Transfusion-transmitted hepatitis B virus (HBV) infection from an individual-donation nucleic acid (ID-NAT) non-reactive donor.

Lookback was initiated upon notification of an acute HBV infection in a repeat Irish donor, 108 days post-donation. The donation screened non-reactive by individual-donation nucleic acid testing (ID-NAT) using the Procleix Ultrio Elite multiplex assay and again when the archived sample was retested, but the discriminatory assay for HBV was reactive. The immunocompromised recipient of the implicated red cell component was tested 110 days post-transfusion, revealing a HBV DNA viral load of 470 IU/ml. Genotype C2 sequences identical across two regions of the HBV genome were found in samples from the donor and recipient.

Data-Driven Models of Foot-and-Mouth Disease Dynamics: A Review.

Foot-and-mouth disease virus (FMDV) threatens animal health and leads to considerable economic losses worldwide. Progress towards minimizing both veterinary and financial impact of the disease will be made with targeted disease control policies. To move towards targeted control, specific targets and detailed control strategies must be defined. One approach for identifying targets is to use mathematical and simulation models quantified with accurate and fine-scale data to design and evaluate alternative control policies. Nevertheless, published models of FMDV vary in modelling techniques and resolution of data incorporated. In order to determine which models and data sources contain enough detail to represent realistic control policy alternatives, we performed a systematic literature review of all FMDV dynamical models that use host data, disease data or both data types. For the purpose of evaluating modelling methodology, we classified models by control strategy represented, resolution of models and data, and location modelled. We found that modelling methodology has been well developed to the point where multiple methods are available to represent detailed and contact-specific transmission and targeted control. However, detailed host and disease data needed to quantify these models are only available from a few outbreaks. To address existing challenges in data collection, novel data sources should be considered and integrated into models of FMDV transmission and control. We suggest modelling multiple endemic areas to advance local control and global control and better understand FMDV transmission dynamics. With incorporation of additional data, models can assist with both the design of targeted control and identification of transmission drivers across geographic boundaries.

Serotype Diversity of Foot-and-Mouth-Disease Virus in Livestock without History of Vaccination in the Far North Region of Cameroon.

Little information is available about the natural cycle of foot-and-mouth disease (FMD) in the absence of control measures such as vaccination. Cameroon presents a unique opportunity for epidemiological studies because FMD vaccination is not practiced. We carried out a prospective study including serological, antigenic and genetic aspects of FMD virus (FMDV) infections among different livestock production systems in the Far North of Cameroon to gain insight into the natural ecology of the virus. We found serological evidence of FMDV infection in over 75% of the animals sampled with no significant differences of prevalence observed among the sampled groups (i.e. market, sedentary, transboundary trade and mobile). We also found antibodies reactive to five of the seven FMDV serotypes (A, O, SAT1, SAT2 and SAT3) among the animals sampled. Finally, we were able to genetically characterize viruses obtained from clinical and subclinical FMD infections in Cameroon. Serotype O viruses grouped into two topotypes (West and East Africa). SAT2 viruses grouped with viruses from Central and Northern Africa, notably within the sublineage causing the large epidemic in Northern Africa in 2012, suggesting a common origin for these viruses. This research will guide future interventions for the control of FMD such as improved diagnostics, guidance for vaccine formulation and epidemiological understanding in support of the progressive control of FMD in Cameroon.

Cardiovascular risk evaluation and antiretroviral therapy effects in an HIV cohort: implications for clinical management: the CREATE 1 study.

AIMS: The aim of this study is to determine the cardiovascular disease (CVD) risk profile of a large UK HIV cohort and how highly active antiretroviral therapy (HAART) affects this. METHODS: It is a cross-sectional study within a large inner city hospital and neighbouring district hospital. A total of 1021 HIV positive outpatients representative of the complete cohort and 990 who had no previous CVD were included in CVD risk analysis. We recorded demographics, HAART history and CVD risk factors. CVD and coronary heart disease (CHD) risks were calculated using the Framingham (1991) algorithm adjusted for family history. RESULTS: The non-CVD cohort (n = 990) was 74% men, 51% Caucasian and 73.1% were on HAART. Mean age was 41 +/- 9 years, systolic blood pressure 120 +/- 14 mmHg, total cholesterol 4.70 +/- 1.05 mmol/l, high-density lipoprotein-C 1.32 +/- 0.48 mmol/l and 37% smoked. Median CVD risk was 4 (0-56) % in men and 1.4 (0-37) % in women; CHD risks were 3.5 (0-36) % and 0.6 (0-16) %. CVD risk was > 20% in 6% of men and 1% of women and > 10% in 12% of men and 4% of women. CVD risk was higher in Caucasians than other ethnicities; the risk factor contributing most was raised cholesterol. For patients on their first HAART, increased CHD risk (26.2% vs. 6.5%; odds ratio 4.03, p < 0.001) was strongly related to the duration of therapy. CONCLUSIONS: Modifiable risk factors, especially cholesterol, and also duration of HAART, were key determinants of CVD risk. DISCUSSION: Regular CHD and/or CVD risk assessment should be performed on patients with HIV, especially during HAART therapy. The effect of different HAART regimens on CHD risk should be considered when selecting therapy.

Adenosine, ketogenic diet and epilepsy: the emerging therapeutic relationship between metabolism and brain activity.

For many years the neuromodulator adenosine has been recognized as an endogenous anticonvulsant molecule and termed a "retaliatory metabolite." As the core molecule of ATP, adenosine forms a unique link between cell energy and neuronal excitability. In parallel, a ketogenic (high-fat, low-carbohydrate) diet is a metabolic therapy that influences neuronal activity significantly, and ketogenic diets have been used successfully to treat medically-refractory epilepsy, particularly in children, for decades. To date the key neural mechanisms underlying the success of dietary therapy are unclear, hindering development of analogous pharmacological solutions. Similarly, adenosine receptor-based therapies for epilepsy and myriad other disorders remain elusive. In this review we explore the physiological regulation of adenosine as an anticonvulsant strategy and suggest a critical role for adenosine in the success of ketogenic diet therapy for epilepsy. While the current focus is on the regulation of adenosine, ketogenic metabolism and epilepsy, the therapeutic implications extend to acute and chronic neurological disorders as diverse as brain injury, inflammatory and neuropathic pain, autism and hyperdopaminergic disorders. Emerging evidence for broad clinical relevance of the metabolic regulation of adenosine will be discussed.

Transmission rates of hepatitis C virus by different batches of a contaminated anti-D immunoglobulin preparation.

BACKGROUND AND OBJECTIVES: The aim of this study was to determine the hepatitis C virus (HCV) infection rate of recipients of different batches of anti-D immunoglobulin associated with an outbreak of HCV infection which occurred in 1977 and its relationship to the polymerase chain reaction (PCR) status of the implicated batches. This study was undertaken to determine the predictive value of HCV genome detection and quantification for subsequent infection in recipients of an HCV-contaminated anti-D immunoglobulin product for intravenous use. MATERIALS AND METHODS: Sera from recipients of anti-D were tested by HCV enzyme immunoassay and if found positive were subsequently tested by recombinant immunoblot assay and HCV PCR in a national HCV anti-D screening programme set up in 1994. The HCV status of 1,342 known recipients of infectious or potentially infectious batches has been compared to the amount of HCV RNA in the anti-D batch they received so as to determine the value of PCR in the prediction of infectivity in immunoglobulin preparations. RESULTS: It has been demonstrated that HCV-infected plasma derived from batches of anti-D showing levels of viral genome in excess of 10(4) genomes per millilitre led to infection of up to 60% of recipients. In contrast, batches with undetectable levels of HCV genome very rarely transmitted infection. CONCLUSIONS: The presence of HCV RNA in intravenous immunoglobulin preparations which have not undergone a specific viral inactivation step is a predictor of HCV infection in recipients.

Cervical cytological screening in HIV-infected women in Dublin--a six-year review.

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%).

Prevalence of HIV and associated risk behaviour in attendees at a Dublin needle exchange.

The aim of this study was to measure the prevalence of HIV infection and assess the level of equipment-sharing and unsafe sexual activity among attendees at a Dublin needle exchange. Using an anonymous unlinked approach, attendees were asked to complete a brief questionnaire and provide a sample of saliva for HIV testing. Of the 144 attendees eligible for inclusion during the study period, 106 agreed to participate and complete a questionnaire, a response rate of 74%. Of the 81 respondents who submitted a usable saliva sample, 14.8% were HIV positive. Half of the respondents claimed that they had not shared equipment during the preceding 28 days, but a third had shared with multiple partners. Half of the respondents claimed that they had multiple sexual partners during the preceding year, but only a quarter said that they always used condoms. The prevalence of HIV infection is similar to that found in routine linked testing of drug users in Ireland. The high level of unsafe injecting and sexual activity makes clear the need for more effective health promotion among drug users in Dublin.

A framework for the continual improvement of behavioral healthcare. Part II--Policy for leadership.

In the first part of this article, published in the November/December 1993 issue of Behavioral Healthcare Tomorrow, the authors presented a framework for understanding the process of continuous quality improvement in the behavioral healthcare setting. Four elements of continual improvement were identified: underlying knowledge, policy for leadership, tools and methods, and daily work applications. They showed how traditional professional knowledge of one's subject, discipline and values must be augmented by improvement knowledge--which quality improvement guru W. Edwards Deming calls "the system of profound knowledge." In Part II, they focus on the second element of continual improvement, the importance of organizational leadership.

Changes in Bacterial Numbers and Leucine Assimilation during Estimations of Microbial Respiratory Rates in Seawater by the Precision Winkler Method.

During incubation of seawater in bottles, the decrease in dissolved oxygen is often nonlinear over time scales frequently used to measure respiration. Numbers of bacteria always increase, and rates of assimilation of dissolved leucine often increase exponentially. This suggests that sample handling disrupts the previously existing food web, leading to shifts of trophic state and unbalanced growth. Potential errors in measuring respiratory rate can be minimized by documenting these variables.

The use of primary care services by drug users attending a HIV prevention unit.

Intravenous drug using clients of a Dublin HIV Prevention Unit were interviewed about their use of general practitioner services. Sixty eight percent of clients had visited a GP within the previous year and 48% were registered with a GP under the General Medical Services (GMS) Scheme. Of 161 interviewees 60 were being treated with a fixed dose regimen of methadone at the Prevention Unit; this group was far less likely to visit a GP with a drug related problem and far less likely to have received methadone from a GP. Members of the GMS were much more likely than non members to have visited a GP and also more likely to have attended a specific GP for all problems besides methadone treatment. Methadone treatment and medical cover within the GMS Scheme emerged as important influences on the behaviour of clients with respect to general practitioners.

Evidence for an enhanced substrate requirement by marine mesophilic bacterial isolates at minimal growth temperatures.

Bacterial isolates from the subtropical southeastern continental shelf were cultured in a matrix of temperature and substrate concentrations encompassing a range of temperature and substrate concentrations equal to and exceeding natural ones. At the annual minimum temperature, marine heterotrophic bacterial isolates required higher concentrations of dissolved substrates for active growth than are usually found in seawater. We show this to result from a nonlinear interaction of the combined effects of temperature and substrate concentration on bacterial growth and respiratory rate. As a result, bacterial and protozoan utilization of phytoplankton production during winter and early spring is low, permitting greater energy flow to zooplankton and benthic animals, while in late spring, summer, and fall, the microbial loop dominates energy flux and organic carbon utilization. Escherichia coli shows a similar nonlinear response to temperature at minimal substrate concentrations, albeit at a higher range of concentrations than were utilized by the marine isolates. Thus, bacteria from subtropical regions are shown to have a differential growth response near the minimum temperature for growth, depending on the concentration of available substrates.

Bacterial growth in the cold: evidence for an enhanced substrate requirement.

Growth responses and biovolume changes for four facultatively psychrophilic bacterial isolates from Conception Bay, Newfoundland, and the Arctic Ocean were examined at temperatures from - 1.5 to 35 degrees C, with substrate concentrations of 0.15, 1.5, and 1,500 mg of proteose peptone-yeast extract per liter. For two cultures, growth in 0.1, 1.0, and 1,000 mg of proline per liter was also examined. At 10 to 15 degrees C and above, growth rates showed no marked effect of substrate concentration, while at - 1.5 and 0 degrees C, there was an increasing requirement for organic nutrients, with generation times in low-nutrient media that were two to three times longer than in high-nutrient media. Biovolume showed a clear dependence on substrate concentration and quality; the largest cells were in the highest-nutrient media. Biovolume was also affected by temperature; the largest cells were found at the lowest temperatures. These data have implications for both food web structure and carbon flow in cold waters and for the effects of global climate change, since the change in growth rate is most dramatic at the lowest temperatures.

Admission for HIV-1 related disease in a Dublin hospital 1987-1990.

Between January 1987 and December 1990, 179 patients (131 men, 48 women) infected with human immunodeficiency virus type 1 (HIV-1) were admitted 408 times to St James's Hospital, Dublin. One hundred and thirty-two (73.7%) patients were intravenous drug users. The commonest cause of admission was bacterial lower respiratory tract infection (84 patients, 21%). At the time of study 95 (53%) patients fulfilled Centers for Disease Control (CDC) criteria for stage IV disease. HIV antibody status in 26 of these patients with stage IV disease was unknown prior to their admission to hospital with symptomatic disease. Pneumocystis carinii pneumonia was the most frequent stage IV defining diagnosis. The mean length of hospital stay for patients with CDC stage II/III and stage IV disease was 8.5 (median 7) and 13.5 (median 8) days respectively.

Prospective study of amikacin versus netilmicin in the treatment of severe infection in hospitalized patients.

PURPOSE: Four previous studies comparing netilmicin and amikacin have yielded inconclusive results concerning efficacy and rates of nephrotoxicity and ototoxicity. For this reason, we conducted a prospective, randomized, controlled trial of the two drugs in the treatment of hospitalized patients with severe infection. PATIENTS AND METHODS: A total of 202 patients were enrolled in the study; 100 received netilmicin and 102 received amikacin. Concomitant antimicrobials were restricted to metronidazole and benzylpenicillin. Peak and trough aminoglycoside levels were assayed within the first 36 hours and at least every 72 hours thereafter. A full blood cell count, serum electrolytes, creatinine, bilirubin, and liver enzymes were measured before therapy, weekly thereafter, and within 48 hours after the discontinuation of therapy. Nephrotoxicity and ototoxicity were assessed in patients. A standard agar dilution procedure was used to determine minimal inhibitory concentrations. RESULTS: No significant pretreatment differences were found between the two groups. Patients in the amikacin group responded significantly better to treatment than did patients in the netilmicin group (90% versus 79%; p less than 0.05). A notable finding was the markedly inferior response rate of Pseudomonas aeruginosa infections to netilmicin as compared with amikacin (13 of 24 with a favorable response compared with 25 of 26). No significant difference in ototoxicity was found, whereas nephrotoxicity appeared to be significantly less with amikacin (4% versus 12%, p less than 0.05). Although amikacin seemed less nephrotoxic than netilmicin, this may have been related to the significantly greater number of patients with initial renal dysfunction who received netilmicin. CONCLUSIONS: Amikacin appears to be significantly more efficacious than netilmicin for the treatment of P. aeruginosa infections, especially those in non-urinary tract sites. There is no apparent difference between the two drugs in terms of ototoxicity.

Human immunodeficiency viruses in patients attending a sexually transmitted disease clinic in London, 1982-7.

OBJECTIVE: To determine the prevalence of infection with the human immunodeficiency virus (HIV) in all patients attending a London sexually transmitted disease clinic over four weeks at the end of 1987 and to see how it varied from that in similar samples studied between 1982 and 1986. DESIGN: Anonymous testing of serum samples from consecutive heterosexual and homosexual patients having routine serological investigations for syphilis. Testing was for anti-HIV-I, anti-HIV-II, and hepatitis B core antibody (anti-HBc) and P24 antigen. Age, nationality, sexual orientation, and past sexually transmitted diseases were recorded for each patient. Gonorrhoea rates by quarters were analysed among homosexual and bisexual men and heterosexual men and women from 1981 to 1987. SETTING: Outpatient department of genitourinary medicine. PATIENTS: A total of 1074 patients attending consecutively for syphilis serology. Thirty five homosexual and bisexual men were excluded (these were regular attenders as part of a prospective study of the natural course of HIV infection). MEASUREMENTS AND MAIN RESULTS: The prevalence of anti-HIV-I in homosexual and bisexual men in 1987 was 25.6% (64/250). Results in the same clinic population between 1982 and 1984 had shown a rise in prevalence, which flattened out in 1985-6 and continued at that level. Among heterosexual attenders in 1987 the prevalence of anti-HIV-I was 1% (women 4/412; men 4/377), which contrasted with a prevalence of 0.5% (women 2/395; men 3/757) in January 1986. One homosexual man was seropositive for anti-HIV-II and seronegative for anti-HIV-I. Among homosexual and bisexual men the rate of gonorrhoea had declined by an average of 2.7% a year since 1981, such that by 1987--and for the first time in the clinic--there was no significant difference in the rates between these men and heterosexual men and women. CONCLUSIONS: The appearance of HIV-I infection among heterosexuals indicates a need for more aggressive education programmes and intervention strategies along the lines adopted for homosexual men. Surveillance for HIV-II infection is needed to provide information for future policy in national screening programmes.

Factors affecting the level of kanamycin resistance in transformed sunflower cells.

A 230 base pair DNA segment containing the sequences 5' to the 700 to 750 nucleotide (nt) transcript 7' (ORF 3; RF Barker, KB Idler, DV Thompson, JD Kemp 1983 Plant Mol Biol 2: 335-350) of the octopine tumor inducing plasmid pTiA6 has been isolated. This region has (a) 180 base pairs of DNA upstream of the TATA box, (b) the start of RNA synthesis, and (c) the entire 5' untranslated region of the gene. We have fused this presumed promoter fragment to the neomycin phosphotransferase II (NPTII) gene from Tn5 in a plant expression cassette. After recombination into a tumor inducing plasmid delivery plasmid, this cassette confers selectable kanamycin resistance to transformed sunflower cells. Removal of the out-of-frame ATG in the 5' leader sequence of the NPTII gene by two different modifications increased both the levels of NPTII enzyme activity and the ID(50) for kanamycin in the tumor cells. The promoter region of the transcript 7 gene gives levels of kanamycin resistance equivalent to the nopaline synthase promoter and octopine synthase promoter when used in the same constructions and assayed in the same tissues.