bluuebunny/crossref_metadata_2025 huggingface dataset:
Environmental changes and human impact as recorded in a sediment sequence offshore from a Viking Age town, Birka, southeastern Sweden
Authors: Risberg Jan , Karlsson Sven , Hansson Ann-Marie , Hedenström Anna , Heimdahl Jens , Miller Urve , Tingvall Carin
Published: October 2002

The Viking Age town of Birka, which existed between AD 750 and 975, on the island of Björkö in the Mälar archipelago of the Baltic Sea, is known as the oldest centre used for large-scale international trading in Sweden. Birka had a strong defence: town rampart, hillfort and a water palisade. Studies of lithology, and microand macroremains in a sedimentary sequence accumulated offshore from Birka, outside the water palisade, revealed a stratigraphically distinct refuse stratum, referred to as the Birka Layer. We argue that the bulk material of the Birka Layer emanates from human activities in the town, e.g., latrine cleanings, cuttings of shore vegetation, cleaning of ditches and storage areas, and domestic animal dung. Organic remains from vegetation and animals, deposited during activities on the ice offshore from the town, e.g., winter markets, may also have contributed to the composition. The material constituting the Birka Layer started to accumulate after the construction of the protecting water palisade. In the Birka Layer and the underlying clay gyttja, there seems to be a succession of five activity phases recorded during the Birka period. After the initial establishment of the town, an expansion took place, followed by a retrogression. The most intense phase with culminating activities is registered prior to abandonment of the site, which approximately coincides with the onset of the extended final isolation process of Lake Mälaren (AD 1000-1300). The sailing routes to Birka from the south and east became too shallow and were finally cut off by the emerging thresholds. After the abandonment of Birka, the town area was utilized for cultivation and cattle-breeding.
Ingestion of medicated oils by adults: the risk of severe salicylate poisoning is related to the packaging of these products
Authors: Chan T YK
Published: October 2002

Ingestion of medicated oils containing methyl salicylate poses the threat of severe, rapid-onset salicylate poisoning. In this retrospective study of 24 adults who had ingested ‘White Flower Oil’ (n=18) or ‘Red Flower Oil’ (n=6), the main objective was to determine if the risk of severe salicylate poisoning was related to the product packaging. ‘Red Flower Oil’ had a large bottle opening so that its content could be emptied much more easily. It also had a larger bottle size and usually had a higher methyl salicylate concentration than ‘White Flower Oil’. Patients tended to ingest a greater amount of ‘Red Flower Oil’ than ‘White Flower Oil’. Five per cent of subjects who had taken ‘White Flower Oil’, but 67% of subjects who had taken ‘Red Flower Oil’, had admission plasma salicy-late level ≥2.2 mmol/L (P=0.006). None of the subjects who had ingested ‘White Flower Oil’, but 50% of subjects who had taken ‘Red Flower Oil’, had moderate to severe symptoms (P=0.010). As a result, none of the subjects who had ingested ‘White Flower Oil’, but 33% of subjects who had taken ‘Red Flower Oil’, required urine alkalinization (P=0.054). One patient who had taken ‘Red Flower Oil’ died because of hospital-acquired pneumonia. All other patients made a complete recovery. To reduce the amount of methyl salicylate that can be readily swallowed during accidental or deliberate ingestion of medicated oils, improvements are needed in the existing packaging of these products.
Scleroderma-like nailfold capillaroscopic abnormalities are associated with anti-U1-RNP antibodies and Raynaud's phenomenon in SLE patients
Authors: Furtado R NV , Pucinelli M LC , Cristo V V , Andrade L EC , Sato E I
Published: October 2002

This study aimed to evaluate the association between nailfold capillary abnormalities and the presence of Raynaud's phenomenon (RP), anti-U1-RNP, and anti-cardiolipin (aCL) antibodies in SLE patients.

One-hundred SLE patients were studied. Widefield nailfold capillaroscopy was considered abnormal according to five criteria. Intercapillary distance, capillary width and capillary length were registered by videomorphometry in two fingers in 100 patients and in four fingers in 40 of these patients.

Both the presence of alterated capillaroscopy and the presence of scleroderma-pattern (SD-pattern), characterized by the presence of avascular areas and enlarged or giant loops, were associated with the isolated presence of RP (P < 0.001) or anti-U1-RNP antibodies (P < 0.01), as well as with the simultaneous presence of RP and anti-U1RNP antibodies (P < 0.001). There was a negative association between the presence of aCL antibodies and SD-pattern (P < 0.05). Higher figures for the videomorphometric parameters capillary width, intercapillary distance and capillary length (measured on four fingers) were observed in patients with RP. Patients presenting both RP and anti-U1-RNP antibodies showed higher figures for intercapillary distance and capillary width.

This study demonstrated significant association between nailfold capillaroscopic abnormalities and either RP or anti-U1-RNP antibodies in SLE patients. The association of RP, anti-U1-RNP antibodies, and ‘scleroderma-like’ findings on nailfold capillaroscopy (SD-pattern) in patients with SLE may suggest a new SLE subset with subclinical features of systemic sclerosis.
Recent advances in antiphospholipid antibodies and antiphospholipid syndromes in pediatric populations
Authors: Avcin T , Cimaz R , Meroni P L
Published: October 2002

In recent years, antiphospholipid antibodies (aPL) and their associated clinical features have been recognized increasingly in various pediatric autoimmune and non-autoimmunediseases. Pathogenic mechanisms involved in pediatric antiphospholipid syndrome (APS) appear to be the same as inadults. However, since pediatric patients do not have prothrombotic risk factors present in adults, there clearly are differences in the spectrum of clinical findings. The frequency of aPL-related thrombotic events is generally low in pediatric populations. On the other hand, various commonly acquired infections are likely to be responsible for higher percentage of non-pathogenic and transient aPL in childhood. Such points have to be considered in clinical judgment of elevated aPL in children. In this review we summarize the recent data on the prevalence and clinical significance of aPL in neonates, children and adolescents.
Relationship of tumour necrosis factor alpha gene polymorphisms and neuropsychiatric lupus
Authors: May L-A , Huang Q , Morris D , Danis V , Manolios N
Published: October 2002

Systemic lupus erythematosus (SLE) is a multisystem disorder which appears to be influenced by genetic make-up. In this study we determine allele frequency and genotype distribution of TNFa polymorphisms in two populations of SLE patients (with and without neuropsychiatric manifestations) in order to determine whether the rare allele (TNF2) confers susceptibility for neuropsychiatric disease in SLE. Patients with SLE were retrospectively reviewed to determine presence (n = 17) or absence (n = 47) of documented neuropsychiatric manifestations attributable to SLE. The DNA from these patients was extracted from peripheral blood mononuclear cells, and PCR amplification, NcoI enzyme digestion and 10% polyacrylamide gel electrophoresis were performed to define the different TNFa alleles. Two alleles were demonstrated, TNF1 (wild-type) and TNF2 (rare type), with three possible genotypes, TNF1,1, TNF1,2 and TNF2,2. A frequency of 24% was found for the TNF2 patients with neuropsychiatricinvolvement and was not statistically different to a frequency of 28% found in SLE patients without neuropsychiatric manifestations. The TNF-2 allele does not confer susceptibility for neuropsychiatric manifestations in SLE patients.
Serum thrombopoietin levels and anti-thrombopoietin antibodies in systemic lupus erythematosus
Authors: Füreder W , Firbas U , Nichol J L , Pistillo J , Winkler S , Hiesberger H , Sperr W R , Smolen J , Schett G
Published: October 2002

Thrombocytopenia is a common phenomenon in patients suffering from systemic lupus erythematosus (SLE). The cause of thrombocytopenia in SLE, however, is poorly understood. In this study, 100 patients with SLE were evaluated for serum thrombopoietin levels, anti-thrombopoietin antibodies and routine laboratory parameters such as peripheral blood counts, parameters of blood chemistry and immunologic parameters of SLE.

The median platelet count of SLE patients was 230 g/l and 19 were thrombocytopenic(range 8–148 g/l). Thrombopoietin levels in SLE patients were found to be significantly higher than in healthy controls (n=96; median, 117 pg/ml vs 64 pg/ml, P < 0.01). When excluding thrombocytopenic SLE patients, thrombopoietinlevels in SLE were still above controls (111 pg/ml, P < 0.01). The thrombopoietin levels were correlated to erythrocyte sedimentation rate and ECLAM score of disease activity, and inversely correlated to complement factor C4, but not to the platelet count. Anti-thrombopoietin antibody reactivity was found in 23% of SLE patients. Interestingly, these patients had lower platelet counts than SLE patients without anti-thrombopoietin antibodies (median 174 g/l and 253 g/l, respectively, P < 0.01), but thrombopoietin levels were not significantly different.

Taken together, thrombopoietin levels are significantly higher in the sera of SLE patients than in healthy controls and anti-thrombopoietin antibodies are frequently found.
Dual antibody reactivity to β2-glycoprotein I and protein S: increased association with thrombotic events in the antiphospholipid syndrome
Authors: Erkan D , Zhang H W , Shriky R C , Merrill J T
Published: October 2002

The antiphospholipid syndrome (APS) is a thrombotic disorder leading to spontaneous abortions, venous thromboses, myocardial infarctions and strokes. Although the syndrome is associated with characteristic autoantibodies, these tests have poor predictive value for thrombosis.

The aim of the study was to determine whether the combined presence of two types of antiphospholipidantibodies can be associated with a high-risk subset of thrombosis-prone patients.

One hundred and thirty-four sera from a lupus clinic were tested for antibodies to β2-glycoprotein I (β2GPI), protein S and prothrombin. In a group of 29 patients for whom plasma was available, free (functional) protein S levels were also measured.

Autoantibodies to β2GPI and protein S are associated with each other. Dual reactivity to β2GPI and protein S correlates with increased history of thrombotic events (69% of doubly reactive patients) when compared to either type of autoantibodyalone (37% of patients with only anti-β2GPI and 38% with only anti-protein S, P=0.04 and P=0.01, respectively) or neither reactivity (37%). Among 29 patients tested for free (functional, anticoagulant)protein S levels, the lowest levels were found in patients with antibodies to β2GPI and/or protein S, and all four patients with a history of thrombosis had below-normal free protein S levels. These associations were not found with antiprothrombin antibodies.

In conclusion dual autoantibodiesto β2GPI and protein S are associated with increased history of thrombosis in the antiphospholipid syndrome.
Hypertension as the presenting feature of the antiphospholipid syndrome
Authors: Karim M Y , Alba P , Tungekar M F , Abbs I C , Khamashta M A , Hughes Grv , Hunt B J
Published: October 2002

The antiphospholipid or Hughes syndrome is the association between antiphospholipid antibodies (aPL), venous and arterial thromboses and pregnancy morbidity.1 Antiphospholipid syndrome (APS) commonly coexists with autoimmune diseases usually systemic lupus erythematosus (SLE), when it is known as secondary APS. When present in isolation it is known as primary APS (PAPS). Although the kidney may be affected in APS, its involvement is perhaps not as well described as that of other organs. Thrombotic microangiopathy (TMA) affecting the kidney has been reported as a manifestation in both primary and secondary APS. This report describes hypertension related to underlying renal TMA as a presenting symptom of APS.
Pregnancy outcome in patients with undifferentiated connective tissue disease: a preliminary study on 25 pregnancies
Authors: Mosca M , Neri R , Strigini F , Carmignani A , Totti D , Tavoni A , Bombardieri S
Published: October 2002

Undifferentiated connective tissue disease (UCTD) is a group of systemic autoimmune conditions not fulfilling the classification criteria for a definite connective tissue disease (CTD). While an average of 20% of UCTD patients develop a defined CTD during follow-up, the remaining patients maintain an undefined disease.

Since pregnancy is considered to be an important factor that may alter the course of autoimmune diseases, we examined 25 pregnancies in 20 UCTD patients being followed at our unit in order to evaluate: (i) the pregnancy outcome; (ii) whether pregnancy is associated with flares of disease activity; and (iii) whether pregnancy may be a trigger for the development of a defined CTD.

Twenty-two pregnancies (88%) were successfully brought to term, while the remaining three (12%) ended in an abortion in the first trimester. Obstetric complications were observed in six out of the 22 successful pregnancies (27%). Six patients (24%) experienced a disease flare during pregnancy or puerperium, one of whom presented a major flare and developed systemic lupus erythematosus. In the other five patients the manifestations at flare were mild and included arthritis, fever and skin rash. The incidence of flares in a control population of non-pregnant UCTD patients over a period of 1 year was 7%.

Although UCTD is a mild condition, the risk of flares during pregnancy appears increased and therefore careful monitoring is as necessary as in other CTD patients. Further prospective studies will be necessary to confirm these preliminary observations.
Engagement of complement receptor 2 on the surface of B cells from patients with systemic lupus erythematosus contributes to the increased responsiveness to antigen stimulation
Authors: Mitchell J P , Enyedy E J , Nambiar M P , Lees A , Tsokos G C
Published: October 2002

B cells from patients with systemic lupus erythematosus (SLE) display increased responses following cross-linking of the surface antigen receptor. We explored the possibility that the increased responses are at least partially due to simultaneous cross-linking of the complement receptor 2 (CR2). To this end, we stimulated fresh B cells from SLE patients with an anti-IgD antibody conjugated to the Epstein–Barr virus gp350 protein, which binds to CR2, and recorded the free intracytoplasmic calcium response during the first 10 min. Despite the fact that SLE B cells were found to express half as many surface CR2 as normal B cells, both peak responses and the percentage of responding cells were significantly increased in the former. These observations suggest that regulatory molecules such as CR2 are involved in the increased B cell responses in SLE patients. We propose that certain immune complexes that circulate in the sera of SLE patients that have anti-surface immunoglobulin specificities and are decorated with natural ligands of CR2, such as C3d, elicit and promote B cell overactivity.
Dysregulation of the granulocyte-macrophage colony stimulating factor receptor is one of the causes of defective expression of CD80 antigen in systemic lupus erythematosus
Authors: Funauchi M , Yoo B S , Nozaki Y , Sugiyama M , Ohno M , Kinoshita K , Kanamaru Akihisa
Published: October 2002

CD80 and CD86, expressed on the antigen-presenting cells (APCs) provide costimulatory signals for T lymphocytes. Recently, defective expression of CD80 has been reported in systemic lupus erythematosus (SLE) although its mechanism is unclear. Here, expression of the B7 antigens induced by interferon-g, interleukin-4 or granulocyte-macrophage stimulating-factor (GM-CSF) along the differentiation process of APCs was investigated. In contrast to CD86, expression of CD80 on the CD14‡ cells induced by GM-CSF was reduced in SLE. GM-CSF receptor (GMCSFR) was down-regulated by GM-CSF or phorbol 12-myristate 13-acetate in both of the normal controls and SLE patients, while this change was more remarkable in the latter. In the presence of 1-(5-isoquinolinsulfonyl)-2-methylpiperazine, an inhibitor of protein kinase C, the PMA-induced down-regulation of GM-CSFR was reversed in the normal controls but not in SLE. These data suggest that dysregulation of the GM-CSFR might be associated with the defective expression of CD80, leading to dysfunction of the APCs in SLE.
Revisiting the anticardiolipin test and its standardization
Authors: Harris E N , Pierangeli S S
Published: October 2002

Although the importance of the anticardiolipin test in diagnosis of antiphospholipid syndrome (APS) is widely accepted, there remains much misunderstanding about the strengths and weaknesses of this assay. Several disorders result in formation of low levels of the antibody, hence the anticardiolipin test is not specific when results are low positive. In general, the higher the anticardiolipin level the greater the likelihood of a diagnosis of APS. Hence there have been numerous efforts to enable reproducible measurement of anticardiolipinlevels. Standard calibrators were introduced to construct calibration curves from which levels of unknown samples can be derived. Those standard calibrators were made by mixing varying quantities of high positive with normal sera. More recently, calibrators derived from monoclonal anticardiolipin antibodies have been introduced. There are advantages and disadvantages with both types of calibrators. Determination of a precise and reproducible anticardiolipin level is difficult, whatever the calibrators used, because the assay is dependent on several variable components, any of which may fail on any given day. Utilization of a semi-quantitative measure (low, medium, high) may suffice in most clinical settings and would be less subject to error. Validated ELISA kits may offer greater reproducibility, since there is less variability than bench assays set up in very different laboratories. Whether using a kit or a bench assay, meticulous attention to detail offers the best opportunity for precision and reproducibility. Lupus (2002) 11, 269–275.
CD40L overexpression on T cells and monocytes from patients with systemic lupus erythematosus is resistant to calcineurin inhibition
Authors: Katsiari C G , Liossis S-NC , Dimopoulos A M , Charalambopoulos D V , Mavrikakis M , Sfikakis P P
Published: October 2002

To explore the regulatory defects underlying the overexpression of CD40 ligand (CD40L, CD154) in human lupus we studied the effects of cyclosporin-A (CsA), which blocks Ca2+/calcineurin-dependent CD40L gene expression, on peripheral blood-derived T cells and monocytes. In contrast to control subjects, CsA failed to inhibit the prolonged CD40L expression observed in vitro on anti-CD3-activated lupus T cells. Resistance to CsA was not restricted to CD4+ or CD8+ T cell subsets and was disease activity-independent. Experiments assessing the effects of dexamethasone on CD40L expression, as well as of CsA on the early activation marker CD69 expression and on surface CD40L cleavage, confirmed the unique regulation of CD40L in lupus T cells. On the other hand, co-culture with anti-CD3-activated T cells caused surface CD40L expression on monocytes, which was not an Fc receptor-mediated event. Lupus monocytes clearly overexpressed CD40L comparing to healthy and disease-control monocytes, and, similarly to lupus T cells, displayed a prominent resistance to CsA inhibitory effects. These findings indicate that, besides Ca2+/calcineurin-dependent mechanisms, other pathways are involved in the dysregulation of CD40L in SLE immune cells, dissection of which may have important therapeutic implications.
Techniques for incorporating longitudinal measurements into analyses of survival data from clinical trials
Authors: Troxel A B
Published: October 2002

This article reviews existing approaches for joint analysis of longitudinal measurements, possibly measured with error or incompletely observed, and event-time data, possibly censored. The models take the form of selection or pattern-mixture models; estimation proceeds via the EM algorithm or Bayesian sampling techniques. The models are compared, their estimation and inferential procedures described, and advantages and disadvantages noted. Examples are discussed from several disease areas, including cancer and AIDS.
Repeated measures with zeros
Authors: Berk K N
Published: October 2002

Consider repeated measures data with many zeros. For the case with one grouping factor and one repeated measure, we examine several models, assuming that the nonzero data are roughly lognormal. One of the simplest approaches is to model the zeros as left-censored observations from the lognormal distribution. A random effectis assumed for subjects. The censored model makes a strong assumption about the relationship between the zeros and the nonzero values. To check on this, you can instead assume that some of the zeros are ‘true’ zeros and model them as Bernoulli. Then the other values are modeled with a censored lognormal. A logistic model is used for the Bernoulli p, the probability of a true nonzero. The fit of the pure left-censored lognormal can be assessed by testing the hypothesis that p is 1, as described by Moulton and Halsey.1 The model can also be simplified by omitting the censoring, leaving a logistic model for the zeros and a lognormal model for the nonzero values. This is approximately equivalent to modeling the zero and nonzero values separately, a two-part model. In contrast to the censored model, this model assumes only a slight relationship (a covariance component) between the occurrence of zeros and the size of the nonzero values. The models are compared in terms of an example with data from children’s private speech.
Development of a Model of Moral Distress in Military Nursing
Authors: Fry Sara T , Harvey Rose M , Hurley Ann C , Foley Barbara Jo
Published: October 2002

The purpose of this article is to describe the development of a model of moral distress in military nursing. The model evolved through an analysis of the moral distress and military nursing literature, and the analysis of interview data obtained from US Army Nurse Corps officers (n = 13). Stories of moral distress (n = 10) given by the interview participants identified the process of the moral distress experience among military nurses and the dimensions of the military nursing moral distress phenomenon. Models of both the process of military nursing moral distress and the phenomenon itself are proposed. Recommendations are made for the use of the military nursing moral distress models in future research studies and in interventions to ameliorate the experience of moral distress in crisis military deployments.
What Matters to the Parents? a qualitative study of parents’ experiences with life-and-death decisions concerning their premature infants
Authors: Støre Brinchmann Berit , Førde Reidun , Nortvedt Per
Published: October 2002

The aim of this article is to generate knowledge about parents’ participation in life-and-death decisions concerning their very premature and/or critically ill infants in hospital neonatal units. The question is: what are parents’ attitudes towards their involvement in such decision making?

A descriptive study design using in-depth interviews was chosen. During the period 1997-2000, 20 qualitative interviews with 35 parents of 26 children were carried out. Ten of the infants died; 16 were alive at the time of the interview. The comparative method (grounded theory) was used to analyse the data. The analysis was carried out continuously and in parallel with data collection.

Six categories were revealed by the analysis: indecision and uncertainty (ambivalence); information and communication; participate, but do not decide; seeming to be included; the parents’ child; and individual consideration.

The findings appear to indicate that parents agree that they should not have the final word in decisions concerning their infants’ future life or death. Such a responsibility would put too heavy a burden on parents who lack the medical knowledge and the professional experience needed to make such a decision, and would be likely to lead to them experiencing strong feelings of guilt. The findings show that parents should be well informed and listened to during the whole decision-making process. Their primary concern was how nurses and physicians communicate with parents who are experiencing a crisis, and how this serious information is presented.
Stories from the Operating Room: moral dilemmas for nurses
Authors: Killen Aileen R
Published: October 2002

This article explores stories related by perioperative nurses when asked to describe ethical judgements and subsequent actions that affected patient outcomes. A total of 214 patient care situations were analysed for moral actions taken and moral outcomes achieved in the perioperative arena. Content analysis of the patient care situations revealed a wide variety of ethical issues. Concerns about informed consent and quality of care were the most frequently identified issues. Respondents reported that 7% of patients underwent unwanted procedures and that positive moral outcomes were achieved in 65% of situations. It is of concern that, despite the fact that more than two-thirds (69%) of the respondents reported undergoing ethics education, only 27% could relate a story of an ethical situation.
Ethical values in health care: an Indian-Swedish co-operation
Authors: Hamrin Elisabeth , Potdar Naina S , Anand Raj K
Published: October 2002

The aim of this report is to present an example of a multidisciplinary Indian-Swedish co-operation on ethics in health care. It is based on a conference held in Asia Plateau, Panchgani, Maharasthra, India in 1998. The emphasis is on ethical values that are important for consumers of health care and professionals, and also for different cultures in developed and developing countries. The importance of human dignity is stressed. Sixteen recommendations are given in an appendix.
Thiopurine methyltransferase activity in a Spanish population sample: decrease of enzymatic activity in multiple sclerosis patients
Authors: Menor C , Fueyo J , Escribano O , Piña M J , Redondo P , Cara C , Román I D , Fernández-Moreno M D , Guijarro L G
Published: October 2002

The present study was performed in order to obtain the thiopurine methyltransferase (TPMT) activity frequency distribution histogram in a Spanish population. A total of 3640 Spanish clinical laboratory samples were evaluated, which included 1249 patients with Crohn’s disease, 589 with ulcerative colitis, 348 with multiple sclerosis (MS), 487 with several autoimmune diseases different from the above-mentioned diseases and 967 a donor group. We have measured the TPMT activity in red blood cells (RBCs) by a radiochemical method, using S-adenosyl-L-[methyl-3H]methionine as methyl donor. The different groups present in their entirety a normal distribution histogram and a wide range of TPMT activity from 0 to 41 U/ml RBCs. The differences found between the Spanish population TPMT activity frequency distribution histogram and the pattern previously described in a North American population were not due to azathioprine treatment or gender. The effect of autoimmune diseases on TPMT activity was evaluated: the enzymatic activity was similar in the donor group (19.9-6.3 U/ml RBCs) and in the patients with Crohn’s disease (20.0-5.8 U/ml RBCs) and ulcerative colitis (19.7-6.1 U/ml RBCs); however, it decreased significantly (p<0.0001) in MS patients (17.1-6.1 U/ml RBCs) with respect to the donor group. In conclusion, our results show that the Spanish population TPMT distribution is closer to that of the Jewish population of Israel than to North American populations, and that in MS the enzymatic activity of TPMT decreases significantly. This observation may take into account the usage of azathioprine as therapeutic agent in Spanish MS patients.
T1 histograms of normal-appearing brain tissue are abnormal in early relapsing-remitting multiple sclerosis
Authors: Griffin C M , Dehmeshki J , Chard D T , Parker G JM , Barker G J , Thompson A J , Miller D H
Published: October 2002

Objective: To use both whole-brain and normal-appearing brain tissue (NABT) T1 relaxation time histograms to investigate abnormalities in early relapsing-remitting (RR) multiple sclerosis (MS). Background: In patients with established MS, both lesions and NABT exhibit an increase in T1 relaxation time. By using T1 histogram analysis, it is hoped that such changes in early disease can be detected. Method: Twenty-seven patients and 14 age- and sex-matched controls underwent magnetic resonance imaging (MRI) of the brain, which included the following sequences: 1) proton density (PD)- and T2-weighted fast spin echo (FSE) to measure T2 lesion load, 2) PD- and T1-weighted gradient echos from which T1 relaxation was calculated, and 3) T1-weighted SE imaging pre- and post-triple dose (0.3 mmol/kg) gadolinium (Gd-DTPA) to measure T1 hypointense and gadolinium-enhancing lesion loads, respectively. All patients had RR MS with disease duration <3 years (median 1.7 years). Statistical parametric mapping (SPM) 99 was used to segment brain from cerebrospinal fluid (CSF), and lesions were segmented using a local thresholding technique. Results: Both whole-brain and NABT histograms were abnormal for all six T1 histogram parameters that were measured. For NABT, the mean T1 was 1027 (-74) ms in patients and 969 (-41) ms in controls (p=0.003). There was little difference between the global and NABT histograms, which indicates that most of the whole-brain histogram abnormality derives from normal-appearing tissues. There was a correlation between the Nine-Hole Peg Test and NABT T1 measures. Conclusion: There are widespread abnormalities of NABT in early RR MS, which were sensitively detected by T1 relaxation time histogram analysis. As such, T1 histogram analysis appears promising for studying the natural history of early RR MS, and in the monitoring of response to treatment.
Review: Subjective criteria for lighting design
Authors: Jay PA
Published: October 2002

A distinction is drawn between two types of lighting installation - functional and subjective. In the first type ease of seeing is the primary requirement, in the second other considerations have equal importance. The characteristics of common examples of each kind of installation are given and it is shown that these are entirely consistent with current ideas of the visual process, as indicated by extracts from recent scientific literature.
A design guide for performance assessment of solar light-pipes
Authors: Zhang X , Muneer T , Kubie J
Published: October 2002

Due to an increasing demand for an improvement in environmental conditions for living and a need for energy saving, development of daylight exploitation products has accelerated. The invention of light-pipes which bring natural light indoors where sunlight cannot reach without generating excessive heat is one such example. Mathematical modelling activities aimed at predicting the daylighting performance achievable by light-pipes with various configurations under all weather conditions in the UK are being undertaken. Two models, one for straight light-pipes and the other for elbowed light-pipes are described. The models enable estimation of daylight provision of the light-pipes with a high degree of accuracy i.e., R2 values of 0.95 and 0.97 for regression between predicted and measured illuminance were respectively obtained for the above models. The maximum Mean Bias Error (MBE) and Root Mean Square Error (RMSE) were -2 lux and 27 lux. A design guide for light-pipe assessment is presented that will obviate the need for use of mathematical models.
Fluid resuscitation in pre-hospital trauma care: a consensus view
Authors: Revell Matthew , Porter Keith , Greaves Ian
Published: October 2002

Fluid administration for trauma in the pre-hospital environment is a challenging and controversial area. The available evidence does not clearly support any single approach. Nevertheless, some provisional conclusions may be drawn. We believe that the following guidelines represent a sound expert consensus. It is intended that they will be modifi ed as future research brings clarity to the area. When treating trauma victims in the pre-hospital arena cannulation should take place en route where possible. Only two attempts at cannulation should be made. Transfer should not be delayed by attempts to obtain intravenous access. Entrapped patients require cannulation at the scene. Normal saline may be titrated in boluses of 250 ml against the presence or absence of a radial pulse (caveats; penetrating torso injury, head injury, infants).
Semiparametric methods in applied econometrics: do the models fit the data?
Authors: Horowitz Joel L , Lee Sokbae
Published: October 2002

Much empirical research in economics and other fields is concerned with estimating the mean of a random variable conditional on one or more explanatory variables (conditional mean function). The most frequently used estimation methods assume that the conditional mean function is known up to a finite number of parameters, but the resulting estimates can be highly misleading if the assumed parametric model is incorrect. This paper reviews several semiparametric methods for estimating conditional mean functions. These methods are more flexible than parametric methods and offer greater estimation precision than do fully nonparametric methods. The various estimation methods are illustrated by applying them to data on the salaries of professional baseball players in the USA. We find that a parametric model and several simple semiparametric models fail to capture important features of the data. However, a sufficiently rich semiparametric model fits the data well. We conclude that semiparametric models can achieve their aim of providing flexible representations of conditional mean functions, but care is needed in choosing the semiparametric specification. Our analysis also provides some suggestions for further research on semiparametric estimation.
Intensive, Very Short-Term Chemotherapy for Advanced Burkitt’s Lymphoma in Children
Authors: Spreafico Filippo , Massimino Maura , Luksch Roberto , Casanova Michela , Cefalo Graziella S. , Collini Paola , Ferrari Andrea , Polastri Daniela , Terenziani Monica , Gasparini Marco , Fossati-Bellani Franca
Published: October 2002

PURPOSE: To improve the 63% event-free survival (EFS) achieved before 1986 in Murphy’s stage III to IV Burkitt’s lymphoma (BL), both chemotherapy and supportive care were intensified.

PATIENTS AND METHODS: From May 1987 to February 2001, 60 children, median age 9 years (range, 2.1 to 17 years), with advanced BL were enrolled onto two sequential institutional studies. From 1987 to 1992, 30 patients were stratified according to the absence (regimen IA, n = 19) or presence (regimen IB, n = 11) of bone marrow (BM) or CNS involvement. After 5-week cytoreductive chemotherapy consisting of vincristine, cyclophosphamide, doxorubicin, high-dose (HD) methotrexate (MTX), and intrathecal MTX or cytarabine, HD cytarabine and cisplatin were provided as a 4-day continuous infusion. Regimen IB was intensified by adding etoposide and HD ifosfamide and escalating MTX doses. Since 1992, regardless of BM or CNS status, 30 patients have been placed on regimen II, which is identical to IB but without ifosfamide. The scheduled duration of regimen II was 45 days.

RESULTS: EFS and disease-free survival at 5 years are 81% ± 5% and 87% ± 5%, respectively, for 59 assessable patients (73% ± 8% and 85% ± 7% for regimen IA + IB, 89% ± 6%, EFS and disease-free survival, for regimen II; median follow-up, 6.7 years; range, 0.6 to 13.5 years). Six patients, two of whom were receiving regimen II, died as a result of initial treatment failure or relapse, and five patients, none receiving regimen II, died as a result of treatment-related complications.

CONCLUSION: This 45-day intensive chemotherapy program is the shortest schedule for disseminated BL and overcomes previously recognized risk factors such as BM and CNS infiltration.
Patient-Tailored Antiemetic Treatment With 5-Hydroxytryptamine Type 3 Receptor Antagonists According to Cytochrome P-450 2D6 Genotypes
Authors: Kaiser Rolf , Sezer Orhan , Papies Anja , Bauer Steffen , Schelenz Claudia , Tremblay Pierre-Benoit , Possinger Kurt , Roots Ivar , Brockmöller Jürgen
Published: October 2002

PURPOSE: The use of serotonin 5-hydroxytryptamine type 3 receptor antagonists has substantially reduced, but not eliminated, nausea and vomiting in cancer chemotherapy. This study sought to investigate whether efficacy of antiemetic treatment with ondansetron and tropisetron depends on cytochrome P-450 2D6 (CYP2D6) genotype, hypothesizing that the rapid and particularly the ultrarapid metabolizers of these drugs are at risk of being undertreated.

PATIENTS AND METHODS: Included in the study were 270 cancer patients receiving their first day of chemotherapy. Nausea and vomiting were documented using standardized interviews. The intensity of nausea was measured with visual analog scales before and twice during the chemotherapy. The relationship between the CYP2D6 genotypes and the tropisetron serum concentrations 3 and 6 hours after drug administration was analyzed in a subgroup of 42 patients. CYP2D6 genotyping was carried out by polymerase chain reaction–restriction fragment length polymorphism analysis.

RESULTS: Genetically defined poor metabolizers had higher serum concentrations of tropisetron than all other patients (P < .03). Approximately 30% of all patients receiving chemotherapy experienced nausea and vomiting. Genetically defined ultrarapid meta-bolizers of CYP2D6 substrates had higher frequency of vomiting within the first 4 hours (P < .001) and within the period 5 to 24 hours (P < .03) after treatment than all the other patients; the tendency for nausea was similar. This difference was more pronounced in patients treated with tropisetron than in those treated with ondansetron.

CONCLUSION: Antiemetic treatment with tropisetron or ondansetron could be improved by adjustment for the CYP2D6 genotype; approximately 50 subjects would have to be genotyped to protect one patient from severe emesis.
Long-Term Follow-Up of Patients Treated With Paclitaxel/Carboplatin-Based Chemotherapy for Advanced Non–Small-Cell Lung Cancer: Sequential Phase II Trials of the Minnie Pearl Cancer Research Network
Authors: Hainsworth John D. , Gray James R. , Morrissey Lisa H. , Kalman Leonard A. , Hon Jeremy K. , Greco F. Anthony
Published: October 2002

PURPOSE: To provide long-term follow-up on the survival of patients with advanced non–small-cell lung cancer treated with paclitaxel/carboplatin-based regimens in a multicenter, community-based setting.

PATIENTS AND METHODS: Between March 1995 and April 1998, 321 patients with newly diagnosed stage IIIB or IV non–small-cell lung cancer were treated on sequential phase II trials with the following combination regimens: paclitaxel/carboplatin, paclitaxel/carboplatin/gemcitabine, and paclitaxel/carboplatin/vinorelbine. Details of these three regimens and patient populations have been previously reported. Responding and stable patients continued treatment until tumor progression or for a recommended six treatment courses.

RESULTS: After a median follow-up of 58 months (minimum follow-up, 40 months), the median survival for the entire group of patients was 8.6 months, with actual 1-, 2-, and 3-year survival rates of 40%, 19%, and 7%, respectively. The actuarial 4-year survival rate for the entire group was 4%. No statistically significant differences in survival were seen among the three regimens. Administration of all three regimens was feasible in a community-based setting; however, myelosuppression and hospitalizations for treatment of neutropenia/fever were more frequent with the three-drug regimens.

CONCLUSION: Paclitaxel/carboplatin-based regimens, in addition to prolonging median survival and improving 1-year survival, result in substantial improvements in the 2-year survival of patients with advanced non–small-cell lung cancer when compared retrospectively with supportive care or traditional cisplatin-based regimens. In these sequential phase II trials, we did not demonstrate any advantages of three-drug regimens when compared with paclitaxel/carboplatin. Because few patients remain alive after 4 years with any of these chemotherapy regimens, future treatment improvements will require the introduction of novel agents.
Evaluation of the in-vitro digestion profiles of long and medium chain glycerides and the phase behaviour of their lipolytic products
Authors: Sek Leab , Porter Christopher J H , Kaukonen Ann Marie , Charman William N
Published: October 2002

An evaluation of the in-vitro digestion profile and phase behaviour of the common formulation lipids Miglyol 812 (medium chain triglyceride, MCT), Capmul MCM (C8/C10 monoglyceride/diglyceride mixture), soybean oil (long chain triglyceride, LCT) and Maisine 35-1 (C18 monoglyceride/diglyceride mixture), is described. Experiments were conducted using titrimetric, high-performance thin-layer chromatographic (HPTLC) and ultracentrifugational techniques under model fasted and post-prandial intestinal conditions. The rate and extent of digestion of the medium chain lipids was greater than the corresponding long chain lipids, and independent of bile salt concentration, with complete conversion to monoglyceride and fatty acid occurring after 30 min digestion. The long chain lipid digests separated into an oily phase (containing undigested triglyceride and diglyceride), an aqueous phase (containing bile salt, fatty acid and monoglyceride) and a pellet phase (containing approximately 5 mM of fatty acid, presumably as an insoluble soap) after ultracentrifugation. Higher proportions of long chain fatty acid and monoglyceride were dispersed into the aqueous phase with increasing bile salt concentrations. In contrast, medium chain lipolytic products separated only into an aqueous phase and a pellet fraction in a bile-salt-independent manner. The digestion of both the C8/C10 and C18 monoglyceride/diglyceride lipid mixtures was more rapid than the corresponding triglyceride, especially at early time points. This investigation provides insight into the relative digestion kinetics of medium chain and long chain lipids and provides information regarding the phase behaviour of their lipolytic products under conditions modelled on those expected after oral administration. The data also provide a background for improved understanding of the potential utility of long chain and medium chain lipid-based formulations.
Safety toxicity study of plasmid-based IL-12 therapy in Cynomolgus monkeys
Authors: Quezada A , Horner M J , Loera D , French M , Pericle F , Johnson R , Perrard J , Jenkins M , Coleman M
Published: October 2002

We have investigated the potential toxicity of hIL-12 DNA plasmid formulated with 5% polyvinylpyrrolidone (PVP) administered twice weekly via subcutaneous injections to Cynomolgus monkeys for four weeks, and have evaluated recovery from any effects of the test article over a four-week treatment-free period. Doses of the formulated hIL-12 plasmid were selected based on anti-tumour efficacy studies previously conducted in mice. The duration of the study and the frequency of dosing were designed to support clinical trials. No clinical signs indicative of an adverse effect of administration of formulated hIL-12 plasmid were observed. There were no apparent effects of the formulated hIL-12 plasmid on body weights or on serum chemistry, haematology, coagulation or urinalysis parameters. No treatment-related ocular abnormalities were evident. In addition, examination of the electrocardiograms from all monkeys at the pre-study, week-4, and week-8 time points did not reveal any treatment-related effects. No treatment-related gross lesions were noted at days 28 or 57. Slight histopathological changes associated with high doses of PVP vehicle were observed at both time points. These results suggested that the administration of formulated hIL-12 plasmid at a dose level up to 18 mg kg−1 dose twice per week for four weeks to experimentally naïve Cynomolgus monkeys did not result in significant toxicity. These results support further testing of this gene therapy in clinical trials.
Hyperhomocysteinaemia and cardiovascular risk in female ovariectomized rats: role of folic acid and hormone replacement therapy
Authors: El-Swefy Sahar E , Ali Sousou I , Asker Mervat E , Mohamed Hoda E
Published: October 2002

Hyperhomocysteinaemia is an independent risk factor for arteriosclerosis, recurrent thromboembolic complications and osteoporosis. After menopause, a high level of total homocysteine seems to be secondary to the altered hormonal status. Hormone replacement therapy (HRT) limits the development of coronary artery disease through a variety of mechanisms. One such mechanism is through affecting homocysteine metabolism. Folate and vitamin B12 deficiencies are considered to be major risks for hyperhomocysteinaemia. This study, therefore, was undertaken to examine whether lowering homocysteine with HRT or folic acid in ovariectomized rats could attenuate cardiovascular complications. Sixty sexually mature female Wistar rats were ovariectomized. Three weeks later, they were treated with estradiol (15 μg kg−1 every two weeks, i.m.) or folic acid (90 μg daily, orally), either alone or in a combined form for four weeks. In addition, groups of ovariectomized rats (positive control) and healthy rats (negative control) were given cottonseed oil. Blood samples were then collected for serum and plasma separation. Serum total homocysteine, folate, estradiol, plasma nitric oxide (NO), lipid profile, and susceptibility of non-high-density-lipoprotein cholesterol (non HDLC) contentto oxidation were determined. In ovariectomized rats, hyperhomocysteinaemia was established and associated with significant increments of both atherogenic indexes (total cholesterol/HDLC, low-density-lipoprotein cholesterol (LDLC)/HDLC) and susceptibility of their non HDLC to oxidation. However, plasma NO, serum folate, and estradiol levels significantly decreased. HRT and folic acid significantly reduced total homocysteine and susceptibility of non HDLC to oxidation and increased plasma NO content. Moreover, a significant negative correlation was found between total homocysteine versus folate and estradiol (r = − 0.5, P< 0.01; r = − 0.25, P< 0.05, respectively). Meanwhile, a positive correlation with the susceptibility of lipoprotein to oxidation was observed (r = 0.85, P< 0.001). In conclusion, a low folate level is found to be associated with elevated total homocysteine. Folic acid supplementation, either individually or in a combined form with HRT, has a beneficial effect in low estrogen status subsequent to ovariectomy.