Tc-99m hydroxymethylene diphosphonate SPECT/CT for the evaluation of osteonecrosis of the jaw: preliminary study on diagnostic ability of maximum standardised uptake value.

AIM: To investigate the diagnostic ability of maximum standardised uptake value (SUVmax) at combined single-photon-emission computed tomography/computed tomography (SPECT/CT) for the evaluation of osteonecrosis of the jaw. MATERIALS AND METHODS: Seven patients with mandibular osteonecrosis (three osteoradionecrosis, three medication-related osteonecrosis of the jaw (MRONJ), and one rheumatoid arthritis) underwent SPECT/CT at 4 hours after injection of technetium 99m hydroxymethylene diphosphonate. The SPECT/CT parameters SUVmax were compared for the osteonecrosis with normal mandible. Statistical analyses among the SUVmax of osteonecrosis were performed by one-way repeated measures analysis of variance with Tukey's HSD (honestly significant difference) test. A p-value <0.05 was considered statistically significant. RESULTS: SUVmax for MRONJ and rheumatoid arthritis (23.24±8.63) were significantly higher than those for osteoradionecrosis (9.05±1.39, p=0.005) and normal mandible (3.57±0.46, p=0.000). CONCLUSIONS: SUVmax derived from bone SPECT/CT could be useful for the evaluation of osteonecrosis of the jaw.

A decadal inversion of CO2 using the Global Eulerian-Lagrangian Coupled Atmospheric model (GELCA): sensitivity to the ground-based observation network.

We present an assimilation system for atmospheric carbon dioxide (CO2) using a Global Eulerian-Lagrangian Coupled Atmospheric model (GELCA), and demonstrate its capability to capture the observed atmospheric CO2 mixing ratios and to estimate CO2 fluxes. With the efficient data handling scheme in GELCA, our system assimilates non-smoothed CO2 data from observational data products such as the Observation Package (ObsPack) data products as constraints on surface fluxes. We conducted sensitivity tests to examine the impact of the site selections and the prior uncertainty settings of observation on the inversion results. For these sensitivity tests, we made five different site/data selections from the ObsPack product. In all cases, the time series of the global net CO2 flux to the atmosphere stayed close to values calculated from the growth rate of the observed global mean atmospheric CO2 mixing ratio. At regional scales, estimated seasonal CO2 fluxes were altered, depending on the CO2 data selected for assimilation. Uncertainty reductions (URs) were determined at the regional scale and compared among cases. As measures of the model-data mismatch, we used the model-data bias, root-mean-square error, and the linear correlation. For most observation sites, the model-data mismatch was reasonably small. Regarding regional flux estimates, tropical Asia was one of the regions that showed a significant impact from the observation network settings. We found that the surface fluxes in tropical Asia were the most sensitive to the use of aircraft measurements over the Pacific, and the seasonal cycle agreed better with the results of bottom-up studies when the aircraft measurements were assimilated. These results confirm the importance of these aircraft observations, especially for constraining surface fluxes in the tropics.

A case of ovarian small cell carcinoma of the pulmonary type that was observed as it developed.

INTRODUCTION: In the case reported here, the authors observed ovarian small cell carcinoma of the pulmonary type as it developed. CASE: The patient was a 48-year-old woman who underwent a hysterectomy for CIN3 in 2007. A year later, the woman underwent screening for ovarian cancer. A gradually growing ovarian mass was noted. This mass was found to be a mixed tumor. This mixed tumor grew to 36 mm in size, and six months later it had enlarged to 119 mm. After surgery, the tumor was pathologically diagnosed as an ovarian small cell carcinoma of the pulmonary type with a neuroendocrine nature that was positive for CD56 and synaptophysin. Postoperatively, the patient received six courses of combined therapy with irinotecan and cisplatin (CPT-P therapy), and the patient has survived disease- free for over two years. CONCLUSION: Findings suggested that ovarian small cell carcinoma of the pulmonary type is a type I ovarian malignancy that develops through an adenoma-carcinoma sequence.

Positive association of free triiodothyronine with pancreatic ß-cell function in people with prediabetes.

AIM: To analyse the effects of thyroid hormones on ß-cell function and glucose metabolism in people with prediabetes who are euthyroid. METHODS: A total of 111 people who were euthyroid underwent 75-g oral glucose tolerance tests, of whom 52 were assigned to the normal glucose tolerance and 59 to the prediabetes groups. Homeostatic model assessment of ß-cell function, insulinogenic index and areas under the curve for insulin and glucose were evaluated as indices of pancreatic ß-cell function. RESULTS: In both groups, BMI, fasting insulin, homeostasis model assessment ratio and HDL cholesterol correlated significantly with all indices of pancreatic ß-cell function. Free triiodothyronine correlated positively with all insulin secretion indices in the prediabetes group. Multiple linear regression analysis showed that free triiodothyronine was an independent variable that had a positive correlation with all indices of ß-cell function in the prediabetes group. By contrast, no such correlation was found in the normal glucose tolerance group. CONCLUSIONS: Free triiodothyronine is associated with both basal and glucose-stimulated insulin secretion in people with prediabetes who are euthyroid; therefore, the regulation of insulin secretion by thyroid hormones is a potentially novel therapeutic target for the treatment of diabetes.

Anticancer effects of gemcitabine are enhanced by co-administered iRGD peptide in murine pancreatic cancer models that overexpressed neuropilin-1.

BACKGROUND: Impaired drug transport is an important factor that reduces the efficacy of anticancer agents against pancreatic cancer. Here, we report a novel combination chemotherapy using gemcitabine (GEM) and internalised-RGD (iRGD) peptide, which enhances tumour-specific drug penetration by binding neuropilin-1 (NRP1) receptor. METHODS: A total of five pancreatic cancer murine models (two cell line-based xenografts (CXs) and three tumour grafts (TGs)) were treated with either GEM (100 mg kg(-1), q3d × 4) alone or GEM plus iRGD peptide (8 µmol kg(-1)). Evaluation of NRP1 expression in xenografts and 48 clinical cancer specimens was performed by immunohistochemistry (IHC). RESULTS: We identified a subset of pancreatic cancer models that showed NRP1 overexpression sensitive to iRGD co-administration. Treatment with GEM plus iRGD peptide resulted in a significant tumour reduction compared with GEM monotherapy in CXs, but not remarkable in TGs. Potential targets of iRGD were characterised as cases showing NRP1 overexpression (IHC-2+/3+), and these accounted for 45.8% of the clinical specimens. CONCLUSIONS: Internalised RGD peptide enhances the effects of co-administered drugs in pancreatic cancer models, its efficacy is however only appreciable in those employing cell lines. Therefore, the clinical application needs to be given careful consideration.

Specific muscle-tendon architecture in elite Kenyan distance runners.

The Achilles tendon moment arm (MA_AT) and foot lever ratio (FLR) can play important roles for force production and movement economy during locomotion. This notion has become more relevant, and suggestion has been given that the Kenyan runners belonging to the world elite would have specific anatomical, mechanical, and functional properties in their lower limbs and that this feature could be responsible for their high running economy. The present study aimed to characterize the AT of elite Kenyan distance runners as compared with Japanese ones, and to examine the potential relationship with their running performance. Ultrasonography was used to measure AT cross-sectional area and AT soleus and gastrocnemius lengths. MA_AT and FLR were calculated from the position of anatomical landmarks using sagittal plane photographs. MA_AT was significantly longer and the FLR lower in Kenyans than in Japanese. Independently of the group, the running performance was positively related to the MA_AT (r = 0.55, P < 0.001) and negatively to the FLR (r = -0.45, P = 0.002). These results suggest that longer MA_AT and lower FLR could be advantageous in elite Kenyan runners, by contributing to effective endurance running performance in a protective and economical way.

A case of synthetic oestrogen-induced autoimmune hepatitis with microvesicular steatosis.

WHAT IS KNOWN AND OBJECTIVE: Drug-induced liver injury (DILI) is a leading cause of acute liver failure in developed countries. Hepatotoxicity is a well-recognized adverse effect associated with synthetic oestrogens, which can cause cholestasis. The current report describes ethinyloestradiol (EE2)-associated highly unusual adverse effects of autoimmune hepatitis (AIH) and microvesicular steatosis (MS). DILI that fulfils the criteria for AIH is referred to as drug-induced autoimmune hepatitis (DIAIH). MS is a potentially severe liver lesion that results from mitochondrial dysfunction. We explore the pathophysiological mechanisms underlying DIAIH and MS. CASE SUMMARY: A 51-year-old woman presented with jaundice, increased liver enzymes and IgG, and positive ANA. She had been taking EE2 for 3 years. Liver biopsy showed prominent interface hepatitis with MS. A drug-lymphocyte stimulation test (DLST) using EE2 was positive. The liver biochemical parameters had normalized after the EE2 discontinuation; however, they exacerbated 5 months post-onset. Repeated liver biopsy showed interface hepatitis with no MS. Considering EE2-induced DIAIH, corticosteroids treatment was initiated. Then, all liver biochemical parameters had normalized, and the corticosteroids were successfully withdrawn. The patient continued to be in complete remission over the next 3 years. WHAT IS NEW AND CONCLUSION: Five remarkable points should be emphasized: (i) a long latency interval, despite the acute presentation; (ii) exacerbation of liver biochemical parameters, even after drug cessation; (iii) the paired liver biopsies indicating continuing inflammation and disappearance of toxic features; (iv) a positive DLST and the absence of fibrosis consistent with DIAIH and not AIH; and (v) a rare histological feature of MS. Intense immunoallergic reactions were likely triggers of MS in the current case. A possibility of DIAIH should be considered in cases of DILI which exhibit overt jaundice, autoantibodies, intense histological inflammation and a long latency period.

Submicrometer particle removal indoors by a novel electrostatic precipitator with high clean air delivery rate, low ozone emissions, and carbon fiber ionizer.

A novel positive-polarity electrostatic precipitator (ESP) was developed using an ionization stage (0.4 × 0.4 × 0.14 m(3) ) with 16 carbon fiber ionizers in each channel and a collection stage (0.4 × 0.4 × 0.21 m(3) ) with parallel metallic plates. The single-pass collection efficiency and clean air delivery rate (CADR) were measured by standard tests using KCl particles in 0.25-0.35 µm. Performance was determined using the Deutsch equation and established diffusion and field charging theories and also compared with the commercialized HEPA filter-type air cleaner. Experimental results showed that the single-pass collection efficiency of the ESP ranged from 50 to 95% and decreased with the flow rate (10-20 m(3) /min), but increased with the voltage applied to the ionizers (6 to 8 kV) and collection plates (-5 to -7 kV). The ESP with 18 m(3) /min achieved a CADR of 12.1 m(3) /min with a voltage of 8 kV applied to the ionization stage and with a voltage of -6 kV applied to the collection stage. The concentration of ozone in the test chamber (30.4 m(3) ), a maximum value of 5.4 ppb over 12 h of continuous operation, was much lower than the current indoor regulation (50 ppb).

Muscle-tendon interaction and EMG profiles of world class endurance runners during hopping.

The present study examined the muscle-tendon interaction of ten international level Kenyan runners. Ultrasonography and kinematics were applied together with EMG recordings of lower limb muscles during repetitive hopping performed at maximal level. The ten Kenyans had longer gastro Achilles tendon at rest (p < 0.01) as compared with ten control subjects matched in height. Conversely, the stretching and shortening amplitudes of the tendinous tissues of the medial gastrocnemius (MG) muscle were significantly smaller in the Kenyans than in controls during the contact phase of hopping. This applied also to the fascicle length changes, which were smaller and more homogeneous among Kenyans. These limited musculo-tendinous changes resulted in higher maximal hopping height and in larger power despite their reduced body weight. The associated finding of a greater shortening to stretching ratio of the MG tendinous tissues during contact could imply that the Kenyan MG muscle-tendon unit is optimized to favor efficient storage and recoil of elastic energy, while operating at optimal muscle fascicle working range (plateau region).

Mutations in the human Jagged1 gene are responsible for Alagille syndrome.

Alagille syndrome (AGS) is an autosomal-dominant disorder characterized by intrahepatic cholestasis and abnormalities of heart, eye and vertebrae, as well as a characteristic facial appearance. Identification of rare AGS patients with cytogenetic deletions has allowed mapping of the gene of 20p12. We have generated a cloned contig of the critical region and used fluorescent in situ hybridization on cells from patients with submicroscopic deletions to narrow the candidate region to only 250 kb. Within this region we identified JAG1, the human homologue of rat Jagged1, which encodes a ligand for the Notch receptor. Cell-cell Jagged/Notch interactions are known to be critical for determination of cell fates in early development, making this an attractive candidate gene for a developmental disorder in humans. Determining the complete exon-intron structure of JAG1 allowed detailed mutational analysis of DNA samples from non-deletion AGS patients, revealing three frame-shift mutations, two splice donor mutations and one mutation abolishing RNA expression from the altered allele. We conclude that AGS is caused by haploinsufficiency of JAG1.

Relationship between quadriceps femoris muscle volume and muscle torque at least 18 months after anterior cruciate ligament reconstruction.

The purpose of this study was to evaluate motor unit recruitment in the quadriceps femoris (QF) after anterior cruciate ligament (ACL) rupture and repair. Subjects included 24 patients at ≥ 18 months after ACL reconstruction and 22 control subjects with no history of knee injury. A series of cross-sectional magnetic resonance images were obtained to compare the QF of patients' injured side with that of their uninjured sides and that of uninjured control subjects. Muscle torque per muscle volume was calculated as isokinetic peak torque divided by QF muscle volume (cm(3)). The mean muscle torque per unit volume of the injured side of patients was not significantly different from that of the uninjured side or control subjects (one-way ANOVA) Results of the present study were contrary to the results of a previous study that evaluated patients at ≤ 12 months after ACL reconstruction. The present study found that high-threshold motor unit recruitment was restored at ≥ 18 months after ACL reconstruction. Thus, clinicians must develop techniques that increase the recruitment of high-threshold motor units in the QF from the period immediately after the injury until approximately 18 months after ACL reconstruction.

Minimally required heat doses for various tumour sizes in induction heating cancer therapy determined by computer simulation using experimental data.

PURPOSE: Although induction heating cancer therapy (IHCT) using magnetic nanoparticles can be a promising approach to treatment-less multi-nodular cancers, the objective requirement for successful clinical application has not clearly been elucidated. We intended to define objective heat doses suitable for IHCT, especially focusing on the sizes of liver cancer nodules. MATERIALS AND METHODS: Alternating magnetic fields were applied to three human pancreatic cancer cell lines, the intercellular space of those cell pellets were filled with magnetic nanoparticles, and confirmed the cytotoxic effect of IHCT. Subsequently, the temperatures of liver cancer nodules in IHCT were simulated using a computer software program and the required heat dose for various sized tumours were determined. RESULTS: Heating the cancer cells up to 50 degrees C for 10 min was sufficient for complete cell killing and the heat dose of 1.7 W/g(tumour) is required for 10 mm tumour. Larger tumours require a smaller heat dose, e.g. 20 mm and 40 mm tumours require 0.7 W/g(tumour) and 0.6 W/g(tumour), respectively, whereas smaller tumours require large amounts of heat, e.g. 5 mm and 1 mm tumours require 5.1 W/g(tumour) and 105 W/g(tumour), respectively. CONCLUSIONS: Integrating the presently available technologies, including high-quality magnetic nanoparticles (1000 W/g(material)) and effective drug delivery systems (1-2 mg(material)/g(tumour)), treatment of a 10 mm tumour seems possible. Since treatment of smaller tumours less than 5 mm require substantial heat dose, researchers involved in IHCT should target cancer nodules of 10 mm or more, and develop a heat delivery system providing a minimum of 1.7 W/g(tumour).

[Operative technique of median sternotomy].

Median sternotomy is the most widely used incision in cardiac surgery. The skin incision should extend from just below the sternal notch to a few centimeters below the xiphoid process. Careful dissection behind sternal notch and xiphoid process should be required to prevent accidental adjacent vessels injuries. The sternotomy should be made on the midline of the sternum after detecting the lateral margin of the sternum by dipping the thumb and the index finger into the intercostal space. Off-midline sternotomy may cause the closure wires to cut through the thinner segment of the bone, which may cause wound infection. There has been an increase in the number of patients who undergo a 2nd or even a 3rd time cardiac surgery. Redo sternotomy is becoming a major technique in cardiac surgery. The sternum could be divided with an oscillating saw safely by lifting previous wires untwisted, which helps prevent possible right ventricular injury. Blunt digital manipulation or dissection can often result in tearing of the right ventricular wall which can be fatal.