bluuebunny/crossref_metadata_2025 huggingface dataset:
Delirium in adults with intellectual disabilities and DC‐LD
Authors: Simpson Neill
Published: October 2003

Background  No systematic studies of delirium in adults with intellectual disabilities have been reported. Reasons for the absence of research are discussed.

Methods  Two cases of delirium are described which meet the Diagnostic Criteria for Psychiatric Disorders for Use with Adults with Learning Disabilities/Mental Retardation [DC‐LD].

Conclusions  DC‐LD offers a diagnostic framework that permits comparison with premorbid cognitive function.
Diagnosis and classification of eating disorders in adults with intellectual disability: the Diagnostic Criteria for Psychiatric Disorders for Use with Adults with Learning Disabilities/Mental Retardation (DC‐LD) approach
Authors: Gravestock Shaun
Published: October 2003

Background  Previous classifications of eating disorders [EDs] employed a narrower concept of EDs. They did not include the wide range of abnormal eating behaviours [AEBs], persistent feeding disorders and EDs psychopathology, aetiological and comorbidity factors seen in adults with intellectual disability [ID].

Methods  The International Classification of Diseases − 10 [ICD‐10], ICD‐10‐MR, Diagnostic and Statistical Manual − IV [DSM‐IV] and Diagnostic Criteria for Psychiatric Disorders for Use with Adults with Learning Disabilities/Mental Retardation[DC‐LD] diagnostic approaches to EDs in adults with ID are compared.

Results  The DC‐LD encourages conceptually clearer and systematic hierarchical differential diagnostic classification of AEBs and EDs. The DC‐LD also allows consideration of relevant aetiological and comorbidity issues. DC‐LD‐based multi‐axial case formulation supports the multimodal clinical assessment of AEBs and EDs.

Conclusions  Further research should develop similar systematic and evidence‐based multicomponent clinical diagnostic, management and service models for adults with ID and EDs.
Diagnostic Criteria for Psychiatric Disorders for Use with Adults with Learning Disabilities/Mental Retardation (DC‐LD) and psychiatric phenotypes
Authors: Clarke David
Published: October 2003

Background  The concept of behavioural phenotypes is reviewed, with emphasis on the need to research reasons for heterogeneity.

Methods/Results  The classification of emotional, behavioural, linguistic and cognitive abnormalities associated with genetic disorders may be improved through the use of the Diagnostic Criteria for Psychiatric Disorders for Use with Adults with Learning Disabilities/Mental Retardation.

Conclusions  Examples of such abnormalities are discussed, showing how more accurate descriptions can result in improved diagnosis and treatment.
Distribution and status of feral wild boar Sus scrofa in Dorset, southern England
Authors: WILSON CHARLES J.
Published: October 2003

1. A recently established feral population of wild boar Sus scrofa in Dorset, southern England, was studied by collecting details of escapes, live sightings and animals killed, by examining field signs and by making direct observations in the field.

2. Records were obtained from 47 national grid kilometre squares. Two or more records were received for 27 km2 and the presence of boar confirmed by field signs in 21 of these. The population appears to have originated from escapes in winter 1994/95 and to have remained largely confined to within 11 km of the escape site. The large number of animals killed, relative to the number of animals which escaped, reports of shot sows carrying foetuses and observations of sows with piglets in the field, confirmed that breeding had taken place.

3. Estimates of live weight, estimated age, or descriptions of the animals killed were used to allocate each to a broad age class and thus construct a retrospective census. This suggested that the minimum population size peaked at about 30 animals in 1998 but that the pre‐breeding population has probably remained at fewer than 20 animals.
The process of dispersal in badgers Meles meles
Authors: ROPER T. J. , OSTLER J. R. , CONRADT L.
Published: October 2003

1. Radio‐telemetry was used to track dispersal in five adult Eurasian badgers Meles meles (four males and one female) from three social groups.

2. All animals moved to a territory immediately neighbouring their home territory. Three of the males dispersed simultaneously as a ‘coalition’; the other two individuals dispersed solitarily.

3. The process of dispersal took from 2 to 9 months. Dispersing animals first made nocturnal forays into the new territory but returned to their own territory to sleep. They then began to sleep progressively more often in setts in the new territory, and less often in their original territory. During this period, dispersers foraged in both the old and the new territory, before eventually settling into a home range centred exclusively on the new territory.

4. We conclude that dispersal can be a lengthy and complex process, even when the distance involved is small.
A traditional healers’ training model in rural Nepal: strengthening their roles in community health
Authors: Poudyal Amod K. , Jimba Masamine , Murakami Izumi , Silwal Ram C. , Wakai Susumu , Kuratsuji Tadatoshi
Published: October 2003

In this paper, we evaluated a western medical training model for traditional healers (THs) in rural Nepal. We used semi‐structured interviews to compare 48 trainees with 30 randomly selected untrained THs, 1 year after the training was completed. We asked them about their knowledge of the causes, prevention and treatment of common illnesses and HIV/AIDS, and their relationship with government health workers (GHWs) in the area. Nine GHWs were also interviewed about their perceptions of THs. We found that trained THs had a better knowledge of allopathic medicine, practised modern treatment using first aid kits, and were more likely to refer patients to GHWs. They also improved their relationships with the GHWs. Up‐scaling this model is a challenge for improving community health care in Nepal in the future.
Home treatment of ‘malaria’ in children in rural Gambia is uncommon
Authors: Clarke Siân E. , Rowley Jane , Bøgh Claus , Walraven Gijs E. L. , Lindsay Steven W.
Published: October 2003

Home treatment with antimalarials is a common practice in many countries, and may save lives by ensuring that more malaria cases receive prompt treatment. Through retrospective surveys we found that home treatment of young children with antimalarials was uncommon in rural Gambia. Few families kept medicines in the home in case of illness, 28% kept paracetamol and only 8% kept chloroquine. Less than 10% of cases of childhood ‘malaria’ had been treated with chloroquine at home, and 69% of those giving home medication did not know the correct dosage for a child. The most common course of treatment was the use of paracetamol and/or tepid sponging to reduce fever, before the child was taken to a government health facility. Treating a child with antimalarials at home was more costly than other forms of treatment. The low cost associated with the use of health services for children and the limited availability of antimalarials outside major towns contribute to the high use of government health services. This shows that that home treatment cannot be assumed to be the predominant mode of malaria treatment throughout Africa, and highlights the need for country‐specific policies based on accurate local knowledge of treatment practices in both rural and urban areas.
Assessing the efficacy of chloroquine and sulfadoxine–pyrimethamine for treatment of uncomplicated Plasmodium falciparum malaria in the Democratic Republic of Congo
Authors: Kazadi Walter M. , Vong Sirenda , Makina Burstein N. , Mantshumba Jean C. , Kabuya Willy , Kebela Benoit I. , Ngimbi Nkuku P.
Published: October 2003

We evaluated the in vivo responses to chloroquine (CQ), the first line antimalarial, and to sulfadoxine–pyrimethamine (SP), the most readily available and affordable alternative treatment, in children under 5 with acute uncomplicated Plasmodium falciparum malaria in seven sites of Democratic Republic of Congo (DRC) between May 2000 and November 2001, using the standard 14‐day WHO protocol. In the CQ group, the overall treatment failure rate was 45.4% (95% CI: 40.1–50.8) of 350 infections successfully tested; in the SP group it was 7.5% (95% CI: 5.0–11.0) of 333 infections. Of 191 patients who had an adequate clinical response (ACR) in the CQ group, 127 (66.5%; range: 62.5–71.4) still had parasitaemia on day 14. In the SP group, only 21 (6.8%; range: 2.2–12.8) of 308 patients with an ACR were still parasitaemic on day 14. Using pooled data from three rural sites, haematological recovery was better in the SP group (mean of haematocrit difference between days 14 and 0 among anaemic children: 4.7 vs. 3.2; P < 0.01, Wilcoxon test). These findings suggest that CQ is no longer effective in DRC and that SP may be a good alternative for its replacement as first line antimalarial treatment. The Ministry of Health (MOH) therefore now recommends SP as the first line antimalarial drug in DRC, as an interim step, 18 months after launching the first study. Additional studies are needed to select alternative therapies that might replace SP or improve its efficacy, should it prove ineffective in the future.
Multicentre laboratory evaluation of Brugia Rapid dipstick test for detection of brugian filariasis
Authors: Rahmah N. , Shenoy R. K. , Nutman T. B. , Weiss N. , Gilmour K. , Maizels R. M. , Yazdanbakhsh M. , Sartono E.
Published: October 2003

A multicentre evaluation of the Brugia Rapid dipstick test was performed using 1263 serum samples in four international laboratories, i.e. T.D. Medical College (TDMC, India), National Institutes of Health (NIH, USA), Swiss Tropical Institute (STI, Switzerland) and Leiden University Medical Centre (LUMC, Netherlands). In comparison with microscopy, the dipstick demonstrated sensitivities of 97.2% (70 of 72) at TDMC, 91.6% (175 of 191) at LUMC and 100% (six of six) at STI. Sera of chronic patients showed a positivity rate of 11.3% (19 of 168) and 61.2% (71of 116) at TDMC and LUMC, respectively. All 266 sera of non‐endemic normals from STI, NIH and LUMC tested negative with the dipstick. At LUMC, sera of ‘endemic normals’ (amicrofilaraemics with no clinical disease) from an area with approximately 35% microfilaria positivity showed 60.8% positive results (31 of 51), thus demonstrating the likelihood of many cryptic infections occuring in this population. Specificities of the test with Onchocerca volvulus sera were 98.8% (80 of 81) and 100% (10 of 10) at the NIH and STI, respectively; while specificity with Loa loa sera at the NIH was 84.6% (44 of 52). At the STI, the dipstick test also demonstrated 100% specificity when tested with 75 sera from various protozoan and helminthic infections.
Effectiveness of feedback for improving case management of malaria, diarrhoea and pneumonia – a randomized controlled trial at provincial hospitals in Lao PDR
Authors: Wahlström Rolf , Kounnavong Sengchanh , Sisounthone Bouathong , Phanyanouvong Ampayvanh , Southammavong Thanakhanh , Eriksson Bo , Tomson Göran
Published: October 2003

Background Standard Treatment Guidelines were introduced to all prescribers at provincial hospitals in Lao PDR and treatment indicators were developed within the National Drug Policy programme to monitor compliance.

Objectives To evaluate the effects of an educational intervention to improve treatment practices of malaria, diarrhoea and pneumonia.

Methods Randomized controlled trial with prescribers at 24 departments at eight provincial hospitals, matched into four pairs. The three departments of internal medicine, paediatrics and out‐patients in each pair were randomized into intervention or control group. The 6‐month intervention was conducted by members of the Drug and Therapeutics Committees, and comprised monthly audit sessions in the form of outcome feedback using indicator scores on recorded treatment of malaria, diarrhoea and pneumonia. We measured treatment indicator scores 6 months after the end of the intervention compared with baseline.

Results The aggregated mean scores for all diseases, and for malaria and diarrhoea, improved significantly. For pneumonia, improvement was seen in both the intervention and control groups. Record keeping was improved for all three diseases. For malaria, there were improvements in recording patients’ history, and in frequency of microscope testing; for diarrhoea, regarding weight measurements, palpation of the fontanel for children under 2 years, and reduction of irrational use of anti‐diarrhoeals and antibiotics; for pneumonia, in recording respiratory count, and reducing irrational use of anti‐histamines and anti‐cough medications.

Conclusions Audit–feedback systems to improve quality of care are feasible and effective also in hospital settings in low‐income countries.
Evaluation of a simple operational approach for monitoring resistance to antimalarial drugs in Peru
Authors: Ruebush Trenton K. , Levin Andrew , Gonzaga Victor , Neyra Daniel , Marquiño Wilmer
Published: October 2003

Since 1994, the Peruvian Malaria Control Program has used a simplified operational approach for monitoring antimalarial drug efficacy, in which blood smears are taken 7 and 14 days after treatment from all patients diagnosed with malaria at Ministry of Health facilities. The proportion of patients with parasitaemia on one of their return visits provides an indication of the efficacy of the drug being administered. We compared this approach for antimalarial drug resistance monitoring to the more labour‐intensive and expensive World Health Organization (WHO) 14‐day in vivo efficacy trial at six sites in the Amazon Basin and the north coast of Peru. Although the proportion of treatment failures at 7 and 14 days identified by the operational monitoring system was considerably lower than the results of the WHO in vivo efficacy test, the operational approach did accurately reflect the overall efficacy or lack of efficacy of the drugs being evaluated. Differences in the results of the two methods were greatest in the Peruvian Amazon region, where fully supervised treatment and patient follow‐up is very difficult due to the widely dispersed population. While the operational approach cannot be considered an alternative to WHO in vivo testing for evaluating the efficacy of antimalarial drugs or for recommending changes in malaria treatment policy, if treatment is supervised and follow‐up blood smears taken as scheduled, this method could serve as a simple, inexpensive and sustainable early warning system for reduced drug efficacy.
How many sputum smears are necessary for case finding in pulmonary tuberculosis?
Authors: Yassin Mohammed A. , Cuevas Luis E.
Published: October 2003

We reviewed the laboratory registers of 42 tuberculosis (TB) diagnostic centres in the southern region of Ethiopia to determine the value of submitting serial sputum samples for the diagnosis of pulmonary TB (PTB) and estimate the proportion of suspects that are smear positive. A total of 15 821 TB suspects submitted three smears each (47 463 smears) in 2000 with a median of 228 per centre. The smear positivity rate (two or more positive smears) was 25%, with a range of 16.8–36.4% per zone. This exceeds the international recommendations of examining 10 suspects to identify one case. A total of 4099 (26%) of the suspects had at least one positive smear with 3753 (91.6%) of the first specimens being positive. A further 303 (7.4%) were negative in the first specimen but had a positive second specimen and 42 (1%) suspects had two negative specimens followed by a positive third smear. The value of the third sputum is negligible as 99% of the cases were identified from the first and second specimens. Reducing the number of specimens to two or even one would have multiple advantages in countries where laboratories are usually over‐burdened and are not easily accessible to the population. Submission of two specimens on the same day could improve compliance in submitting samples and collecting results as the number of diagnostic visits would be reduced without significant loss of sensitivity.
Mumbai disease in far western Nepal: HIV infection and syphilis among male migrant‐returnees and non‐migrants
Authors: Poudel Krishna C. , Okumura Junko , Sherchand Jeevan B. , Jimba Masamine , Murakami Izumi , Wakai Susumu
Published: October 2003

Objective To measure the seroprevalence of human immunodeficiency virus (HIV) infection and syphilis, and to assess the behavioural risk factors for these infections among migrant‐returnees and non‐migrants in far western Nepal.

Methods In April 2001, we recruited 97 male migrant‐returnees and 40 non‐migrants from five rural villages in Doti district where migration to Mumbai is common. For data collection, we conducted a serological examination for HIV and syphilis, and a perception and behaviour survey on HIV and other sexually transmitted infections.

Results We found that 11 of 137 men (8%) were positive for HIV infection and 30 men (22%) for syphilis. The respondents, especially the migrant‐returnees from Mumbai, were engaging in risky behaviours such as pre‐ or extramarital sex, and sex with multiple partners, including sex workers.

Conclusions This study revealed high HIV and syphilis prevalence among the male migrant‐returnees and non‐migrants in far western Nepal where migration to Mumbai is common. The prevalent behaviours, particularly among the migrant‐returnees, imply urgent needs of the behavioural modification programme in this area to prevent the spread of HIV infection to general population.
Maternal mortality and access to obstetric services in West Africa
Authors: Ronsmans C. , Etard J. F. , Walraven G. , Høj L. , Dumont A. , de Bernis L. , Kodio B.
Published: October 2003

Summary Objectives Process evaluation has become the mainstay of safe motherhood evaluation in developing countries, yet the extent to which indicators measuring access to obstetric services at the population level reflect levels of maternal mortality is uncertain. In this study we examine the association between population indicators of access to obstetric care and levels of maternal mortality in urban and rural West Africa.

Methods In this ecological study we used data on maternal mortality and access to obstetric services from two population‐based studies conducted in 16 sites in eight West African countries: the Maternal Mortality and Obstetric Care in West Africa (MAMOCWA) study in rural Sénégal, Guinea‐Bissau and The Gambia and the Morbidité Maternelle en Afrique de l'Ouest (MOMA) study in urban Burkina Faso, Côte d'Ivoire, Mali, Mauritanie, Niger and Sénégal.

Results In rural areas, maternal mortality, excluding early pregnancy deaths, was 601 per 100 000 live births, compared with 241 per 100 000 for urban areas [RR = 2.49 (CI 1.77–3.59)]. In urban areas, the vast majority of births took place in a health facility (83%) or with a skilled provider (69%), while 80% of the rural women gave birth at home without any skilled care. There was a relatively close link between levels of maternal mortality and the percentage of births with a skilled attendant (r = −0.65), in hospital (r = −0.54) or with a Caesarean section (r = −0.59), with marked clustering in urban and rural areas. Within urban or rural areas, none of the process indicators were associated with maternal mortality.

Conclusion Despite the limitations of this ecological study, there can be little doubt that the huge rural–urban differences in maternal mortality are due, at least in part, to differential access to high quality maternity care. Whether any of the indicators examined here will by themselves be good enough as a proxy for maternal mortality is doubtful however, as more than half of the variation in mortality remained unexplained by any one of them.
Defining equity in physical access to clinical services using geographical information systems as part of malaria planning and monitoring in Kenya
Authors: Noor A. M. , Zurovac D. , Hay S. I. , Ochola S. A. , Snow R. W.
Published: October 2003

Distance is a crucial feature of health service use and yet its application and utility to health care planning have not been well explored, particularly in the light of large‐scale international and national efforts such as Roll Back Malaria. We have developed a high‐resolution map of population‐to‐service access in four districts of Kenya. Theoretical physical access, based upon national targets, developed as part of the Kenyan health sector reform agenda, was compared with actual health service usage data among 1668 paediatric patients attending 81 sampled government health facilities. Actual and theoretical use were highly correlated. Patients in the larger districts of Kwale and Makueni, where access to government health facilities was relatively poor, travelled greater mean distances than those in Greater Kisii and Bondo. More than 60% of the patients in the four districts attended health facilities within a 5‐km range. Interpolated physical access surfaces across districts highlighted areas of poor access and large differences between urban and rural settings. Users from rural communities travelled greater distances to health facilities than those in urban communities. The implications of planning and monitoring equitable delivery of clinical services at national and international levels are discussed.
Rapid diagnostic testing for malaria
Authors: Murray Clinton K. , Bell David , Gasser Robert A. , Wongsrichanalai Chansuda
Published: October 2003

Malaria rapid diagnostic devices (MRDD) have been developed with the hope that they would offer accurate, reliable, rapid, cheap and easily available alternatives to traditional methods of malaria diagnosis. The results from early malaria rapid diagnostic studies were quite promising, especially for detecting Plasmodium falciparum at densities of more than 100–500 parasites/μl. Despite the introduction of these devices over a decade ago, only a few target antigens have been introduced. Of greater concern, these devices have shown limitations in sensitivity, ability to differentiate species and robustness under field conditions in the tropics. Recent trials have revealed wide variability in sensitivity both within and between products. We review the recent trials assessing MRDD use for the diagnosis of P. falciparum and non‐P. falciparum infections in endemic and non‐endemic countries and describe the various aspects of these devices which need further improvement. High quality, accurate, rapid and affordable diagnostic tools are urgently needed now that new antimalarial regimens, characterized by higher cost and increased toxicity, have been introduced more widely in response to emerging multi‐drug resistance.
La maladie de sommeil dans la région Ville de Kinshasa: une analyse rétrospective des données de surveillance sur la période 1996–2000
Authors: Ebeja A. Kadima , Lutumba P. , Molisho D. , Kegels G. , Miaka mia Bilenge C. , Boelaert M.
Published: October 2003

En République Démocratique du Congo, la réémergence de la maladie du sommeil n'est plus limitée aux zones rurales. Au cours de la dernière décennie, de plus en plus de cas sont déclarés dans des centres urbains comme Kinshasa, Mbuji‐mayi, Matadi et Boma. Nous présentons une analyse rétrospective de l'information disponible pour la région Ville de Kinshasa sur la période 1996–2000. Nous avons procédéà une revue de toute l'information du système de surveillance épidémiologique, y compris les fiches individuelles des malades, ainsi que des données entomologiques disponibles. Nous avons classé les 22 zones de santé de la région comme urbaine si la densité de population dépassait 5.000 habitants/km2. Le programme de contrôle a déclaré 2.451 nouveaux cas de T.H.A. parasitologiquement confirmés entre 1996–2000 pour l'ensemble de la région Ville de Kinshasa. Soixante‐six pour‐cent des cas ont entre 15 et 49 ans. Chacune des 22 zones de santé a déclaré des cas, et 956 cas (39%) résidaient dans une zone de santé classée comme urbaine. Des captures de glossines ont mis en évidence la présence de Trypanosoma spp. en 1999. La transmission locale de la T.H.A. dans la région est plausible mais non confirmée. Le nombre important de cas nécessite la conception de stratégies de lutte adaptées au milieu urbain.
Plasmodium falciparum multiplicity correlates with anaemia in symptomatic malaria
Authors: Mockenhaupt Frank P. , Ehrhardt Stephan , Eggelte Teunis A. , Markert Miriam , Anemana Sylvester , Otchwemah Rowland , Bienzle Ulrich
Published: October 2003

In 366 Ghanaian children with symptomatic Plasmodium falciparum malaria, low haemoglobin levels and severe anaemia were associated with a high multiplicity of infection (MOI) and with distinct merozoite surface protein alleles. High MOI not only reflects premunition but may also contribute to anaemia in symptomatic malaria.
Prevalence of intestinal parasitic infections in northern Vietnam
Authors: Verle P. , Kongs A. , De N. V. , Thieu N. Q. , Depraetere K. , Kim H. T. , Dorny P.
Published: October 2003

We surveyed the prevalence of parasitic infections in the mountainous province of Hoa Binh, north‐west Vietnam, involving 526 households of six ethnic groups: Muong, Kinh, Dao, Thai, Tay and Hmong. Eggs or cysts of at least one parasite species were detected in 88% of stool samples (n = 2522). Prevalences of nematodes were high among all ethnic groups: hookworm (52%), Trichuris trichiura (50%) and Ascaris lumbricoides (45%). Ascaris infection appeared to be lower in households owning a latrine, was highest among children and decreased with age. Prevalence of hookworm rose during childhood, remained high until old age, was highest among adult women, but was not linked to anaemia. Eggs of Chlonorchis spp. were found in 126 (5%) individuals (of the Muong, Kinh or Thai groups only). Chlonorchiasis increased with age and was highest among adult men. Taenia eggs were found in three individuals (0.1%). Giardia lamblia was found in all districts and among all groups and the prevalence of infection was estimated at 3%.
Chagas’ disease diagnosis: comparative analysis of recombinant ELISA with conventional ELISA and the haemagglutination test
Authors: Gadelha A. Á. M. , Verçosa A. F. A. , Lorena V. M. B. , Nakazawa M. , Carvalho A. B. , Souza W. V. , Ferreira A. G. P. , Silva E. D. , Krieger M. A. , Goldenberg S. , Gomes Y. M.
Published: October 2003

Background and Objectives  Serological screening for Chagas’ disease in the blood banks of South America is carried out by using two different assays that generally show a high number of inconclusive results. To establish a combination of two tests that can minimize the number of inconclusive results, we compared a recombinant enzyme‐linked immunosorbent assay (ELISA) with two conventional tests.

Materials and Methods  Serum samples from chagasic patients (n = 112), from non‐chagasic individuals (n = 143) and from patients with other diseases (n = 32) were tested using three assays: recombinant ELISA (Rec‐ELISA); conventional ELISA (Con‐ELISA); and the indirect haemagglutination (IHA) test.

Results  When we evaluated the data by matching the Rec‐ELISA and the IHA test, 52 inconclusive results were obtained. When Rec‐ELISA and Con‐ELISA were matched, only four inconclusive results were observed.

Conclusions  Our investigation indicates that the use of two ELISAs with different antigen preparations provides an effective test combination for blood bank screening of Chagas’ disease.
Elastic properties of stored red blood cells from sickle trait donor units
Authors: Brandão M. M. , Saad S. T. O. , Cezar C. L. , Fontes A. , Costa F. F. , Barjas‐Castro M. L.
Published: October 2003

Background and Objectives  Red blood cells (RBCs) from patients with sickle cell disease present reduced deformability. The aim of this study was to analyse the elasticity of stored RBCs from patients with the sickle cell trait (AS).

Materials and Methods  The cell elasticity was studied, using laser optical tweezers, on storage days 1, 14, 21, 28 and 35.

Results  The elasticity of RBC from AS units stored for 1, 14 and 21 days was significantly greater compared with that of control RBC cells stored for the same time‐period. More than 30% of the cells from AS units stored for 28 or 35 days were very rigid and escaped from the optical trap.

Conclusions  RBCs became rigid during storage, suggesting that haemoglobin S might compromise the cell elasticity.
Alanine aminotransferase cut‐off values for blood donor screening using the new International Federation of Clinical Chemistry reference method at 37 °C
Authors: Brinkmann T. , Dreier J. , Diekmann J. , Götting C. , Klauke R. , Schumann G. , Kleesiek K.
Published: October 2003

Background and Objectives  Serum alanine aminotransferase (ALT) determination is recommended, or even required by law, in the screening of blood donors in many countries, and donors with an increased catalytic activity of ALT are excluded from blood donation. In most countries, the ALT cut‐off value for blood donor screening for men and women is twice the upper limit of the normal range. The introduction, in 2002, of the new International Federation of Clinical Chemistry (IFCC) reference method, performed at 37 °C, required new ALT reference values to be established for healthy individuals and a new cut‐off point to be determined for blood donor screening.

Materials and Methods  We compared ALT values of donor blood units using the previous German standard method, which measures ALT values at 25 °C, and the new IFCC reference procedure, where ALT levels are measured at 37 °C.

Results  We found a linear correlation between the ALT values obtained by the method at 25 °C and the new IFCC reference method (37 °C) (r = 0·983), and a gender‐ and age‐independent ratio of 0·523. Using this ratio we calculated the new ALT cut‐off for blood donations and now propose a new upper limit of 132 U/l (2·20 µkat/l) for men and 86 U/l (1·43 µkat/l) for women. Only 220 of 151 678 blood donations collected over a period of 5 years showed an ALT value higher than the cut‐off. None were hepatitis C virus (HCV) positive in serological or nucleic acid amplification technology (NAT) assays. Only 0·006% of all blood donations were positive for antibody to HCV and thus excluded.

Conclusions  With the implementation of the new IFCC reference method for ALT determination at 37 °C, we propose a new ALT cut‐off for blood donor screening, which, for men, is about three times the upper limit of the normal range and for women about 2·5 times. Our results show that a lower cut‐off would probably not yield a higher safety of blood products in terms of detecting viral infections, but would result in a loss of ≈ 0·75% of suitable blood donors.
Preclinical safety profile of plasma prepared using the INTERCEPT Blood System
Authors: Ciaravino V. , McCullough T. , Cimino G. , Sullivan T.
Published: October 2003

Background and Objectives  The newly developed INTERCEPT Blood System for plasma uses the addition of a new psoralen, amotosalen HCl (AMOTOSALEN), followed by illumination with ultraviolet A light, to inactivate viruses, bacteria, protozoa and leucocytes that may contaminate fresh‐frozen plasma (FFP). Extensive toxicology studies were performed to characterize the safety of the photochemical treatment process for its intended use with plasma.

Materials and Methods  The studies of general toxicology, safety pharmacology, phototoxicity, reproductive toxicity and venous irritation, summarized in this review, provide a comprehensive toxicology profile for photochemically treated 100% plasma.

Results  No specific target organ toxicity (based on clinical or histological pathology), phototoxicity, or reproductive toxicity was observed.

Conclusions  The results of an extensive series of studies have demonstrated no toxicologically relevant effects of photochemically treated 100% plasma prepared using the INTERCEPT Blood System for plasma.
Storage of platelets in additive solutions: a multicentre study of the in vitro effects of potassium and magnesium
Authors: Gulliksson H. , AuBuchon J. P. , Cardigan R. , Van Der Meer P. F. , Murphy S. , Prowse C. , Richter E. , Ringwald J. , Smacchia C. , Slichter S. , De Wildt‐Eggen J.
Published: October 2003

Background and Objectives  In a preliminary study, the presence of potassium and magnesium in a modified synthetic medium (PAS‐III) was found to have a significant influence on platelet metabolism (using apheresis‐derived, as well as buffy‐coat‐derived platelets) when compared with standard PAS‐III. The differences included reduced glycolysis, as evidenced by lower consumption of glucose and lower production of lactate, but also better preservation of pH and hypotonic shock response reactivity. The results suggested that storage in modified PAS‐III containing 20% plasma was comparable to storage in standard PAS‐III containing 30% plasma. To confirm the preliminary results and to evaluate the effects of different preparation protocols, an international multicentre study, which included 11 different sites, was conducted.

Materials and Methods  Platelets from 30 pools of ≈ 20 buffy coat (BC) units each and 24 pooled apheresis platelet units were aliquoted for storage in plasma (reference) or synthetic medium using either a specific additive solution (PAS‐III) containing 30% plasma or a modification of PAS‐III containing 5·0 mm potassium and 1·5 mm magnesium (PAS‐IIIM) and either 30% or 20% plasma. Units were stored at room temperature with agitation for 7 days during which in vitro testing was carried out for biochemical, haematological and functional parameters.

Results  Storage of platelets in PAS‐IIIM resulted in a reduction in the rate of glycolysis and better retention of pH and hypotonic shock response reactivity. Storage in PAS‐IIIM containing 20% plasma appeared to result in the retention of in vitro properties, similar to those observed during storage in standard PAS‐III containing 30% plasma.

Conclusions  The results of this study confirm the preliminary results. Similar results were seen with platelets prepared by BC and apheresis methods, despite differences in equipment, the preparation technique and in the final platelet contents achieved in the platelet units. Storage of platelets in PAS‐IIIM should be considered to improve platelet function and allow plasma reduction to 20%.
The origin and identification of unknown events associated with low‐level leucocyte counting by flow cytometry
Authors: Bashir S. , Cardigan R.
Published: October 2003

Background and Objectives  Flow cytometric enumeration of residual leucocytes (WBC) in leucocyte‐depleted components occasionally reveals a population of events that stain with propidium iodide, but which are outside the main counting region. These extraregional events may result in discrepancies in residual WBC counts.

Materials and Methods  To identify the origin of these unknown events, separate populations of mononuclear cells and polymorphonuclear neutrophils (PMNs) (prepared by density‐gradient centrifugation) were spiked into leucocyte‐depleted red cell concentrates (RCC) to a concentration of 150 cells/µl and assessed, using LeucoCount and DNA Prep reagents, by flow cytometry. In addition, isolated WBC nuclei, DNA in saline, or enzymatically digested free DNA, was spiked into diluted whole blood (final concentration 5 µg/ml).

Results  Isolated WBC nuclei fell in the main counting region of the dot plot. Extraregional events were generated in leucocyte‐depleted RCC spiked with PMN (17/µl by day 4), but not with mononuclear cells, and increased with sample storage (4 days). A significantly (P < 0·01) greater number of extraregional events was observed using the LeucoCount reagent, compared with the DNA Prep reagent. Enzymatically digested WBC nuclei or free DNA, added to diluted whole blood, generated extraregional events using LeucoCount, but not the DNA Prep reagent. When free DNA was enzymatically digested, no extraregional events were observed.

Conclusions  These previously unidentified events are probably fragmented nuclei or free DNA originating from PMN owing to a combination of ageing and reagent addition. Currently, in our protocols, the region used for WBC enumeration counts intact WBC nuclei. To achieve WBC counting consistency, flow cytometric gating protocols must be standardized, and a decision taken as to whether to include extraregional events in the count.
Composition of the additive solution affects red blood cell integrity after photodynamic treatment
Authors: Besselink G. A. J. , Ebbing I. G. , Hilarius P. M. , De Korte D. , Verhoeven A. J. , Lagerberg J. W. M.
Published: October 2003

Background and Objectives  Photodynamic treatment is a promising technique for pathogen inactivation of red blood cell concentrates. For protocol optimization, the influence of the composition of the storage solution on the integrity of phototreated red cells was studied.

Materials and Methods  Red blood cells were resuspended in the storage solutions SAG‐M or AS‐3 to a haematocrit (Hct) of 30%. After addition of the photosensitizer, 1,9‐dimethylmethylene blue (DMMB) (25 µm), the suspensions were illuminated with red light, and potassium leakage and delayed haemolysis were determined. In some experiments, the cells were washed after illumination and resuspended in modified storage solutions.

Results  Illumination of red cells in the presence of DMMB resulted in an immediate, light‐dose‐dependent increase in potassium leakage. The illumination conditions used induced no detectable haemolysis immediately after photodynamic treatment. Potassium leakage was higher when the illumination was performed in AS‐3. In contrast, delayed haemolysis, measured after overnight storage, was considerably lower when cells were stored in AS‐3. This protection was mainly a result of the presence of citrate in AS‐3. In addition, other impermeant solutes protected against haemolysis.

Conclusions  The additive solution strongly influences the integrity of red cells after photodynamic treatment. Whereas the solution in which the cells are illuminated has a small effect on red cell integrity, the main influence of the additive solution is during post‐treatment storage. Red cell integrity is best maintained when illumination is performed in SAG‐M followed by storage in AS‐3. The presence of non‐permeant solutes, such as citrate, in the solution used for storage, prevents haemolysis of the phototreated, cation‐permeable cells by counterbalancing the osmotic activity of haemoglobin.
Storage of platelets in additive solutions: the effects of magnesium and potassium on the release of RANTES, β‐thromboglobulin, platelet factor 4 and interleukin‐7, during storage
Authors: Shanwell A. , Falker C. , Gulliksson H.
Published: October 2003

Background and Objectives  Several studies have suggested that the accumulation of cytokines during storage of platelet concentrates may mediate non‐haemolytic transfusion reactions. Prestorage leucodepletion can prevent the release of cytokines from white blood cells during storage, but not the release of platelet‐derived cytokines. Therefore, we investigated whether the addition of magnesium and potassium to platelets stored in a platelet additive solution (PAS) would affect the generation of cytokines during platelet storage.

Materials and Methods  Platelets were prepared from buffy coats using different suspension media: plasma; 70% PAS‐III + 30% plasma; 70% PAS‐III supplemented with magnesium and potassium +30% plasma; and 80% PAS‐III supplemented with magnesium and potassium +20% plasma. The levels of certain cytokines – regulated on activation, normal, T‐cell expressed, and secreted (RANTES), β‐thromboglobulin (β‐TG), platelet factor 4 (PF4) and interleukin‐7 (IL‐7) – were measured by enzyme‐linked immunosorbent assay (ELISA) on days 1, 5 and 7.

Results The concentrations of RANTES, β‐TG, PF4 and IL‐7 increased, during storage, in all units. The increase was significantly greater in units stored in 70% PAS‐III +30% plasma than in the other three suspension media. The storage of platelets in 70% PAS‐III supplemented with magnesium and potassium +30% plasma significantly reduced the concentrations of platelet derived‐cytokines during storage, as compared to platelets stored in 70% PAS‐III + 30% plasma alone.

Conclusions  The concentrations of platelet‐derived cytokines increased, to a significantly greater extent, when platelets were stored in PAS‐III than in plasma. However, when magnesium and potassium were added to PAS‐III, the concentrations of platelet‐derived cytokines obtained during storage were about the same as those produced by platelets stored in plasma.
Fission yeast decaprenyl diphosphate synthase consists of Dps1 and the newly characterized Dlp1 protein in a novel heterotetrameric structure
Authors: Saiki Ryoichi , Nagata Ai , Uchida Naonori , Kainou Tomohiro , Matsuda Hideyuki , Kawamukai Makoto
Published: October 2003

The analysis of the structure and function of long chain‐producing polyprenyl diphosphate synthase, which synthesizes the side chain of ubiquinone, has largely focused on the prokaryotic enzymes, and little is known about the eukaryotic counterparts. Here we show that decaprenyl diphosphate synthase from Schizosaccharomyces pombe is comprised of a novel protein named Dlp1 acting in partnership with Dps1. Dps1 is highly homologous to other prenyl diphosphate synthases but Dlp1 shares only weak homology with Dps1. We showed that the two proteins must be present simultaneously in Escherichia coli transformants before ubiquinone‐10, which is produced by S. pombe but not by E. coli, is generated. Furthermore, the two proteins were shown to form a heterotetrameric complex. This is unlike the prokaryotic counterparts, which are homodimers. The deletion mutant of dlp1 lacked the enzymatic activity of decaprenyl diphosphate synthase, did not produce ubiquinone‐10 and had the typical ubiquinone‐deficient S. pombe phenotypes, namely hypersensitivity to hydrogen peroxide, the need for antioxidants for growth on minimal medium and an elevated production of H2S. Both the dps1 (formerly dps) and dlp1 mutants could generate ubiquinone when they were transformed with a bacterial decaprenyl diphosphate synthase, which functions in its host as a homodimer. This indicates that both dps1 and dlp1 are required for the S. pombe enzymatic activity. Thus, decaprenyl diphosphate from a eukaryotic origin has a heterotetrameric structure that is not found in prokaryotes.
Fra‐1 targets the AP‐1 site/2G single nucleotide polymorphism (ETS site) in the MMP‐1 promoter
Authors: Tower Grant B. , Coon Charles I. , Belguise Karine , Chalbos Dany , Brinckerhoff Constance E.
Published: October 2003

The matrix metalloproteinase (MMP) family degrades the extracellular matrix. One member of this family, MMP‐1, initiates the breakdown of interstitial collagens. The expression of MMP‐1 is controlled by the mitogen activated protein kinase (MAPK) pathway(s) via the activity of activator protein‐1 (AP‐1) and polyoma enhancing activity‐3/E26 virus (PEA3/ETS) transcription factors through consensus binding sites present in the promoter. Another ETS site in the MMP‐1 promoter is created at −1607 bp by a single nucleotide polymorphism (SNP), which contains two guanines (5′‐GGAT‐3′; ‘2G SNP’), rather one guanine (5′‐GAT‐3′; ‘1G SNP’), adjacent to an AP‐1 binding site at −1602 bp. The 2G SNP displays greater transcriptional activity than the 1G SNP, and AP‐1 and Ets families of transcription factors cooperate to increase transcription. The 2G SNP has been linked to the incidence and the progression of several cancers and is also associated with non‐neoplastic diseases; although the underlying mechanism(s) has yet to be elucidated. In this study we demonstrate that the expression of Fos‐like region antigen (Fra‐1), an AP‐1 transcription factor component that also correlates strongly with neoplastic disease, is necessary for MMP‐1 transcription in A2058 melanoma cells. The inhibition of Fra‐1 expression preferentially downregulates transcription from the MMP‐1 promoter DNA containing the 2G SNP, compared to DNA containing the 1G SNP. This study provides evidence that, in cooperation with the 2G DNA polymorphism, the AP‐1 family member, Fra‐1, contributes to the high constitutive expression of MMP‐1 in melanoma cells.
Synthesis and cytogenetic characterization of intergeneric hybrids of Diplotaxis siifolia with Brassica rapa and B. juncea
Authors: Ahuja I. , Bhaskar P. B. , Banga S. K. , Banga S. S. , Rakow G.
Published: October 2003

Intergeneric hybrids involving a wild crucifer, Diplotaxis siifolia (2n = 20; DsDs), and two crop Brassica species, namely Brassica rapa (2n = 20; AA) and B. juncea (2n = 36; AABB), were developed through sequential ovary/ovule culture. Hybridization was successful only when D. siifolia was used as the female parent, indicating unilateral cross incompatibility. Hybrids were intermediate between the parents for morphological characteristics but had low male as well as female fertility. Meiotic studies of hybrids revealed partial homoeology between Ds and A/B genomes.
Enarthrocarpus lyratus‐based cytoplasmic male sterility and fertility restorer system in Brassica rapa
Authors: Deol J. S. , Shivanna K. R. , Prakash S. , Banga S. S. , Robbelen G.
Published: October 2003

Substituting the nuclear genome of Brassica rapa into the cytoplasmic background of Enarthrocarpus lyratus through backcross substitution helped in developing cytoplasmic male sterility (CMS). Alloplasmic male sterile plants had pale green leaves, small flowers with narrow petals and rudimentary anthers. Female fertility, low initially, improved considerably with advanced backcross generations. Male sterility expression was stable throughout the growing season. Except for EC 339014, all B. rapa accessions (38) evaluated were partial maintainers of the male sterility. Introgression of gene(s) for fertility restoration from the cytoplasm donor species was facilitated by homoeologous pairing between B. rapa and E. lyratus genomes, as was apparent from the very frequent occurrence of a trivalent in the monosomic addition plants (2n = 10 II + 1 I). Backcrossing of fertile monosomic addition plants with B. rapa led to the recovery of male fertile plants possessing the stable euploid chromosome number (2n = 20). These plants restored male fertility in crosses with different (lyr) CMS B. rapa genotypes, confirming the introgression of fertility restorer gene(s) from E. lyratus, the cytoplasm donor species.
Effects of the 7DL.7Ag translocation from Lophopyrum elongatum on wheat yield and related morphophysiological traits under different environments
Authors: Monneveux P. , Reynolds M. P. , Aguilar J. González , Singh R. P. , Weber W. E.
Published: October 2003

The 7DL.7Ag translocation from Lophopyrum elongatum that carries Lr19, a leaf rust resistance gene, was found to be associated with a significant increase in grain yield under irrigated, disease‐free conditions, but a generally lower yield under moisture stress conditions. These studies, however, involved a limited number of genetic recipients and environments, and the effect of the translocation on physiological traits was not considered. We examined the translocation effect in six different recipient genotypes and under five environmental conditions, including drought and heat stress. The increase in grain yield under irrigated conditions was associated with a higher rate of biomass production in the 7DL.7Ag lines and may be attributed to higher sink strength. Effect of the translocation on physiological traits was noted only under heat stress and was not associated with difference in yield. Under moisture stress conditions, 7DL.7Ag lines yielded less than their corresponding recipients, possibly because of a longer growing cycle. It is concluded that the effect of the 7DL. 7Ag translocation may very much depend on the phenological adaptation of the recipient genotype and the translocation may be useful for enhancing yield, mainly under favourable conditions.