Development of miliary tuberculosis under infliximab in a patient with spondyloarthritis and suspected Crohn's disease.

Tuberculosis (TB) infection is a major concern in patients with chronic autoimmune conditions under immunosuppressive therapy. Gastrointestinal tuberculosis can be misdiagnosed as Crohn's disease with detrimental consequences for the patient. We report on a 40-year old ethnic Turkish patient with HLA-B27 positive spondyloarthritis who developed gastrointestinal symptoms under immunosuppressive treatment with infliximab. Crohn's disease was diagnosed at a primary care hospital and immunosuppressive treatment was escalated. Initial diagnostic tests for tuberculosis were negative. When the clinical condition deteriorated, the patient was transferred to our intensive care unit for further diagnosis and treatment. Tuberculosis was suspected due to clinical presentation and radiological signs and anti-tuberculous treatment was initiated. After the onset of treatment, first microbiological results confirmed the diagnosis of miliary TB with Mycobacterium bovis. As an infection route we assume primary gastrointestinal infection with M. bovis during the patient's annual holidays in Turkey with a rapid development of miliary TB under infliximab and escalated immunosuppressive therapy. This case report demonstrates the difficulties in differentiating intestinal TB from other granulomatous conditions such as Crohn's disease. The diagnostic tools for gastrointestinal tuberculosis are discussed in detail regarding their sensitivity, specificity as well as positive and negative predictive values.

Diagnosis of presence and extent of deep infiltrating endometriosis by preoperative MRI-improvement of staging accuracy by expert training.

INTRODUCTION: This study evaluates the clinical utility of magnetic resonance imaging (MRI) for the determination of presence and extent of DIE with special emphasis on effects of MRI reporting training MATERIAL AND METHODS: Data from 80 patients with clinically suspected DIE presented at our certified endometriosis center between 2015 and 2018 were analyzed. For all patients an ENZIAN score (describing DIE related to individual anatomical localizations) was obtained based on the preoperative MRI findings. The intraoperatively determined ENZIAN score served as the reference for assessment of diagnostic performance of the MRI. RESULTS: Overall, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the diagnosis of DIE by MRI were 76.9%, 53.3%, 87.7% and 34.8%, respectively. Analysis by compartment revealed a sensitivity, specificity, PPV and NPV of 59.5%, 88.2%, 86.2% and 63.9%, respectively, for compartment A, with similar values for compartment B, and 50.0%, 88.9%, 64.7% and 81.4%, respectively, for the less often affected compartment C. Expert training (n = 32 before, n = 48 after) led to a considerable increase in sensitivities for the overall detection of DIE (84.6% vs. 65.4%, p = 0.071) and for the detection of DIE in compartment A (71.4% vs. 35.7%, p = 0.026), compartment B (66.7% vs. 37.5%, p = 0.057) and compartment C (75.0% vs. 20.0%, p = 0.010), without significant loss in specificity (all p > 0.50). DISCUSSION: After expert training, MRI has a good sensitivity with fair specificity regarding preoperative assessment of presence, location and extent of DIE.

Delusional parasitosis and the dopamine transporter. A new insight of etiology?

Delusional parasitosis (DP) is a psychotic condition in which a person has the unshakeable and mistaken belief (delusion) and/or aberrant perception (hallucination) of being infested with parasites. The disorder will be usually classified in a primary DP-group without a detectable cause (so-called pure forms), while secondary DP-groups are associated with general organic conditions, psychiatric illnesses and drugs (substance induced). Etiology and pathophysiology of DP remain however unknown. In the present paper we hypothesize for the first time a decreased striatal dopamine transporter (DAT)-functioning (corresponding with an increased extracellular dopamine-level) as etiologic condition for DP (primary and secondary groups). The DAT as key regulator of the dopamine-reuptake in the human brain is well known (regulation of the extracellular dopamine concentration). It is a presynaptic plasma membrane protein highly dense represented in the striatum. The hypothesis of a decreased DAT-functioning as etiologic condition by DP is revealed in case reports which show that DAT-inhibitors, such as cocaine, pemoline, methylphenidate and other amphetamine-derivatives can induce the clinical expression of DP. Several other associated causes of secondary DP-groups (medications, parkinson, chorea huntington, multiple system atrophy, diabetes, cerebrovascular diseases, alcoholism, traumatic brain injury, hyperuricemia, human immunodeficiency virus, iron deficiency, schizophrenia, depression) suggest that the clinical expression of DP may be related to a decreased striatal DAT-functioning (blocking, reduced ligand binding, reduced density, reduced activity). Our examined DP-cases (2-females) show means of magnetic resonance imaging a structurally damaged striatum. Furthermore, we presume that by the primary DP-group, the physiologically age-related decline of the DAT-density is pathologically elevated. Based on this hypothesis we show in the present paper the relation between DP and decreased striatal DAT-functioning, trying to give a new insight into the pathophysiologically mechanism involved. The hypothesis provides supporting evidence that increased levels of extracellular dopamine in the striatum of DP-patients is likely to be the result of decreased DAT-functioning and not increased rates of release. The hypothesis can be investigated simply by dopamine transporter imaging in patients with DP.

Telomerase activity in fine needle aspiration biopsy samples: application to diagnosis of human thyroid carcinoma.

BACKGROUND: The diagnosis of thyroid follicular carcinoma by fine needle aspiration biopsy is a well known problem in thyroid pathology. METHODS: We evaluated telomerase activity (TA) in 85 fine needle aspiration biopsy (FNAB) samples from patients with thyroid nodules. Surgery samples from patients with tumor or follicular adenomas were also analyzed. RESULTS: Twenty of the FNAB samples corresponded to carcinomas and were positive to telomerase assay (TA >10 Units). Among them, 4 follicular carcinomas and 1 papillary carcinoma were labeled as indeterminate by FNAB cytological examination. Four percent false positive cases and no false negative cases for TA in FNABs were reported. FNAB samples from follicular adenomas were diagnosed as indeterminate by cytological examination, but they showed no detectable TA. Tumor tissues from patients with follicular or papillary thyroid carcinomas presented TA >10 Units, whereas follicular adenoma tissues (benign nodules) showed no TA. CONCLUSION: Our results showed a good correlation between TA in FNAB samples and tumor/nodule thyroid tissue. This suggested that use of TA as a biological marker of malignancy might be a useful tool in the diagnosis of follicular thyroid carcinomas or follicular thyroid adenomas using FNAB samples.

Diagnostic findings in adenomyosis: a pictorial review on the major concerns.

Adenomyosis is a benign pathology with a marked impact on women in reproductive age. The prevalence of adenomyosis ranges from 5 to 70%. Dysmenorrhea, metrorrhagia, chronic pelvic pain, dyspareunia and infertility often occur, while a third of the women is asymptomatic. This pictorial review focuses on the peculiar patterns of presentation in adenomyosis. They are identified by means of non-invasive or minimally invasive techniques, with particular reference to 2D- and 3D-transvaginal sonography, sonohysterosalpingography, magnetic resonance imaging, and endoscopic techniques (i.e. hysteroscopy and laparoscopy).

Dorsoventral compartmentalization of mesoderm in heart-forming area of chick embryo.

In early chick development (stages 5-8) the seemingly homogeneous mesoderm in the heart-forming area splits to somatic and splanchnic cardiogenic layers. Little is known about dorsoventral compartmentalization before splitting. Electron microscopic analysis shows the early dorsoventral polarization of precardiomyocytes. The dorsal compartment has epithelial and the ventral compartment mesenchymal features with numerous protrusions. At stage 5+-6 staining for wheat germ agglutinine (WGA) transiently demarcates the ventral part of mesoderm. The glycosomes (beta-glycogen) show a dorsoventral gradient in the mesoderm of the cardiogenic field during the initial step of the compaction. The differential expression of glycosomes depends on the activity of glycogen synthase kinase 3-beta, a component of the wnt-signaling pathway, and might in this spatiotemporal developmental window be involved in the commitment of presumptive cardiogenic and somatic cells. To verify this hypothesis simulation experiments with LiCl in vitro were carried out. The normal splitting of the mesoderm and the development of heart primordia were disturbed. Blocking the receptors of WGA by WGA in vitro at stage 5-5+ perturbs the migration of mesoderm to anterio-medial direction. It appears that early specification of dorsal and ventral compartments of the mesoderm in the heart-forming area correlates with the gradient of glycosomes. Our results suggest that the target of LiCl action (glycogen synthase kinase 3-beta) might be involved in the specification of heart primordia and that WGA receptors mediate the migration of mesoderm to the anteriomedial direction.

Liver and iron metabolism--a comprehensive hypothesis for the pathogenesis of genetic hemochromatosis.

It is hypothesized that a homozygous C282Y mutation of the HFE gene prohibits the assembly of the transferrin-receptor 1 (TFR1) with the divalent metal transporter (DMT1) as the main iron update complex in hepatocytes membrane. Thus, the cellular influx of transferrin-bound iron from the endosomal compartment into the cytasol is compromised. As a consequence, transferrin saturation increases while concomitantly a cytosolic iron deficiency state develops. This in turn triggers the suppression of hepcidin synthesis in hepatocytes. Its impaired release into the bloodstream, causes the increased intestinal iron absorption of hemochromatosis. Excessively absorbed iron cannot be used by the erythron as a surplus for hemoglobin synthesis and is therefore trapped in ferritin complexes of RES macrophages. The ferritin is thereafter released into the bloodstream and taken up by hepatocytes for final disposal. In the lysosomal compartment ferritin is degraded to hemosiderin. Here, the release of excessive iron molecules may induce cellular injury via free radicals. The phenotypic expression of genetic hemochromatosis may depend on the activity of the erythron to use transferrin-bound-iron for heme synthesis. Therefore, a high erythron requirement for iron can utilize excess iron and may represent the rationale of phlebotomy therapy in this disease.

Determination of Active Marine Bacterioplankton: a Comparison of Universal 16S rRNA Probes, Autoradiography, and Nucleoid Staining.

We compared several currently discussed methods for the assessment of bacterial numbers and activity in marine waters, using samples from a variety of marine environments, from aged offshore seawater to rich harbor water. Samples were simultaneously tested for binding to a fluorescently labeled universal 16S rRNA probe; (sup3)H-labeled amino acid uptake via autoradiography; nucleoid-containing bacterial numbers by modified DAPI (4(prm1),6-diamidino-2-phenylindole) staining; staining with 5-cyano-2,3-ditolyl tetrazolium chloride (CTC), a compound supposed to indicate oxidative cell metabolism; and total bacterial counts (classical DAPI staining), taken as a reference. For the universal-probe counts, we used an image intensifying and processing system coupled to the epifluorescence microscope. All of the above-mentioned methods yielded lower cell counts than DAPI total counts. Universal-probe counts averaged about half of the corresponding DAPI count and were highly correlated to autoradiography counts (r(sup2) = 0.943; n = 7). Nucleoid-containing cell counts could be lower than DAPI counts by as much as 1 order of magnitude but sometimes matched autoradiography or probe counts. CTC counts were 2 orders of magnitude below DAPI counts. Universal 16S rRNA probe counts correlated well with autoradiography results, indicating a population with at least minimal metabolic activity. The greater variability of the nucleoid-containing cell counts calls for further investigation of the processes involved, and CTC counts were well below the range of the other methods tested.

Bacterial activity along a trophic gradient.

Bacterial biomass, secondary production, and extracellular enzymatic activity [α-glucosidase and leucine-aminopeptidase, measured as cleavage of artificial fluorogenic substrates 4-methyl umbelliferyl (MVF) α-D-glucopyranoside and L-leucine 7-amido-4-methyl coumarin (MCA)] were measured along a trophic gradient in the Northern Adriatic Sea in four ecologically different situations. Bacterial parameters were compared with chlorophyll a and inorganic and organic nutrient concentrations. Bacterial secondary production and extracellular enzymatic activity markedly changed among different seasons and along the trophic gradient. Average bacterial secondary production increased from 0.61 to 2.09 µg Cl(-1) hour(-1) preceding a bloom, to 2.09 µg Cl(-1) hour(-1) during the bloom, decreasing again to 0.81 and 0.83 µg Cl(-1) hour(-1) in the post-bloom and summer periods, respectively (values from 0.5 m depth). Leucine-aminopeptidase activity showed more consistent trends than α-glucosidase activity. Average values of leucine-aminopeptidase activity, measured by enzymatic release of MCA, increased from a pre-bloom value of 164.0 to 1,712.0 (nM MCA) hour(-1) released during a bloom, decreasing to 298.5 and 133.7 (nM MCA) hour(-1) released for the post-bloom and summer situation, respectively (values from 0.5 m depth). Average growth rates decreased during the bloom, whereas average extracellular enzymatic activity levels expressed on a cell basis increased by an average factor of 2. Along the trophic gradient, a consistent increase in bacterial secondary production could be observed in all but the summer situation (values from 0.5 m depth). Leucine-aminopeptidase activity also showed positive trends along the gradient, while α-glucosidase activity did not exhibit such a clear trend. Bacterial biomass trends were less obvious considering both seasonal changes and the tropic gradient. Highly significant interrelations were detected between bacterial proteolytic activity, secondary production, chlorophyll a content, and nitrate concentrations, especially in the surface horizon.

Archaeal dominance in the mesopelagic zone of the Pacific Ocean.

The ocean's interior is Earth's largest biome. Recently, cultivation-independent ribosomal RNA gene surveys have indicated a potential importance for archaea in the subsurface ocean. But quantitative data on the abundance of specific microbial groups in the deep sea are lacking. Here we report a year-long study of the abundance of two specific archaeal groups (pelagic euryarchaeota and pelagic crenarchaeota) in one of the ocean's largest habitats. Monthly sampling was conducted throughout the water column (surface to 4,750 m) at the Hawai'i Ocean Time-series station. Below the euphotic zone (> 150 m), pelagic crenarchaeota comprised a large fraction of total marine picoplankton, equivalent in cell numbers to bacteria at depths greater than 1,000 m. The fraction of crenarchaeota increased with depth, reaching 39% of total DNA-containing picoplankton detected. The average sum of archaea plus bacteria detected by rRNA-targeted fluorescent probes ranged from 63 to 90% of total cell numbers at all depths throughout our survey. The high proportion of cells containing significant amounts of rRNA suggests that most pelagic deep-sea microorganisms are metabolically active. Furthermore, our results suggest that the global oceans harbour approximately 1.3 x 10(28) archaeal cells, and 3.1 x 10(28) bacterial cells. Our data suggest that pelagic crenarchaeota represent one of the ocean's single most abundant cell types.

Antioxidants in the treatment of Graves disease.

An antioxidant mixture (LAROTABE) was evaluated in the treatment of Graves disease. Fifty-six hyperthyroid patients were treated with methimazol (MMI) (A), LAROTABE (B), or MMI plus LAROTABE (C). According to a clinical score, improvement was obtained at 8 weeks in A and 4 weeks in B and C. Group A diminished their thyroid hormone concentration to normal levels, while patients with LAROTABE did not reduce T3 and T4 unless MMI was introduced. Hyperthyroid patients had increased malondialdehyde (MDA) content and SOD activity and decreased catalase activity compared to controls. Within group A, MDA decreased to control values while SOD was reduced 38.3% and catalase increased 21.6%. Similar results were obtained for MDA and for both enzymes after treatment with LAROTABE. Signs and symptoms of Graves disease might be related to an increase in free radicals; antioxidants could be a new therapeutic tool to improve the clinical manifestation of this illness.

Kinematical analysis of handwriting movements in depressed patients.

OBJECTIVE: Motor disturbances are a relevant aspect of depression. Kinematical analysis of movements can be applied to explore which type of motor dysfunction is associated with depression. We hypothesized that depressed patients draw and write significantly slower than controls and that motor disturbances become more pronounced under bi-manual demands. METHOD: We examined 37 depressed patients and 37 healthy controls using a digitizing graphic tablet and subsequent kinematical analysis of handwriting and rapid drawing movements. RESULTS: Depressed patients performed drawing with significantly less regular velocity than controls (P < 0.001), but normal velocity. Motor differences between patients and controls did not increase under bi-manual demands. Handwriting of patients was abnormally slow (P = 0.04). CONCLUSION: Irregular patterns of velocity peaks in depressed patients point to basal ganglia dysfunction and/or deficient activity of the sensorimotor cortex and the supplementary motor area as a possible substrate of hand-motor disturbances in depression.

Relationship between the level of c-myc mRNA and histologic aggressiveness in thyroid tumors.

We investigated the relationship between the level of c-myc mRNA and histologic aggressiveness in thyroid tumors obtained at surgery. In thyroid carcinomas, there was a positive correlation between these two parameters, while in benign tumors there was no correlation between cellularity and the expression of the proto-oncogene c-myc. These results might be useful in the prognosis of thyroid tumors and consequently helpful in the management of the patient.