bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated community‐directed treatment for the control of onchocerciasis, schistosomiasis and intestinal helminths infections in Uganda: advantages and disadvantages
Authors: Ndyomugyenyi Richard , Kabatereine Narcis 
Published: October 2003

SummaryOnchocerciasis is co‐endemic with schistosomiasis and intestinal helminths infections, which are all diseases of the rural and the poorest communities in Africa. Community‐directed treatment (ComDT) for the control of onchocerciasis is the only functional health approach in most of these communities and the strategy has proven to be effective for onchocerciasis control. This study was conducted to assess the feasibility of integrating ComDT with ivermectin for the control of onchocerciasis, and with praziquantel (PZQ) and mebendazole (MBD) for the control of schistosomiasis and intestinal helminths infections in children aged 5–14 years, and to assess advantages and disadvantages of the integrated ComDT over the routine ComDT and the school‐based treatment approach. Integrated ComDT achieved higher treatment coverage (85%) for PZQ and MBD than the school‐based treatment approach (79%) among children aged 5–14 years (P = 0.03). There were more reported adverse reactions after treatment with a combination of PZQ and MBD in the school‐based treatment approach (33%) than for the combination of ivermectin and MBD on day 1 and PZQ on day 2 in the integrated ComDT (18%). However, all adverse reactions were mild (headache, nausea/vomiting and abdominal pain). The integrated ComDT also achieved higher ivermectin treatment coverage for all ages (81.3%) than routine ComDT (77.2%) (P = 0.0003). To achieve even better coverage for PZQ and MBD among the targeted high risk groups, integrated ComDT should treat all age groups in areas where the prevalence of schistosomiasis and intestinal helminths infections is >50%. This would minimize the shortage of the drugs targeted to treat the high risk groups, as the non‐targeted groups, will inevitably demand and receive the treatment from the distributors. The results of this study show that PZQ and MBD treatment for the control of schistosomiasis and intestinal helminths, respectively, can be integrated with ivermectin treatment for the control of onchocerciasis without negatively affecting ivermectin treatment coverage.
Field efficacy of thermally expelled or live potted repellent plants against African malaria vectors in western Kenya
Authors: Seyoum Aklilu , Killeen Gerry F. , Kabiru Ephantus W. , Knols Bart G. J. , Hassanali Ahmed 
Published: October 2003

SummaryObjective To estimate the effectiveness of live potted plants and thermal expulsion of plant materials in repelling African malaria vectors in traditional houses in western Kenya.Methods Ocimum americanum, Lantana camara and Lippia ukambensis were tested in live, intact potted form whereas leaves of Corymbia citriodora, leaves and seeds of O. kilimandscharicum and O. suave were tested by thermal expulsion from modified traditional stoves. A latin square design was applied for randomly assigning the treatment and control plants to experimental houses over different nights.Results All plant species showed significant repellency against Anopheles gambiae sensu lato Giles (Diptera: Culicidae) (81.5%An. arabiensis Patton and 18.5%An. gambiae sensu stricto Giles), the main vectors of malaria in Africa, with the highest repellency by C. citriodora (48.71%, P < 0.0001) followed by an equal level of repellency of O. kilimandscharicum and O. suave (44.54%, P = 0.001) during application of plant material by thermal expulsion. All three plant species also showed a residual effect against An. gambiae s.l. with 36–44% repellency post‐application period (22.30–06.30 hours) after a period of thermal expulsion. Similarly, intact potted plants of O. americanum and L. camara repelled An. gambiae s.l. significantly (37.91%, P = 0.004; and 27.22%, P = 0.05, respectively). Thermal expulsion of leaves and seeds of O. kilimandscharicum significantly repelled An. funestus Giles, although none of the potted plants repelled this species.Conclusion Both methods of application may offer cost‐effective alternatives as additional means of household protection, and a useful complement to bed nets, particularly for the early part of the evening before bedtime.
CTLA‐4 positive T cells in contrast to procalcitonin plasma levels discriminate between severe and uncomplicated Plasmodium falciparum malaria in Ghanaian children
Authors: Braun Nele , Marfo Yeboah , Von Gärtner Christiane , Burchard Gerd D. , Zipfel P. F. , Browne N. Edmund N. , Fleischer Bernhard , Bröker Barbara M. 
Published: October 2003

SummaryProcalcitonin (PCT) plasma levels and the fraction of CTLA‐4‐positive T cells are both elevated in acute Plasmodium falciparum malaria in human adults and the degree of elevation is positively correlated with other markers of disease severity, for example with parasitaemia. However, the clinical manifestations of malaria are strongly age‐dependent and children from endemic areas carry the main disease burden. Therefore, we measured PCT plasma levels and CTLA‐4 expression by T cells in four groups of children from the Ashanti Region in Ghana: asymptomatic children with or without parasitaemia, children with uncomplicated P. falciparum malaria and children with severe disease. PCT levels were highly elevated in both groups with acute malaria but they did not discriminate between uncomplicated and severe disease. In contrast, CTLA‐4‐expression by T cells was increased only in severe malaria. The fraction of CTLA‐4 positive T cells in the blood of children with severe disease differed significantly from that in uncomplicated malaria, which was not elevated in spite of the high parasite loads observed in these children. This was unexpected, as in adults uncomplicated malaria is associated with a dramatic sixfold increase of the fraction of CTLA‐4‐positive T cells. The data from this study support the hypothesis that strong T cell activation as measured here by CTLA‐4 expression is not just the by‐product of a high parasite burden, but that it contributes to the pathogenesis of P. falciparum malaria.
Use of glycerol as an alternative to freeze‐drying for long‐term preservation of antigen for the direct agglutination test
Authors: Harith Abdallah el , Mutasim Mohamed el , Mansour Durria , Fadil Mustafa El , Arvidson Harold 
Published: October 2003

SummaryThe potential of glycerol for long‐term preservation of the direct agglutination test (DAT) antigen was evaluated at a fluctuating laboratory temperature of 25–37 °C and at constant temperatures of 37 and 45 °C for a period of 222 days. DAT titres recorded for the three antigen aliquots preserved in 50% (v/v) glycerol and stored at 25–37, 37 or 45 °C at 11 time intervals were within the same range of the control antigen kept at 4 °C. Performance of the glycerol‐preserved antigen stored at 45 °C was compared with that of a freeze‐dried version on 24 visceral leishmaniasis (VL) and 54 non‐VL patients. For all non‐VL patients, a maximum DAT titre of 1/800 was recorded for either of the two antigens. For all VL patients, in comparison with the freeze‐dried, the glycerol‐preserved antigen always had equal or higher titre; in 16 of the 24 VL sera tested, the latter antigen scored three‐ to sixfold higher titres. As this glycerol preservation method is economical and easy to perform, it has better potential for wider‐scale application than freeze‐drying.
Treatment of amoebic liver abscess with metronidazole alone or in combination with ultrasound‐guided needle aspiration: a comparative, prospective and randomized study
Authors: Blessmann Joerg , Binh Ho Duy , Hung Duong Manh , Tannich Egbert , Burchard Gerd 
Published: October 2003

SummaryThirty‐nine patients with amoebic liver abscess (ALA), admitted to the Central Hospital of Hué (Vietnam), were evaluated in a comparative, prospective and randomized study for the treatment of ALA. Adult patients with an abscess located in the right liver lobe and an abscess diameter of 6 to 10 cm were included. Bacterial abscesses were excluded by microbiological examination of abscess fluid in all patients. Nineteen patients were treated with metronidazole for 10 days alone and 20 patients were punctured under ultrasound guidance with aspiration of abscess fluid in addition to drug administration. The clinical symptoms fever, pain in right upper abdomen and liver tenderness, and the laboratory parameters erythrocyte sedimentation rate, white blood cells, haemoglobin and C‐reactive protein and the abscess size were determined on the day of admission and followed during an observation period of 38 days. Improvement of liver tenderness was significantly faster in the aspiration group during the first 3 days (P < 0.001), whereas all the other parameters showed no differences between the two groups. This minor benefit is obviously not sufficient to justify routine needle aspiration and advocates drug treatment alone for uncomplicated amoebic liver abscesses with a diameter up to 10 cm located in the right liver lobe.
Comparison of combination inhalers vs inhaled corticosteroids alone in moderate persistent asthma
Authors: Lee Daniel K. C. , Jackson Catherine M. , Currie Graeme P. , Cockburn Wendy J. , Lipworth Brian J. 
Published: October 2003

Aims  Inhalers combining long acting β2‐adrenoceptor agonists (LABA) and corticosteroids (ICS) are indicated at Step 3 of current asthma guidelines. We evaluated the relative effects of LABA + ICS combination vs ICS alone on pulmonary function, bronchoprotection, acute salbutamol recovery following methacholine bronchial challenge, and surrogate inflammatory markers in patients with moderate persistent asthma.Methods  Twenty‐nine patients with mean FEV1 (± SEM) of 78 ± 3% predicted completed a randomized, double‐blind, double‐dummy, cross‐over study. Patients received either 4 weeks of budesonide 400 µg + formoterol 12 µg (BUD + FM) combination twice daily followed by 1 week of BUD 400 µg alone twice daily, or 4 weeks of fluticasone propionate 250 µg + salmeterol 50 µg (FP + SM) combination twice daily followed by 1 week of FP 250 µg alone twice daily. Measurements were made at baseline and following each randomized treatment.Results  FEV1 increase from pretreatment baseline as mean (± SEM) % predicted was significantly higher (P < 0.05) for BUD + FM (8 ± 1%) vs BUD (2 ± 1%), and for FP + SM (8 ± 1%) vs FP (2 ± 1%). The fall in FEV1 following methacholine challenge as percentage change from prechallenge baseline FEV1 was not significantly different in all four groups; BUD + FM (22 ± 1%), BUD (24 ± 1%), FP + SM (23 ± 1%) and FP (23 ± 1%). Salbutamol recovery over 30 min following methacholine challenge as area under curve (AUC %.min) was significantly blunted (P < 0.05) with BUD + FM (486.7 ± 35.5) vs BUD (281.1 ± 52.8), and with FP + SM (553.1 ± 34.1) vs FP (368.3 ± 46.7). There were no significant differences between respective combination inhalers or between respective ICS alone. Decreases in exhaled nitric oxide (NO) and serum eosinophilic cationic protein (ECP) from baseline were not significantly different between treatments.Conclusions  Combination inhalers improve pulmonary function without potentiating anti‐inflammatory effects on exhaled NO and serum ECP as compared with ICS alone, but delay acute salbutamol recovery after bronchoconstriction.
Ultramolecular homeopathy has no observable clinical effects. A randomized, double‐blind, placebo‐controlled proving trial of Belladonna 30C
Authors: Brien Sarah , Lewith George , Bryant Trevor 
Published: October 2003

Aims  To investigate if ultramolecular homeopathy has any clinical effects. This was assessed using the proving of the homeopathic remedy Belladonna given at an ultramolecular dose (30C), as a model. A proving states that when a homeopathic remedy is given to a healthy person, they will experience symptomatic effects specific to that remedy. If ultramolecular doses are clinically active, the Belladonna 30C group should experience more true Belladonna proving symptoms than the placebo group.Methods  Healthy subjects (n = 253), aged 18–30 years, took part in this double‐blind, randomized placebo‐controlled study. Total study duration was 4 weeks. Subjects were randomized before 1 week placebo run‐in. They received 2 weeks of treatment intervention (Belladonna 30C or placebo) and were followed up for 1 week. Subjects recorded any symptoms experienced during the total study period on a daily basis using a structured questionnaire. Symptom diaries were analysed blind to determine if each subject had proved or not (based on predefined criteria). The main outcome was the proportion of subjects who had proved in each treatment group.Results  No significant group differences in proving rates were observed [Belladonna provers N = 14 (13.9%); placebo provers N = 15 (14.3%); mean difference − 0.4%, 95% confidence interval − 9.3, 10.1] based on intention to treat analysis. Primary outcome was not affected by seasonality or the individual's attitude to complementary medicine.Conclusion  Ultramolecular homeopathy had no observable clinical effects.
Changes in antipsychotic drug prescribing by general practitioners in the United Kingdom from 1991 to 2000: a population‐based observational study
Authors: Kaye James A. , Bradbury Brian D. , Jick Hershel 
Published: October 2003

Aim  To estimate changes in the frequency of use of various antipsychotic drugs in the UK from 1991 to 2000 and to relate these changes to patients’ characteristics.Methods  We conducted a population‐based observational study using data from general practices that contribute information to the General Practice Research Database (GPRD). The study population comprised men and women 10–99 years old. We estimated annual use, first‐time use, duration of use and, in a sample of 200 patients, indications for use of various antipsychotic drugs, and we observed how these measures had changed over the past decade.Results  The annual use of antipsychotic drugs increased from 10.5 per thousand in 1991 to 12.2 per thousand in 2000, an overall increase of 16%. The increase was greater in men (25.2%) than women (2.7%). At the same time, the rate of new use of antipsychotic drugs was stable in men and decreased by 21% in women. The difference between patterns of annual use and rates of new use is attributable to the increasing average annual duration of treatment in both men and women during the past decade. Thioridazine, which the UK Committee on the Safety of Medicines (CSM) recently recommended should be used only for second‐line treatment of schizophrenia in adults, was the most commonly prescribed antipsychotic throughout the study period. Its use increased as a proportion of all antipsychotic drug use from 1991 to 2000 in men and women aged 10–69 years, but decreased in older users. More than half of all first‐time use of antipsychotic drugs in the sample of patients we evaluated was for treatment of depression, anxiety states, and panic disorders, while less than 10% was for treatment of schizophrenia and other psychoses.Conclusion  The use of antipsychotic drugs has increased in the UK during the past decade, primarily due to increased average annual duration of use rather than higher rates of new use. Most antipsychotic drug use appears to have been prescribed to treat nonpsychotic disorders. It will be of interest to see whether the use of thioridazine, which was the most widely prescribed antipsychotic during 1991–2000, decreases during the next decade in response to the recent CSM recommendation.
Free and bound propofol concentrations in human cerebrospinal fluid
Authors: Dawidowicz Andrzej L. , Kalitynski Rafal , Fijalkowska Anna 
Published: October 2003

Aims  The aim of this study was to define the relationship between unbound propofol concentrations in plasma and total drug concentrations in human cerebrospinal fluid (CSF), and to determine whether propofol exists in the CSF in bound form.Methods  Forty‐three patients (divided into three groups) scheduled for elective intracranial procedures and anaesthetized by propofol target control infusion (TCI) were studied. Blood and CSF samples (taken from the radial artery, and the intraventricular drainage, respectively) from group I (17 patients) were used to investigate the relationship between unbound propofol concentration in plasma and total concentration of the drug in CSF. CSF samples taken from group II (18 patients) were used to confirm the presence of the bound form of propofol in this fluid. The CSF and blood samples taken from group III (eight patients) were used to monitor the course of free and bound CSF propofol concentrations during anaesthesia.Results  For group I patients the mean (and 95% confidence interval) total plasma propofol concentration was 6113 (4971, 7255) ng ml−1, the mean free propofol concentration in plasma was 63 (42, 84) ng ml−1, and the mean total propofol concentration in CSF was 96 (76, 116) ng ml−1 (P < 0.05 for the difference between the last two values). For group II patients the fraction of free propofol in CSF was 31 (26, 37)%. For group III patients the fraction of free propofol in CSF during TCI was almost constant (about 36%).Conclusions  The unbound propofol concentration in plasma was not equal to its total concentration in CSF and cannot be directly related to the drug concentration in the brain. Binding of propofol to components of the CSF may be an additional mechanism regulating the transport of the drug from blood into CSF.
An in vitro interethnic comparison of monoamine oxidase activities between Japanese and Caucasian livers using rizatriptan, a serotonin receptor 1B/1D agonist, as a model drug
Authors: Iwasa T. , Sano H. , Sugiura A. , Uchiyama N. , Hara K. , Okochi H. , Nakagawa K. , Yasumori T. , Ishizaki T. 
Published: October 2003

Aims  Monoamine oxidase (MAO) is located in human liver, and catalyses the oxidative deamination step of many xenobiotics. However, whether there exists an interethnic difference in MAO activities has, to our knowledge, not been clarified. We aimed to assess the MAO type A (MAO‐A) involvement in the metabolic pathway of rizatriptan (RIZ), an antimigraine 5‐hydroxytryptamine (5‐HT)1B/1D agonist, and the interethnic difference in MAO activities between Caucasians and Japanese using RIZ as a model drug in in vitro experiments.Methods  Oxidative deaminase activities were determined with the subcellular fractions of Japanese livers and the microsomal fraction of Caucasian livers using RIZ, 5‐HT (MAO‐A substrate) and 2‐phenylethylamine (PEA) (MAO‐B substrate) as substrates.Results  The oxidative deaminase activities of RIZ vs. 5‐HT were highly (r = 0.87 and 0.96, P < 0.001) correlated with each other in both the microsomal and mitochondrial fractions of Japanese livers. Subsequent results were obtained from in vitro experiments using liver microsomes based upon these findings. The oxidative deaminase activities of RIZ were inhibited completely by the nanomolar‐order concentration of clorgyline and Ro 41‐1049 (MAO‐A selective inhibitors), but not by that of Ro 16‐6491 (MAO‐B selective inhibitor). The majority of the mean Michaelis–Menten values for three substrates toward MAO obtained from six Japanese and six Caucasian liver microsomes reached no significant differences between the two ethnic groups. The mean microsomal oxidative deaminase activities assessed in 18 Japanese and 20 Caucasian livers using the three substrates also showed no significant differences between the two ethnic groups.Conclusions  RIZ is mainly metabolized by MAO‐A and the in vitro oxidative deaminase activities mediated via MAO‐A and ‐B do not appear to differ between Japanese and Caucasians.
Evaluation of two carrier protein–angiotensin I conjugate vaccines to assess their future potential to control high blood pressure (hypertension) in man
Authors: Downham M. R. , Auton T. R. , Rosul A. , Sharp H. L. , Sjöström L. , Rushton A. , Richards J. P. , Mant T. G. K. , Gardiner S. M. , Bennett T. , Glover J. F. 
Published: October 2003

Aims  We aim to modulate the renin–angiotensin system (RAS) by active immunization against angiotensin I hormone (AI), potentially providing a novel conjugate vaccine treatment for hypertension in man.Methods  Immunization studies in rat and human subjects compare the effectiveness of tetanus toxoid (TT) and keyhole limpet haemocyanin (KLH) vaccines for immunotherapy following conjugation with an AI peptide analogue (AI). Cardiovascular responses were assessed in immunized rats and human subjects (two‐dose trial only), following increasing i.v. infusions of either AI or angiotensin II hormone (AII).Results  The AI–TT and AI–KLH conjugate vaccines induced an equivalent immune response, and inhibition of the pressor effects to exogenous AI in rats. Single‐dose clinical trials with both conjugate vaccines only resulted in an immune response to the KLH carrier protein. A two‐dose clinical trial of AI–KLH conjugate vaccine resulted in a significant immune response to AI. A shift in diastolic blood pressure (DBP) dose–response was demonstrated following challenge with AI and AII for the study volunteer showing the largest anti‐AI IgG induction.Conclusion  KLH was shown to be a suitable alternative to TT as a carrier protein for AI, thus supporting continued evaluation of our AI–KLH conjugate vaccine for treatment of hypertension in man.
Steady‐state pharmacokinetics and pharmacodynamics of cysteamine bitartrate in paediatric nephropathic cystinosis patients
Authors: Belldina Eric B. , Huang Mei Y. , Schneider Jerry A. , Brundage Richard C. , Tracy Timothy S. 
Published: October 2003

Aims  Cysteamine is used to reduce tissue cystine content in patients suffering from nephropathic cystinosis. The objectives of the current study were to investigate pharmacokinetics and pharmacodynamics of cysteamine bitartrate in children and young adults with nephropathic cystinosis.Methods  Cysteamine bitartrate was administered to 11 cystinosis patients at their regular dose level in a single‐dose, open‐label, steady‐state study. Blood samples were collected and analysed for plasma cysteamine and white blood cell cystine content and pharmacokinetic and pharmacodynamic parameters estimated by NONMEM analysis using a linked pharmacokinetic–pharmacodynamic model.Results  Cysteamine was rapidly cleared from the plasma (mean CL/F = 32.3 ml min−1 kg−1, range = 17.3–52.2), appeared to be extensively distributed (mean Vss/F = 15.1 l, range 2.7–32.3) and exhibited a mean Tmax of 1.4 h. White blood cell cystine content post‐dosing was significantly decreased compared with pre‐ and post‐dose values (average decrement approximately 47%). A counter‐clockwise hysteresis was noted in all patients, suggestive of a lag time (mean Tlag = 0.44 h, range 0.22–0.92) between drug concentration and effect.Conclusions  The results of this study establish that cysteamine is rapidly cleared from the plasma but that an every 6 h dosing interval adequately maintains white blood cell cystine content below the target of 1 nmol cystine per mg protein.