Comparison of benign and malignant insulinoma

BackgroundHow malignant insulinomas present relative to benign insulinomas is unknown.MethodsA single-institution retrospective study identified patients with insulinoma. Malignancy was defined by distant metastases, positive lymph node(s), T stage of 4, direct invasion into surrounding peripancreatic tissue, or presence of lymphovascular invasion. Wilcoxon Rank Sum tests and Kaplan-Meier analysis were used.ResultsA total of 311 patients were identified: 51 malignant and 260 benign. Patients with malignant insulinoma presented with higher levels of insulin, proinsulin, and c-peptide. Malignant lesions were larger: 4.2 ± 3.2 vs 1.8 ± 0.8 cm in benign lesions, p < 0.01. Overall survival at 5 years was 66.8% vs 95.4% for malignant and benign insulinoma respectively, p < 0.01.ConclusionsLarger size of insulinoma and increased serum β-cell polypeptide concentrations were associated with malignancy. Malignant insulinoma has poorer survival. Further work-up to rule out malignancy may be indicated for larger pancreatic lesions and for patients with higher pre-operative insulin and pro-insulin.     

The C. elegans microRNA let-7 binds to imperfect let-7 complementary sites from the lin-41 3'UTR

Caenorhabditis elegans let-7, a founding member of the microRNA family, is predicted to bind to six sites in the 3'UTR of the mRNA of its target gene, lin-41, to down-regulate LIN-41. Here, we demonstrate that wild-type let-7 microRNA binds in vitro to RNA from the lin-41 3'UTR. This interaction is dependent on two conserved let-7 complementary sites (LCSs). A 27-nucleotide sequence between the LCSs is also necessary for down-regulation in vivo. LCS mutations compensatory to the lesion in let-7(n2853) can partially restore lin-41 3'UTR function in a let-7(n2853) background, providing the first experimental evidence for an animal miRNA binding directly to its validated target in vivo.     

Growth control of human mammary cancer cells (MCF-7 cells) in culture: effect of estradiol and growth factors in serum-containing medium

The growth control of estrogen-dependent mammary cancer is very complex and only partly understood. The present study was undertaken in order to establish conditions for growth control of MCF-7 cells in monolayer culture with focus on the effect of estradiol-17 beta, fetal calf serum, and growth factors. The effect of charcoal-stripped fetal calf serum (CSFCS) on cell growth was dependent upon the presence of hormones or growth factors in the medium. In the presence of insulin (or insulin-like growth factor 1) and in the absence of estradiol-17 beta, increasing concentrations of CSFCS, 0.625-20%, produced a bell-shaped growth response curve. Serum concentrations greater than 2.5% inhibited cell growth in the absence of estradiol-17 beta, whereas CSFCS in a dose-dependent way up to 10% stimulated growth in the presence of estradiol-17 beta (5 x 10(-10) mol/liter). The growth inhibitory effect of CSFCS could not be demonstrated in the absence of insulin (or insulin-like growth factor 1) and estradiol-17 beta. CSFCS stimulated growth in a dose-dependent way in the presence of estradiol-17 beta and also in the absence of insulin. Both the putative growth inhibitor and stimulator were found to be heat stable and not dialyzable. Epidermal growth factor stimulated growth but was unable to eliminate the growth inhibitory effect of 5-10% CSFCS. Interleukin-1 alpha inhibited MCF-7 cell growth in a dose-dependent way and produced a 75% reduction in cell number at a concentration of 5 x 10(-10) mol/liter. This inhibition was almost totally overcome by estradiol-17 beta. It is concluded that serum appears to contain factors with both stimulatory and inhibitory effects on the growth of MCF-7 cells. The inhibitory effect can be eliminated by estradiol (5 x 10(-10) mol/liter). In the presence of estradiol cell growth is stimulated by CSFCS in a dose-related way up to 5-10%. Taken together these data seem to indicate that estradiol stimulates cell growth in two principal ways: partly by eliminating the effect of an inhibitor, in support of a "negative hypothesis," and partly by an effect whereby estradiol permits a growth stimulator in CSFCS to be expressed, in support of the "indirect positive hypothesis."     

Local lymph node assay responses to paraphenylenediamine: intra- and inter-laboratory evaluations.

The murine local lymph node assay (LLNA) is a method for the prospective identification of skin sensitizing chemicals. Proliferative responses induced in lymph nodes draining the site of topical application of the test chemical are measured and those chemicals that induce a stimulation index of three or more compared with concurrent vehicle-treated controls are considered to have the potential to cause skin sensitization. Dose-response data from the LLNA may be used to derive an estimate of relative skin sensitizing potency, based upon derivation of the concentration of chemical required to cause a stimulation index of 3 (EC3 value) as calculated by linear interpolation. The purpose of the present investigations was to examine the stability of LLNA responses and the consistency of derived EC3 values induced by the contact allergen paraphenylenediamine (PPD). Analyses were conducted once a month over a 4-month period in each of two independent laboratories. In all assays, and in both laboratories, PPD elicited a positive response. Although some minor differences in responses between and within laboratories were observed, the derived EC3 values were generally very consistent. In Laboratory 1, EC3 values varied between 0.06 and 0.09% PPD, whereas in Laboratory 2 the range was 0.09-0.20%. These EC3 values are consistent with clinical experience of this material insofar as it is a common and relatively potent cause of allergic contact dermatitis in humans. Taken together, these data confirm the stability of LLNA responses both with time and between laboratories and provide additional support for the use of derived EC3 values in the assessment of relative skin sensitizing potency.     

Effects of eating an uncooked vegetable diet for 1 week

Biochemical and metabolic indicators were monitored in a group of volunteers suffering from a variety of chronic illnesses participating in a week's course on a special uncooked vegetable diet, known as "living food". Unmatched healthy controls ate the same diet cooked for 2 min in a microwave oven. After 1 week on the regimen, serum protein and urea contents decreased and alanine aminotransferase (ALAT) activity increased in both groups, although all within the normal range. Blood glucose increased in both groups to slightly above normal limits but total serum cholesterol dropped about 1 mmol/l from normal starting levels. Serum tocopherol and retinol increased only in the group eating the uncooked diet. In both groups urinary sodium dropped drastically without a significant change in potassium. Serum and urinary phenol and p-cresol diminished also significantly. It is concluded that this vegetable diet may be of some benefit in the short term but any longer-term use requires evaluation.     

Antiretroviral therapy in adults: updated recommendations of the International AIDS Society-USA Panel

OBJECTIVE: To update recommendations for antiretroviral therapy for adult human immunodeficiency virus type 1 (HIV-1) infection, based on new information and drugs that are available. PARTICIPANTS: A 17-member international physician panel with antiretroviral research and HIV patient care experience initially convened by the International AIDS Society-USA in December 1995. EVIDENCE: Available clinical and basic science data including phase 3 controlled trials; data on clinical, virologic, and immunologic end points; research conference reports; HIV pathogenesis data; and panel expert opinion. Recommendations were limited to therapies available (US Food and Drug Administration approved) in 1999. CONSENSUS PROCESS: The panel assesses new research reports and interim results and regularly meets to consider how the new data affect therapy recommendations. Recommendations are updated via full-panel consensus. Guidelines are presented as recommendations if the supporting evidence warrants routine use in the particular situation and as considerations if data are preliminary or incomplete but suggestive. CONCLUSIONS: The availability of new antiretroviral drugs has expanded treatment choices. The importance of adherence, emerging long-term complications of therapy, recognition and management of antiretroviral failure, and new monitoring tools are addressed. Optimal care requires individualized management and ongoing attention to relevant scientific and clinical information in the field.     

Antiretroviral drug resistance testing in adult HIV-1 infection: recommendations of an International AIDS Society-USA Panel

Martin S. Hirsch, MD; Françoise Brun-Vézinet, MD; Richard T. D'Aquila, MD; Scott M. Hammer, MD; Victoria A. Johnson, MD; Daniel R. Kuritzkes, MD; Clive Loveday, MD, PhD; John W. Mellors, MD; Bonaventura Clotet, MD, PhD; Brian Conway, MD; Lisa M. Demeter, MD; Stefano Vella, MD; Donna M. Jacobsen; Douglas D. Richman, MD

JAMA. 2000;283:2417-2426.

Objective  Assays for drug resistance testing in human immunodeficiency virus type 1 (HIV-1) infection are now available and clinical studies suggest that viral drug resistance is correlated with poor virologic response to new therapy. The International AIDS Society–USA sought to update prior recommendations to provide guidance for clinicians regarding indications for HIV-1 resistance testing.

Participants  An International AIDS Society–USA 13-member physician panel with expertise in basic science, clinical research, and patient care involving HIV resistance to antiretroviral drugs was reconvened to provide recommendations for the clinical use of drug resistance testing.

Evidence and Consensus Process  The full panel met regularly between January and October 1999. Resistance and resistance testing data appearing in the last decade through April 2000 and presentations at national and international research conferences were reviewed. Recommendations and considerations were developed by 100% group consensus, acknowledging that definitive data to support final recommendations are not yet available.

Conclusions  Emerging data indicate that despite limitations, resistance testing should be incorporated into patient management in some settings. Resistance testing is recommended to help guide the choice of new regimens after treatment failure and for guiding therapy for pregnant women. It should be considered in treatment-naive patients with established infection, but cannot be firmly recommended in this setting. Testing also should be considered prior to initiating therapy in patients with acute HIV infection, although therapy should not be delayed pending the results. Expert interpretation is recommended given the complexity of results and assay limitations.

     

Food, health, the environment and consumers' dietary choices

The aim of this paper is to examine some of the issues that surround food and the environment, particularly conventional and organic agriculture and food distribution, and to look at some of the health implications. It is argued that the links between food, health and the environment are strong. Consumers have the power to have an impact positively or negatively on the environment via their dietary choices. By providing information and advice about the environmental as well as the health impact of food choices, health and nutrition professionals could increase consumers' awareness of such issues.     

Evolution of atherogenic diets in South Asian and Italian women after migration to a higher risk region

BACKGROUND: To identify differences in the evolution of the diets of South Asian and Italian migrants, a cross-sectional, multiethnic study was undertaken in Glasgow, Scotland. METHODS: Five groups of women aged 20-42 years comprising general population (n = 35), South Asian migrants (n = 35) British-born controls (n = 37), Italian migrants (n = 30) and British-born (n = 38) participated in an interviewer administered structured questionnaire on issues relating to health, diet and food selection. Anthropometric measurements were made and subjects completed a 7-day weighed diet inventory. RESULTS: Compared with the general population, dietary differences were greatest amongst first generation migrant groups. There were major differences between the two migrant groups. South Asian migrants tended to display a more atherogenic profile (fat 42.4% energy, saturated fat 15.0% energy, vitamin C 5.1 mg per 1000 kJ) than the general population (fat 39.1% energy, saturated fat 13.5% energy, vitamin C 6.8 mg per 1000 kJ), and Italian migrants (fat 35.7% energy, saturated fat 12.1% energy, vitamin C 10.9 mg per 1000 kJ). However, South Asian groups had higher intakes of polyunsaturated fatty acids which may be cardioprotective. CONCLUSIONS: South Asian migrants to Scotland appear to develop adverse dietary elements in the first generation, which are modified in subsequent generations, whereas Italians' diets remain cardioprotective in the migrant generation but deteriorate in subsequent generations.