Association of serum 25-hydroxyvitamin D concentration with HLA-B, -DRB1 and -DQB1 genetic polymorphisms.

BACKGROUND/OBJECTIVES: The human leukocyte antigen (HLA) gene region associates with the risk for several autoimmune diseases, including type 1 diabetes. An association between vitamin D deficiency and several autoimmune diseases has been suggested. We tested the association between serum 25-hydroxyvitamin D (25OHD) concentrations and HLA alleles in pregnant Finnish women. SUBJECTS/METHODS: HLA-B (n=395), HLA-DRB1 (n=501) and HLA-DQB1 (n=475) alleles were genotyped in pregnant women (mothers of children who later developed type 1 diabetes and mothers of non-diabetic children). HLA-B alleles were divided into supertypes that share similar peptide-binding specificity. Serum 25OHD concentration had been previously measured in these women from sera collected during the first trimester of pregnancy. Multiple testing was controlled for using the false discovery rate method. RESULTS: An association was found between 25OHD concentration and HLA-B44 supertype (P=0.009); women with HLA-B44 supertype (B*18, B*37, B*40 and B*44 alleles) had lower 25OHD concentrations. No association was found between HLA-DRB1 or -DQB1 alleles and 25OHD concentration. CONCLUSIONS: In this study we found for the first time an association between HLA genetic polymorphisms and 25OHD concentration. In future studies, the mechanistic background of this association and the role of vitamin D in the regulation of HLA gene expression should be investigated.

Nurses' hospital orientation and future research challenges: an integrative review.

AIM: This study aimed to describe the research on registered nurses' orientation processes in specialized hospital settings in order to illustrate directions for future research. BACKGROUND: The complex healthcare environment and the impact of nursing shortage and turnover make the hospital orientation process imperative. There is a growing recognition regarding research interests to meet the needs for evidence-based, effective and economically sound hospital orientation strategies. METHODS: An integrative literature review was performed on publications from the period 2000 to 2013 included in the CINAHL and PubMed databases. English-language studies were included. Themes guiding the analysis were definition of the hospital orientation process, research topics, data collection and instruments and research evidence. Narrative synthesis was used. RESULTS: Eleven papers met the inclusion criteria. The conceptualization of orientation process reflected the complexity of the phenomenon. Less attention has been paid to designs to establish correlations or relationships between selected variables and hospital orientation process. The outcomes of hospital orientation programmes were limited primarily to retention and job satisfaction. The research evidence therefore cannot be evaluated as strong. CONCLUSION: The lack of an evidence-based approach makes it difficult to develop a comprehensive orientation process. Further research should explore interventions that will enhance the quality of hospital orientation practices to improve nurses' retention and job satisfaction. IMPLICATIONS FOR NURSING AND HEALTH POLICY: To provide a comprehensive hospital orientation process, hospital administrators have to put in place human resource development strategies along with practice implications and research efforts. Comprehensive hospital orientation benefits and outcomes should be visible to policy makers.

Dynamin inhibition interferes with inflammasome activation and cytokine gene expression in Streptococcus pyogenes-infected human macrophages.

In the present study, we have analysed the ability of Streptococcus pyogenes [Group A streptococcus (GAS)] to activate the NACHT-domain-, leucine-rich repeat- and PYD-containing protein 3 (NALP3) inflammasome complex in human monocyte-derived macrophages and the molecules and signalling pathways involved in GAS-induced inflammatory responses. We focused upon analysing the impact of dynamin-dependent endocytosis and the role of major streptococcal virulence factors streptolysin O (SLO) and streptolysin S (SLS) in the immune responses induced by GAS. These virulence factors are involved in immune evasion by forming pores in host cell membranes, and aid the bacteria to escape from the endosome-lysosome pathway. We analysed cytokine gene expression in human primary macrophages after stimulation with live or inactivated wild-type GAS as well as with live SLO and SLS defective bacteria. Interleukin (IL)-1ß, IL-10, tumour necrosis factor (TNF)-α and chemokine (C-X-C motif) ligand (CXCL)-10 cytokines were produced after bacterial stimulation in a dose-dependent manner and no differences in cytokine levels were seen between live, inactivated or mutant bacteria. These data suggest that streptolysins or other secreted bacterial products are not required for the inflammatory responses induced by GAS. Our data indicate that inhibition of dynamin-dependent endocytosis in macrophages attenuates the induction of IL-1ß, TNF-α, interferon (IFN)-ß and CXCL-10 mRNAs. We also observed that pro-IL-1ß protein was expressed and efficiently cleaved into mature-IL-1ß via inflammasome activation after bacterial stimulation. Furthermore, we demonstrate that multiple signalling pathways are involved in GAS-stimulated inflammatory responses in human macrophages.

A review of the success and failure characteristics of resin-bonded bridges.

OBJECTIVES: This literature review was designed to assess and compare the success rates and modes of failure of metal-framed, fibre-reinforced composite and all-ceramic resin-bonded bridges. MATERIALS AND METHOD: A Medline search (Ovid), supplemented by hand searching, was conducted to identify prospective and retrospective cohort studies on different resin-bonded bridges within the last 16 years. A total of 49 studies met the pre-set inclusion criteria. Success rates of 25 studies on metal-framed, 17 studies on fibre-reinforced composite and 7 studies on all-ceramic resin-bonded bridges were analysed and characteristics of failures were identified. RESULTS: The analysis of the studies indicated an estimation of annual failure rates per year to be 4.6% (±1.3%, 95% CI) for metal-framed, 4.1% (±2.1%, 95% CI) for fibre-reinforced and 11.7% (±1.8%, 95% CI) for all-ceramic resin-bonded bridges. The most frequent complications were: debonding for metal-framed, resin-bonded bridges (93% of all failures); delamination of the composite veneering material for the fibre-reinforced bridges (41%) and fracture of the framework for the all-ceramic bridges (57%). CONCLUSIONS: All types of resin-bonded bridges provide an effective short- to medium-term option, with all-ceramic performing least well and having the least favourable mode of failure. The methods of failures were different for different bridges with metal frameworks performing the best over time.

Minor histocompatibility antigens as determinants for graft-versus-host disease after allogeneic haematopoietic stem cell transplantation.

Minor histocompatibility antigens (minor H antigens) are genetically polymorphic peptides that have been shown to elicit immune response when mismatched between donor and recipient of haematopoietic stem cell transplantation (HSCT). Depending on the expression profiles, mismatches in these genes may either lead to harmful graft-versus-host (GvH) reaction or desired graft-versus-leukaemia (GvL) effect. We analysed retrospectively the effect of HLA-restricted matching 11 established autosomal minor H antigens on the risk of graft-versus-host disease and relapse in 311 HLA-matched sibling HSCT of a single centre. Increased incidence of chronic GvH disease was shown to be associated with mismatches in the HA-8 and ACC-1. The mRNA expression profiles in a large set of healthy and malignant tissue samples of minor H antigen genes demonstrated in silico that the expression profiles of HA-8 and ACC-1 were surprisingly different: HA-8 gene was expressed in practically all tissues, whereas ACC-1 gene had a restricted profile. The results demonstrated that mismatches in minor H antigens HA-8 and ACC-1 predisposed to chronic graft-versus-host disease (GvHD).

Serum 25-hydroxyvitamin D level during early pregnancy and type 1 diabetes risk in the offspring.

AIMS/HYPOTHESIS: Vitamin D deficiency during the fetal period or infancy is one of the suggested environmental factors for type 1 diabetes and for its increasing incidence. To test this hypothesis we compared serum 25-hydroxyvitamin D (25(OH)D) levels during early pregnancy in mothers of children who subsequently developed type 1 diabetes (case mothers) with mothers of non-diabetic healthy children (control mothers) of the same age. METHODS: Children with type 1 diabetes were identified from the nationwide prescription register. 25(OH)D concentration was measured from serum samples collected during the first trimester of pregnancy from all Finnish women (Finnish Maternity Cohort). A total of 343 case mothers and 343 control mothers were included in the study. Samples were collected throughout the year. Samples from case and control mothers were matched on the day of collection. RESULTS: Mean 25(OH)D levels in case mothers (43.9 nmol/l) and control mothers (43.7 nmol/l) were not different. Of all mothers, 481 (70.1%) were vitamin D-deficient or -insufficient. CONCLUSIONS/INTERPRETATION: No difference was found in serum 25(OH)D concentrations during first trimester of pregnancy between mothers whose children later on developed type 1 diabetes, and mothers of non-diabetic ' healthy' children of the same age. It is difficult to detect possible effects of mothers' vitamin D deficiency during early pregnancy on the development of type 1 diabetes in the offspring in this population, as such a large proportion of mothers were vitamin D-deficient or -insufficient.

A nonrandom association of gastrointestinal stromal tumor (GIST) and desmoid tumor (deep fibromatosis): case series of 28 patients.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) and desmoid tumors (DTs) are two rare mesenchymal tumor. Anecdotal reports of individuals with both diseases led us to make the hypothesis that the association is a nonrandom event as the probability would be extremely low to observe such cases if they were independent events. PATIENTS AND METHODS: We evaluated the existence of patients with GIST and DT in a large multicenter cohort at 10 institutions in the United States, Australia and Europe. Data on gender, age at diagnosis, KIT, PDGFRA, CTNNB1 mutation status and follow-up time after diagnosis were collected. RESULTS: We identified 28 patients diagnosed with both tumors. DT was diagnosed after GIST in 75% of patients and concomitantly in 21%. In only one case (4%), GIST was diagnosed after DT. KIT or PDGFRA mutations were detected in 12 of 14 GIST, 9 in KIT exon 11, 2 in KIT exon 9 and 1 in PDGFRA. CONCLUSION: A statistical analysis of these 28 cases suggests a nonrandom association between GIST and DT. Further studies may be able to elucidate the underlying biology responsible for this association.

Glomerulonephritis emerging shortly after Puumala hantavirus infection: a report on 7 patients.

AIMS: Nephropathia epidemica (NE) is mild type of hemorrhagic fever caused by Puumala (PUU) hantavirus. Renal biopsy typically shows acute tubulointerstitial nephritis and complete recovery is the usual outcome. We previously described 5 patients with membranoproliferative glomerulonephritis (MPGN) after acute NE. We now report on 7 more patients who developed biopsy-confirmed glomerulonephritis (GN) during the convalescent phase of NE. MATERIAL AND METHODS: We present case histories of 7 patients with nephrotic-range proteinuria concomitant with hematuria after serologically verified NE. RESULTS: Renal biopsy specimens disclosed MPGN in 5 patients, membranous GN (MGN) in 1 and mesangial GN (MesGN) in 1. All patients achieved remission of nephrotic syndrome within a median time of 0.6 years (range 0.5 - 5.5 y). The median follow-up time was 1.7 years (0.7 - 15.6 y). CONCLUSIONS: As a rare phenomenon, nephrotic syndrome may emerge during the convalescent phase of acute PUU hantavirus infection. In most cases the prognosis of GN caused by NE seems to be favorable.

Lactobacillus rhamnosus GG and Streptococcus thermophilus induce suppressor of cytokine signalling 3 (SOCS3) gene expression directly and indirectly via interleukin-10 in human primary macrophages.

In the present study we have characterized T helper type 2 (Th2) [interleukin (IL)-10]/Th1 (IL-12) cytokine expression balance in human primary macrophages stimulated with multiple non-pathogenic Gram-positive bacteria used in the food industry and as probiotic substances. Bacteria representing Lactobacillus, Bifidobacterium, Lactococcus, Leuconostoc, Propionibacterium and Streptococcus species induced anti-inflammatory IL-10 production, although quantitative differences between the bacteria were observed. S. thermophilus was able to induce IL-12 production, while the production of IL-12 induced by other bacteria remained at a low level. The highest anti-inflammatory potential was seen with bifidobacteria, as evidenced by high IL-10/IL-12 induction ratios. All studied non-pathogenic bacteria were able to stimulate the expression of suppressor of cytokine signalling (SOCS) 3 that controls the expression of proinflammatory cytokine genes. Lactobacillus and Streptococcus species induced SOCS3 mRNA expression directly in the absence of protein synthesis and indirectly via bacteria-induced IL-10 production, as demonstrated by experiments with cycloheximide (CHX) and anti-IL-10 antibodies, respectively. The mitogen-activated protein kinase (MAPK) p38 signalling pathway played a key role in bacteria-induced SOCS3 gene expression. Enhanced IL-10 production and SOCS3 gene expression induced by live non-pathogenic Lactobacillus and Streptococcus is also likely to contribute to their immunoregulatory effects in vivo.

Hormonal deficiencies during and after Puumala hantavirus infection.

Previous reports have described panhypopituitarism associated with severe cases of hemorrhagic fever with renal syndrome (HFRS), but the prevalence of hormonal deficiencies after nephropathia epidemica (NE), a milder form of HFRS, has not been studied. This study was conducted in order to determine the prevalence of hormonal defects in patients with acute NE and during long-term follow-up. Fifty-four patients with serologically confirmed acute NE were examined by serum hormonal measurements during the acute NE, after 3 months, and after 1 to 10 (median 5) years. Thirty out of 54 (56%) patients had abnormalities of the gonadal and/or thyroid axis during the acute NE. After a median follow-up of 5 years, 9 (17%) patients were diagnosed with a chronic, overt hormonal deficit: hypopituitarism was found in five patients and primary hypothyroidism in five patients. In addition, chronic subclinical testicular failure was found in five men. High creatinine levels and inflammatory markers during NE were associated with the acute central hormone deficiencies, but not with the chronic deficiencies. Hormonal defects are common during acute NE and, surprisingly, many patients develop chronic hormonal deficiencies after NE. The occurrence of long-term hormonal defects cannot be predicted by the severity of acute NE.

Maternal vitamin D status determines bone variables in the newborn.

CONTEXT: Vitamin D regulates 3% of the human genome, including effects on bone health throughout life. Maternal vitamin D status may program neonatal skeletal development. The objective here was to determine the association of mothers' vitamin D status with bone variables of their newborns. SUBJECTS AND METHODS: In a birth hospital, pregnant women (n = 125) participated in a cross-sectional study with a longitudinal follow-up of the pregnancy. The mean (sd) values for age, body mass index before pregnancy, pregnancy weight gain, and total vitamin D intake in mothers were 31 (4) yr, 23.5 (3.7) kg/m(2), 13.1 (4.3) kg, and 14.3 (5.8) microg, respectively. All newborns were full-term, 99% were appropriate for gestational age, and 53% were boys. Blood samples were collected from mothers during the first trimester and 2 d postpartum and from umbilical cords at birth for analysis of serum 25-hydroxyvitamin D (S-25-OHD), PTH, and bone remodeling markers. Bone variables were measured by pQCT at the 20% site of the newborn tibia on an average of 10 (11) d postpartum. Bone contour was analyzed with a single threshold of 180 mg/mm(3) for the detection of total bone mineral density (BMD), bone mineral content (BMC), and cross-sectional area (CSA). RESULTS: Mean S-25-OHD was 41.0 (13.6), 45.1 (11.9), and 50.7 (14.9) nmol/liter during the first trimester, postpartum, and in the umbilical cord, respectively. The median value of the individual means for first trimester and the 2-d postpartum S-25-OHD was 42.6 nmol/liter, which was used as cutoff to define two equal-sized groups. Groups are called below median and above median in the text. Newborns below median were heavier (P = 0.05), and 60% were boys. Tibia bone mineral content was 0.047 (95% confidence interval, 0.011-0.082) g/cm higher (P = 0.01), and cross-sectional area was 12.3 (95% confidence interval, 2.0-22.6) mm(2) larger (P = 0.02), but no difference in bone mineral density was observed, above median compared with below median group. These results were adjusted for newborn Z-score birth weight, maternal height, and newborn age at the measurement. A positive, significant correlation was observed between remodeling markers in mothers at different time points and above median group in the cord. CONCLUSIONS: Although the mean total intake of vitamin D among mothers met current Nordic recommendations, 71% of women and 15% of newborns were vitamin D deficient during the pregnancy. Our results suggest that maternal vitamin D status affects bone mineral accrual during the intrauterine period and influences bone size. More efforts should be made to revise current nutrition recommendations for pregnant women that may have permanent effects on the well-being of children.

Development of a highly controlled gas-phase nanoparticle generator for inhalation exposure studies.

We have developed a gas-phase nanoparticle generator that produces stable and well-defined size distributions for TiO(2). The online analyses of the gas-phase compounds and total number concentration of the generated particles as well as the off-line analysis of the filter samples confirmed the stability of the production. The major advantage of this reactor is that the test substance is directly in the aerosol phase, and thus no preprocessing is needed. This eliminates the physicochemical changes between bulk and administrated material during storing or processing. This system is easy to adjust to different experimental setups and precursors. As a result, well-characterized nanomaterials for inhalation exposure studies can be produced. At mass concentration of 30 mg/Nm(3), the count mean diameter was 126 nm (geometric SD 1.6), mass mean diameter was 161 nm (2.0), mass median aerodynamic diameter was 125 nm, and the concentrations of harmful gas-phase by-products remained low. The produced powder consisted of crystals of anatase (77 vol%) and brookite (23 vol%), and its specific surface area was 69 m(2)/g.

Clinical significance of oncogenic KIT and PDGFRA mutations in gastrointestinal stromal tumours.

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. Despite clinicopathological differences, GISTs share oncogenic KIT or platelet-derived growth factor-alpha (PDGFRA) mutations. Imatinib, KIT and PDGFRA inhibitor, has been successfully used in the treatment of metastatic GISTs. There are primary KIT or PDGFRA mutations diagnosed before imatinib treatment, linked to GIST pathogenesis, and secondary mutations detected during treatment, causing drug resistance. KIT exon 11 mutations are the most common. Gastric GISTs with exon 11 deletions are more aggressive than those with substitutions. KIT exon 11 mutants respond well to imatinib. Less common KIT exon 9 Ala502_Tyr503dup mutants occur predominantly in intestinal GISTs and are less sensitive to imatinib. An Asp842Val substitution in exon 18 is the most common PDGFRA mutation. GISTs with such mutation are resistant to imatinib. PDGFRA mutations are associated with gastric GISTs, epithelioid morphology and a less malignant course of disease. GISTs in neurofibromatosis 1, Carney triad and paediatric tumours generally lack KIT and PDGFRA mutations. Secondary KIT mutations affect exons 13-17. GISTs with secondary mutations in exon 13 and 14 are sensitive to sunitinib, another tyrosine kinase inhibitor. KIT and PDGFRA genotyping is important for GIST diagnosis and assessment of sensitivity to tyrosine kinase inhibitors.

A population-specific diabetogenic haplotype HLA-A2,Cw1,B56,DR4,DQ8 is associated with high birthweight in Finnish diabetic families.

Children with type 1 diabetes (T1D) susceptibility HLA genotypes are shown to have an increased birthweight. We investigated to what extent T1D-predisposing HLA haplotypes were associated with increased birthweight. A total of 1255 Finnish children comprising those with T1D and their non-diabetic siblings were investigated. A total of 342 children and their non-diabetic parents were HLA genotyped. Birthweight data were obtained from the national Medical Birth Registry. The population-specific diabetogenic haplotype HLA-A2,Cw1,B56,DR4,DQ8 was associated with high birthweight (P=0.0280) in families with a diabetic offspring. Other T1D-predisposing HLA haplotypes showed nonsignificant tendency with high birthweight. More infants with a birthweight >or=4000 g were born in families with a T1D offspring than in the general Finnish population (P=0.0139). The previously observed direct association between birthweight and T1D risk may be mediated through the modulating effects that T1D susceptibility HLA genes have on weight. High birthweight and subsequent weight gain may accelerate the ongoing pancreatic autoimmune process in genetically susceptible individuals. The high proportion of infants having a birthweight >or=4000 g in families with a diabetic offspring raises a concern of potential adverse health outcomes that high birthweight can have.

Measurement of oedema in irritant-exposed skin by a dielectric technique.

BACKGROUND: Easily applicable water-specific instruments measuring local oedema in skin are not available. The aim of this study is to demonstrate quantitative assessment of skin oedema with the dielectric technique by measuring increase of skin water content related to sodium lauryl sulphate (SLS)-induced irritant contact dermatitis. METHODS: Irritant skin reaction and resulting oedema were induced by an irritant patch test on volar forearms in 12 healthy volunteers with the application of 1% SLS for 6 h. After occlusion the volunteers were divided into two groups: the patch test site of group I (six volunteers) received no treatment other than a base cream for the skin reaction, while for group II (six volunteers) a strong corticosteroid (clobetasol propionate) was applied on the irritant skin. During a follow-up of 72 h, erythema was scored visually, and irritant-induced oedema was measured with a novel water-specific instrument MoistureMeter-D. RESULTS: In the untreated irritant skin, a maximum increase of 45% in skin water content was found at 10 h postocclusion and water content was still elevated at 72 h. With these persons, the degree of oedema agreed well with the ultrasound-measured skin thickness (P=0.053). In the corticosteroid-treated skin, an increase of 8% in water content was measured during 72 h but there was no correlation between oedema and skin thickness. There was no correlation between erythema and oedema in untreated or corticosteroid-treated skin. CONCLUSION: The new instrument can easily be applied for noninvasive quantitative evaluation of local oedema and fluid retention in irritant-exposed skin.

Ten-year prognosis of Puumala hantavirus-induced acute interstitial nephritis.

Nephropathia epidemica (NE) is a hemorrhagic fever with renal syndrome caused by Puumala hantavirus. Its long-term prognosis is considered favorable. There are, however, some reports about subsequent hypertension, glomerular hyperfiltration, and proteinuria after previous hantavirus infection. Therefore, we studied 36 patients 5 and 10 years after acute NE, with 29 seronegative controls. Office blood pressure, ambulatory 24-h blood pressure (ABP), glomerular filtration rate (GFR), and proteinuria were examined. Hypertensive subjects were defined as those patients having increased ambulatory or office blood pressure, or receiving antihypertensive therapy. Office blood pressure was used to define hypertension only if ABP was not determined. At 5 years, the prevalence of hypertension was higher among NE patients than in controls (50 vs 21%, P=0.020). At 10 years, the difference between the groups was no more significant (39 vs 17%, P=0.098). Five years after NE, patients showed higher GFR (121+/-19 vs 109+/-16 ml/min/1.73 m(2), P=0.012) and urinary protein excretion (0.19 g/day, range 0.12-0.38 vs 0.14 g/day, range 0.09-0.24, P=<0.001) than controls. At 10 years, there were no more differences in GFR or protein excretion between the groups (GFR: 113+/-20 vs 108+/-17 ml/min/1.73 m(2), P=0.370; proteinuria: 0.14 g/day, range 0.07-0.24 vs 0.13 g/day, range 0.06-0.31, P=0.610). In conclusion, the 10-year prognosis of NE is favorable, as glomerular hyperfiltration and slight proteinuria detected at 5 years disappeared during the longer follow-up. However, the possibility exists that NE may predispose some patients to the development of hypertension.

Evaluation of biological potential of smooth muscle tumours.

Smooth muscle tumours (SMTs) have been traditionally divided into benign leiomyomas (LM) and malignant leiomyosarcomas (LMS) based on cytological atypia, mitotic activity and other criteria. In most instances, this dichotomous approach works, but in some instances the biological potential cannot be determined with certainty. This is often because some, but not all criteria for malignancy have been met or because the tumours are occurring in unusual settings for which there are sparse substantive data. Tumours falling into the latter categories are often designated as 'smooth muscle tumours of uncertain malignant potential'. For most non-hormonally influenced SMTs, the presence of significant atypia plus mitotic activity equates with a diagnosis of LMS. However, not all tumours classified as LMSs have a similar prognosis, as a number of other factors, including tumour size, depth, grade and resectability, affect outcome. For example, cutaneous SMTs, regardless of mitotic activity and atypia, have potential largely limited to local recurrence, whereas subcutaneous and deep LMSs have a definite metastatic potential. Angioleiomyoma is the most common SMT of peripheral soft tissues, but deep peripheral LMs are distinctly rare and should be approached with caution. Hormonally influenced oestrogen- and progesterone receptor-positive uterine and extrauterine SMTs in women have unique criteria, including the allowance of higher mitotic activity for the benign LM designation. SMTs of female genital tract can be assessed with criteria similar to uterine tumours. Because of the rarity of these tumours, experience is more limited, and more caution is needed to assess the potential of tumours with mitotic activity and atypia. This review summarizes the current knowledge, guidelines, prognostic data and controversies for the classification of SMTs of soft tissue and most visceral sites.

KIT-positive gastrointestinal stromal tumor in a 22-year-old male chimpanzee (Pan troglodites).

Gastrointestinal stromal tumors (GIST), KIT-positive and KIT signaling driven or platelet-derived growth factor receptor alpha (PDGFRA) signaling driven mesenchymal tumors, are poorly known in nonhuman primates. Availability of KIT- and PDGFRA-inhibitor drug imatinib mesylate has greatly raised the interest for these tumors. At necropsy of a 22-year-old male chimpanzee, a round, firm 2-cm intramural tumor was incidentally found in the midbody of the stomach and diagnosed as a GIST. Histologically, the mass was composed of spindle to polygonal epithelioid cells arranged in short to intermediate-length, interlacing streams, bundles, and nodular whorls often separated by hyalinized eosinophilic matrix. The mitotic rate was a maximum 1/50 high-power field. Immunohistochemically, the tumor cells were diffusely positive for KIT and CD34, focally positive for alpha-smooth muscle actin, and negative for muscle specific actin, desmin, S-100 protein, synaptophysin, and glial fibrillary acidic protein. Because the majority of human GISTs have gain-of-function KIT or PDGFRA mutations, genomic sequences of KIT exons 9, 11, 13, and 17 and PDGFRA exons 12 and 18 from this chimpanzee GIST were polymerase chain reaction amplified and sequenced. However, no mutation was identified in the analyzed "mutational hot spots." This study is the first extensive histomorphologic, immunohistochemical, and molecular genetic analysis of a chimpanzee GIST. More cases of nonhuman primate GISTs should be analyzed to discover the clinicopathologic spectrum of GISTs in these species.

The metabolic syndrome and incident diabetes: assessment of four suggested definitions of the metabolic syndrome in a Chinese population with high post-prandial glucose.

AIMS: To assess the sensitivity and specificity of the four definitions of the metabolic syndrome for incident diabetes in both men and women. METHODS: The screening survey for type 2 diabetes was conducted in 1994. A follow-up study on 627 high-risk non-diabetic individuals at baseline was carried out in 1999 in Beijing area. 70 men and 76 women developed diabetes during the five-year follow-up. Sensitivity and specificity of four definitions of the metabolic syndrome based on the NCEP, WHO, EGIR and AACE recommendations were compared by McNemar's test. RESULTS: The metabolic syndrome based on all four definitions identified men at a 3.7-4.5-fold and women at a 1.6-2.8-fold risk of developing diabetes during 5-year follow-up. The AACE definition had the highest sensitivity for predicting diabetes (men: 0.61; women: 0.58) and lowest specificity (men: 0.71; women: 0.70). The WHO definition identified 53 % of male and 42 % female incident diabetes. The NCEP definition of adiposity as waist girth > 102 cm was the least sensitive, detecting only 27 % of incident diabetes in men; however, it was the most specific (0.91). The EGIR definition identified the lowest number of female cases (28 %) and fewer male cases (28 %) of incident diabetes, but was specific (women: 0.87; men: 0.91). CONCLUSIONS: Further studies on definition of the metabolic syndrome should focus on the potential ethnic differences in insulin resistance and anthropometric indicators for obesity.

Lingual alveolar soft part sarcoma; 14 cases: novel clinical and morphological observations.

AIMS: Alveolar soft part sarcoma (ASPS) is a rare sarcoma in the buttocks or thigh of young adults, often with metastases to lung, brain, or bone. This study examines the morphological and clinical features of lingual ASPS. METHODS AND RESULTS: Fourteen cases, in eight males and six females (ages 3-21 years, median 5 years), ranged from 8 to 50 mm, median 25 mm. All tumours were intramuscular, circumscribed and multinodular. Tumours from all but the oldest patient exhibited a predominantly solid (non-alveolar) growth pattern. Vascular invasion was common. Crystals varied in number from none or extremely rare to nearly 100% of tumour cells. Immunohistochemical results: Fifty percent desmin positive, all focally smooth muscle antigen (SMA) positive; negative for vimentin, neural/melanocytic, myoid, histiocytic, and epithelial markers. All tumours were surgically excised; only two patients received chemotherapy. Follow-up on 10 patients showed that all patients were alive without disease (4-32, median 22 years). Only one patient had a microscopic metastasis to lung (3 years) but was without disease at 11 years. CONCLUSIONS: Lingual ASPS is a tumour of childhood with a distinctive, predominantly solid growth pattern. Despite typical vascular invasion, the early diagnosis and small tumour size may explain its relatively good outcome.