In vitro assessment of the efficacy of thermal therapy in human benign prostatic hyperplasia.

The successful management of BPH with minimally invasive thermal therapies requires a firm understanding of the temperature-time relationship for tissue destruction. In order to accomplish this objective, the present in vitro study assesses the cellular viability of human BPH tissue subjected to an experimental matrix of different temperature-time combinations. Hyperplastic prostate tissue was obtained from 10 radical prostatectomy specimens resected for adenocarcinoma. A portion of hyperplastic tissue from the lateral lobe of each prostate was sectioned into multiple 1 mm thick tissue strips, placed on a coverslip and thermally treated on a controlled temperature copper block with various temperatures (45-70 degrees C) for various times (1-60 min). After heat treatment, the tissue slices were cultured for 72 h and viability was assessed using two independent assays: histology and dye uptake for stromal tissue and using histology alone for the glandular tissue. The hyperplastic human prostate tissue showed a progressive histological increase in irreversible injury with increasing temperature-time severity. The dye uptake and histology results for stromal viability were similar for all temperature-time combinations. In vitro thermal injury showed 85-90% stromal destruction (raw data) of human BPH for temperature-time combinations of 45 degrees C for 60 min, 50 degrees C for 30 min, 55 degrees C for 5 min, 60 degrees C for 2 min and 70 degrees C for 1 min. Apoptosis was also identified in the control and milder treated tissues with the degree of glandular apoptosis (about 20%) more than that seen in the stromal regions (< 5%). The Arrhenius model of injury was fitted to the data for conditions leading to a 90% drop in viability (normalized to control) obtained for stromal tissue. The activation energies (E) were 40.1 and 38.4 kcal/mole for the dye uptake study and histology, respectively, and the corresponding frequency factors (A) were 1.1 x 10(24) and 7.78 x 10(22)/s. This study presents the first temperature-time versus tissue destruction relation for human BPH tissue. Moreover, it supports the concept that higher temperatures can be used for shorter durations to induce tissue injury comparable with the current clinically recommended lower temperature-longer time treatments (i.e. 45 degrees C for 60 min) for transurethral microwave thermotherapy of the prostate.     

Occupational exposure to polychlorinated biphenyls and cancer risk.

Polychlorinated biphenyls (PCBs) are a class of chemicals characterized by a long-term persistence and diffusion in the environment, and by bioaccumulation through the food chain. The highest exposures occurred in occupational cohorts through inhalation or skin absorption in work environments. These cohorts can therefore provide important information on health risk from exposure to PCBs in the general population. To provide comprehensive evidence on cancer risk from PCB exposure, we have thus reviewed the epidemiological studies on workers occupationally exposed to PCBs. Overall, no excess for all cancer mortality was observed in the six studies providing information (573 cancer deaths versus 630.4 expected, corresponding to a standardized mortality ratio (SMR) of 91). Among neoplasms potentially related to PCB exposure, there were 12 deaths from liver cancer compared with 9.5 expected (SMR=126). No excess was found for cancers of the breast (40 observed versus 47.4 expected, SMR=84) and of the lymphatic and haematopoietic system (51 observed versus 53.2 expected, SMR=96). Therefore, studies on occupational exposure to PCBs do not show any excess in all cancer mortality, or in mortality for specific cancer sites of interest.     

The recent decline in gallbladder cancer mortality in Europe.

Mortality from gallbladder cancer has been traditionally high in Eastern Europe, and lower in northern countries. Trends in 18 European countries, including the European Union (EU) and selected Eastern European countries, have been updated using official death certification data abstracted from the WHO database over the period 1980-1999. In the EU, age-standardized rates declined by about 30% between the late 1980s and 1999 to reach 1.8/100 000 for women, and by about 10% to reach 1.4/100 000 for men. In the Czech Republic and Hungary, rates for women were over 6/100 000 until the early 1990s, and declined by about 25% thereafter. For males, gallbladder cancer mortality showed no consistent trend, with rates over 3/100 000. Thus, a high mortality area from gallbladder cancer is still evident for both sexes in Central and Eastern Europe. The trends in mortality from gallbladder cancer are probably influenced by changes in risk factor exposure, such as diet, nutrition or tobacco, but essentially reflect more widespread and earlier adoption of cholecystectomy in the EU, since gallstones are the major risk factor for gallbladder cancer. The data also indicate the scope for further improvement of the management of gallbladder disease in Eastern Europe.     

Dietary glycemic index, glycemic load and ovarian cancer risk: a case-control study in Italy.

BACKGROUND: Dietary carbohydrates vary in their ability to raise blood glucose and insulin levels, which, in turn, influence levels of sex hormones and insulin-like growth factors. We analyzed the effect of type and amount of carbohydrates on ovarian cancer risk, using the glycemic index (GI) and the glycemic load (GL) measurement in a large case-control study conducted in Italy. MATERIALS AND METHODS: Cases included 1031 women with incident, histologically confirmed epithelial ovarian cancer, from four Italian regions. Controls included 2411 women admitted to the same hospital networks for acute, non-neoplastic conditions. Average daily GI and GL were calculated from a validated food frequency questionnaire. Odds ratios (OR) and the corresponding 95% confidence intervals (CI) were computed using multiple logistic regression. RESULTS: Ovarian cancer was directly associated with dietary GI (OR for highest versus lowest quartile = 1.7, 95% CI 1.3-2.1) and GL (OR = 1.7, 95% CI 1.3-2.1). The associations were observed in pre- and postmenopausal women, and they remained consistent across strata of major covariates identified. CONCLUSIONS: This study supports the hypothesis of a direct association between GI and GL and ovarian cancer risk and, consequently, of a possible role of hyperinsulinemia/insulin resistance in ovarian cancer development.     

Cigarette tar yield and risk of upper digestive tract cancers: case-control studies from Italy and Switzerland.

BACKGROUND: Tobacco smoking is one of the main risk factors for oral, pharyngeal and oesophageal cancers in developed countries. Information on the role of the tar yield of cigarettes in upper digestive tract carcinogenesis is sparse and needs to be updated because the tar yield of cigarettes has steadily decreased over the last few decades. PATIENTS AND METHODS: We analysed two case-control studies, from Italy and Switzerland, conducted between 1992 and 1999, involving 749 cases of oral and pharyngeal cancer and 1770 controls, and 395 cases of squamous-cell oesophageal carcinoma and 1066 matched controls. Odds ratios (ORs) were estimated by unconditional multiple logistic regression models, including terms for age, sex, study centre, education and alcohol consumption. RESULTS: Based on the brand of cigarettes smoked for the longest time, the multivariate ORs for current smokers compared with never smokers were 6.1 for <20 mg and 9.8 for >or=20 mg tar for oral and pharyngeal neoplasms, and 4.8 and 5.4 for oesophageal cancer, respectively. For the cigarette brand smoked in the previous six months, the ORs for >or=10 mg compared with <10 mg were 1.9 for cancer of the oral cavity and pharynx and 1.8 for oesophageal cancer, after allowance for number of cigarettes and duration of smoking. CONCLUSIONS: The present study confirms the direct relationship between the tar yield of cigarettes and upper digestive tract neoplasms, and provides innovative information on lower tar cigarettes, which imply reduced risks compared with higher tar ones. However, significant excess risks were observed even in the lower tar category, thus giving unequivocal indications for stopping smoking as a priority for prevention of upper digestive tract neoplasms.     

Immunomodulator properties of ecstasy (MDMA)

In vitro exposure to ecstasy (3,4-methylenedioxymethamphetamine, MDMA) alters some immune parameters such as T-cell regulatory function, cytotoxic T-lymphocyte activity, natural killer cell activity and macrophage function. Administration of MDMA in rats produces a suppression of lympho-proliferation response and a decrease in circulating lymphocytes, accompanied by an increase in plasma corticosterone. It was postulated a direct action of MDMA on lymphocytes or rather an indirect action mediated by the hypothalamic pituitary adrenal axis (HPA-AXIS) and/or the sympathetic nervous system (SNS). Acute MDMA treatment effected on healthy-volunteers produces an immune dysfunction associated with pharmaceutical characteristics and so with MDMA plasma concentrations. There is a decrease in CD4+ T-cells and functional responsiveness of lymphocytes, while percentage of natural killer cells increases. A contemporary rise of cortisol plasma concentrations supports the hypothesis of MDMA-induced release of corticotrophin-releasing factor from the hypothalamus and subsequent HPA-axis and SNS activation.     

Hypoglycémie hyperinsulinémique persistante du nouveau-né et du nourrisson

Persistent hyperinsulinemic hypoglycaemia of infancy (PHHI) is the most frequent cause of hypoglycaemia in infancy. Clinical presentation is heterogeneous, with variable onset of hypoglycaemia and response to diazoxide, and presence of sporadic or familial forms. Underlying histopathological lesions can be focal or diffuse. Focal lesions are characterised by focal hyperplasia of pancreatic islet-like cells, whereas diffuse lesions implicate the whole pancreas. The distinction between the two forms is important because surgical treatment and genetic counselling are radically different. Focal lesions correspond to somatic defects which are totally cured by limited pancreatic resection, whereas diffuse lesions require a subtotal pancreatectomy exposing to high risk of diabetes mellitus. Diffuse lesions are due to functional abnormalities involving several genes and different transmission forms. Recessively inherited PHHI have been attributed to homozygote mutations for the beta-cell sulfonylurea receptor (SUR1) or the inward-rectifying potassium-channel (Kir6.2) genes. Dominantly inherited PHHI can implicate the glucokinase gene, particularly when PHHI is associated with diabetes, the glutamate dehydrogenase gene when hyperammonaemia is associated, or another locus.     

Durable remission of locally advanced breast cancer with multimodality management

We treated 20 women with locally advanced breast cancer between January 1991 and September 1996, The treatment regimen included 4 cycles of intensive doxorubicin (30 mg/m2/ d on 3 consecutive days every 2 weeks with G-CSF support), followed by appropriate surgery, followed by high dose therapy with cyclophosphamide, carboplatin and thiotepa (STAMP V, CTCb). Of the 20 patients, seven presented with inflammatory breast cancer, three with Stage HIB, seven with stage IIIA, one with multifocal Stage IIB and two with Stage IV M1 (ipsilateral supraclavicular lymph node involvement) (including one who had an inflammatory primary) disease. Six patients had not undergone mastectomy at the time of entering the protocol. These six received the doxorubicin in a neoadjuvant fashion and were thus evaluable for tumor response. The remaining 14 received doxorubicin as adjuvant therapy prior to intensification and transplantation. All patients underwent local-regional radiation therapy and were placed on oral tamoxifen. Doxorubicin was well tolerated in this schedule with ali but three patients receiving all their cycles on schedule. Both BM and PBPC were easily collected after this regimen and, when reinfused, resulted in the prompt recovery of granulocytes (median 11 days to 500 absolute granulocyte count) and platelets (median 13 days to 20000 platelets). The six patients who received doxorubicin prior to mastectomy all had major clinical responses, but were found to have microscopic focii of breast cancer in the mastectomy specimens. The overall treatment was well tolerated with the exception of one treatment-related death (5%). The overall and relapse free survival are 70% and 58% respectively with a median follow-up of 40 months (range 12–74 months). When the Stage IV patients are censored, the relapse-free survival rate is 69%. In the bone marrow transplant phase of treatment, the major non-hematologic toxicities were stomatitis (70%) and anorexia requiring parental nutrition (75%).     

Is conservative treatment of HELLP syndrome safe?

HELLP syndrome is associated with a high rate of maternal and perinatal morbidity and mortality, and often leads to immediate fetal extraction. However, this condition may occur very early in pregnancy and conservative approaches have been recently proposed. The limits of this approach are discussed with two cases of conservative management of HELLP syndrome complicated by abruptio placentae.     

Radiation damage to triplex DNA induced by gamma-rays: a footprinting study and Monte Carlo simulation

PURPOSE: This study is aimed at comparing the radiosensitivity of a 21-mer DNA fragment in duplex and triplex form (Py x Pu duplex and Py x Pu:Py triplex) and to give insights into the fine structural features due to the different strandedness. MATERIALS AND METHODS: The triplex sample was characterized by means of electrophoretic mobility, circular dichroism spectra and UV melting experiments. Triplex and duplex, labelled on the homopyrimidine or homopurine strand, were irradiated with 60Co gamma-rays. The samples were analysed by sequencing gel electrophoresis and the patterns of relative probabilities of frank strand breakage (FSB) and alkali-revealed breakage (ARB) at each nucleotide site were determined. Relative probabilities of OH* radical attack to duplex and triplex DNA built up with a molecular modelling software were calculated using a previously reported simulation procedure (Sy et al. 1997). The experimental data were compared with the results of the theoretical simulations of OH* radical attack to DNA. RESULTS: Globally, the duplex is more attacked than the triplex, mainly in the Pu strand. Sequence-dependent variations of FSB and FSB+ARB probabilities in both duplex and triplex were revealed. No significant differences between the patterns of damage in the triplex and in the duplex were observed. CONCLUSIONS: The presence of the third Py strand located in the major groove of the DNA duplex modifies the total yields of radiation-induced DNA damage, but not the sequence-dependent patterns of relative probability of damage at each nucleotide site.