[Reduction of trigeminal neuralgia complaints after recovery of the vertical dimension]. / Afname klachten trigeminusneuralgie na herstel van de verticale dimensie.

A 56-year-old man was referred by his dentist to an orthodontist as part of an interdisciplinary treatment plan for a complete dental rehabilitation. The patient presented with a mutilated dentition with a restricted envelope of function and generalized severe tooth wear with loss of vertical dimension. The patient showed a history of multiple endodontically treated and subsequently extracted elements associated with unexplained symptoms until a neurologist diagnosed trigeminal neuralgia. The orthodontic treatment in which the restricted envelope of function was eliminated and the vertical dimension was reestablished resulted in a significant reduction of the number of triggers experienced by the patient.

Thrombotic complications in patients with PMM2-CDG.

Many proteins regulating coagulation, including factor IX, factor XI, Antithrombin-III, Protein C and Protein S are deficient or decreased in activity in congenital disorders of glycosylation (CDG). Because of the imbalance of coagulation and anticoagulation factors, some patients develop acute vascular events, such as thrombosis. Identifying patients with increased risk for thrombotic events could prevent serious complications and even mortality. We performed a systematic review on patients diagnosed with the most common CDG form; PMM2-CDG, reported between 1990 and 2012 in medical literature. We also evaluated our PMM2-CDG patient-cohort of 15 patients. In total, based on the availability of comprehensive clinical descriptions, 100 patients were included in the study. Patients with and without thrombotic events were compared based on the alterations of the following glycosylated coagulation and anticoagulation factors: Antithrombin-III, Protein C, Protein S, factors IX and XI. We also assessed the global hemostasis, family history and provoking events. In the group of 100 PMM2-CDG patients 14 had suffered a venous or arterial thrombotic event. Low activity of several anticoagulation factors correlated with thrombotic events. Relatively high factor IX and XI activities were not associated with thrombosis. Prolonged PT and aPTT did not seem to protect against thrombosis in patients. Surgical procedures were frequently associated with thrombotic events. Based on the association of thrombosis and surgery in PMM2-CDG we advise to avoid elective surgical procedures in PMM2-CDG patients. Easily preventable risk factors like immobility should be treated with regular physiotherapy. We suggest a yearly follow-up for Antithrombin-III and Protein C levels and parent education for early thrombotic signs in CDG.

Redo pull-through surgery in Hirschsprung disease: Short-term clinical outcome.

INTRODUCTION: Although surgery is effective in most patients with Hirschsprung disease (HD), some have persistent obstructive symptoms. Additional medical treatment is generally sufficient, but a small fraction of these patients needs secondary surgery. Series on redo surgery are scarce. Aim of this study is to evaluate complications and clinical outcome of patients in need of redo surgery for HD. MATERIALS AND METHODS: Sixteen patients underwent redo endorectal pull-through surgery in our center between 2007 and 2015. Medical records were reviewed and demographics, indication for redo surgery, surgical procedures, complications, and clinical outcome were scored. RESULTS: The median age at the time of redo was 4.6years (range: 2months-21years). Median follow-up after redo was 3years (range: 9months-7years). Before redo surgery, all patients (100%) had obstructive symptoms, one patient had recurrent enterocolitis, and four patients were fecally incontinent despite adequate attempts of bowel management. Surgical procedure consisted of a transanal endorectal pull-through (TERPT) in all patients, with additional laparotomy in 7 (44%) and protective stoma in 8 patients (50%). Complications within 30days after redo surgery were anastomotic dehiscence (3; 19%), wound abscess (2; 13%), rectovaginal fistula (1; 7%) or enterocutaneous fistula (1; 7%). During follow-up, nine patients needed additional surgery, mainly to close the stoma. At final follow-up there were no patients with stenosis, obstructive symptoms, remaining rectovaginal fistula, or small bowel obstruction. Only one patient experienced enterocolitis. Six patients (43%) reported soiling or fecal incontinence. CONCLUSION: TERPT for redo surgery for HD is effective in resolving sustained severe obstructive symptoms after primary surgery, but the outcome is complicated by a relatively high rate of soiling and fecal incontinence.

[Approaching psychological problems like a general practitioner]. / Psychische problemen benaderen als een huisarts.

An important cause of the high prescription levels of psychotropic medication for psychological symptoms is that these symptoms are assessed according to the same model as applied for physical symptoms, the disease model. This has led to a one-sided medical approach to psychological symptoms. A person-centred approach offers an alternative; the positive aspects of the disease-centred approach are retained and attention for the patient and his/her context become the central focal point for the general practitioner. Important elements of the person-centred approach are empathy, a good doctor-patient relationship, a shared approach to problem definition and understanding of the patient's problem, development of a therapeutic alliance, and a focus on the patient's hopes and expectations. If additional primary care-based treatment by mental health practice nurses is indicated, this model could be suitable since it is based on patients' strengths and focuses on personal growth rather than reduction of symptoms.

Acute stimulation of glucose transport by histamine in cardiac microvascular endothelial cells.

The purpose of the present work was to study the acute regulation of glucose uptake in cultured cardiac endothelial cells (CEC). Two types of potential stimuli were considered: (1) agents that are known to acutely stimulate glucose transport (i.e., within minutes) in fat and muscle tissues and (2) agents that influence endothelial cell function. Among the former agents, neither insulin, nor catecholamines (adrenaline, dopamine, phenylephrine), nor serotonin affected the rate of glucose transport in CEC, while SH-group reagents (phenylarsine oxide, diamide or menadione) were inhibitory. Among the factors of the second group that were tested (heparin, ADP, histamine, bradykinin), histamine was found to stimulate glucose transport in CEC by 10-50%. This effect was concentration-dependent (with an EC50 value approximately equal to 12 microM) and reached a maximum within 5 min upon histamine addition. This stimulation of glucose transport was suppressed by pyrilamine (100 nM), a specific H1-receptor antagonist, but not by cimetidine (100 microM), a H2-selective antagonist. Northern blot and Western blot analysis of CEC extracts revealed the presence of the ubiquitous glucose transporter isoform GLUT1 mRNA and protein, but not of the 'insulin-regulatable' isoform GLUT4. In conclusion, this is the first report on an acute stimulation of glucose transport in cardiac endothelial cells, in particular, and in an insulin-unresponsive cell type, in general. The effect of histamine is most likely mediated by H1-receptors and cannot be accounted for by a recruitment of GLUT4.

Uptake kinetics of technetium-99m-methoxyisobutylisonitrile and thallium-201 in adult rat heart endothelial and fibroblast-like cells in comparison to myocytes.

Endothelial and fibroblast-like cells comprise 5%-10% of total cardiac cell volume and are more resistant to hypoxia than cardiomyocytes. However, their role in the uptake of radiotracers used for myocardial perfusion imaging has largely been ignored. Net uptake of 201TI and 99mTc-hexakis-2-methoxyisobutylisonitrile (99mTc-sestamibi) by cultured rat heart endothelial and fibroblast-like cells and quiescent myocytes was examined. Over a 30-min period, endothelial cells continuously accumulated 99mTc-sestamibi. Initial 201TI accumulation paralleled that of 99mTc-sestamibi; however, after 7 min 201TI accumulation plateaued whereas there was continued slow accumulation of 99mTc-sestamibi. Net uptake of the two radiotracers by fibroblast-like cells was similar to that of 201TI by endothelial cells. In the quiescent myocytes, there was an initial accumulation of both tracers with 201TI net uptake quickly reaching a plateau, whereas 99mTc-sestamibi accumulation continued throughout the 30-min period reaching a level 15-fold greater than that for 201TI. Myocyte uptake of 99mTc-sestamibi was approximately eight times greater than by the endothelial cells when expressed either as activity per mg protein or activity per cell volume. Although significant uptake differences exist among the three cell types, the fact that there is uptake by endothelial and fibroblast-like cells should be considered during image interpretation, particularly in situations in which the hypoxia resistant endothelial and fibroblast-like cells might be the remaining healthiest cell types.

Nimesulide, indomethacin, BW 755 C, phenidon, mepacrin and nedocromil inhibit the activation of human and rat leucocytes.

This study confirms the strong inhibition of therapeutic concentrations of the antiinflammatory agent nimesulide (NI) on the chemiluminescence (CL) of human leucocytes (HL) after stimulation with opsonized zymosan (C3Z), and extends the findings to peritoneal (RPL) and bronchoalveolar leucocytes (RBAL) collected from actively immunized rats 24 h after i.v. injection of Sephadex. Additionally we demonstrate that NI is a strong inhibitor of proteinase release (PR) from HL. The reference drugs tested for comparison were indomethacin (I), BW 755 C (BW), phenidon (PH), mepacrin (M) and nedrocromil (NE). The rank order of potency for suppression of PR and CL was nearly independent of the cell type and stimulus: PH greater than or equal to BW greater than M greater than NI = 4-OH-NI much greater than I greater than NE. NI was the superior inhibitor of HL activation compared with I as measured either by PR or CL (factor 7), and also of CL of RPL and RBAL (factor 2-3). NI inhibited the PR from HL and CL of RPL or RBAL almost equipotently (IC30: 10-20 micrograms/ml), whereas PH, BW, M and I were 6-10 times more effective as CL inhibitors compared with their PR inhibition. In contrast NE showed a preferential inhibition of PR. This unique inhibition profile on leucocyte activation in vitro may be related to the differences of NI and I which are also existing in their antiinflammatory activities in vivo.

A new device for the treatment of female stress urinary incontinence.

Treatment for stress urinary incontinence (SUI) comprises a broad range of possible interventions. Non-surgical options include absorbent pads, vaginal weights and cones, biofeedback and minimally invasive techniques such as urethral bulking agents (UBAs). Surgical interventions range in complexity from sling surgery and suspension techniques to more major surgeries such as burch colposuspension. Each option has its challenges and limitations. This paper will focus on UBAs, which are implantable materials whose purpose is to augment urethral tissue function and restore continence. The characteristics required of such materials, and the challenges to be overcome when incorporating them in a successful product design, will be described and discussed. Particular attention will be given to the latest developments in the administration of polydimethylsiloxane elastomer UBA.

Increased mortality in systemic inflammatory response syndrome patients with high levels of coagulation factor VIIa.

BACKGROUND: The tissue factor (TF)- Factor VIIa (FVIIa) complex has a pivotal role in inflammatory and coagulation responses in patients with systemic inflammatory response syndrome (SIRS) and sepsis. Because zymogen FVII (FVII) and FVIIa compete for binding to TF, their plasma levels determine if a catalytically active TF-FVIIa complex will be formed. OBJECTIVE: To study mortality in SIRS patients as a function of FVIIa and FVII levels in plasma. METHODS: This was a cohort study of 275 patients presenting with SIRS, aged 18 years or older and with an anticipated Intensive Care Unit (ICU) stay of at least 24 h. FVIIa was measured using a novel, quantitative assay that recognizes FVIIa, but not FVII. All-cause hospital mortality was followed over a period of 60 days. RESULTS: The percentage of FVII measured as FVIIa was higher in non-survivors than survivors (2.8%, IQR = 1-5.5% vs. 1.5%, IQR = 0.6-3.3%; P = 0.034). High levels of FVIIa were associated with decreased 60-day cumulative survival (62% vs. 81%, P = 0.030); the opposite was observed for FVII (84% vs. 76%, P = 0.039). Patients with high-FVIIa and low-FVII levels had a three-fold increased hazard ratio (HR) compared with the patients that had low-FVIIa and high-FVII levels (HR = 3.24, 95% confidence interval [CI] = 1.41-7.36). This association persisted after adjusting for the APACHE IV score (adjusted HR = 2.75, 95% CI = 1.2-6.27). CONCLUSIONS: SIRS patients with high-FVIIa and low-FVII on admission have an increased mortality risk, an association that is independent from the parameters included in the APACHE IV score.

Chemiluminescence of bronchoalveolar lavage cells as an indicator of leukocyte activation in rats with a hyperreactive bronchus.

Activation and generation of inflammatory mediators by different leukocytes may be important in the pathogenesis of airway hyperreactivity. We studied the effect of active sensitization with ovalbumin as antigen and i.v. treatment with Sephadex particles on bronchial reactivity (BR) in rats and its possible relation to leukocyte infiltration (LI) and activation (LA) in bronchoalveolar lavage (BAL). A marked BR to aerosols of serotonin (5-HT) and ovalbumin was found in Sephadex treated animals but not in control animals. In parallel to this a marked increase in BAL cell count from Sephadex-treated animals compared to controls was seen. This increase in BAL cell count corresponded with a clear augmentation of spontaneous, buffer-induced and C3Z-induced, luminol-amplified CL. We deduce that detection of CL of BAL cells from rats might be used for studying inflammatory mechanisms which lead to a hyperreactive bronchus.

Late phase increase of thrombin-like proteinase, protein, leukocytes in bronchoalveolar lavage (BAL) fluid and chemiluminescence of BAL after ovalbumin aerosol inhalation by actively immunized rats.

A thrombin-like proteinase (THROLP) was detected colorimetrically as the main proteolytic activity (PROA) in bronchoalveolar lavage fluid (BALF) 4 and 24 h after ovalbumin aerosol (OVA) challenge of actively immunized rats. Other proinflammatory parameters increased also significantly in BALF, like chemiluminescence of leukocytes (1 h), protein and cell number (24 h after challenge). In parallel, increased bronchoconstrictions against 5-HT aerosols are detected 24 h post OVA challenge. THROLP is an indicator for plasma leakage, activation of the clotting reaction and the protracted inflammation in the airways, which induced bronchial hyperreactivity.

Animal models for testing anti-inflammatory drugs for treatment of bronchial hyperreactivity in asthma.

In the first part of this review the important role played by the bronchial hyperreactivity caused by chronic bronchopulmonary inflammation in asthma is described. Deliberately, more emphasis is placed on the role of pro-inflammatory eosinophils, alveolar macrophages, lymphocytes and platelets rather than on mast cells and neutrophils or the numerous mediators. The reason for this is that, on account of the large number of mediators and their multitude of functions and interactions in asthma, antagonism of a specific mediator will probably not be clinically relevant for optimally effective curative treatment of asthma. Inhibition of the infiltration and activation of pro-inflammatory cells is likely to be a more successful approach. In the second part, various animal models of bronchial hyperreactivity, which could be suitable for testing anti-asthmatic drugs, are discussed. Most animal models pay too little attention to chronic bronchopulmonary inflammation as the cause of bronchial hyperreactivity in asthma. In various models the bronchial hyperreactivity is provoked by a single mediator and this leads to selection of specific antagonists which are unlikely to be of clinical benefit. Rats appear to have certain advantages over guinea-pigs as experimental animals for bronchial hyperreactivity.

Time course of immediate release and relationships between thrombin-like proteinase, other proteinases, histamine, protein and dye extravasation in rat passive peritoneal anaphylaxis.

A thrombin-like proteinase (THROLP) was detected colorimetrically as the main proteolytic activity (PROA) in the lavage fluid some minutes after antigen challenge of rats for passive peritoneal anaphylaxis (PPA) reaction. THROLP is equivalent to histamine (H) as parameter for the early phase of PPA: both increased significantly after 6 min, but decreased to prechallenge levels 20 min after challenge. H was released from serosal mast cells, in contrast THROLP originates predominantly from plasma leakage and activation of the clotting reaction in PPA. These findings underline the importance of PROA in the sequence of allergic reactions.

Intratracheal application of Sephadex in rats leads to massive pulmonary eosinophilia without bronchial hyperreactivity to acetylcholine.

Fourteen Brown-Norway rats were pretreated with physiological saline (n = 7) or 500 micrograms Sephadex (n = 7) intratracheally. 24 h later, a bronchial provocation test was performed under pentobarbital anaesthesia using increasing doses of acetylcholine aerosol and the degree of bronchospasm was measured using a modified Konzett-Rössler method. Subsequently, leucocyte counts were determined in the bronchoalveolar lavage fluid (BALF), BALF cells were differentiated, and the chemiluminescence of the BALF leucocytes were measured. Finally, the lungs were removed and histologically examined. The cell count in the BALF was significantly (p less than 0.05) increased in the animals pretreated with Sephadex compared to those in the saline group (mean value +/- SEM: 0.38 +/- 0.07 vs. 0.15 +/- 0.02 x 10(6)/ml). This difference was also reflected in the chemiluminescence measurements (2.51 +/- 0.53 vs. 0.20 +/- 0.03 x 10(6) counts/0.5 ml). In the Sephadex-treated animals there was also a significant increase in the absolute number of neutrophil (0.040 +/- 0.010 vs. 0.011 +/- 0.002 x 10(6)/ml) and, in particular, eosinophil granulocytes (0.188 +/- 0.055 vs. 0.003 +/- 0.001 x 10(6)/ml) in the total leucocytes of the BALF. Lung histology showed massive perialveolar and peribronchial oedema and granulomatous infiltrates, primarily with eosinophils, after intratracheal application of Sephadex; these findings were not observed in the saline group. None of these changes in the rats pretreated with Sephadex manifested themselves in increased bronchial reactivity to acetylcholine aerosol. It is uncertain if the Sephadex-induced increase in the eosinophil count is accompanied by an activation of this cell population, which appears to be of importance for the occurrence of bronchial hyperreactivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Arachidonic acid incorporation in cardiomyocytes, endothelial cells and fibroblast-like cells isolated from adult rat heart.

The incorporation of radiolabeled arachidonic acid (3[H]-AA) in normoxic cardiomyocytes (MC), cardiac endothelial cells (EC) and fibroblast-like cells (FL) isolated from adult rat heart was studied. Deposition of 3[H]-AA in the cellular lipid pool was assessed with biochemical and autoradiographic techniques. Extraction and subsequent analysis of lipids from the three different cell types revealed that MC contained significantly more triacylglycerols than EC and FL. The proportion of (unlabeled) AA was also higher in MC triacylglycerols than in EC and FL. The quantity of phospholipids did not differ among the three cell types studied. However, the content of (unlabeled) AA in the MC phospholipid pool was twice as high as in EC and FL. The amount of 3[H]-AA incorporated in the cellular lipid pool of MC, EC and FL depended on the concentration of AA in the incubation medium and the incubation time. In EC and FL incorporation of 3[H]-AA was highest in the cellular phospholipid pool (0.01 microM AA, 30 min incubation). With increased concentration of AA and longer incubation times, the cellular triacylglycerol pool became more important as site of 3[H]-AA incorporation. In MC, comparable amounts of 3[H]-AA were incorporated in the cellular triacylglycerol and phospholipid pools (0.01 and 1 microM AA). At higher AA concentrations (10 microM) the triacylglycerol pool was the preferred site of 3[H]-AA deposition. Autoradiographic analysis at the light microscopic level revealed that the extra-nuclear space was readily stained when the three cell types were incubated with 3[H]-AA. These findings indicate that all cellular lipid pools and membranes are most likely site of deposition of radiolabeled arachidonic acid.

Interstitial noradrenaline concentration of rat hearts as influenced by cellular catecholamine uptake mechanisms.

Marked concentration differences of noradrenaline (NA) between the vascular and the interstitial compartment were detected by sampling interstitial transudate from isolated perfused rat hearts. The ratios of vascular/interstitial concentration amounted to 7.4 to 1.3 depending on the concentration of NA administered (3 x 10(-9) to 10(-6) M). These concentration differences were abolished by inhibitors of uptake1 [desipramine (DMI)] and uptake2 (O-methyl-isoprenaline (OMI)). Neuronal uptake1 was characterized by a Km of 0.22 mumol/l and a Vmax of 370 pmol x min-1 x gWWT-1, extraneuronal uptake2 by a KUPTAKE of = 0.313 min-1. The apparent permeability surface area (P x S)-product calculated from uptake rate and transcapillary concentration difference was significantly decreased by administrating 100 mumol/l (NA) in presence of DMI. A presumed endothelial uptake mechanism contributing to catecholamine translocation was investigated in endothelial cells in culture. These cells showed a specific noradrenaline uptake with a K(m) of 4.35 mumol/l and a Vmax of about 75 pmol x min-1 x gWWT-1. Any inhibition by inhibitors of both of the two noradrenaline uptakes was lacking. The uptake rate of this mechanism is insufficient to contribute to the diffusive conductivity of the capillary wall (P x S-product). We conclude from our investigations on interstitial concentrations of catecholamines and transcapillary concentration differences, that the capillary wall, owing to its metabolic and diffusional characteristics, influences the exchange of catecholamines to a substantial and physiologically relevant extent.

Fatty acid oxidation capacity and fatty acid-binding protein content of different cell types isolated from rat heart.

Heart tissue contains appreciable amounts of fatty acid-binding protein (FABP). FABP is thought to play a crucial role in the transport of fatty acids from the cellular membrane to the intracellular site of oxidation and also, in case of endothelial cells, in the transfer of fatty acids from the vascular to the interstitial compartment through the endothelial cytoplasm. The present study was designed to delineate a possible quantitative relationship between the capacity of different cell types in the heart to oxidize fatty acids and the presence of FABP. Palmitate oxidation capacity, measured in homogenates of cells isolated from adult rat hearts, was 2 nmol/min per mg tissue protein in freshly isolated cardiomyocytes (CMC), but only 0.09 and 0.31 nmol/min per mg tissue protein in cultivated endothelial (CEC) and fibroblast-like cells (CFLC), respectively. Palmitate oxidation rates were closely related to the cytochrome C oxidase activity and, hence, to the mitochondrial density in the cells under investigation. In CMC the content of cytosolic H-FABP (H-FABPc) was about 4.5 micrograms/mg tissue protein. However, in CEC and CFLC the FABP content was less than 0.01 and 0.004 micrograms/mg tissue protein, respectively, corresponding to at maximum 0.2% of the FABP content of CMC. These findings indicate a marked difference between CMC and non-myocytal cells in the heart regarding their capacity to oxidize fatty acids, and a marked disproportion between the fatty acid oxidation capacity and immunochemically determined FABP content in both CEC and CFLC. The functional implication of these observations remains to be elucidated.

Production of arachidonic acid metabolites in adult rat cardiac myocytes, endothelial cells, and fibroblast-like cells.

Cells were incubated in the presence of the Ca2+ ionophore A23187 (10 microM) and arachidonic acid (AA, 80 microM). The release of eicosanoids from subcultivated cardiac endothelial and fibroblast-like cells amounted to 23.3 +/- 4.5 and 2.0 +/- 0.4 nmol/mg cellular protein per 30 min, respectively. The release from isolated cardiomyocytes remained below the detection limit of the high-performance liquid chromatography assay (< 0.00015 nmol/assay). When a very sensitive radioimmunoassay was applied, cardiomyocytes released 0.002 +/- 0.0001 nmol prostacyclin per milligram cellular protein per 30 min. Prostaglandin (PG) E2 and PGF2 alpha, 12-hydroxyheptadecatrienoic acid, 11- and 15-hydroxyeicosatetraenoic acid, and thromboxane B2 were the main eicosanoids released by endothelial cells. The stable product of prostacyclin, 6-keto-PGF1 alpha, contributed relatively little to the total amount of eicosanoids formed by endothelial cells. Fibroblast-like cells released predominantly PGE2 and 6-keto-PGF1 alpha and, to a lesser extent, 12-hydroxyheptadecatrienoic and 15-hydroxyeicosatetraenoic acids. Neither endothelial cells nor fibroblast-like cells released leukotrienes. A23187 stimulated eicosanoid release from endothelial cells when exogenous AA was below 40 microM. Addition of albumin reduced the amount of eicosanoids produced. Histamine and bradykinin did not influence 6-keto-PGF1 alpha and PGE2 production in cardiomyocytes. Histamine only gave rise to a slight but significantly higher release of 6-keto-PGF1 alpha in endothelial cells.