Uptake and intracellular distribution of idarubicin in secondary cultures of normal and neoplastic urothelium

This study analyzes the uptake and endocellular distribution of idarubicin (IDA) in normal and neoplastic urothelial secondary cultures in relation to the changes in concentration and time of exposure. The urothelial lines were isolated by Freshney's method from biopsy fragments taken from five patients with superficial bladder cancer. Pharmacological experiments were carried out on subcultures previously immunophenotypically characterized and did not exceed ten passages. The uptake and endocellular distribution of IDA was analyzed by densitometric image analysis on cells treated for 10, 20, 30 and 60 min and 2 h with scalar dosages from 10 ng/ml to 2430 ng/ml. Microscopic observations and densitometric analyzes revealed that in the cells treated with IDA, fluorescence was higher in the cytoplasm compared to the nucleus and increased with the change in dosage. Moreover, densitometric data showed that IDA uptake in the first 20 min was higher in the neoplastic cells, but after that period its behavior became heterogeneous at 30 and 60 min, while at 2 h there was an inversion of the trend. These results suggest that the in vitro cytotoxicity should be evaluated in order to verify whether the elevated uptake of IDA in the first 20 min of treatment is really correlated to a more elevated toxicity in the neoplastic cells with respect to the normal cells. This is presently under investigation.     

Organization of intensive care units in Europe: lessons from the EPIC study

Objective: To study differences related to intensive care unit (ICU) structure and patient demography between the various countries of Western Europe. Design: Application of data collected by the European Prevalence of Infection in Intensive Care (EPIC) study, a one-day prevalence study. Setting: Voluntary participation of all Western European ICUs. A total of 1417 ICUs responded. Patients: All patients, older than 10 years of age, occupying a bed in the participating ICUs over a 24-h period. 10 038 patient case reports were submitted. Results: The study revealed important differences. In particular, there seems to be a north/south divide with fewer ICU beds and more severely ill patients in the south. The United Kingdom seemed more similar to southern European countries than to the north. Conclusion: While there are similarities between European countries, large differences still remain and are important to identify to enable us to work together to create a more uniform system of intensive care, which will in turn give more effective and efficient patient care. Received: 7 February 1997 Accepted 8 July 1997     

Primary Aldosteronism

ABSTRACT A follow-up examination was performed one month to 20 years after adrenalectomy in 28 cases with surgically treated primary aldosteronism due to adrenal adenoma. The mean age at diagnosis was 45, and the mean duration of hypertension seven years. Severe hypertension with a diastolic blood pressure of 130 mmHg or more was observed in 35%. Postoperatively cerebrovascular catastrophe developed in two cases, both of which belonged to the group of patients with severe hypertension. Normalization of blood pressure was observed in 70% and in the remaining subjects the blood pressure was lower than at diagnosis. The blood pressure response to adrenalectomy appeared unpredictable in view of such parameters as the initial blood pressure, age at diagnosis, and duration of the hypertensive state. Toxicosis during pregnancy and metrorrhagia was observed with unexpectedly high frequency in this study population. Low ambulatory plasma renin activity was recorded at the follow-up in 15 out of 18 subjects studied in the absence of evidence of hyperaldosteronism.     

Prediction of lactose malabsorption in referral patients

Two hundred forty-two patients referred for various gastrointestinal complaints were evaluated for clinical parameters that would predict findings of lactose malabsorption. Breath hydrogen and blood glucose lactose tests were performed after ingestion of 50 g lactose. Presenting complaints, duration of symptoms, and patient demographics such as age, sex, and ethnic heritage were not different between lactose malabsorbers and absorbers as defined by the breath hydrogen lactose test. Foodrelated symptoms in general and after specific foods such as milk, ice cream, cheese, and yogurt were also similar between groups. Prior to testing, 30% of malabsorbers (N=161) and 36% of absorbers (N=81) reported lactoserelated symptoms (P=NS). The blood glucose response to lactose was abnormal in 60% of malabsorbers and 15% of absorbers. This study confirmed our impression that it is difficult to predict lactose absorption status by clinical parameters. The majority of our lactose malabsorber patients were unaware of lactose-associated symptoms. Furthermore, symptom assessment, demographics, food history, and blood glucose testing did not predict abnormal hydrogen responses to lactose.The opinions and assertations expressed herein are those of the authors and are not to be construed as reflecting opinions of the United States Air Force or the Department of Defense.This work has been presented in part at the Annual Scientific Session of the American Gastroenterological Association, San Francisco, California, May 19, 1986, and published as an abstract (Gastroenterology 90:1562, 1986).     

Photodynamic therapy of tumours: value of quantum chemical procedures for characterization of new drugs. Prediction of the electronic structure of zinc(II) phthalocyanine with special emphasis on triplet state excitation energies

Zinc(II) phthalocyanine is the active component of the liposomal formulation CGP 55847 which showed a high activity in photodynamic therapy in a variety of animal tumours. The photophysical properties of zinc(II) phthalocyanine have been studied in detail and compared to those of Photofrin, the only sensitizing agent approved so far for phase III/IV clinical trials. Since the efficacy of photodynamic therapy intrinsically depends on the spectroscopic features of the sensitizer, quantum chemical methods have proven to be an efficient means for optimizing chemical structures. As will be shown, a simple modification of the time-honoured INDO model of Pople allows a prediction of the singlet and triplet state properties of molecules of the size of zinc(II) phthalocyanine with an rms error of ≤ 1000 cm⁻¹.     

橡胶木粉填充LLDPE复合材料的结构和力学性能

用橡胶木粉填充线性低密度聚乙烯(LLDPE)，研究了酸、碱溶液预处理木粉的效果和硅烷偶联荆(KH-570)、MMA接枝的天然橡胶胶乳(MGL-30)两种改性剂对橡胶木粉表面改性的效果，以及未粉粒径和填充量等对木粉／LLDPE复合材料力学性能的影响，并用SEM对复合材料拉伸断面的形态结构进行了分析。结果表明：木粉的拉径、木粉填充量和改性荆用量对复合材料的力学性能有较大的影响，经碱溶液预处理再用改性荆改性后的木粉能有效地改善木粉与LLDPE的界面粘结强度，提高橡胶木粉／LLDPE复合材料的力学性能。     

Calciphylaxis – a topical overview

'Calciphylaxis', a calcification syndrome associated with ischaemic cutaneous necrosis, is acquired naturally in humans in disease states. It is a life and limb-threatening complication, usually observed in patients with renal disease and secondary hyperparathyroidism, but known to occur in the absence of renal or parathyroid disease. The reported mortality rate, which ranges from 60-80%, relates to wound infection, sepsis and organ failure. It is a small-vessel vasculopathy, which is estimated to occur in about 4% of haemodialysis patients. Clinically, violaceous, reticulate areas of cutaneous necrosis and eschar may be evident, particularly in the extremities. In addition to the clinical picture, a raised calcium phosphorous product, an elevated parathyroid hormone level, radiographic evidence of vessel and soft-tissue calcification and the finding of mural calcification affecting small arteries and arterioles on histopathology help to confirm the diagnosis of this entity which generally has a poor prognosis. A high index of suspicion and an active multidisciplinary management approach, with rigorous attention to wound care and prevention of sepsis, are vital in the management of these patients. In this overview, we discuss the pathophysiology, clinical features and associations, risk factors, diagnosis and management issues relating to calciphylaxis.     

Clinical predictors of suicidal acts after major depression in bipolar disorder: a prospective study

Objective:  This study determined the clinical predictors of suicidal behavior during a 2-year follow-up of patients with bipolar disorder presenting with a major depressive episode (MDE).
Method:  Sixty four patients with DSM-III-R bipolar disorder were assessed at presentation for treatment of an MDE. Correlates of past suicidal behavior were determined by comparing patients with and without a history of suicide attempts using a t -test, Wilcoxon test or chi-squared test of independence on individual explanatory variables. Putative predictors of attempts during the follow-up period were tested separately using Cox proportional hazards regression analysis.
Results:  Twelve of 64 patients had at least one suicide attempt in the follow-up period, five of them attempted in the first 2 months and seven around or shortly after the 1-year follow-up visit. All attempters had a history of past suicide attempts. Most predictors of future suicidal behavior were correlates of past suicidal behavior. Family history of suicide acts and comorbid borderline personality disorder predicted early attempts, while younger age, high hostility scores, number of past attempts, subjective pessimism as reflected in depression and suicidal ideation, and few reported reasons for living predicted suicidal acts during the whole period.
Conclusion:  In this data set of bipolar patients we noted an intriguing picture of two clusters of suicide attempts. Hostility was the strongest risk factor. These findings may have implications in both the identification of at-risk patients and the timing of clinical interventions including aggressive pharmacotherapeutic prophylaxis to prevent relapse or recurrence of depressive symptomatology.