Health status of male preparatory school students lodging at a dormitory in Japan

An investigation on the health status of 79 male preparatory school students lodging at a dormitory in Japan was carried out by questionnaire on lifestyles, subjective symptoms and mental status, as compared with two control groups: 73 medical students and 36 new employees. About 83 % of them slept less than 6 hours and 70 % of them did not exercise. Many students are troubled with back pain or lumbago(47%), sensation of incomplete bladder emptying(l6%), loss of visual acuity(55%) and eye fatigue(65%). Self-rating depression scale score of preparatory school students was not significantly higher than those of the control groups. The lifestyles of preparatory school students found to be very restricted and strained. However, no significant differences on mental adverse health effects was found among three groups.     

Use of ultrasound-guided percutaneous needle biopsy in the diagnosis of mediastinal tumors

We herein report the usefulness of ultrasoundguided percutaneous needle biopsy for histological diagnosis in 18 patients with mediastinal tumors. Computed tomography revealed these tumors to be in contact with the chest wall. The preoperative diagnosis was thymoma in 7 patients, germinoma in 5, neurogenic tumor in 3, and other in 3. The most commonly encountered indication for an ultrasound-guided percutaneous needle biopsy was an anterior mediastinal lesion (78%; 14 of 18 patients). In 16 (89%) of the 18 patients, the biopsy diagnosis corresponded to the post-operative diagnosis. No complications were encountered in any of the patients. This new technique of ultrasound-guided percutaneous needle biopsy is both relatively simple and highly accurate and may thus be useful for outpatients. Preoperative ultrasound-guided percutaneous needle biopsy is thus considered to be a safe and reliable method for the histological diagnosis of mediastinal tumors, and a good alternative to traditional biopsy techniques such as mediastinoscopy or thoracotomy.Presented at the 11th Biennial Asian Congress on Thoracic and Cardiovascular Surgery, Kuala Lumpur, Malaysia, November, 21–25, 1993.     

Aprindine blocks the sodium current in guinea-pig ventricular myocytes

Summary Aprindine is a class Ib antiarrhythmic agent. We studied effects of aprindine (3 µmol/l) on the Na⁺ current using whole cell voltage clamp (tip resistance = 0.5 , [Na]_i and_o = 10 mmol/l at 18°C). Aprindine revealed tonic block (Kd_rest = 37.7 µmol/l, Kd_i = 0.74 µmol/l; n = 4). Aprindine, shifted inactivation curve to hyperpolarizing direction by 11.4 ± 3.5 mV (n = 4) without changes in slope factor. In the presence of 3 µmol/l aprindine, aprindine showed phasic block, i.e., duration-dependent block at 2 Hz (64% ±3070 at 1.5 ms, 82%±6% at 20 ms, 93%±7% at 200 ms; n = 4). Short single prepulse also produced aprindine-induced phasic block (12% at 1.5 ms, 22% at 100 ms; n = 2). After removal of fast inactivation of Na⁺ current by 3 mmol/l tosylchloramide sodium, aprindine revealed phasic block, independent of holding potential. The recovery time constant from aprindine-induced phasic block was 4.8 s at holding potential = –100 mV and 5.0 s at holding potential = –140 mV. This use-dependent block of aprindine had pH dependency. Under acidic condition (pH 6.0), 3 µmol/l aprindine showed smaller use-dependent block (14% ± 7% at 2 Hz; n = 4) comparing with either at pH 7,4 (68% ± 13%; n = 4) or at pH 8.0 (90% ±12%; n = 4).The results suggest that aprindine could bind to the receptor via activation process through channel pore, resulting in decrease of Na⁺ current, and egress from the receptor through the lipid bilayer. These effects might be attenuated under acidic condition due to changes in intracellular ratio of charged to neutralized form of drug molecule. Send offprint requests to: R. Sato at the above address     

Modulation of BUdR labeling index in rat brain tumors following intracarotid ACNU administration

Summary Chloroethy1nitrosourea (CENU) chemotherapy has yielded limited benefit on survival of malignant brain tumors. Intracarotid administration of CENU is expected to have the advantage of increasing drug concentration reaching tumors. To understand basic knowledge of intracarotid chemotherapy, we monitor changes of proliferating rate after intracarotid injection of 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2chloroethyl)-3-nitrosourea hydrochloride (ACNU), using a bromodeoxyuridine (BUdR) labeling index (LI) in transplanted brain tumors of three cell strains.C6-2 tumor cells were in vitro sensitive to ACNU, and C6-2/ACNU and C6-1 cells were resistant. The drug sensitivity to ACNU was as follows: 11.9 tM in the C6-2 cells, 46.0 M in the C6-2/ACNU cells, and 49.7 M in the C6-1 cells at SD10, which gives 10% survival of clonogenic cells. The intracarotid ACNU at a dose of 30 mg/kg abruptly decreased the LI to 11% (mean) from 36% in C6-2 transplanted tumors. The LI remained low between 12 and 48 hours after, and then increased to the pretreatment level by 96 hours. In contrast, the LI of C6-1 tumors transiently fell to 15% from 42% at 12 hours after the injection, and subsequently increased to 36% at 24 hours and 37% at 48 hours.These results indicate that intracarotid ACNU administration shortly suppresses proliferating activity of tumors and that combined and alternating chemotherapy are mandatory for enhancing effectiveness of brain tumor chemotherapy.     

Regulation of p27 by S-phase kinase-associated protein 2 is associated with aggressiveness in non-small-cell lung cancer.

PURPOSE: The F-box protein S-phase kinase-associated protein 2 (Skp2) is one of the positive regulators of the cell cycle that promote ubiquitin-mediated proteolysis of the cyclin-dependent kinase inhibitor p27. In this study, we investigated the significance of Skp2 expression in human non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Clinicopathologic features and immunohistochemical expression of Skp2 and p27 proteins were studied in 138 patients with NSCLC. Survival analyses were performed using the Kaplan-Meier method and the Cox regression model. To analyze the role of Skp2 in vitro, NSCLC cells were transfected with an Skp2-expressing vector or small interfering RNA. RESULTS: Skp2 was overexpressed in males, smokers, patients with squamous cell carcinomas, and patients with poorly differentiated cancers (P = .034, < .0001, < .0001, and .002, respectively). The multivariant analysis revealed that Skp2 expression is an independent prognostic factor for survival in NSCLC. An inverse relationship of Skp2 with p27 expression was observed (P = .012), and patients with both a higher expression of Skp2 and a lower expression of p27 showed a significantly unfavorable prognosis (P = .0002). In vitro ectopic expression of Skp2 in NSCLC cells reduced the protein level of p27. Conversely, induction of Skp2 siRNA increased the protein level of p27, leading to growth inhibition in NSCLC cells. CONCLUSION: Skp2 overexpression is closely associated with the suppression of p27 and the aggressiveness in NSCLC. It also could be a therapeutic target in NSCLC.     

The prognostic and therapeutic relevance of p27kip1 in Ewing's family tumors.

PURPOSE: Ewing's family tumors (EFTs) display the characteristic fusion gene EWS-Fli1. We have reported EWS-Fli1 may promote the cell cycle progression accompanied by the suppression of the expression of cyclin-dependent kinase inhibitor p27(kip1) in EFT cells. Here, we describe the prognostic and therapeutic relevance of p27 in EFTs. EXPERIMENTAL DESIGN: We examined tumor samples taken from 21 patients with primary EFTs for the expression of p27 protein immunohistochemically and evaluated its correlation with clinical outcome. We also investigated the usefulness of p27 as a therapeutic strategy in vitro and in vivo using p27 expression adenovirus. Finally, we examined the process of EWS-Fli1-mediated reduction of p27 expression. RESULTS: Immunohistochemical analysis showed that a low expression level of p27 protein was related to poor event-free survival in an univariate analysis and that the expression level of p27 correlated more significantly with patient survival than several clinical factors in a multivariate survival analysis. Overexpression of p27 with the adenoviral vector remarkably inhibited the cell growth in all EFT cells tested and further induced apoptosis in the wild-type p53 EFT cells. In vivo studies demonstrated a reduction in tumor growth of EFT xenograft in nude mice treated with the intratumoral injection of p27-expressing adenovirus. EWS-Fli1 did not significantly affect the p27 promoter activity and p27 mRNA levels. However, the challenge of the proteasome inhibitor caused accumulation of p27 protein in EFT cells. These data strongly suggest EWS-Fli1 might attenuate p27 protein level via activation of the proteasome-mediated degradation pathway. CONCLUSIONS: Our findings provide the first evidence of the prognostic relevance of p27 expression in EFTs. We propose p27 as a novel and powerful therapeutic factor for the molecular target therapy of EFTs.     

Functional impact of breast cancer by age at diagnosis.

PURPOSE: To explore changes in physical and psychosocial function before and after breast cancer by age at diagnosis. PATIENTS AND METHODS: A total of 122,969 women from the Nurses' Health Study (NHS) and NHS 2, ages 29 to 71 years, who responded to pre- and postfunctional status assessments were included; 1,082 women were diagnosed with breast cancer between 1992 and 1997. Functional status was measured using the Medical Outcomes Study Short Form 36 (SF-36). Mean change in health-related quality of life (HRQoL) scores was computed across categories representing the combination of incident breast cancer (yes or no) and age at diagnosis (< or = 40, 41 to 64, or 65+ years). RESULTS: Compared with women < or = 40 years without breast cancer, women with breast cancer experienced significant functional declines. Young (age < or = 40) women who developed breast cancer experienced the largest relative declines in HRQoL (as compared with middle-aged and elderly women) in multiple domains including physical roles (-18.8 v -11.5 and -7.5 points, respectively), bodily pain (-9.0 v -2.7 and -2.7 points), social functioning (-11.3 v -4.3 and -4.4 points) and mental health (-3.1 v 0.0 and +0.4 points). Much of the decline in HRQoL among elderly (age > or = 65) women with breast cancer was age related. CONCLUSION: Young women may fare worse than middle-aged or elderly women in both physical and psychosocial dimensions after breast cancer diagnosis. The needs of women facing breast cancer may be better understood within a life stage framework.     

Pelvic insufficiency fractures in postmenopausal woman with advanced cervical cancer treated by radiotherapy.

PURPOSE: To assess the predisposing factors and clinical characteristics of pelvic insufficiency fractures (PIF) in postmenopausal women with pelvic irradiation. MATERIAL AND METHODS: A total 335 postmenopausal patients with cervical cancer of the intact uterus treated with radiation therapy between 1983 and 1998 were reviewed. Total external dose was delivered between 45 and 50.4 Gy with parallel opposed anteroposterior portals. Total brachytherapy dose at point A was delivered between 10 and 36 Gy. PIF were diagnosed by bone scintigraphy and confirmed by computed tomography. The cumulative incidence of symptomatic PIF was estimated by actuarial methods. Potential risk factors (age, weight, type II diabetes, delivery, menopause, total external dose, total brachytherapy dose) were assessed. RESULTS: Fifty-seven (17.0%) of 335 patients were diagnosed as having PIF. Forty-seven patients were symptomatic and ten were asymptomatic. Parameters carrying a significant association with PIF were body weight 49 kg or below (P=0.044) in stepwise logistic regression analysis. The cumulative incidence of symptomatic PIF at 5 years was 17.9% calculated by the Kaplan-Meier method. A body weight of 49 kg or below and more than three deliveries were identified as having a significant effect on symptomatic PIF in univariate analysis (P=0.021, P=0.003, log-rank test) and Cox life table regression analysis (P=0.038, P=0.013). Five patients required narcotic agents and eight patients required hospital admission. CONCLUSIONS: We should consider reducing the dose contribution to the sacrum and sacroilac joints, without underdosing the tumor, especially in postmenopausal women with many deliveries or low body weight.     

Reduced MLH1 expression after chemotherapy is an indicator for poor prognosis in esophageal cancers.

PURPOSE: Loss of function or expression of the mismatch repair gene MLH1 has been implicated in experimentally acquired resistance to cisplatin (CDDP) and other anticancer agents. The clinical significance of MLH1 expression was evaluated in advanced thoracic squamous cell carcinoma of the esophagus (ESCC) treated by neoadjuvant chemotherapy. EXPERIMENTAL DESIGN: We investigated MLH1 and P53 expression by immunohistochemistry in the surgical specimens of 107 patients who had undergone preoperative chemotherapy using CDDP along with 5-FU and ADM. These findings were correlated with the clinical outcome for this treatment. Biopsy samples before chemotherapy in 20 of these patients, and another 43 surgical specimens without chemotherapy, were also examined as control samples. RESULTS: In surgical specimens of ESCC, low MLH1 expression was not frequent without chemotherapy, whereas it was commonly observed after chemotherapy (14 versus 37%, P = 0.0057). Comparison between samples before and after chemotherapy revealed that MLH1 expression was unchanged during chemotherapy in 12 of 20 patients (60%) but was from high to low in 8 of 20 patients (40%). In the surgical specimen after neoadjuvant chemotherapy, MLH1 expression was not correlated with any clinicopathological factors, including the response to chemotherapy. However, low MLH1 showed poorer prognosis than high MLH1 (5-year survival 40.6 versus 19.3%, P = 0.0393), and in multivariate analysis, MLH1 was an independent prognostic factor for this multimodal treatment, following lymph node metastasis and clinical response to chemotherapy. Positive p53 expression, which was not affected by chemotherapy, was weakly associated with a poor response and clinical outcome, although this trend was not significant. CONCLUSIONS: In advanced ESCC, expression of MLH1 is reduced during CDDP-based chemotherapy, and this may partly account for poor postoperative survival.     

Transarterial Infusion of Cisplatin and Doxorubicin in Bladder Cancer: Original Article

Forty-five patients (median age 63 years) with muscle invasive bladder cancer were treated with transcatheter intraarterial infusion (TAI) of cisplatin (CDDP) and doxorubicin. They received a total of 114 courses (median 3 courses per patient) of TAI. Complete response was obtained in 20 patients (44%), partial response in 17 (38%), stable disease in 6(13%), and progression of disease in 2 patients (5%). The overall response rate was 82% at a median follow-up of 36 months. The actuarial survival of the patient population was 72% at 5 years; 36 patients were alive and 9 had died of cancer progression. The treatment was generally extremely well tolerated without major complications. The current study also revealed the fact that papillary carcinomas were more sensitive to this therapy than were non-papillary tumors. Overall, response rate and local control were significantly higher in low-grade than in high-grade tumors. The observed high complete response and good survival rate suggest that intraarterial CDDP and doxorubicin might be highly effective for localized invasive bladder cancer.