Bronchial hyper-responsiveness predicts the development of mild clinical asthma within 2 yr in school children with hay-fever

In children with mild asthma, symptoms are not always apparent. Therefore, results of tests play an important role for the diagnosis. First, to investigate whether children with bronchial hyper-responsiveness (BHR) but no symptoms of asthma in 1992 had developed clinical asthma at follow up in 1994. The second aim was to find out the diagnostic properties of tests for asthma/allergic inflammation, using either doctor diagnosed asthma (DDA), self-assessed symptoms of asthma or iso-capnic hyperventilation of cold air (IHCA), as the standard, to diagnose asthma in a group of children with hay fever. Twenty-eight children with pollinosis, 12 of them with a history of asthma for the first time during the season 1992, were studied during the birch pollen season and in the autumn of 1994. During both periods, the bronchial hyper-reactivity was estimated by methacholine bronchial provocation tests (MBPT), bronchial variability by peak expiratory flow rate variability, subjective symptoms of asthma by visual analogue scale (VAS) and bronchial inflammation by serum and urine levels of inflammatory mediators. In 1994 IHCA was added during both seasons. Eight of 16 children with BHR but without clinical asthma in 1992 had developed asthma in 1994, 14 of 16 reacted to IHCA and 13 to MBPT. All 12 children with DDA in 1992 had still asthma in 1994 and 14 children with BHR in 1992 had persistent BHR in 1994. Of 23 children with BHR in 1992, 17 had DDA in 1994 and all maintained their BHR. Furthermore, 20 of them reacted to IHCA in 1994. In 1994, 24 of 28 hay-fever children had a positive IHCA tests and 24 had positive MBPT. In relation to VAS, the sensitivity of IHCA and MBPT to predict present asthma was high, but the specificity low, whereas the specificity of most other tests was high, but based on few individuals. In relation to DDA both the IHCA test (65-80%) and the MBPT test (79-85%) had a high sensitivity and it was three to six times more likely to find a positive test among asthmatics than in non-asthmatics. Children with hay fever without clinical asthma have a high risk of developing asthma within 2 yr. In relation to DDA, inhalation of cold air and the MBPT showed a high sensitivity.     

Botanical nomenclature in pharmacovigilance and a recommendation for standardisation.

Nomenclature of plants in pharmacology can be presented by pharmaceutical names or scientific names in the form of Linnaean binomials. In this paper, positive and negative aspects of both systems are discussed in the context of the scientific nomenclatural framework and the systems' practical applicability. The Uppsala Monitoring Centre (UMC) runs the WHO Programme for International Drug Monitoring and is responsible for the WHO Adverse Drug Reaction (ADR) database that currently contains 3.6 million records. In order for the UMC to monitor pharmacovigilance through ADRs to herbal medicine products the following nomenclatural criteria are important: (i) the name should indicate only one species of plant; (ii) the source for this name must be authoritative; (iii) the name should indicate which part of the plant is used. Based on these criteria, the UMC investigated four options: (i) adopt main names used in recognised (inter-) national pharmacopoeias or authoritative publications; (ii) adopt option 1, but cite the publication for all names in abbreviated form; (iii) three-part pharmaceutical names consisting of Latinised part name plus Latinised genus name, plus Latinised specific epithet; (iv) scientific binomial names, optionally with author and plant part used. The UMC has chosen the latter option and will at its adoption utilise the scientific botanical nomenclature as defined by the International Code of Botanical Nomenclature. This decision satisfies all criteria set by the UMC and renders the necessity of creating a new system or upgrading an old inconsistent system obsolete. The UMC has also issued an extensive synonymy checklist of vernacular, pharmaceutical and scientific names for the herbals in the WHO ADR database. We strongly recommend the adoption of scientific names to denote plant ingredients in medicine.     

Dose-related changes in retinal function and PKC-alpha expression in rabbits on vigabatrin medication

Background  To investigate, in a rabbit model, the effect of two different doses of vigabatrin (VGB) on retinal function and morphology. Methods  Twenty-nine rabbits of mixed strain were divided into two groups, receiving either high-dose (n = 15) or low-dose (n = 14) oral VGB treatment (cumulative dose 29.8 ± 2.9 g and 14.2 ± 0.6 g respectively). Ten rabbits receiving water served as control animals. The rabbits underwent three baseline ff-ERG measurements before initiation of VGB medication and two ff-ERG registrations during treatment, after 8 and 12–14 weeks respectively. At the end of the study, the expression of protein kinase C-alpha (PKC-alpha), gamma amino butyric acid (GABA) A receptors, vimentin, glial fibrillary acidic protein (GFAP) and peanut agglutinin (PNA) was examined in retinal sections from all rabbits. Results  In animals of the high-dose group, the ff-ERG measurements revealed a significant decrease of isolated rod b-wave amplitudes, combined rod-cone b-wave amplitudes and amplitudes of oscillatory potentials (OPs); OP1, OP2 and OP3. In the low-dose group, the b-wave amplitudes of combined rod-cone responses as well as OP2 and OP3 were significantly reduced. PKC-alpha labeling demonstrated a dose-related translocation of the enzyme in rod bipolar cells, also revealing a significant decline of the number of PKC-alpha labeled rod bipolar cells in treated animals. Vimentin labeling showed a dose-related deviant labeling pattern of Müller cells, with strikingly low labeling intensity in the outer parts of the cells; in the outer limiting membrane (OLM) as well as the outer nuclear layer (ONL). Labeling with antibodies against GABA A receptors and GFAP, as well as PNA staining, revealed no differences between treated animals and controls. Conclusions  In this study, VGB medication was associated, in a dose-related manner, with a decrease of ff-ERG amplitudes as well as with altered protein expression in rod bipolar cells and Müller cells, suggesting alterations of inner retinal function. The dose-related morphological and electrophysiological changes indicate a retinal pathology that may explain the constricted visual fields seen in some patients treated with VGB. The authors have no financial interest in the material presented, and none of the authors has any conflict of interest to disclose. The authors have full control of the primary data, and agree to allow Graefe’s Archive for Clinical and Experimental Ophthalmology to review the data upon request.     

Costs and quality of life of multiple sclerosis in Sweden

The study objective was to analyse the costs and quality of life (QOL) of multiple sclerosis (MS) related to disease severity in Sweden as part of a study in nine European countries. Information on demographics, disease, resource utilisation, informal care needs, work capacity and QOL (utility) was collected using a questionnaire that was sent to patients registered with the Swedish organisation of patients with neurological disabilities (Neurologiskt Handikappades Riksförbund). The study used a prevalence-based and cross-sectional approach, and costs were estimated from a societal perspective. A total of 1,339 patients were included in the analysis. Seventy-three percent of patients were female, and the mean age was 53 years (standard deviation [SD], 12 years). The mean Expanded Disability Status Scale (EDSS) score was 5.1 (SD, 2.2); only 29% of patients had mild disease (EDSS score <4), 46% had moderate disease and 25% had severe disease (EDSS score ≥7). Costs were significantly correlated with disease severity, increasing sevenfold from around € 16.000 at EDSS scores of 0–1 to € 116.000 at EDSS scores of 8–9. At the same time, utility decreased with worsening disease from 0.825 to 0.047, with a mean established at 0.546 (SD, 0.287). This is significantly lower than utilities for an age- and gender-matched sample of the general population, which would be estimated at 0.80–0.85. Patients with a relapse during the last 3 months had a significant cost increase, of € 3.080, and a utility loss of 0.088. Costs and utilities are highly correlated with EDSS score, and the mean cost per patient in the sample is thus heavily influenced by the severity distribution in the sample. Compared to European estimates, patients with moderate and severe disease in our sample appear to be overrepresented, and costs can therefore not be directly extrapolated to the overall MS population in Sweden without adjustment. When correcting for estimated actual prevalence and use of disease modifying drugs (DMDs), the total cost of MS in Sweden is estimated at € 600 million. Compared to an earlier cost study in 1998 that included a similar sample, and adjusting for differential timing and estimated national use of DMDs, costs have increased by approximately 5% between 1998 and 2005.     

Evaluation of the Response of the Swedish Healthcare System to the Tsunami Disaster in South East Asia

Objectives  When the tsunami in South East Asia hit the coast of Thailand on December 26, 2004, approximately 20,000 Swedish tourists were in the disaster zone. Of these, 548 died or were lost and more than 1500 were injured. The aim of this study was to evaluate the response of the Swedish health care system to the disaster in terms of assessment and support in the disaster zone, evacuation back to Sweden and continued treatment in Sweden. Methods  The evaluation was carried out based on (1) structured questionnaires to the staff of Thai hospitals, injured Swedish citizens and Swedish voluntary workers in the disaster zone; (2) semi-structured interviews with representatives of involved authorities, regional health care centres in Thailand and Sweden, hospital command centres, individuals treated for injuries and volunteer workers involved with supporting the injured; (3) on-site visits in the disaster zone; (4) analysis of reports following the tsunami. Results  A total of 11,000 injured were treated during the first 3 days following the tsunami at the six major hospitals in the Phang Nga, Phuket and Krabi provinces where the majority of the Swedish citizens were primarily taken care of. Of these 11,000, 3000 required hospital admission against a total bed capacity of 1400. Almost 1500 surgical operations were performed during the first 3 days across 33 operating theatres. Thai health care representatives and staff confirmed the requirement for teams from countries with many tourists in the area for practical and psychological support, interpretation, assessment for evacuation and undertaking early evacuation to home nations to release local health care resources. This need was also supported by the injured. Sweden, having the highest number of injured citizens next to the host country, was very late compared to other countries in sending assessment teams to the area and in supplying the needed support. Conclusions  With increased international travelling, many countries today have large numbers of their citizens in other parts of the world. For Sweden, this has been estimated to be 400,000 at any one time, often in areas known to be risk zones for natural disasters and terrorism. This fact of modern-day life demands well-designed plans to support both citizens in the area and the local health care in several ways: non-medical support by mediating contact between injured and local medical staff, psychological and practical support, support in evacuating own citizens from the area to release local health care and (under specific conditions) medical support. This planning has to include prepared assessment teams that can be rapidly deployed to the scene and a command structure permitting rapid and accurate decisions on a governmental level. The authors were medical experts in the Swedish Governmental Tsunami Commission 2005     

Adverse Effects after Radical External Beam Radiotherapy of Localized Prostatic Adenocarcinoma Using Two-Dimensional Dose-Planning and a Limited Field Technique

Adverse effects were assessed after definitive limited field, 2-dimensional CT-planned radiation treatment of localized prostatic adenocarcinoma. In 66 surviving patients, out of a total of 176 treated patients, personal interviews were performed and self-administered questionnaires distributed. The average follow-up was 6.6 years. Adverse effects with regard to bowel function and micturition were investigated, and graded 0-4 with increasing severity and impact on performance status, essentially according to the RTOG toxicity scoring system. Sexual functions were registered on visual analogue scales. The majority of adverse effects were considered minor (grade 1) and did not require any treatment. Late adverse effects on bowel and bladder or urethra that required treatment (grade 2-4) were reported in up to 8% (n=5) of cases respectively. Late bowel side-effects that interfered with life style (grade 3-4) occurred in up to 3% (n=2) of patients; the majority were rectal complications. Corresponding urinary side-effects were registered in up to 6% (n=4) of the patients. Major surgical interventions were not required. Sexual functions were substantially affected in 60% of cases not administered endocrine treatment. Multivariate analyses could not identify patient or treatment risk factors related to complications.     

Neuroendocrine metastases of the liver

Neuroendocrine liver metastases are rare, yet they represent an entity that has attracted much attention lately. The protracted course of neuroendocrine tumors and the hormone origin of their typical incapacitating symptoms constitute a logical basis for well founded and bespoke treatment. Demonstration of the liver secondaries is best done by ultrasonography (US) and contrast-enhanced computed tomography (CT), which on the whole have replaced the invasive angiography techniques. By use of histochemical and molecular biologic methods the exact nature of the tumor can be typified in tissue samples obtained percutaneously, laparoscopically, or surgically. Localization of nonpalpable metastases of the liver is best done by intraoperative US. Surgical removal of liver metastases is curative in some cases and is usually effective in relieving the symptoms. Also, palliative debulking or cytoreductive surgery is often worthwhile as it offers a chance of prolonged survival and symptom relief. Similar benefits are achieved by ischemic therapy preferably by temporary dearterialization, which in our department is done on an outpatient basis using a specially designed (externally controlled) occluder applied during a single laparotomy that includes debulking when appropriate as well as cholecystectomy. Hormonal therapy with somatostatin analogs may be used as a single treatment or in combination with ischemic therapy. It has an ensured symptom-reducing effect, whereas its influence on tumor growth is unsettled. Lately similar effects have been ascribed to human leukocyte interferon. In conclusion the specific characteristics of neuroendocrine tumors and the available treatment arsenal favor an active treatment approach in patients who have developed liver metastases.

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Resumen Las metástasis hepáticas de tumores neuroendocrinos son raras; sin embargo, representan una entidad que ha atraído considerable atención en tiempos recientes. La evolución prolongada y lenta de los tumores neuroendocrinos y el origen típicamente hormonal de sus incapacitantes síntomas constituyen una base lógica para un tratamiento racional y bien fundamentado. La demostración de las lesiones secundarias en el hígado se logra en forma óptima mediante ultrasonografía (US) y tomografía computadorizada con contraste (CT), técnicas que han desplazado las de angiografía invasora. Mediante métodos histoquímicos y de biología molecular se puede identificar la naturaleza exacta del tumor en tejido obtenido por acceso percutáneo, laparoscópico o quirúrgico. En el curso de la cirugía, la localización de las metástasis no palpables del hígado se logra mejor por medio de la US intraoperatoria. La remoción quirúrgica de las metástasis puede resultar curativa en muchos casos y generalmente es eficaz en cuanto al control de los síntomas. Así mismo, la cirugía paliativa de debultamiento o citoreducción es con frecuencia de utilidad al ofrecer una oportunidad de prolongar la sobrevida y de controlar la sintomatología. Efectos benéficos similares pueden ser logrados por la terapia isquémica, preferencialmente por desarterilización temporal, método que en nuestro departamento se realiza como procedimiento ambulatorio utilizando un sistema que es aplicado en el curso de una laparotomía única, durante la cual se practica debultamiento y colecistectomía según estén indicados. La terapia hormonal con análogos de la somastotatina puede ser utilizada tanto como modalidad única de tratamiento o en combinación con terapia isquémica. Aunque exhibe una garantía en lo referente a reducción de sintomatología, no está bien definido su efecto sobre el crecimiento del tumor. Ultimamente se han informado efectos similares con el interferón leucocítico humano. En conclusión, las características específicas de los tumores neuroendocrinos y la disponibilidad de un verdadero arsenal terapéutico, favorece un enfoque de tratamiento activo aun en pacientes que hayan desarrollado metástasis hepáticas.

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Résumé Les métastases d'origine neuroendocrine sont rares, mais elles sollicitent beaucoup d'attention, surtout depuis peu de temps. L'évolution habituellement prolongée et l'origine hormonale des symptômes sont deux arguments bien connus pour souligner l'intérêt d'un traitement agressif. Mettre en évidence de telles métastases se fait au mieux par l'échographie et la tomodensitométric avec injection de produit de contraste, qui ont pratiquement remplacé les techniques d'artériographie. En utilisant des techniques d'histochimie et de biologie moléculaire, on peut déterminer facilement l'origine exacte des tissus tumoraux obtenus par biopsic percutanée, par laparoscopie ou par chirurgie. La localisation des tumeurs non palpables se fait au mieux par l'échographie. L'exérèse de ces métastases peut dans certains cas être un geste curatif et soulage souvent les symptômes en rapport. L'exérèse ou la chirurgie cytoréductrice, même incomplète, est également souvent suivie d'une amélioration des symptômes et d'une prolongation de la survie. L'ischémie provoquée de ces tumeurs, habituellement par desartérialisation temporaire, est effectuée dans notre département en externe en utilisant un système occlusif (contrôlé par voie externe), conçu spécialement dans ce but, et inséré habituellement lors de la laparotomie de réduction tumorale. On effectue également une cholécystectomie dans le même temps opératoire. On peut aussi utiliser des analogues de la somatostatine, soit isolément soit en association avec l'ischémie provoquée des métastases. Cette thérapeutique a une action certaine sur les symptômes mais son effect sur la croissance tumorale reste un sujet de débat. On a dernièrement décrit des effects similaires en utilisant l'interféron des leucocytes humains. En conclusion, les caractéristiques spécifiques de ces tumeurs neuroendocrines et l'arsenal thérapeutique disponible à présent sont autant d'arguments en faveur d'un traitement actif, même chez le patient qui a développé des métastases hépatiques.

     

Identification of Lin(-)Sca1(+)kit(+)CD34(+)Flt3- short-term hematopoietic stem cells capable of rapidly reconstituting and rescuing myeloablated transplant recipients

In clinical bone marrow transplantation, the severe cytopenias induced by bone marrow ablation translate into high risks of developing fatal infections and bleedings, until transplanted hematopoietic stem and progenitor cells have replaced sufficient myeloerythroid offspring. Although adult long-term hematopoietic stem cells (LT-HSCs) are absolutely required and at the single-cell level sufficient for sustained reconstitution of all blood cell lineages, they have been suggested to be less efficient at rapidly reconstituting the hematopoietic system and rescuing myeloablated recipients. Such a function has been proposed to rather be mediated by less well-defined short-term hematopoietic stem cells (ST-HSCs). Herein, we demonstrate that Lin(-)Sca1(+)kit(hi)CD34+ short-term reconstituting cells contain 2 phenotypically and functionally distinct subpopulations: Lin(-)Sca1(+)kit(hi)CD34(+)flt3- cells fulfilling all criteria of ST-HSCs, capable of rapidly reconstituting myelopoiesis, rescuing myeloablated mice, and generating Lin(-)Sca1(+)kit(hi)CD34(+)flt3+ cells, responsible primarily for rapid lymphoid reconstitution. Representing the first commitment steps from Lin(-)Sca1(+)kit(hi) CD34(-)flt3- LT-HSCs, their identification will greatly facilitate delineation of regulatory pathways controlling HSC fate decisions and identification of human ST-HSCs responsible for rapid reconstitution following HSC transplantations.     

Anion and osmolal gaps in the diagnosis of methanol poisoning: clinical study in 28 patients

Objective To evaluate anion and osmolal gaps as diagnostic tools in methanol poisoning.Design and setting Clinical observational study.Patients and methods In a recent methanol outbreak, the initial triage and treatment decisions in 28 patients were based mainly upon the values of the osmolal and anion gaps on admission. Methanol and formate levels were later compared to these gaps by linear regression analysis.Results The correlation between the osmolal gaps and serum methanol concentrations on admission was linear (y = 1.03x+12.71, R² = 0.94). The anion gaps correlated well with the serum formate concentrations (y = 1.12x+13.82, R² = 0.86). Both gaps were elevated in 24 of the 28 subjects upon admission. Three patients had an osmolal gap within the reference area (because of low serum methanol), but elevated anion gap because of formate accumulation. One patient with probable concomitant ethanol ingestion had a high osmolal gap and a normal anion gap.Conclusion Osmolal and anion gaps are useful in the diagnosis and triage of methanol-exposed subjects. Confounders are low serum methanol and concomitant ethanol ingestion.