Absolute and relative activities of platinum-complexes on human tumors as evaluated by an antimetabolic in vitro assay

An in vitro assay, which evaluates drug effect on ³H-thymidine incorporation, was used to investigate the absolute and relative activities of cisplatin (DDP), carboplatin (CBDCA) and iproplatin (CHIP) on 317 specimens from untreated tumors, including breast and ovarian cancers and malignant melanomas. Similar activities were generally observed for DDP and CHIP, whereas CBDCA exhibited a lower, although not significantly different cytotoxicity on breast and ovarian cancers. The relative activities of Platinum analogues were analyzed on 239 two-way drug sensitivity comparisons. The overall agreement rates ranged from 80.2 to 83.9% for the different comparisons. High coresistance, from 61.1 to 93.8%, was observed for all the comparisons, regardless of the tumor type. Cosensitivity rates were poor for breast and ovarian cancers, from 0 to 37.5%, whereas for melanomas an association in sensitivity was observed in 80% of the cases.     

Spontaneous Splenic Rupture in a Patient with Acute Lymphoblastic Leukemia of Burkitt Type

We describe a case of spontaneous splenic rupture occurred in a patient with acute lymphoblastic leukemia of Burkitt type before starting cytotoxic chemotherapy. Left hypochondrial pain radiating to the homolateral shoulder was the only clinical symptom. Emergency computed tomography showed splenic laceration and hemoperitoneum. The patient underwent immediate laparotomy with splenectomy and experienced an uneventful postoperative recovery. Eight days after surgery, chemotherapy could be administered and complete remission was achieved. Although spontaneous rupture of the spleen is rare in leukemia and related disorders, this diagnosis should be taken in account also when clinical symptoms are mild. Following immediate operative management, patients may completely recover and receive cytotoxic chemotherapy with substantial possibilities of achieving complete remission.     

Soft budget constraints in health care: evidence from Italy

The reforms that have reshaped the public health care systems have often been coupled with devolution. However, this process has frequently been accompanied by widespread soft budget constraint policies. In this paper we argue that the soft budget constraint arises from a cooperative game between local authorities that force Central Government to bail them out. Our theoretical model is tested using data for Italian regions for the period 2002–2006 and our hypothesis is verified. Although the model uses Italy as a benchmark, we believe that the framework we propose could be extended to other federal contexts where resources are distributed unevenly and preferences are asymmetric.     

Intrafamilial phenotypic variability in four families with Anderson‐Fabry disease

We analysed the clinical history of 16 hemizygous males affected by Anderson‐Fabry Disease, from four families, to verify their intrafamilial phenotypic variability. Seven male patients, ranging from 26 to 61 years of age, died, whereas nine (age range 23–55) are alive. Eleven patients have undergone enzyme replacement therapy (ERT) for a period of 5–10 years. We have found a wide range of intrafamilial phenotypic variability in these families, both in terms of target‐organs and severity of the disease. Overall, our findings confirm previous data from the literature showing a high degree of intrafamilial phenotypic variability in patients carrying the same mutation. Furthermore, our results underscore the difficulty in giving accurate prognostic information to patients during genetic counselling, both in terms of rate of disease progression and involvement of different organs, when such prognosis is solely based on the patient's family history.     

Single-run reversed-phase HPLC method for determining sertraline content,enantiomeric purity,and related substances in drug substance and finished product

A direct enantio-, diastereo-, and chemo-selective high-performance liquid chromatographic method was developed for determining the content, enantiomeric purity, and related substances of the chiral antidepressant drug sertraline HCl in a single chromatographic run. The separation was achieved on a chiral stationary phase based on amylose tris(3-chloro-5-methylphenylcarbamate) under reversed-phase conditions. The method was optimized by evaluating the influence of the temperature and mobile phase composition on the retention and selectivity. The application of the single-run approach allowed to baseline resolve all investigated species in less than 15 min, without using buffers or tandem-coupled columns. The chromatographic method was validated according to the guidelines of the Official Medicines Control Laboratory and applied to control the content of sertraline HCl and related chiral substances in a generic antidepressant formulation.     

Serum uric acid is inversely proportional to estimated stroke volume and cardiac output in a large sample of pharmacologically untreated subjects: data from the Brisighella Heart Study

Serum uric acid is representative for xanthine-oxidase, the key enzyme involved in the production of uric acid, which is up-regulated in the failing heart, and may play an important role in the pathophysiologic process that leads to heart failure. In our study, we investigated the relation between stroke volume, cardiac output and serum uric acid in a large sample of overall healthy pharmacologically untreated subjects. The Brisighella Heart Study included 2,939 men and women between the ages of 14–84 without prior coronary heart disease or cerebrovascular disease who were not taking antihypertensive therapy at baseline. For this study, we selected 734 adult subjects enrolled in the last Brisighella population survey not taking antihypertensive, antidiabetic, lipid-lowering and uric acid-lowering drugs, and who were also not affected by chronic heart failure or by gout. The main predictors of cardiac functionality parameters were mean arterial pressure (MAP), HR, SUA and age (all p < 0.001), while gender, BMI, LDL-cholesterol, HDL-cholesterol, triglycerides, fasting plasma glucose, creatinine, estimated glomerular filtration rate, physical activity and smoking habit were not significantly associated (all p > 0.05). In particular, there is a strong relation between estimated cardiac output and serum uric acid (B = ?0.219, p < 0.001) and between stroke volume and serum uric acid (B = ?3.684, p < 0.001). These observations might have an impact on future considerations about serum uric acid as an early inexpensive marker of heart function decline in the general population.