Sjögren's Syndrome with Chronic Pancreatitis, Sclerosing Cholangitis, and Pulmonary Infiltrations

We report a patient with Sjögren's syndrome and multiple gastrointestinal manifestations who successfully responded to therapy with ursodeoxycholic acid. Our patient had sialoadenitis with dry mouth, dry eyes, arthralgia, chronic pancreatitis, sclerosing cholangitis, and pulmonary inflitrations. The first signs of disease were the symptoms of chronic pancreatitis followed by icterus, caused by extrahepatic bile duct obstruction. Sclerosing cholangitis was diagnosed by liver biopsy and endoscopic retrograde cholangiography. Sialoadenitis, causing dry mouth, was verified by buccal biopsy. Pulmonary infiltrations were seen on standard chest x-ray, and also shown by high-resolution computed tomography examination. Obstructive icterus and even pulmonary infiltration responded successfully to treatment with ursodeoxycholic acid.     

Inequality in oral health‐related quality of life before and after a major subsidization reform

In Finland, a dental subsidization reform, implemented in 2001–2002, abolished age restrictions on subsidized dental care. We investigated income‐related inequality in oral health‐related quality of life (OHRQoL) and its determinants among adult Finns before and after the reform. Three cross‐sectional postal surveys, focusing on perceived oral health and the use of dental services among people born before 1971, were conducted in 2001 (n = 2,046), 2004 (n = 1,728), and 2007 (n = 1,560). Five measures, based on the Oral Health Impact Profile‐14, were used as indicators of OHRQoL. Income‐related inequality and associated factors were analysed using the concentration index and its decomposition. Prevalence, extent, and severity of oral health impacts were slightly lower in 2007 than in 2001. The oral health impacts were concentrated, at all study time points, among individuals with lower income. Most of the inequality was related to self‐perceived general health, tooth loss, and income. Contributions of time since the last dental visit and satisfaction with the last treatment period to the inequality decreased from 2001 to 2007. However, the contributions of these factors were already small (10–20%) in 2001. In general, OHRQoL improved slightly; however, no clear or dramatic change in inequality in OHRQoL was seen after the reform.     

Mononuclear cell response to enterobacteria and Gram-positive cell walls of normal intestinal microbiota in early rheumatoid arthritis and other inflammatory arthritides

OBJECTIVE: To study whether enterobacteria and Gram-positive bacterial cell walls (BCW) derivedfrom normal intestinal microbiota are involved in the etiopathogenesis of early rheumatoid arthritis (RA). METHODS: Peripheral blood mononuclear cells (PBMC) and synovial fluid mononuclear cells (SFMC) were isolatedfrom patients with early RA (the average duration of 5 months) and the controls (other types of inflammatory arthritis). The mononuclear cell proliferation and tumor necrosis factor-alpha (TNF-alpha) responses to heat-killed Salmonella enteritidis (SE). Yersinia enterocolitica (YE), and Escherichia coli (EC), and to Gram-positive BCW derived from four common intestinal indigenous bacteria, Eubacterium aerofaciens (EA), Eubacterium limosum (EL), Lactobacillus casei (LC), and Lactobacillus fermentum (LF), and a BCW derived from a pathogen, Streptococcus pyogenes (SP) were investigated. RESULTS: 39% or 56% of patients with early RA showed significant proliferation responses by PBMC or SFMC against enterobacteria, respectively. In other types of arthritis, corresponding figures were 59% or 66%. When BCW were used as antigens, 8.1% or 23% of patients with early RA showed proliferation responses by PBMC or SFMC, respectively. In other types of arthritis the corresponding figures were 7.5% or 35%, respectively. However, TNF-alpha production by SFMC stimulated by EA BCW, SE, YE or EC, was significantly higher in early RA than in other types of arthritis. CONCLUSION: These results suggest that SFMC reacting with enterobacteria or BCW exist in some patients with early RA, but also in other types of inflammatory arthritis. Intestinal bacterial agents may play a role in the etiopathogenesis of RA, but the effect appears to be non-specific.     

HLA-DR-DQ haplotypes and genotypes in Finnish patients with rheumatoid arthritis

OBJECTIVES: To elucidate the contribution of HLA-DR-DQ haplotypes and their genotypic combinations to susceptibility to rheumatoid arthritis, and to evaluate the various models for HLA associated risk for the disease in a series of Finnish patients. METHODS: 322 Finnish patients with rheumatoid arthritis were typed for common north European HLA-DR-DQ haplotypes and compared with a series of 1244 artificial family based control haplotypes. RESULTS: The association of the so called shared epitope (SE) haplotypes (DRB1*0401, *0404, *0408, and *01) with rheumatoid arthritis was confirmed. The DRB1*0401 haplotypes carried a far stronger risk for the disease than the (DRB1*01/10)-(DQA1*01)-DQB1*0501 haplotypes. Seven protective HLA haplotypes--(DRB1*15)-(DQA1*01)-DQB1*0602; (DRB1*08)-(DQA1*04)-DQB1*04; (DRB1*11/12)-DQA1*05-DQB1*0301; (DRB1*1301)-(DQA1*01)-DQB1*0603; (DRB1*1302)-(DQA1*01)-DQB1*0604; (DRB1*07)-DQA1*0201-DQB1*0303; and (DRB1*16)- (DQA1*01)-DQB1*0502--were identified. In accordance with the reshaped shared epitope hypothesis, all the protective DRB1 alleles in these haplotypes share either isoleucine at position 67 or aspartic acid at position 70 in their third hypervariable region motif. However, differences in the disease risk of haplotypes carrying the same DR but different DQ alleles were also found: (DRB1*07)-DQA1*0201-DQB1*0303 was protective, while (DRB1*07)-DQA1*0201-DQB1*02 was neutral. The same haplotypes carried different risks for rheumatoid arthritis depending on their combination in genotypes. CONCLUSIONS: When assessing the influence of HLA genes on the susceptibility to rheumatoid arthritis, not only should the HLA-DR or -DQ alleles or haplotypes be unravelled but also the genotype. The effect of HLA class II region genes is more complicated than any of the existing hypotheses can explain.     

Incremental cost‐effectiveness of double‐reading mammograms

Background. Double reading is a widely used criterion standard in breast cancer screening despite a lack of evidence of the costeffectiveness of the second reading. This study evaluates the incremental costeffectiveness of such a strategy.Design. Costeffectiveness analysis: Nationwide populationbased semiannual screening program for women aged 50–59 in Finland. Participation rate was 91%. All mammograms (95,423) performed during 1990–1995 in three screening centers of the Finnish Cancer Society were read by two radiologists with gradings recorded. The effectiveness of the double reading was the difference in cancers detected in the double compared to that of the single reading. Incremental costs of the double reading for the health care and nonhealth care and the time costs were estimated. The main outcome measure was the incremental cost per additional cancer found as a result of the doublereading strategy.Results. The total number of cancers detected with the double and single reading were 290 and 261, respectively. A significantly higher ratio of carcinoma in situ was the causative pathology in cancers detected only by the second reader. The cost per cancer detected with a single reading was US$ 18,340. The incremental cost of any additional cancer found was US$ 25,523, that is, a 39% higher cost per additional cancer found by double reading.Conclusions. The additional cost per cancer detected by double reading is not drastically higher than with single reading. However, the additional cost per life year saved may be much higher.     

Senile dementia of the Alzheimer type treated with aniracetam: a new nootropic agent

Forty-four patients with senile dementia of the Alzheimer type were randomly allocated into double-blind treatment with either aniracetam (RO 13-5057) 1 g or placebo daily for 3 months. Neurological examinations were made before and after treatment and psychometric tests were performed before and after 1 month's and after 3 month's treatment. Treatment was interrupted due to occurrence of confusion in four cases in the aniracetam group and in one case in the placebo group. During treatment, an improvement was seen in several cognitive tests, especially those associated with memory, but this improvement occurred in the placebo as well as in the aniracetam-treated group. In clinical evaluation no difference was seen in efficacy between the two treatment groups.     

IL-1beta disrupts postnatal lung morphogenesis in the mouse

Pulmonary inflammation and increased production of the inflammatory cytokine IL-1beta are associated with the development of bronchopulmonary dysplasia (BPD) in premature infants. To study the actions of IL-1beta in the fetal and newborn lung in vivo, we developed a bitransgenic mouse in which IL-1beta is expressed under conditional control in airway epithelial cells. Perinatal pulmonary expression of IL-1beta caused respiratory insufficiency that was associated with increased postnatal mortality. While intrauterine growth of IL-1beta-expressing mice was normal, their postnatal growth was impaired. IL-1beta disrupted alveolar septation and caused abnormalities in alpha-smooth muscle actin and elastin deposition in the septa of distal airspaces. IL-1beta disturbed capillary development and inhibited the production of vascular endothelial growth factor in the lungs of infant mice. IL-1beta induced the expression of CXC chemokines KC (CXCL1) and macrophage inflammatory protein-2 (CXCL2) and of CC chemokines monocyte chemotactic protein (MCP)-1 (CCL2) and MCP-3 (CCL7), consistent with neutrophilic and monocytic infiltration of the lungs. IL-1beta caused goblet cell metaplasia and bronchial smooth muscle hyperplasia. Perinatal expression of IL-1beta in epithelial cells of the lung caused a lung disease that was clinically and histologically similar to BPD.     

Income-related inequality in perceived oral health among adult Finns before and after a major dental subsidization reform

Objectives In Finland, a dental subsidization reform, implemented in 2001–2002, abolished age restrictions on subsidized dental care. The aim of this study was to investigate income-related inequality in the perceived oral health and its determinants among adult Finns before and after the reform. Materials and methods Three identical cross-sectional nationally representative postal surveys, concerning perceived oral health and the use of dental services among people born before 1971, were conducted in 2001 (n?=?2157), in 2004 (n?=?1814) and in 2007 (n?=?1671). Three measures of perceived oral health were used: toothache or oral discomfort during the past 12 months, current need for dental care and self-reported oral health status. Concentration index was used to analyse the income-related inequalities. Its decomposition was used to study factors related to the inequalities. Results The proportion of respondents reporting need for dental care decreased from 2001 to 2007, while no changes were seen in reports of toothache or self-reported oral health status. Income-related inequalities in reports of toothache and perceived need for care widened, while the inequality in self-reported oral health remained stable. Most of the inequalities were related to income itself, perceived general health and the time since the last visit to dental care. Conclusions It seems that the income-related inequalities in perceived oral health remained or even widened after the reform.     

Dementia in Parkinson's disease is related to neuronal loss in the medial substantia nigra

Regional neuronal loss in the substantia nigra was studied in relation to extrapyramidal symptoms and dementia in 12 patients with idiopathic Parkinson's disease (PD) and in 18 control subjects. Four areas of the right substantia nigra were investigated at the level of the superior colliculus and caudal red nucleus. In Parkinson's disease, the percentages of neurons, from the medial to the lateral part of the substantia nigra, were reduced to 49%, 31%, 41%, and 25% of the control values. The number of neurons in the lateral part showed a negative correlation with the severity of rigidity and hypokinesia, whereas tremor was less noticeable in patients with few neurons. The degree of dementia of the patients had a significant correlation only with neuronal loss in the medial part of the substantia nigra, suggesting, in view of the topographical organization of the neurons in the substantia nigra, that intact projections to the caudate nucleus and limbic and cortical areas are a prerequisite for normal cognitive functioning and that their dysfunction leads to clinical dementia.