bluuebunny/crossref_metadata_2025 huggingface dataset:
A Dosing Study of Nonoxynol-9 and Genital Irritation
Authors: Roddy R E , Cordero M , Cordero C , Fortney J A
Published: January 2017

The objective of the study was to assess the symptoms and signs of genital irritation produced by different frequencies of nonoxynol-9 (N-9) use. Thirty-five women were randomized to each of 5 groups and used a vaginal suppository for 2 weeks. Group 1: N-9 once every other day; Group 2: N-9 once a day; Group 3: N-9 twice a day; Group 4: N-9 4 times a day; and Group 5: placebo 4 times a day. Study women were examined at admission, one week and 2 weeks with a colposcope for erythema and epithelial disruption, and were interviewed about vaginal itching and burning. The rates of reported symptoms for N-9 users were not significantly different from that of placebo users. The rate of epithelial disruption for women using N-9 every other day was essentially the same as that of women using placebo. The rates of epithelial disruption for women using N-91/day and 2/day were 2.5 times greater than that of placebo users. The rate of epithelial disruption for women using N-9 4/day was five times greater than that of placebo users. Genital irritation was located primarily on the vagina or cervix, and vulvitis was not a significant problem. Women who infrequently use N-9 products may not experience an increase in genital irritation. Women who choose to use N-9 frequently may experience an increase in epithelial disruption.
The Suppressive Effect of Serum Samples from Patients with Chancroid on Human Mononuclear Cells Correlates with the Clinical Picture and is Interleukin-2-Dependent
Authors: Korting H C , Zaba R , Ballard R C , Abeck D
Published: January 2017

Plasma samples from patients with chancroid diagnosed both on clinical and microbiological grounds were assessed for their ability to inhibit mitogen-induced proliferation of human lymphocytes from healthy donors. All serum samples analysed suppressed phytohaemagglutinin A (PHA) blastogenic response. A significant difference in the observed extent was seen when serum samples from patients with and without associated lymphadenopathy were compared ( P < 0.05). Using an interleukin-2 (IL-2)-dependent cell line it could be demonstrated that the addition of patients' plasma to cultured cells markedly depressed mitogen-induced IL-2 synthesis. Results presented suggest that cell-mediated mechanisms play a role in the pathogenesis of infection due to Haemophilus ducreyi.
Concurrent Partnerships Could Cause AIDS Epidemics
Authors: Hudson Christopher P.
Published: January 2017

There is a need for new hypotheses to supplement existing explanations for the observed differences in HIV prevalence between countries and within countries. Due to high levels of viraemia during the initial phase of HIV infection, networks of concurrent regular partnerships in a community could be the determining factor in the development of an AIDS epidemic. If this hypothesis is true, projections of the future development of the epidemic could be altered. Simple health education messages based on the hypothesis might make a major contribution to the prevention and control of AIDS epidemics.
Clinical Management of HIV Disease in Intravenous Drug-Users
Authors: Sherrard J S , Bingham J S , Onen T S
Published: January 2017

Intravenous drug-users comprise a major group of HIV-infected individuals in the developed world and, whilst progression of HIV disease in them appears little different from other risk groups, their medical presentations may be altered by continuing drug use. Drug-users are particularly susceptible to bacterial infections irrespective of their HIV status; they may present with symptoms directly caused by their drugs, which can be difficult to differentiate from non-drug-related causes and may closely resemble symptoms directly attributable to HIV. In addition, the life style associated with drug use can make compliance difficult, but in clinics combining HIV care and methadone prescribing these problems can be overcome.
Assessing Statistics for the Measurement of Workload at a Genitourinary Medicine Clinic
Authors: Williams P
Published: January 2017

Since January 1985 James Pringle House, the genitourinary medicine (GUM) clinic at London's Middlesex Hospital, has built up an extensive computerized patient database. Yearly statistics relating to 1) individual patients, 2) diagnoses, 3) attendances, and 4) an activity estimator (combining features of attendances and their corresponding diagnoses) are extracted. Each is assessed as a potential tool for quantifying the rising workload associated with the clinic's increased staffing levels and expanded services. Only the activity estimator identifies an upward trend, rising 26.3% from 1985–86 to 1991–92, caused largely by human immunodeficiency virus (HIV) and hepatitis B related attendances. This activity estimator could provide the basis for a workload reporting facility on all GUM computer systems.

The 4 statistics exhibit other useful information, including a 21.0% rate of non-attendance (a substantial hidden addition to workload) and a strong allegiance to the clinic from patients residing outside of the local Health Authority region.
Endemic versus Non-Endemic Gonorrhoea in Stockholm: Results of Contact Tracing
Authors: Rudén A-K , Jonsson A , Lidbrink P , Allebeck P , Bygdeman S M
Published: January 2017

The aim of the present study was to characterize endemic versus non-endemic gonorrhoea to identify risk groups for transmission and to evaluate the effects of intensified contact tracing performed by specially trained social workers at venereal clinics. A total of 671 gonorrhoea patients (283 women and 388 men) comprised the study group. Seventy percent of the women and 48% of the men had an endemic infection ( P<0.001). Men without a steady partner had an increased risk of non-endemic infection.

A decrease from 75% to 40% was noted in the proportion of endemic infection in Stockholm from the first quarter of the study period (2 years) to the last.

Contact tracing resulted in 1.2 identified partners per patient. A total of 736 partners were examined either as a result of contact tracing efforts or because they had sought medical care on their own prior to intervention. Forty-seven percent of these partners were infected, 44% were not infected and 9% were examined outside the study with results unknown to us. The partner notification efforts yielded 161 new untreated cases. Contact tracing of women generated one new case per 4.0 interviewed women and contact tracing of men one new case per 4.3 interviewed men. Interviewing index patients with endemic infection yielded the highest number of new cases.

Forty-three percent of the patients were infected outside Stockholm but only a smaller part of these patients spread their infection further into the community.

The experiences of the contact tracing and analysis of risk factors for transmission of gonorrhoea provide valuable knowledge that can be used to discourage spread of gonorrhoea.
Anti-Bovine Viral Diarrhoea Virus Antibodies in Adult Zambian Patients Infected with the Human Immunodeficiency Virus
Authors: Giangaspero M , Vacirca G , Morgan D , Baboo K S , Luo N P , DuPont H L , Zumla A
Published: January 2017

Bovine viral diarrhoea (BVD) virus is a cosmopolitan pestivirus of animals which is associated with diarrhoea, immunosuppression and synergy with other pathogens. This study was conducted to establish the prevalence of anti-BVD virus antibodies in healthy Zambian adults and those with asymptomatic and symptomatic HIV disease. Sera from 1159 adults were tested for anti-BVD virus antibodies using the indirect immunofluorescence test and the confirmatory Western blot. Of the 1159 sera examined, 180 (15.5%) showed significantly elevated titres of anti-BVD antibodies. These included 70 out of 477 (14.7%) HIV-negative healthy adults; 73 out of 480 (15.2%) of HIV-positive asymptomatic individuals; 23 out of 129 (17.8%) HIV-seropositive patients with associated illnesses excluding diarrhoea; and 14 out of 73 (19.2%) of HIV-seropositive patients with chronic diarrhoea. HIV-seropositive patients with chronic diarrhoea or associated illnesses appear to have significantly increased seroprevalence of anti-BVD virus antibodies ( P = >0.01). The mechanism of interaction between BVD virus and HIV infections and the synergistic effects with other opportunistic pathogens in humans requires definition.
Why Do Condoms Break or Slip off in Use? An Exploratory Study
Authors: Richters Juliet , Gerofi John , Donovan Basil
Published: January 2017

Men attending 3 sexually transmissible disease clinics and a university health clinic in Sydney, Australia, were invited to complete a questionnaire on their use of condoms. Respondents were 108 male condom user volunteers aged 18 to 62 years; in the last five years 47 had had sex with men, 18 with both men and women and 43 only with women. They reported using a total of 4809 condoms in the previous 12 months (condoms worn by a male partner were not included). The overall breakage rate was 4.9% (including condoms breaking during application), while 3.1% of condoms reportedly slipped off. On a multivariate analysis, condom breakage correlated with: (1) male sexual partner(s), (2) infrequent condom use, (3) rolling the condom on as per conventional instructions (modified application methods appeared protective) and (4) having trouble with condoms partially slipping. Factors associated with condoms slipping off were (1) young age, (2) being circumcised, (3) having less life-time condom experience, (4) roiling the condom on conventionally, and (5) having trouble with condoms partially slipping. Few men used inappropriate lubricants and no association between lubricant type and breakage was found. Though common among our respondents, negative attitudes towards condoms, loss of erection during condom application or use, finding condoms uncomfortable, and prolonged sexual intercourse were not related to success in use. Almost half (49%) of the men reported having deliberately removed a condom after the beginning of intercourse; 17% had done so 3 or more times. Counselling protocols should acknowledge the complexity of condom use. As no single easily corrected factor was found to correlate with condoms breaking or slipping off, the development of stronger and better retained products should be encouraged. The validity of conventional instructions for applying condoms should be questioned.
Sexual Behaviour in the City of Lisbon
Authors: Amaro Fausto , Dantas Ana M. , da Cunha Teles Louise
Published: January 2017

This study of sexual behaviour in the city of Lisbon is based on data obtained from 2 random samples, one of individuals aged 16–20 ( n = 400) and another of individuals over the age of 20 ( n = 400). Samples have been stratified by district, gender and age. Data were obtained by personal interview and by questionnaires completed confidentially by the interviewees.

The data include the age of first sexual intercourse, the number of sexual partners, the prevalence of casual relations and the type of sexual practices according to sex and age group. Results show that despite the high risk of exposure to HIV in a significant percentage of the population, AIDS is seen as a personal threat by only 20% of the population. Six per cent of the adults (aged 21 and over) and 12% of the young people (16–20) replied that they had not yet considered the problem; 73.5% of the adults and 67.4% of the young people stated that they did not feel threatened by the disease. Data suggest that the differences between men and women have decreased.

Among the sexually active population, only 12% of individuals under 21 and 8% of the adults use condoms regularly. The awareness of infidelity among couples is much lower than in reality. A significant discrepancy was found between the ‘awareness' and ‘reported reality’ for men and women who carry on casual extramarital relations: 14.9% of the women were convinced that their husbands or companions are unfaithful; 27.7% of the men reported they had been unfaithful in the years preceding the study; 3.7% of the men believed their wives had been unfaithful, whereas 8.9% of the women admitted to having been unfaithful over the same period.

Data on sexual initiation reveal that contrary to young people (3.5%), 25.0% of the men over 20 begin their sexual life by resorting to prostitutes.

At least one of the following behaviours can be attributed to two-thirds of the adults (21 and over) in the year preceding the study; extramarital relations; 2 or more sexual partners; did not use condoms; sexual relations with prosititutes, sexual relations with people whose sexual past they did not know.

In conclusion, our study illustrates that the pattern of sexual behaviour in this population is associated to a significant risk of exposure to HIV and that a marked unawareness of such risk prevails. The differences in sexual behaviour patterns between men and women and between young and older people are important to formulate appropriate educational programmes.
Experience of HIV Disease in a London District General Hospital
Authors: Coker R J , Desmond N , Poznansky M , Smith C , Shafi M S , Bell D , Riordan J F , Murphy S
Published: January 2017

The aim of this paper is to describe and discuss the experience of HIV disease in Central Middlesex Hospital, London up to June 1993. A retrospective study of the total number of HIV-positive patients cared for was performed. In addition, prospectively collected data as part of local epidemiological surveillance from January 1987 to June 1993 on all HIV test requests was analysed. Between January 1987 and June 1993 3695 individuals were tested for HIV-1 antibody at Central Middlesex Hospital. Of these, 101 HIV-1 seropositive individuals were identified and have attended this District General Hospital. Seven HIV-1 seropositive individuals were identified from before December 1986. Sixty (56%) had acquired their infection heterosexually. Thirty-eight (35%) originated from the UK and 47 (44%) from sub-Saharan Africa; the remaining 23 (21%) originated from the rest of Europe, South America and the Caribbean. Thirty-four (31%) of the patient group developed AIDS during follow-up at the hospital and in 26 individuals AIDs developed within 2 months of their first positive HIV result. The mean survival of 20 patients after AIDS-defining diagnoses was 7 months 18 days. This unselected group of HIV-1 seropositive patients present late in the course of their HIV disease and survival following AIDS is poor.
Cervical Cytological Screening in HIV-Infected Women in Dublin—A Six-Year Review
Authors: Murphy M , Pomeroy L , Tynan M , Murphy J F , Mulcahy F M
Published: January 2017

A retrospective study of the results of cervical cytological screening of HIV-infected women attending an inner city ambulatory HIV clinic over a 6-year period between 1987 and 1992 was carried out. During this time a total of 165 HIV-infected women attended for management of their HIV disease. The results of cervical cytological specimens (smears) were available in 136 (82.4%) women. The risk categories for HIV infection of these 136 women were intravenous drug use 110 (80.9%), heterosexual sex 24 (17.6%) and undetermined 2 (1.5%). Eighty-five (62.5%) of the 136 women were classified CDC group 2, 30 (22%) CDC group 3, and 21 (15.5%) CDC group 4 at the time of initial cytological screening. Forty-one (30.1%) women had mild dysplasia/CIN 1, 21 (15.4%) had moderate dysplasia/CIN 2 and 17 (12.5%) had severe dysplasia/CIN 3. The overall prevalence of dysplasia/CIN was 58.1%. Twenty-seven (34.2%) of the women with dysplasia/CIN had cytological evidence of human papillomavirus infection. No association between the clinical stage of HIV disease and the presence or degree of dysplasia/CIN was demonstrated. Women with cytological evidence of CIN were significantly more likely to have had genital warts than those with no evidence of CIN (OR 3.1, CI 1.1–10). In those women with cervical dysplasia who underwent colposcopic examination, CIN was confirmed in a high proportion of cases. The default rate from colposcopy, however, was high (35.4%).
The Activity of Candidate Virucidal Agents, Low pH and Genital Secretions against HIV-1 In Vitro
Authors: O'Connor T J , Kinchington D , Kangro H O , Jeffries D J
Published: January 2017

The effect of low pH, normally present in the female genital tract, on HIV viability was examined. HIV is more acid stable than previously reported with no substantial reduction in infectivity occurring until pH levels are reduced below 4.5. The virucidal activity of 3 topical spermicides and chlorhexidine was assessed in vitro using previously established and newly modified assay systems. None of the agents tested had a selectivity index (SI) greater than 5.2. Semen and cervical secretions were assessed for their ability to inhibit HIV-1. While no virucidal effect was found in the latter, seminal fluid was found to have significant activity against HIV-1 and a SI of approximately 50.
HIV Seroprevalence in Healthy Blood Donors in Northeastern Zaire
Authors: Fischer Philip R , Toko Remy M
Published: January 2017

Despite high seroprevalence rates in some parts of Africa, there is notable variation in prevalence between population subgroups. To document changes and trends in HIV seroprevalence in northeastern Zaire, 1989 to 1992 blood donor data were reviewed. Overall, 2453 donors were tested with seropositivity varying from 2.8% in 1989 to 6.9% in 1992. The increase in seropositivity was significant for men (2.5 to 5.8%, P = 0.017) and for people residing in rural areas (2.0 to 6.1%, P = 0.0008) but not for women (5.4 to 8.6%, P = 0.15) nor for urban individuals (10.5 to 8.6%, P = 0.55). These findings suggest that: 1) HIV infection is spreading in previously less-affected population subgroups rather than increasing widely in the entire population, 2) the HIV epidemic could be reaching a plateau or endemic phase in northeastern Zaire, and, 3) continued blood donor screening and wise transfusion practices are needed.
Patients Misrepresenting Their Risk Factors for AIDS
Authors: Brody Stuart
Published: January 2017

To determine the truthfulness of patients' and research subjects' self-reports of their sexual and drug use histories in studies of human immunodeficiency virus (HIV) transmission and acquired immunodeficiency syndrome (AIDS) risk factors, studies of or pertinent to lying about AIDS risk factors were extracted from MEDLINE and PSYCLIT. The present paper describes normal and pathological motives for misrepresenting risk factors, and reviews the literature on such underreporting. There is much evidence for lying about anal intercourse and intravenous drug use risk factors, implying that the estimates of risk for vaginal transmission of HIV (particularly in Pattern-I industrialized countries) have been inflated. Research on HIV/AIDS behavioural risk factors must include sophisticated methods for the assessment of self-report validity, such as the use of behavioural markers, improved lie scales and interview methods, and physical methods.
Preoperative HIV Antibody Testing: The Views of Surgeons and Patients
Authors: Meadows Jean , Irving Gillian , Chapman Kate , Gazzard Brian , Catalan Jose
Published: January 2017

Fifty surgeons and 72 preoperative patients in 2 central London hospitals were asked their views on preoperative HIV antibody testing, who is at risk of HIV infection and HIV test counselling. A substantial proportion of both surgeons and preoperative patients, 48% and 54% respectively, supported compulsory HIV antibody testing without patient consent. They believed this should occur as a routine practice prior to surgery. However, surgeons and patients differed in the preoperative patients to be considered for such testing. All surgeons advocating compulsory testing believed that it was only necessary for those patients belonging to high risk groups whilst preoperative patients believed that all patients should be HIV tested prior to surgery. Surgeons and patients also differed in their views on who was at risk of HIV infection. Surgeons believed those at risk to be members of identifiable risk groups whilst patients believed everyone was at risk, especially those engaging in high risk behaviours. Finally, when asked which health professionals they thought should be involved in HIV test counselling, both surgeons and patients agreed that hospital doctors, including surgeons themselves, should take on the responsibility of test counselling. The implications of this and routine HIV antibody testing are discussed.
Energy from the Wind
Authors: Dawber K.R.
Published: January 2017

A general overview of wind energy conversion is given and the case for greater world use of wind turbines for the generation of electricity is presented. It is argued that the environmental impact of wind energy conversion on a large scale is likely to be small in most respects, although not visually, and is likely to be acceptable to most communities. A review of the present status of wind turbine manufacturing and pricing is given. Installation prices and operating costs now appear to be close to those of other forms of electricity generation, provided large accessible high wind sites are used. It is suggested that there is a need for continued financial support for wind energy research and development.
The Contribution of Solar Architecture to Energy Saving and Quality of Living.
Authors: Gruber Edelgard , Reichert Jürgen
Published: January 2017

A demonstration project with 22 solar houses funded by the Ministry of Research and Technology was carried out in order to study the contribution of solar energy use to the room heating under the climatic conditions of the Federal Republic of Germany. Measurements of energy flows over three years and interviews with the inhabitants have shown that an excellent heat insulation is the most effective measure. Solar components such as large south-faced glazings can contribute a small part to the energy savings if they are adequately designed and used. The most important benefit of solar houses is that they cause a high quality of living. Heating behaviour and ventilation has a large influence on energy consumption. The handling of solar houses must not be very difficult. With the help of “intelligent” heating and controlling systems many functions can be performed automatically.
Heat Exchangers for Waste-Heat Recovery
Authors: Al-Rabghi O.M. , Akyurt M. , Najjar Y.S.H. , Alp T.
Published: January 2017

A survey is made of the equipment used for heat recovery and utilization. Types and merits of commonly employed heat exchangers are presented, and criteria for selecting heat exchangers are summarized. Applications for waste heat recovery are emphasized. It is concluded that careful selection and operation of such equipment would be expected to result in energy savings as well as problem-free operation.
Preclinical toxicology of a novel polymeric antitumour agent: HPMA copolymerdoxorubicin (PK1)
Authors: Duncan R , Coatsworth J K , Burtles S
Published: January 2017

N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-doxorubicin (PK1) is a novel polymeric anticancer agent containing doxorubicin (approximately 8 wt%) bound to the polymer backbone via a Gly-Phe-Leu-Gly peptidyl linker. The approximate LD50 of PK1 in MF1 mice after a single i.v. injection was 63 mg/kg (doxorubicin-equivalent). Single doses of PK1 were administered to MF1 mice at 22.5 or 45 mg/kg and blood samples taken on days 3, 7 and 14 for haematological examination and clinical chemistry. At day 14 all animals were sacrificed for necropsy. In a multiple dose study, PK1 was administered i.v. to MF1 mice or Wistar rats (20 animals per group) weekly for five consecutive weeks at doses of 12.0 or 22.5 mg/kg (mice) or 3 and 5 mg/kg (rats). After 31 days 10 animals from each group were sacrificed for necropsy and the remainder were sacrificed after 59 days. Blood samples were taken 3 days after administration of each dose and at the end of the experiment, and urine samples were collectedonthe day prior to sacrifice.Mortality inthe single dose mouse and multiple dose rat studies was low. In the multiple dose mouse study 4/10 animals were killed in extremis before the scheduled day 31 and all animals died before day 37. PK1 induced a reduction in WBC and platelets in rats and mice shortly after treatment and RBC at later times, and in the single dose study alanine and aspartate aminotransferase levels were elevated at higher doses. Liver damage was seen only in rat tissue during histological examination. Other histological changes induced by PK1 include thymic and testicular atrophy, bone marrow depletion gastrointestinal tract changes and in the multiple dose study an increase in nuclear size in the proximal tubules of the kidney (although no changes in urine were seen). Recovery from these effects was seen in rats at 59 days. A PK1 dose of 20 mg/m2 (doxorubicin equivalent) was recommended as a safe dose for the start of Phase I clinical trials.
Enzyme-based assay for quantification of paraoxon in blood of parathion poisoned patients
Authors: Eyer Florian , Eyer Peter
Published: January 2017

1 Paraoxon concentration was estimated by means of inhibition kinetics observed with electric eel acetylcholinesterase (AChE) which was determined by a modified Ellman procedure. In human plasma, paraoxon was stabilized by inactivation of paraoxonase with EDTA and aluminon and by inhibition of butyrylcholinesterase with ethopropazine. Paraoxon (1-50 ng) was recovered at 86+1.7% (mean+s.e.m.) in ether extracts from 0.5 ml samples of spiked stabilized plasma. It could be stored without loss at 7208C for at least 1 month.

2 The enzyme-based assay was applied to follow the paraoxon plasma concentrations in three suicidal patients with severe parathion poisoning. In poisoning with excessive doses and initial paraoxon concentrations above 500 nM, therapeutic obidoxime concentrations of approximately 10 mM failed to essentially reactivate erythrocyte AChE in vivo, while reactivat-ability ex vivo was nearly complete. With the plasma concentrations of paraoxon dropping below 100 nM, however, reactivation by obidoxime became signifi-cant. Unexpectedly, paraoxon levels occasionally re-increased during treatment and resulted in re-inhibition of AChE, bearing some resemblance to the Intermediate Syndrome.

3 The paraoxon concentrations measured fitted satisfactorily the values calculated from the kinetic constants previously obtained for AChE inhibition and obidoxime-induced reactivation in vitro. This indicates that diethylphosphoryloxime formation during obidoxime-induced reactivation does not markedly contribute to the re-inhibition of AChE as observed in vitro.
Microsomal metabolism of carbamazepine and oxcarbazepine in liver and placenta
Authors: Myllynen P , Pienimäki P , Raunio H , Vähäkangas K
Published: January 2017

Metabolism of both carbamazepine (CBZ) and oxcarbaze-pine (OCBZ) were catalyzed by human liver microsomes and microsomes from livers of CBZ-induced or non-induced C57BL/6 mice. Human placental microsomes metabolized only OCBZ. Mouse liver microsomes metabolized CBZ to carbamazepine-10,11-epoxide (CBZ-E), 10- hydroxy-10,11-dihydro-carbamazepine (10-OH-CBZ), 3- hydroxy-carbamazepine (3-OH-CBZ), 10,11-trans-dihydroxy-10,11-dihydro-carbamazepine (10,11-D) and to an unidentified metabolite. CBZ-pretreatment of mice increased both ethoxyresorufin O-deethylase activity in the liver and the amount of CBZ-E in microsomal incubations regardless of the age of mice.

Human liver microsomes catalyzed the formation of CBZ to 9-hydroxymethyl-10-carbamoyl acridan (9-AC) in addition to CBZ-E, 3-OH-CBZ and 10-OH-CBZ. OCBZ was metabolized to its active metabolite in all incubations. An unknown metabolite was also present in some of the incubations. Human liver microsomes catalyzed only minute covalent binding of CBZ and OCBZ to DNA. Binding of OCBZ was, however, one order of magnitude greater than binding of CBZ. Human placental micro-somes from the mothers on CBZ therapy did not catalyze CBZ metabolism. The same microsomes catalyzed OCBZ metabolism to 10-OH-CBZ and to an unknown metabolite.

These results indicate autoinduction in CBZ metabolism in mouse liver. Due to the higher binding of OCBZ than CBZ to DNA in vitro, further studies on the potential mutagenicity of OCBZ may be warranted.
Determination of glutathione S-transferase μ and τ polymorphisms in neurological disease
Authors: Stroombergen Maudy CMJ , Waring Rosemary H
Published: January 2017

1 Correlations between deletions in two glutathione S-transferase (GST) genes, GSTM1 and GSTT1 and susceptibility to Alzheimer's disease (AD), motor neuron disease (MND) and Parkinson's disease (PD) have been investigated by PCR, using primers specific for both genes.

2 It was found that males with a deletion of the GSTM1 gene were more susceptible to PD and males with a deletion of the GSTT1 gene more susceptible to MND and PD, possibly implying that environmental factors which specifically target men may be involved. Furthermore, subjects with a deletion of the GSTT1 gene were more susceptible to AD.
IGF-I in experimental daunorubicin-induced cardiomyopathy in rabbits
Authors: Geršl V , Cerman J , Šuba P , Mazurová Y , Hrdina R , Macháčková J
Published: January 2017

1 The occurrence of IGF-I was investigated in rabbits with experimentally daunorubicin-induced cardiomyopathy. IGF-I was measured in the heart, serum, liver and skeletal muscle.

2 A significant increase in the IGF-I was found in the left heart ventricle in daunorubicin cardiomyopathy (152.9±10.0 ng/g vs 95.1±4.2 ng/g in the control group). This site of increased IGF-I activity corresponded well with the maximum of morphological changes (dispersed cytolysis of cardiomyocytes mostly without developed subsequent interstitial myofibrosis).

3 The highest levels of IGF-I were present in right and left cardiac atrium (but without significant differences between the groups). Furthermore, in skeletal muscle, the levels of IGF-I in the daunorubicin group (839.0±142.1 ng/g) were significantly higher in comparison with the control group (482.5±83.1 ng/g).

4 The level of IGF-I in the left ventricle in the daunorubicin group (but not in the control group) was significantly higher than that in the liver. There were no correlations observed between the levels of IGF-I in the heart and in the serum.

5 The increase in IGF-I concentrations in the left heart ventricle after the administration of daunorubicin may thus reflect possible autocrine/paracrine role of IGF-I in cardiomyopathy.
The toxicity of cyanobacterial toxins in the mouse: II Anatoxin-a
Authors: Fawell J K , Mitchell R E , Hill R E , Everett D J
Published: January 2017

Blooms of cyanobacteria are known to have caused poisoning in fish, waterfowl, animals and man. One of the low molecular weight toxins responsible for this is the neurotoxin anatoxin-a which has been detected in reservoirs used for domestic water supplies. While the acute behaviour of this alkaloid is clear, there is uncertainty regarding the effects on man of ingestion of anatoxin-a at low levels over longer periods. In order to assess this risk, a series of in vitro and in vivo experiments were undertaken to investigate the pharmacology, sub-acute toxicity, and the teratogenicity of anatoxin-a in the mouse. The results of this work were as follows: (1) Pharmacological screening studies confirmed that anatoxin-a is a potent nicotinic agonist which can produce neuromuscular blockade and death by respiratory arrest. Recovery from a single sub-lethal dose is rapid and complete; (2) Repeated sub-lethal oral administration over 28 days in the mouse did not produce any reliable evidence of treatment-related toxicity; (3) From a preliminary screening study anatoxin-a does not appear to be a developmental toxicant in the mouse. These results indicate that a guideline value for anatoxin-a in drinking water of 1 μg l-1 would provide an adequate margin of safety.
Functional impairment of blood-brain barrier following pesticide exposure during early development in rats
Authors: Gupta Alka , Agarwal Renu , Shukla Girja S
Published: January 2017

1 The effect of certain pesticides on the functional integrity of the developing blood-brain barrier (BBB) was studied following single and repeated exposure, and after subsequent withdrawal in rats.

2 Ten-day-old rat pups exposed orally to quinalphos (QP, organophosphate), cypermethrin (CM, pyre-throid) and lindane (LD, organochlorine) at a dose of 1/50th of LD50, showed a significant increase in the brain uptake index (BUI) for a micromolecular tracer, sodium fluorescein (SF), by 97, 37 and 72%, respectively, after 2 h. Residual increases in the BUI were found even after 3 days of the single treatment of QP (28%) and LD (23%).

3 Repeated exposure for 8 days (postnatal days (PND) 10-17) with QP, CM and LD increased the BBB permeability by 130, 80 and 50%, respectively. Recovery from these changes was complete in QP and LD-treated animals after 13 days (PND 18-30) of withdrawal. However, CM showed persistent effects that were normalized only after 43 days (PND 18-60) of withdrawal.

4 A single dose reduced to 1/100th of LD50 also increased BUI in 10-day-old rat pups following QP (20%) and CM (28%) exposure at 2 h.

5 An age-dependent effect of these pesticides was evident from the study showing higher magnitude of BUI changes in 10-day-old rats as compared to that in 15- day-old rats. Furthermore, adult rats did not show any effect on BBB permeability even at a higher dose (1/25th of LD50) of these pesticides given alone or in combination with piperonyl butoxide (600 mg/kg, i.p.) for 3 consecutive days.

6 This study showed that developing BBB is highly vulnerable to single or repeated exposure of certain pesticides. The observed persistent effects during brain development even after withdrawal of the treatment may produce some neurological dysfunction at later life as well.
Influence of uranium(VI) speciation for the evaluation of in vitro uranium cytotoxicity on LLC-PK1 cells
Authors: Mirto H , Barrouillet M P , Hengé-Napoli M H , Ansoborlo E , Fournier M , Cambar J
Published: January 2017

Very few data are available concerning the in vitro toxicity of uranium. In this work, we have determined the experimental chemical conditions permitting the observation of uranium(VI) cytotoxicity on LLC-PK1 cells. Uranium solutions made either by dissolving uranyl acetate or nitrate crystals, or by complexing uranium with bicarbonate, phosphate or citrate ligands, were prepared and tested. Experiments demonstrated that only uranium solutions containing citrate and bicarbonate ligands concentrations tenfold higher than the metal, were soluble in the cell culture medium. Cytotoxicity studies of all these uranium compounds were performed on LLC-PK1 cells and compared using LDH release, neutral red uptake and MTT assays. Dose dependent cytotoxicity curves were only obtained with uranium-bicarbonate medium. This study has revealed a toxicity of uranium-bicarbonate complexes for 24 h expositions and for concentrations ranging from 7×10-4- 10-3 M, under these conditions, the CI50 (cytotoxicity index) was evaluated between 8.5 and 9×10-4 M. In contrast, we noticed a lack of cytotoxicity response for uranium(VI)-citrate complexes. Electron transmission microscopy studies revealed, when LLC-PK1 cells were exposed to the uranium-bicarbonate system, that uranium penetrated and precipitated within the cytoplasmic compartment. Morphological studies conducted with citrate complexes did not show any cellular intake of uranium.
An asymptotically unbiased estimator of exposed versus non-exposed odds ratio from reported dose-response data
Authors: Tan Frans ES , Zeegers Maurice PA
Published: January 2017

Summary effect measures in meta-analysis of published epidemiological cohort or case control studies are often based on odds ratios reported for several exposure levels with varying arrangements and number of levels across primary studies. Usually only two-way contingency tables together with exposure specific adjusted odds ratios and corresponding standard errors are presented in articles. An asymptotically unbiased estimate of exposed versus non-exposed adjusted odds ratio from reported dose-response data is proposed. This estimate is based on the weighted sum of the exposure specific odds ratios, with the prevalences of the control group as weights. Large sample variance is derived accounting for the dependency between exposure specific adjusted odds ratios. The exposed versus non-exposed adjusted odds ratio could then be used in systematic reviewing.
Adaptive designs for binary treatment responses in phase III clinical trials: controversies and progress
Authors: Biswas Atanu
Published: January 2017

In phase III clinical trials the problem is to compare two treatments or therapies for their effects. The randomized 50: 50 allocation to the two competing treatments is popular in most of the cases. In contrast there is a class of adaptive designs available in literature for this purpose. The object is to treat a larger number of patients by the eventual better treatment. A few such adaptive designs were conducted out in practical applications and consequently a lot of controversy arose. In spite of that there is steady theoretical progress in this area over the past three decades. The present paper reviews some of the real-life adaptive clinical trials and discusses some logistics of such trials.
Non-normal variation and regression to the mean
Authors: Chesher Andrew
Published: January 2017

Non-normal variation across repeated measurements leads to nonlinear and heteroskedastic regression to the mean unlike the simple linear and homoskedastic regression to the mean found in normal models. This paper investigates the nature of the regression to the mean phenomenon in non-normal settings using (a) small variance approximations and (b) exact results obtained using normal mixtures to approximate non-normal distributions.
Using regression models for prediction: shrinkage and regression to the mean
Authors: Copas J B
Published: January 2017

The use of a fitted regression model in predicting future cases, either as a diagnostic tool or as an instrument for risk assessment is discussed. The regression to the mean effect implies that the future values of the response variable tend to be closer to the overall mean than might be expected from the predicted values. The extent of this shrinkage is studied for multiple and logistic regression models, and is found to be related to simple goodness-of-fit statistics of the original regression. Shrinkage is a particularly serious problem if the sample size is small and/or the number of covariates is large. Shrinkage of predictors is illustrated by two examples. A more general formulation is suggested.
Uncovering the effects of smoking: historical perspective
Authors: Doll Richard
Published: January 2017

Tobacco was introduced into Europe from America at the end of the fifteenth century. At first used primarily for medicinal purposes it came to be burnt in pipes for pleasure on a large scale nearly 100 years later, at first in England and subsequently in Europe and throughout the world. Pipe smoking gave way to the use of tobacco as snuff and, in turn, to cigars and cigarettes at different times in different countries until cigarette smoking became the dominant form in most of the developed world between the two world wars. Societies were formed to discourage smoking at the beginning of the century in several countries, but they had little success except in Germany where they were officially supported by the government after the Nazis seized power.

In retrospect it can now be seen that medical evidence of the harm done by smoking has been accumulating for 200 years, at first in relation to cancers of the lip and mouth, and then in relation to vascular disease and cancer of the lung. The evidence was generally ignored until five case-control studies relating smoking to the development of lung cancer were published in 1950. These stimulated much research, including the conduct of cohort studies, which, by the late 1950s, were beginning to show that smoking was associated with the development of many other diseases as well. The interpretation that smoking caused these various diseases was vigorously debated for some years but came to be generally accepted in respect of lung cancer by the late 1950s and of many other diseases in the subsequent two decades.

Cigarette smoking has now been found to be positively associated with nearly 40 diseases or causes of death and to be negatively associated with eight or nine more. In some instances the positive associations are largely or wholly due to confounding, but the great majority have been shown to be causal in character. The few diseases negatively associated with smoking are for the most part rare or nonfatal and their impact on disease incidence and mortality as a result of smoking is less than 1% of the excess of other diseases that are caused by smoking. The most recent observations show that continued cigarette smoking throughout adult life doubles age-specific mortality rates, nearly trebling them in late middle age.

All the diseases related to smoking that cause large numbers of deaths should now have been discovered, but further nonfatal diseases may remain to be revealed by cohort studies that are able to link individuals' morbidity data with their personal characteristics.
Securing the Anthropocene? International policy experiments in digital hacktivism: A case study of Jakarta
Authors: Chandler David
Published: January 2017

This article analyses security discourses that are beginning to self-consciously take on board the shift towards the Anthropocene. It first sets out the developing episteme of the Anthropocene, highlighting the limits of instrumentalist cause-and-effect approaches to security, which are increasingly becoming displaced by discursive framings of securing as a process generated through new forms of mediation and agency and capable of grasping interrelations in a fluid context. This approach is the methodology of hacking: creatively composing and repurposing already existing forms of agency. It elaborates on hacking as a set of experimental practices and imaginaries of securing the Anthropocene, using as a case study the field of digital policy activism with a focus on community empowerment through social-technical assemblages being developed and applied in ‘the City of the Anthropocene’: Jakarta, Indonesia. The article concludes that policy interventions today cannot readily be grasped in modernist frameworks of ‘problem solving’ but should be seen more in terms of evolving and adaptive ‘life hacks’.
Joseph Henry Green (1791–1863): Surgeon, Philosopher and Coleridgean Transcendentalist
Authors: Sheldrake John S
Published: January 2017

This article examines the life and work of the eminent surgeon and philosopher Joseph Henry Green. It details the influence on his literary output of his close friend Samuel Taylor Coleridge and shows the ways in which transcendental philosophy underpinned his scientific outlook.
John Darwall, MD (1796–1833): The Short Yet Productive Life of a Birmingham Practitioner
Authors: Reinarz Jonathan , Williams Andrew N
Published: January 2017

This paper summarizes the life and work of John Darwall, a Birmingham physician whose work helped develop several fields of medicine, including occupational health, medical journalism and paediatrics.
The Rod of Aesculapios: John Haygarth (1740–1827) and Perkins' Metallic Tractors
Authors: Booth Christopher
Published: January 2017

James Gillray's cartoon Metallic Tractors, published in 1801, portrays Benjamin Perkins treating a boil on the nose of an alcoholic John Bull with a pair of metallic tractors. The tractors had been invented by his father, Elisha Perkins of Connecticut, and were supposed to relieve pain and other symptoms through the agency of animal magnetism. The tractors were revealed as nothing more than an expensive sham by Dr John Haygarth in Bath, who showed that wooden tractors were equally effective. Thus, he was one of the first to use a placebo in a single-blind clinical trial.
The Personality and Health of King Henry VIII (1491–1547)
Authors: Keynes Milo
Published: January 2017

The projection of Henry VIII in the first half of his reign, which began in 1509, is of a magnificent and accomplished ‘imperial prince’, the possessor of superb physical health. In 1528, when aged 37, he showed a marked change in personality due, it is here argued, to depressive illness, from which he recovered by the mid-1530s. Such ill health has not been recognized previously and it engenders a need for a reassessment of his character and actions during these years of illness. He did not suffer from syphilis and the well-known leg ulcers were less incapacitating than has been described in the past. This truly enormous and overweight man was 55 years old when he died in 1547 in chronic heart failure.
A Modified Serum Neutralization Test for the Detection of Antibody to Porcine Reproductive and Respiratory Syndrome Virus in Swine Sera
Authors: Yoon J. , Joo Han S. , Goyal Sagar M. , Molitor Thomas W.
Published: January 2017

Various conditions were evaluated and modified to improve the sensitivity of the serum neutralization (SN) test for detecting antibody in pigs infected with porcine reproductive and respiratory syndrome virus (PRRSV). Higher SN titers were consistently obtained by the addition of 20% fresh swine serum to the virus diluent and by the use of a permissive cell clone (MARC-145) derived from the MA-104 cell line. Test sera used to assess the SN test were obtained from 2 groups of 3-week-old pigs infected intranasally with PRRSV (MN-1b). Using the modified method, SN antibody was first detected 9–11 days postinoculation (PI), with a peak evident at 11–21 days PI. The antibody subsequently declined, and a second peak was observed between 41 and 45 days PI. The first antibody peak was not observed and the SN antibody was only detectable between 32 and 41 days PI when the test was done with 20% heated swine serum or without supplemental swine serum. The SN antibody during 2–3 weeks PI was found to be sensitive to 2-mercaptoethanol or anti-swine IgM treatment. The SN antibody titers were high when homologous PRRSV isolate was used in the test but were markedly low for heterologous PRRSV isolates. No difference in antibody titers was observed when homologous and heterologous PRRSV isolates were tested by indirect fluorescent antibody assay. These results indicate that the modified SN method is useful in detecting earlier and higher PRRSV antibody and that it can differentiate among PRRSV isolates.
Nursing Students’ Experiences With Type 2 Diabetes in Jordan: A Qualitative Content Analysis
Authors: Cadier Filip , Jallow Göransson Isalee , Rosengren Kristina
Published: January 2017

Prevalence of type 2 diabetes has increased worldwide due to lifestyle factors, such as obesity and inactivity, and nurses have an essential role in supporting healthy life situations. The aim was to describe nursing students’ experiences with type 2 diabetes in Jordan with regard to prevention and nursing care. Interviews with eight nursing students were performed. Data were analyzed using content analysis. One category and two subcategories were generated: managing challenges in daily life to prevent type 2 diabetes and promote patient safety, managing risk factors, and dealing with difficulties. Empowerment and person-centered care are tools to increase patients’ self-care to motivate them to live a healthy lifestyle within the whole family to prevent and decrease illness.