The multidirectional assessment of moderate caloric restriction and metformin treatment in obese patients.

Obesity treatment is often burdensome for patients. We used the combination of moderate caloric restriction (CR) with hypoglycemic metformin to assess their multidirectional effect in obese patients. One group was treated only with moderate CR (n=21) the second was treated with moderate CR and 800 mg metformin twice daily (n=23). Serum was drawn before and after treatment. The following parameters were monitored: anthropometric, cardiovascular, inflammatory, metabolic, and markers characteristic for thyroid, liver, pancreas, and kidney functions. Both tested groups did not significantly differ in most tested parameters after the treatment. Two groups reduced anthropometric parameters (body mass, body mass index (BMI), waist circumference) and fat mass but also muscle and fat-free mass, improving systolic blood pressure, insulin and leptin concentration, insulin sensitivity, leptin to adiponectin ratio, and inflammatory markers. Unfortunately, there was little impact on improving dyslipidemia and the thyroid and liver parameters. Free triiodothyronine (fT3) and gamma glutamyl transferase (GGT) activity were decreased in both groups, but triglycerides were reduced only in patients treated with moderate CR. Metformin with CR treatment decreases uric acid and aspartate aminotransferase (AspAT) activity. Metformin treatment with moderate CR in obese patients mainly improved insulin sensitivity, resulting in a reduction of patients with glucose intolerance, improved anthropometric, cardiovascular, and inflammatory mediators, and only slightly enhanced liver and thyroid function. No changes in kidney and pancreas function were observed during the treatment. In conclusion, eight weeks of CR alone and CR with metformin in obese adults improved anthropometric and metabolic markers, reduced muscle mass, fT3, GGT, proinflammatory, and CV parameters, and displayed no changes in kidney and pancreas function. The group treated with metformin after the treatment was still more obese and had higher C-reactive protein (CRP) and homeostasis model assessment-an index of insulin resistance (HOMA-IR), but despite this, considerably reduced the number of patients with glucose intolerance.

Assessment of the main pathogens associated with clinical and subclinical endometritis in cows by culture and MALDI-TOF mass spectrometry identification.

Clinical endometritis (CE) and subclinical endometritis (SCE) are diseases that affect dairy cows during the puerperium, causing negative effects on the animals' milk production and fertility. The objective of this study was to assess the main bacteria related to cases of CE and SCE from uterine samples of dairy cows in Brazilian herds. Selective and differential media were used for isolation of aerobic and anaerobic bacteria and further MALDI-TOF mass spectrometry (MS) identification. A total of 279 lactating dairy cows with 28 to 33 d in milk from 6 commercial farms were evaluated. Initially, cows were classified in 3 groups: cytologic healthy cows (n = 161), cows with CE (n = 83), and cows with SCE (n = 35). Healthy animals presented 97 species, followed by the CE group with 53 identified species, and SCE cows presented only 21 bacterial species. We found a significantly higher isolation rate of Trueperella pyogenes in CE (26.5%) cows compared with healthy and SCE cows. Some anaerobic species were exclusively isolated from the CE group, even though they presented lower frequency. Interestingly, 18.1% of samples from CE cows and 40% of SCE cows were negative to bacterial isolation. Despite the use of culture-dependent methods instead of molecular methods, the present study enabled the identification of a complex community of 127 different species from 48 genera, composed of aerobic and anaerobic bacterial species among the 3 different animal groups. The method of sample collection, culture, and identification by MALDI-TOF MS were essential for the success of the analyses.

Safety assessment of the Clostridium butyricum MIYAIRI 588® probiotic strain including evaluation of antimicrobial sensitivity and presence of Clostridium toxin genes in vitro and teratogenicity in vivo.

Probiotics are live microorganisms ingested for the purpose of conferring a health benefit on the host. Development of new probiotics includes the need for safety evaluations that should consider factors such as pathogenicity, infectivity, virulence factors, toxicity, and metabolic activity. Clostridium butyricum MIYAIRI 588(®) (CBM 588(®)), an anaerobic spore-forming bacterium, has been developed as a probiotic for use by humans and food animals. Safety studies of this probiotic strain have been conducted and include assessment of antimicrobial sensitivity, documentation of the lack of Clostridium toxin genes, and evaluation of CBM 588(®) on reproductive and developmental toxicity in a rodent model. With the exception of aminoglycosides, to which anaerobes are intrinsically resistant, CBM 588(®) showed sensitivity to all antibiotic classes important in human and animal therapeutics. In addition, analysis of the CBM 588(®) genome established the absence of genes for encoding for α, ß, or ε toxins and botulin neurotoxins types A, B, E, or F. There were no deleterious reproductive and developmental effects observed in mice associated with the administration of CBM 588(®) These data provide further support for the safety of CBM 588(®) for use as a probiotic in animals and humans.

Cost-Effectiveness Analysis of the Diagnosis and Treatment of Primary Aldosteronism in Japan.

Approximately 10% of cases of hypertension in Japan are caused by primary aldosteronism (PA), amounting to about 4 million patients in total. Primary aldosteronism due to unilateral aldosterone hypersecretion is potentially curable by adrenalectomy. The clinical benefits of identifying and treating PA have been reported internationally, but its cost-effectiveness is unclear. We examined whether diagnosing and treating hidden PA in hypertensive population was cost-effective compared with suboptimal treatment. Our hypothetical patient was a 50-year-old man diagnosed with stage I-III hypertension. We established a Markov decision model based on plausible clinical pathways and prognoses of PA. We applied cost-effectiveness analysis comparing a comprehensive diagnostic strategy for PA (measurement of plasma aldosterone/renin ratio, 2 loading tests, imaging, and selective adrenal venous sampling) with a suboptimal strategy to manage hypertension by medication unless the typical signs of PA or other complication were manifest. Outcome measures were expected costs, expected effectiveness, and incremental cost-effectiveness ratio. The robustness of the findings was established by one-way and scenario sensitivity analyses. The comprehensive PA diagnostic strategy increased the expected costs by 64 004 JPY and expected life-years by 0.013 compared with standard treatment. The incremental cost-effectiveness ratio for the diagnosis of PA was 4 923 385 JPY per year. Our findings were sensitive to the outcomes of screening and treatment, and the costs of continuous or periodic medication for hypertension and the treatment of stroke and its complications.

Economic evaluation of a preemptive treatment strategy for invasive fungal infection in neutropenic patients with hematological diseases.

We compared the expected medical costs of empirical and preemptive treatment strategies for invasive fungal infection in neutropenic patients with hematological diseases. Based on the results of two clinical trials with different backgrounds reported by Oshima et al. [J Antimicrob Chemother 60(2):350-355; Oshima study] and Cordonnier et al. [Clin Infect Dis 48(8):1042-1051; PREVERT study], we developed a decision tree model that represented the outcomes of empirical and preemptive treatment strategies, and estimated the expected medical costs of medications and examinations in the two strategies. We assumed that micafungin was started in the empirical group at 5 days after fever had developed, while voriconazole was started in the preemptive group only when certain criteria, such as positive test results of imaging studies and/or serum markers, were fulfilled. When we used an incidence of positive test results of 6.7 % based on the Oshima study, the expected medical costs of the empirical and preemptive groups were 288,198 and 150,280 yen, respectively. Even in the case of the PREVERT study, in which the incidence of positive test results was 32.9 %, the expected medical costs in the empirical and preemptive groups were 291,871 and 284,944 yen, respectively. A sensitivity analysis indicated that the expected medical costs in the preemptive group would exceed those in the empirical group when the incidence of positive test results in the former was over 34.4 %. These results suggest that a preemptive treatment strategy can be expected to reduce medical costs compared with empirical therapy in most clinical settings.

Microbiological quality assessment of sand and water from three selected beaches of South Coast, São Paulo State, Brazil.

This study aimed to assess the sanitary quality of water, and wet and dry sand from three beaches located in the South Coast region of São Paulo State, Brazil, selected taking into account the frequency of tourists and the water quality (good, fair and poor). Thirty-six water samples each of wet and dry sand and seawater were collected monthly over a period of one year and analyzed for fecal indicator bacteria (FIB: thermotolerant coliforms, Escherichia coli, and enterococci), presumptive Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans and dermatophytes. The results revealed FIB concentrations more elevated in dry sand followed by wet sand and water. P. aeruginosa and presumptive S. aureus were detected with a similar frequency in water and sand samples, but maximum concentrations and geometric means were higher in dry sand. C. albicans was detected only in water samples whereas the dermatophyte Microsporum sp. was isolated exclusively from dry and wet sand samples. This evaluation showed also that the environment had a significant influence on P. aeruginosa but not on presumptive S. aureus concentrations. According to threshold values proposed in the literature for E. coli and enterococci dry sand densities, none of the beaches would be considered of sufficient quality for recreational activities.

Skin advanced glycation end-product accumulation is negatively associated with calcaneal osteo-sono assessment index among non-diabetic adult Japanese men.

UNLABELLED: This study aims to determine the relationship between advanced glycation end-product (AGE) accumulation in skin tissue and bone strength, assessed by quantitative ultrasound, among healthy adult Japanese men. The results of the study suggest that men with higher AGE accumulation in skin tissue have a lower osteo-sono assessment index. INTRODUCTION: AGE accumulate in bone collagen with age and diabetes and decrease the mechanical properties of bone. Although increased AGE levels are associated with fractures among diabetic patients and elderly women, it is unclear whether a relationship between increased AGE levels and bone strength is present in apparently healthy adult males. The aim of this study was to determine the relationship between AGE accumulation in tissue and the mechanical properties of bone among adult Japanese men, using quantitative ultrasound as a surrogate measure of the latter. METHODS: Skin autofluorescence (AF), which is a noninvasive method for measuring tissue AGEs, and osteo-sono assessment index (OSI), which is determined by quantitative ultrasound, were measured in 193 adult Japanese men (median age 43 years; interquartile range 37.0-55.0 years). RESULTS: Adjusted for age, BMI, calcium intake, physical activity, smoking status, and education level, log-transformed skin AF had a negative association with log-transformed OSI (ß = -0.218, P < 0.01). Adjusted geometric means (95% CI) for OSI across the tertiles of skin AF were 2.81 (2.75-2.87) for the lowest tertile, 2.81 (2.74-2.87) for the middle tertile, and 2.66 (2.61-2.73) for the highest tertile; thus, OSI for the highest skin AF appeared to be 5.0% lower than that for the lowest and middle skin AF tertiles (P < 0.01). CONCLUSION: Among apparently healthy adult Japanese men, those with higher skin AF had a lower OSI, indicating a relationship between AGE accumulation and bone strength. A long-term prospective study is required to clarify the causality.

[Assessment of proximal aortic anastomosis device in coronary artery bypass grafting].

The aim of this study was to assess the feasibility and safety of a new proximal anastomotic device (PAD) "Enclose II" in coronary artery bypass grafting (CABG). PAD enables the construction of a proximal aortic anastomosis without the use of partial clamp of the ascending aorta, thus reduces the incidence of adverse perioperative neurologic injury related to atheroembolic events. This device was used in 41 off-pump CABG and 11 on-pump beating heart CABG patients for performing 46 radial artery (RA) and 9 vein anastomoses to the aorta. The subjects were 43 males and 9 females, with a mean age of 63.6 years. Thirteen (25%) patients had severe atherosclerotic cerebrovascular lesions preoperatively. The mean flow in the RA graft was 52.4 +/- 26.9 ml/min and that of saphenous vein graft (SVG) was 61.1 +/- 31.9 ml/min. Angiography showed all grafts patent. There was no procedure-related adverse events or cerebrovascular complication. Enclose II device can be a valuable tool to perform RA and vein anastomoses in CABG.

Structural change of crystalline and amorphous-Ge(2)Sb(2)Te(5) by reverse Monte Carlo analysis of x-ray diffraction data and extended x-ray absorption fine structure data.

Reverse Monte Carlo analyses of crystalline and amorphous Ge(2)Sb(2)Te(5) thin films were carried out using x-ray diffraction data and three spectra from extended x-ray absorption fine structure measurements. To produce a crystal model, we employed a large system with 12 800 Ge, 12 800 Sb and 32 000 Te atoms. The obtained model for the crystal structure was used for the initial configuration of the amorphous model. As a result of a series of reverse Monte Carlo analyses with various constraints, we found that the partial pair distribution function in the amorphous state with the largest deviation from the crystal state is a Ge-Sb pair and the distance is less than 2.7 Å. This suggests that Sb atoms in amorphous Ge(2)Sb(2)Te(5) thin film have a four-coordinate within 3.2 Å.

[Assessment of mode of recurrence after surgical treatment for thymic carcinoma].

In order to establish an appropriate treatment for thymic carcinoma, clinical courses of 15 patients with type C thymoma of WHO classification were reviewed. Five-years survival rate in all patients was 37.6%. In cases underwent complete resection, survival was 48.5%. The induction chemotherapy was done in 7 cases, and complete resection was possible in all these cases, suggested the possibility of improving the survival by the induction therapy. Upper mediastinal lymph node dissection each performed in 9 cases, and they showed significantly better survival than those without lymph node dissection. In conclusion, we have found that induction chemoradiotherapy and complete tumor resection with lymphnode dissection would contribute to improvement of the results in treatment for thymic carcinoma.

Envelope size tuning for stereo-depth perception of small and large disparities.

Stereopsis is the sense of depth derived from binocular disparities that are formed between targets that are matched between the two retinal images. Binocular matches for sustained stereopsis are based on similarity of orientation, spatial frequency and contrast of the two retinal images whereas matches for transient stereopsis depend on these parameters to a very limited extent. In this investigation we have tested the possibility that transient stereopsis forms matches between objects of similar overall size. The tuning of sustained and transient stereopsis to contrast-envelope size was investigated by presenting narrow-band Gabor targets of unequal size to the two eyes. Bandwidth for envelope-size tuning was estimated from the range of dichoptic size-differences over which stereo performance remained above chance level. An equal bandwidth of 2 octaves was found for the sustained and transient stereo systems when stimulated with parallel orientation Gabors that subtended a small disparity. Sustained-stereo performance with orthogonal carriers was reduced with large envelope sizes. Bandwidth of the transient stereo system increased to 3 octaves when tested with a larger disparity stimulus and it was independent of carrier orientation. Reducing the contrast of the larger-size Gabor improved transient-stereo performance from near chance (48-58%) to 85-95%. Thus the bandwidth for envelope-size tuning is much broader than indicated with equal physical contrast stimuli. The observed tuning to envelope size, while broad, is tighter than that observed for carrier spatial-frequency [Vis. Res. 38 (1998) 3057], carrier orientation [Vis. Res. 39 (1999) 2717] and contrast polarity [Vis. Res. 39 (1999) 4010] of the stimulus. Thus it would appear that envelope size and, to a greater extent, temporal synchrony of the dichoptic stimuli [Perception 24 (1995) 33] are the primary means for selecting matched binocular inputs for transient stereopsis.

Envelope size-tuning for transient disparity vergence.

Our prior studies have demonstrated that the transient-vergence system responds preferably to dichoptic stimulus pairs that contain the highest combined energy, regardless of dichoptic differences in spatial frequency, contrast, orientation, or luminance polarity (Edwards, M., Pope, D. R., & Schor, C. M. (1998), Vision Research 38, 705; Pope, D. R., Edwards, M., & Schor, C. M. (1999) Vision Research 39, 575). This broadband tuning for spatial frequency, orientation and contrast is indicative of a second order (non-linear) extraction system. The current study examined the potential size-tuning of binocular channels to the contrast envelope that is extracted by a non-linear process. Stimuli were size-scaled Gabor patches with parallel and orthogonal carrier orientations that subtended a large (3.8 degrees ) disparity. Results indicate that the transient-vergence system exhibits broad band-pass tuning to overall size of dichoptic targets, independent of interocular differences in carrier orientation, spatial frequency or contrast. Equal sizes elicited a higher proportion of vergence responses than unequal sizes, however responses to unequal size still occurred over a 2-octave range, illustrating broad band-pass tuning. Size tuning was found to be broader for small than large envelope sizes. The broad tuning for envelope size is likely to result from the overlapping extracted low-pass frequency spectra of the contrast envelopes. However, the transient-vergence system also responds to monocular, hemi-retinal stimuli over a larger (3-octave) range. Thus some of the observed "binocular tuning" may be due to these monocular responses.

Effects of disparity-perspective cue conflict on depth contrast.

The role of disparity-perspective cue conflict in depth contrast was examined. A central square and a surrounding frame were observed in a stereoscope. Five conditions were compared: (1) only disparity was introduced into either the centre or surround stimulus, (2) only perspective was introduced into the centre or surround, (3) concordant perspective and disparity were introduced into the centre or surround, (4) disparity was introduced into one stimulus and perspective into the other, and (5) only the centre stimulus was presented with horizontal shear disparity and perspective manipulated independently. The results show that individual differences in depth contrast were related to individual differences in the weighting of disparity and perspective in the single-stimulus conditions. We conclude that conflict between disparity and perspective contributes to depth contrast. However, significant depth contrast occurred when there was no disparity-perspective cue conflict, indicating that this cue conflict is not the sole mechanism producing depth contrast.

Treatment of asymptomatic unruptured intracranial aneurysms. A clinical decision analysis.

SUMMARY: The indication of preventive surgery for patients who harbor asymptomatic un ruptured intracranial aneurysms remains controversial. To evaluate the benefit of this treatment, we investigated the management outcome in 128 patients with 157 unruptured aneurysms. Surgery was planned in patients 70 years old or younger without serious systemic complications. A total of 77 patients underwent surgery including four endovascular interventions, and conservative management was chosen in 51 patients. There was no mortality and 6.5% morbidity as postoperative results, and no complication was found after endovascular treatment. Among the patients in conservative management, four patients suffered from subsequent rupture during the total follow-up period of 148 person-years. The annual rupture rate was estimated at 2.7%. According to the clinical decision analysis based on our data, preventive surgery is beneficial for a Japanese 70 years old or younger. However, the expected utility decreases if the rupture rate is set at 0.5% or 0.05%, posing a doubt about the benefit of the surgery. Decision analysis provides an aid for logical and objective choice in the management of unruptured aneurysms. The actual risk of rupture has a major impact on decision making in therapeutic strategy.

Multi-layer energy filter for realizing conformal irradiation in charged particle therapy.

A new type of filter for charged particle radiotherapy is developed to reduce unwanted dose transfer to the normal tissues around a tumor. The new filter can make a static irradiation field where the width of the spread-out Bragg peak (SOBP) is two-dimensionally adjusted. That makes the field conformal to the tumor three-dimensionally. The filter is made of many layers produced by using stereolithography. The layer has a miniaturized structure that has geometrical similarity to the conventional ridge filter. Shapes of cone and pyramid are also usable for the unit-cell constructing the layer. The spread of the field in the depth direction is decided by the thickness of the filter, or by the number of layers. The experimental result of the irradiation using the ridge-type construction shows a good agreement with an estimate by the Monte Carlo calculation. By combining this technique with intensity modulation that has lateral position dependence, the conformal irradiation can be achieved by a simple procedure.

[Home anti-cancer therapy with a venous port].

Home anti-cancer chemotherapy and palliation in the terminal stage were performed for patients with advanced cancer of the digestive system, using a venous port implanted beneath the skin via the subclavian vein. Patients under 75 years of age (5 with esophageal, 61 gastric, 59 colorectal, 5 cholangio, 5 pancreatic, 1 hepatic and 1 ileal cancer) were treated. With two portable balloon pumps, continuous intravenous infusion of 5-FU (300 or 400 mg/body/day) combined low-dose injection of cisplatin (5 mg/body/day) was continued for 10 days, and repeated 3 times for 6 weeks. The response rate was 17.9% in 78 patients according to valuation of the tumor mass. In 119 patients also undergoing a tumor marker evaluation, an effect was seen in 26.1%. No severe side effects such as renal dysfunction or bone marrow suppression were seen, and no special infusion was needed. Therefore, such treatment can be continued for a long time. Use of a venous port should make easy the switchover to HPN and the amelioration of the symptoms of the terminal stage, such as pain, and helps patients cope with the worry. Therefore, the present technique is useful in a series of cancer treatments including surgery, chemotherapy and the amelioration of symptoms.

Environmental education praxis toward a natural conservation area.

A non-formal Environmental Education (EE) Program has been implemented in the natural conservation area (Ecological Station of Jataí, Luiz Ant nio, São Paulo State), through (EE) paradigms, which consider the objectives of education about, in and for the environment within cultural and natural perspectives. The aim of this Program is to support information and scientific knowledge to provide opportunities to the local population to be aware of environmental impacts and risks resulting from the soil use that threaten the environmental quality and the bio diversity of the Ecological Station of Jataí. The Program understands that the promotion of community empowerment could bring the sense of participation and the directives to management for decision-making for local sustainable. The model was projected on local reality, but considering the global issues of environmental paradigms. The environmental characterization (biophysical components) through a Geographical Information Systems was related to the hydrographic basin analysis. The environmental perception was utilized as a main tool to analyse population understanding of local environment, and (EE) pedagogical tools were produced to promote environmental awareness. Since the ecological dimension of (EE) was the main approach, the programme intends to assemble the cultural perspective, achieving the global view of (EE).

Expression of alpha-smooth muscle actin in small bronchioloalveolar adenocarcinoma of the lung: assessment and comparison with noguchi criteria.

The Noguchi criteria are useful in assessing the prognosis of patients with small lung adenocarcinoma. Although there is a significant difference in prognosis between type A or B and type C, it is difficult in some cases to distinguish these types accurately by microscopy. In this study, we used immunohistochemistry to examine alpha-smooth muscle actin (alpha-SMA) produced by active fibroblasts in 25 pulmonary adenocarcinomas less than 2 cm in diameter. Eleven of type C (61%) showed positive staining for alpha-SMA, whereas no positive cases were seen in type A or B. The incidence of cancerous blood vessel and lymphatic invasion were significantly higher in alpha-SMA positive cases than in negative cases, and the positive cases showed poorer prognosis. These findings indicate that immunohistochemical detection of alpha-SMA is useful and essential for histological typing by the Noguchi criteria.

Assessment of resectability of pancreatic carcinoma by color Doppler sonography.

This study was undertaken to evaluate the role of color Doppler sonography in the preoperative assessment of vascular involvement in patients with pancreatic carcinoma. Twenty-six pancreatic carcinomas were investigated with color Doppler sonography and angiography, and the results of these examinations were compared with those of surgical findings. Color Doppler sonography was more sensitive than angiography in depicting vascular involvement of carcinoma. Thus, it seems rational to perform a preoperative assessment in suspected pancreatic carcinoma patients initially with color Doppler sonography to improve patient management.