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Unlabelled: Aims/Introduction:  Morphological changes to corneal C-fibers in Japanese type 1 diabetic patients were visualized by corneal confocal microscopy (CCM). The effects of prior glycemic control and blood pressure on morphological parameters were clarified., Materials and Methods:   Corneal nerve fibers were visualized by CCM in 38 Japanese type 1 diabetic patients (14 with and 24 without neuropathy) and 38 controls. Morphological parameters were compared and related to annual mean HbA1c, blood pressure, and serum lipid levels of previous years prior to CCM examination., Results:   Compared with controls, diabetic patients had reduced corneal nerve fiber length (CNFL; 9.80 ± 0.38 vs 13.65 ± 0.88 mm/mm(2); P < 0.001), reduced density (CNFD; 25.32 ± 1.04 vs 36.62 ± 2.37/mm(2); P < 0.0005), lower frequency of beading (22.38 ± 0.73 vs 30.44 ± 1.03/0.1 mm; P < 0.0001), and increased tortuosity (3.13 ± 0.09 vs 1.74 ± 0.06; P < 0.0001). These changes were found in patients without neuropathy. There was no difference in nerve branches between controls and diabetic patients. The mean annual HbA1c level for the 7-10 years prior to CCM examination was an independent predictor of reduced CNFL and CNFD; HbA1c levels obtained 1-3 months and 1 year prior to CCM, as well as blood pressure 3, 5, and 6 years prior to CCM, were independent predictors of reduced beading frequency., Conclusions:   Corneal confocal microscopy is a novel, noninvasive technique to evaluate morphological changes of corneal C-fibers in type 1 diabetes. Antecedent hyperglycemia and blood pressure have different time-dependent effects on CNFL and CNFD and the frequency of beading. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2011.00157.x, 2011).

The management of the radiation dose is very important in interventional radiology (IVR), especially in percutaneous coronary intervention (PCI). Therefore, we measured entrance surface doses at the interventional reference point of 27 cardiac intervention procedures in 22 cardiac catheterization laboratories around Hiroshima, and compared these doses. Recently, for cardiac interventional radiology, the X-ray machines using flat-panel detectors (FPD) instead of image intensifiers (I.I.) is increasing; 13 systems used FPD and 14 systems used I.I. For fluoroscopy rate, the difference between laboratories was 9 times. For cineangiography rate, the difference between laboratories was 7 times. In addition, between both devices, the I.I. group is bigger than the FPD group. When comparing by the same condition, for the dose at the interventional reference point, no significant difference was detected between the FPD group and the I.I. group. This study shows that FPD is not available for reducing the radiation dose simply. Therefore, it is necessary that we think of the balance with image quality and radiation dose. The optimization of the devices and cardiac intervention procedures becomes very important.

A conceptual/computational framework for exposure reconstruction from biomarker data combined with auxiliary exposure-related data is presented, evaluated with example applications, and examined in the context of future needs and opportunities. This framework employs physiologically based toxicokinetic (PBTK) modeling in conjunction with numerical "inversion" techniques. To quantify the value of different types of exposure data "accompanying" biomarker data, a study was conducted focusing on reconstructing exposures to chlorpyrifos, from measurements of its metabolite levels in urine. The study employed biomarker data as well as supporting exposure-related information from the National Human Exposure Assessment Survey (NHEXAS), Maryland, while the MENTOR-3P system (Modeling ENvironment for TOtal Risk with Physiologically based Pharmacokinetic modeling for Populations) was used for PBTK modeling. Recently proposed, simple numerical reconstruction methods were applied in this study, in conjunction with PBTK models. Two types of reconstructions were studied using (a) just the available biomarker and supporting exposure data and (b) synthetic data developed via augmenting available observations. Reconstruction using only available data resulted in a wide range of variation in estimated exposures. Reconstruction using synthetic data facilitated evaluation of numerical inversion methods and characterization of the value of additional information, such as study-specific data that can be collected in conjunction with the biomarker data. Although the NHEXAS data set provides a significant amount of supporting exposure-related information, especially when compared to national studies such as the National Health and Nutrition Examination Survey (NHANES), this information is still not adequate for detailed reconstruction of exposures under several conditions, as demonstrated here. The analysis presented here provides a starting point for introducing improved designs for future biomonitoring studies, from the perspective of exposure reconstruction; identifies specific limitations in existing exposure reconstruction methods that can be applied to population biomarker data; and suggests potential approaches for addressing exposure reconstruction from such data.

Biomonitoring Equivalents (BEs) are screening tools for interpreting biomonitoring data. However, the development of BEs brings to the public a relatively novel concept in the field of health risk assessment and presents new challenges for environmental risk communication. This paper provides guidance on methods for conveying information to the general public, the health care community, regulators and other interested parties regarding how chemical-specific BEs are derived, what they mean in terms of health, and the challenges and questions related to interpretation and communication of biomonitoring data. Key communication issues include: (i) developing a definition of the BE that accurately captures the BE concept in lay terms, (ii) how to compare population biomonitoring data to BEs, (iii) interpreting biomonitoring data that exceed BEs for a specific chemical, (iv) how to best describe the confidence in chemical-specific BEs, and (v) key requirements for effective communication with health care professionals. While the risk communication literature specific to biomonitoring is sparse, many of the concepts developed for traditional risk assessments apply, including transparency and discussions of confidence and uncertainty. Communication of BEs will require outreach, education, and development of communication materials specific to several audiences including the lay public and health care providers.

Biomonitoring Equivalents (BEs) are defined as the concentration of a chemical (or metabolite) in a biological medium (blood, urine, human milk, etc.) consistent with defined exposure guidance values or toxicity criteria including reference doses and reference concentrations (RfD and RfCs), minimal risk levels (MRLs), or tolerable daily intakes (TDIs) [Hays, S.M., Becker, R.A., Leung, H.W., Aylward, L.L., Pyatt, D.W., 2007. Biomonitoring equivalents: a screening approach for interpreting biomonitoring results from a public health risk perspective. Regul. Toxicol. Pharmacol. 47(1), 96-109]. The utility of the BE is to provide a screening tool for placing biomonitoring data into a health risk context. A Panel of experts took part in the Biomonitoring Equivalents Expert Workshop to discuss the various technical issues associated with calculating BEs and developed a set of guidelines for use in the derivation of BEs. Issues addressed included the role of the point of departure (POD) in BE derivation, the appropriate application of human and animal kinetic data and models, consideration of default uncertainty factor components in the context of internal dose-based extrapolations, and relevance of mode of action to technical choices in kinetic modeling and identification of screening values. The findings from this Expert Panel Workshop on BE derivation are presented and provide a set of guidelines and considerations for use in BE derivation.

We report a rare case of pseudo-Meigs' syndrome due to metastasis of breast cancer to both ovaries. A 34-year-old woman with exertional dyspnea was admitted to our hospital. Before entry the patient had undergone radical mastectomy for left breast cancer in June 1998. Resection and reconstruction of the chest wall for recurrence of the breast cancer had been performed in April 2001. Right pleural effusion was found on admission to our hospital in October 2002. Continuous thoracic drainage obtained 500-2000 ml of fluid per day. Cytologic results were both normal and benign, and cultures for bacteria and acid-fast bacilli were negative. During treatment of the pleural effusion, which proved to be cryptogenic and intractable, a huge pelvic tumor was found. The primary site was unknown. Surgery was performed in November 2002, and tumors were removed from both ovaries. The right pleural effusion vanished after surgery. Pseudo-Meigs' syndrome with metastasis of breast cancer to both ovaries was diagnosed. The patient died of cachexia related to the carcinoma in January 2005.

We devised a procedure for the placement of a double-pigtail endoscopic retrograde biliary drainage (ERBD) tube as an alternative to the placement of a T-tube. We used the procedure, after primary closure of the common bile duct, in three patients undergoing surgery for choledocholithiasis. All three patients were in their eighties, and all were diagnosed with cholecystolithiasis and choledocholithiasis. In all three, there were concerns about possible complications with the use of a T-tube. Two of the patients were senile and were thought to be likely to pull out the tube, and incomplete fistulation was considered possible in the third patient. Thus, there was an increased risk of bile peritonitis in all three patients. Placement of the ERBD tube was successful in all three patients, and there were no postoperative complications. The hospital stay was a few weeks shorter than the usual stay with the placement of a T-tube. We conclude that primary closure of the common bile duct with the placement of a double-pigtail ERBD tube is clinically safe and advantageous for choledocholithiasis patients with senile dementia and for patients with possible incomplete fistulation.

Chlorpyrifos is a common agricultural insecticide and has been used residentially in the United States until the year 2000 when this use was restricted by the U.S. Environmental Protection Agency (U.S. EPA). A chlorpyrifos metabolite, 3,5,6-trichloro-2-pyridinol (TCPy) has been found in urine samples collected during exposure field studies. In this work, we use urinary biomarker data and the inverse solution of a simple pharmacokinetic (PK) model for chlorpyrifos to estimate the magnitude and timing of doses. Three urine samples were collected on separate days from each of 15 children (ages 3-12) who were participants in the Minnesota Children's Pesticide Exposure Study (MNCPES). The total volume of urine was noted and samples analyzed for TCPY: The urinary data was used along with constraints imposed on dose timing, based on responses of the individuals to pesticide-use surveys. We predicted the time and magnitude of multiple "event" exposures characterized by short-term, relatively high doses superimposed over a continuous background exposure. The average dose of chlorpyrifos predicted by the model was 1.61 microg/kg per reported event. Average background dose rate for these children that reported exposure events was 0.0062 microg/kg/h, or 0.15 microg/kg/day. In addition to predicting the total dose of chlorpyrifos received by an individual from urinary biomarker measurements, the model can then be run in a forward manner once the exposure regime is determined. This will allow the prediction of the total amount of TCPy eliminated in the urine over any time period of interest.

The ingestion of raw vegetables represents an important means of transmission of several infectious diseases. The objective of the present study was to perform a microbiological and parasitological evaluation of the vegetables commercially sold in the municipality of Ribeirão Preto, SP, Brazil. Of a total of 172 commercial concerns analyzed, 115 (67%) presented irregularities in the vegetables they sold, such as elevated concentration of fecal coliforms in 63%, presence of Salmonella in 9%, and presence of enteroparasites in 33%. The commercial concerns with the highest frequencies of vegetables showing inadequate results were: grocery stores (92%), CEAGESP (75%), fruit and vegetables stores (71%), traveling vendors (71%), fairs (69%), supermarkets (52%), and vegetable gardens (18%). The type of contamination was uniformly distributed among these commercial concerns. Most of the contaminated vegetables (61%) were from gardens located in the municipality of Ribeirão Preto. Considering the high frequency of fecal contamination and the potential risk of disease transmitted by vegetables, we suggest greater enforcement in the sanitary surveillance of the food offered to the population.

The ingesting of raw vegetables plays an important role in the transmission of several infectious diseases due to the high frequency of irrigation with wastewater. The objective of this study was to evaluate the sanitary conditions of all lettuce producing crops in Ribeirão Preto through microbiological and parasitological analysis of both irrigation water and lettuce together with the implantation of an effective crop monitoring. Laboratory analysis of 129 crops showed irregularities in 26 (20.1%) of these: high concentration of fecal coliforms in 17% of the lettuce, presence of Salmonella in 3.1% and several enteroparasites (Ascaris sp, Ancylostomidae, Strongyloides sp, Hymenolepis nana, and Giardia sp ) in 13.1%. Persistent irregularities determined the definitive closing down of one producer; all of the remaining 128 crops were eventually approved, thus demonstrating the efficacy of lettuce crop monitoring. Crops approved in the laboratory analysis were awarded a Sanitary Inspection Certificate - an unprecedented procedure in our Country - that resulted in a better acceptance of the monitoring.

A case of mucosa-associated lymphoid tissue (MALT) lymphoma of the rectum is reported. A 64 year-old woman was referred to us for the evaluation of occult blood in the stool. A hard mass was palpable on digital examination. Biopsy specimens revealed a histologic picture compatible with MALT lymphoma. Abdominoperineal excision of the rectum was carried out. Chemotherapy was not performed, and the post-operative course was uneventful, with no evidence of recurrence for 2 years and 11 months. Surgical resection is an effective therapy for MALT lymphoma of the rectum.

The relationship was examined between the tumoricidal effect and the electrical variables of in vivo electrical impulse chemotherapy. Donryu rats subcutaneously inoculated with AH-109AY hepatocellular carcinomas were given a single high-voltage electrical impulse of varying voltage and duration, 30 min after an intramuscular injection of 4 mg/kg bleomycin. As the voltage (V) was increased from 0 to 5 kV, the tumoricidal effect (E) increased in proportion to the square of the voltage. As the pulse duration (D) was increased from 2.5 to 5.8 ms, the tumoricidal effect increased in direct proportion to it. Combining these results yielded the formula, E = gamma V2D, which indicates that tumoricidal efficacy was proportional to the applied electrical energy. When the electrical energy was kept constant while varying the voltage and duration of pulse, the anticancer effect was the same, confirming this relationship for lower energy levels.

The correlation between the dose of menatetrenone and the incidence of post-laparotomy peritoneal adhesion in Ryan's model was investigated with the use of rats. In the menatetrenone treated group, the menatetrenone was intramuscularly given in a dosage of 10 mg immediately after closure of the abdominal wound and every 24 hours for two days. In this group, the incidence of ceco-colonic adhesion was 54% (20/37), whereas the incidence in non-treated group was 26% (10/39) (p less than 0.012). Especially in cases with an air-drying time of 1-2 minutes, the difference between incidences of ceco-colonic adhesion in the menatetrenone and that of the non-treated group was high. The former incidence was 61% (17/28) and that of the latter was 21% (6/29) (p less than 0.01). In addition, the incidence of peritoneal adhesion was proportionally dose-dependent to the menatetrenone. In our clinical retrospective study, the incidence of post-gastrectomy adhesive ileus increased with menatetrenone treatment to a significant degree. It is concluded that prophylactic administration of a large dose of menatetrenone should be avoided, because the incidence of post-laparotomy peritoneal adhesion could be increased.

Giving a high voltage electrical stimulation (5 kv/cm, 2 msec) under bleomycin administration (5 mg/body, im) resulted in a significant size decrease of subcutaneously inoculated AH-109A hepatocellular carcinomas in Donryu rats. The tumor size decreased to an average 17 per cent of the initial mass 4 days after the treatment and the average survival period was extended to almost 200 per cent of that of the control. However, neither high voltage electrical stimulation nor bleomycin administration alone demonstrated an anticancer effect. It was thus concluded that the concomitant use of a high voltage electrical stimulation and an anticancer drug has the potential to be effectively applied in cancer treatment.

Application of a high-voltage electrical impulse (5 kV/cm, 2 msec) after bleomycin administration resulted in a significant size decrease of subcutaneously inoculated AH-109A hepatocellular carcinoma in Donryu rats. The tumor size decreased to an average of 17% of the initial mass 4 days after the treatment. Neither the high-voltage electrical impulse nor bleomycin administration alone showed an inhibitory effect on the tumor growth. It was concluded that the concomitant use of a high-voltage electrical impulse and an anticancer drug has the potential to be applicable for cancer treatment.

A case of spinal cord melanoma at the level of C2 was reported. A 27-year-old house-wife, in the 8th month of an uncomplicated pregnancy, complained of motor weakness and sensory impairment in the left arm. Then, left lower limb and right upper and lower limbs were gradually involved and she suffered from tetraplegia when she was first admitted to our hospital about two months after the beginning of her symptoms. Neurological and roentogenological examination revealed an upper cervical intradural extramedullary tumor, and laminectomy from C1 to C4 was performed. The tumor was totally removed and diagnosed as a melanocytic melanoma histopathologically. Postoperatively, she had complete recovery. In order to exclude the possibility of a metastatic melanoma, the patient was seen in repeated consultations by dermatology, gastro-enterology, otorhinolaryngology, urology and gynecology services. But, there was no evidence of pigmented lesions anywhere, so we considered this case as a primary melanoma of the spinal cord clinically. Finally, a brief discussion about correlation between the melanoma and the pregnancy was added.