Mechanical properties of hydroxyapatite-reinforced gelatin as a model system of bone.

The elastic Young's modulus of hydroxyapatite-reinforced gelatin as a mechanical model system of bone was measured as a function of the volume fraction of hydroxyapatite, phi h. Initially, the Young's modulus gradually increased with an increase in phi h and then increased rapidly in the vicinity of phi h approximately 0.2. The phi h dependence of the Young's modulus was analysed by means of the theory of composite materials. It was found that with the increase in phi h the initial uniform stress deformation mode of the sample changed to the uniform strain deformation mode. The non-linear character in phi h dependence of the Young's modulus of this system was considered to reproduce well the novel behaviour of the mechanical properties of bone as a function of the mineral fraction. The situation was considered to be similar to a percolation problem. A preliminary analysis revealed that the critical exponent about the viscosity of the system accorded with the theoretically expected value. The result may present the evidence that the discontinuous point in mechanical properties of bone would be originated from an interaction such as a percolation of mineral particles on a matrix protein.

An experimental study of the osteogenicity of free periosteal allografts with cyclosporine A administration.

Free tibial periosteum was grafted onto the dorsum (m. cutaneous trunci) of Sprague-Dawley rats to examine its osteogenic potential. The animals were divided into 3 groups based on type of: A. autogenous periosteum, B. allogeneic periosteum and C. allogeneic periosteum, and treated with cyclosporine A immunosuppression. The osteogenic response was evaluated radiologically and histologically. This study indicates that in this model periosteal allografts with immunosuppression of the recipient result in osteogenesis. Clinical application of the technique will only be possible if immunosuppressive methods with minimal morbidity are developed so that they can be used for prolonged periods.

Costochondral graft construction/reconstruction of the ramus/condyle unit: long-term follow-up.

This is a retrospective study of 26 patients (seven growing and 19 non-growing) who received costochondral grafts (n = 33) for construction or reconstruction of the ramus/condyle unit (RCU). Facial appearance, jaw motion, occlusion, contour, and linear growth changes were documented preoperatively, immediately postoperatively, and long-term (> 1 year). Average follow-up was 48.6 months for growing and 46.4 months for nongrowing patients. Facial asymmetry and malocclusion were successfully corrected in all patients except for those with hemifacial microsomia, where partial correction was most common. For the growing patients mean change in RCU length (n = 8) during the observation period was +3.1 mm on the constructed/reconstructed side and +3.2 mm on the unoperated side. For nongrowing patients, mean change in the RCU length (n = 25) was -5.7 mm for the reconstructed side. Three patients developed lateral contour overgrowth of the articulating surface; no patients developed clinically significant linear overgrowth with malocclusion. The results of this study indicate that a costochondral graft may be used successfully to construct/reconstruct the RCU and that linear overgrowth of the graft does not appear to be a clinical problem with the method described in this paper.

[Clinical study of aztreonam on respiratory tract infections caused by gram-negative pathogens].

Aztreonam (E-0734, AZT) was administered to pneumonia and chronic respiratory tract infections. The results were as follows: AZT was administered to 29 patients. Twenty-six cases were evaluable and 3 cases were excluded from evaluation of efficacy because 1 was Gram-positive infection, 2 were unclear symptom of infection. Pneumonia was 4 cases. Chronic respiratory tract infections were 22 cases. Clinical efficacy was judged as follows; excellent in 7 cases, good in 10 cases, fair in 5 cases and poor in 4 cases, then the efficacy rate was 65.4%. Efficacy rate in pneumonia, acute aggravation of diffuse panbronchiolitis and bronchiectasis with infection was 50%, 67% and 83%, respectively. Bacteriological response was judged on 21 cases with eradication rate was 66.7%. Bacteriological response classified by pathogen was as follows: All 6 isolates of H. influenzae, 2 in 6 isolates of P. aeruginosa, 4 in 5 isolates of H. parainfluenzae and all 3 isolates of K. pneumoniae were cleared. Total eradicated rate was 74.1%. Eruption was observed in 1 case as side effect. Abnormal laboratory findings were observed in 4 cases. Elevation of GOT and GPT was in 3 cases. Increase of eosinophil and basophil was in 1 case. AZT was considered to be a useful antibiotic for the treatment of respiratory tract infections, especially chronic respiratory tract infections, caused by Gram-negative pathogens.

[Evaluation of T-2588 in the treatment of respiratory tract infection].

T-2588 was used on 55 patients with respiratory tract infections and 44 cases were evaluated; 23 patients with pneumonia, 12 patients with acute bronchitis, 2 patients with chronic bronchitis, 1 patient with diffuse panbronchiolitis and 6 patients with bronchiectasis with infection. Clinical effects of T-2588 were as follows; excellent in 6 and good in 28 patients. The efficacy rate was 77.3% (34/44). Bacteriological effects of T-2588 were prominent in 8 patients infected with B. catarrhalis, H. influenzae, K. pneumoniae and E. coli, but not in a patient infected with P. putida. The elimination rate was 90.0% (9/10 strains). As side effects, stomatitis, anorexia, diarrhea X vomiting and pruritus were observed in one patient each. Abnormal laboratory findings were observed in 4 patients with elevated GOT and/or GPT. These side effects and abnormal laboratory findings were not serious. The usefulness of T-2588 was 68.2% (30/44). Therefore, T-2588 is a useful drug and its effects are promising in clinical management of respiratory tract infections.

[Clinical studies of cefoxitin for the treatment of respiratory tract infections (author's transl)].

A total of 42 patients who were suffering from respiratory tract infections were treated with cefoxitin, and the following results were obtained. 1. Out of 32 patients clinically evaluated, excellent or good responses were observed in 30 patients (94%). 2. Presumed causative organisms were isolated in 14 patients. The organisms were eradicated in 11 patients and the eradication rate was 79% (11/14). The number of the organisms decreased or unchanged in 1 patient each. In other 1 patient the pathogenic agent was replaced with other agents during the course of treatment. 3. As for the side effects, skin eruption was observed in 3 patients. One patient received drugs other than cefoxitin concomitantly that might have caused the eruption. Another patient had an allergic history to many antibiotics. In 4 patients slight elevations of S-GOT and S-GPT were observed but improved soon after the completion of cefoxitin treatment. In 1 patient an elevation of serum creatinine was observed but this was not attributed to the administration of cefoxitin. 4. From the results stated above, cefoxitin is considered to be a safe and effective antibiotic which can be one of the first-choice antibiotics for the treatment of respiratory tract infections.

[Transurethral balloon laser thermotherapy for benign prostatic hyperplasia].

Between April 1994 and March 1995, transurethral balloon laser thermotherapy (TUBAL-T) using Prostalase was performed on 53 patients with benign prostatic hyperplasia. Clinical efficacy was evaluated at 3 months after TUBAL-T. The mean international prostate symptom score (I-PSS) decreased from 21.5 at baseline to 11.3 after 3 months (p < 0.0001). Irritative (the sum of items 1, 2, 4 and 7 of I-PSS) decreased by 55%, while obstructive symptoms (the sum of items 3, 5 and 6 of I-PSS) by 45%. However, other objective parameters such as maximum flow rate, voided volume, percent postvoid residual volume and prostate volume showed no significant change (7.8 to 7.2 ml/s, 130 to 147 ml, 33 to 28% and 39.7 to 41.0 ml, respectively). In conclusion, significant improvement after TUBAL-T was observed for subjective symptoms, especially irritative symptoms, but not for objective parameters.

[The significance of free-type PSA and complex-type PSA in patients with prostatic carcinoma--the characteristics of ACS-PSA method compared with that of Delfia- and Eiken-PSA method].

We studied the clinical significance of free-type prostate specific antigen (PSA) and bound-type PSA in serum of the patients with prostatic carcinoma and benign prostatic hypertrophy. The levels of PSA, gamma-seminoprotein and prostatic acid phosphatase (PAP) in 17 healthy adult males, 20 patients with benign prostatic hypertrophy and 23 patients with prostatic carcinoma were measured by ACS-PSA, Delfia and Eiken-PSA method. The levels of PSA in serum from prostatic carcinoma patients was significantly elevated as compared with that from benign prostatic hypertrophy. Linear regression analysis of the data showed that, although overall correlations were well, different assays gave different PSA concentrations. We have studied the forms of PSA in serum by gel filtration technique and measured PSA levels in each fractions using three methods. Moreover, the characteristics of ACS-PSA method was compared with that of Delfia and Eiken-PSA method. Two peaks of PSA were detected on the elution profiles from three prostatic carcinoma patients sera. Those were estimated complex-type PSA (90kDa) and free-type PSA (30kDa). The complex-type PSA fractions detected by ACS-PSA method were almost identical with that detected by Delfia-PSA method, while free-type PSA fractions detected by ACS-PSA method were greater quantity than those by Delfia and Eiken method. Many factors were contributory to the difference between the assay kits on serum complex-type PSA and free-type PSA levels. The present results suggest that there are some quantitative differences in the immunorecognition of complex-type PSA and free-type PSA between the assay kits.

[A case of concurrent bilateral adrenocortical adenoma causing Cushing's syndrome].

A 43-year-old woman presented with obesity and lumbago. Endocrinological examinations revealed normal plasma cortisol levels and a suppressed serum adrenocorticotropic hormone (ACTH) level. On venous sampling, markedly elevated plasma cortisol levels were observed for bilateral adrenal veins (243 and 62.3 micrograms/dl on the right and left sides, respectively). Although the computed tomogram revealed bilaterally enlarged adrenal glands, 131I-adosterol scintigram showed a strong uptake only on the right side. Right adrenalectomy successfully relieved Cushing's syndrome. Pathological diagnosis was adrenocortical adenoma, 3.5 cm in diameter. Cushing's syndrome recurred in 9 years. At that time, she underwent left subtotal adrenalectomy including a 3-cm adrenocortical adenoma. Postoperative convalescence has been uneventful with oral steroid supplementation. All 14 previously reported cases of bilateral adrenocortical adenoma (BAA) causing Cushing's syndrome as well as the present case were concurrent and dominant in females of reproductive age. This suggests that some cofactors other than ACTH, such as estrogen, contribute to the pathogenesis of BAA.

[Studies on changes in the ratio of free to total PSA after endocrine treatment of prostate carcinoma].

The post-diagnostic changes in the free to total PSA ratio in the serum of patients with prostate carcinoma, after the initiation of endocrine treatment were examined. Two-week pretreatment with either chlormadinone acetate (100 mg/day) or flutamide (375 ng/day) was administered orally to 14 patients with newly diagnosed advanced prostate carcinoma (clinical stage was C in 2, Dl in 1 and D2 in 11). Then the LH-RH analogue was injected. Total and free PSA in the serum of these patients were measured every 4 weeks by the Ab bead PSA (Eiken) and the recently developed assay for free PSA by Eiken, respectively. The follow-up period ranged from 3 to 9 months with a median of 6 months. Levels of both total and free PSAs decreased significantly following the endocrine treatment, while free to total PSA ratio at 4 to 16 weeks after the start of LH-RH analogue was increased significantly compared to the pretreatment level (p < 0.05). These findings suggest that the rate of decrease of complex PSA during the first 4 months after the beginning of treatment may exceed that of free PSA in the serum of patients with advanced prostate carcinoma initially treated with endocrine therapy.

[Determination of free type and complex type prostate-specific antigen (PSA): differences in immunorecognition by Delfia PSA, ACS-PSA and Eiken PA kits].

To study immunorecognition of free type and complex type prostate-specific antigen (PSA) by current commercial PSA assays, sera from 3 patients with stage D2 prostate cancer were separated by Sephacryl S-200 chromatography and determined by Delfia PSA, ACS-PSA and Eiken PA kits. Two antibodies used in the 3 kits are 2 monoclonal, 1 monoclonal and 1 polyclonal and 2 polyclonal antibodies, respectively. Following chromatography, two PSA peaks were obtained in all patients. One was about 100 kDa and the other about 30 kDa. The former was considered to be the complex type PSA (complex with alpha-1 antichymotrypsin) and the latter to be free type PSA. As to free type PSA, the ACS-PSA kit and Eiken PA kit quantitated PSA values approximately 5.1 and 2.5 times higher than the Delfia PSA kit. For complex type PSA, the quantity determined by ACS-PSA kit was approximately 1.3 times higher than that determined by the Delfia PSA kit, while the quantity determined by the Eiken PA kit was about one third of that determined by Delfia PSA kit. The ratio of complex type PSA to total PSA (free type PSA + complex type PSA) was 74.8 +/- 14.9% (mean +/- SD) when determined by Delfia PSA kit, 59.3 +/- 18.4% by ACS-PSA kit and 52.9 +/- 13.8% by Eiken PA kit. The range of this ratio determined by ACS-PSA kit was from 47.3% to 80.5% in the 3 patients. These findings suggest that there are qualitative differences in immunorecognition of free type PSA and complex type PSA among current commercial PSA assays and that there are quantitative differences in the ratio of the 2 forms of PSA in serum among prostatic cancer patients. The measurement and follow-up of both free type and complex type PSA might be important for diagnosis and monitoring of prostate cancer.

[A case of polyorchidism with embryonal carcinoma].

Polyorchidism is a rare anomaly with approximately 70 cases reported in the literature. We reported a case of polyorchidism with embryonal carcinoma, the first case, in one of 4 testes. Polyorchidism with malignancy had been reported in 5 cases and bilateral polyorchidism in 3 cases. Authors have not been clarified whether the incidence of malignancy in polyorchidism is high or low. But we have to treat the patients with polyorchidism carefully, because polyorchidism is highly associated with cryptorchidism.

[Studies of prostate-specific antigen (PSA) immunoassays--differences in characteristic of immunoreactivity and reference materials among the kits].

PURPOSE: We conducted this study to examine differences in characteristics of immunoreactivity for free PSA and alpha(1)-antichymotrypsin complex PSA (ACT-PSA) as well as in compositions and concentrations of PSA reference materials among commercially available PSA kits. METHODS: Fractionated serum samples using a Sephacryl S-200 column were measured by Tandem-R, Delfia-PSA, Ab bead PSA, ACS-PSA, Markit-M and gamma-seminoprotein (gamma-Sm) kits. The calibrators of Tandem-R, Delfia-PSA, Ab bead PSA and Markit-M were fractionated by the same method and measured by Tandem-R. The calibrators of Delfia-PSA, Ab bead PSA and Markit-M and control serums of ACS-PSA were measured by Tandem-R. RESULTS: Although the characteristic of immunoreactivity of Tandem-R, Delfia-PSA, and Ab bead PSA were found to be similar, they were not shown identical. ACS-PSA was proved to recognize free PSA greater than above three PSA kits, while Markit-M could scarcely detect free PSA. gamma-Sm recognized only free PSA. The calibrators of Tandem-R, Delfia-PSA, Ab bead PSA and Markit-M were proved to be only free PSA. The linear correlation was obtained between Tandem-R and Delfia-PSA or Ab bead PSA or Markit-M. The ratio of Delfia-PSA to Tandem-R, Ab bead PSA to Tandem-R and Markit-M to Tandem-R was 0.66, 0.93 and 2.2, respectively. With regard to relation of ACS-PSA and Tandem-R, two ratios of 0.22 and 0.25 were obtained between the two kits according to the different concentrations of control sera. CONCLUSION: The present studies suggest that the difference in PSA values among the commercial PSA kits results from (1) different characteristics of immunoreactivity for ACT-PSA and free PSA among PSA kits, (2) compositions of PSA calibrators among the kits, and (3) different concentrations of PSA calibrators among the kits.

[Studies of type I collagen related substances as bone metastatic markers of prostate carcinoma with special regard to serum carboxyterminal propeptide of type. I. Procollagen (PICP), cross-linked carboxyterminal telopeptide of type I collagen (ICTP) and Urinary deoxypyridinoline levels].

BACKGROUND: To investigate if serum levels of carboxyterminal propeptide of type I procollagen (PICP), cross-linked carboxyterminal telopeptide of type I collagen (ICTP) and urinary levels of deoxypyridinoline (D-Pyr) are useful markers of bone metastasis in patients with prostate carcinoma, we measured these markers in patients with untreated benign prostatic hyperplasia (BPH) and untreated prostate carcinoma (PCA). METHODS: Serum PICP, ICTP and urinary D-Pyr levels were determined in 53 patients; 16 patients with BPH, 15 patients with PCA without bone metastasis (stage A, B, C and D1) and 22 patients with PCA with bone metastasis (stage D2). At the same time correlations among these markers and serum total alkaline phosphatase (ALP) activity were studied. RESULTS: Serum PICP, ICTP and urinary D-Pyr levels in the PCA patients with bone metastasis were significantly higher than those of BPH. The serum levels of PICP in patients with PCA with bone metastasis group were significantly higher than those of without bone metastasis group. The serum levels of ICTP in patients with PCA without bone metastasis group were significantly higher than those of BPH group, while no significant difference was observed between PCA group with and without bone metastasis. In the PCA patients with bone metastasis, serum PICP and serum total alkaline phosphatase (ALP) activity were significantly correlated (r = 0.80). In these patients, serum ICTP and urinary D-Pyr levels were also significantly correlated (r = 0.70). CONCLUSION: These results suggest that serum PIPC, ICTP and urinary D-Pyr are the useful markers to quantitate bone metastasis in the patients with PCA. Moreover, the determination of serum ICTP levels may be significant for detecting occult bone metastasis in the patients with PCA.

Protective effect of hedgehog signaling on cytokine-induced cytotoxicity in pancreatic beta-cells.

BACKGROUND: Hedgehog (Hh) signaling plays an important role in pancreas development. However, its role in the developed endocrine pancreas remains to be elucidated. To clarify whether Hh signaling participates in beta-cell survival, we investigated the role of Hh signaling in cytokine-induced apoptosis in pancreatic beta-cells. METHODS: Insulin-producing INS-1E cells were transfected with Sonic Hh (Shh) expression vector or siRNA against Indian Hh (siIhh). The Hh signal inhibitor cyclopamine were pretreated in INS-1E cells and rat islets. The cells were exposed to 200 U/ml IL-1ß and 200 U/ml IFN-γ for 48 h. Apoptosis was estimated by flow cytometory and immunofluorescence staining for cleaved caspase-3. Nitric oxide generation was measured by Griess reaction. RESULTS: We found that exposure to proinflammatory cytokines increased Ihh expression in rat islets and INS-1E cells. Overexpression of Shh reduced cytokine-induced apoptosis. By contrast, treatment with cyclopamine increased cytokine-induced apoptosis in INS-1E cells and rat islets. Treatment with the siIhh showed same results in INS-1E cells. Forced expression of Shh suppressed cytokine-induced nuclear factor-κB promoter activity, leading to attenuation of nitric oxide synthase 2 expression and nitric oxide production, while Ihh knockdown enhanced this pathway in INS-1E cells. CONCLUSION: Our findings suggest that Hh signaling is implicated in protecting beta-cells from cytokine-induced cytotoxicity.