Is it possible to improve the patch‐test diagnostics for isocyanates? A stability study of petrolatum preparations of diphenylmethane‐4,4′‐diisocyanate and polymeric diphenylmethane diisocyanate

We have previously shown that the concentration of diphenylmethane-4,4'-diisocyanate (4,4'-MDI) in commercial test preparations was so low that patch testing with the same was not reliable. The stability of 4,4'-MDI in petrolatum (pet.) was compared with pet. preparations of polymeric diphenylmethane diisocyanate (PMDI), which consists of a complex mixture of monomeric isomers and oligomers of MDI. Preparations of 4,4'-MDI and PMDI were stored under 3 different conditions, i.e. at room temperature, refrigerated and frozen. They were analysed continuously during 1 year with regard to the content of 4,4'-MDI, 3-ring oligomers and 4-ring oligomers using liquid chromatography-mass spectrometry. PMDI preparations kept frozen were stable for a year. All other preparations failed to fulfil the requirements of stability, i.e. +/-20% of the initial concentration. Storage in a freezer prolonged the lifetime for 4,4'-MDI. The decrease in concentration for preparations kept at room temperature and refrigerated was less rapid in PMDI preparations than in 4,4'-MDI preparations. PMDI preparations are better suited for patch testing patients exposed to MDI because they are more stable and homogeneous than 4,4'-MDI preparations. They better reflect possible allergens that workers are exposed to because products used in industry contain both monomers and oligomers.     

Lipolysis--not inflammation, cell death, or lipogenesis--is involved in adipose tissue loss in cancer cachexia

BACKGROUND.: Cancer cachexia is an important, negative prognostic marker that has been linked to systemic inflammation and cell death through unclear mechanisms. A key feature of cancer cachexia is loss of white adipose tissue (WAT) because of increased adipocyte lipolysis and possibly reduced lipid synthesis (lipogenesis). In this study, the authors investigated whether alterations in fat cell numbers, lipogenesis, or cytokine and/or leukocyte infiltration could account for some of the functional changes observed in WAT in cancer cachexia. METHODS.: Blood and subcutaneous WAT samples were obtained from a 10 weight-stable patients, from 13 weight losing (cachexia) patients with cancer, and from 5 patients without cancer (noncancer patients) who initially were classified with cancer. RESULTS.: Systemic inflammation (increased circulating levels of interleukin 6 [IL-6]) and enhanced lipolysis were confirmed in the cachectic patients compared with the other patients. However, the messenger RNA expression of IL-6 and other cytokine or leukocyte markers, as well as WAT secretion of IL-6, were not altered in the patients with cachexia. Thus, the elevated serum levels of IL-6 that were observed in cachexia were not derived from WAT. Insulin-induced lipogenesis in adipocytes from patients with cachexia was the same as that in adipocytes from patients with weight-stable cancer and from noncancer patients (2.5-fold maximal stimulation; half-maximum effective concentration, approximately 0.03 nmol/L). Fat cell size was decreased but adipocyte numbers were normal in cancer patients with cachexia, suggesting that there was no major fat cell death. CONCLUSIONS.: The current findings indicated that subcutaneous WAT does not contribute to the systemic inflammatory reaction and does not induce adipocyte insulin resistance in cancer cachexia. Moreover, increased fat cell lipolysis, not reduced lipogenesis or adipocyte cell death, appeared to be the primary cause of fat loss in this condition. Cancer 2008. (c) 2008 American Cancer Society.     

Prolonged n-3 polyunsaturated fatty acid supplementation ameliorates hepatic steatosis in patients with non-alcoholic fatty liver disease: a pilot study

BACKGROUND: Recent studies suggest a role of n-3 long-chain polyunsaturated fatty acids (n-3 PUFA) as peroxisome proliferator-activated receptor-alpha ligands in improving non-alcoholic fatty liver disease (NAFLD) in rodents. However, data in humans are still lacking. AIM: To evaluate the efficacy of prolonged PUFA supplementation in patients with NAFLD. METHODS: Fifty-six patients with NAFLD were enrolled. Among the overall eligible patients, 42 assumed n-3 PUFA 1-g capsule daily for 12 months, whereas 14 refused the treatment and were analysed as controls. All patients underwent haematochemical and ultrasound follow-up. RESULTS: Polyunsaturated fatty acid supplementation significantly decreased serum aspartate transaminase (P = 0.003), alanine transaminase (P = 0.002), gamma-glutamyl transpeptidase (P = 0.03), triglycerides (P = 0.02) and fasting glucose (P = 0.02) in comparison with controls. Circulating arachidonate and n-6/n-3 fatty acid ratio was reduced (P = 0.0002, and P = 0.0001 respectively) in treated patients. Moreover, ultrasonography demonstrated improvement of liver echotexture after PUFA (P = 0.0001), and increase of Doppler perfusion index (P = 0.001), whereas no significant changes occurred in controls. CONCLUSIONS: Supplementation with n-3 PUFA improves biochemical, ultrasonographic and haemodynamic features of liver steatosis. Our study supports the efficacy of n-3 PUFA as a new therapeutic approach in the treatment of NAFLD.     

Epidemiology of organising pneumonia in Iceland

BACKGROUND: Cryptogenic organising pneumonia (COP) has also been called idiopathic bronchiolitis obliterans organising pneumonia. In secondary organising pneumonia (SOP) the causes can be identified or it occurs in a characteristic clinical context. The aim of this study was to determine the incidence and epidemiological features of COP and SOP nationwide in Iceland over an extended period. METHODS: A retrospective study of organising pneumonia (OP) in Iceland over 20 years was conducted and the epidemiology and survival were studied. All pathological reports of patients diagnosed with or suspected of having COP or SOP in the period 1984-2003 were identified and the pathology samples were re-evaluated using strict diagnostic criteria. RESULTS: After re-evaluation, 104 patients fulfilled the diagnostic criteria for OP (58 COP and 46 SOP). The mean annual incidence of OP was 1.97/100 000 population (1.10/100 000 for COP and 0.87/100 000 for SOP). The mean age at diagnosis was 67 years with a wide age range. The most common causes of death were lung diseases other than OP, and only one patient died from OP. Patients with OP had a lower rate of survival than the general population, but there was no statistical difference between COP and SOP. CONCLUSIONS: The incidence of OP is higher than previously reported, suggesting that OP needs to be considered as a diagnosis more often than has been done in the past.     

The development and course of patch-test reactions to 2-hydroxyethyl methacrylate and ethyleneglycol dimethacrylate

Because Methacrylic monomers are used in dental work, dental personnel, technicians, and patients are at risk of being sensitized. 2-hydroxyethyl methacrylate (2-HEMA) and ethyleneglycol dimethacrylate (EGDMA) are commonly used. Allergic test reactions to them sometimes appear beyond D7. This study was designed to study the development and course of positive test reactions to 2-HEMA and EGDMA in allergic patients as a mean to elucidate the issue of patch-test sensitization. 12 patients with contact allergy to 2-HEMA and EGDMA were retested with dilution series. The clinical course was followed for 1 month. During the study, 25 positive test reactions to 2-HEMA and 19 to EGDMA were diagnosed. Within the 1st week, 21 were noted for 2-HEMA and 18 for EGDMA. After 10 days, another 2 reactions appeared for 2-HEMA and 1 for EGDMA. All but 1 patient with the latter reactions also had positive reactions within the 1st week. After 1 month, 12 reactions for 2-HEMA and 10 for EGDMA remained. Patch-test reactions to 2-HEMA and EGDMA are long-lasting. The patch-test concentrations of 2.0% for 2-HEMA and EGDMA may be continually used. Positive test reactions emerging after 10 days do not automatically imply active sensitization.     

Screening for pulmonary hypertension in systemic sclerosis: the longitudinal development of tricuspid gradient in 227 consecutive patients, 1992-2001

OBJECTIVE: To evaluate the longitudinal development of the tricuspid gradient (TG) for screening for pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc). METHODS: Doppler echocardiography was performed 506 times in order to estimate TG in 227 consecutive patients with SSc. The value of biochemical markers for predicting TG levels and development was assessed through analyses of pro-brain natriuretic peptide (proBNP), calcitonin-gene related peptide, thrombomodulin and von Willebrand factor in 76 patients with a borderline increase in TG, defined as TG 24-38 mmHg, and for the purpose of comparison also in 10 patients with a normal TG (< 23 mmHg) and in 10 patients with increased TG (TG > 38 mmHg). RESULTS: TG > 23 mmHg was found in 102 patients (44.9%) at the first assessment point and in 139 patients (61.2%) respectively, cumulatively at follow-up. TG values > 33 mmHg were measured in 24 patients (10.6%) initially and in 38 patients (16.7%) cumulatively in a subsequent assessment. Age and the presence of interstitial lung disease (ILD) were associated with more frequent occurrence of TG > 23 and > 33 mmHg initially and at follow-up, but were not associated with progression rate. The change in TG (mean +/- S.D.) was 1.34 +/- 4.55 mmHg/yr. ProBNP correlated to TG. CONCLUSION: An increased TG, indicating possible PAH, is common and progressive in SSc. Age and ILD increase the risk of increased TG. Patients with or without ILD have similar progression of TG. ProBNP has potential as an adjunct to TG in selecting patients eligible for invasive treatment.     

Platelet vesicular monoamine transporter density in untreated patients diagnosed with social phobia

The vesicular monoamine transporter (VMAT2) is important in the storage and release of monoamines. Platelet VMAT2 was characterized using high-affinity [(3)H]dihydrotetrabenazine ([(3)H]TBZOH) binding in untreated social phobia (SP) patients (n=20) compared with sex- and age-matched healthy controls (n=15). No significant differences in VMAT2 density (B(max)) and affinity constants (K(d)) were observed.     

Quality of life and impairment in patients with multiple sclerosis

OBJECTIVES: The aims of this study were to describe the quality of life in patients with multiple sclerosis (MS) given immunological treatment and in those not given immunological treatment and to investigate the relationship between impairment and quality of life. METHODS: Twenty nine patients given immunological treatment were matched with the same number of patients not given such treatment. Matching variables were sex, Kurtzke's Expanded Disability Status Scale (EDSS), years since diagnosis, and age (total n = 58). The patients were interviewed using the self-reported impairment checklist and they answered two questionnaires on quality of life, the 36-Item Short-Form Health Survey (SF-36) and the Subjective Estimation of Quality of Life (SQoL). RESULTS: The self-reported impairment checklist captured a more differentiated picture of the patients' symptoms of MS than the EDSS. Health related quality of life was markedly reduced, while the subjective quality of life was less affected. There was a stronger association between self-reported ratings of impairment and health related quality of life on the SF-36 than between impairment and global ratings of quality of life on the SQoL. Subjective quality of life on the SQoL was not directly dependent on impairment expressed in physical limitations. There were no statistically significant differences between the treated and untreated groups. A non-significant trend towards better health related quality of life was found in favour of the treated group with respect to emotional role, physical role, and social function on the SF-36. CONCLUSIONS: The self-reported impairment checklist and SF-36 proved to be valuable complements to the well established EDSS in describing the diverse symptoms of MS. Measuring both health related quality of life and subjective wellbeing provides valuable knowledge about the consequences of MS.