bluuebunny/crossref_metadata_2025 huggingface dataset:
Household drinking water in developing countries: a systematic review of microbiological contamination between source and point‐of‐use
Authors: Wright Jim , Gundry Stephen , Conroy Ronan
Published: January 2004

Objective  To assess the extent and causes of microbiological contamination of household drinking water between source and point‐of‐use in developing countries.

Methods  A systematic meta‐analysis of 57 studies measuring bacteria counts for source water and stored water in the home to assess how contamination varied between settings.

Results  The bacteriological quality of drinking water significantly declines after collection in many settings. The extent of contamination after water collection varies considerably between settings, but is proportionately greater where faecal and total coliform counts in source water are low.

Conclusions  Policies that aim to improve water quality through source improvements may be compromised by post‐collection contamination. Safer household water storage and treatment is recommended to prevent this, together with point‐of‐use water quality monitoring.
The changing epidemiology of malaria in Ifakara Town, southern Tanzania
Authors: Schellenberg David , Menendez Clara , Aponte John , Guinovart Caterina , Mshinda Hassan , Tanner Marcel , Alonso Pedro
Published: January 2004

Between 1995 and 2000 there were marked changes in the epidemiology of malaria in Ifakara, southern Tanzania. We documented these changes using parasitological and clinical data from a series of community‐ and hospital‐based studies involving children up to the age of 5 years. There was a right shift and lowering in the age‐specific parasite prevalence in the community‐based cohort studies. The incidence of clinical malaria in placebo‐receiving infants in additional study cohorts dropped from 0.8 in 1995 to 0.43 episodes per infant per year in 2000, an incidence rate ratio of 0.53 (95% confidence interval: 0.404, 0.70, P < 0.0001). At the same time, there was an increase in the total number of malaria admissions and a marked right shift in the age pattern of these admissions (median age in 1995 1.55 years vs. 2.33 in 2000, P < 0.0001). However, the burden of malaria deaths remained in infants. We discuss how these dramatic changes in the epidemiology of malaria may have arisen from the use of currently available malaria control tools. Caution is required in the interpretation of hospital‐based data as it is likely to underestimate the impact of anaemia on mortality in the community, where most paediatric deaths occur. Even in low/moderate malaria transmission settings, where older children suffer most malaria episodes, targeting effective malaria control at infants may produce important reductions in infant mortality caused by malaria.
Malaria transmission dynamics at a site in northern Ghana proposed for testing malaria vaccines
Authors: Appawu Maxwell , Owusu‐Agyei Seth , Dadzie Samuel , Asoala Victor , Anto Francis , Koram Kwadwo , Rogers William , Nkrumah Francis , Hoffman Stephen L. , Fryauff David J.
Published: January 2004

We studied the malaria transmission dynamics in Kassena Nankana district (KND), a site in northern Ghana proposed for testing malaria vaccines. Intensive mosquito sampling for 1 year using human landing catches in three micro‐ecological sites (irrigated, lowland and rocky highland) yielded 18 228 mosquitoes. Anopheles gambiae s.l. and Anopheles funestus constituted 94.3% of the total collection with 76.8% captured from the irrigated communities. Other species collected but in relatively few numbers were Anopheles pharoensis (5.4%) and Anopheles rufipes (0.3%). Molecular analysis of 728 An. gambiae.s.l. identified Anopheles gambiae s.s. as the most dominant sibling species (97.7%) of the An. gambiae complex from the three ecological sites. Biting rates of the vectors (36.7 bites per man per night) were significantly higher (P < 0.05) in the irrigated area than in the non‐irrigated lowland (5.2) and rocky highlands (5.9). Plasmodium falciparum sporozoite rates of 7.2% (295/4075) and 7.1% (269/3773) were estimated for An. gambiae s.s. and An. funestus, respectively. Transmission was highly seasonal, and the heaviest transmission occurred from June to October. The intensity of transmission was higher for people in the irrigated communities than the non‐irrigated ones. An overall annual entomological inoculation rate (EIR) of 418 infective bites was estimated in KND. There were micro‐ecological variations in the EIRs, with values of 228 infective bites in the rocky highlands, 360 in the lowlands and 630 in the irrigated area. Approximately 60% of malaria transmission in KND occurred indoors during the second half of the night, peaking at daybreak between 04.00 and 06.00 hours. Vaccine trials could be conducted in this district, with timing dependent on the seasonal patterns and intensity of transmission taking into consideration the micro‐geographical differences and vaccine trial objectives.
Genetic markers of resistance to pyrimethamine and sulfonamides in Plasmodium falciparum parasites compared with the resistance patterns in isolates of Escherichia coli from the same children in Guinea‐Bissau
Authors: Kofoed Poul‐Erik , Alfrangis Michael , Poulsen Anja , Rodrigues Amabelia , Gjedde Susanne Borum , Rønn Anita , Rombo Lars
Published: January 2004

The antifolate drugs sulphadoxine and pyrimethamine are used for treatment of chloroquine‐resistant Plasmodium falciparum in Africa. Resistance to pyrimethamine has been associated with point mutations in the dhfr‐gene and resistance to sulphadoxine with mutations in the dhps‐gene. There is concern that the use of the antifolates trimethoprim and sulphamethoxazole for treatment of other infectious diseases will result in the selection of malaria parasites with mutations in these genes. In Guinea‐Bissau, where sulfonamide and trimethoprim‐containing drugs have been used extensively, we decided to assess the prevalence of mutations in the dhfr‐and dhps‐gene in P. falciparum isolated from children suffering from acute malaria and to assess the resistance patterns to trimethoprim/sulphamethoxazole in Escherichia coli isolated from the same patients. A thick film and a blood sample for polymerase chain reaction (PCR) were obtained from 100 children attending the Bandim Health Centre in Bissau with symptoms compatible with malaria. Furthermore, a stool sample was collected from the same children and cultured for E. coli. Of the cultured E. coli, 67% were resistant both to sulfonamides and trimethoprim, 4% to sulfonamides alone, 3% to trimethoprim alone while 26% were fully sensitive to both drugs. PCR was successfully performed in 97 blood samples. Of these, 41% had triple mutations at the dhfr‐gene (at codons 51, 59 and 108), and 15% had triple mutations plus mutation at codon 437 in the dhps‐gene. Only 45% harboured the wild‐type dhfr‐gene. Thus both bacterial resistance and mutations in the parasitic genes were common, but not linked in the individual child. As sulphadoxine–pyrimethamine has only been used as a second line treatment for chloroquine resistant malaria in Guinea‐Bissau for a few years, it is worrying to find a high prevalence of mutations in the parasitic genes coding for resistance to these drugs. Therefore, restricting the use of sulphadoxine–pyrimethamine for the treatment of chloroquine resistant malaria might not be sufficient to prevent the development of resistance in the parasites as long as antifolate drugs are used extensively.
Epidemiological and entomological surveillance of the co‐circulation of DEN‐1, DEN‐2 and DEN‐4 viruses in French Guiana
Authors: Fouque Florence , Garinci Romuald , Gaborit Pascal
Published: January 2004

We surveyed the disease epidemiology of dengue in French Guiana after the first dengue haemorrhagic fever epidemic from 1991 to 1993 and during an endemic period from 1993 to 1995. DEN‐1, DEN‐2 and DEN‐4 viruses were isolated from patients and DEN‐4 was also isolated from Aedes aegypti mosquitoes. Cases of dengue were reported from all over the country, not only from urban areas, but also from rural areas and isolated human settlements, indicating widespread circulation of the viruses. The mosquito vector A. aegypti was found in all inhabited areas of French Guiana and small outdoor containers were the most common breeding grounds. Some ecological features of A. aegypti, such as larvae breeding in Bromeliad plants in the rainforest, a non‐exclusive anthropophily and a high vertical transmission rate for dengue viruses, indicate that A. aegypti can behave as a reservoir for dengue viruses in silent areas. Dengue viruses may survive at an endemic level and cause outbreaks when unknown conditions become more favourable. This finding adds to our knowledge of the natural history of dengue viruses in the Americas.
The efficacy of chloroquine, sulfadoxine–pyrimethamine and a combination of both for the treatment of uncomplicated Plasmodium falciparum malaria in an area of low transmission in western Uganda
Authors: Ndyomugyenyi Richard , Magnussen Pascal , Clarke Siân
Published: January 2004

We conducted an efficacy study of chloroquine (CQ), sulfadoxine–pyrimethamine (SP) and a combination of both (SP + CQ) for the treatment of uncomplicated malaria in an area of low transmission with low drug pressure. On day 3, fever clearance was 97.4% (95% CI, 86.8–99.9), 100% (95% CI, 87.2–100) and 96.6% (95% CI, 82.2–99.9) in the CQ, SP and SP + CQ groups, respectively, (P = 0.65). On day 14, clinical success was 92.5% (95% CI, 79.6–98.4), 100% (95% CI, 87.2–100) and 100% (95% CI, 88.1–100) in the CQ, SP and CQ + SP groups, respectively. Clinical failure was seen in 7.5% with 5% (95% CI, 0.61–16.9) early treatment failure and 2.5% (95% CI, 0.06–13.2) late treatment failure of cases in the CQ group and 0% in the SP and SP + CQ groups. Parasitological resistance was observed at RI level in 10% (95% CI, 2.8–23.7), 18.5% (95% CI, 6.3–38.1) and 6.9% (95% CI, 0.85–22.8) for the CQ, SP and SP + CQ, respectively (P = 0.37). There was no age‐dependent difference in clinical failure or parasitological resistance in any of the treatment groups and prior CQ use within the last 2 weeks did not affect CQ treatment outcome. The findings of this study suggest that CQ is still effective for the treatment of uncomplicated malaria in this area of low transmission and SP. However, combination therapy of SP + CQ is recommended to delay the development SP resistance, and regular surveillance for emerging CQ and SP resistance is needed to plan for alternative antimalarial drug regimens.
Addition of artesunate to chloroquine for treatment of Plasmodium falciparum malaria in Gambian children causes a significant but short‐lived reduction in infectiousness for mosquitoes
Authors: Drakeley Christopher J. , Jawara Musa , Targett Geoffrey A. T. , Walraven Gijs , Obisike Uche , Coleman Rosalind , Pinder Margaret , Sutherland Colin J.
Published: January 2004

Objectives  Combination therapy using existing anti‐malarials together with artesunate (AS) has been advocated as a method to slow the spread of drug resistance. We assessed the effect on Plasmodium falciparum transmissibility of the addition of AS to chloroquine (CQ) in an area of The Gambia where resistance to CQ is increasing.

Methods  Gambian children with acute uncomplicated P. falciparum malaria were treated with either CQ monotherapy (n = 120) or the combination of CQ plus three doses of AS (CQ/AS; n = 352). Post‐treatment sexual‐stage parasitaemia was assessed during a 4‐week follow‐up period. Experimental infections of Anopheles gambiae s.s. mosquitoes were performed with blood from patients who were carrying gametocytes 7 days after starting treatment (n = 69).

Results  The addition of AS significantly reduced post‐treatment prevalence and mean density of gametocytes in the first 14 days (day 7: 43.7%vs. 12.4%, 62.4/μl vs. 6.2/μl; day 14: 32.9%vs. 3.7%; 21.9/μl vs. 5.2/μl; CQ vs. CQ/AS), although by day 28 the benefits of the combination were substantially less marked (40.5%vs. 21.8%; 23.0/μl vs. 63.1/μl; CQ vs. CQ/AS). The duration of gametocyte carriage over the study period was significantly lower in the CQ/AS group (5.2 days vs. 1.5 days; CQ vs. CQ/AS). The estimated infectious proportion of children at day 7 was also lower in the combination group (19.2%vs. 3.4%; CQ vs. CQ/AS), as were the proportion of mosquitoes infected and mean oocyst density (11.5%vs. 0.9%; 0.3 vs. 0.01; CQ vs. CQ/AS). Treatment failure was associated with threefold and twofold higher gametocyte carriage rates during follow‐up in CQ and CQ/AS groups, respectively (P < 0.001 in both cases), and 26‐fold and 2.3‐fold higher intensity of infection at day 7 among CQ‐ and CQ/AS‐treated children, respectively (P = 0.002 and 0.30, respectively).

Conclusion  The benefits of adding AS to CQ monotherapy in lowering gametocyte prevalence and density were transient, suggesting that the addition of AS delayed, but did not prevent, the emergence of gametocytes. This is consistent with our finding that treatment failure, and thus the presence of CQ‐resistant parasites, was significantly associated with a higher gametocyte carriage rate in both treatment groups. At day 7, CQ monotherapy significantly favoured transmission of resistant infections, which showed an 11‐fold greater intensity of transmission compared with infections that were successfully treated. In contrast, the combination of CQ/AS did not significantly favour resistant infections at day 7. We conclude that significant transmission‐reduction is achieved by the combination but is not maintained because of the recrudescence of CQ‐resistant parasites.
Use of antenatal care services and intermittent preventive treatment for malaria among pregnant women in Blantyre District, Malawi
Authors: Holtz Timothy H. , Patrick Kachur S. , Roberts Jacquelin M. , Marum Lawrence H. , Mkandala Christopher , Chizani Nyson , Macheso Allan , Parise Monica E.
Published: January 2004

Malaria in pregnancy contributes to low birth weight and increased infant mortality. As part of WHO's Roll Back Malaria initiative, African heads of state pledged that by 2005, 60% of pregnant women will receive malaria chemoprophylaxis or intermittent preventive treatment (IPT). We performed a cluster sample survey to study the use of sulfadoxine–pyrimethamine (SP) for IPT among recently pregnant women in February 2000 in Blantyre District, Malawi. Among 391 women in the sample, 98.6% had attended antenatal clinic at least once and 90.2% knew that SP/IPT was recommended during pregnancy. Overall, only 36.8% received the full recommended two‐dose regimen of SP/IPT. Using data from 187 women with antenatal clinic cards, we found that residence location, housing type and gender/age/education of the head of household were not associated with failure to receive SP/IPT. Adjusting for education, multigravid women were more likely not to receive the recommended SP/IPT regimen (RR 1.2, 95% CI 1.02–1.5, P = 0.03). A substantial effort to improve the delivery and use of SP/IPT in Malawi will be necessary, but the Roll Back Malaria 2005 goal appears achievable.
ONO‐8815Ly, an EP2 agonist that markedly inhibits uterine contractions in women
Authors: Steinwall M. , Åkerlund M. , Bossmar T. , Nishii M. , Wright M.
Published: January 2004

Objective  To determine the effect of ONO‐8815Ly on uterine contractions.

Design  A randomised, double‐blind, placebo‐controlled, dose‐ascending, cross‐over study.

Setting  Department of Obstetrics and Gynaecology, University Hospital of Lund, Sweden.

Population  Seventeen, healthy, parous and permanently sterilised women.

Methods  Intrauterine pressure was recorded on days 1–3 of bleeding of two menstruations. Subjects were intravenously treated with 4 or 8 μg/minute of ONO‐8815Ly or placebo for 130 minutes. Intravenous bolus injections of oxytocin, 50 pmol/kg body weight, were given 10 minutes before, during infusion after 60 and 120 minutes and 60 minutes after completion of infusion. The plasma concentrations of ONO‐8815Ly were measured in samples obtained immediately before each oxytocin injection.

Main outcome measure  Area under pressure recording curve (AUC) 10 minutes before and after each oxytocin injection.

Results  Twelve women, six in each dose group, completed both recordings. Of these, two women of each group were not included in efficacy analysis due to non‐responsiveness to oxytocin or missing baseline value. The AUC over 10 minutes before oxytocin injection after 60 minutes of infusion of ONO‐8815Ly at 4 and 8 μg/minute was reduced to 21% and 37% of that before infusion, respectively. The AUC after oxytocin at that time amounted to 21% and 19%, respectively, of that before infusion. The activity and responsiveness remained low after 120 minutes but started to return to baseline 60 minutes after stopping infusion. Placebo had no effect.

Conclusions  ONO‐8815Ly is a potent inhibitor of spontaneous uterine contractility in non‐pregnant women and it reduces the uterine response to oxytocin injections.
Are reported preterm birth rates reliable? An analysis of interhospital differences in the calculation of the weeks of gestation at delivery and preterm birth rate
Authors: Balchin Imelda , Whittaker John C. , Steer Philip J. , Lamont Ronald F.
Published: January 2004

We investigated the possibility of preterm birth misclassification as a determinant of variation in its reported rates. Using a database of 497,105 deliveries from 17 hospitals, the best estimate of gestational age made at delivery and entered into the database at that time was recalculated from the menstrual dates and mid‐trimester ultrasound scan. The recalculated completed weeks of gestation at delivery was compared with that made at birth. Calculation of estimated gestational age varied between hospitals due to inconsistencies in ‘rounding’ and ‘truncating’ the weeks of gestation at delivery. This resulted in preterm birth misclassification rates of up to 10.1%.
Women's perceptions of decision‐making about hysterectomy
Authors: Skea Z. , Harry V. , Bhattacharya S. , Entwistle V. , Williams B. , MacLennan G. , Templeton A.
Published: January 2004

Objective  To explore women's views of decision‐making relating to hysterectomy.

Design  Structured questionnaire and in‐depth interview surveys.

Setting  A teaching hospital and a district general hospital in northeast Scotland.

Sample  Women scheduled for hysterectomy for benign menstrual problems.

Methods  Pre‐operative questionnaires were sent to a consecutive sample of women booked for hysterectomy. A purposive sample was interviewed post‐operatively.

Main outcome measures  Women's experiences of, and satisfaction with, information provision, communication and decision‐making processes; the relationship between views of decision‐making processes and decisions made.

Results  One hundred and four women (66%) returned questionnaires. Most responded positively to structured questions about the process by which the decision to have a hysterectomy was reached. Almost all (97%) reported satisfaction with the decision made. Twenty women were interviewed post‐operatively. A number, including some who had responded positively on the questionnaire, described aspects of the decision‐making process that were suboptimal. Women's perceptions of the decision‐making process, including the way their doctors communicated with them, did impinge on their views of the course of action selected. Some women had residual doubts about the appropriateness of hysterectomy.

Conclusions  In a significant minority of women, there are important shortcomings in current patterns of information provision and communication relating to decision‐making. These are unlikely to be picked up by conventional structured patient feedback surveys. Further efforts are required to ensure that women are adequately informed and involved in decisions about gynaecological treatments.
Feasibility of central co‐ordinated EMA/CO for gestational trophoblastic disease in the Netherlands
Authors: van der Houwen Clasien , Rietbroek Ron C. , Lok Christianne A.R. , Ten Kate‐Booij Marianne J. , Lammes Frits B. , Ansink Anca C.
Published: January 2004

Objective  In the Netherlands, high risk gestational trophoblastic disease (GTD) patients are treated in different referral hospitals with a national working party on trophoblastic tumours having a co‐ordinating function. Our purpose was to evaluate whether this policy is a satisfactory alternative to complete centralisation.

Design  A retrospective study of all etoposide, methotrexate, actomycin D, cyclophosphamide and vincristine (EMA/CO)‐treated women in the Netherlands between 1986 and 1997. Data regarding risk factors, treatment results and toxicity were collected.

Setting  Ten hospitals; 2 general, 6 academical and 2 oncology centres.

Population  Fifty EMA/CO‐treated women registered by the central registration unit of the Dutch Working Party on Trophoblastic Disease.

Methods  Patients files and quarterly reports of the Dutch Working Party.

Main outcome measures  Cure rate and consistency of treatment in different hospitals.

Results  EMA/CO treatment was administered in 10 different hospitals. All patients were discussed during the meetings of the Dutch Working Party and overall, 86% of patients were cured. Consistency in treatment was good.

Conclusions  Cure rates were comparable with results of single institution series. We conclude that treatment of high risk GTD patients in different referral hospitals with concentration of expertise in a working party is a good alternative to centralisation of treatment in GTD specialised hospitals.
The use of oral misoprostol for pre‐abortion cervical priming: a randomised controlled trial of 400 versus 200 μg in first trimester pregnancies
Authors: Oppegaard Kevin S. , Abdelnoor Mikael , Nesheim Britt‐Ingjerd , Jerve Fridtjof , Eskild Anne
Published: January 2004

Objective  To compare the impact of 200 and 400 μg oral misoprostol on pre‐operative cervical priming in both primi‐ and multigravidae prior to first trimester termination of pregnancy. Pre‐operative cervical dilatation and bleeding were assessed.

Design  Randomised controlled trial.

Setting  Norwegian university teaching hospital.

Sample  Five hundred and fifty‐one women undergoing surgical termination of pregnancy between 7 and 12 weeks of gestation.

Methods  Patients were randomised to either 200 or 400 μg of oral misoprostol 10–16 hours before vacuum aspiration. The degree of cervical dilatation prior to abortion by vacuum aspiration was measured. Pre‐operative bleeding and pain were recorded and vaginal bleeding was measured.

Main outcome measures  Degree of pre‐operative cervical dilatation and pre‐operative bleeding.

Results  The mean cervical dilatation was 5.8 mm (SD 1.7) for the women who received 400 μg misoprostol and 5.4 mm (SD 1.4) for those who received 200 μg (P= 0.004). The pre‐operative dilatation was larger in multigravidae than in primigravidae in both dosage groups. The odds ratio (OR) of pre‐operative bleeding was 3.3 (95% confidence interval [CI] 2.1–5.0) in the 400 μg dosage group, as compared with the group receiving 200 μg misoprostol. The occurrence of bleeding was dose‐dependent. Frequency of bleeding was similar in multigravidae compared with primigravidae in the 400 μg dosage group, whereas the occurrence of bleeding was less in primigravidae than multigravidae in the 200 μg dosage group. Only 89 out of 551 patients bled one or more grams. The volumes measured were not statistically significantly different. Complications were minor, and were distributed equally between the two dosage groups.

Conclusions  The 200 μg oral misoprostol compared with the 400 μg oral misoprostol given 10–16 hours before first trimester surgical abortions results in less pre‐operative vaginal bleeding and in a statistically, although not clinically significant reduction in cervical dilatation.
Recurrent persistent occipito‐posterior position in subsequent deliveries
Authors: Gardberg Mikael , Stenwall Olga , Laakkonen Eero
Published: January 2004

A nine year follow up study of the delivery pattern of 119 women after delivery in the persistent occiput posterior position and their occipito‐anterior controls. The studied parameters were: number of deliveries, number of repeated cases of persistent occiput posterior position and operative deliveries. Deliveries in the occipito‐posterior position were more common in the study group than in the controls (P= 0.031). Except for this, no statistically significant differences were found between the groups. According to the results, recurrence of the persistent occiput posterior position is common. A history of delivery in the persistent occiput posterior position does not seem to have any major impact on future childbearing.
NF‐κB Activation at Implantation Window of the Mouse Uterus
Authors: Nakamura Hitomi , Kimura Tadashi , Ogita Kazuhide , Nakamura Takafumi , Takemura Masahiko , Shimoya Koichiro , Koyama Sinsuke , Tsujie Tomoko , Koyama Masayasu , Murata Yuji
Published: January 2004

Problem:  Nuclear factor kappa B (NF‐κB) is one candidate transcriptional modulator, which might regulate many kinds of molecules that play sequential roles at implantation in the endometrium. However, temporal and spatial activation of NF‐κB at implantation window is unknown.

Methods:  Activation of NF‐κB in the mouse uterus was determined by electrophoretic mobility shift assays. Localization of p50 and p65, components of NF‐κB, was analyzed by immunohistochemistry.

Results:  NF‐κB was activated in the proestrus and estrus phases in non‐pregnant uterus. In the pregnant uterus, NF‐κB was activated after day 1.5 post‐coitum, and the activation continued during implantation period. The immunoreactivities of p50 and p65 were mainly localized in endometrial epithelium, and were weaker in endometrial stroma cells.

Conclusion:  NF‐κB activity is dynamically regulated during the sexual cycle as well as during the implantation period in the endometrium, where the biochemical interaction between mother and conceptus first occurs.
Estrogen Decreases Expression of Chemokine Receptors, and Suppresses Chemokine Bioactivity in Murine Monocytes
Authors: Janis Kelly , Hoeltke Janice , Nazareth Michael , Fanti Peter , Poppenberg Kristin , Aronica Susan M.
Published: January 2004

Problem:  We propose that the ability of estrogen exposure to increase the probability of a woman developing breast cancer may be related to decreased chemokine activity and suppression of immune surveillance in mammary tissue. The present study was conducted to determine whether estrogen could decrease monocyte bioactivity through alteration of chemokine receptor expression.

Method of study:  We examined the effect of estrogen and tamoxifen on the expression of the chemokine receptors CCR2 and CXCR3 on murine monocytes treated in culture and in vivo. Effects of estrogen on chemokine activation of monocytes were also evaluated.

Results:  Estrogen and tamoxifen significantly decreased expression of CCR2 and, to a lesser extent, CXCR3 on murine monocytes. Estrogen decreased chemotaxis of monocytes towards MCP‐1/JE. The chemokines MCP‐1/JE and MIP‐1α were unable to evoke increases in intracellular calcium in murine monocytes treated with estrogen, alone or in combination with tamoxifen.

Conclusions:  Our results show that estrogen suppresses the ability of monocytes to respond to certain chemokines, suggesting that estrogen exposure might decrease immune surveillance in tissues where the action of specific chemokines is involved.
Tissue Eosinophilia in Pemphigoid Gestationis: Association with Eotaxin and Upregulated Activation Markers on Transmigrated Eosinophils
Authors: Günther Claudia , Wozel Gottfried , Dreßler Jan , Meurer Michael , Pfeiffer Christiane
Published: January 2004

Problem:  We studied chemotactic cytokines and activation of skin‐homed eosinophils in pemphigoid gestationis, a rare autoimmune bullous disease of late pregnancy.

Method of study:  Eotaxin and interleukin (IL)‐5 were analysed in patients’ blister fluid and serum by enzyme‐linked immunosorbent assay. Lesional tissue was investigated for eotaxin deposition by immunohistochemistry. Adhesion molecules and activation markers on tissue eosinophils were analysed by immunofluorescence staining.

Results:  Eotaxin was elevated in serum of two pemphigoid gestationis patients compared with nine healthy pregnant women. Blister fluid contained even higher amounts of eotaxin and in addition IL‐5. Eotaxin was mainly expressed in subepidermal tissue in close proximity to eosinophils that expressed high levels of adhesion molecules (CD11b, CD11c, CD18 and CD49d) and the activation marker HLA‐DR.

Conclusions:  High local levels of eotaxin and IL‐5 as present in the blister fluid correspond to the high state of activation of the infiltrated eosinophils.
Expression of IL‐4, IL‐8 and IL‐18 Messenger RNAs in Maternal Peripheral Blood and Relationships with the HbF‐γ chain mRNA in it
Authors: Kato Chikako , Tamura Takaya , Okuda Tomohiro , Kojima Hidenori , Kinoshita Yoshiyuki , Honjo Hideo
Published: January 2004

Problem:  This study was designed to examine immunological changes in maternal peripheral blood and the relationship of these changes with the amount of fetal cells in the blood.

Method of study:  The expression of interleukin‐4 (IL‐4), IL‐8, IL‐18 and fetal hemoglobin gamma chain (HbF‐γ chain) messenger RNAs (mRNAs) in maternal peripheral blood was measured by a quantitative reverse transcription‐polymerase chain reaction method.

Results:  In maternal peripheral blood, the expression of IL‐4 mRNA was up‐regulated from the second gestational month (GM) to delivery. The expression of IL‐8 and IL‐18 mRNAs was down‐regulated from the third or fourth GM until the eighth or ninth GM, respectively, and both increased before the onset of labor, though IL‐4 mRNA decreased. The expression of IL‐8 and IL‐18, but not IL‐4, mRNAs was correlated with that of HbF‐γ chain mRNA.

Conclusions:  Immunological interactions between maternal peripheral immune cells and fetal cells appear to be related to the onset of labor.
Relationship between Cytokine Concentrations (FGF, sICAM‐1 and SCF) in Serum, Follicular Fluid and ICSI Outcome
Authors: Hammadeh Mohamad Eid , Fischer‐Hammadeh Constanze , Hoffmeister Heidrun , Herrmann Wolfgang , Rosenbaum Peter , Schmidt Werner
Published: January 2004

Objective:  The aim of this study was (i) to investigate the existence of fibroblast growth factor (FGF), soluble intracellular adhesion molecule‐1 (sICAM‐1), and stem cell factor (SCF) in serum and human follicular fluid (FF) of intracytoplasmic sperm injection (ICSI) patients, and (ii) to determine the relationship between these parameters and ICSI outcome.

Material and method:  Seventy‐five patients undergoing controlled ovarian hyperstimulation with human menopausal gonadotropin (hMG) after down‐regulation with GnRHa were included in this study. The concentrations of FGF, SCF, and sICAM‐1 were measured by using commercially available enzyme‐linked immunosorbent assay test kits.

Results:  The FGF, sICAM‐1, and SCF concentrations in the serum of women who become pregnant (group I) were 8.5 ± 1.5 pg/mL, 235.8 ± 81.1 ng/mL, and 597.7 ± 139.9 pg/mL, and the corresponding concentrations of women who did not (group II) were 6.4 ± 3.6 pg/mL, 230.6 ± 66.5 ng/mL, and 569.6 ± 91.4 pg/mL respectively. No significant difference was observed between the two investigated groups with regard to the number of hMG ampoules administered for controlled ovarian hyperstimulation, estradiol concentration on the day of human chorionic gonadotropin (hCG) injection, number of retrieved oocytes and fertilization rate.

Conclusion:  The concentration of FGF, sICAM‐1, and SCF did not differ significantly between the two groups in serum or in FF. Besides, the ICSI outcome was not related to their concentrations in serum or FF. Therefore, these parameters could not be used as a prognostic factor in ICSI program.
Analysis of Macrophage Presence in Murine Placenta: Influence of Age and Parity Status
Authors: Lagadari M. , Blois S. , Margni R. , Miranda S.
Published: January 2004

Problem:  Beneficial effects of multiparity status have been previously reported by different authors. However, this fact has not been fully explained. Taking into consideration the influence of the parity status on the in vitro asymmetric/protective antibodies and the fact that interleukin‐6 (IL‐6) is involved in the production and immune‐regulatory functions of placental macrophages, the aim of this work was to compare the placental IL‐6 production and tissue macrophage presence in mice with different age and parity status.

Method of study:  Three groups of mice (CBA/J × CBA/J) were analyzed: primiparous young (PY: 3.0 ± 0.5 months old), primiparous old (PO: 8.5 ± 0.5 months old), and multiparous old (MO: 8.5 ± 0.5 months old, with three to four previous pregnancies). Macrophage and IL‐6 were identified in placental tissue by immunohistochemistry employing anti‐F4/80 or anti‐IL‐6 antibodies. IL‐6 secretion was analyzed in the placental culture supernatants by enzyme‐linked immunosorbent assay.

Results:  The results obtained indicate that, despite the level of macrophages observed in the PO placentae was higher than in PY ones, their expression in MO placentae was very much increased, appearing like a thick layer between decidua and trophoblast. However, no significant difference was found among the groups in the tissue expression of IL‐6 and in IL‐6 secreted in vitro.

Conclusions:  Our data indicate that parity status influences the number of local macrophages and might provide evidence that could explain the known beneficial effect of multipaternity. We suggest that the number of previous pregnancies favor the production of a ‘protective’ population of macrophages.
Regulation of Numbers of Macrophages in the Endometrium of the Sheep by Systemic Effects of Pregnancy, Local Presence of the Conceptus, and Progesterone
Authors: Tekin Şaban , Hansen Peter J.
Published: January 2004

Abstract:  Many species exhibiting hemochorial placentation experience an accumulation of macrophages in the endometrium during pregnancy. For the present study, it was tested whether macrophages also accumulate in the endometrium of the sheep, which is a species undergoing an epitheliochorial placentation. An additional objective was to determine whether regulation of endometrial macrophage number occurs via systemic or local signals and whether progesterone is one of these signals. The approach was to evaluate presence of macrophages immunohistochemically using antibodies to CD68 and CD14. Tissues examined were from cyclic ewes in the luteal phase of the estrous cycle, unilaterally‐pregnant ewes at day 140 of pregnancy in which pregnancy was surgically confined to one uterine horn, ovariectomized ewes, and ovariectomized ewes treated with progesterone for 44 days. Macrophages were localized predominately to the stromal compartment of the stratum compactum region of the endometrium. In non‐pregnant ewes, macrophages were not abundant regardless of physiological status. Increased numbers of endometrial macrophages were seen for both the pregnant and non‐pregnant uterine horns of unilaterally pregnant ewes. Numbers of macrophages were higher in the endometrium from the pregnant uterine horn than from endometrium from the non‐pregnant uterine horn. Results indicate that macrophages accumulate in the endometrium by day 140 of pregnancy in the sheep and that this induction is because of both systemic and local signals. Progesterone appears not to be an important regulator of numbers of endometrial macrophages.
Shall We properly Re‐examine the Status of Allogeneic Lymphocyte Therapy for Recurrent early Pregnancy Failure?
Authors: Clark David A.
Published: January 2004

Problem:  How to evaluate immunological therapy advocated for recurrent spontaneous abortion and implantation failure. I was invited to comment on the opinion article of Chaouat (AJRI December 2003).

Methods:  A critical examination of key beliefs and application of the principles of evidence and logic utilizing current data.

Results and Conclusions:  Although rationale has no bearing on efficacy of proposed treatments and is not sufficient justification for routine practice, insufficient attention to data concerning patient selection, insufficient attention to treatment methodology, and lack of full disclosure in some clinical trials needs to be corrected. A more systematic collection of follow‐up data is needed.
An Alternate Multiple‐Choice Scoring Procedure in a Macroeconomics Course
Authors: Bradbard David A. , Parker Darrell F. , Stone Gary L.
Published: January 2004

In the standard scoring procedure for multiple‐choice exams, students must choose exactly one response as correct. Often students may be unable to identify the correct response, but can determine that some of the options are incorrect. This partial knowledge is not captured in the standard scoring format. The Coombs elimination procedure is an alternate scoring procedure designed to capture partial knowledge. This paper presents the results of a semester‐long experiment where both scoring procedures were compared on four exams in an undergraduate macroeconomics course. Statistical analysis suggests that the Coombs procedure is a viable alternative to the standard scoring procedure. Implications for classroom instruction and future research are also presented.
Unequal Division of Type I Risk in Statistical Inferences
Authors: Meek Gary E. , Ozgur Ceyhun O.
Published: January 2004

Introductory statistics texts give extensive coverage to two‐sided inferences in hypothesis testing, interval estimation, and one‐sided hypothesis tests. Very few discuss the possibility of one‐sided interval estimation at all. Even fewer do so in any detail. Two of the business statistics texts we reviewed mentioned the possibility of dividing the risk of a type I error unequally between the tails for a two‐sided confidence interval. None of the textbooks that were reviewed even considered the possibility of unequal tails for two‐sided hypothesis tests. In this paper, we propose that statistics courses and texts should cover both one‐sided tests and confidence intervals. Furthermore, we propose that coverage, at least in two semesters and advanced courses, should also be given to unequal division of the nominal risk of a type I error for both tests and confidence intervals. Examples are provided for both situations.
Changes in sexual selection resulting from novel habitat use in the sand goby
Authors: Lehtonen Topi , Lindström Kai
Published: January 2004

Resource availability may determine local breeding systems and may also vary locally between different habitats, affecting the way individuals distribute themselves between these habitats. For nest‐breeding fishes, nest site availability is a crucial resource that has been found to affect local sexual selection regimes and thus breeding systems. In this study, we compared the availability and size distribution of nest sites and their consequences for habitat preference, fish distributions and the breeding system in sand gobies (Pomatoschistus minutus) breeding in two different habitats. The usual breeding sites of sand gobies are shallow sandy beaches, but here we report their breeding in a novel environment, on rocky bottoms. We found obvious differences between the two habitats. The density of occupied nests was nearly 50 times higher in rock habitat than on sand bottoms. However, competition for nest sites was stronger on sand; nearly all natural nest sites found were in use and empty nest sites were occupied at a much higher rate on sand than in rock habitat. In addition to the numerical differences, nests were larger and contained more eggs in rock habitat than in sand habitat. Moreover, we found significant habitat‐specific differences in fish size distribution. The intensity of intrasexual competition as a result of the degree of nest site availability explains the observed patterns within the habitats, but not between them. These habitat‐related differences are better explained by the larger average size of nests on rocky bottoms. The effect of nest size on habitat preference was confirmed experimentally by laboratory experiments. When nest size did not differ between the habitats, gobies originating in the two environments showed an equal preference for the sand habitat.
Rings, circles, and null‐models for point pattern analysis in ecology
Authors: Wiegand Thorsten , A. Moloney Kirk
Published: January 2004

A large number of methods for the analysis of point pattern data have been developed in a wide range of scientific fields. First‐order statistics describe large‐scale variation in the intensity of points in a study region, whereas second‐order characteristics are summary statistics of all point‐to‐point distances in a mapped area and offer the potential for detecting both different types and scales of patterns. Second‐order analysis based on Ripley's K‐function is increasingly used in ecology to characterize spatial patterns and to develop hypothesis on underlying processes; however, the full range of available methods has seldomly been applied by ecologists. The aim of this paper is to provide guidance to ecologists with limited experience in second‐order analysis to help in the choice of appropriate methods and to point to practical difficulties and pitfalls. We review (1) methods for analytical and numerical implementation of two complementary second‐order statistics, Ripley's K and the O‐ring statistic, (2) methods for edge correction, (3) methods to account for first‐order effects (i.e. heterogeneity) of univariate patterns, and (4) a variety of useful standard and non‐standard null models for univariate and bivariate patterns. For illustrative purpose, we analyze examples that deal with non‐homogeneous univariate point patterns. We demonstrate that large‐scale heterogeneity of a point‐pattern biases Ripley's K‐function at smaller scales. This bias is difficult to detect without explicitly testing for homogeneity, but we show that it can be removed when applying methods that account for first‐order effects. We synthesize our review in a number of step‐by‐step recommendations that guide the reader through the selection of appropriate methods and we provide a software program that implements most of the methods reviewed and developed here.
A unified mathematical framework for the measurement of richness and evenness within and among multiple communities
Authors: Olszewski Thomas D.
Published: January 2004

Biodiversity can be divided into two aspects: richness (the number of species or other taxa in a community or sample) and evenness (a measure of the distribution of relative abundances of different taxa in a community or sample). Sample richness is typically evaluated using rarefaction, which normalizes for sample size. Evenness is typically summarized in a single value. It is shown here that Hurlbert's probability of interspecific encounter (Δ1), a commonly used sample‐size independent measure of evenness, equals the slope of the steepest part of the rising limb of a rarefaction curve. This means that rarefaction curves provide information on both aspects of diversity. In addition, regional diversity (gamma) can be broken down into the diversity within local communities (alpha) and differences in taxonomic composition among local communities (beta). Beta richness is expressed by the difference between the composite rarefaction curve of all samples in a region with the collector's curve for the same samples. The differences of the initial slopes of these two curves reflect the beta evenness thanks to the relationship between rarefaction and Δ1. This relationship can be further extended to help interpret species‐area curves (SAC's). As previous authors have described, rarefaction provides the null hypothesis of passive sampling for SAC's, which can be interpreted as regional collector's curves. This allows evaluation of richness and evenness at local and regional scales using a single family of well‐established, mathematically related techniques.
How important is the statistical approach for analyzing categorical data? A critique using artificial nests
Authors: Lewis Keith P.
Published: January 2004

Ecologists rely heavily upon statistics to make inferences concerning ecological phenomena and to make management recommendations. It is therefore important to use statistical tests that are most appropriate for a given data‐set. However, inappropriate statistical tests are often used in the analysis of studies with categorical data (i.e. count data or binary data). Since many types of statistical tests have been used in artificial nests studies, a review and comparison of these tests provides an opportunity to demonstrate the importance of choosing the most appropriate statistical approach for conceptual reasons as well as type I and type II errors.

Artificial nests have routinely been used to study the influences of habitat fragmentation, and habitat edges on nest predation. I review the variety of statistical tests used to analyze artificial nest data within the framework of the generalized linear model and argue that logistic regression is the most appropriate and flexible statistical test for analyzing binary data‐sets. Using artificial nest data from my own studies and an independent data set from the medical literature as examples, I tested equivalent data using a variety of statistical methods. I then compared the p‐values and the statistical power of these tests. Results vary greatly among statistical methods. Methods inappropriate for analyzing binary data often fail to yield significant results even when differences between study groups appear large, while logistic regression finds these differences statistically significant. Statistical power is is 2–3 times higher for logistic regression than for other tests. I recommend that logistic regression be used to analyze artificial nest data and other data‐sets with binary data.
Sexual abstinence and the cost of reproduction in adult male water snakes, Nerodia sipedon
Authors: Brown Gregory P. , Weatherhead Patrick J.
Published: January 2004

Low frequency of reproduction among iteroparous organisms is most often observed among female ectothermic vertebrates and is thought to be a strategy used to defer reproductive costs. We assessed reproductive costs of male water snakes (Nerodia sipedon) to determine why half of adult males abstain from reproduction each year. There was no evidence of a short‐term energetic cost of reproduction. Change in mass did not differ between reproductive and non‐reproductive males during the one‐month mating season or during the entire four‐month activity season. Changes in mass of reproductive males were similar at two sites in which the spatial distribution of females differed. However, there were size‐specific differences in growth and survival between reproductive and non‐reproductive males. Among reproductive males growth rate decreased with body size at a lower rate than among non‐reproductive males. Survival increased with body size for reproductive males, but decreased with body size among non‐reproductive males. Most of the differential survival between reproductive and non‐reproductive males did not occur during the mating season but rather during hibernation. Size‐related differences between reproductive and non‐reproductive males may reflect selection having eliminated low quality males from the larger size classes. Overall our results appear most consistent with there being high variance in male quality, such that the best males can bear the cost of reproducing and still grow and survive as well or better than low quality males that abstain from reproduction.