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Background: Pain is a widely neglected symptom in patients with amyotrophic lateral sclerosis (ALS), even though it may be common and have a significant impact on the quality of life., Objective: The aim of this study was to determine the frequency and characteristics of pain and its treatment in ALS patients., Design: A multicenter cross-sectional study., Setting/subjects: Eighty patients with ALS from eight hospitals., Measurements: Data on demographics, functional status, and pharmacological treatment were collected. The Barthel Index (BI) was used to assess functional status. Pain was measured using the 0-5-point Wong-Baker FACES Pain Rating Scale., Results: Pain was reported by 53.8% of ALS patients, and 36.3% reported receiving pain medication. Opioids were the drugs most commonly used to treat pain. The differences in pain frequency according to functional status were not statistically significant (p = 0.38). The pain intensity in patients whose functional status was total dependence (BI 0-20, 2.5 ± 1.2) was significantly worse than that in those with better functional status (BI 21-60, 1.4 ± 0.7; BI 61-99, 1.4 ± 0.5; p < 0.01)., Conclusions: Our study indicates that all patients with ALS have the potential to suffer from pain, the intensity of which increases with decreased functional status.

Protein is a main nutrient involved in overall iron metabolism in vivo. In order to assess the prevention of iron deficiency anemia (IDA) by diet, it is necessary to confirm the influence of dietary protein, which coexists with iron, on iron bioavailability. We investigated the usefulness of the egg structural protein in recovery from IDA. Thirty-one female Sprague-Dawley rats were divided into a control group (n = 6) fed a casein diet (4.0 mg Fe/100 g) for 42 days and an IDA model group (n = 25) created by feeding a low-iron casein diet (LI, 0.4 mg Fe/100 g) for 21 days and these IDA rats were fed normal iron diet with different proteins from eggs for another 21 days. The IDA rats were further divided into four subgroups depending on the proteins fed during the last 21 days, which were those with an egg white diet (LI-W, 4.0 mg Fe/100 g, n = 6), those with an ovalbumin diet (LI-A, 4.0 mg Fe/100 g, n = 7), those with an egg yolk-supplemented diet (LI-Y, 4.0 mg Fe/100 g, n = 6), and the rest with a casein diet (LI-C, 4.0 mg Fe/100 g, n = 6). In the LI-Y group, recovery of the hematocrit, hemoglobin, transferrin saturation level and the hepatic iron content were delayed compared to the other groups (p < 0.01, 0.01, 0.01, and 0.05, respectively), resulting in no recovery from IDA at the end of the experimental period. There were no significant differences in blood parameters in the LI-W and LI-A groups compared to the control group. The hepatic iron content of the LI-W and LI-A groups was higher than that of the LI-C group (p < 0.05). We found that egg white protein was useful for recovery from IDA and one of the efficacious components was ovalbumin, while egg yolk protein delayed recovery of IDA. This study demonstrates, therefore, that bioavailability of dietary iron varies depending on the source of dietary protein.

Iron deficiency anemia (IDA) is one of the most serious forms of malnutrition. This experiment was conducted to investigate whether acidic xylooligosaccharide (U-XOS), expected to have a high iron bioavailability, was useful in the prevention of iron deficiency. Experiment 1: Nineteen female Sprague-Dawley rats (20 wk old) were fed three different diets for 28 d; a U-XOS-supplemented low-iron diet (LI-X, n=7), a low-iron diet (LI, n=6), and a control diet (C, n=6). On day 28, the LI-X and LI groups showed iron deficiency without anemia. A significant difference in the total and unsaturated iron binding capacity, and serum transferrin saturation level was shown in the LI-X and LI groups, compared with the C group. However, the decrease of hepatic iron content of the LI-X group was suppressed compared with the LI group. Experiment 2: Eleven male Sprague-Dawley rats (7 wk old) were fed a U-XOS-supplemented diet (X, n=5) or a control diet (C, n=6) for 7 d. No significant difference in body weight gain or food intake was demonstrated between the two groups; the apparent iron absorption rate of the X group increased clearly compared with that of the C group. These results suggested that a U-XOS diet could preserve storage of hepatic iron in adult female rats fed a low-iron diet and could prevent IDA by promotion of dietary iron absorption, inhibition of iron excretion, and/or improvement of iron bioavailability.

We report a case of successful endopyelotomy using the Acucise cutting balloon device for secondary ureteropelvic junction obstruction (UPJO). A 23-year-old man was hospitalized with the chief complaint of left lumbago and left hydronephrosis due to left UPJO. He underwent antegrade endopyelotomy with a nephroscope and open pyeloplasty. However, left lumbago and hydronephrosis did not show improvement. Acucise endopyelotomy was performed under epidural anesthesia. The operative time was 55 minutes and the hospital stay after the operation was 4 days. There were no operative complications and 3 months later, the operative results were satisfactory as determined by drip infusion pyelography and the disappearance of the lumbago.

Intratubular germ cell neoplasia (ITGCN) is the preinvasive phase of testicular germ cell tumors. ITGCN can spread into the rete testis in a pagetoid manner, but there are very few published data about this phenomenon. Furthermore, the tumor-like mass formed by ITGCN with pagetoid spread into the rete testis has not been documented to date, and the present case is the first to be reported. A tumor-like mass was found close to the superior pole of the left testis in a 39-year-old male and was unrelated to the epididymis. Three other nodules of seminoma surrounded by fibroconnective tissue existed next to the mass. Histological sections revealed ITGCN which was characterized by the presence of large and polygonal germ cells exhibiting clear cytoplasm with distinct cell borders. The cytoplasm was rich in glycogen and the cell membrane was immunohistochemically positive for placental alkaline phosphatase. The nuclei had less coarse chromatin than that of seminoma. ITGCN cells spread in between the lining epithelium of the rete and the basement membrane. This characteristic spread was consistent with pagetoid spread into the rete testis.

The immunolocalization of the p16 and cdk4 proteins was investigated in 65 retinoblastoma gene product (pRB)-positive and 20 pRB-negative breast carcinomas. These proteins were expressed in similar lesions in 84.6% of the pRB-positive and 100% of the pRB-negative carcinomas. Diffuse expression of p16 was observed in 73.8 and 70.0% of the pRB-positive and -negative cases, respectively. cdk4 and p16 expression was significantly more heterogeneous in tumors of larger sizes and/or at higher stages. These findings suggest that p16 can be induced regardless of pRB status and Rb gene function in primary breast carcinoma and that it modulates the cell cycle progression in association with cdk4.

p21/Cip1/Waf1 (wild-type p53 activated fragment 1/cyclin-dependent kinase [Cdk]-interacting protein 1) is a prominent Cdk inhibitor and has been shown to be a downstream mediator of p53. In this study, we sought to clarify the clinical significance of Waf1 and the relationship between Waf1 and p53 in breast cancer. For this purpose, the expressions of Waf1 and p53 were evaluated immunohistochemically in a series of 104 patients. Waf1 was expressed in 51 (49%) of 104 tumors tested, and p53 in 33 tumors (32%). Inverse expression of these two proteins was seen in 76 cases (73%); 47 were Waf1-positive and p53-negative, and 29 were Waf1-negative and p53-positive. A comparison with clinicopathologic parameters showed that Waf1 expression correlated with negative lymph nodes (P<.01), a low histologic grade (P<.0001), and positive estrogen receptor status (P<.01). Recurrence-free survival was lower for patients with Waf1-negative tumors than for those with Waf1-positive tumors (P<.0001). In multivariate analysis, Waf1 expression and low histologic grade (1 or 2) tumors had an independent prognostic significance for recurrence-free survival. These results suggest that Waf1 is induced mainly by a p53-dependent pathway and could be a reliable indicator of recurrence in breast cancer.

A 70-year-old male was hospitalized for right scrotal mass without pain in October 1991. Right orchiectomy was performed under a diagnosis of right epididymal tumor. Histopathological diagnosis was testicular adenomatoid tumor. In June 1992, he was admitted with a mass in the right inguinal region and a tumor was resected. Histopathological diagnosis was malignant testicular mesothelioma. Therefore, retroperitoneal lymphadenectomy was performed as additional therapy. One year after surgery he showed signs of recurrence and was admitted for treatment and further examination. Computed tomography demonstrated right inguinal and femoral mass. Thus he underwent total penectomy and radical ilioinguinal lymphadenectomy under a diagnosis of metastatic and recurrent mesothelioma of the testis. Three months postoperatively he developed a recurrence in the skin and lung field. After combination chemotherapy, the metastatic skin lesion was in remission but the lung lesion did not respond. Metastatic lung tumor grew rapidly and the patient died. The incidence of malignant mesothelioma of the tunica vaginalis testis is rare and 48 cases have been reported in the literature.

The expression of midkine (MK), a growth/differentiation factor, was assessed in 34 surgically resected specimens of primary breast cancer or mastopathy. Using reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, all of the non-cancerous and cancerous tissues were found to express MK except for one breast cancer specimen. Northern blot analysis revealed that MK mRNA was also expressed in the normal breast tissues examined. Immunohistochemical analysis of the MK protein was performed on a limited number of the specimens, showing that some cancerous tissues were immunoreactive with anti-MK antibodies. Furthermore, using RT-PCR analysis, expression of not only the wild-type but also a truncated form of MK, which was recently found in various human tumor cell lines, was detected in 6 of 26 cancerous tissues but not in non-cancerous tissues.

In this study, 26 cases of nonpalpable breast cancer with nipple discharge treated at our department were reviewed. Their discharge was either bloody or serous with a positive hematest, but all except for one were negative for cytology, while CEA value of the discharge was high in 72.7%. Mammograms were found to be unreliable for diagnosis, while abnormal findings were observed in 84.6% by ductography. However, final diagnosis was determined histopathologically from surgical specimens, showing 14 intraductal and 12 invasive ductal cancers, none with components of comedo carcinomas. Seventeen patients underwent mastectomy following duct-lobular segmentectomy and a small remnant of intraductal carcinoma was found microscopically in only one patient. All patients except for one have survived for 98 months on average with no symptoms of metastasis. These findings suggest that duct-lobular segmentectomy with an adequate surgical margin should be adopted as the final operation for selected patients with nonpalpable breast cancer involving nipple discharge.

In the present study, we investigated immunolocalization of the modulators of G(1)-S transition by using monoclonal or polyclonal antibodies for each of the modulators in 65 cases of clinical breast cancer. Two prominent cyclin dependent kinase(cdk)-cyclin complexes, cdk4-cyclin D and cdk2-cyclin E, were proved to have different modes of mutual expression. cdk4-positive lesions were found to equal cyclin D-expressing lesions in 55 cases, while the former were more extensive than the latter in 9 cases. On the other hand, cyclin E expression was detected in all the cases examined and was more dominant than that of cdk2/cdc2 in as many as 40 cases whereas the reverse was seen in only 1 case. Interestingly, cdk4(P<0.01)and cyclin E(P<0.05)expressions showed an inverse relationship with the tumor size and the cancer stage. A similar tendency was also detected for two other positive modulators of G(1)-S transition, indicating that cell cycle progression must be regulated by the cancer itself once it has grown to a certain extent. p21, which has been regarded as a universal inhibitor of the cell cycle, was expressed in 43.1% of the cases examined and its immunoreactivity showed an inverse relationship with lymph node metastasis(P<0.05). It also tended to be absent more frequently in T3 or larger cancers and stage III cases. Moreover, two patients who died as a result of cancer and three patients with recurrence were all p21 negative, suggesting that p21 is prognosticably the most significant of all these modulators.

Immunohistochemical staining (immunostaining) has been frequently used with breast cancer in order to give definite histological diagnosis and information for treatment or prognosis. In the histological diagnosis, immunostaining is used for differential diagnoses of tumor origin and malignancy. Immunostainings for hormone receptors and c-erbB-2 are useful for the prediction of the effect of endocrine therapy and prognosis. In the future, more important substances examined by immunohistochemistry are awaited for the diagnosis and treatment of the breast cancer.

A 47-year-old female was admitted with colicky pain in the left flank. Ultrasonography and abdominal CT revealed left perirenal hematoma. Abdominal CT revealed a multilocular cystic lesion in the upper pole of the left kidney. Renal angiography revealed left renal cell carcinoma. Left nephrectomy was performed under a tentative diagnosis of left renal cell carcinoma. However, pathological diagnosis was xanthogranulomatous pyelonephritis. Xanthogranulomatous pyelonephritis is an atypical form of chronic renal parenchymal infection that can be classified as diffuse type or focal type. Preoperative diagnosis of focal xanthogranulomatous pyelonephritis is difficult because of clinical and radiological similarities to renal cell carcinoma. Our case is presented with a brief review of the literature.

The plasminogen activation system is one of the prominent factors in tumour progression since it enhances both distant metastasis and direct invasion. In this study we investigated the expression and localization of this system in clinical thyroid tumours. It was found that urokinase-type plasminogen activator (uPA), its receptor (uPAR) and plasminogen activator inhibitor type 1 (PAI-1) were expressed diffusely in most thyroid carcinomas. The lesions positive for the latter two were equal to or sometimes even a litter more extensive than those positive for uPA. The immunoreactivity of plasminogen activator inhibitor type 2 (PAI-2), however, was often partially or even entirely absent, and only 56% of the carcinomas expressed it diffusely, indicating that the two types of inhibitors in this carcinoma have quite different characteristics. No relationship between the expression of these proteins and clinicopathological parameters could be determined. THese findings suggest that the plasminogen activation system is functionally active in thyroid carcinoma but that is has hardly any effect on its general characteristics, that is, slow growth and excellent prognosis of usual types and the exceptionally sudden progression of the anaplastic type. In benign tissues, too, this system was often expressed and appeared to enhance their growth to some extent.

A statistic survey was made on the patients undergoing cadaveric renal transplantation between June, 1980 and December, 1993. The total number of patients was sixty-seven. The number of patients per year increased annually. The graft survival rate was 73.8% at 1 year and 63.1% at 5 years. Some transition was seen in immunosuppressive regimens using cyclosporin.

Although thyroid cancer tends to metastasize early in children, it is generally associated with a good prognosis. In this study, the expression of p53, mutations of which are found in many cancers, including anaplastic thyroid cancer, was examined to determine the relationship between cell proliferation and the clinical course of thyroid cancer. The clinicopathological findings and clinical courses of 15 children who underwent surgery before the age of 18 years at our hospital between 1972 and 1992 were examined, and the expression of p53 was studied using immunohistochemical techniques and an RNase protection assay. Postoperative follow-up ranged from 1 to 20 years, with a median of 12 years. No abnormal expression of p53 was detected in the thyroid cancer of any of the children tested, and none of them have died. The findings of this study therefore strongly suggest that p53 may play a role in the regulation of cell proliferation, and in this capacity slow the growth of and be related to the prognosis of differentiated thyroid cancer in children.

OK-432 is an immunomodulatory agent prepared from a strain of Streptococcus pyogenes. We have previously reported that intratumoral injection of a mixture of OK-432 and fibrinogen (hereinafter referred to as OK/fbg) is very effective in the local immunotherapy for colorectal cancer. However, we found that the intratumoral injection of OK/fbg into tumor tissues of breast cancers did not always induce a strong antitumor effect. With conventional OK/fbg treatment, tumor necrosis observed in breast cancer tumors was significantly less than that in colorectal cancer tumors; the formation of fibrin meshwork and macrophage infiltration, in particular, were poor. In this study, the OK/fbg mixture was supplemented with activated macrophages for local immunotherapy of breast cancers. Macrophages were prepared from peripheral blood of breast cancer patients and activated with 0.05 mg/ml of OK-432. Between 2-7 days before operation, a single intratumoral injection of the above mixtures was done. The addition of activated macrophages to the OK/fbg mixture resulted in marked degrees of fibrin meshwork formation, macrophage infiltration and cancer cell necrosis. These findings suggest that the recruitment of macrophages in tumor stroma and their activation are necessary for sufficient induction of antitumor immunity, and supplementation of activated macrophages at the site of immune reaction may be an alternative method for reinforcement of the antitumor effect of local immunotherapy.