Clinical significance of p21 expression in non-small-cell lung cancer.

PURPOSE: The clinical significance of p21 expression remains unclear, whereas many experimental studies have demonstrated that p21, the product of the WAF1/CIP1/SDI1 gene, plays an important role in regulation of the cell cycle as an inhibitor of cyclin-dependent kinases. The purpose of this study was to clarify the clinical significance in resected non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A total of 233 consecutive patients with completely resected pathologic stage I to IIIA NSCLC were retrospectively reviewed. Expression of p21 and the status of p53 were examined immunohistochemically. Proliferative activity was also evaluated immunohistochemically. The incidence of apoptotic cell death was evaluated by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling staining. RESULTS: Expression of p21 was positive in 120 patients (51.5%). The 5-year survival rate of p21-positive patients was 73.8%, significantly higher than that of p21-negative patients (60.7%; P =.006). Aberrant expression of p53 was positive in 98 patients (42.1%). When combined with p53 status, the prognostic value of p21 status was enhanced: the 5-year survival rate of p21-positive and p53-negative patients was 80.7%, markedly higher than that of p21-negative and p53-positive patients (50.0% for both; P =.001). Multivariate analysis confirmed that positive expression of p21 was a significant factor for predicting a favorable prognosis. There was no significant correlation between p21 expression and p53 status, proliferative activity, or incidence of apoptosis. CONCLUSION: p21 expression was shown to be an independent prognostic factor in NSCLC.     

Change in plasma viral load, and viral DNA and mRNA burdens, in peripheral blood mononuclear cells from patients infected with HIV-1

OBJECTIVES: To clarify the virological state of human immunodeficiency virus (HIV)-1-infected patients, we compared the plasma HIV-1 RNA copy number (plasma viral load (VL)), viral DNA and mRNA burdens in peripheral blood mononuclear cells (PBMCs), and the other clinical predictors. METHODS: One hundred and thirty-one samples of PBMCs and plasma from 26 patients infected with HIV-1 were obtained during 20 consecutive months for the measurement of VL, viral DNA and mRNA burdens, and CD4 positive (CD4+) cells count. The quantitative polymerase chain reaction (PCR) method with detection by solid phase DNA was utilized for the assay of VL, viral DNA and mRNA burdens. RESULTS: Eighty-six VL, 101 viral mRNA and 129 viral DNA out of 131 samples were detected. There was a significant positive correlation between VL and the viral mRNA burden (r = 0.600, P < or = 0.001), and between VL and the viral DNA burden (r = 0.368, P < or = 0.001). Focused on individuals, the viral mRNA burdens varied in a manner relatively dependent on VL when both values were detectable. However, viral DNA burdens varied relatively independently of VL and the viral mRNA burdens. In six patients the viral mRNA burden was detectable and changed even if the VL was undetectable throughout the observation period. CONCLUSIONS: Both viral DNA and viral mRNA burdens still showed detectable changes even when the VLs became undetectable in most patients. The measurement of viral mRNA or DNA burdens may be clinically available to identify viral replication when VL is undetectable.     

Low frequency of allelic loss in skin tumours from immunosuppressed individuals.

Organ transplant recipients receiving immunosuppression show a dramatically increased risk of non-melanoma skin cancer. The cause of this increase is not known. We report that the rate of loss of heterozygosity (at all the loci we examined) was significantly lower in tumours from immunosuppressed individuals than in tumours from immunocompetent subjects [20 out of 148 (14%) vs 157 out of 428 (37%); P< 0.0001]. These results suggest that tumours in immunosuppressed individuals have a different molecular pathogenesis.     

Analysis of Japanese occupational health services for small-scale enterprises, in comparison with the recommendations of the Joint WHO/ILO Task Group

Objectives: To evaluate Japanese occupational health services (OHSs) for small-scale enterprises (SSEs). Methods: The current Japanese OHSs for SSEs were compared with 15 recommendations of the Joint WHO/ILO Task Group. The status of OHSs was analyzed using the published papers collected by means of a computerized literature search. Thirty-five papers were used in the analysis, which was first conducted by the four authors separately, followed by discussion among the authors. Evaluation was conducted by classifying the status of Japanese OHSs for SSEs into three classes (A: good, B: average, C: poor) based on comparison with each recommendation. Results: Six issues were evaluated as “A”: establishment of a national policy for the provision of OHSs for SSEs, occupational health and safety inspection for SSEs, legislation to ensure services for SSEs and provision of financial incentives, adoption of occupational health programs using multiple channels, training in occupational health issues, and establishment of national data collection and registration systems. Nine issues were evaluated as “B”: provision of OHSs for all SSEs as a part of the “national Health for ALL” strategy, intervention combining economic development and OHSs, extension of OHSs to vulnerable groups, coverage of migrant and seasonal workers by OHSs, the establishment of a national collaborative and coordinative body on OHSs, control of transfer of hazardous technology, encouragement of applied research, employers' commitment and worker participation, and integration of OHSs with primary health care. None of them was evaluated as “C”. Conclusions: Japanese OHSs for SSEs were fairly well established in terms of compliance with the recommendations of the Joint WHO/ILO Task Group, although evaluation may be somewhat subjective and rather qualitative. Received: 08 September 1999 / Accepted: 31 January 2000     

Malnutrition as a prognostic factor in lymphoblastic leukaemia: a multivariate analysis

One hundred and twenty eight Brazilian children with lymphoblastic leukaemia were intensively treated with a Berlin-Frankfurt-Munich based protocol. More children had a white cell count above 50 x 10(9)/l (31%) then observed in developed countries. After a median follow up of 31 months (11-58 months), the estimated probability of relapse free survival was 41% (7%) for the whole group. After adjustment in the Cox's multivariate model, malnutrition was the most significant adverse factor affecting duration of complete remission. Age above 8 years and high peripheral white cell count were also significant adverse factors. Among the nutritional indices, the height for age and weight for age z scores were both significant, whether the cut off points of z-2 or z = -1.28 were chosen to define malnutrition. A strong statistical association between the two indices was found; the contribution of height for age z score to the prediction of relapse free survival was more significant. Children with height for age z score < -2 had a relapse risk of 8.2 (95% confidence interval 3.1 to 21.9) relative to children with z score > -2. The results of this study suggest that socioeconomic and nutritional factors should be considered in the prognostic evaluation of children with leukaemia in developing countries.     

Effect of midodrine on chlorpromazine-induced orthostatic hypotension in rabbits: comparison with amezinium, etilefrine and droxidopa

Orthostatic hypotension was produced in urethane-anesthetized rabbit by a combination of chlorpromazine (0.1 mg/kg, i.v.) and 45 degrees head-up tilt. The effect of midodrine (1 and 3 mg/kg, i.d.) was investigated in comparison with amezinium (10 and 30 mg/kg, i.d.), etilefrine (10 and 30 mg/kg, i.d.) and droxidopa (30 and 100 mg/kg, i.d.). The higher doses of each drug significantly mitigated the chlorpromazine-induced orthostatic hypotension, while none of the lower doses caused a significant effect. The effect of midodrine developed most rapidly; a significant effect was observed 25 min after administration. The order of onset time was midodrine < etilefrine < amezinium < droxidopa. The effect of droxidopa was significant only at 130 to 160 min after administration. The amplitude of effect was in the following order; midodrine = droxidopa > or = etilefrine > amezinium. Midodrine (3 mg/kg, i.d.) mitigated orthostatic hypotension induced by prazosin (0.1 mg/kg, i.v.), but not by pentolinium (0.6 mg/kg, i.v.). It is suggested that midodrine competes with chlorpromazine at alpha1-adrenoceptors and subsequently recovers reflex vasoconstriction. Midodrine may be useful to protect patients with impaired baroreflex activity from accidental orthostatic hypotension during treatment with neuroleptics.     

Combination of nedaplatin and vindesine for treatment of relapsed or refractory non-small-cell lung cancer

Purpose: A phase II study of nedaplatin and vindesine was conducted to evaluate their efficacy and safety for treatment of relapsed or refractory non-small-cell lung cancer (NSCLC). Methods : Between August 1996 and September 1998, 48 patients who had previously received chemotherapy, thoracic radiotherapy, and/or surgery were enrolled in the study. Patients were required to have an Eastern Cooperative Oncology Group performance status of 0 to 2 and an age between 20 and 79 years. Treatment consisted of nedaplatin (80 mg/m², day 1) and vindesine (3 mg/m², days 1 and 8) every 3 to 4 weeks. Results: Of 48 patients, 7 (14.6%) exhibited an objective response. Four (50%) of eight chemotherapy-naive patients had a partial response. However, of the 40 patients who had received prior chemotherapy, a partial response was observed in only 3 (7.5%). At a median follow-up time of 85.1 weeks, the median survival time was 43.6 weeks (95% confidence interval 34.4–52.7) for patients who had received chemotherapy, with a survival rate of 40% at 1 year. Grade 3 or 4 neutropenia occurred in 43 of 48 patients (90%), and neutropenic fever was observed in 3 of the 43 patients, one of whom died of sepsis. Pharmacokinetic and pharmacodynamic analyses of platinum were performed in 43 patients during the first cycle of chemotherapy. Percent reduction in absolute neutrophil count was correlated not only with the area under the plasma ultrafilterable platinum concentration versus time curve (r=0.41, P=0.007) but also with the duration of ultrafilterable platinum concentration above 1 μg/ml (r=0.41, P=0.007). Patients with progressive disease exhibited a shorter duration of ultrafilterable platinum concentration over 1 μg/ml (P=0.046) than those with other responses. Conclusion: A combination of nedaplatin and vindesine was unsatisfactory as second-line chemotherapy for NSCLC, although the combination was well tolerated. The duration of ultrafilterable platinum concentration above 1 μg/ml was an important pharmacokinetic parameter for predicting both chemotherapy-induced neutropenia and treatment outcome. Received: 4 November 1999 / Accepted: 28 April 2000     

The anterior junction line: a radiographic sign of bilateral pneumothorax in neonates

The anterior junction line is a normal anatomic landmark on chest radiographs of healthy adults and older children caused by the visceral and parietal pleurae of the two lungs meeting anteriorly at the midline. It is not seen on chest radiographs of healthy infants. When this sign is identified on the supine frontal view of a neonate, it signifies bilateral pneumothorax. In this situation the line is formed by the meeting of the medial parietal pleurae on each side as they herniate anteriorly in front of the thymus and heart. The sign is best seen when the patient is rotated slightly to the left. It is not seen when there is unilateral pneumothorax or a concomitant pneumomediastinum. Although the anterior junction line is not a highly sensitive indicator of bilateral pneumothorax, it is highly specific and its recognition can promote faster diagnosis.