Determination of DNA single strand breaks and selective DNA amplification by N-nitrodimethylamine and analogs,and estimation of the indicator cells' metabolic capacities

Summary N-nitrodimethylamine is metabolized oxidatively to N-nitrohydroxymethylmethylamine, which decomposes to yield formaldehyde and N-nitromethylamine. All four compounds and N-nitroethylamine were tested for their ability to induce DNA single strand breaks in hepatocytes and in SV 40-transformed Chinese hamster embryo cell lines. Only the two monoalkylnitramines were positive. They induced single strand breaks in hepatocytes, but were not effective in the other cells. Formaldehyde and N-nitrohydroxymethylmethylamine were toxic to the cells. None of the compounds tested was able to induce selective DNA amplification in the two transformed cell lines.Enzymes involved in drug metabolism were assayed in the hamster cell lines. The activity of UDP-glucuronosyltransferase and cytosolic epoxide hydrolase were not detectable. N-nitrodimethylamine demethylation was low. The content of reduced glutathione and the activities of glutathione transferase and membrane bound epoxide hydrolase were comparable to values obtained in the rat liver.Dedicated to Professor Dietrich Schmähl on the occasion of his 60th birthday     

Pediatric patients who receive antibiotics for fever and neutropenia in less than 60 min have decreased intensive care needs

Background

Antibiotic delivery to patients with fever and neutropenia (F&N) in <60 min is an increasingly important quality measure for oncology centers, but several published reports indicate that a time to antibiotic delivery (TTA) of <60 min is quite difficult to achieve. Here we report a quality improvement (QI) effort that sought to decrease TTA and assess associated clinical outcomes in pediatric patients with cancer and F&N.

Procedure

We used Lean‐Methodology and a Plan‐Do‐Study‐Act approach to direct QI efforts and prospectively tracked TTA measures and associated clinical outcomes (length of stay, duration of fever, use of imaging studies to search for occult infection, bacteremia, intensive care unit (ICU) consultation or admission, and mortality). We then performed statistical analysis to determine the impact of our QI interventions on total TTA, sub‐process times, and clinical outcomes.

Results

Our QI interventions significantly improved TTA such that we are now able to deliver antibiotics in <60 min nearly 100% of the time. All TTA sub‐process times also improved. Moreover, achieving TTA <60 min significantly reduced the need for ICU consultation or admission (P = 0.003) in this population.

Conclusion

Here we describe our QI effort along with a detailed assessment of several associated clinical outcomes. These data indicate that decreasing TTA to <60 min is achievable and associated with improved outcomes in pediatric patients with cancer and F&N. Pediatr Blood Cancer 2015;62:807–815. © 2015 The Authors. Pediatric Blood & Cancer, published by Wiley Periodicals, Inc.     

Traditional sex counselling and STI/HIV prevention among young women in rural Uganda

This study examined the potential of traditional ways of passing on sexual knowledge from adult to younger women (the senga institution) among the Baganda of central Uganda, as a potential tool for STI/HIV prevention today. Traditional and contemporary forms of the institution were studied, and their strengths and weaknesses assessed. Data were collected using qualitative research methods. The senga institution comprises four components: Social responsibility, moral authority, appropriate knowledge and a suitable socio-economic environment. Although senga practises have been weakened and the way in which they are viewed by adolescent girls and the community in general has changed, the institution can still be exploited to develop more culturally appropriate forms of sex education for girls, particularly out of school girls and adolescent mothers.     

Antigenotoxic properties of lactic acid bacteria in the S. typhimurium mutagenicity assay

A high percentage of human tumors is reported to be related to dietary habits. One way to improve the nutritional impact is to increase the intake of protective factors, such as inhibitors of DNA damage and other types of anticarcinogens. Specific strains of lactic acid bacteria used to ferment milk are promising candidates that may be antimutagenic and anticarcinogenic. We have studied the antimutagenicity of 10 isolated strains of beneficial lactic acid bacteria. Four types of fermented milk products were also studied for their protective properties. The effect of these bacteria on the yield of revertants induced by nitrosated beef extract was investigated in the Salmonella typhimurium mutagenicity assay. Eight of 10 isolated Lactobacillus strains reduced the yield of his+ revertants almost back to the levels of the untreated controls. Different fermented fresh yogurts containing viable bacteria (probably Lactobacillus delbrueckii ssp. bulgaricus and Streptococcus thermophilus or Lactobacillus acidophilus and Bifidobacteria) showed protective effects as well. The degree of suppressing revertants was independent of the yogurt's fat content. In contrast, yogurt products that had been heat treated were not inhibitory. The other fresh fermented milk products (e.g., buttermilk, kefir, and “Dickmilch”) were not antimutagenic in this study. The results imply that some bacteria used in milk processing have an antimutagenic potential and that this property is specific for the bacterial strain.     

The negotiation of sexual relationships among school pupils in south-western Uganda

The objective of the study was to explore how school-going adolescents in south-western Uganda negotiate sexual relationships. Qualitative data were obtained from 15 boys and 15 girls (14-18 years old), during a series of role plays, focus group discussions and one-to-one interviews. A questionnaire was administered to 80 pupils (12-20 years old) from the same school. Most of the pupils were sexually active. Sexual relationships between boys and girls were mediated by peers. Boys initiated relationships. Exchange played an important role in the negotiation of sexual relationships. Money or gifts were given and received in exchange for sexual favours and to strengthen the relationship. To maximize gains, some adolescents had sexual relationships with adults. Sexual relationships were characterized by ambiguity. Love is intertwined with sexual desire, money and prestige. Girls have to be explicit enough to get a good deal; if they are too explicit they will be stigmatized as 'loose' but if they are not interested in money they may be suspected of wanting to spread HIV. Boys try to persuade girls that they have money, but do not want to emphasize this too much. In sexual negotiations a boy must persuade a girl that although he is modern and sophisticated (i.e. experienced) he does not chase after every girl; the girl does not want to come over as an unsophisticated virgin, but does not want to give the impression that she is loose either. There is a tension between the traditional ideal of female chastity and submissiveness and the modern image of sexual freedom. Multiple partnerships were highly valued as a sign of sophistication. Condoms were not considered important. Interventions aimed at reducing the spread of HIV do not seem to be having an effect on the behaviour of this group of adolescents. On the contrary, risky attitudes and behaviour are part of an adolescent ideal of modernity and sophistication. New approaches are needed to persuade this group of the need for change. Shifting the source of interventions from adults to the adolescents themselves, encouraging girls to try other means of earning money and debunking the idea that having many partners is sophisticated may be productive alternatives.     

Understanding sexual behaviour change in rural southwest Uganda: a multi-method study

Studies report substantial sexual behaviour change in Africa in response to HIV/AIDS. Generally there seems to be an increase in condom use and a reduction in partners, with men reporting more change than women. However, it is not only important to know whether people are changing their sexual behaviour but also their reasons for changing and the consistency and extent of change. Between 1996 and 2000 a study involving 196 respondents was carried out in rural southwest Uganda to investigate the exact nature of behaviour change and the reasons for change or lack of change since people became aware of HIV/AIDS. Data were collected from three rounds of questionnaire surveys, four rounds of open in-depth interviews, six rounds of semi-structured interviews and from informal conversations and participant observation. In order to obtain a comprehensive assessment of behaviour change the data for each participant from all sources were compared and discrepancies were then followed up by re-interviewing participants. After triangulation between all sources of data, 48% of respondents had ever used a condom. Condom use in 76% of all cases was at least partly AIDS related, while 19% was exclusively for protection against HIV. Condom use tended to be sporadic: only 13% of condom users currently used a condom regularly and most of this use was for family planning. After triangulation, 45% had reduced the number of sexual partners. Of all partner reductions, 93% was at least partly AIDS related; 29% was exclusively to avoid HIV. Half of those who had reduced the number of partners either stuck to one partner or abstained. Men reported more change than women. Of those who reported no partner reduction, 89% could not reduce the number of partners because they already had only few or a single partner or abstained; most of these were women. Most of those who could change their sexual behaviour had already changed, though the degree of change (particularly condom use) was often minimal. Not only behaviour change, but also the maintenance of safe behaviour is important. Also, understanding reasons for change and extent and consistency of change are important when planning and evaluating interventions.     

Treatment of supraventricular arrhythmias with encainide

Encainide has been used to treat 230 patients with supraventricular arrhythmias, including patients with reentry supraventricular tachycardia of the atrioventricular reentry (Wolff-Parkinson-White syndrome) and the atrioventricular nodal reentry types associated with atrial fibrillation, paroxysmal supraventricular tachycardia or both, as well as incessant supraventricular tachycardia. The available data are summarized in this review. The short- and long-term response to encainide for preventing recurrence or lessening symptoms was excellent in most cases. There was little arrhythmia aggravation, and side effects, which were mostly central nervous system and visual in nature, did not cause discontinuation of the drug. Anterograde accessory pathway block was clearly an important effect. Whether retrograde block or refractoriness in the accessory pathway is the most important mechanism remains to be resolved. Pediatric patients with tachycardia-related cardiomyopathy responded well to encainide. Oral encainide's absence of effect on blood pressure or myocardial contractility is an added benefit.     

Amlodipine once a day in stable angina: Double-blind crossover comparison with placebo

Although calcium antagonists form a mainstay of therapy in patients with angina pectoris, the currently available agents have significant limitations. Nifedipine, diltiazem, and verapamil are all high-clearance agents with significant hepatic extraction and rapid clearance, leading to limited and shortlived bioavailability necessitating frequent daily administration. In contrast, amlodipine, a dihydropyridine calcium antagonist, has a long half-life of 35–50 h (compared with 3 to 4 h elimination half-life of diltiazem, verapamil, and nifedipine).¹ After oral doses, the relative bioavailability of amlodipine is high (64%) and absorption is smooth, with peak plasma levels being achieved 6–12 h postdose.¹ Bioavailability is not affected by the consumption of food.² In common with other dihydropyridine calcium antagonists, amlodipine is eliminated mainly by metabolism.³ None of the metabolites of amlodipine has significant calcium antagonist effects in humans.³ In contrast to verapamil or diltiazem, amlodipine has no effect on sinus or atrioventricular node⁴ and little or no effect on the resting heart rate.⁵ Amlodipine does not have any appreciable negative inotropic effect with the relevant clinical dose.⁶ Other clinical studies have shown amlodipine to be effective when used once-daily in chronic stable angina and vasospastic angina.⁷ Comparative studies indicate that the antianginal efficacy of amlodipine is comparable to the beta blocker nadolol⁸ and the benzothiazepine calcium antagonist diltiazem.⁹ Amlodipine has also been found to provide improved antianginal effects when combined to treatment with beta blockers and/or long-acting nitrates.^{10, 11} Treatment with amlodipine either as monotherapy or combined with other antianginal therapy for up to 26 weeks shows that efficacy is maintained, with no evidence of tolerance.¹¹ We evaluated the antianginal efficacy and safety of amlodipine in a placebo-controlled multicenter randomized crossover study in patients with chronic stable angina.     

Community attitudes towards individuals living with HIV in rural KwaZulu-Natal, South Africa

Antenatal sero-prevalence rates of 30% and more have been reported in KwaZulu-Natal since 1998 and over 50% of all adult deaths in 2000 were due to AIDS. Understanding the changing social and cultural attitudes to AIDS is important in providing contextual information to aid the design of interventions. This paper examines community attitudes towards individuals living with HIV. Eleven focus groups were conducted with men and women. Participants were asked to discuss how people living with HIV were treated within the family and community. The discussions were recorded and transcribed in isiZulu and then translated into English. These were coded using Nud*ist 6 software to identify key themes and sub-themes using content analysis. Gender and area differences were investigated. Generally participants expressed positive attitudes to the treatment of AIDS patients and felt that people living with HIV were being cared for within families. However, they reported more negative attitudes to those living with HIV by the general community and suggested these attitudes and acts of discrimination influenced disclosure. Discrimination included physical isolation and symbolism such as referring to them using a 'three finger' gesture. Participants also reported mixed responses to known HIV-positive individuals, ranging from sympathy to a lack of care, on the grounds that the person is certain to die. There are gender differences in terms of the attitudes towards people living with HIV. Compassion and hopelessness seem to be more common among women than men.