Pediatric head and neck manifestations associated with multiple endocrine neoplasia syndromes.

INTRODUCTION: Multiple endocrine neoplasia (MEN) syndromes are a group of hereditary cancer syndromes that can predispose children to endocrine neoplasms developing within the head and neck. OBJECTIVE: To examine the neoplastic manifestations of MEN type 1 (MEN1) and MEN type 2 (MEN2) in the pediatric head and neck. METHODS: Single-institution, retrospective review of pediatric MEN between 2005 and 2022. RESULTS: Fifty-three children were genetically confirmed with MEN (15 MEN1, 34 MEN2A, and 4 MEN2B), while three patients received clinical diagnoses of MEN1. The male to female ratio was essentially equal (1.15:1), and a documented family history of cancer was present in 89% (50/56). After multidisciplinary evaluation, a familial MEN diagnosis was confirmed in 91% (51/56). The mean ages of initial presentation and surgical intervention were 8.9 years (SD 5) and 9.8 years (SD 4.8), respectively. Although patients with MEN2 received surgery earlier than patients with MEN1 (8.7 vs 12.7 years), surgical patients with MEN2 in this cohort were older relative to current American Thyroid Association (ATA) guidelines primarily due to late presentation. Thyroid malignancies were identified in 36% (9/25) of thyroidectomy specimens (21 MEN2A, 4 MEN2B), with medullary thyroid carcinoma (MTC) present in five MEN2A patients and three MEN2B patients (89%), and papillary thyroid carcinoma (PTC) present in one MEN2A patient (11%). Nearly 90% (8/9) of thyroid malignancies were occult, with some occurring earlier than predicted by current guidelines (ATA-MOD and ATA-H). Central neck dissections were performed in 24% (2 MEN1, 2 MEN2A, and 4 MEN2B), with two MEN2B (50%) demonstrating cervical lymph node (LN) metastases. Additional histopathologic findings included C-cell hyperplasia in 57% (12/21) of MEN2A thyroidectomy patients. Of the eight MEN1 parathyroidectomy patients, four demonstrated parathyroid hyperplasia and four presented with parathyroid adenoma. CONCLUSION: Nearly 60% required head and neck procedures. While MEN1 guidelines were appropriate for our cohort, we identified patients with MEN2 that developed MTC earlier than expected based on current ATA guidelines, including children in categories considered lower risk. In conjunction with a multidisciplinary approach, pediatric head and neck surgeons should be aware of the potential need for earlier surgical intervention in the pediatric MEN2 population.

Waterborne and diet-related effects of inorganic and organic fungicides on the insect leaf shredder Chaetopteryx villosa (Trichoptera).

It is well-documented that fungicides can affect crustacean leaf shredders via two effect pathways, namely waterborne exposure and their diet (i.e., via dietary uptake of fungicides adsorbed to leaf material and an altered microorganism-mediated food quality). As a consequence of different life history strategies, the relevance of these effect pathways for aquatic shredders belonging to other taxonomic classes, for instance insects, remains unclear. Therefore, we investigated waterborne and diet-related effects in larvae of the caddisfly leaf shredder Chaetopteryx villosa (Insecta: Trichoptera) and compared our observations to previous reports on effects in adults of the crustacean leaf shredder Gammarus fossarum (Malacostraca: Amphipoda). We assessed acute waterborne effects of an organic fungicide mixture (OFM) and the inorganic fungicide copper (Cu) on the leaf consumption (n = 30) of the fourth-/fifth-instar larvae of C. villosa and their food choice (n = 49) when offered leaf material, which was either conditioned in presence or in absence of the respective fungicide(s). Moreover, the larval leaf consumption (n = 50) and physiological fitness (i.e., growth as well as lipid and protein content) were examined after subjecting C. villosa for 24 days towards the combination of both effect pathways at environmentally relevant concentrations. G. fossarum and C. villosa exhibited similar sensitivities and the same effect direction when exposed to the OFM (either waterborne or dietary pathways). Both shredders also showed the same effect direction when exposed to dietary Cu, while with regards to mortality and leaf consumption C. villosa was less sensitive to waterborne Cu than G. fossarum. Finally, as observed for G. fossarum, the combined exposure to OFM over 24 days negatively affected leaf consumption and the physiology (i.e., growth and lipid reserves) of C. villosa. While no combined Cu effects were observed for larval leaf consumption, contrasting to the observations for G. fossarum, the physiology of both shredders was negatively affected, despite partly differing effect sizes and directions. Our results suggest that C. villosa and G. fossarum are of comparable sensitivity towards waterborne and diet-related organic fungicide exposure, whereas the trichopteran is less sensitive to Cu-based waterborne fungicide exposure. However, when both pathways act jointly, organic and inorganic fungicides can affect the physiology of shredder species with completely different life history strategies. As caddisflies represent a subsidy for terrestrial consumers, these observations indicate that fungicide exposure might not only affect aquatic ecosystem functioning but also the flux of energy across ecosystem boundaries.

Chlamydia trachomatis genotypes A and B from urogenital specimens of patients in Spain: molecular characterization.

OBJECTIVES: Chlamydia trachomatis ompA genotypes A and B, primarily associated with trachoma, were unexpectedly detected in urogenital samples of patients in Spain, a trachoma-free country. In this study, we aimed to explain this finding using analysis of organotropism-related genes and a multilocus sequence typing (MLST) technique. METHODS: C. trachomatis genotypes A or B were detected in 8/930 (0.9%) infection episodes between 2006 and 2012. In these strains, organotropism-related genes (polymorphic membrane protein gene H, tryptophan synthase gene A, CTA0934, and cytotoxin) were studied. Further, the strains were analysed by MLST, using a polymerase chain reaction that amplifies five highly variable genomic loci (hctB, CT058, CT144, CT172, and pbpB). Amplicons were sequenced and phylogenetic analysis was conducted. RESULTS: Seven strains were detected in the eight infection episodes (in one patient, an identical strain being found in two episodes). Analysis of organotropism-related genes showed that these strains shared genetic features characteristic of genitotropic genotypes but not of trachoma strains. Three strains of genotype A showed a unique and new MLST-sequence type (ST551, allele profile 8-8-2-27-69). The four strains of genotype B belonged to ST138. CONCLUSIONS: C. trachomatis ompA genotypes A and B associated with trachoma, but detected sporadically in urogenital samples in trachoma-free countries, may be the result of recombination between strains adapted to trachoma and strains adapted to sexual transmission.

First case of human bacteraemia by Catabacter hongkongensis in Scandinavia.

Catabacter hongkongensis was isolated and cultured from human blood for the first time in Scandinavia. The patient, an 83-year-old man from Dalarna, Sweden, recovered without antibiotic treatment, although a high mortality rate associated with C. hongkongensis infection had been reported from China, Canada and France. The genome of the strain ABBA15k was sequenced, assembled and analysed. In contrast to the type strain of the species HKU16T, no antibiotic resistance was observed in Scandinavian strain ABBA15k. The strain was deposited as CCUG 68271, and the draft genome sequence is available from the DNA Data Bank of Japan (DDBJ), the European Molecular Biology Laboratory (EMBL), and GenBank under the accession number LLYX00000000.

Identification of bacterial species by untargeted NMR spectroscopy of the exo-metabolome.

Identification of bacterial species is a crucial bottleneck for clinical diagnosis of infectious diseases. Quick and reliable identification is a key factor to provide suitable antibiotherapies and avoid the development of multiple-drug resistance. We propose a novel nuclear magnetic resonance (NMR)-based metabolomics strategy for rapid discrimination and identification of several bacterial species that relies on untargeted metabolic profiling of supernatants from bacterial culture media. We show that six bacterial species (Gram negative: Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis; Gram positive: Enterococcus faecalis, Staphylococcus aureus, and Staphylococcus saprophyticus) can be well discriminated from multivariate statistical analysis, opening new prospects for NMR applications to microbial clinical diagnosis.

Transgenic expression of oncogenic BRAF induces loss of stem cells in the mouse intestine, which is antagonized by ß-catenin activity.

Colon cancer cells frequently carry mutations that activate the ß-catenin and mitogen-activated protein kinase (MAPK) signaling cascades. Yet how oncogenic alterations interact to control cellular hierarchies during tumor initiation and progression is largely unknown. We found that oncogenic BRAF modulates gene expression associated with cell differentiation in colon cancer cells. We therefore engineered a mouse with an inducible oncogenic BRAF transgene, and analyzed BRAF effects on cellular hierarchies in the intestinal epithelium in vivo and in primary organotypic culture. We demonstrate that transgenic expression of oncogenic BRAF in the mouse strongly activated MAPK signal transduction, resulted in the rapid development of generalized serrated dysplasia, but unexpectedly also induced depletion of the intestinal stem cell (ISC) pool. Histological and gene expression analyses indicate that ISCs collectively converted to short-lived progenitor cells after BRAF activation. As Wnt/ß-catenin signals encourage ISC identity, we asked whether ß-catenin activity could counteract oncogenic BRAF. Indeed, we found that intestinal organoids could be partially protected from deleterious oncogenic BRAF effects by Wnt3a or by small-molecule inhibition of GSK3ß. Similarly, transgenic expression of stabilized ß-catenin in addition to oncogenic BRAF partially prevented loss of stem cells in the mouse intestine. We also used BRAF(V637E) knock-in mice to follow changes in the stem cell pool during serrated tumor progression and found ISC marker expression reduced in serrated hyperplasia forming after BRAF activation, but intensified in progressive dysplastic foci characterized by additional mutations that activate the Wnt/ß-catenin pathway. Our study suggests that oncogenic alterations activating the MAPK and Wnt/ß-catenin pathways must be consecutively and coordinately selected to assure stem cell maintenance during colon cancer initiation and progression. Notably, loss of stem cell identity upon induction of BRAF/MAPK activity may represent a novel fail-safe mechanism protecting intestinal tissue from oncogene activation.

Unusual increase of psittacosis in southern Sweden linked to wild bird exposure, January to April 2013.

Free-living wild birds worldwide act as reservoir for Chlamydia psittaci, but the risk of transmission to humans through contact with wild birds has not been widely documented. From 12 January to April 9 2013, a total of 25 cases of psittacosis were detected in southern Sweden, about a threefold increase compared with the mean of the previous 10 years. A matched case-control study investigating both domestic and wild bird exposure showed that cases were more likely than controls to have cleaned wild bird feeders or been exposed to wild bird droppings in other ways (OR: 10.1; 95% CI: 2.1-47.9). We recommend precautionary measures such as wetting bird feeders before cleaning them, to reduce the risk of transmission of C. psittaci when in contact with bird droppings. Furthermore, C. psittaci should be considered for inclusion in laboratory diagnostic routines when analysing samples from patients with atypical pneumonia, since our findings suggest that psittacosis is underdiagnosed.

European proficiency study with control serum for the tumor marker CA 19-9 measured on different test systems.

BACKGROUND: Reliable and precise CA 19-9 testing is required for the long-term follow-up of patients with pancreatic carcinoma during therapy. The aim of this longitudinal proficiency study was to evaluate the comparability, linearity, and precision of CA 19-9 determinations performed in different laboratories using currently available test systems under routine conditions. METHODS: During the one year study period, 15 laboratories applied 7 different tests and included a liquid BIOREF control serum with pancreatic carcinoma derived CA 19-9 in their routine testing and quality control procedures. The results were collected centrally and evaluated statistically. RESULTS: The comparability of CA 19-9 results is limited especially when different tests are used, albeit, some tests show a good correlation: The CA 19-9 values obtained by different laboratories using different test systems vary up to a factor of 2. The precision of CA 19-9 determinations was acceptable in most laboratories with coefficients of variation ranging between very low 3.2% and high 17.8%. The imprecision was slightly increased when automatic dilution procedures of the analysers were used. CONCLUSIONS: The comparability of CA 19-9 test results must be improved. The precision is acceptable in most cases. In order to monitor key performance parameters, every laboratory should participate in external quality assessment schemes and should perform a routine internal quality control with a control serum independent from the test kit manufacturer.

Comparison of insulin aspart vs. regular human insulin with or without insulin detemir concerning adipozytokines and metabolic effects in patients with type 2 diabetes mellitus.

BACKGROUND: In type 2 diabetes mellitus, treatment with insulin is initiated when HbA1c is reduced inadequately with oral antidiabetic drugs or incretin mimetics. Whether insulin analogues vs. regular human insulin have favorable effects in terms of efficacy and metabolism is under discussion. PATIENTS: 29 patients with type 2 diabetes mellitus (19 males, 10 females) with a mean age 59±11(mean±SD) years (range 24-75) and treated with oral drugs for at least 6 months and a HbA1c >7.0% were included in an open, randomised, prospective, controlled, multicenter parallel-group study over a period of 24 months. METHODS: 11 patients were randomized in the regular human insulin-group (RHI-group) and 18 patients in the insulin aspart group (IA-group). Insulin aspart or regular human insulin should be treated to <140 mg/dl postprandial and insulin detemir should be treated to <110 mg/dl in the morning (fasting) after a previous dose titration of insulin aspart or regular human insulin over 6 months of treatment. Adiponectin, HbA1c, fasting plasma glucose, BMI, triglycerides and cholesterol levels were determined every 3 months. RESULTS: 7/11 of the RHI-group received additional insulin detemir and 13/18 of the IA-group. HbA1c levels decreased significantly in both groups (8.7±1.6 to 7.2±0.9 in the RHI-group (p<0.05) vs. 8.7±1.6 to7.3±0.9 in the IA-group (p<0.05)) without significant difference between the groups. No significant changes were seen between the 2 groups during the 24 months period in terms of BMI, fasting plasma glucose, lipids. Adiponectin serum levels decreased over the time without difference between the groups (7.9±4.0 to 5.0±2.0 in the RHI-group (p<0.03) vs. 7.3±3.4 to 4.8±2.8 in the IA-group (p<0.0001)). During the first 9 months, the insulin dosage to reach the postprandial blood glucose <140 mg/dl, were significantly lower in the IA-group, but approached the following the RHI-group without significant changes after 24 months. CONCLUSION: After stopping oral antidiabetic drugs in type 2 diabetes mellitus, insulin aspart in comparison to human regular insulin decreased effectively HbA1c levels without significant difference. Moreover, insulin aspart in comparison to human regular insulin does not have any substantial benefits concerning metabolic effects and adipocytokines in type 2 diabetes mellitus over a 24 months treatment period.

Nanogel vaccines targeting dendritic cells: contributions of the surface decoration and vaccine cargo on cell targeting and activation.

Dendritic cells (DCs) play crucial roles in initiating and promoting immune defences, providing a pivotal target for vaccines. Although nanoparticle/nanogel-based delivery vehicles are showing potential for delivering vaccines to the immune system, there is little information on their characteristics of interaction with DCs. While particle uptake by DCs has been shown, the mechanism of cell targeting has not been studied. Moreover, it is still unclear how particle surface decoration influences the handling of such vaccines by DCs. Accordingly, chitosan nanogels carrying a model antigen, ovalbumin (ova), were analysed for interaction with and processing by DCs. Nanogel surfaces decorated with alginate (alg) or mannosylated alginate (alg-man), were used for targeting particular DC receptors. DC uptake of particles was observed, being dependent on endosomal-based processes. Inhibiting PI3-kinase or lipid raft activities impaired the uptake, which was only reduced, indicating the involvement of more than one endocytic pathway; notably, this was observed with both nanogel-delivered or free ova. Importantly, surface decoration of particles was less influential on particle uptake, contrasting with the ova cargo which played the major role. Such influence of the vaccine cargo has to date been largely ignored. When receptors interacting directly with ova were blocked, this altered the uptake of alg-nanogels and alg-man-nanogels carrying ova. The nanogels did have an influential role, in that modulation of DC functional activity owed more to the nanogel structure. Using an in vitro restimulation assay with ova-specific lymphocytes, nanogel-delivered and free ova were similarly effective at inducing specific antibody. Nanogel-delivered ova with mannose surface decoration was superior to free ova for inducing interferon-γ production by T-lymphocytes. Together, the data demonstrates that particle-based vaccine delivery should consider the influences of both the surface decoration and the vaccine cargo; each can influence different aspects of the interaction with DCs. Such combined influences are likely to impinge on the characteristics of the immune response induced.

Sexual abuse in prepubertal children and adolescents.

Medical involvement in the diagnosis and treatment of child sexual abuse (CSA) has a well-defined role within a multidisciplinary concept. Due to the increasingly high rate of normal anogenital findings in victims of CSA, forensic aspects are of limited value in establishing the diagnosis. In selected cases however, medical findings may play an important role in corroborating a child's history. Correct evaluation of normal and abnormal findings, normal variations and several differential diagnoses requires sound knowledge in pediatric gynecology. In some cases, physical consequences of CSA (injuries, infections, and pregnancy) need to be diagnosed and treated (prevented) accordingly. The majority of abused children have an altered and distorted body image. It is of paramount importance to reassure the child that its body is normal, physically undamaged, intact or that it will heal ('primary therapeutic aspect of the medical examination'). Thus, the medical examination has an enormous potential to incorporate a therapeutic message into the diagnostic procedure if performed in a qualified and sensitive manner. By communicating with the psychosocial und jurisdictional systems, physicians may initiate proper child protection and therapy. Therefore, medical evaluation of sexually abused children must always be integrated into a multiprofessional concept of child protection.

Prevalence trends in Sweden for the new variant of Chlamydia trachomatis.

In 2006, a new variant of Chlamydia trachomatis (nvCT) was discovered in Sweden that was not detectable with Abbott m2000 (Abbott) and Amplicor/COBAS Amplicor/TaqMan48 (Roche). The proportion of nvCT was 20-64% of the detected Chlamydia cases in counties using Abbott/Roche test systems. Although the ProbeTec system from Becton Dickinson (BD) could detect nvCT, the proportion of nvCT in counties using BD was 7-19%. The objective of the current study was to follow the nvCT proportions from 2007 to 2009 in two counties that used Roche and had introduced test systems able to detect nvCT in late 2006. The nvCT was also followed in two counties that used BD, and in all four counties the effect of nvCT on the serotype distribution of C. trachomatis wild-type strains was analysed. A total of 2576 specimens positive for C. trachomatis were collected in the four counties at three time points, and analysed for nvCT and serotype E. The proportion of nvCT declined significantly in the two counties using Roche, from 65% and 48% in 2007 to 24% for both counties in 2009 (p <0.001). The nvCT proportion increased in Norrbotten county, which used BD, from 9% in 2007 to 19% in 2009 (p 0.03). In Uppsala county, which also used BD but was surrounded by counties using detection systems from Roche, the proportion of nvCT declined from 24% in 2007 to 18% in 2009 (p <0.03). No major difference in the level of serotype E was seen. The proportion of nvCT seems to rapidly converge in the Swedish counties after the selective diagnostic advantage for nvCT has been lost in the Abbott/Roche counties.

Acromegaly: a cross-sectional analysis of the oral and maxillofacial pathologies.

CONTEXT: It is well established that clinical features of acromegaly concern the teeth and the jaw, but less is known about the degree of oral and maxillofacial pathologies. PATIENTS: 28 acromegalics (13 females, 15 males) with a mean age 49±11 (mean±SD) years (range 31-70) were included in the study. 32% had active disease, 68% were well-controlled under the somatostatin analogue octreotide, the dopamine agonist cabergoline, and the GH receptor antagonist pegvisomant, or were cured after pituitary surgery and/or radiation. METHODS: All subjects undergone intensive and complex examinations of a plaster model and facial arch with articulator, an intra-oral bracket-pen registration, analysis of a digital picture, panoramic and lateral radiographs with cephalometry in comparison with a reference group (n=201). RESULTS: 42% had a diastema mediale (0.9±1.1 mm). Overbite and overjet (vertical overbite) correlated with the disease duration (r²=0.2237; p=0.011 respectively r²=0.3364; p=0.015). 96% had an asymmetric movement of the mandible. 57% had a prognathism. The protrusion of the mandible correlated significantly with the disease duration (r²=0.1784; p=0.028). The degree of the mandibular prognathism (SNB-angle) was higher in the acromegalic group (84°±7° vs. 81°±3°, p<0.05). The ANB-angle indicates the relation between maxilla and mandible and was negative in the acromegalic group and positive in the controls (-0.3°±5.0° vs. 1.6°±2.1°, p=<0.05) and correlated negative with the disease duration (r²=0.2553; p=0.0061). The mandibular angle was significantly greater in the acromegalic group (126°±9° acromegalic group vs. 121°±7°control group, p=0.003). The length of the mandible correlated with the disease duration (r²=0.2801; p=0.0038). 86% had an asymmetric face. The high of the midface was in the acromegalic group higher (6.1±0.7 vs. 5.5±0.4 cm, p=0.0009) as well as the lower bony high of the face (9.5±1.0 acromegalics vs. 6.9±0.5 cm controls, p=0.0009). The high of the lower bony face correlated with as well with the disease duration (r²=0.3224; p=0.0016). CONCLUSIONS: Patients with acromegaly suffer not only from cardiovascular, metabolic and neoplastic complications, but also from dental and jaw disorders. The high incidence of these manifestations and its relation to the disease duration requires a carefully work-up of oral and maxillofacial examinations in close collaboration with endocrinologists, dentists and dental surgeons.

[Guidelines and evidence. Recent developments in medical child protection]. / Leitlinien und Evidenz. Neue Entwicklungen im somatischen medizinischen Kinderschutz.

Medical child protection comprises different types of involvement of physicians in order to protect children and adolescents from abuse and neglect. This review gives an overview of historical and recent developments in medical child protection. The professional foundation of medical involvement in this field requires a debate on the following questions: Is there evidence for the diagnostic criteria of child abuse and neglect? How far are the principles of evidence-based medicine applicable to the development of guidelines in child protection?

Calcitonin screening and pentagastrin testing: predictive value for the diagnosis of medullary carcinoma in nodular thyroid disease.

CONTEXT: Serum calcitonin (hCT) measurement may be useful for detecting medullary thyroid carcinoma (MTC), but the routine use of hCT after pentagastrin stimulation to screen patients with nodular thyroid disease remains controversial. PATIENTS: A total of 1007 patients (567 females and 440 males) with nodular thyroid disease and a mean age of 55+/-14 (mean+/-S.D.) years were included in the study. All patients did not have impaired renal function, bacterial infection, alcohol and drug abuse, pseudohypoparathyroidism, or proton-pump inhibitor therapy. Individuals referred with known elevation of hCT, Graves' disease, or autoimmune thyroid disease were not considered or included in this investigation. METHODS: Serum hCT levels were determined under basal conditions, and when basal values were >or=10 and <100 pg/ml, testing was repeated after pentagastrin stimulation. Patients with basal or stimulated levels >100 pg/ml were referred for surgery. RESULTS: hCT levels >10 pg/ml were increased in 17 patients (1.7%). One patient had a basal hCT level of 4400 pg/ml with a histological confirmation of a MTC. In this patient, pentagastrin test was not performed. Sixteen patients with basal hCT between 10 and 100 pg/ml underwent pentagastrin-stimulated hCT measurement. Of 16 patients, 4 had stimulated hCT>100 pg/ml. Of 17 patients with hCT>10 pg/ml, 2 had MTC, and of 17 patients, 3 had C-cell hyperplasia. In total, two patients (0.20%) had a histologically verified MTC. CONCLUSIONS: Basal hCT measurement together with pentagastrin-stimulated hCT measurement in cases of basal hCT>10 pg/ml detects MTC in 0.20% of patients with nodular thyroid disease. Whether this high incidence of MTC has major implications or not has to be discussed, but it should be considered as a useful and recommended tool for early detection of MTC and to save patients' life.

Usefulness of real-time PCR for lytA, ply, and Spn9802 on plasma samples for the diagnosis of pneumococcal pneumonia.

In the present study, we evaluated rapid real-time PCR assays for ply, Spn9802, and lytA applied to plasma samples for the detection of Streptococcus pneumoniae in patients with community-acquired pneumonia (CAP). In a prospective study of CAP aetiology, an EDTA plasma sample was collected together with blood culture in 92 adult CAP patients and 91 adult controls. Among the 92 CAP patients, lytA PCR was positive in eight (9%), Spn9802 PCR was positive in 11 (12%) and ply PCR was positive in 19 (21%) cases. Of 91 controls, the ply PCR was positive in eight cases (9%), but no positive cases were noted by Spn9802 or lytA PCRs. Ten CAP patients had pneumococcal bacteraemia. Compared to blood culture, PCR for lytA, Spn9802 and ply had sensitivities of 70% (7/10), 60% (6/10) and 70% (7/10), and specificities of 96% (79/82), 94% (77/82) and 85% (70/82) respectively. With blood culture and/or culture of representative sputum, and/or urinary antigen detection, S. pneumoniae was identified in 31 CAP patients. Compared to these tests in combination, PCR for lytA, Spn9802 and ply showed sensitivities of 26% (8/31), 32% (10/31) and 42% (13/31), and specificities of 100% (61/61), 98% (60/61) and 90% (55/61) respectively. We conclude that Spn9802 and lytA PCRs may be useful for the rapid detection of bacteraemic pneumococcal pneumonia, whereas ply PCR is not specific enough for routine use and blood PCR with small plasma volumes is not useful for the detection of nonbacteraemic pneumococcal pneumonia.

Prevalence of anterior pituitary dysfunction in patients following traumatic brain injury in a German multi-centre screening program.

INTRODUCTION: We determined the prevalence of anterior pituitary dysfunction in a multi-centre screening program across five German endocrine centres in patients rehabilitating from TBI (GCS<13). PATIENTS & METHODS: 246 patients (39+/-14 yrs; 133 males, 12+/-8 months after TBI) underwent a series of baseline endocrine tests with central assessment of TSH, free T4, prolactin, LH, FSH, testosterone (m), estradiol (f), cortisol, GH, and IGF-I. If IGF-I was <-2 SDS dynamic testing was performed. GHD was defined according to BMI-dependent cut-off values for GH response to GHRH+arginine of <4.2, <8.0 and <11.5 ng/ml in obese, overweight and lean subjects, respectively, or <3 micro g/l in ITT. Hypocortisolism was suggested when basal cortisol was <200 nmol/l and confirmed by ITT (peak<500 nmol/l). RESULTS: In TBI patients some degree of impaired pituitary function was shown in 21% (n=52/246). Total, multiple and isolated deficits were present in 1%, 2% and 18%, respectively. 19% had an IGF-I of <-1 SDS, 9% of <-2 SDS. In 5% GHD was confirmed. 9% had hypogonadism. 4% had hypocortisolism and 1% of patients had confirmed ACTH-deficiency. 12% had TSH-deficiency. SUMMARY: In summary, in this large series carried out on an unselected group of TBI survivors we have found hypopituitarism in every fifth patient with predominantly secondary hypogonadism and hypothyreosis. Regarding somatotrope insufficiency IGF-I is decreased in 50% of GHD patients. CONCLUSION: These findings strongly suggest that patients who suffer head trauma should routinely undergo endocrine evaluation.

In vivo proliferation of rat lamina propria T lymphocytes: general hyporesponsiveness but increased importance of the CD2 and CD28 pathways.

Lamina propria T lymphocytes (LPL-T) have a low proliferative potential in vitro. We asked whether LPL-T are also hyporesponsive in vivo and whether this is specific for the alphabeta T cell receptor (TCR). Mitogenic mAb directed at the alphabeta TCR, CD2, CD28, or control mAbs plus IL-2 were injected into rats. Proliferation and/or apoptosis were detected by double staining using 5-bromo-2'-deoxyuridine/TUNEL and the alphabeta TCR. LPL-T were hyporesponsive to various stimuli compared to other T cells. The strongest proliferation was found upon CD2/CD28 stimulation (LPL-T: 281 +/- 6%; spleen: 642 +/- 31%). LPL-T proliferation was only detectable at 24 h while proliferation in other compartments also occurred later. Hyporesponsiveness was not caused by enhanced T cell apoptosis upon alphabeta TCR stimulation. In conclusion, stimulation of LPL-T results in much shorter and weaker in vivo proliferation than in other lymphoid organs. Overall, CD2/CD28 costimulation is the strongest T cell stimulus in vivo.

Influence of disease control with pegvisomant on sleep apnoea and tongue volume in patients with active acromegaly.

OBJECTIVES: Sleep apnoea has been consistently reported to occur in acromegaly. In uncontrolled patients, the severity of sleep apnoea influences physical activity in the daytime. We investigated the influence of disease activity on tongue volume and sleep apnoea treated with the GH receptor antagonist pegvisomant in poorly controlled patients with acromegaly under octreotide. DESIGN AND METHODS: A total of 12 patients with active acromegaly (six females; six males; mean age 57+/-15 years; body mass index 29.4+/-4.2 kg/m(2); mean+/-S.D.) were treated with pegvisomant (13.5+/-5.0 mg/die) for 6 months. Tongue volume was examined by magnetic resonance imaging, and sleep apnoea was characterized by polysomnography before and after 6 months of treatment with pegvisomant. The mandibular length was determined by lateral X-ray films. RESULTS: IGF1 levels decreased after 6 months in all patients (407+/-114 to 199+/-23 microg/l; P=0.0001). The tongue volume decreased (105+/-33 to 83+/-33 ml; P=0.007) as well as the apnoea-hypnoea index (23+/-22 to 18+/-18/h; P=0.0066). The mandibular length correlated with the initial tongue volume (r(2)=0.6072, P=0.0028). CONCLUSION: In conclusion, successful treatment with pegvisomant can decrease tongue volume, which has benefits for coexisting sleep disordered breathing.

Is quantitative PCR for the pneumolysin (ply) gene useful for detection of pneumococcal lower respiratory tract infection?

The pneumolysin (ply) gene is widely used as a target in PCR assays for Streptococcus pneumoniae in respiratory secretions. However, false-positive results with conventional ply-based PCR have been reported. The aim here was to study the performance of a quantitative ply-based PCR for the identification of pneumococcal lower respiratory tract infection (LRTI). In a prospective study, fibreoptic bronchoscopy was performed in 156 hospitalized adult patients with LRTI and 31 controls who underwent bronchoscopy because of suspicion of malignancy. Among the LRTI patients and controls, the quantitative ply-based PCR applied to bronchoalveolar lavage (BAL) fluid was positive at >or=10(3) genome copies/mL in 61% and 71% of the subjects, at >or=10(5) genome copies/mL in 40% and 58% of the subjects, and at >or=10(7) genome copies/mL in 15% and 3.2% of the subjects, respectively. Using BAL fluid culture, blood culture, and/or a urinary antigen test, S. pneumoniae was identified in 19 LRTI patients. As compared with these diagnostic methods used in combination, quantitative ply-based PCR showed sensitivities and specificities of 89% and 43% at a cut-off of 10(3) genome copies/mL, of 84% and 66% at a cut-off of 10(5) genome copies/mL, and of 53% and 90% at a cut-off of 10(7) genome copies/mL, respectively. In conclusion, a high cut-off with the quantitative ply-based PCR was required to reach acceptable specificity. However, as a high cut-off resulted in low sensitivity, quantitative ply-based PCR does not appear to be clinically useful. Quantitative PCR methods for S. pneumoniae using alternative gene targets should be evaluated.