bluuebunny/crossref_metadata_2025 huggingface dataset:
Vascular endothelial growth factor (VEGF)–C signaling through FLT-4 (VEGFR-3) mediates leukemic cell proliferation, survival, and resistance to chemotherapy
Authors: Dias Sergio , Choy Margaret , Alitalo Kari , Rafii Shahin
Published: October 2002

Similar to solid tumors, growth of leukemias may also be angiogenesis dependent. Furthermore, tyrosine kinase receptors specific to endothelial cells are expressed on certain subsets of leukemias. We have previously demonstrated the existence of a VEGF/VEGFR-2 autocrine loop on leukemic cells that supports their growth and migration. Here, we demonstrate that in response to leukemia-derived proangiogenic and proinflammatory cytokines such as basic fibroblast growth factor and IL-1, endothelial cells release increasing amounts of another vascular endothelial growth factor (VEGF) family member, VEGF-C. In turn, interaction of VEGF-C with its receptor VEGFR-3 (FLT-4) promotes leukemia survival and proliferation. We demonstrate in 2 cell lines and 5 FLT-4+ leukemias that VEGF-C and a mutant form of the molecule that lacks the KDR-binding motif induce receptor phosphorylation, leukemia proliferation, and increased survival, as determined by increased Bcl-2/Bax ratios. Moreover, VEGF-C protected leukemic cells from the apoptotic effects of 3 chemotherapeutic agents. Because most leukemic cells release proangiogenic as well as proinflammatory cytokines, our data suggest that the generation of a novel paracrine angiogenic loop involving VEGF-C and FLT-4 may promote the survival of a subset of leukemias and protect them from chemotherapy-induced apoptosis. These results identify the VEGF-C/FLT-4 pathway as a novel therapeutic target for the treatment of subsets of acute leukemia.
Tumor cell dissemination in follicular lymphoma
Authors: Oeschger Sabine , Bräuninger Andreas , Küppers Ralf , Hansmann Martin-Leo
Published: October 2002

The derivation of follicular lymphomas (FLs) from germinal centers is not only supported by their morphologic appearance with a nodular growth pattern and a germinal center–like cellular composition, but also by the presence of ongoing somatic hypermutation (a germinal center B cell–specific process) during their clonal expansion. The intraclonal sequence diversity of the tumor cells and their follicular growth pattern allows one to analyze lymphoma cell dissemination and the way the tumor “metastasizes” to distinct follicles. In the present study, we analyzed individual follicles of 3 FLs by micromanipulation of single cells from individual lymphoma follicles and amplification of immunoglobulin V region genes. Genealogical trees for the VH and the VL gene rearrangements were constructed to analyze the clonal relationship among individual cells of 3 distinct follicles of each case. In all 3 cases there is evidence that distinct tumor follicles are founded by many tumor cells, suggesting that there is extensive migration of the tumor cells among follicles. The observation that the tumor cells of FLs retain their follicular growth patterns despite this cellular migration supports the idea that they depend on the follicular microenvironment for their clonal expansion.
Regression of lymphoproliferative disorder after treatment for hepatitis C virus infection in a patient with partial trisomy 3, Bcl-2 overexpression, and type II cryoglobulinemia
Authors: Casato Milvia , Mecucci Cristina , Agnello Vincent , Fiorilli Massimo , Knight Glenn B. , Matteucci Caterina , Gao Lei , Kay Jonathan
Published: October 2002

A patient with type II cryoglobulinemic vasculitis and hepatitis C virus (HCV) infection presented with a leukemiclike proliferation of B cells bearing marginal zone B-cell phenotypic markers. A partial trisomy 3 (bands 3q11–29) and overexpression of Bcl-2 without t(14;18) translocation was detected in the monoclonal B cells that were classic rheumatoid factor–producing B cells bearing the WA cross-idiotype. Treatment with interferon-α produced a complete clinical remission and synchronous marked decreases in viremia and monoclonal B-cell prevalence. This is the first report of partial trisomy 3 and Bcl-2 overexpression in type II cryoglobulinemic vasculitis associated with HCV infection. Further studies of HCV-infected patients with and without type II cryoglobulinemia are required to determine the prevalence and possible physiologic and/or pathophysiologic significance of these findings.
Iatrogenic adrenal insufficiency as a side-effect of combined treatment of itraconazole and budesonide
Authors: Skov M. , Main K.M. , Sillesen I.B. , Müller J. , Koch C. , Lanng S.
Published: October 2002

A recent case of iatrogenic Cushing's syndrome and complete suppression of the pituitary-adrenal-axis in a patient with cystic fibrosis (CF) and allergic bronchopulmonary aspergillosis treated with itraconazole as an antifungal agent, and budesonide as an anti-inflammatory agent led to a systematic assessment of this axis and gonadal function in all patients treated with itraconazole in the authors' CF centre. Itraconazole can inhibit CYP3A, thus interfering with synthesis of gluco- and mineralocorticoids, androgens and oestradiol as well as the metabolism of budesonide. The aim of this study was to evaluate adrenal and gonadal function in patients treated with itraconazole with or without budesonide.

An adrenocorticotrophic hormone (ACTH) test (250 µg tetracosactid) was performed in 25 CF patients treated with both itraconazole and budesonide, and in 12 patients treated with itraconazole alone (six patients with CF and six with chronic granulomateous disease). Mineralocorticoid and gonadal steroid function were evaluated by measurements of plasma-renin, follicle stimulating hormone, luteinising hormone, progesterone, oestradiol, testosterone, serum-inhibin A and B. ACTH tests performed as part of a pretransplantation programme in an additional 30 CF patients were used as controls.

Eleven of the 25 patients treated with both itraconazole and budesonide had adrenal insufficiency. None of the patients on itraconazole therapy alone nor the control CF patients had a pathological ACTH test. Mineralocorticoid and gonadal insufficiency was not observed in any of the patients. Only one patient with an initial pathological ACTH-test subsequently normalised, the other 10 patients improved but had not achieved normalised adrenal function 2–10 months after itraconazole treatment had been discontinued.

Suppression of the adrenal glucocorticoid synthesis was observed in 11 of 25 cystic fibrosis patients treated with both itraconazole and budesonide. The pathogenesis is most likely an itraconazole caused increase in systemic budesonide concentration through a reduced/inhibited metabolism leading to inhibition of adrenocorticotrophic hormone secretion along with a direct inhibition of steroidogenesis. In patients treated with this combination, screening for adrenal insufficiency at regular intervals is suggested.
Does long-term oxygen therapy reduce hospitalisation in hypoxaemic chronic obstructive pulmonary disease?
Authors: Ringbaek T.J. , Viskum K. , Lange P.
Published: October 2002

The aim of this study was to determine whether long-term oxygen therapy (LTOT) reduces hospitalisation in hypoxaemic patients with chronic obstructive pulmonary disease (COPD). The circumstances of initiation of LTOT (start during hospitalisationversusstart as an outpatient) and compliance with oxygen were also investigated (continuous oxygen therapy (COT) ≥15 h dailyversusnoncontinuous oxygen therapy (NCOT) <15 h daily).

A total 246 COPD patients were studied, with each patient acting as their own control. Patients were divided into four groups: 125 patients on COT who started LTOT in conjunction with hospitalisation, 37 patients on COT who started LTOT as outpatients, 58 patients on NCOT who started LTOT in conjunction with hospitalisation and 26 patients on NCOT who started LTOT as outpatients. Admission rates, days spent in hospital and number of patients with at least one hospitalisation (ever hospitalised) were compared in two periods of 10 months before and after initiation of LTOT.

Overall during the LTOT period, in comparison with the preoxygen period, the admission rates, hospital days and “ever hospitalised” were reduced by 23.8%, 43.5% and 31.2%, respectively. Among patients who started LTOT as outpatients, a tendency towards a higher effect in the compliant group was observed.

This study shows that in hypoxaemic chronic obstructive pulmonary disease patients, long-term oxygen therapy is associated with a reduction in hospitalisation.
Nutritional depletion in patients on long-term oxygen therapy and/or home mechanical ventilation
Authors: Cano N.J.M. , Roth H. , Court-Fortuné I. , Cynober L. , Gérard-Boncompain M. , Cuvelier A. , Laaban J-P. , Melchior J-C. , Pichard C. , Raphaël J-C. , Pison C.M.
Published: October 2002

The purpose of this study was to estimate the prevalence of malnutrition in outpatients on long-term oxygen therapy or home mechanical ventilation, to determine the relationships between malnutrition and impairment/disability and smoking and also to identify relevant tools for routine nutritional assessment.

In 744 patients (M:F 1.68, aged 65±15 yrs) with chronic obstructive pulmonary disease (COPD, 40%), restrictive disorders (27%), mixed respiratory failure (15%), neuromuscular diseases (13%) and bronchiectasis (5%), body mass index (BMI), fat-free mass (FFM), serum albumin, transthyretin, 6-min walking test, forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and blood gases were recorded.

FFM was the most sensitive parameter for detecting malnutrition, being abnormal in 53.6% of patients, while BMI was <20 in 23.2%, serum albumin <35 g·L−1in 20.7 %, and serum transthyretin <200 mg·L−1in 20%. FFM depletion predominated in neuromuscular, bronchiectasis and restrictive disorders. BMI and FFM were correlated with FEV1, FVC and 6-min walking test. In multivariate analysis a BMI<20 was related to FEV1and smoking habits, and a low FFM to smoking, FEV1and female sex.

Malnutrition is highly prevalent in home-assisted respiratory patients and is related to causal disease, forced expiratory volume in one second, smoking and disability. Fat-free mass appeared to be the most sensitive and relevant nutritional parameter according to impairment and disability.
Effects of oxygen on autonomic nervous system dysfunction in patients with chronic obstructive pulmonary disease
Authors: Scalvini S , Porta R , Zanelli E , Volterrani M , Vitacca M , Pagani M , Giordano A , Ambrosino N
Published: October 2002

Chronic hypoxaemia can play a pathological role in abnormalities of the autonomic nervous system (ANS). In patients with chronic obstructive pulmonary disease (COPD), chronic hypoxaemia is associated with increased mortality and only long-term oxygen therapy is able to improve their survival. Normoxaemic COPD patients have been shown to suffer from abnormalities in ANS function. The aims of this study were to evaluate ANS function in COPD patients with chronic hypercapnic respiratory insufficiency and to test whether oxygen supplementation could reverse any ANS dysfunction. Eleven stable COPD patients with chronic hypercapnic respiratory insufficiency underwent evaluation of ANS by analysis of variability in cardiac frequency at rest and during both vagal (controlled breathing) and sympathetic (tilting) stimuli breathing with and without oxygen supplementation. Thirteen male, healthy, nonsmoking volunteers served as controls. Evaluation of ANS in COPD patients during hypoxic conditions showed alterations both at rest and in response to vagal and sympathetic stimuli. Oxygen supply reversed hypoxaemia without significant changes in arterial carbon dioxide tension and, therefore, ANS alterations were corrected during sympathetic stimulus only. Breathing room air and oxygen, the resting low-frequency (LF) powers were 45+/-15 and 148+/-55 ms2 x Hz(-1), respectively, and controlled breathing LF were 107+/-41 and 141+/-113 ms2 x Hz(-1), respectively. In stable patients with chronic obstructive pulmonary disease with chronic respiratory insufficiency, hypoxaemia is associated with derangements in the autonomic nervous system which may be partially reversed by oxygen administration.
An imbalance in plasma prostanoids in patients with Raynaud's phenomenon and pulmonary vasospasm
Authors: Sakamoto K , Houya I , Inoue K , Tanaka M , Suzuki T , Sakamoto Y , Matsuo H
Published: October 2002

Raynaud's phenomenon has been suggested as a predisposing factor for pulmonary vasospasm which may lead to pulmonary hypertension, but the occurrence of cold stimulus-induced pulmonary vasospasm has been inconsistent. Such inconsistent pulmonary vascular responses may be caused by differences in the production of endogenous vasodilators and vasoconstrictors among patients. Fourteen patients with Raynaud's phenomenon associated with mixed connective tissue disease (n=10) or systemic sclerosis (n=4) participated in the study. Right heart catheterization was performed before and after a cold pressor test, immersing a hand in cold water (15 degrees C) for 5 min. Plasma levels of 6-keto prostaglandin (PG)F1alpha, thromboxane (TX)B2 and endothelin (ET)-1 in the mixed venous blood were measured. Mean pulmonary artery pressure increased after the cold pressor test in five of 14 patients, and the patients were divided into those with pulmonary vasospasm (responders) and those without vasospasm (nonresponders). After the cold pressor test, levels of 6-keto PGF1alpha increased significantly in nonresponders (p<0.01) and decreased significantly in responders (p<0.05). The ratios of 6-keto PGF1alpha to TXB2 significantly increased in nonresponders (p<0.01) but not in responders and the difference between responders and nonresponders after the cold pressor test was also statistically significant (p<0.05). No significant change in plasma ET-1 levels occurred in either responders or nonresponders. The results suggest that an impaired production of prostaglandin I2 and an imbalance between prostaglandin I2 and thromboxane A2 are associated with the occurrence of pulmonary vasospasm induced by Raynaud's phenomenon.
Mechanisms underlying effects of nocturnal ventilation on daytime blood gases in neuromuscular diseases
Authors: Annane D , Quera-Salva MA , Lofaso F , Vercken JB , Lesieur O , Fromageot C , Clair B , Gajdos P , Raphael JC
Published: October 2002

The hypothesis that, in neuromuscular and chest wall diseases, improvement in central respiratory drive explains the effects of night-time ventilation on diurnal gas exchanges was tested. The effects at 6 months, 1, 2 and 3 yrs of intermittent positive pressure ventilation (IPPV) on arterial blood gas tension, pulmonary function, muscle strength, sleep parameters, respiratory parameters during sleep and ventilatory response to CO2 were evaluated in 16 consecutive patients with neuromuscular or chest wall disorders. As compared with baseline, after IPPV daytime arterial oxygen tension (Pa,O2) increased (+2.3 kPa at peak effect) and arterial carbon dioxide tension (Pa,CO2) and total bicarbonate decreased (-1.8 kPa and -5 mmol x L(-1), respectively) significantly; vital capacity, total lung capacity, maximal inspiratory and expiratory pressures and alveolar-arterial oxygen gradient did not change; the apnoea-hypo-opnoea index and the time spent with an arterial oxygen saturation (Sa,O2) value <90% decreased (-24 and -101 min, respectively), sleep efficiency and mean Sa,O2 increased (+16% and +5%, respectively); and ventilatory response to CO2 increased (+4.56 L x min(-1) x kPa(-1)) significantly. The reduction in Pa,CO2 observed after IPPV correlated solely with the increase in the slope of ventilatory response to the CO2 curve (r=-0.68, p=0.008). In neuromuscular or chest wall diseases, improvement of daytime hypoventilation with nocturnal intermittent positive pressure ventilation may represent an adaptation of the central chemoreceptors to the reduction of profound hypercapnia during sleep or reflect change in the quality of sleep.
Key elements of total seismic field design using Mathematica—A tutorial
Authors: Benyamin Ninos
Published: October 2002

This tutorial reviews the basics of total seismic field design and provides personal‐computer–based computer language codes that can readily be used, with some modification, to design seismic surveys in the field. The finite effective dynamic range of seismic recording systems together with an overlap of signal and noise spectra suggest that a certain amount of prefiltering is needed during the acquisition phase to insure that a weak signal does not fall below the system noise, which would render the signal useless. The key elements of a total seismic field design are reviewed and, by way of a hypothetical 3‐D field example, their implementation is illustrated. The recommended solution consists of parameters for spread geometry that will record maximum geologic dips without aliasing, and shot and receiver arrays that optimize the signal‐to‐noise ratio.
LocalizedS‐inversion of time‐domain electromagnetic data
Authors: Zhdanov Michael S. , Pavlov Dmitriy A. , Ellis Robert G.
Published: October 2002

Interpretation of time‐domain electromagnetic (TDEM) data over inhomogeneous geological structures is a challenging problem of geophysical exploration. The most widely used approach of interpreting TDEM data is based on the smooth 1‐D layered resistivity inversion. We have developed an effective technique of fast TDEM inversion based on thin‐sheet conductance approximation that we call S‐inversion. In this paper we extend the S‐inversion technique, approximating the conductivity cross‐section by adding a local inhomogeneous disk with an excess conductance ΔS to the horizontal conductive thin sheet used in S‐inversion. Localized S‐inversion determines the distribution of this excess conductance as a function of a depth and a horizontal coordinate. This new method takes into account the limited horizontal extent of the inhomogeneities, localizing inversion. The numerical modeling results and inversion of practical TDEM data demonstrate that the method resolves local geological targets better than traditional 1‐D inversion and original S‐inversion. The method can be applied to interpret both ground and airborne TDEM data sets.
Numerical modeling of borehole georadar data
Authors: Holliger Klaus , Bergmann Tim
Published: October 2002

High‐frequency electromagnetic (EM) wave propagation phenomena associated with borehole georadar experiments are complex. To improve our understanding of the governing physical processes, we present a finite‐difference solution of Maxwell's equations in cylindrical coordinates. This approach allows us to model the full EM wavefield associated with borehole georadar experiments and to assess the adequacy of ray‐based methods currently used to interpret the observed amplitudes. Our results indicate that because shallow boreholes are often water filled, the finite length of the boreholes as well as changes in material properties along a borehole wall can have major effects on the amplitude behavior of borehole georadar data. As a result of waveguide phenomena, the radiation pattern of a vertical electric dipole source located in a water‐filled borehole may be distorted significantly with respect to the corresponding reference radiation pattern in a homogeneous medium. Even greater distortions of the radiation pattern result when the electric dipole source is located near material boundaries or near the upper or lower end of a borehole. This study indicates that some of the basic assumptions of conventional ray‐based amplitude tomography often are not fulfilled for borehole georadar data and that the derived constraints on the attenuation and conductivity structure should be regarded as qualitative in nature. The algorithm and the results presented in this study do, however, offer the perspective to alleviate some of these inherent problems and thus help to make ray‐based georadar attenuation tomography a more reliable and effective tool for probing the shallow subsurface.
The London Heat Island: results from summertime monitoring
Authors: Watkins R , Palmer J , Kolokotroni M , Littlefair P
Published: October 2002

This paper reports results from a study investigating the variation of air temperature across London. The paper focuses on the description of temperature measurements in summer 1999 and the analysis of the results. The intensity of the London Heat Island has been assessed using a radial grid of 68 stations recording simultaneous hourly air temperatures. The urban heat island has been found to be predominantly a nocturnal phenomenon and its intensity reaches 7 K on occasion. It was found that the thermal centre is in the City of London which is characterized by tall buildings and high anthropogenic heat emissions. The nighttime temperature pro” le of London tends to follow a simple pattern with contours arranged roughly circularly around the centre; it is found that 77% of the variance of the mean night-time temperature across London is related to distance from the thermal centre. The more complicated pattern in the daytime precludes such a simple relationship.
An urban geographer before his time: C. Warren Thornthwaite's 1930 doctoral dissertation
Authors: Wheeler James O. , Brunn Stanley D.
Published: October 2002

In 1930, a time when human geography was not considered to be among the emerging analytic social sciences and when urban geography barely existed as an identifiable subfield, C. Warren Thornthwaite, later a gargantuan figure in American climatology, was awarded a doctorate under Carl O. Sauer at the University of California, Berkeley. In his dissertation, ‘Louisville, Kentucky: a study in urban geography’, Thornthwaite analysed land-use zonation, commercial strip development, daytime–night-time populations, community formation, elevation and land values, functional regions and cultural areas, spatial competition and optimal location, buying power and residential distribution. Thornthwaite's urban geography was centered unmistakably in the spatial tradition, and his innovative research – based on aerial photographs, intensive field observations, city directories and detailed mapping – treated concepts that were to become central to urban geography as it developed in the late 1950s and the 1960s. Urban geography, however, evolved independently of Thornthwaite's contributions. Thornthwaite directed no graduate students, and his unpublished dissertation was not cited until a perfunctory reference in 1954. A second citation, not appearing until almost 30 years later, described it as ‘a major synthesis’. Thornthwaite's dissertation was not only an anomaly in the career of its author but also an anachronism in the history of urban geography.
Amitraz intoxication in children in the rural Black Sea region: analysis of forty-three patients
Authors: Kalyoncu M , Dilber E , Ökten A
Published: October 2002

Amitraz is used topically in the treatment of demodicosis and other ectoparasitic infestations. Amitraz poisoning in children has been reported in a few cases. We presented 43 cases with amitraz intoxication. Of the patients, 14 had skin exposure. We compared the skin to peroral exposure group considering intoxication findings and outcome. In the peroral exposure group symptoms and recovery were more severe than in the skin exposure group, but mortality was not seen in two groups.
Effect of a single treatment (imprinting) with genistein or combined treatment with genistein+benzpyrene on the binding capacity of glucocorticoid and estrogen receptors of adult rats
Authors: Csaba G , Inczefi-Gonda Á
Published: October 2002

Hormonal imprinting takes place perinatally at the first encounter between the hormone and its target receptor. This is needed for the normal finishment of the maturation of the receptor–signal transduction system. In excess of foreign molecules, which can also bind to the receptor, faulty imprinting develops with life-long consequences. Genistein, a soybean phytosteroid (isoflavone), has estrogen-like effects and can be bound by steroid receptors. In the present experiments, single neonatal treatment (imprinting) with 20 m g of genistein, or combined treatment with 20 m g of genistein+20 m g of benzpyrene was done and liver and thymus glucocorticoid receptors of adult male and female rats and uterine estrogen receptors were studied. There was no difference in the binding capacity of uterine estrogen receptors. Genistein treatment alone caused a significant reduction of liver glucocorticoid receptor density in males; however, there were no other significant alterations. After combined genistein+benzpyrene treatment, more than half of the thymus and liver glucocorticoid receptor values significantly changed. The results call attention to the imprinting-modifying effect of a second (environmental) imprinter.
Toxicity of a GM3 cancer vaccine inMacaca fascicularis monkey: a 12-month study
Authors: Bada A , Parada A Casacó , Arteaga M , Martínez J , León A , Santana E , Hernández O , Orphee R , González A , Mesa C , González C , Montero E , Fernández L E
Published: October 2002

GM3 is a ganglioside that has been biochemically identified as dominating the cell surface of several human tumours, but is also found on human normal cells at much lower density. Since GM3 is widely distributed in essentially all types of animal cells, there is a conflict with the concepts of tumour-associated antigen, immunogen, and toxicity. We have designed a GM3-based cancer vaccine for the treatment of human breast and melanoma tumours. Prior to the Phase I clinical trial, we carried out a 12-month dose repeated toxicity study in five male Macaca fascicularismonkeys. Four male monkeys were treated with placebo in a similar way. During the study, no differences were observed between control and treated monkeys related to daily clinical observations (other than local damage) including rectal temperature, blood pressure, respiratory and cardiac rates, weight gain, biochemical and hematological parameters (with the exception of transitory pathological changes), and anti-DNA and anti-nuclear antibodies, although treated monkeys consistently developed both IgM-and IgG-specific anti-GM3 antibodies. Sixty per cent of treated monkeys developed moderate local reactions at the injection site, which disappeared without sequels. We concluded that this GM3 cancer vaccine overcame in monkeys the natural tolerance to GM3 gang-lioside evidenced by a strong immune response, while the local reactions elicited were transitory without apparent important systemic toxicity effects.
Ochratoxin A in human plasma in Morocco: a preliminary survey
Authors: Filali A , Betbeder A M , Baudrimont I , Benayada A , Soulaymani R , Creppy E E
Published: October 2002

Available epidemiological information seems to indicate that Balkan endemic nephropathy is associated with consumption patterns involving foodstuffs contaminated with ochratoxin A (OTA) and with a higher frequency of OTA-positive blood samples. The aim of this preliminary study was to assess OTA concentrations in human plasma in Morocco. Therefore, samples from 309 healthy volunteers (213 males, 96 females) were analysed. The analyses revealed that 60% of the human plasma sampled was positive for OTA (61.5% in the male and 56% in the female population), and an average concentration of 0.29 ng// /mL (0.31 ng///mL in males, 0.26 ng// /mL in females). The highest concentration found was 6.59 ng// /mL. The results suggest that the Moroccan population is exposed to OTA, even though the OTA plasma levels are lower than that reported in some North African countries.
An investigation of new toxicity test method performance in validation studies: 2. comparison of three measures of toxicity test performance
Authors: Bruner L H , Carr G J , Harbell J W , Curren R D
Published: October 2002

An area that requires further research is how best to measure test method performance in validation studies and how to set criteria that should be used to judge the adequacy of this performance. The studies reported here were designed to begin an investigation of these questions. Computer simulations were used to generate data sets similar to those that might be obtained from a large validation study. These data were then analysed using three procedures including determination of the 95% prediction interval (PI), calculation of Pearson's correlation coefficient and calculation of the contingent probability statistics (CPS), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The results of this work suggest that of the three approaches examined, quantitative measurements with calculation of the 95% PI provide the most information to allow discrimination between the performance of several different NTMs. The results also suggest that dividing data sets into positive and negative toxicity classifications followed by the calculation of CPS leads to considerable information loss. This loss of information may be so significant that it is not possible in certain circumstances to distinguish between NTMs that are adequate and those that are not.
Promising role of a-ketoglutarate in protecting against the lethal effects of cyanide
Authors: Bhattacharya R , Vijayaraghavan R
Published: October 2002

Treatment of cyanide poisoning generally includes amyl nitrite and//or sodium nitrite (SN) in combination with sodium thiosulphate (STS). However, in many instances of cyanide poisoning, use of nitrites is contraindicated due to their strong vasoactive properties. a-Ketoglutarate (a-KG) antagonizes cyanide poisoning by cyanohydrin formation. Protective efficacy of graded doses of a-KG (p.o.) as pretreatment, simultaneous treatment or post-treatment was evaluated against acute potassium cyanide (KCN) poisoning (p.o.) in female rats. Pretreatment with a-KG (0.125–2.0 g//kg) exhibited dose-and time-dependent effects and was found to be effective even when given up to 60 min prior to KCN. Addition of STS significantly enhanced the protective efficacy of a-KG at all the doses and time intervals. A 10-min pretreatment with a-KG increased the LD50 of KCN by 7-fold, which was further increased 28-fold by the addition of both SN and STS. Simultaneous treatment with a-KG (2.0 g//kg) increased the LD50 of KCN by 7-fold, which was doubled by the addition of STS. However, addition of SN did not confer any additional protection. Post-treatment with a KG+STS minimized the mortality by 50% but did not significantly extend the survival time in KCN (2 LD50)-administered rats. KCN (0.75 LD50) inhibited rat brain cytochrome oxidase, which was significantly protected by pretreatment or simultaneous treatment with a-KG and STS. Considering the efficacy and safety of peroral a-KG, a promising treatment regimen consisting of a-KG +STS or a-KG+SN+STS is proposed depending upon the situation.
Yellow oleander poisoning in Sri Lanka: outcome in a secondary care hospital
Authors: Fonseka M MD , Seneviratne S L , de Silva C E , Gunatilake S B , de Silva H J
Published: October 2002

Cardiac toxicity after self-poisoning from ingestion of yellow oleander seeds is common in Sri Lanka. We studied all patients with yellow oleander poisoning (YOP) admitted to a secondary care hospital in north central Sri Lanka from May to August 1999, with the objective of determining the outcome of management using currently available treatment. Patients with bradyarrhythmias were treated with intravenous boluses of atropine and intravenous infusions of isoprenaline. Temporary cardiac pacing was done for those not responding to drug therapy. During the study period 168 patients with YOP were admitted to the hospital (male:female=55:113). There were six deaths (2.4%), four had third-degree heart block and two died of undetermined causes. They died soon after delayed admission to the hospital before any definitive treatment could be instituted. Of the remaining 162 patients, 90 (55.6%) patients required treatment, and 80 were treated with only atropine and/or isoprenaline while 10 required cardiac pacing in addition. Twenty-five (14.8%) patients had arrhythmias that were considered life threatening (second-degree heart block type II, third-degree heart block and nodal bradycardia). All patients who were treated made a complete recovery. Only a small proportion of patients (17%) admitted with YOP developed life-threatening cardiac arrhythmias. Treatment with atropine and isoprenaline was safe and adequate in most cases.
Gonadal function in adolescents and young women with juvenile systemic lupus erythematosus
Authors: Silva C A A , Leal M M , Leone C , Simone V P , Takiuti A D , Saito M I , Kiss M H B
Published: October 2002

The authors analysed the gonadal function and age of menarche of 23 female adolescentsand young women with SLE, and correlated these with clinical, SLEDAI and therapeutic parameters. The presence of one or more clinical and laboratory parameters defined normal gonadal function: normal menstrual cycles with or without dysmenorrhea; elevated cervical mucus length; normal levels of plasma FSH, LH, estradiol, progesterone, prolactin and testosterone; normal urinary hormonal cytology; serial pelvic ultrasound compatible with ovulatory pattern; and present or previous pregnancy. The mean age of menarche (13.5§ 1.4 years) was greater than that found among 2578 healthy Brazilian adolescents (12.5§ 1.3 years; P = 0.0002). The delay in menarche correlated with an increase in the duration of the disease (P = 0.0085) and the cumulative dose of prednisone (P = 0.0013) used until the appearance of the menarche. The mean phase length in SLE was 31.5§ 10.3. Sixteen female (70%) patients showed normal and seven (30%) abnormal gonadal function. Gonadal function was not correlated with parameters of SLE. These results suggest that the patients of this study reach adulthood with a high chance of fertility.
Allergic disorders in systemic lupus erythematosus: prevalence and family history
Authors: Sekigawa I , Yoshiike T , Iida N , Hashimoto H , Ogawa H
Published: October 2002

The relationship between allergic disorders (such as atopic dermatitis, asthma, allergic rhinitis and allergic conjunctivitis) and systemic lupus erythematosus (SLE) is still unclear and controversial. We investigated the prevalence of these allergic disorders in SLE patients and their families. A questionnaire about the history of allergy was completed by 52 SLE patients and by 52 matched (including race, age, sex and region) non-SLE controls. Our results indicated that there was a signi” cantly lower incidence of these allergic diseases in SLE patients, especially those who had an allergic family histories, when compared with the controls. These ” ndings may be related to the immunological similarities and differences between SLE and various allergic diseases.
The immune development in a child born to a cyclosporin A-treated woman with systemic lupus erythematosus/polymyositis
Authors: Airó P , Antonioli C M , Motta M , Faden D , Chirico G , Cattaneo R , Tincani A
Published: October 2002

The case of a woman affected by an overlap syndrome systemic lupus erythematosus/polymyositis (PM), who presented with active myositis at the start of the pregnancy, is reported. Therapy with cyclosporin, corticosteroids, hydroxychloroquine and high-dose intravenous immunoglobulin induced a progressive remission of clinical and laboratory signs of myositis. At 33 weeks of gestation, after a premature pre-term rupture of membrane, a male child was delivered. Although premature, and small for gestational age, he had a normal growth, and did not show any clinical sign suggestive of immune deficiency. Lymphocyte phenotypical and functional studies, as well as response to vaccination, were also normal.
Characterization of CD3+CD4-CD8- (double negative) T cells in patients with systemic lupus erythematosus: production of IL-4
Authors: Dean G S , Anand A , Blofeld A , Isenberg D A , Lydyard P M
Published: October 2002

Systemic lupus erythematosus (SLE) is a chronic autoimmune rheumatic disease that may affect every organ or system in the body. We have shown previously that the TCR ab‡ subpopulation of CD3‡CD47CD87, DN T cells is expanded in patients with SLE and that double negative T cells express increased levels of activation markers compared both with healthy people and with patients with rheumatoid arthritis, (RA) as autoimmune controls. The aim of this study was to characterize these cells in terms of their ability to produce IL4, a Th2 cytokine, both spontaneously and after mitogen stimulation. It was found that a higher percentageof TCR ab‡ double negative T cells from patients with SLE contained IL4 constitutively than did the same population of cells from healthy people or from those with RA. After mitogen stimulation, there was no signi” cant difference in the amount of IL4 produced by each of the three groups. Further study of patients producing high levels of IL4 (about one third of the patients) indicated that they had a lower percentageof ab‡T cells in the double negative compartment than did patients with fewer IL4 containing cells.
Reflections on the management of reproductive failure in the antiphospholipid syndrome—the clinician’s perspective
Authors: Balasch J , Cervera R
Published: October 2002

It is well known that women with systemic lupus erythematosus (SLE) who have antiphospholipid antibodies (aPL) are at increased risk for pregnancy loss. Additionally, other reproductive processes, such as unexplained infertility and implantation failure after in vitro fertilization and embryo transfer may be affected by aPL. Thus, clinical manifestations of the so-called ‘gynaecoobstetrical antiphospholipid syndrome’ have been expanded into the concept of the ‘reproductive autoimmune failure syndrome’. However, this is still a matter of debate with no general agreement with respect to both pathophysiological signi” cance of the presence of aPL and patient management. This article analyses a number of controversies in the management of reproductive failure potentially associated with aPL in order to help clinicians dealing with such condition in daily clinical practice.
Histopathology of lupus-like nephritis in Dnase1-deficient mice in comparison to NZB/W F1 mice
Authors: Jacob M , Napirei M , Ricken A , Dixkens C , Mannherz H G
Published: October 2002

Deoxyribonuclease 1 (Dnase1)-de”cient mice develop symptoms of Systemic lupus erythematosus (SLE). Here we analysed the renal histopathology of these animals in comparison to F1 hybrids of New Zealand black and white mice (NZB/W F1), an established model of SLE. Animals were divided into three groups according to the presence of anti-nuclear antibodies (ANA) and renal lesions. Groups 1a–1c were healthy, whereas group 2 and 3 were classified as lupus-prone and affected. Subendothelial and/or mesangial immune complex deposits, mesangial and endocapillary proliferation,haematoxylin bodies and platelet aggregation were detected in both mouse strains but were more severe in the NZB/W F1 mice. The lupus nephritis was classi”ed as a proliferating (WHO type III or IV), which appeared to be preceded by a mesangial form (WHO type II). Subclassification of the ANA revealed a high prevalence of anti-nucleosome antibodies in Dnase1-deficient mice, whereas NZB/W F1 mice developed autoantibodies against a broad range of chromatin constituents. Mapping of the murine Dnase1 gene locus to chromosome 16A1-3 did not coincide with one of the reported susceptibility loci in the NZB/W F1 model, although a reduced Dnase1 serum and urine activity has been described previously in these mice.
Low-dose pulse methylprednisolone for systemic lupus erythematosus flares is efficacious and has a decreased risk of infectious complications
Authors: Badsha H , Kong K O , Lian T Y , Chan S P , Edwards C J , Chng H H
Published: October 2002

We sought to test our clinical impression that using a low dose methylprednisolone pulse (MEP; µ1500 mg over 3 days) in treating flares of systemic lupus erythematosus (SLE) was effective and associated with fewer serious infections.

We retrospectively studied SLE patients who received MEP between 1989 and 2000. A ‘low dose’ group of 26 patients who had received 1–1.5 g and a ‘high dose’ group of 29 patients who received 3–5 g of MEP were identified. SLEDAI scores and prednisolone doses were recorded at the time of MEP pulses and 6 months later. All serious infections (requiring admission and i.v. antibiotics) occurring during this 6 month period and their outcomes were recorded.

Both groups had similar demographic data, initial SLEDAI scores, i.v. cyclophosphamide use, and SLE organ involvement. Despite high-and low-dose MEP being efficacious in controlling disease activity (lowering of SLEDAI scores and subsequent prednisolone dose) there were only nine episodes of serious infection in seven patients in the low-dose group compared with 20 episodes in 17 patients from the high-dose group (P ^ 0.04). In both groups a majority of infections (75 and 77% in the high-and low-dose groups) occurred in the first month after MEP. Those with a low serum albumin (< 20 g/l) had an increased risk of mortality (OR 44, 90% CI 6.19–312.98) and a trend towards greater numbers of infections.

Low-dose MEP was effective in controlling SLE flares and associated with fewer serious infections than traditional high-dose MEP.
Estimating the incidence of systemic lupus erythematosus in a tropical region (Natal, Brazil)
Authors: Vilar M J Pereira , Sato E I
Published: October 2002

The objective of the study was to evaluate the incidence of Systemic Lupus Erythematosus (SLE) in a tropical urban community (Natal city, Brazil). Only patients living in Natal, a city in the northeastern area of Brazil, older than 15 years, and who fulfilled at least four of the American College of Rheumatology criteria between 1 January 2000 and 31 December 2000, were included. Four sources were used to identify new cases of SLE: (1) the University Hospital; (2) ‘health units’ and hospitals of the public health network; (3) specialists at private hospitals and outpatient clinics; and (4) three laboratories performing antinuclear antibody (ANA) determination. Census data from 2000 for Brazilian population was used to calculate incidence rate. The standardized mortality ratio (SMR) method and 95% confidence intervals (95% CI) were calculated.

Forty-three patients were diagnosed as new SLE cases in 2000. The calculated incidence was 8.7/100 000/year (95% CI 6.3–11.7). Thirty-eight patients were female 14.1/100000/year (95% CI 10.0–19.3) and five were male 2.2/100 000/year (95% CI 0.7–5.2). The mean age of new SLE cases was 31.8 years old. (95% CI 27.8–35.8). The mean age for females was 31.4 and for males was 35.0 years old. The median of disease duration (time between onset of the first ACR criterion for SLE and diagnosis) was 10 months (1–72 months).

This study demonstrated a high incidence of SLE in Natal, apparently higher than reported in other places. The mean age at diagnosis seems lower than referred by other studies. The observed differences may be due to ethnic and/or environmental factors.
The ocular stress monitor: a new device for measuring discomfort glare
Authors: Murray IJ , Plainis S , Carden D
Published: October 2002

Discomfort glare is always accompanied by a strong contraction or spasm in the muscles surrounding the eye. A portable device for measuring the electrical activity generated by this muscle spasm is described. The device samples the signal from electrodes placed around the eye. It is composed of a narrow-band amplifier/transmitter, a receiver/frequency converter and a tone generator. The signal amplitude is proportional to the vertical illuminance at the eye and can therefore be used as an objective index of the discomfort induced. The results compare favourably with subjective assessment.
Circadian photobiology: an emerging framework for lighting practice and research
Authors: Rea MS , Figueiro MG , Bullough JD
Published: October 2002

A century of research and practice have optimized the use of electric lighting in buildings to support human vision. However, recent lines of research show that light is also important to human circadian regulation, as reflected in such diverse phenomena as depression, sleep quality, alertness, and, perhaps, even health. Although light is essential to both vision and circadian regulation, research shows that the biophysical processes that govern circadian regulation are very different from those that govern vision. This growing body of research will probably influence the architectural lighting community and manufacturers to reoptimize the use of electric lighting in buildings to support both human vision and circadian functions. The present paper is concerned with establishing a framework for lighting practice and applied research that will assist lighting practitioners and manufacturers in interpreting this emerging research.
Use of drugs, alcohol and tobacco by people with schizophrenia: case–control study
Authors: McCreadie Robin G.
Published: October 2002

Background

Specialised services should be developed to help people with schizophrenia and associated substance misuse. The extent of the problem therefore needs to be known.

Aims

To determine the use of drugs, alcohol and tobacco by people with schizophrenia drawn from rural, suburban and urban settings, and to compare use by general population control subjects.

Method

People with schizophrenia (n=316) and general population controls of similar gender distribution, age and postcode area of residence (n=250) were identified in rural, urban and suburban areas of Scotland. Use of drugs and alcohol was assessed by the Schedules for Clinical Assessment in Neuropsychiatry, and use of tobacco by a questionnaire.

Results

More patients than controls reported problem use of drugs in the past year (22 (7%)v.5 (2%)) and at some time before then (50 (20%)v.15 (6%)) and problem use of alcohol in the past year (42 (17%)v.25 (10%)) but not at sometime previously (99 (40%)v.84 (34%)). More patients were current smokers (162 (65%)v.99(40%)).

Conclusions

Problem use of drugs and alcohol by people with schizophrenia is greater than in the general population, but absolute numbers are small. Tobacco use is the greatest problem.
Focus on psychiatry in East Africa
Authors: Njenga Frank
Published: October 2002

East Africa is made up of Kenya, Uganda and Tanzania, all previous colonies of the British Empire which attained their independence in the early 1960s. At the time of independence, the East African community held the three countries together. Political expedience broke up the community in 1977 but greater wisdom and economic reality have brought the three countries back together in December 2001, in the form of a common Legislative Assembly and Court of Appeal. A Customs Union is expected soon, ahead of full political integration.
Ethics Seminars: Teaching Professionalism to “Problem” Residents
Authors: Marco Catherine A.
Published: October 2002

Professional skills, which include communication, compassion, honesty, integrity, altruism, service, commitment, suspension of self‐interest, commitment to excellence, authority, and accountability, are essential skills that should be taught during residency. A variety of approaches can be used, which include didactic teaching, bedside teaching, leadership, evaluation, and individualized mentorship. Deficiencies in professional skills should be identified early in the residency program, and should be addressed on an individual level.