Family physician consultation by patients with rheumatoid arthritis or gonarthrosis/coxarthrosis

OBJECTIVE: To determine how often patients with rheumatic joint disease consult their general practitioner (GP), and if there are disease and patient characteristics that influence GP consultation of gonarthrosis/coxarthrosis patients. DESIGN: Prospective record investigation. SETTING: Seven GP centres in the southeast of the Netherlands. METHOD: All patient contacts were registered prospectively in the seven GP centres: 46 concerned patients with rheumatoid arthritis (RA), 122 patients with gonarthrosis/ coxarthrosis. Patient and disease characteristics were collected on intake sheets. RESULTS: Three-quarters of the RA patients were periodically seen (mostly by a specialist), and 47% of the gonarthrosis/coxarthrosis patients (as often by their GP as by a specialist). Of the RA patients and of the gonarthrosis/coxarthrosis patients 74% and 89% respectively consulted their GPs in one year (the average numbers of contacts were 4.7 and 5.0); 50% and 57% did so because of the chronic joint disease (with 2.2 and 1.6 contacts respectively). No disease characteristics and only a few patient characteristics (arthroplasty, chronic use of medication) of patients with gonarthrosis/coxarthrosis influenced GP consultation. CONCLUSION: Patients with rheumatic joint disease often consult their GP, but not always because of this illness. If they consult their GP, they usually do so more than once a year.     

Prognostic significance of methyl-p-hydroxy-phenyllactate-esterase activity in laryngeal squamous cell carcinoma

We assayed methyl-p-hydroxyphenyllactate esterase (MeHPLAase) activity in 63 cases of primary laryngeal squamous cell carcinoma. MeHPLAase activity did not show any correlation with oestrogen, progesterone and epidermal growth factor (EGF) receptor levels. No significant relationship was found between MeHPLAase activity and age, sex, tumour site, T classification, stage of disease and EGFR status, whereas a significant inverse relationship was found between enzymatic activity and neck lymph node positivity at presentation. The median value of MeHPLAase activity tended to be higher in tumours with low histopathological grade than in those with high histopathological grade. During the follow-up period (median 50 months, range 2-90 months) locoregional recurrences were observed in 31 out of 63 (49%) cases. At the end of the study, 27 out of 63 (43%) patients had died of cancer. Cox univariate analysis using MeHPLAase activity as a continuous covariate showed that the levels of enzymatic activity were inversely associated with the risk of death and relapse. Assuming the mean value of enzymatic activity as the cut-off value, we found a statistically significant relationship between high MeHPLAase activity and longer relapse-free and overall survival. MeHPLAase activity status retained its prognostic significance also in the lymph node-negative subgroup of patients. On multivariate analysis, both EGFR and MeHPLAase activity proved to be independent factors for predicting a short relapse and the overall survival.     

Hostility, cigarette smoking and alcohol consumption in the general population

Hostility has been associated with coronary heart disease, and hostility may affect coronary risk through its influence on risk factors such as cigarette smoking and alcohol consumption. The objective of this study was to determine relationships between hostile personality, cigarette smoking and alcohol consumption in the general population. The Edinburgh Artery Study comprises a cross-sectional survey of 1592 men and women aged 55-74 years sampled from age-sex registers of 10 general practices throughout the city. The Bedford-Foulds Personality Deviance Questionnaire was used to elicit extrapunitiveness (including hostile thoughts), dominance (including hostile acts) and intropunitiveness. Social class, age and deprivation score were controlled for in multivariate analyses. The hostile thoughts scale emerged as a significant independent predictor of alcohol consumption in men and women (P < or = 0.01), and the models accounted for 4-9% of the variance in alcohol consumption. Hostile acts were independently predictive of smoking in men (P < or = 0.001), with the model accounting for 5% of the variance in smoking. Hostile thoughts were independently predictive of smoking in women (P < or = 0.001), and the model accounted for 4% of the variance in their smoking. We conclude that hostility may affect coronary risk through its influence on lifestyle-related coronary risk factors, although in future further elucidation of hostility type and standard measurement of hostility are necessary.     

The cell wall porin of Nocardia farcinica: biochemical identification of the channel-forming protein and biophysical characterization of the channel properties

The doctrine of sovereign or official immunity has protected medical examiners in cases alleging negligent performance of the autopsy and in cases involving negligent harvesting of organs. It has not protected examiners in cases alleging performance of autopsy without authorization. The medical examiner, therefore, is well advised to determine whether there may be any objection by the next-of-kin to an autopsy and particularly any religious objection-and if there is such an objection, to proceed only after making contemporaneous and documented decision that there is a compelling need for the autopsy.     

Alterations of microsatellites in neurofibromas of von Recklinghausen's disease

von Recklinghausen's disease, or type I neurofibromatosis, a common familial tumor syndrome, is characterized by the occurrence of multiple benign neoplasms of nerve sheath cells. The disease is caused by germ-line mutations of the NF1 gene, which encodes a member of the GTPase-activating superfamily of Ras regulatory proteins. We analyzed 5 dinucleotide repeat loci in DNAs from neurofibromas and matched normal skin from 16 NF1 patients. Eight cases (50%) manifested microsatellite alterations. Expansions or compressions of dinucleotide repeats were observed at one locus in four cases and at two loci in one case. Banding patterns compatible with the loss of a microsatellite allele were observed in four cases, including one that also presented microsatellite instability. The surprisingly high frequency of microsatellite alterations suggests that the NF1 gene or another gene(s) contributing to the pathogenesis of neurofibromas might be directly or indirectly implicated in the control of genomic integrity.     

Initial characterization of autoprocessing and active-center mutants of CMV proteinase

Human cytomegalovirus (CMV) encodes a unique serine proteinase that is required in the maturation of the viral capsid. The CMV proteinase can undergo autocatalytic activation and is subject to proteolytic self-inactivation. Mutant enzyme forms were prepared to eliminate the initial autoprocessing site and thus form an active single-chain protein for structure-function studies. Two mutants of CMV proteinase were cloned and expressed in Escherichia coli. The A143V mutant was a conservative substitution at the first internal cleavage site. The S132A mutant modified one of the triad of residues responsible for catalytic activity. Through the use of computer-controlled high-cell-density fermentations the mutant proteins were expressed in E. coli at approximately 170 mg/L as both soluble (approximately 40% of total) and inclusion-body forms (approximately 60% of total). The soluble enzyme was purified by standard methods; inclusion-body protein was isolated by standard methods after refolding and solubilization in guanidine or urea. Sedimentation equilibrium and sedimentation velocity analyses reveal that the enzyme undergoes concentration-dependent aggregation. It exhibits a monomer <==> dimer equilibrium (Kd = 1 microM) at low concentrations and remains dimeric at high concentrations (28 mg/ml). Differential scanning calorimetry data for protein thermal unfolding fit best to a non-two-state model with two components (Tm = 52.3 and 55.3 degrees C) which subsequently aggregate upon unfolding. Analysis of the short-UV circular dichroism spectra of protein forms resulting from expression as soluble molecules (not refolded) reveals that the two mutants have very similar secondary structures which comprise a mixed structural motif of 20% alpha-helix, 26% beta-sheet, and 53% random coil. Though soluble and active (A143V mutant only), CD analysis revealed that protein refolded from inclusion bodies did not exhibit spectra identical to that of protein expressed only in soluble form.     

Characterization of the anatomical structures involved in the contractile response of the rat lung periphery

1. When lung parenchymal strips are challenged with different smooth muscle agonists, the tensile and viscoelastic properties change. It is not clear, however, which of the different anatomical elements present in the parenchymal strip, i.e., small vessel, small airway or alveolar wall, contribute to the response. 2. Parenchymal lung strips from Sprague Dawley rats were suspended in an organ bath filled with Krebs solution (37 degrees C, pH = 7.4) bubbled with 95%O2/5%CO2. Resting tension (T) was set at 1.1 g and sinusoidal oscillations of 2.5% resting length (L0) at a frequency of 1 Hz were applied. Following 1 h of stress adaptation, measurements of length (L) and T were recorded under baseline conditions and after challenge with a variety of pharmacological agents, i.e., acetylcholine (ACh), noradrenaline (NA) and angiotensin II (AII). Elastance (E) and resistance (R) were calculated by fitting changes in T, L and delta L/ delta t to the equation of motion. Hysteresivity (eta, the ratio of the energy dissipated to that conserved) was obtained from the equation eta = (R/E)2 pi f. 3. In order to determine whether small airways or small vessels accounted for the responses to the different pharmacologic agents, further studies were carried out in lung explants. Excised lungs from Sprague Dawley rats were inflated with agarose. Transverse slices of lung (0.5-1.0 mm thick) were cultured overnight. By use of an inverted microscope and video camera, airway and vascular lumen area were measured with an image analysis system. 4. NA, ACh and AII constricted the parenchymal strips. Airways constricted after all agonists, vessels constricted only after All. Atropine (Atr) pre-incubation decreased the explanted airway and vessel response to AII, but no difference was found in the parenchymal strip response. 5. Preincubation with the arginine analogue N omega-nitro-L-arginine (L-NOARG) did not modify the response to ACh but mildly increased the oscillatory response to NA after co-preincubation with propranolol (Prop). 6. These results suggest that during ACh and NA challenge, small vessels do not contribute substantially to the parenchymal strip response. The discrepancy between results in airways, vessels and strips when Atr was administered prior to AII implicates a direct contractile response in the parenchymal strip.