Clinical diagnosis of deep venous thrombosis after hip replacement surgery

Hip replacement surgery is associated with a high frequency of postoperative deep vein thrombosis. This prospective study was performed in order to investigate if routine bedside questioning and examination by the visiting doctor could reveal deep vein thrombosis in the legs of patients who had received a hip replacement. 258 patients were evaluated. Thromboprophylaxis (dextran-70, low molecular weight heparin and graded elastic stockings) was given during the first week after operation. Bilateral venography was performed in all patients on day seven after operation, and showed an overall deep vein thrombosis incidence of 16%. The visiting doctors had not suspected deep vein thrombosis in any of the patients. This may have been because postoperative painful and swollen legs effectively masked any signs and symptoms of deep vein thrombosis. Our results show that deep vein thrombosis during the first week after hip replacement surgery cannot be discovered by clinical diagnostics. The high subclinical frequency of deep vein thrombosis indicates the importance of improving thromboprophylaxis in order to further minimise the occurrence of deep vein thrombosis and the risk of thromboembolic complications.     

The impact of industrial factors of oil processing plant on serum lipoproteins

The study covered serum lipoproteins in workers engaged into production of higher fatty alcohols at oil-processing plant. The industrial factors appeared to induce changes in serum lipoproteins composition: lower share of High Density Lipoproteins and higher share of Very Low Density Lipoproteins. On the background of cardiovascular and gastrointestinal diseases, the occupational hazards may precipitate and aggravate alterations of serum lipoproteins composition in the workers.     

The luminescence immunoassay S-100: a sensitive test to measure circulating S-100B: its prognostic value in malignant melanoma

In this study we measured S-100B using a recently developed luminometric immunoassay with a detection limit of 0.02 microg l(-1). By measuring serum S-100B concentrations in 58 apparently healthy individuals a reference value of 0.16 microg l(-1) was found. To assess the sensitivity of the assay we measured levels of S-100B protein in the serum of 251 patients with cutaneous malignant melanoma before the start of treatment. Only one of 179 patients with limited disease had a serum concentration higher than the reference value, whereas elevated levels were seen in 79% of patients with metastasized disease. In the latter group the NSE serum concentration was elevated in 42%. Using a receiver operating characteristic (ROC) curve it is shown that S-100B is a significantly better parameter than neuron-specific enolase (NSE) for distinguishing patients with limited disease from those with extensive melanoma. Pretreatment S-100B values were highly predictive for the period of survival. Patients with limited disease have increased risk for early death with increasing levels of S-100B protein. Within the group of patients with positive lymph nodes and/or with distant metastases, elevated S-100B levels strongly identified high-risk patients. Our study indicates that the measurement of S-100B as a tumour marker in the management of patients with cutaneous malignant melanoma has clinical significance.     

Papillary thyroid carcinoma oncogene (RET/PTC) alters the nuclear envelope and chromatin structure

Current evidence suggests the papillary thyroid carcinoma oncogene (RET/PTC) generates papillary thyroid carcinomas in one genetic step. We tested a resulting prediction that RET/PTC expression in thyroid epithelium should be sufficient to cause the changes in nuclear morphology diagnostic of this tumor. Primary cultures of human thyroid epithelial cells were infected with a RET/PTC retroviral construct. Morphological scoring by two independent cytopathologists shows RET/PTC expression by immunohistochemistry to be highly associated (p < 0.0001) with an irregular nuclear contour and a euchromatic appearance compared with non-expressing cells in the same cultures. The altered nuclear morphology is not due to gene transfer or transformation per se as primary thyroid cell cultures infected with a retroviral H-RAS construct differ from RET/PTC-infected cells by showing round nuclear envelopes and coarser chromatin, as determined by the independent scoring of two cytopathologists (p < 0.0001). In addition, RET/ PTC-transfected cells appear to disperse, whereas RAS-transfected cells grow as discrete colonies. The results provide additional support for the hypothesis that RET/PTC is sufficient to cause papillary thyroid carcinomas. A signaling pathway downstream of RET/ PTC leads to restructuring of the nuclear envelope and chromatin, and the signal does not depend entirely, if at all, on a RAS pathway.     

Karyotypic anomalies and chromosomal sites of increased fragility in colorectal cancer

Karyotypic structural aberrations in tumor cells and chromosome constitutive fragile sites (cFSs) in peripheral blood lymphocytes were studied in ten patients with colorectal adenocarcinoma Most chromosome breakpoints (38 out of 40, i.e., 95.0%) were shown to be located within cFSs in tumor cells. Expression of 24 out of 137 cFSs in patients was higher than that in healthy donors. Four of these cFSs (6q26, 7q36, 16q23, and 17q21), were involved in the formation of nonrandom tumor cell chromosome markers most characteristic of colorectal neoplasms. The frequency of damages induced within these sites was analyzed in each patient. Expression of 7q36, 16q23, and 17q21 was increased in blood cells of patients carrying specific chromosome rearrangements with the breakpoints within these sites. The association between nonrandom chromosome aberrations in tumor cells and cFSs in normal cells is discussed.     

Prognostic value of some biochemical and immunologic factors in the management of multiple myeloma

The aim of this study was to measure serum carbohydrate-deficient transferrin (CDT) in consecutive patients attending a general medical clinic with a range of alcohol intakes to determine its value in assessing such intake. Eighty-one consecutive patients (42 male, 39 female) aged 20-85 years (median = 49.5 years) attending an out-patient clinic were selected for the study. Each patient completed an alcohol diary detailing the units of alcohol consumed in the previous week, a CAGE questionnaire and an alcohol history, and underwent conventional blood tests including mean corpuscular volume (MCV), liver function tests, and gamma-glutamyl transferase (GGT). CDT was estimated using an enzyme immunoassay (CDTect, Pharmacia). The group comprised of 17 teetotallers, 28 light (<100 g/week), 23 moderate (100-400 g/week), and 13 heavy (>400 g/week) drinkers. Median serum CDT for heavy drinkers (25.5 U/l) was significantly higher than for the rest (median = 17 U/l, Kruskal-Wallis test, P = 0.01). Serum CDT correlated significantly with the CAGE score (Mann-Whitney test, P = 0.01), but poorly with alcohol diary records (r = 0.1, P = 0.4). However the correlations between GGT and diary records (r = 0.43, P = 0.001) and MCV with diary records (r = 0.5, P < 0.001) were significant. Sensitivity, specificity, and positive predictive value for elevated serum CDT were 69, 81 and 41% respectively in detecting heavy drinking. The positive predictive values for the various parameters were 43% for elevated serum GGT, 41% for raised erythrocyte MCV, and 75% for a positive score on the CAGE questionnaire. When a combination of the markers CDT, GGT, and MCV was used, elevation in two of the three markers detected heavy drinking with sensitivity of 85%, specificity of 88%, and positive predictive value of 61%. We conclude that, in out-patients with a wide range of alcohol intakes conventional markers such as serum GGT and erythrocyte MCV were more suitable than serum CDT for assessing alcohol intake. Serum CDT when used in combination with serum GGT and erythrocyte MCV was useful in detecting heavy drinking. The importance of careful history-taking including a standardized questionnaire is emphasized.     

Atrial natriuretic peptide-induced release of cyclic guanosine monophosphate by coronary bypass grafts

BACKGROUND: Superior long-term patency rates of the internal mammary artery (IMA) versus saphenous vein (SV) after coronary artery bypass grafting are well documented. Higher production rates of vasodilating and platelet-inhibiting mediators (prostacyclin and nitric oxide) by the IMA seem to have a major impact on its long-term durability and resistance to coronary artery graft disease. For the right gastroepiploic artery (RGEA) marked release of protective mediators is reported as well. The vasodilating effect of cyclic guanosine monophosphate (cGMP) released after stimulation by atrial natriuretic peptide might serve as another graft protective system. The aim of the present study was to determine cGMP release by IMA, RGEA, and SV after atrial natriuretic peptide challenge. METHODS: Samples of human IMA (n = 19), RGEA (n = 7), and SV (n = 18) discarded during coronary artery bypass grafting were stimulated with 10(-6) mol/L atrial natriuretic peptide after a resting phase in nutrient medium. Release of cGMP was determined by 125-iodide radioimmunoassay. RESULTS: Basal cGMP production rates of the IMA (759.9 +/- 277.0 fmol/cm2) and RGEA (739.9 +/- 186.0 fmol/cm2) were higher than production rates of SV (281.2 +/- 64.0 fmol/cm2). Application of atrial natriuretic peptide led to a statistically significant increase of cGMP release in IMA grafts (1,939.3 +/- 778.0 fmol/cm2), whereas RGEA (618.4 +/- 141.3 fmol/cm2) and SV (221.7 +/- 64.5 fmol/cm2) remained at basal levels (p < 0.05). CONCLUSIONS: From these data we conclude that the IMA in comparison with the RGEA and SV produces more extracellular cGMP when stimulated by atrial natriuretic peptide. This effect might support the cGMP-mediated protective properties of nitric oxide and could underline the extraordinary suitability of the IMA as a bypass conduit.     

Prognostic impact of morphometric nuclear grade of endometrial carcinoma

BACKGROUND & AIMS: The pathogenesis of Clostridium difficile toxin A-induced intestinal inflammation is not completely understood. The aim of this study was to define the contribution of mast cells to the fluid secretion and neutrophil infiltration associated with toxin A-induced enteritis. METHODS: Fluid secretion and neutrophil infiltration in toxin A- or buffer-challenged ileal loops were assessed in normal, mast cell-deficient, and mast cell-deficient KitW/KitW-v mice that had undergone selective repair of their mast cell deficiency. The effect of a specific substance P-receptor antagonist was also studied. RESULTS: Intestinal fluid secretion and neutrophil recruitment were significantly diminished in mast cell-deficient KitW/KitW-v and mast cell-deficient MgfSl/MgfSl-d mice compared with the respective normal mice. Mast cell-reconstituted KitW/KitW-v mice showed responses similar to the normal congenic mice. Administration of a specific substance P-receptor antagonist (CP-96,345) reduced toxin A-induced intestinal fluid secretion and inhibited neutrophil infiltration in normal, mast cell-deficient KitW/KitW-v, and mast cell-reconstituted KitW/KitW-v mice. CONCLUSIONS: C. difficile toxin A elicits intestinal fluid secretion and neutrophil infiltration by both mast cell-dependent and -independent pathways, and substance P participates in both pathways.