Antiproliferative effects of NKH477, a forskolin derivative, on cytokine profile in rat lung allografts.

OBJECTIVE: NKH477 was recently identified as a water-soluble forskolin derivative and was reported to prolong survival of murine cardiac allografts. However, the mechanism of the efficacy is not clear in vivo. The aim of this study was to investigate the immunosuppressive effects of NKH477 on acute lung allograft rejection in the rat model and its mechanism of action in vivo. METHODS: Left lungs were transplanted orthotopically from Brown-Norway donors to Lewis recipients. Recipient rats were untreated or treated daily with different doses of NKH477. Grafts were excised on Day 3 or Day 5 to determine histopathological rejection and expressions of interleukin (IL)-2, IL-4, IL-10, and interferon (IFN)-gamma by enzyme-linked immunosorbent assay. The cytokine expression at Day 3 or Day 5 was also evaluated in recipient spleens by immunohistochemistry. Furthermore, mesenteric lymph node cells from recipients at Day 5 were cultured alone or stimulated with donor antigens for 72 hours to determine cell proliferation by means of thymidine incorporation. RESULTS: NKH477 significantly extended allograft survival time in a dose-dependent manner and reduced histopathological rejection. Treatment with NKH477 inhibited IFN-gamma and IL-10 expression, whereas expression of these cytokines were markedly upregulated in the untreated allografts. Expression of IL-2 and IL-10 also increased in the spleen of untreated allorecipients. NKH477 suppressed expression of both cytokines in the spleen. In addition, lymphocyte proliferation was inhibited in NKH477-treated recipients as compared with untreated recipients. CONCLUSION: These results suggest that NKH477 exerts an antiproliferative effect on lymphocytes in vivo with an altered cytokine profile in rat recipients of lung allografts.     

Case of autosomal dominant polycystic kidney disease associated with congenital hepatic fibrosis

A 31-year-old man was admitted to the hospital because of a low-grade fever, general malaise, nausea, vomiting, and a poor appetite. On admission his renal function was severely deteriorated (serum creatinine 16.12 mg/dl, BUN 163 mg/dl), and he had severe anemia (Hb 7.5 g/dl) and thrombocytopenia (67,000/microl). A radiological examination revealed the presence of multiple cysts in his kidneys bilaterally. The patient was diagnosed as having end-stage renal disease due to polycystic kidney disease, and hemodialysis was started on the day of admission. After the initiation of hemodialysis, his symptoms and laboratory tests improved, except for anemia and thrombocytopenia. He was noted to have marked splenomegaly and dilation of the portal vein, raising the suspicion of portal hypertension as the cause of the splenomegaly and pancytopenia. To treat his pancytopenia (anemia and thrombocytopenia) and to determine the reason for his portal hypertension, a splenectomy and open-wedge biopsy of the liver were performed. Histological findings in the liver included extensive fibrosis of the portal areas with an excess of moderately dilated bile ducts, compatible with a diagnosis of congenital hepatic fibrosis. After splenectomy, his red blood cell and platelet counts returned to normal, and he was discharged on maintenance dialysis. Congenital hepatic fibrosis is often associated with autosomal recessive polycystic kidney disease (ARPKD), but not with autosomal dominant polycystic kidney disease (ADPKD). However, both his mother and older brother had multiple renal cysts, indicating that this was an unusual case of ADPKD complicated by congenital hepatic fibrosis.     

A novel method of cryopreservation of rat and human hepatocytes by using encapsulation technique and possible use for cell transplantation

Encapsulated hepatocyte transplantation is a promising approach to cell transplantation without immunosuppression as an alternative to whole organ liver transplantation. However, the shortage of donor cells for hepatocyte transplantation has not been resolved, and at this critical point, it seems necessary to establish a method of hepatocyte cryopreservation to allow clinical application of hepatocyte transplantation and the development of a bioartificial liver system in the near future. In this study we demonstrated that cryopreserved microencapsulated rat and human hepatocytes can retain their hepatic function and that cryopreserved microencapsulated human hepatocytes transplanted into rat spleen remain viable without immunosuppression. Rat and human hepatocytes were isolated by a collagenase digestion method, and they were microencapsulated with poly-L-lysine. The microencapsulated rat hepatocytes were transferred to culture medium (DMEM containing 10% FBS and 10% DMSO) and immediately frozen in liquid nitrogen. A warm water bath (37 degrees C) was used to thaw the microencapsulated hepatocytes. Hepatic function, drug metabolism, and cell morphology were assessed after 90 days of cryopreservation. After 1 week of cryopreservation, microencapsulated hepatocytes were cultured for up to 2 weeks to assess their hepatic function and morphology. The morphology of human hepatocytes was assessed after 30 days of cryopreservation. Cryopreserved human hepatocytes were transplanted into rat spleen to assess their morphology. Cryopreserved microencapsulated hepatocytes retained their viability and were strongly positive for expression of albumin, OAT2, CYP3A2, and CYP3A9. Two weeks after cultivation, the cryopreserved microencapsulated rat hepatocytes had retained their hepatic function (urea synthesis). Cryopreserved microencapsulated human hepatocytes also mainly survived and retained their hepatic function for at least 30 days after cryopreservation. Moreover, entrapped cryopreserved human hepatocytes also survived and expressed albumin in rat spleen after transplantation. We demonstrated a novel method of long-term cryopreservation of rat and human hepatocytes by using an encapsulation technique, with retention of biological activity and excellent survival of the cryopreserved microencapsulated human hepatocytes transplanted into rat spleen. We believe that this novel approach to hepatocytes cryopreservation provides a new direction in encapsulated cell therapy with the goal of clinical application in the near future.     

Systematic node dissection by VATS is not inferior to that through an open thoracotomy: a comparative clinicopathologic retrospective study

BACKGROUND: Major pulmonary resection with systematic node dissection (SND) for early lung cancer by video-assisted thoracic surgery (VATS) is performed in many institutes, but the feasibility of SND for early lung cancer by VATS remains controversial. The aim of this study was to elucidate the feasibility and safety of SND by VATS. METHODS: Three hundred fifty patients with clinical stage I lung cancer who underwent pulmonary major resection with SND between 1998 and 2003 were enrolled in this study. Of these patients, 191 (VATS group) underwent pulmonary resection with SND by VATS; 159 patients (open thoracotomy [OT] group) did so through anterolateral thoracotomy. The clinical and pathologic data, including the number of dissected nodes in each nodal station, of the 2 groups were compared to evaluate the feasibility of SND by VATS. RESULTS: Pathologic data showed that, in the VATS group, more patients had adenocarcinoma (P = .0078) and fewer patients had advanced factors than the OT group. The greatest tumor diameter was 24.5 mm and 29.6 mm in the VATS group and OT group, respectively (P < .0001). The total number of mediastinal nodes dissected in right upper lobectomy plus right middle lobectomy (RUL+RML), right lower lobectomy (RLL), left upper lobectomy (LUL), and lower left lobectomy (LLL) also did not differ between the 2 groups. The total number of mediastinal nodes dissected in RUL+RML, RLL, LUL, and LLL was 19.7 in the VATS group versus 22.0 in the OT group (P = .122), 23.4 versus 21.0 (P = .241), 14.8 versus 17.5 (P = .123), and 18.8 versus 15.8 (P = .202), respectively. The number of dissected nodes in each nodal station in RUL+RML, RLL, LUL, and LLL was similar between the 2 groups. Operative mortality, morbidity, or recurrence did not differ between the 2 groups. CONCLUSIONS: With regard to the number of dissected nodes, SND by VATS was not inferior to that of OT. SND by VATS is technically feasible and safe, and seems acceptable for clinical stage I lung cancer.     

Quantitative assessment of cross-sectional area of small pulmonary vessels in patients with COPD using inspiratory and expiratory MDCT

Objectives

Structural and functional changes in pulmonary vessels are prevalent at the initial stages of chronic obstructive pulmonary disease (COPD). These vascular alterations can be assessed using cross-sectional area (CSA) of small pulmonary vessels. However, neither in non-COPD smokers nor in COPD patients it has been defined whether the structural changes of pulmonary vessels detected by paired inspiratory and expiratory CT scans are associated with emphysematous changes. We quantified the CSA and low attenuation area (LAA) and evaluated the changes in these parameters in the inspiratory and expiratory phases.

Materials and methods

Fifty consecutive non-COPD smokers and COPD patients were subjected to multi detector-row CT and the percentage of vessels with a CSA less than 5 mm² as well as the percentage LAA for total lung area (%CSA < 5, %LAA, respectively) were calculated.

Results

The %CSA < 5 correlated negatively with %LAA. The %CSA < 5 was lower in COPD patients with emphysema as compared with non-COPD smokers and COPD patients with or without mild emphysema. In addition, the %CSA < 5 was lower in the no/mild emphysema subgroup as compared with non-COPD smokers. The respiratory phase change of %CSA < 5 in COPD patients was greater than that in non-COPD smokers.

Conclusion

The percentage of small pulmonary vessels decreased as emphysematous changes increase, and this decrease was observed even in patients with no/mild emphysema. Furthermore, respiratory phase changes in CSA were higher in COPD patients than in non-COPD smokers.     

Computer-aided detection in computed tomography colonography: current status and problems with detection of early colorectal cancer

PURPOSE: The aim of this study was to evaluate the usefulness of computer-aided detection (CAD) in diagnosing early colorectal cancer using computed tomography colonography (CTC). MATERIALS AND METHODS: A total of 30 CTC data sets for 30 early colorectal cancers in 30 patients were retrospectively reviewed by three radiologists. After primary evaluation, a second reading was performed using CAD findings. The readers evaluated each colorectal segment for the presence or absence of colorectal cancer using five confidence rating levels. To compare the assessment results, the sensitivity and specificity with and without CAD were calculated on the basis of the confidence rating, and differences in these variables were analyzed by receiver operating characteristic (ROC) analysis. RESULTS: The average sensitivities for the detection without and with CAD for the three readers were 81.6% and 75.6%, respectively. Among the three readers, only one reader improved sensitivity with CAD compared to that without. CAD decreased specificity in all three readers. CAD detected 100% of protruding lesions but only 69.2% of flat lesions. On ROC analysis, the diagnostic performance of all three readers was decreased by use of CAD. CONCLUSION: Currently available CAD with CTC does not improve diagnostic performance for detecting early colorectal cancer. An improved CAD algorithm is required for detecting flat lesions and reducing the false-positive rate.     

Primary symptoms of 301 patients with prostate cancer: Nagoya Urology Hospital experience

PURPOSE: Primary symptoms were reviewed retrospectively in patients with prostate cancer diagnosed in our hospital with the aim of promoting early detection. MATERIALS AND METHODS: The subjects included 301 cases with prostate cancer diagnosed histologically in Nagoya Urology Hospital from August, 1988 to December, 2001. The mean age was 72.7 years, and the median PSA was 20.0 ng/ml. Primary symptoms were classified according to the General Rule for Clinical and Pathological Studies on Prostate Cancer (The 3rd Edition). RESULTS: Out of 301 cases, 274 (91%) visited our hospital with clinical symptoms. Of them, 272 had primary urological symptoms. In these 272 cases, 250 (92%) and 19 (7%) had lower urinary tract symptoms (LUTS) and macroscopic or microscopic hematuria, respectively. The majority of patients (82%) referred from other urologists had already undergone PSA measurement, compared to 50% in those referred from physicians other than urologists (p < 0.0005). CONCLUSION: The present data revealed that LUTS were important primary symptoms for the detection of prostate cancer, particularly in an area like Nagoya where the mass screening for prostate cancer is still unavailable. In terms of the early detection of prostate cancer, PSA has to be measured in patients with LUTS even when they visit physicians who are not urologists.     

Correlation between Hydroxyapatite Crystallite Orientation and Ultrasonic Wave Velocities in Bovine Cortical Bone

The mineral component of bone is mainly composed of calcium phosphate, constituting 70% of total bone mass almost entirely in the form of hydroxyapatite (HAp) crystals. HAp crystals have a hexagonal system and uniaxial elastic anisotropy. The objective of this study was to investigate the effect of HAp crystallite preference on macroscopic elasticity. Ultrasonic longitudinal wave velocity and the orientation of HAp crystallites in bovine cortical bone are discussed, considering microstructure, density, and bone mineral density (BMD). Eighty cube samples of cortical bone were made from two bovine femurs. The orientation of HAp crystallites was evaluated by integrated intensity ratio of (0002) peak using an X-ray diffractometer. Ultrasonic longitudinal wave velocity was investigated with a conventional pulse system. The intensity ratio of HAp crystallites and velocity were measured in three orthogonal directions; most HAp crystallites aligned in the axial direction of the femurs. Our results demonstrate a linear correlation between velocity and intensity ratio in the axial direction. Significant correlation between velocity and BMD values was observed; however, the correlation disappeared if we focused on the identical type of microstructure. In conclusion, differences in microstructure type have an impact on density and BMD, which clearly affects the velocity. In addition, at the nanoscopic level, HAp crystallites aligned in the axial direction also affected the velocity and anisotropy.     

Herbert螺钉在年轻运动员舟状骨骨折中的应用

背景 舟状骨骨折是竞技体育中常发生的致残性外伤.本研究评估使用捷迈公司生产的Herbert螺钉治疗年轻运动员舟状骨骨折的效果.方法 30例舟状骨骨折的运动员接受治疗.根据Herbert分类标准,其中10例为急性骨折(Ⅰ组),另外包括6例纤维连接(Ⅱ组)和14例为假关节(Ⅲ组);20例患者由于漏诊或内固定失败形成骨不连.结果 Ⅰ、Ⅱ、Ⅲ组术后形成明显骨连接的平均时间分别为9.2、8.0、11.9周,恢复运动能力的时间分别为10.7、14.0、22.9周.使用Mayo腕关节评分评价临床效果,Ⅰ、Ⅱ组表现优秀(分别为97.5和93.3分),Ⅲ组表现良好(85.4分).结论 及早确诊和治疗可使年轻运动员早期恢复运动能力.捷迈公司生产的Herbert螺钉技术治疗舟状骨骨折的临床效果出色.     

Robotic intragastric surgery: A new surgical approach for the gastric lesion

Background

Intragastric surgery is accepted as a minimally invasive procedure for mucosal or submucosal lesions. Robotic surgery promises to extend the capabilities of the minimally invasive surgeon and many surgical specialties are applying this new technology. However, there is no report of robotic intragastric surgery. We describe the use of the da Vinci^® Surgical System for intraluminal mucosal resection of the stomach.

Methods

We developed our porcine intragastric surgery model using the Tuebingen MIS Trainer. We set a tentative lesion on the posterior wall near the esophagocardiac junction (ECJ) of the stomach and performed mucosal resection of the lesion using the da Vinci Surgical System. We also performed closure of the defect after mucosal resection and subsequent closure of the intentional gastric perforation.

Results

Using our porcine intragastric surgery model, we successfully performed mucosal resection of the tentative lesion. We also smoothly completed closure of the defect and closure of the perforation without any complications. The mean size of the mucosa was 6 cm and the mean duration of the procedure was only 12 min.

Conclusions

The safety and efficacy of robotic intragastric surgery was preliminarily established in this study. However, further studies are needed to prove its practical feasibility in humans using the da Vinci Surgical System to make it an effective operation.