Circadian organization of serum electrolytes in physiological aging

Age-related structural and neurochemical changes occurring in the central nervous system have been related to changes in some rhythmometric parameters. In spite of their clinical importance, only a few studies have investigated the modifications over time of serum electrolytes in senescence. The aim of our study was to evaluate the circadian pattern of serum potassium, chloride, sodium, calcium and phosphorus in 30 clinically healthy elderly subjects, with no cognitive impairment, and to compare the findings with those given by 24 healthy young controls. The subjects were synchronized as regards their daily activities, sleeping/waking habits, time/quality of meals and dietary electrolyte intake. After an overnight fast, samples were taken beginning at 08.00 and every 4 h thereafter until 20.00, and every 2 h from 20.00 to 04.00. Both the young and the elderly subjects exhibited statistically significant circadian rhythms for all serum electrolytes considered. Our findings suggest that circadian organization of serum electrolytes is maintained in physiological aging, even though it should be noted that sodium and phosphorus acrophases differed significantly in the two experimental groups.     

Epidemiological monitoring of legionellosis: a case-control study in an university general hospital

The authors report the early results of a case-control study carried out about the risk of legionellosis. During the first year, they have tested urine samples from patients with unknown pneumonia, using a legionella-sensitive test for the detection of its antigen. Out of 171 samples, 9 have turned out to be positive (5.3%). Lifestyles, predisposing factors, possible sources of infection and stressful events were investigated.     

Accrual issues for chemoprevention trials: the example of the 4-HPR study for the prevention of contralateral breast cancer

This paper describes the accrual of the controlled clinical trial with fenretinide for the prevention of contralateral breast cancer. Accrual screened 4,030 potentially eligible patients of whom 1,815 were randomized. Two strategies of recruitment were used, i.e. retrospective and prospective. In the retrospective accrual, the medical staff reviewed the records of breast cancer patients who had received curative surgery to select those who fulfilled the eligibility criteria of the study. For the prospective recruitment operated, patients were contacted after the beginning of the trial. The study started in March 1987 and accrual closed on July 31, 1993. The planned accrual period was extended by 19 months. The yearly accrual tended to decrease with time. This was mainly due to the end of the retrospective recruitment and to the introduction of adjuvant chemotherapy, a reason for exclusion from the trial, also for patients with negative axillary nodes. The known accrual difficulties of chemoprevention studies proved also to be true for the high-risk population of this trial.     

An antibody‐free strategy for screening putative HDM2 inhibitors using crude bacterial lysates expressing GST‐HDM2 recombinant protein

Targeting the interaction of p53 with its natural inhibitor MDM2 by the use of small synthetic molecules has emerged as a promising pharmacological approach to restore p53 oncosuppressor function in cancers retaining wild‐type p53. The first critical step in the experimental validation of newly synthesized small molecules developed to inhibit MDM2‐p53 interaction is represented by the evaluation of their efficacy in preventing the formation of the MDM2‐p53 complex. This can be achieved using the in vitro reconstructed recombinant MDM2‐p53 complex in cell‐free assays. A number of possible approaches have been proposed, which are however not suitable for screening large chemical libraries, due to the high costs of reagents and instrumentations, or the need of large amounts of highly pure recombinant proteins. Here we describe a rapid and cheap method for high‐throughput screening of putative inhibitors of MDM2‐p53 complex formation – based on the use of GST‐recombinant proteins – that does not require antibodies and recombinant protein purification steps from bacterial cell lysates. Copyright © 2013 John Wiley & Sons, Ltd.     

Clinically useful measures to assess the effectiveness of treatments: hints for a proper choice with special emphasis on cancer research

Several absolute and relative measures useful to assess the consequences of treatments in cancer research are presented together with statistical methods suitable for computing the pertinent confidence intervals. The relationship of these measures with the parameters of the regression models commonly used in the analysis of survival data is elaborated upon. Three examples are elaborated, and conditions of interchangeability of the measures are discussed in detail. Finally, suggestions for the choice of the measure most appropriate for a specified data set are given.     

Safety of the synthetic retinoid fenretinide: long-term results from a controlled clinical trial for the prevention of contralateral breast cancer.

PURPOSE: To describe the pattern of occurrence of adverse events commonly arising during treatment with fenretinide, a synthetic retinoid under investigation for cancer prevention. PATIENTS AND METHODS: The series includes 2,867 women accrued in a trial aimed at assessing the effect of fenretinide on the prevention of second breast malignancy. Women were randomly assigned to receive no treatment (1,435 patients) or 5-year fenretinide treatment (1,432 patients). In terms of disease recurrence in the breast, the trial showed a possible beneficial effect of the compound in premenopausal women, and an opposite trend in postmenopausal women. End points considered for safety assessment were the occurrence of diminished dark adaptation, dermatologic disorders, gastrointestinal symptoms, disorders of the ocular surface, and abnormal laboratory values. RESULTS: The most common adverse events were diminished dark adaptation (cumulative incidence, 19.0%) and dermatologic disorders (18.6%). Less common events were gastrointestinal symptoms (13.0%) and disorders of the ocular surface (10.9%). In comparison, incidence figures in the control arm were 2.9% for diminished dark adaptation, 2.9% for dermatologic disorders, 5.4% for gastrointestinal symptoms, and 3.2% for disorders of the ocular surface. Symptoms occurring during fenretinide treatment tended to recover with time. No between-group difference was observed for the occurrence of laboratory data abnormalities. Overall, 63 (4.4%) treatment discontinuations were caused by adverse events. CONCLUSION: Given the number of patients involved in the study and the prolonged intake of the drug, the experience on fenretinide tolerability can be considered sufficiently reassuring to justify further testing of the retinoid.     

Arthroscopic treatment of acute acromioclavicular joint dislocation with double flip button

The ideal treatment for acute acromioclavicular joint dislocation is still controversial, both in terms of indications and surgical technique. The clinical and radiographic outcomes of 16 patients affected by acute AC joint dislocation (type III–V) and arthroscopically treated with a coracoclavicular double flip button are presented. Despite the excellent clinical results both in terms of Constant score (mean 97 points) and patient satisfaction, at a mean follow-up of 31 months the radiographs showed partial loss of reduction due to distal migration of the flip button within the upper third of the clavicle in one-fourth of the cases. The technique presented here proved to be safe and minimally invasive while delivering good aesthetic results and allowing for the treatment of associated lesions. Furthermore, the technique could benefit from more advanced retention devices, which ought to reduce or avoid migration of the flip buttons.     

Primary mammary focus of malignant non-Hodgkin's lymphoma. Apropos of 10 cases

The authors describe 10 cases of malignant non-Hodgkin's lymphoma in a mammary site in women aged 38 to 82 years. The clinical examination and the sometimes suggest an adenocarcinomatous lesion, thus leading to a useless surgical exeresis. An initial histological study provides the diagnosis. A complete assessment of extension allows an accurate staging and the refinement of the therapeutic schedule. Exclusive radiation therapy seems to be justified in low-malignancy forms remaining strictly confined to the breast. For the high- and medium-malignancy forms, the essential weapon is chemotherapy, which seems to improve the duration and rate of remission.     

Role of p27 in Prostate Carcinogenesis

The cyclin dependent kinase inhibitor p27 binds to and inhibits preferentially S-phase kinases thereby halting cell cycle progression. Loss of p27 expression has been shown to be associated with aggressive behavior in a variety of human epithelial tumors including prostate cancer. In this review, the role of p27 in cell cycle progression as well as its regulation by the ubiquitin-proteasome pathway are discussed. The experimental evidence pointing to the role of p27 as a tumor suppressor gene is outlined. The data generated to date on the prognostic significance of loss of p27 protein expression in human prostate cancers are summarized. Finally, the implications of the changes in p27 expression which occur as a result of androgen ablation in normal and neoplastic prostate are discussed.