Presence of functionally active β-adrenoceptors in rat mast cells

Summary The correlation between the binding of a -adrenoceptor antagonist, (–)[³H]-dihydroalprenolol (DHAP), and the adrenergic inhibition of histamine release by acetylcholine and by compound 48/80 was studied with isolated purified rat mast cells and in rat mast cell crude membrane fractions.Acetylcholine-evoked histamine release was inhibited by catecholamines, in the order isoprenaline > adrenaline > noradrenaline. Pretreatment of cells with (–)alprenolol antagonized the inhibitory effect of isoprenaline on acetylcholine-induced histamine release.40/80-evoked histamine release was bocked by isoprenaline at significantly higher concentrations than those required to inhibit cholinergic histamine release. The inhibitory effect of isoprenaline was equally antagonized by preincubating mast cells with (–)alprenolol.Specific binding sites for DHAP have been demonstrated in rat mast cell membranes. The specific binding of DHAP was inhibited by adrenoceptor agonists and antagonists according to the stereospecificity of these compounds.A close correlation between the binding-inhibitory potency of various adrenergic compounds and the data obtained in the pharmacological experiments was found, thus indicating the presence of -adrenoceptors in rat mast cells.     

Diagnostic reliability of scintigraphy in hepatic metastases of breast cancer

The authors have reviewed their experiences in determining the presence of liver metastases in 103 patients by radiocolloid scanning. The sensitivity of liver scanning proved to be quite low if the presence of focal defects of tracer's distribution was chosen as the diagnostic criterion. The inclusion of less restrictive criteria, such as liver enlargement or irregular distribution of the tracer, resulted in an higher sensitivity without lowering the predictive value of a negative scan. Using the more extensive diagnostic criterion, sensitivity, specificity and accuracy were in the range of 90%. Abnormal liver scans are common in patients classified as T3-T4 or N+ and their chances of to be "true positives" are high. Conversely, abnormal scans are seldom found in patients classified as T1-T2 or N0 and chances of "false positives" are high.     

Conservative surgery for Stage I ovarian carcinoma in women of childbearing age

Objective To assess the results of a policy of tailored conservative surgical management for young women with stage I ovarian carcinomas.
Design Retrospective study.
Participants Ninety-nine women aged 40 years or younger who underwent either primary surgery in our department or were referred after primary surgery performed elsewhere.
Methods Of the 99 women in our study, 56 underwent fertility-sparing surgery and 43 more radical surgery. Minimal requirements for conservative management were adequate staging and complete information about the therapeutic options. Factors important in the choice of the treatment were, age, wish to preserve fertility, histologic type and grade, and the stage of the tumour.
Results Conservative treatment was conducted in 84% of nulliparous and in 33% of parous women; 62% of grade 1 tumours, 48% of grade 2, and 50% of grade 3 were treated conservatively. With a median follow up of seven years, we observed five recurrences (9%) of carcinoma in women treated conservatively and five (12%) in those treated more radically. Two women (one in each treatment arm) were saved after recurrence. Two recurrences after conservative surgery involved the residual ovary (3.6%). Two women developed borderline tumour in the contralateral ovary and both were treated by surgery.
Conclusion After adequate staging and accurate information is given to the patient, conservative treatment may be safe in some women with early ovarian cancer. The risk of recurrence in the contralateral ovary is low. Conservative surgery may be also considered in some Stage I grade 3 tumours and in some women with stage IC tumours.     

Polyunsaturated fatty acid concentrations in human hindmilk are stable throughout 12-months of lactation and provide a sustained intake to the infant during exclusive breastfeeding: an Italian study

While a wealth of data on the fatty acid composition of mature human milk has been published, limited information is available on the quantities of individual fatty acids supplied to the suckling infant with maternal milk, through the whole first year of life. Our aim was to qualitatively and quantitatively evaluate the fatty acid composition of human milk from Italian mothers, throughout extended lactation with particular emphasis on the long-chain polyunsaturated fatty acids. We have thus measured the total fat content and the concentrations of major fatty acids by quantitative GLC in pooled breast hindmilk collected from all feedings over 24 h at colostrum, 1, 3, 6, 9 and 12 months in ten mothers recruited after delivery of full-term infants. Total saturated fatty acids progressively increase and total monounsaturated progressively decrease as percentage levels, while among long-chain polyunsaturated fatty acids, percentages of arachidonic acid and docosahexaenoic acid decrease from colostrum up to the third month. Hindmilk total lipids (mg/dl) rise more than twofold up to 3 months, and then remain stable. The amounts (mg/dl) of linoleic acid and alpha-linolenic acid progressively increase, following the trend of total fat, while arachidonic and docosahexaenoic concentrations (mg/dl) remain stable throughout the whole nursing period. Assessment of the intakes per kg body weight shows different trends for the individual major long-chain polyunsaturated fatty acids supplied to the infant from hindmilk during exclusive breast-feeding (3 months). This information may be useful for the evaluation of infant intakes during extended lactation.     

Reduction in mortality with availability of antiretroviral therapy for children with perinatal HIV-1 infection. Italian Register for HIV Infection in Children and the Italian National AIDS Registry

CONTEXT: Since the introduction of combined antiretroviral therapy, mortality rates in adults with human immunodeficiency virus type 1 (HIV-1) infection have decreased. However, little information is available outside the setting of controlled trials on survival of perinatally HIV-infected children treated with antiretroviral therapy. OBJECTIVE: To assess effect of availability of antiretroviral therapy on decreasing mortality in perinatally HIV-infected children. DESIGN: Population-based, multicenter longitudinal study involving data collected by the Italian Register for HIV Infection in Children. SETTING: A network of 106 pediatric clinical centers. SUBJECTS: A total of 1142 children born between November 1980 and December 1997 with perinatally acquired HIV infection with a median follow-up of 5.9 years. MAIN OUTCOME MEASURE: Time to HIV-related death calculated for birth cohort and calendar period and grouped by distribution of predominant type of antiretroviral therapy administered over time. RESULTS: Survival was longer in the 1996-1997 birth cohort (crude relative hazard [RH] of death, 0.39; 95% confidence interval [CI], 0.15-0.96) and 1996-1998 calendar period (crude RH of death, 0.65; 95% CI, 0.45-0.95) than in birth cohort and calendar period 1980-1995, but not when adjusted for maternal antiretroviral treatment during pregnancy and clinical condition at time of delivery, gestational age, and birth weight (adjusted RH of death, 0.55; 95% CI, 0.20-1.50, for birth cohort; and adjusted RH of death, 0.71, 95% CI, 0.43-1.16, for calendar period). In a multivariate model with 1980-1995 as comparison, the 1996-1997 birth cohort had an RH of 0.57 (95% CI, 0.22-1.47; P=.27) but RH for calendar period 1996-1998 was 0.63 (95% CI, 0.47-0.85; P<. 01). When the effects of birth cohort, calendar period, and type of antiretroviral therapy were evaluated simultaneously in the same model, the RH of death was not significantly different from 1.0 for the 1996-1997 birth cohort (P=.19) and calendar period 1996-1998 (P=. 83) suggesting a causal relationship between decreased risk of death and use of combination therapy. The RH of death in children receiving monotherapy or double or triple combination therapy was 0. 77 (95% CI, 0.55-1.08), 0.70 (95% CI, 0.42-1.17), and 0.29 (95% CI, 0.13-0.67), respectively, vs no antiretroviral therapy. CONCLUSION: Survival of perinatally HIV-infected children improved in 1996-1998 as a result of the introduction of combined antiretroviral therapies. JAMA. 2000;284:190-197     

Videothoracoscopic approach in the treatment of intralobar pulmonary sequestration. Report of a case

The Authors report on the use of a videothorascopic approach in the treatment of a patient with intralobar bronchopulmonary sequestration. The latter is a rare malformation which more often than not manifests itself in young patients with hemophthisis, recurrent infection and cough. The condition is difficult to diagnose and is often diagnosed intraoperatively. The treatment is surgical resection. The videothorascopic approach was used in a young patient presenting a lesion of the left inferior lobe with polycyclic contours suspected of being an intralobar bronchopulmonary sequestration, along with medical history findings of cough and hyperpyrexia. The approach permitted identification of the lesion in the context of the left inferior lobe, safe identification and section of the abnormal systemic vessel supplying the lesion and subsequent inferior lobectomy. The postoperative course was uneventful and the patient was discharged on postoperative day 5 with an excellent esthetic and functional outcome. The videothorascopic approach should be taken into consideration for the diagnosis and treatment of intralobar bronchopulmonary sequestrations.     

Health risk assessment of chemicals – A commentary on requirements for the provision of training

Today, only a limited number of training courses specifically in human health risk assessment are available in Europe and although some basic training in health risk assessment is part of most toxicology university programmes, the preparation is often not enough. The purpose of this commentary is to present provision of training program in risk assessment based on common European criteria, easily adopted by institutions across Europe and focusing on risk assessment methodology and procedure. It is worth mentioning that the following paper does not deal with microbiological risk assessment and ecotoxicological risk assessment but mainly with chemical risk assessment. The project focuses on understanding the profile and training requirements of risk assessors in order to design a modular training program covering a range of disciplines in risk assessment and providing a model to establish guidelines for the training and recognition of risk assessors in accordance to a well-defined and properly acknowledged training standard.