Routine chest X-ray is not required after a low-risk central venous cannulation

Background: Knowledge of the radiographic catheter tip position after central venous cannulation is normally not required for short-term catheter use. Detection of a possible iatrogenic pneumothorax may nevertheless justify routine post-procedure chest X-ray. Our aim was to design a clinical decision rule to select patients for radiographic evaluation after central venous cannulation.
Methods: A total of 2230 catheterizations performed using external jugular, internal jugular or subclavian venous approaches during a 4-year period were included consecutively. Information on patient data and corresponding procedures was recorded prospectively. A post-procedure chest X-ray was obtained after each cannulation.
Results: Thirteen cases (0.58%) of cannulation-associated pneumothorax were identified. The risk of pneumothorax after a technically difficult (1.8%) or subclavian (1.6%) cannulation was significantly higher than after cannulation not considered as difficult (0.37%) or performed using other routes (0.33%). Clinical signs of pneumothorax within 8 h of cannulation were found in all seven patients with pneumothorax requiring specific treatment. A new clinical decision rule for radiographic evaluation after central venous cannulation based on the results of the present study shows that 48% of the post-procedure chest X-rays performed in our patients were clinically redundant.
Conclusion: Clinical symptoms were reported in all patients with pneumothorax requiring specific treatment. Approximately half of the post-procedure chest X-ray controls could be avoided using the proposed clinical decision rule to select patients for radiographic evaluation after central venous cannulation. A large prospective multi-centre study should be carried out to further evaluate this decision rule.     

Selegiline and blood pressure in patients with Parkinson's disease

OBJECTIVES: Parkinson's disease (PD) frequently affects both the extrapyramidal system and the autonomic nervous system (ANS), the latter also being sometimes disturbed by PD medications. Specifically selegiline is known to disturb cardiovascular ANS functions and may cause or enhance orthostatic hypotension. METHODS: In order to study the effect of the withdrawal of selegiline on the regulation of blood pressure (BP) in advanced PD, an orthostatic test was performed in 14 PD patients with wearing-off before the morning levodopa dose and thereafter repetitively at 1-h intervals for up to 4 h. A Unified Parkinson's Disease Rating Scale motor score evaluation was also carried out hourly. The tests were repeated after a 4-week selegiline washout period. RESULTS: Selegiline withdrawal decreased systolic BP significantly during the on-stage in a supine position as well as during the orthostatic test. The initial drop of BP in the orthostatic test was significantly smaller after selegiline withdrawal. The heart rate remained unaffected.     

Is D‐dimer helpful in evaluating stroke patients? A systematic review

D-dimer (DD) is a fibrin degradation product present in negligible amounts in healthy individuals, but in thrombotic/fibrinolytic conditions substantially increases in plasma. Over the last two decades numerous studies have explored whether DD measurements would help stroke clinicians. An easy, reliable, and inexpensive test for stroke diagnosis, determination of stroke subtype, severity, prognosis, and recurrence risk is being sought. We searched the database, of studies indexed in English on MEDLINE, using the keywords 'cerebral venous thrombosis, D-dimer, deep vein thrombosis, intracerebral hemorrhage, ischemic stroke, outcome, prognosis, and subarachnoid hemorrhage' for relevant studies. Here, we systematically review current evidence on plasma DD levels in patients with ischemic and hemorrhagic strokes, transient ischemic attacks, and cerebral venous thrombosis. Numerous studies showed that patients with various strokes and stroke-related diseases had acutely increased plasma DD levels. Plasma DD levels, however, are neither sensitive nor specific enough to be utilized in stroke diagnostics and cannot replace either clinical or radiological evaluation. Regarding prediction of patient outcome, good clinical evaluation is clearly superior to DD testing.     

The Development of a Novel Cancer Immunotherapeutic Platform Using Tumor-targeting Mesenchymal Stem Cells and a Protein Vaccine

An ideal anticancer strategy should target only the malignant cells but spare the normal ones. In this regard, we established a platform, consisting of an antigen-delivering vehicle and a protein vaccine, for developing an immunotherapeutic approach with the potential for eliminating various cancer types. Mesenchymal stem cells (MSCs) have been demonstrated capable of targeting tumors and integrating into the stroma. Moreover, we have developed a protein vaccine PE(ΔIII)-E7-KDEL3 which specifically recognized E7 antigen and elicited immunity against cervical cancer. Taking advantage of tumor-homing property of MSCs and PE(ΔIII)-E7-KDEL3, we used E6/E7-immortalized human MSCs (KP-hMSCs) as an E7 antigen-delivering vehicle to test if this protein vaccine could effectively eliminate non-E7-expressing tumor cells. Animals which received combined treatment of KP-hMSCs and PE(ΔIII)-E7-KDEL3 demonstrated a significant inhibition of tumor growth and lung-metastasis when compared to PE(ΔIII)-E7-KDEL3 only and KP-hMSCs only groups. The efficiency of tumor suppression correlated positively to the specific immune response induced by PE(ΔIII)-E7-KDEL3. In addition, this combined treatment inhibited tumor growth via inducing apoptosis. Our findings indicated that KP-hMSCs could be used as a tumor-targeting device and mediate antitumor effect of PE(ΔIII)-E7-KDEL3. We believe this strategy could serve as a platform for developing a universal vaccine for different cancer types.     

HUMAN PANCREATIC GROWTH HORMONE RELEASING HORMONE FAILS TO STIMULATE HUMAN GROWTH HORMONE BOTH IN CUSHING''S DISEASE AND IN CUSHING''S SYNDROME DUE TO ADRENOCORTICAL ADENOMA

An absent or severely blunted hGH response to an i.v. bolus injection (100 micrograms) of human pancreatic growth hormone releasing hormone (hpGRF 1-44) was found in seven female patients with Cushing's syndrome (five with pituitary dependent Cushing's disease and two due to an adrenal adenoma) and four men with pituitary dependent Cushing's disease. Three of the female and three of the male patients had an adequate hypoglycaemia after insulin administration. All these patients showed an absent or blunted hGH response after insulin induced hypoglycaemia. The GHRH data in these patients are in agreement with those in older literature on hGH responsiveness to stimuli such as L-dopa, arginine and insulin induced hypoglycaemia. It is concluded that hypercortisolism inhibits hGH release to various stimuli at the pituitary level.     

Secretion of Tumour Necrosis Factor α and Lymphotoxin α in Relation to Polymorphisms in the TNF Genes and HLA-DR Alleles. Relevance for Inflammatory Bowel Disease

The genes for tumour necrosis factor alpha (TNFα) and lymphotoxin alpha (LTα; TNFβ) are tandemly arranged in the central region of the MHC. They may, therefore, be of importance for the aetiology of MHC-associated diseases. The authors have prospectively studied the secretion of TNFα and LTα in relation to polymorphisms at positions -308 and -238 in the TNFα gene (TNFA), and two polymorphisms in the first intron of the LTα gene (LTA), as well as HLA-DR in 30 patients with chronic inflammatory bowel diseases (IBD) and 12 healthy controls. In the Dutch population, the alleles of these four polymorphisms are present in only five combinations, called TNF-haplotypes: TNF-C, -E, -H, -I, and -P. Significant associations between TNF haplotypes and TNFα and LTα secretion were found when PBMC were cultured with T-cell activators, irrespective of disease. Mean TNFα secretion of individuals carrying the HLA-DR3 associated TNF-E haplotype was significantly higher, as compared to individuals without this haplotype (26 441 pg/ml versus 19 629 pg/ml; P = 0.014). Individuals carrying the TNF-C haplotype produced the lowest amount of TNFα (17 408 pg/ml; P = 0.022). The TNF-C and TNF-E haplotypes differ only at position -308 in the promoter of TNFA. Individuals carrying the HLA-DR1 associated TNF-I haplotype produced significantly less LTα when compared to those who lack this haplotype (1979 pg/ml versus 3462 pg/ml; P = 0.006). As the TNF-I haplotype is also associated with low TNFα secretion, this haplotype thus defines a ‘low secretor phenotype’. In conclusion, this is the first study to show associations between TNF haplotypes and TNFα and LTα secretion when T-cell stimulators are used. These findings will contribute to define disease heterogeneity in IBD and may be of relevance for understanding the pathogenesis of autoimmune diseases.     

Capsaicin-sensitive extrinsic afferents are involved in acid-induced activation of distinct myenteric neurons in the rat stomach

Challenge of the rat gastric mucosa with 0.5 mol L(-1) HCl activates nitrergic neurons in the myenteric plexus as visualized by c-Fos immunohistochemistry. In the present study, we characterized the activated neurons more extensively by their chemical coding and investigated whether a neural pathway that involves capsaicin-sensitive extrinsic afferents and/or cholinergic neurons transmitting via nicotinic receptors contributes to the activation of myenteric neurons. In multiple labelling experiments, c-Fos was examined for co-localization with nitric oxide synthase (NOS), vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), enkephalin (ENK), gastrin-releasing peptide (GRP), substance P (SP), calbindin D-28k (CALB) and neurofilament 145 (NF 145). All c-Fos-positive neurons were immunoreactive for NOS, VIP, NPY and NF 145, but not for SP, ENK, GRP and CALB. Nerve fibres co-expressing NOS, VIP and NPY were predominantly found in the external muscle layer and in the muscularis mucosae but rarely in the mucosa. Pre-treatment with capsaicin or hexamethonium or a combination of both pre-treatments reduced HCl-induced c-Fos expression by 54, 66 and 63%, respectively. Acid challenge of the stomach, therefore, leads to activation of presumably inhibitory motor neurons responsible for muscle relaxation. Activation of these neurons is partly mediated by capsaicin-sensitive afferents and involves ganglionic transmission via nicotinic receptors.     

Effect of nasal anaesthesia on lacrimal function after nasal allergen challenge

Ocular symptoms in allergic rhinoconjunctivitis arise partly from direct contact of the allergen with the conjunctiva and presumably partly from a naso-lacrimal reflex. The aim was to study the importance of this reflex in allergic rhinitis after topical anaesthesia of the nose. Ten patients with allergic rhinoconjunctivitis lo birch pollen were challenged with increasing intranasal doses of allergen until allergic symptoms occurred. The same dose of allergen was used in two other provocations, when the nasal cavity was anaesthetized with topical lidocaine in a double-blind rundomized cross-over manner. The effect on the eyes was evaluated by Shirmer's test, a routine method for measuring tear production. Lidocaine per se and/or allergen challenge had no significant effect on tear production. The naso-lacrimal reflex was not involved in the eye symptoms, in allergic conjunctivitis.