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PURPOSE/OBJECTIVE(S) Reducing radiation doses to the heart and/or cardiac segments are crucial to decrease the risk of radiation-induced coronary artery diseases (RICAD) for patients with left-sided breast cancer. However, dosimetric advantages for these structures between three-dimensional conformal radiation therapy plus electron boost (3D-CRT+EB) and simultaneous integrated boost volumetric modulated arc therapy (SIB-VMAT) remain unclear, especially in the patients with a potential risk of RICAD. The aim of this study was to compare some dosimetric parameters between the 3D-CRT + EB and SIB-VMAT in left-sided breast cancer patients with a potential risk of RICAD. MATERIALS/METHODS A total of 57 patients with left-sided breast cancer treated with SIB-VMAT between 2018 and 2020 were enrolled. All patients were identified as the potential risk of RICAD by radiation oncologists using maximum heart distance (MHD), and met the MHD ≧ 1 cm. All patients were prescribed a dose of 42.56 Gy/ 16 fractions to planning target volume and a total dose of 53.2 Gy (N = 21) or 51.2 Gy (N = 36) for a concomitant-boosted target. The 3D-CRT + EB plans were retrospectively created for a comparison purpose, using field-in-field technique followed by electron beam irradiations. Some dosimetric parameters for clinical target volume (CTV), heart, left anterior descending coronary artery (LAD), middle LAD (mLAD), lungs, and contralateral breast were compared using the Wilcoxon signed rank test. RESULTS The Dmean, Dmax and D98% for CTV were significantly improved in the SIB-VMAT plans. For cardiac-related structures, the median doses of SIB-VMAT versus 3D-CRT + EB were as follows: Dmean for heart, 2.9 Gy vs. 1.9 Gy (P < 0.001); Dmean, V20 and V30 for LAD, 12.6 Gy vs. 15.4 Gy (P < 0.001), 23.0% vs. 33.3% (P = 0.0049) and 2.0% vs. 24.7% (P < 0.001); Dmean, V20 and V30 for mLAD, 16.0 Gy vs. 21.1 Gy (P = 0.0014), 29.9% vs. 51.4% (P = 0.0040) and 0.5% vs. 31.1% (P < 0.001), respectively. The Dmean, V5 and V20 for the lungs and the Dmean for contralateral breast were significantly reduced in the 3D-CRT + EB plans (P < 0.001, for all). The doses to the LAD and mLAD tended to be higher in lateral cohort (upper outer and lower outer quadrants of breast) than in medial cohort (upper inner and lower inner quadrants of breast), while these doses were significantly reduced by the SIB-VMAT. CONCLUSION Although 3D-CRT + EB technique can reduce the mean dose to the heart, the doses to LAD and mLAD can be significantly decreased by SIB-VMAT, which could be a benchmark for selecting the most appropriate irradiation technique in the patients with a potential risk of RICAD.

Cathepsin K inhibitors are new drugs with the potential for the treatment of osteoporosis because they sustain bony remodelling better than bone resorption inhibitors such as bisphosphonates. The treatment of osteoporosis with inhibitors of bony resorption is associated with osteonecrosis of the jaw, as the deterioration in bony quality that they induce is thought to be one of its causes. The quality of bone is delineated by structural and material characteristics (which include the degree and quality of mineralisation, and depends on the content of proteoglycan and the structural integrity of the bony collagen).1,2 Animal and clinical studies have shown that cathepsin K inhibitors improve the mineral density and structural characteristics of bone, but their effect on the rest remains unknown. We therefore hypothesised that these inhibitors will affect the material characteristics of newly-formed mandibular bone. To verify our hypothesis, we used Raman microspectroscopy to examine such bone in rats that were given a cathepsin K inhibitor, and found unusual crystallinity and an increased substitution of carbonate (CO32-) in its crystal structure.

Bone quality is defined by structural and material characteristics. Most studies on the mandible have focused on the analysis of structural characteristics, with insufficient investigation of material characteristics. This study tested whether zoledronate affects the material characteristics of newly formed mandibular bone. Thirty-six female Wistar rats were assigned to three groups: sham-ovariectomized rats (SHAM, n=12), ovariectomized rats (OVX, n=12), and ovariectomized rats treated with zoledronate (ZOL, n=12). The left side of the mandibular ramus of all rats was drilled bicortically. Twenty-eight days after surgery, all surviving rats were euthanized and all mandibles were removed. Raman microspectroscopy was performed, and five spectra per specimen of newly formed mandibular bone were analysed. Compared with OVX rats, the mineral/matrix ratio in ZOL rats was significantly increased (5.43±1.88 vs. 7.86±2.05), while crystallinity (0.055±0.002 vs. 0.050±0.002), relative proteoglycan content (0.43±0.10 vs. 0.31±0.05), and collagen structural integrity (1.16±0.21 vs. 0.72±0.06) were significantly decreased. These changes in material characteristics may explain why rats that received zoledronate exhibited peculiar biological phenomena such as bisphosphonate-related osteonecrosis of the jaw.

Varronia multispicata (Cham.) Borhidi (Cordiaceae), an herbaceous plant distributed in tropical and subtropical regions is native of Brazil and widely used in folk medicine to treat respiratory and digestive diseases, inflammation, and some types of infections. Thus, this study aimed to investigate acute oral toxicity, antinociceptive, and anti-inflammatory activities of dry aqueous extract of V. multispicata (AEVm) and to identify its compounds. Extract was obtained by lyophilized leaf infusion and its composition was analyzed by ultra-performance liquid chromatography-high resolution mass spectrometry (LC-MS). Acute oral toxicity was evaluated in female rats treated with AEVm (2,000 mg/kg) in a single oral dose. Mortality, body weight changes, feed and water intake, organ weights, histological and biochemical parameters were screened for 14 days. Antinociceptive activity was evaluated by writhing (WT), formalin (FT), and hot plate (HP) tests in male mice while anti-inflammatory activity was performed by carrageenan (CPE) and dextran (DPE)-induced paw edema tests and carrageenan-induced peritonitis (CP) test in male rats. Additionally, spontaneous open-field (OF) locomotion was evaluated. LC-MS analysis revealed the presence of flavonoids with biological activity. In toxicity evaluation, extract did not cause deaths in dose of 2,000 mg/kg, and there were no significant behavioral or biochemical alterations. Additionally, evidence of hepatoprotective and antioxidant activity was observed. In pharmacological evaluation AEVm showed dose-dependent antinociceptive activity in WT, with a median effective dose of 146.89 mg/kg, which showed selectivity by inflammatory base processes (FT first phase; p < 0.001), showing no activity in neuropathic nociception components (FT second phase and HP) or about consciousness and locomotion in OF. AEVm also showed significant anti-inflammatory activity, inhibiting CPE (p < 0.001) and cell migration (p < 0.05) and nitric oxide (NO) production (p < 0,01) in CP test. These data demonstrate that AEVm has low oral toxicity—with evidence of hepatoprotective and antioxidant properties—antinociceptive and anti-inflammatory activity, supporting V. multispicata traditional use, possibly related to flavonoids present in its constitution.

Background Methotrexate (MTX) is a well-known anchor drug for rheumatoid arthritis (RA); however, dose regimens vary. We previously reported in EULAR2015 that split dose weekly oral methotrexate induced elevation of AST and ALT in association with elevation of MTX with 2 glutamates (MTX-PG2) in a single-centre trial. Objectives We performed a multi-centre randomised controlled trial to compare the incidence of adverse events using single and split dose regimens. Methods Six hospitals and 2 rheumatology clinics participated in this study. Seventy-eight patients with insufficient control on MTX 8 mg/week were randomly assigned to 2 groups, i.e., a single weekly dose regimen with 39 patients and a 3 dose per week regimen with 39 patients. The MTX dose in all patients was gradually increased to 16 mg/week. The primary endpoint was the occurrence of liver dysfunction during the observation period (20 weeks). Other endpoints included the incidence of adverse events and the changes from baseline in the disease activity score (DAS28) based on ESR or CRP, the Simplified Disease Activity Index (SDAI), and MTX-PG at week 20. Results There were no differences between the groups in baseline data and MTX dose at 20 weeks (single dose: 10.2±0.8 vs. 3-dose: 10.2±0.9 mg/week). Liver dysfunction occurred in 3 patients (7.7%) receiving the single dose regimen and in 5 patients (13.2%) receiving the 3-dose regimen, but there was no significant difference in the incidence in both groups (p=0.455). There was a significant difference in the incidence of adverse events (gastrointestinal disorder was most common) between single dose (11 patients, 28.9%) and 3-dose (20 patients, 52.6%) regimens (p=0.036). There was no significant difference in the changes from baseline in DAS28-ESR (−1.55 vs. −1.36), DAS28-CRP (−1.31 vs. −1.26), or SDAI (−9.45 vs. −10.11). Compared to the single dose regimen, MTX-PG2 was significantly increased in the 3-dose regimen, and MTX-PG3, -PG4, and -PG5 were significantly increased in the single dose regimen (table 1). Conclusions There were no differences in the incidence of liver dysfunction and efficacy according to the oral MTX dose regimen; however, split weekly dosing compared with single weekly dosing reduced polyglutamylation and increased the risk of adverse events. Acknowledgements Clinical registration: UMIN000021157 Disclosure of Interest Y. Yoshioka: None declared, K. Katayama: None declared, T. Kasama: None declared, M. Sato: None declared, S. Ohno: None declared, Y. Amasaki: None declared, H. Kataoka: None declared, D. Kanai: None declared, A. Suda: None declared, M. Okamoto Employee of: AYUMI Pharmaceutical Corporation, M. Sasano: None declared, S. Nagaoka: None declared, A. Sagawa: None declared

Background Remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) syndrome is a rare inflammatory arthritis, characterised by absence of rheumatoid factor, symmetrical distal synovitis, pitting oedema of the hands and feet. In recent years the use of dipeptidyl peptidase-4 (DPP4) inhibitor has increased and some reports have described the association of RS3PE syndrome with DPP4 inhibitor. Objectives: We have tried to investigate the association of RS3PE syndrome with DPP4 inhibitor in our hospital. Methods: In Japan DPP4 inhibitor was released in December 2009, so we retrospectively analysed background, treatment and clinical course of 25 patients with RS3PE syndrome diagnosed between December 2009 and December 2016 in our hospital. We divided them in two groups according to DPP4 inhibitor prescription and compared two groups. Results: Our cases included 18 males and 7 females, and the mean age of RS3PE syndrome onset was 76 years old. The mean follow-up period was 32.5 months. Six patients had diabetes mellitus and DPP4 inhibitor was prescribed in five of six patients (83.3%). (sitagliptin 3 cases, teneligliptin 1 case, alogliptin 1case). The duration of RS3PE syndrome onset after DPP4 inhibitor prescription was mean 22.9 months, and two cases developed within a half year, two cases after two years. Compared with non DPP4 inhibitor group, the mean age of RS3PE syndrome onset was significantly low (70 vs 78.5, p=0.023), and HbA1c (NGSP) was high (7.3% vs 6.02%, p=0.00022) in DPP4 inhibitor group. The occurrence of flare was four cases in non DPP4 inhibitor group and zero in DPP4 inhibitor group, but was not statistically different (p=0.275). Other clinical features were not significantly different. Conclusions: DPP4 inhibitor group was significantly younger than non DPP4 inhibitor group, and the possibility that DPP4 inhibitor contributed to the early onset of RS3PE syndrome was suggested. References [1] Oyama K, Taniguchi J, et al. Remitting seronegative symmetrical synovitis with pitting edema syndrome in individuals with type 2 diabetes mellitus or impaired glucose tolerance. Diabetes Res Clin Pract. 2015Oct;110(1):e5–8. [2] McCarty DJ, O’Duffy JD, et al. Remitting Seronegative Symmetrical Synovitis with Pitting Edema (RS3PE Syndrome). JAMA 1985; 254: 2763–2767. Disclosure of Interest None declared

Intermittent parathyroid hormone (PTH) administration is known to promote bone healing after surgical procedures. However, the mechanism and influence of PTH on the mineral and collagen quality of the jaw are not well understood. Most studies have focused on analyzing the bone density and microstructure of the mandible, and have insufficiently investigated its mineral and collagen quality. Oxidative stress activates osteoclasts, produces advanced glycation end products, and worsens mineral and collagen quality. We hypothesized that PTH induces oxidation and affects the mineral and collagen quality of newly formed mandibular bone. To test this, we examined the mineral and collagen quality of newly formed mandibular bone in rats administered PTH, and analyzed serum after intermittent PTH administration to examine the degree of oxidation. PTH administration reduced mineralization and worsened mineral and collagen quality in newly formed bone. In addition, total anti-oxidant capacity in serum was significantly decreased and the oxidative-INDEX was increased among PTH-treated compared to vehicle-treated rats, indicating serum oxidation. In conclusion, intermittent administration of PTH reduced mineral and collagen quality in newly formed mandibular bone. This effect may have been induced by oxidation.

We present a case of paediatric Stage IV sporadic Burkitt's leukaemia presenting as cheek enlargement with osteolysis of the maxilla. An 8-year-old boy was referred to our department with diffuse swelling of both cheeks. Head and neck examination revealed bilateral diffuse nontender swelling, non-fluctuant but slightly compressible. Computed tomography imaging showed enhancing bilateral bulky lesions expanding the maxillary sinuses, with associated osteolysis in the posterior walls of both sinuses. Laboratory results included blast cells in the peripheral blood, suggesting a haematopoietic tumour. We referred the patient to the Department of Paediatric Haematology and Oncology. Additional examinations eventually led to the diagnosis of Stage IV sporadic Burkitt's leukaemia.

Background The p53 tumor-suppressor gene is one of the most frequently mutated genes in cancers, and its mutations affect various biological actions, such as tumor growth, apoptosis, and so on. During hypoxia, p53 is stabilized by interaction with hypoxia-inducible factor-1 (HIF-1). This interaction raised the possibility for regulating HIF-1 activity by p53, which is still to be elucidated. Methods First, we introduced various types of the p53 mutant gene into Hep3B and evaluated the role of p53 in hypoxic responses, including vascular endothelial growth factor (VEGF) production and HIF-1 activation. Second, Hep3B-vector cells and Hep3B-p53 cells were subcutaneously injected into BALB/c (nu/nu) mice, and tumor progression and the hypoxic responses were analyzed. Finally, we investigated the role of the p53 mutant genes in the level of vascularity in human pancreatic neoplasia. Results Here, we showed that expression of wild-type p53, but not null or mutated p53, significantly suppressed HIF-1 activity and production of VEGF, which mostly depends on the HIF-1β protein level. In a tumor xenograft model, we consistently found that loss of p53 promotes VEGF production, neovascularization, and tumor progression via accumulation of HIF-1β protein. Furthermore, in clinical pancreatic neoplasia, tumors with mutated p53 have significantly higher levels of vascularity than those with wild-type p53. Conclusion These results indicate that loss of p53 contributes to neovascularization through regulation of HIF-1.

Cancer gene therapy by adenovirus vectors (Advs) for metastatic cancer is limited because systemic administration of Adv produces low therapeutic effect and severe side effects. In this study, we generated a dual cancer-specific targeting vector system by using PEGylation and the telomere reverse transcriptase (TERT) promoter and attempted to treat experimental metastases through systemic administration of the vectors. We first optimized the molecular size of PEG and modification ratios used to create PEG-Ads. Systemic administration of PEG-Ad with 20-kDa PEG at a 45% modification ratio (PEG[20K/45%]-Ad) resulted in higher tumor-selective transgene expression than unmodified Adv. Next, we examined the effectiveness against metastases and side effects of a TERT promoter-driven PEG[20K/45%]-Ad containing the herpes simplex virus thymidine kinase (HSVtk) gene (PEG-Ad-TERT/HSVtk). Systemic administration of PEG-Ad-TERT/HSVtk showed superior antitumor effects against metastases with negligible side effects. A cytomegalovirus (CMV) promoter-driven PEG[20K/45%]-Ad also produced antimetastatic effects, but these were accompanied by side effects. Combining PEG-Ad-TERT/HSVtk with etoposide or 5-fluorouracil enhanced the therapeutic effects with negligible side effects. These results suggest that modification with 20-kDa PEG at a 45% modification ratio is the optimal condition for PEGylation of Adv, and PEG-Ad-TERT/HSVtk is a prototype Adv for systemic cancer gene therapy against metastases.

In order to establish a design rule of the plasma reactors, a fundamental investigation was carried out. The results show that important points of the design criteria were flow speed of gas and power input to the discharge tubes. An engineering model of plasma reactor for 100 kVA diesel engine generating system was designed, constructed and tested. The reactor is composed of 3 blocks, 30 discharge tubes with 1 m long and they are driven by a high voltage inverter power source. The test results show that the fundamental data were applicable to the engineering model reactor and the required energy yield of NO oxidation process was almost attained. A scale up rule has also been confirmed

Prevention of hypoxic cell death is a key to successful liver transplantation. We developed a new method for preventing liver hypoxic cell death by introducing an anti-cell death gene directly into rat livers. When the human bcl-2 gene (hbcl-2) was directly transfected into rat livers together with non-histone chromosomal protein high mobility group 1 (HMG1) by the hemagglutinating virus of Japan (Sendai virus; HVJ)-liposome method, human Bcl-2 protein (hBcl-2) was efficiently expressed. Electron microscopy and fluorescence microscopy revealed that hepatocytes expressing exogenous hBcl-2 were almost completely protected the hypoxic cell necrosis. The expression of the hBcl-2 also inhibited activation of caspase-3 (-like) proteases and liver dysfunction. Thus, we conclude that transfection of the hbcl-2 gene through HVJ-liposome method is useful to prevent liver cell necrosis induced by hypoxia. This finding could lead to new strategies to avoid the hypoxic cell death, the major problem in liver transplantation.

The prevalence of cigarette smoking among Japanese men has been consistently high compared with Western males over the past 30 years. However, during the same period, the incidence of and mortality rates for lung cancer have consistently been lower in Japan than in Western countries (‘Japanese smoking paradox’). The odds ratio/relative risk of cigarette smoking for lung cancer mortality/incidence relative to the same number of cigarettes smoked per capita in Japan, were apparently lower than those in Western countries. This must be the cause driving the ‘Japanese smoking paradox’. Furthermore, low carcinogenic ingredients in Japanese cigarettes and a congenitally-related resistance to smoking-related lung carcinogenesis emerged as the main factors which have brought the ‘Japanese smoking paradox’.

Every year, many people are injured by slipping and falling accidents when walking. Clarification of the mechanism of slipping and falling may provide insight into possible solutions. The purpose of this study was to reveal the behavior of the shoe sole contact during walking by measuring both contact pressure distribution and the slippage of shoe sole blocks. A force plate with a walkway made of glass was produced to observe the contact area between the walkway and the shoe sole. The total internal reflection of light was used to distinguish the contact area and noncontact area of the shoe sole. The slippage of the shoe sole was measured by time-sequence position variations of each block. As a result, a large traction coefficient and a large slippage of the shoe sole block were found to occur immediately after the heel strike. Slippage was also detected at the period of toe off. Moreover, the maximum contact pressure of each block varied from 1.0MPa to 3.0MPa in the contact area.Copyright © 2011 by ASME

The post-operative changes in the serum levels of CRP and serum amyloid A (SAA) were investigated prospectively in 106 patients after posterior lumbar interbody fusion. In 96 patients who did not have complications related to infection within the first year after operation, the median levels of CRP before operation and on days 3, 7 and 13 after were 0.02 (0.01 to 0.03), 9.12 (2.36 to 19.82), 1.64 (0.19 to 6.10) and 0.53 (0.05 to 2.94) mg/dl, respectively and for SAA, 2.6 (2.0 to 3.8), 1312.1 (58.0 to 3579.8), 77.3 (1.8 to 478.4), 14.1 (0.5 to 71.9) μg/ml, respectively. The levels on day 3 were the highest for both CRP and SAA and significantly decreased (p < 0.01) by day 7 and day 13. In regard to CRP, no patient had less than the reference level (0.1 mg/dl) on day 7. In only three had the level decreased to the reference level, while in 93 it was above this on day 13. However, for SAA, the levels became normal on day 7 in 10 cases and on day 13 in 34 cases. The ratios relative to the levels on day 3 were significantly lower for SAA compared with CRP on day 7 and day 13. Of the ten patients with infection in the early stages, the level of CRP decreased slightly but an increase in SAA was observed in six. We concluded that SAA is better than CRP as a post-operative inflammatory marker.

Two influenza A viruses were isolated from pigs in Thailand in January 1988 during the early febrile stage of an influenza-like illness. The isolates contained hemagglutinin and neuraminidase antigens related to those of swine H1N1 influenza virus. This result based on the virus isolation is compatible with the epizootiological evidence that, unlike the human influenza with peak activity in summer (May-July), swine influenza virus is prevalent in the winter season (November-January) in Thailand. The proportion of sera with hemagglutination-inhibiting antibody was higher to A/NJ/8/76 than to A/sw/Iowa/15/30. Likewise, hemagglutination-inhibition tests with monoclonal antibodies indicated that hemagglutinin antigen of the isolates was very similar to that of A/NJ/8/76 virus. In agreement with the serological survey and antigenic characteristic, genetic relatedness between the isolates from Thailand and A/NJ/8/76 virus was also demonstrated by the oligonucleotide mapping of RNA, suggesting that they may be of the same origin.

The relaxation times (T1 and T2) of water proton in nuclear magnetic resonance (NMR) were measured with solutions containing bovine fibrinogen (Fbg), fibrin degradation products (FDP) and with fibrin-gel (Gel), at varying protein concentrations (0.7-70 mg/ml). Both T1 and T2 declined exponentially with increasing protein concentration. At a protein concentration of 35 mg/ml, the T1 of Fbg, Gel and FDP were 2.32, 2.12 and 2.82 s and the T2 values were 0.35, 0.17 and 0.70, respectively. The relaxation times for the control samples (0.2 M borate buffer) were 3.41 (T1) and 2.28 (T2). When the relaxation rates (the inverse of T1 and T2), R1 and R2 were plotted against the protein concentration, there were positive linear correlations between them. Using the slopes of the plots, the hydration value of each protein was calculated. The hydration value (g of H2O/g of protein) was 0.24 for Fbg, 0.34 for Gel and 0.14 for FDP.

A very rare developmental anomaly showing bilaterally persistent sciatic arteries was found in a cadaver of 89 year old female. Both right and left sciatic arteries arose from the internal iliac arteries and appeared between the piriformis and superior gemellus muscles at the buttock, being about 10 mm in diameter. Each artery, which accompanied by the companion vein, i.e. sciatic vein, sent the branches to the gluteus maximus and the flexor muscles of thigh. On the other hand, the femoral arteries of both lower limbs were smaller than usual, measuring 4.7 mm in left and 5.2 mm in right. The terminal vessels of those were joined to the sciatic arteries at the popliteal fossa. In addition, the present case also had another developmental anomaly, i.e. superficial brachial artery in the right upper limb.

Purpose: Hypo-fractionated stereotactic body radiation therapy (SBRT) with intensity modulated radiation therapy (IMRT) is nowadays one of the treatment strategies for prostate cancer. There are few reports on planning study of prostate cancer by CyberKnife with respect to the urethral dose because of the invisibility in CT. We have investigated a planning method using fixed collimators with considering dose homogeneity, conformity and urethral dose. Methods: Radiotherapy treatment planning of prostate cancer were under a clinical trial approved by the institutional review board. The prescription dose of 35 Gy were delivered to the PTV in five fractions with the urethral catheter. Urethra position was identified by pretreatment CT and catheter, which was inserted before treatment planning CT and released after the treatment. All plans agreed to the criteria as shown in table 1, and the following constraints were recommended as well: the prescribed iso-dose line should be from 70% to 90%; the total MU should be below 50,000 MU; the minimum MU per beam should be larger than 15 MU; the estimated delivery time (excluding patient setup time) by Multiplan with image time interval of 60 s should be less than 35 min. Collimator size and position were decided as shown in figure 1. Fixed collimator of 15 mm was positioned around urethra and PTV for avoiding high dose of urethra and achieving conformity, and fixed collimator of 30 or 40 were positioned around PTV for achieving dose homogeneity. Results: With this method, all constraints were achieved. (Table 1, Figure 2) Max dose of urethra was ranging from 103.9% to 114.2%, because urethra position was identified by pretreatment CT and urethral catheter. Conclusion: Hypo-fractionated SBRT with IMRT utilizing urethral catheter could be a promising new treatment option for prostate cancer. This work was supported by JSPS Core-to-Core program Number 23003.

Caspase-3 is a member of the cysteine protease family, which plays a crucial role in apoptosis. We applied the human caspase-3 gene as a novel form of anticancer gene therapy. Overexpression of human caspase-3 alone could not induce apoptosis of tumor cell lines, but apoptosis was markedly enhanced by the addition of etoposide. In an AH130 liver tumor model, transduction of human caspase- 3, but not the empty vector, induced extensive apoptosis and reduced tumor volume when combined with etoposide administration. However, this effect was not observed with a Bcl-2 overexpressing tumor. In conclusion, caspase-3 gene transduction accompanied by an additional death stimulus may be a useful method of anticancer gene therapy, except for Bcl-2 overexpressing tumors.

This paper reports a premature infant with a congenital diaphragmatic hernia (CDH) who underwent an abdominal wall plasty to enlarge the abdominal cavity, one of twin infants born at 32 weeks weighing 1,255 g. After stabilization, the herniated viscera were reduced from the pleural cavity and the abdominal wall muscle and skin layers were replaced by a Gore-tex patch without closure of the diaphragmatic defect. Respiratory and circulatory conditions were stable during the perioperative period. Postoperatively, a roentogenogram showed expansion of the lung. However, his condition deteriorated 24 h after surgery, triggered by intratracheal suction, and he died on the 4th day of life despite the use of high-frequency oscillation, catecholamines, and vasodilators. Postmortem examination showed severely hypoplastic lungs. Abdominal wall plasty may be a less invasive initial procedure, however, further studies, such as comparison with the standard method or conservative management, are needed using a large clinical group or animal models to justify the usefulness of this procedure.

This article describes a prenatal ultrasonographic finding of an infarcted intestinal volvulus. Ultrasonography showed polyhydramnios, multiple dilated intestinal loops, increased transverse abdominal area, and ascites. After cesarean section due to premature rupture of membranes and fetal distress, derotation of the infarcted volvulus caused postoperative thrombocytopenia, hyperkalemia, and acidosis and a subsequent resection was required. A high output of intestinal juice from the jejunostomy caused severe hypovolemia and electrolyte imbalance with resultant death. Increased transverse abdominal area caused by marked intestinal dilatation, ascites, fetal distress, and hydrops fetalis may suggest an infarcted intestinal volvulus.

Necrotizing enterocolitis (NEC) sometimes occurs in term infants with congenital heart disease. This article reports a rare case of a term infant with coarctation of the aorta complex who developed NEC on the 8th day after birth. Spontaneous closure of the ductus arteriosus in the 1st week of life may cause intestinal ischemia and hypoxia with resultant NEC.

Linear and angular measurements were made on thirty-two cadaveric femora with respect to the mechanical (functional) axes of the bone. The long axis was defined as a line from the center of the femoral head to the anterolateral attachment of the posterior cruciate ligament. The transverse axis was defined as a line through the posterior cruciate ligament parallel to the line connecting each epicondyle. The condylar width, the length of each interepicondylar line, correlated well with depth, but the projections of the condyles from the transverse plane revealed significant variations from specimen to specimen. Considerable variation also was found between femora in terms of angular dimensions (that is, the angle of anteversion and the neck-shaft angle proximally, and the valgus angle of the femoral shaft distally). Considerable interspecimen variation in the angles between the transcondylar plane and the femoral center, in accord with the valgus angle of the femoral shaft distally, was also noted. The mean transcondylar valgus angle (described as the tangent of the condyles to the perpendicular of the long axis) was 3.8 degrees. In contrast, little variation among specimens was noted for the angle made by the shaft and the long axis.

This study describes a clinically oriented anatomical assessment of anteversion on 32 cadavers ranging from 61 to 89 years. The method used a three-dimensional reference system based on functional axes of the femur. Each soft tissue-free femur was mounted on an osteometric table and aligned to its functional axes. The long axes were defined as passing from the centre of the femoral head to the femoral attachment of the posterior cruciate ligament (PCL). A line that ran through the PCL attachment (equal distal origin of this system) and was parallel to a transepicondylar line served as transverse axis. Anteversion of the femur was defined as an angle formed to the transverse axis by a line running through the centre of the femoral head through the midpoint of the narrowest segment of the femoral neck. The measurement mean for anteversion among these specimens was 7.4 degrees with a range from -10.8 degrees (retroversion) to 22.1 degrees. There was no statistical difference in mean values (p less than 0.05) between sexes or between right and left sides of the group; however, there were large variations for anteversions when each side in the same individual was compared (although there was no dominant side). Retroversions were observed in four of 32 femurs (12.5%). No correlation was found between the anteversion in these femurs and rotational geometry at the knee. We compared our data with those obtained by conventional techniques, by which anteversion for each femur was measured after the bone had been placed on a flat surface.(ABSTRACT TRUNCATED AT 250 WORDS)

Growth characteristics of a wide range of influenza A viruses from different mammals and bird species were examined in an established line of canine kidney (MDCK) cells at an ordinary (37 degrees C) and a high temperature (42 degrees C). Although all viruses employed in the present study possessed a capability of replicating at 37 degrees C, virus growth at 42 degrees C showed considerable variation and reflected differences in the natural hosts of the isolates. All reference strains and isolates from bird species grew well in the MDCK cells maintained at 42 degrees C, but human viruses did not, showing an asymmetrical growth behavior. In contrast to this, growth of swine and equine viruses showed growth characteristics intermediate between human and avian viruses. Of the two swine viruses examined, replication of one strain occurred equally well at both temperatures and another failed to grow at 42 degrees C. Similarly, two of the three equine viruses tested belonging to H3N8 antigenic subtypes grew at 42 degrees C. However, the results obtained from comparison of plaque sizes and growth curves indicated that the replication of the above swine and equine viruses was restricted under a stringent temperature when compared to avian viruses. The detailed analysis of cloned viruses revealed that some of the swine and equine viruses contained two variants which are readily distinguished by growth behavior at 42 degrees C. Genome analysis of parental and virus clones by oligonucleotide mapping and migration profiles of RNA segments did not detect any differences among the above variants exhibiting the asymmetrical growth characteristics at 42 degrees C.

Echocardiographic features of two cases of ruptured congenital aneurysm of Valsalva sinus with (case1) and without (case 2) a supracristal ventricular defect were studied before and after surgery by standard echocardiography. M-mode scan and two-dimensional echocardiography. Discontinuity was observed in the echo from the aneurysm wall of the Valsalva sinus in case 1 with ruptured aneurysm, but was not observed in a similar case of unruptured aneurysm. Herniation of the right coronary cusp of the aortic valve into the right ventricular outflow tract was also observed in case 1. After surgical correction the echo from the aneurysm wall and from the herniated right coronary cusp of the aortic valve disappeared. Discontinuity in the echo from the anterior aortic wall and the interventricular septum also disappeared. In case 2, discontinuity in the echo from the anterior aortic wall, and tricuspid flutter with an abnormally low early diastolic peak were observed. These abnormalities disappeared after surgery. The ability of echocardiography to detect ruptured Valsalva aneurysm is discussed.

Articular geometry of the tibia has been studied in relation to the functional axis and extra-articular bone landmarks, using a Cartesian coordinate system. Thirty-one cadaver limbs were used, 26 of them paired. The donor age range was 61 to 89 years (17 females, 14 males), none of whom showed evidence of significant arthritic deterioration. Most linear parameters were greater in males than females (p less than 0.005), and correlations between these parameters were noted, e.g., tibial length versus plateau width (r = 0.7, p less than 0.01) with both genders combined. Gender differences occurred in only two of the angular parameters--tibial torsion (p less than 0.025) and foot rotation (p less than 0.005). For the latter, mean rotation was internal (-5 degrees) for males, and external (11 degrees) for females. No correlations between angular parameters were found. In the paired limbs, there was asymmetrical distribution of just two parameters--varus tilt of the tibial plateau margins (p less than 0.005) and lateral deviation of the tuberosity (p less than 0.025). The data complement a previous report on the femur. These studies are relevant to the kinematics of the lower limb, design and sizing of resurfacing components, and possibly to the pathogenesis of osteoarthritis.

Two patients with rapidly progressive chondrolysis of the hip are reported. Immunofluorescent staining showed deposits of immunoglobulins and complement components in the synovium and the remaining femoral head cartilage. Seven patients with osteoarthritis of the hip and knee, or femoral neck fractures, were used as controls and all had a negative immunofluorescent staining reaction in the synovium. We suggest that an autoimmune reaction against articular cartilage antigens may play a role in the development of chondrolysis.