Measurement of the abdominal circumference for the detection of intra-abdominal hemorrhage has no diagnostic value

BACKGROUND: Measuring the circumference of the abdomen is still commonly used when treating a patient with suspicion of intra-abdominal bleeding. In the present study the usefulness of this method for a diagnostic purpose is questioned because of the assumed method-related interindividual variation. METHODS: The study group consisted of 34 end-stage renal failure (ERSF) patients treated with peritoneal dialysis. Each patient was measured by the same nurse at the level of the umbilicus and the level of the iliac crest both before and after an infusion of 2000 ml of peritoneal dialysis fluid into the peritoneal cavity. One healthy female served as a control. Her abdominal circumference was measured at the level of the umbilicus by 10 different emergency medical technicians (EMTs), each of whom performed the measurement three times. The measuring tape was blank and the place of the first measurement was marked as performed in clinical practice. RESULTS: The mean abdominal circumference at the level of the umbilicus before an infusion of peritoneal fluid was 93.2 +/- 9.5 cm (SD), and after filling the peritoneal cavity 96.3 +/- 9.5 cm (difference 3.1 +/- 1.7 cm). These figures at the level of the iliac crest were 96 +/- 8.3 and 97.2 +/- 8.4 cm (difference 1.2 +/- 1.4 cm) (P < 0.0001), respectively. The mean value between the smallest and largest values when measuring the circumference of a healthy control person was 1.85 +/- 1.11 (P < 0.0005). The mean difference in circumference in the peritoneal dialysis patients was smaller than the largest difference among the three measurements taken by the same EMT. CONCLUSION: Measuring the abdominal circumference should not be used as a diagnostic tool when intra-abdominal bleeding is suspected.     

Standard, routine and non-routine processes in health care

Quality management methods have been introduced into health care with variable success. Industrial approaches, such as standardization, are not always applicable professional services, because of fundamental differences in conceptions of aims and the predictability of the results of action. Processes in health care can be classified into standard, routine and non-routine depending on the level of repetition and amount of variation, variety and uncertainty. Quality problems are different in each type: standard processes may produce deviations from targets, routines errors in classification, and non-routines failures in interpretation. Different management approaches for each type are discussed. A metaphor to assist discussion, The Broom, is introduced.     

Role of 24-hydroxylase in vitamin D3 growth response of OVCAR-3 ovarian cancer cells

Vitamin D and its analogues are potent regulators of cell growth and differentiation both in vivo and in vitro. We studied the effects of 25-hydroxyvitamin D(3) [25(OH)D(3)], 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] and vitamin D analogue, EB 1089, on the growth of a human ovarian cancer cell line, OVCAR-3. We also studied the expression of vitamin D metabolising enzymes 24-hydroxylase (24OHase) and 1alpha-hydroxylase (1alphaOHase). Our results showed that high concentrations (10 and 100 nM) of 1,25(OH)(2)D(3) inhibited a cell proliferation, whereas low concentration (0.1 nM) stimulated growth of the OVCAR-3 cells. In the concentration range of 10-500 nM a prohormone, 25(OH)D(3), stimulated growth. An amount of 1 nM EB 1089 and 100 nM 1,25(OH)(2)D(3) inhibited growth with an equal magnitude. The expression of 24OHase was strongly induced by 1,25(OH)(2)D(3) and EB 1089 in OVCAR-3 cells, and analysis of vitamin D metabolites showed the functionality of 24OHase. An inhibition of 24OHase activity with a novel 24OHase inhibitor enhanced growth-inhibiting effects of 1,25(OH)(2)D(3) and suppressed the growth stimulation of 100 nM 25(OH)D(3). We also report the expression of a vitamin D activating enzyme, 1alphaOHase, in 7 ovarian cancer cell lines. The production of 1,25(OH)(2)D(3) in OVCAR-3 cells was low, possibly due to an extensive activity of 24OHase or a low 1alphaOHase activity. These results suggest that in ovarian cancer cells vitamin D metabolizing enzymes might play a key role in modulating the growth response to vitamin D. The possible mitogenic effects of vitamin D should be considered when evaluating treatment of ovarian cancer with vitamin D.     

Behavioural correlates of an altered balance between synaptic and extrasynaptic GABAAergic inhibition in a mouse model

GABAA receptors mediate fast phasic inhibitory postsynaptic potentials and participate in slower tonic extrasynaptic inhibition. Thy1alpha6 mice with ectopic forebrain expression of GABAA receptor alpha6 subunits exhibit increased extrasynaptic GABAA receptor-mediated background conductance and reduced synaptic GABAA receptor currents in hippocampal CA1 neurons [W. Wisden et al. (2002) Neuropharmacology 43, 530-549]. Here we demonstrate that isolated CA1 neurons of these mice showed furosemide-sensitivity of GABA-evoked currents, confirming the functional expression of alpha6 subunit. In addition, receptor autoradiography of the CA1 region of Thy1alpha6 brain sections revealed pharmacological features that are unique for alpha6betagamma2 and alpha6beta receptors. The existence of atypical alpha6beta receptors was confirmed after completely eliminating GABAA receptors containing gamma1, gamma2, gamma3 or delta subunits using serial immunoaffinity chromatography on subunit-specific GABAA receptor antibodies. Behaviourally, the Thy1alpha6 mice showed normal features with slightly enhanced startle reflex and struggle-escape behaviours. However, they were more sensitive to GABAA antagonists DMCM (shorter latency to writhing clonus) and picrotoxinin (shorter latency to generalized convulsions). Tiagabine, an antiepileptic GABA-uptake inhibitor that increases brain GABA levels, delayed picrotoxinin-induced convulsions at a low dose of 3.2 mg/kg in Thy1alpha6 mice, but not in control mice; however, the overall effect of higher tiagabine doses on the convulsion latency remained smaller in the Thy1alpha6 mice. Altered balance between extrasynaptic and synaptic receptors thus affects seizure sensitivity to GABAergic convulsants. Importantly, the increased extrasynaptic inhibition, even when facilitated in the presence of tiagabine, was not able fully to counteract enhanced seizure induction by GABAA antagonists.     

Kainate down-regulates a subset of GABA<Subscript>A</Subscript> receptor subunits expressed in cultured mouse cerebellar granule cells

The effect of kainate, an agonist selective for ionotropic AMPA/kainate type of glutamate receptors, on GABAA receptor subunit expression in cultured mouse cerebellar granule cells was studied using quantitative RT-PCR, ligand binding and electrophysiology. Chronic kainate treatment, without producing excitotoxicity, resulted in preferential, dose- and time-dependent down-regulation of alpha1, alpha6 and beta2 subunit mRNA expression, the expression of beta3, gamma2 and delta subunit mRNAs being less affected. The down-regulation was reversed by DNQX, an AMPA/kainate-selective glutamate receptor antagonist. A 14-day kainate treatment resulted in 46% decrease of total [3H]Ro 15-4513 binding to the benzodiazepine sites. Diazepam-insensitive [3H]Ro 15-4513 binding was decreased by 89% in accordance with very low amount of alpha6 subunit mRNA present. Diazepam-sensitive [3H]Ro 154513 binding was decreased only by 40%, contrasting >90% decrease in alpha1 subunit mRNA expression. However, this was consistent with lower potentiation of GABA-evoked currents in kainate-treated than control cells by the alpha1-selective benzodiazepine site ligand zolpidem, suggesting compensatory expression of alpha5 (and/or alpha2 or alpha3) subunits producing diazepam-sensitive but zolpidem-insensitive receptor subtypes. In conclusion, chronic kainate treatment of cerebellar granule cells selectively down-regulates oil, alpha6 and beta2 subunits resulting in altered GABAA receptor pharmacology.     

The extracellular matrix in skin tumor development – a morphological study

The development of cancer involves epithelial-stromal interactions. Alterations in the synthesis and deposition of type I and III collagens are related to the tumor morphology. Skin carcinogenesis in experimental animals provides a reliable model for the development of neoplasia. Ultraviolet (UV) irradiation is the main etiological factor for epidermal dysplasia and malignant tumors in man, but also for dermal degeneration. Non-neoplastic dermal changes and skin tumors induced by ultraviolet irradiation and 7,12-dimethylbenz(a)anthracene were investigated in various mouse strains with different susceptibilities to tumor formation. UVB irradiation resulted in an increased immunoreactivity of collagens in the dermis, in comparison with 7,12-dimethylbenz(a)anthracene. Increased synthesis and deposition of type I and III collagens were found in the stroma adjacent to benign alterations. In well-differentiated squamous cell carcinomas, a similar induction of collagen synthesis and deposition was observed. The destruction of fibrillary structures was more pronounced during the decrease of differentiation from moderately to poorly differentiated squamous cell carcinomas. Anaplastic carcinomas with spindle cell morphology displayed a delicate meshwork of reticular fibers and collagen III, and abnormal expression of mRNA for collagens in some malignant cells with epithelial characteristics. The underlying stroma reacts to the development of epithelial tumors in a reproducible way, which is related to the carcinogenic agent involved.     

Human hepatic stem cells from fetal and postnatal donors

Human hepatic stem cells (hHpSCs), which are pluripotent precursors of hepatoblasts and thence of hepatocytic and biliary epithelia, are located in ductal plates in fetal livers and in Canals of Hering in adult livers. They can be isolated by immunoselection for epithelial cell adhesion molecule-positive (EpCAM+) cells, and they constitute approximately 0.5-2.5% of liver parenchyma of all donor ages. The self-renewal capacity of hHpSCs is indicated by phenotypic stability after expansion for >150 population doublings in a serum-free, defined medium and with a doubling time of approximately 36 h. Survival and proliferation of hHpSCs require paracrine signaling by hepatic stellate cells and/or angioblasts that coisolate with them. The hHpSCs are approximately 9 microm in diameter, express cytokeratins 8, 18, and 19, CD133/1, telomerase, CD44H, claudin 3, and albumin (weakly). They are negative for alpha-fetoprotein (AFP), intercellular adhesion molecule (ICAM) 1, and for markers of adult liver cells (cytochrome P450s), hemopoietic cells (CD45), and mesenchymal cells (vascular endothelial growth factor receptor and desmin). If transferred to STO feeders, hHpSCs give rise to hepatoblasts, which are recognizable by cordlike colony morphology and up-regulation of AFP, P4503A7, and ICAM1. Transplantation of freshly isolated EpCAM+ cells or of hHpSCs expanded in culture into NOD/SCID mice results in mature liver tissue expressing human-specific proteins. The hHpSCs are candidates for liver cell therapies.