyzed. Results The study included 116 patients (mean age, 38 years) and 4 faculty surgeons. Total cost was primarily driven by operative time (74%), with a smaller portion of total cost arising from supplies (26%). Time cost ( P < .0001) and supply cost ( P = .006) varied significantly among surgeons. A resident was involved in 46.6% of cases. When subanalyzed by resident year, no-resident and senior resident (postgraduate years 4 and 5) cases had nearly identical mean times, while junior resident (postgraduate years 1-3) cases had mean times and operative time costs that were 39% greater ( P < .001). Conclusion For septoplasty with inferior turbinate reduction, the greatest driver of cost variation was operative time. Resident involvement correlated with increased time and cost. Supply costs had a much smaller impact. When subanalyzed by resident year, junior resident-involved cases were significantly longer than no-resident cases.


Regulation of intestinal phosphate transport. II. Metabolic acidosis stimulates Na(+)-dependent phosphate absorption and expression of the Na(+)-P(i) cotransporter NaPi-IIb in small intestine.
During metabolic acidosis, P(i) serves as an important buffer to remove protons from the body. P(i) is released from bone together with carbonate buffering protons in blood. In addition, in the kidney, the fractional excretion of phosphate is increased allowing for the excretion of more acid equivalents in urine. The role of intestinal P(i) absorption in providing P(i) to buffer protons and compensating for loss from bone during metabolic acidosis has not been clarified yet. Inducing metabolic acidosis (NH(4)Cl in drinking water) for 2 or 7 days in mice increased urinary fractional P(i) excretion twofold, whereas serum P(i) levels were not altered. Na(+)-dependent P(i) transport in the small intestine, however, was stimulated from 1.89 +/- 3.22 to 40.72 +/- 11.98 pmol/mg protein (2 days of NH(4)Cl) in brush-border membrane vesicles prepared from total small intestine. Similarly, the protein abundance of the Na(+)-dependent phosphate cotransporter NaPi-IIb in the brush-border membrane was increased 5.3-fold, whereas mRNA levels remained stable. According to immunohistochemistry and real-time PCR NaPi-IIb expression was found to be mainly confined to the ileum in the small intestine, and this distribution was not altered during metabolic acidosis. These results suggest that the stimulation of intestinal P(i) absorption during metabolic acidosis may contribute to the buffering of acid equivalents by providing phosphate and may also help to prevent excessive liberation of phosphate from bone.


Antiaflatoxigenic activity of eugenol is due to inhibition of lipid peroxidation.
Eugenol inhibited aflatoxin production by Aspergillus parasiticus NRRL 2999 in a dose-dependent manner up to a concentration of 0.75 mmol l-1 without inhibiting growth. When the mould was grown for 3 d in the presence of 0.45 mmol l-1 eugenol (concentration inhibiting aflatoxin production by 50%), in vivo activities of components of polysubstrate monooxygenase were decreased at idiophase, concomitant with decreased activities of enzymes involved in free radical scavenging, lipid peroxidation and maintenance of redox potential. These results indicate that antiaflatoxigenic actions of eugenol may be related to inhibition of the ternary steps of aflatoxin biosynthesis involving lipid peroxidation and oxygenation.


Preliminary evaluation of the correlation between in vitro release and in vivo bioavailability of two aminophylline slow-release tablets.
An in vitro dissolution study has been carried out with a USP rotating paddle apparatus using the stepwise pH change method. The dissolution kinetics of two different matrix-type aminophylline slow-release (SR) tablets were compared. both aminophylline SR tablets show similar release rates and slow release behavior. The bioavailability of these two aminophylline SR tablets was also evaluated in eight healthy male Chinese volunteers and correlated with in vitro dissolution results by moment analysis. The preliminary results suggest that there is no evidence indicating that the two different matrix types of aminophylline SR tablets are not bioequivalent, and a good in vitro-in vivo correlation for these aminophylline SR tablets may therefore be presumed.


Right ventricular outflow tract reconstruction in Ross patients: does the homograft fare better?
In the Ross aortic valve replacement (AVR) procedure, the right ventricular outflow tract (RVOT) conduit is inserted in an orthotopic position. In complex congenital RVOT obstruction, the right ventricular-pulmonary artery (RV-PA) conduit is placed in a more heterotopic position. We hypothesized that durability of homograft RVOT reconstruction in the Ross AVR is improved secondary to orthotopic positioning and the ability to oversize the RV-PA homograft conduit in the Ross AVR. Between June 1993 and May 2007, 183 consecutive patients (mean age, 23.3 +/- 15.2; median, 22; range, 1 month to 61 years) underwent Ross AVR with RVOT reconstruction using a cryopreserved pulmonary homograft (n = 156), decellularized pulmonary homograft (n = 22), and bovine jugular vein conduit (n = 5). Three patients died (2 early, 1 late; mean follow-up, 5.7 +/- 3.3 years). Twenty-four patients (13%) had a peak systolic RVOT gradient exceeding 20 mm Hg, 5 (3%) had a gradient exceeding 40 mm Hg, and 7 (4%) had more than 2+ RVOT insufficiency. Eight patients (4%) underwent conduit replacement for RV dysfunction. Freedom from RVOT reoperation at 10 years is 96%. Freedom from RV failure and dysfunction are 98% and 96% at 5 years and 96% and 93% at 10 years, respectively. Independent predictors of pulmonary homograft RV-PA conduit dysfunction are smaller (< 14 mm) RVOT conduit size (p = 0.03) and follow-up exceeding 5 years (p = 0.05). Stenosis and regurgitation of the RV-PA conduit in adults and children following Ross AVR is infrequent. The most logical reasons for the superior performance of the homograft in Ross patients are: (1) orthotopic positioning, (2) older age of implant, and (3) the ability to significantly oversize the homograft in Ross patients.


Research directions for bone healing.
Recently our knowledge has vastly expanded in the pathophysiological mechanisms governing the healing process of fractures. Research is ongoing in every aspect of tissue engineering and regeneration. Several molecular mediators have entered phase III clinical trials in order to evaluate their efficacy in enhancing the biological activity of fractures. Despite these developments several issues of importance remain obscured. For instance the timing of intervention, the appropriate dose of agents, the length of intervention, the routine use of available growth factors in clinical practice or not represent some of the important areas requiring further investigation. This article highlights issues relating to bone regeneration which could potentially be the focus of research in the near future.


Safety of a quadrivalent human papillomavirus vaccine in a Phase 3, randomized, double-blind, placebo-controlled clinical trial among Chinese women during 90 months of follow-up.
A quadrivalent human papillomavirus (qHPV) vaccine (HPV6/11/16/18) has demonstrated efficacy and acceptable safety in international studies. However, these studies did not include participants from mainland China, which has a substantial burden of HPV-related disease. This is the first safety report with a follow-up period of up to 90 months from a randomized, double-blind, placebo-controlled trial of qHPV vaccine in Chinese women 20-45 years of age. Participants were randomized 1:1 to receive three doses of qHPV vaccine or placebo (Day1, Month 2, and Month 6). Efficacy outcomes are reported elsewhere. Injection-site and systemic adverse events (AEs) were collected using vaccination report cards (VRCs) for 15 days following each vaccination. Serious AEs (SAEs), pregnancy outcomes, new medical conditions, and fetal/infant SAEs were collected during the entire study. Of 3006 participants randomized, AEs were reported by 926 (61.8%) qHPV vaccine recipients and 856 (57.1%) placebo recipients over the entire study. Four participants (two in each group) discontinued the study vaccination due to AEs that were considered vaccination-related. Within 15 days following any vaccination, injection-site AEs prompted for on the VRC were more frequent among qHPV vaccine recipients (37.6% vs 27.8%), and systemic AEs prompted for on the VRC were similar in frequency between qHPV vaccine and placebo groups (46.8% vs 45.1%). Thirty-eight and 43 participants reported SAEs in qHPV vaccine and placebo groups, respectively. No SAE was considered qHPV vaccine-related. Pregnancy outcomes, fetal/infant SAEs, and new medical conditions were generally similar in frequency between the qHPV vaccine and placebo groups, and within normal ranges. The qHPV vaccine was well tolerated and demonstrated a favorable safety profile in Chinese women 20-45 years of age, consistent with findings from global trials and safety surveillance studies. clinicaltrials.gov; NCT00834106.


Adenomyoma of the cervix: report of a case and review of the literature.
Adenomyoma of the cervix is a rare benign neoplasm, one of a group of benign endocervical lesions that may histologically be confused with an aggressive cervical carcinoma, adenoma malignum. We recently encountered a case that distorted the cervix and pushed it under the pubic symphysis. We present this case, review the literature of this rare lesion, and discuss the differential diagnosis of this group of endocervical lesions.


Prediction of goal orientation and perceived competence on intensity and direction of precompetitive anxiety among adolescent handball players.
This study explored the main and interactive effects of goal orientations and perceived competence on intensity and direction of the symptoms of precompetitive cognitive and somatic anxiety. 109 handball players from 16 high school teams (M = 16.2 yr., SD = 1.5) participated. All were asked to complete the Task and Ego Orientation in Sport Questionnaire, Perceived Competence Questionnaire, and a modified version of the Competitive State Anxiety Inventory-2. Using separated multiple hierarchical regression analyses, direction of the symptoms of precompetitive somatic anxiety was predicted by perceived competence and interaction of ego orientation x perceived competence. Perceived competence and the interaction of ego orientation x task orientation x perceived competence were significant predictors of direction of the symptoms of precompetitive cognitive anxiety. The results suggest that perceptions of competence and task orientation moderate the relationship between ego orientation and direction of the symptoms of precompetitive anxiety.


Film characteristics pertinent to coherent optical data processing systems.
Photographic film is studied quantitatively as the input mechanism for coherent optical data recording and processing systems. The two important film characteristics are the amplitude transmission vs exposure (T(A) - E) curve and the film noise power spectral density. Both functions are measured as a function of the type of film, the type of developer, developer time and temperature, and the exposing and readout light wavelengths. A detailed analysis of a coherent optical spatial frequency analyzer reveals that the optimum do bias point for 649-F film is an amplitude transmission of about 70%. This operating point yields minimum harmonic and intermodulation distortion, whereas the 50% amplitude transmission bias point recommended by holographers yields maximum diffraction efficiency. It is also shown that the effective ac gain or contrast of the film is nearly independent of the development conditions for a given film. Finally, the linear dynamic range of one particular coherent optical spatial frequency analyzer is shown to be about 40-50 dB.


Feasibility of iliosacral screw placement in patients with upper sacral dysplasia.
Exact knowledge of the sacral anatomy is crucial for the percutaneous insertion of iliosacral screws. However, dysplastic anatomical patterns are common. In addition to a preoperative computed tomography (CT) analysis, conventional radiographic measures may help to identify upper sacral dysplasia and to avoid damage to surrounding structures. Aiming to further increase safety in percutaneous iliosacral screw placement in the presence of sacral dysmorphism, this study examined the prevalence of previously established radiographic signs and, in addition, defined the "critical SI angle" as a new radiographic criterion. Pelvic CT scans of 98 consecutive trauma patients were analysed. Next to assessment of established signs indicating upper sacral dysplasia, the critical sacroiliac (SI) angle was defined in standardized pelvic outlet views. The critical SI angle significantly correlates with the presence of mammillary bodies and an intraarticular vacuum phenomenon. With a cut-off value of - 14.2°, the critical SI angle detects the feasibility of a safe iliosacral screw insertion in pelvic outlet views with a sensitivity of 85.9% and a specificity of 85.7%. The critical SI angle can support the decision-making when planning iliosacral screw fixation. The clinical value of the established signs of upper sacral dysplasia remains uncertain.


Characterization and immunolocalization of beta-D-glucuronidase in mouse testicular germ cells and spermatozoa.
Spermatozoa released from the seminiferous tubules are terminally differentiated cells with no known synthetic activity. Their components are synthesized in the spermatogenic cells during spermatogenesis. In this study, we report the characterization and immunolocalization of beta-glucuronidase in mouse testicular germ cells and spermatozoa. The enzyme is an exoglycohydrolase with dual localization, being present in lysosomes and endoplasmic reticulum of several mouse and rat tissues. The purified germ cell preparations (spermatocytes, round spermatids, and condensed/elongated spermatids) when assayed for beta-glucuronidase activity showed that the spermatocytes contained five times more enzyme activity per cell than the spermatids. Polyacrylamide gel electrophoresis, carried out under native and denaturing conditions, demonstrated that the germ cells express only the lysosomal form of the enzyme (pI 5.5-6.0) with a subunit molecular mass of 74 kDa. Immunocytochemical studies revealed a positive reaction in the Golgi membranes, Golgi-associated vesicles, and lysosomes of late spermatocytes (pachytene spermatocytes) and a stage-specific localization during spermiogenesis. The forming or formed acrosome of the elongated spermatids (stages 9-16) and epididymal spermatozoa was highly immunopositive. Comparison of immunoprecipitation curves and kinetic properties of the enzyme present in spermatocytes and spermatozoa revealed no major differences. Taken together, our results demonstrate that beta-glucuronidase activities present in the lysosomes of spermatocytes and the sperm acrosome are kinetically and immunologically similar.


Adherence to Selective Serotonin and Serotonin-Norepinephrine Reuptake Inhibitor Prescriptions Affects Overall Medication Adherence in Older Persons: Evidence From the Italian Nationwide OsMed Health-DB Database.
This study aimed to evaluate prevalence of prescription of and adherence to selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) and whether adherence to these classes of drugs affects overall medication adherence in older persons. In a cross-sectional analysis of administrative data comprehensive of all prescribed drugs reimbursed by the Italian national health care system, new prescriptions of SSRIs and SNRIs to persons aged 65 years or older were analyzed (n = 380,400 in 2011; 395,806 in 2012; 409,741 in 2013, from a total sample of 3,762,299 persons aged 65 years or older) as well as prescriptions of antihypertensives, statins, other psychiatric drugs, antidiabetics, antiplatelets, anticoagulants, drugs for chronic obstructive pulmonary disease, and antiosteoporotics. Adherence was estimated by calculating the proportion of days covered by drugs dispensed during a period of 365 days. Adherence was defined as a proportion of days covered of more than 80%. Prevalence of SSRI and SNRI prescriptions varied from 11.4% in 2011 to 12.1% in 2013. Adherence to SSRI and SNRI prescriptions ranged from 31.2% in persons aged ≥ 95 years in 2011 to 41.8% in persons aged 75-84 years in 2013. Persons adherent to SSRI and SNRI prescriptions were more likely to be adherent to the other medications, after adjustment for age, gender, and number of drugs prescribed. The highest association was found for adherence to psychiatric drugs (OR = 1.9; 95% CI, 1.8-2.0). Adherence to SSRI and SNRI prescriptions is poor in older persons. However, people adherent to these classes of antidepressants are more likely to be adherent to the other medications they are prescribed. Studies are needed to evaluate the reasons for and the potential benefits of increasing adherence to antidepressants on overall adherence.


Risk factors for heart failure.
Despite remarkable therapeutic advances in the management of patients with heart failure (HF), the mortality due to this syndrome remains high. Identifying free-living individuals who are at high risk for developing HF may allow implementing strategies that can prevent HF. Prospective epidemiologic studies have identified several risk factors and risk markers for HF. This article reviews current knowledge regarding conventional and newer risk markers for HF, outlines possible underlying mechanisms for the increased HF risk, and provides a framework for clinical multivariate risk prediction using HF risk factors.


[Laveran, Marchiafava and paludism].
The discovery in 1880 of the malaria parasite by the French investigator Alphonse Laveran found for almost ten years the obstinate refusal from the italian Ettore Marchiafava, who saw in the parasitic elements only degenerative forms of the erythrocytes. The acknowledgement for Laveran came in 1889 with the Bréant Prize and later the Nobel of 1907, half of which he gave to the Pasteur Institute. By his side, Marchiafava demonstrated the transmission of malaria man to man by the blood of the sick, through experiences to day inadmissible for any ethical committee. From the classic textbook of Laveran Du paludisme et de son hématozoaire, published in 1891, the history of this discovery is revised in the author's words.


[Determination of metronidazole in serum and cerebrospinal fluid with reversed-phase high performance liquid chromatography].
A reversed-phase high performance liquid chromatographic method for the determination of metronidazole (MTZ) in rabbit serum and cerebro-spinal fluid has been developed. The method is simple and convenient. The analysis was carried out with Zorbax C8 column, NaH2PO4(0.0075mol/L, pH 4.0)-CH3OH(4:11) as mobile phase and UV detector at 320nm, by using hydrochlorothiazide as internal standard. The standard curve is linear over the range from 0.5ng/L to 80.0ng/L in sample with correlation coefficient of 0.9998. The recovery of metronidazole from rabbits serum and cerebrospinal fluid are 97.1% +/- 1.5% and 97.4% +/- 1.6% respectively. The minimum detectable quantity is 80ng/mL in sample (S/N = 3). Under the chromotographic condition, the consistency of MTZ of the serum and cerebrospinal fluids of rabbits were detected separately after taking MTZ (0.1mg/g) orally. The drug-time curve was obtained and a satisfactory result was achieved. The new findings provide conditions for further exploration of the process of pharmacokinetics.


[Febrile neutropenia at the emergency department of a cancer hospital].
Febrile neutropenia is an important cause of fever in the cancer patient. When he/she is undergoing chemotherapy, the priority is to exclude that complication because it requires rapid administration of empiric broad-spectrum antibiotics. We have studied the rate and characteristics of febrile neutropenia in cancer patients consulting in a emergency department. We have conducted a retrospective study in the emergency department of a cancer hospital over the year 2008. Every patient with cancer and fever > or = 38 degrees C was included. Over 2.130 consultations, 408 were selected (313 patients) including 21.6% (88) for febrile neutropenia. A focal symptom or physical sign was present in the majority of the cases. 88% were assessed as low risk for severe complications and about half of them received oral antibiotics. There were only a few patients with a nude fever for which it was difficult to make a hypothetical diagnosis in order to administer a probabilistic treatment. The majority of the consultations lead to hospital admission. Over the 80 hospitalisations, 6 deaths occurred. There was no death among the patients who remained ambulatory. In conclusion, our study shows that febrile neutropenia is frequent in ambulatory cancer patients presenting with fever and that in the majority of the cases, it is associated with a low risk. In such a situation, ambulatory management is more and more often considered or, at least, a rapid discharge after a short admission in case of low risk febrile neutropenia. In that context, the role of the general practioner has to be emphasised and to facilitate the outpatient management, we propose an algorithm that requires validation.


Natural orifices transluminal endoscopic surgery (NOTES): an overview of technical challenges and complications of transgastric procedures in anesthetized pigs.
Natural orifice transluminal endoscopic surgery (NOTES) is a new reality that is progressively gaining popularity in the scientific community. The aim of this study was to report the authors' experience with various peroral transgastric procedures performed on the porcine model. The technical difficulties and challenges that arose were also analyzed. Ten anesthetized pigs, divided into an acute (3) and a survival group (7) underwent the following procedures using a double channel endoscope: peritoneoscopy (10), cholecystectomy (6),splenectomy (3), and gastrojejunostomy (3). All the procedures were completed successfully. There was one complication related to the gastric wall incision. In the survival experiment group all pigs (4) submitted to biliare procedures made an uncomplicated recovery after a follow-up period of 2 weeks. Gastrojejunostomies (3) were instead graved by one technical failure (anastomosis disruption at post-mortem examination) and one case of mortality (premature euthanasia for evidences of sepsis). Complete gastric cleansing was impossible to achieve and overinflation was a common problem. The creation of gastro-enteric anastomoses was technically difficult with the current available devices. Transgastric endoscopic surgery is technically feasible in a porcine model. A new instrumentation is needed and could strongly help to overcome the technical difficulties highlighted. More extensive animal studies are mandatory in order to evaluate the benefits and the limitations of this new technique.


Molecular cloning and expression profile of Xenopus calcineurin A subunit(1).
We have cloned a cDNA encoding a catalytic subunit of calcineurin (CnA) expressed in Xenopus oocytes. The deduced amino acid sequence indicates 96.3% and 96.8% identities with the mouse and human CnAalpha isoforms, respectively. Xenopus CnA (XCnA) RNA and protein are expressed as maternal and throughout development. Recombinant XCnA protein interacted with calmodulin in the presence of Ca(2+). Deletion of calmodulin binding domain and auto-inhibitory domain revealed calcium independent phosphatase activity, thereby showing that XCnA is likely to be modulated by both calmodulin and calcium.


The Expression of HSD17B12 Is Associated with COX-2 Expression and Is Increased in High-Grade Epithelial Ovarian Cancer.
The aim of this study was to characterize the expression of hydroxysteroid (17β) dehydrogenase type 12 (HSD17B12), an enzyme involved in the synthesis of arachidonic acid (AA), in ovarian cancer, and to study its coexpression with its upstream and downstream enzymes in the AA pathway, namely elongation of very long chain fatty acids protein 5 (ELOVL5) and cyclooxygenase-2 (COX-2), respectively. Samples from benign and malignant ovarian neoplastic lesions were immunohistochemically stained with HSD17B12, ELOVL5, and COX-2. The staining intensities were quantified with the QuantCenter program, and the results were confirmed with visual inspection. Statistical significances were calculated with the Student t test, the Mann-Whitney test, linear regression, or ANOVA. The expression of the HSD17B12, ELOVL5, and COX-2 enzymes increased according to the grade of the endometrioid ovarian adenocarcinomas. In contrast, in serous adenocarcinomas, staining with ELOVL5 was constantly weak, whereas the expression of HSD17B12 and COX-2 increased with the grade or FIGO stage of the cancer, respectively. The expression of HSD17B12 increased along with the severity of ovarian cancer, and the expression mimicked COX-2 expression and intensity. This further suggests the involvement of HSD17B12 in AA production, and its coexpression with COX-2 indicates a role for the enzyme in the increased prostaglandin production during ovarian cancer progression.


Primary atherothrombotic occlusive vascular events in premenopausal women with history of adverse pregnancy outcome.
To determine if adverse pregnancy outcomes are associated with atherothrombotic occlusive vascular disease (AOVD) in premenopausal women. Retrospective matched case-control study. Tertiary, university-affiliated medical center. Women aged less than 50 years treated for an AOVD (primary cerebrovascular, myocardial, or peripheral arterial ischemic event) from 1995 to 2004. The files were reviewed for classical risk factors for AOVD and complications of pregnancy (abortions, pregnancy-induced hypertension, preeclampsia, gestational diabetes, intrauterine growth restriction (IUGR), fetal loss and preterm delivery). Findings were compared with healthy women matched for age and body mass index. Past pregnancy complications in premenopausal women with AOVD. Of the 101 women with AOVD, 53 had a myocardial ischemic event, 33 a cerebrovascular event, and 15 a peripheral ischemic arterial event. On multivariate analysis, IUGR (OR 8.41, 95% CI 2.36-29.9, p=0.001) and more than one pregnancy complication (OR 13.7, 95% CI 1.56-120, p=0.02) were found to be independent significant variables associated with AOVD. IUGR and composite pregnancy complications are independent significant variables associated with AOVD in premenopausal period. Pregnancy outcome might serve as a means to identify patients who may require increased medical surveillance and preventive measures for later vascular disease.


The impact of female gender on bladder cancer-specific death risk after radical cystectomy: a meta-analysis of 27,912 patients.
To perform a first meta-analysis on the association between female gender and cancer-specific death risk after radical cystectomy. A comprehensive literature search of the MEDLINE and EMBASE databases was conducted for relevant studies published till November 11, 2014. The meta-analysis was performed by estimating the hazard ratios (HRs) and confidence intervals (CIs) through a random-effect approach. A total of 17 studies were included in the meta-analysis with a total population of 27,912 patients. Female gender was associated with a worse survival outcome (pooled HR 1.20; 95 % CI 1.09-1.32) compared with male gender after radical cystectomy. Subgroup analysis found the correlation was significant in North American and European studies (HR 1.17, 95 % CI 1.02-1.32 and HR 1.34, 95 % CI 1.19-1.51, respectively) and studies from larger size of samples (HR 1.24, 95 % CI 1.11-1.38). We also found studies adjusted for the key elements (T stage, N stage and grade) obtained positive correlation (HR 1.21, 95 % CI 1.09-1.35). Female demonstrated worse survival outcomes than male after radical cystectomy for bladder cancer. The adoption of more intense cares for female patients was suggested after radical cystectomy.


A computational model for glycogenolysis in skeletal muscle.
A dynamic model of the glycogenolytic pathway to lactate in skeletal muscle was constructed with mammalian kinetic parameters obtained from the literature. Energetic buffers relevant to muscle were included. The model design features stoichiometric constraints, mass balance, and fully reversible thermodynamics as defined by the Haldane relation. We employed a novel method of validating the thermodynamics of the model by allowing the closed system to come to equilibrium; the combined mass action ratio of the pathway equaled the product of the individual enzymes' equilibrium constants. Adding features physiologically relevant to muscle-a fixed glycogen concentration, efflux of lactate, and coupling to an ATPase--alowed for a steady-state flux far from equilibrium. The main result of our analysis is that coupling of the glycogenolytic network to the ATPase transformed the entire complex into an ATPase driven system. This steady-state system was most sensitive to the external ATPase activity and not to internal pathway mechanisms. The control distribution among the internal pathway enzymes-although small compared to control by ATPase-depended on the flux level and fraction of glycogen phosphorylase a. This model of muscle glycogenolysis thus has unique features compared to models developed for other cell types.


Nuclear IL-33 is a transcriptional regulator of NF-κB p65 and induces endothelial cell activation.
Interleukin (IL)-33, an IL-1 family member, acts as an extracellular cytokine by binding its cognate receptor, ST2. IL-33 is also a chromatin-binding transcriptional regulator highly expressed in the nuclei of endothelial cells. However, the function of IL-33 as a nuclear factor is poorly defined. Here, we show that IL-33 is a novel transcriptional regulator of the p65 subunit of the NF-κB complex and is involved in endothelial cell activation. Quantitative reverse transcriptase PCR and Western blot analyses indicated that IL-33 mediates the expression of intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 in endothelial cells basally and in response to tumor necrosis factor-a-treatment. IL-33-induced ICAM-1/VCAM-1 expression was dependent on the regulatory effect of IL-33 on the nuclear factor (NF)-κB pathway; NF-κB p65 expression was enhanced by IL-33 overexpression and, conversely, reduced by IL-33 knockdown. Moreover, NF-κB p65 promoter activity and chromatin immunoprecipitation analysis revealed that IL-33 binds to the p65 promoter region in the nucleus. Our data provide the first evidence that IL-33 in the nucleus of endothelial cells participates in inflammatory reactions as a transcriptional regulator of NF-κB p65.


Predictors of outcome after single-event multilevel surgery in children with cerebral palsy: a retrospective ten-year follow-up study.
Single event multilevel surgery (SEMLS) has been shown to improve gait in children with cerebral palsy (CP). However, there is limited evidence regarding long-term outcomes and factors influencing them. In total 39 children (17 females and 22 males; mean age at SEMLS ten years four months, standard deviation 37 months) with bilateral CP (20 Gross Motor Function Classification System (GMFCS) level II and 19 GMFCS level III) treated with SEMLS were included. Children were evaluated using gait analysis and the Gait Deviation Index (GDI) before SEMLS and one, two to three, five and at least ten years after SEMLS. A linear mixed model was used to estimate the effect of age at the surgery, GMFCS and follow-up period on GDI. There was a mean improvement of 12.1 (-15.3 to 45.1) GDI points one year after SEMLS (p < 0.001) and 10.3 (-23.1 to 44.2) GDI points ten years after SEMLS compared with before SEMLS (p < 0.001). GMFCS level III children aged ten to 12 years had the most improvement. The GMFCS III group had more surgical procedures at the index SEMLS (p < 0.001) and during the follow-up period (p = 0.039). After correcting for other factors, age at surgery was the only factor predictive of long-term results. Our model was able to explain 45% of the variance of the change in GDI at the different time points. Children with GMFCS III level aged ten to 12 are the benchmark responders to SEMLS in the long-term.


The relationship between the development and progression of microalbuminuria and arterial blood pressure in type 1 (insulin-dependent) diabetes mellitus.
to investigate the association between urinary albumin excretion and arterial blood pressure in type 1 (insulin-dependent) diabetes. urinary albumin excretion and blood pressures were followed prospectively for a mean period of 26 months (range 18-29 months) in 46 young type 1 (insulin-dependent) diabetic subjects without overt nephropathy. Supine blood pressures (BP) were measured by a single observer using a random zero sphygmomanometer. Albumin excretion was assessed at baseline by a timed clinic excretion rate (AER; microalbuminuria = AER greater than 33 micrograms/min), and at follow-up in at least two urine specimens by the albumin/creatinine (A/Cr) ratio (micro-albuminuria = A/Cr greater than 3.7 mg/mmol). 39 subjects initially had normal AERs. Seven had developed microalbuminuria at follow-up: their mean BP rose from 114 +/- 13/62 +/- 13 to 119 +/- 7/77 +/- 5 mmHg (for diastolic BP, P less than 0.05), while there was no change in the mean BP in the remaining 32 patients. A rise in diastolic BP of greater than 10 mmHg occurred in five of the seven subjects who developed microalbuminuria, and in only seven of 32 who did not (P = 0.02). In the seven patients in whom microalbuminuria persisted (n = 3) or progressed to overt proteinuria (n = 4), BP increased from 123 +/- 12/70 +/- 14 to 139 +/- 12/88 +/- 10 mmHg (P less than 0.02 for both). this study has shown that BP is normal before the onset of microalbuminuria, and that a rise in diastolic BP accompanies the development or progression of microalbuminuria. The rate of rise in BP may be more important than the absolute level in defining 'hypertension' in young diabetic patients with microalbuminuria.


Cultural adaptation of the Pieper-Zulkowski Pressure Ulcer Knowledge Test for use in Brazil.
To carry out the cultural adaptation of the Pieper-Zulkowski Pressure Ulcer Knowledge Test (PZ-PUKT) for use in Brazil and analyze the internal consistency of the adapted version. This was a methodological study. The PZ-PUKT is a knowledge test consisting of 72 items, divided into: prevention, staging, and wound description. The present study was developed in two phases: (1) translation of the questionnaire from English to Brazilian Portuguese, back-translation, and assessment of equivalence between the original and back-translated version by an expert panel; (2) pre-testing with nurses. The questionnaire showed face and content validity according to the opinions of the experts. Cronbach's alpha for the total test score was higher than 0.70. The adapted version presented satisfactory internal consistency for the studied sample. The adapted version of the instrument for Portuguese can be used in intervention studies as a tool to measure "nursing knowledge about pressure injury/ulcers" as a dependent variable.


Amifostine: mechanisms of action underlying cytoprotection and chemoprevention.
Amifostine is an important drug in the new field of cytoprotection. It was developed by the Antiradiation Drug Development Program of the US Army Medical Research and Development Command as a radioprotective compound and was the first drug from that Program to be approved for clinical use in the protection of dose limiting normal tissues in patients against the damaging effects of radiation and chemotherapy. Its unique polyamine-like structure and attached sulfhydryl group give it the potential to participate in a range of cellular processes that make it an exciting candidate for use in both cytoprotection and chemoprevention. Amifostine protects against the DNA damaging effects of ionizing radiation and chemotherapy drug associated reactive species. It possesses anti-mutagenic and anti-carcinogenic properties. At the molecular level, it has been demonstrated to affect redox sensitive transcription factors, gene expression, chromatin stability, and enzymatic activity. At the cellular level it has important effects on growth and cell cycle progression. This review focuses on relating its unique chemical design to mechanisms of action that underlie its broad usefulness as both a cytoprotective and chemopreventive agent for use in cancer therapy.


A novel approach to assess the population health impact of introducing a Modified Risk Tobacco Product.
Based on the Food and Drug Administration's Modified Risk Tobacco Product (MRTP) Application draft guideline, Philip Morris International (PMI) has developed a Population Health Impact Model to estimate the reduction in the number of deaths over a period following the introduction of an MRTP. Such a model is necessary to assess the effect that its introduction would have on population health, given the lack of epidemiological data available prior to marketing authorization on any risks from MRTPs. The model is based on publicly available data on smoking prevalence and on the relationships between smoking-related disease-specific mortality and various aspects of the smoking of conventional cigarettes (CCs), together with an estimate of exposure from the MRTP relative to that from CCs, and allows the exploration of possible scenarios regarding the effect of MRTP introduction on the prevalence of CC and MRTP use, individually and in combination. By comparing mortality attributable in a scenario where the MRTP is introduced with one where it is not, the model can estimate the mortality attributable to CCs and the MRTP, as well as the reduction in the deaths attributable to the introduction of the MRTP.


[Flavor and meridian tropism classification analysis of Callianthemum taipaicum].
To explore the flavor and meridian tropism classification of Callianthemum taipaicum by principal components analysis(PCA) and partial least square analysis(PLS). Meanwhile,to establish a high performance liquid chromatography-tandem mass spectrometry(HPLC-ESI-MS) method for the simultaneous determination of 55 active components from 13 kinds of Ranunculaceae of Chinese traditional herbs. Samples were separated on HPLC system by Agilent 5 TC-C₁₈（2）（4.6 mm×250 mm，5 μm）column and eluted with acetonitrile and 0.1% formic acid at the flow rate of 0.6 mL·min⁻¹. The data were performed by HPLC-ESI-MS with multiple reaction monitoring（MRM）scanning mode under positive and negative ion modes and quantified by external standards. The data from 13 Ranunculaceae herbs were analyzed by the PLS-tree and cooman's prediction of PCA and PLS to evaluate the similarities and differences of C. taipaicum in flavor and meridian tropism. The results showed that calibration curves of 55 components all showed good linearity, r>0.99,with good precision, repeatability and stability. After compared to other 12 herbs,PCA and PLS results revealed that the C. taipaicum belonged to lung and bladder meridians while its flavor attributive to pungent,warm in nature. In conclusion,the analysis approach of chemometric calculation combined with multi-components quantification is suitable for the classification of meridian tropism and flavor of Chinese traditional medicine,which can be used for alternative research of rare herbs.


Giant cell tumours of tendon sheath: classification and recurrence rate.
Forty-three consecutive cases of giant cell tumour of tendon sheath were included in a prospective study. The tumours were classified into two main types, depending on whether the entire tumour was, or was not, surrounded by one pseudocapsule as assessed by the surgeon during surgery. Each type was then sub-classified according to the thickness of the capsule, lobulation of the tumour, the presence of satellite lesions, and the diffuse or multicenteric nature of the tumour: these factors were also assessed by the surgeon. The mean follow-up period was 4 (range, 2-6) years. None of the type I tumours (n=30) recurred, but recurrence occurred in five out of 13 type II tumours. Second recurrences were seen with type II B and C, but not type II A tumours.


Hatching rhythms in three species of Diclidophora (Monogenea) with observations on host behaviour.
Eggs of three species of Diclidophora were incubated in alternating 12 h periods of light and darkness at 13 degrees C. Eggs of D. merlangi collected at Arbroath hatched during the illumination period with most larvae being recovered in the first 4-6 h; some evidence of a seasonal difference in hatching of these eggs was found. Eggs of D. merlangi collected at Plymouth hatched with a peak of larval recovery in the 2 h period before the light came on. Eggs of D. luscae hatched over 'dusk' while those of D. denticulata hatched after the light was switched off. Neither mechanical disturbance nor the proximity of host tissue caused hatching in D. merlangi or D. luscae. Observations on the behaviour of the host fishes suggest that the hatching rhythms are adapted to specific host behaviour patterns.


Placental transfer of thiamphenicol.
The placental transfer of thiamphenicol was studied in 29 subjects at term after intravenous bolus injection of 500 mg of the drug. Detectable plasma levels were present in umbilical blood and amniotic fluid as early as 5 and 18 minutes, respectively, after maternal administration. With the dosage applied, minimum concentrations required for the inhibition of many organisms causing intrauterine infections were reached in maternal and fetal plasma and in amniotic fluid. The value of thiamphenicol for the treatment of intrauterine infections is discussed.