Erythropoietin doping in athletes: possible detection through measurement of fibrinolytic products.
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Biomedical subjects
Publications and source records attributed to C Caron.
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The tumor targeting potential of two monoclonal antibodies (mAbs) reacting with growth-regulated surface glycoproteins of human bladder cancer was investigated. The mAb T16 reacts more intensely with stationary cells while the mAb T43 is preferentially reactive with exponentially growing cells. The test target was T24 human bladder cancer cells grown subcutaneously in 30 nude mice. Controls for tumor specificity were human lung cancer cells grown on the contralateral side. Purified mAb's T16 and T43, and Om5, a non-reactive control, were radiolabeled with 131-Iodine and injected intravenously in doses ranging from 50 to 300 microCi in tumor-bearing animals. Consistent images of the bladder cancer xenografts were obtained at 48 and 72 hours with tumors as small as 0.1 gm. High resolution tumor images were obtained only with the reactive antibodies and according to their in vitro specificity. These results demonstrate that the two mAbs T16 and T43 can specifically and sensitively localize human bladder cancer cells in vivo.
A case of acquired von Willebrand's disease (AvWD) associated with an adrenal cortical carcinoma is reported. The circulating highest molecular weight multimers (HMWM) of von Willebrand factor (vWF) were decreased when assessed by SDS-agarose plasma electrophoresis, leading to the diagnosis of type II AvWD. No forms of inhibitor could be detected in the plasma of the patient. In contrast, indirect immunoperoxidase studies with a monoclonal antibody to vWF demonstrated an absorption of vWF into malignant cells. Infusion of a vWF-FVIII concentrate, containing significant amounts of HMWM of vWF, allowed surgical resection of the tumour. After the first infusion of the concentrate, the vWF-RCo recovery was found to be low (38%) compared to the vWF:Ag (75%) and FVIII:C (163%) recoveries. The resolution of all biological signs of vWD, including the abnormal multimeric pattern, in the post-operative period was prompt and permanent. Therefore, the absorption of the HMWM of vWF by carcinomatous cells appears to represent a likely pathophysiological mechanism responsible for the AvWD syndrome in this patient.
This study was carried out to assess the clinical efficacy in von Willebrand's disease (vWD) of a new, very high purity (VHP), solvent/detergent (SD)-treated, vWF concentrate (VHP Human von Willebrand Factor Concentrate, Biotransfusion) characterized by a high specific ristocetin cofactor (vWF:RCo) activity and a low factor VIII (FVIII) coagulant activity (FVIII:C). Nine patients (four type I, one type IIA, one type IIB, one type IIC, one type III and one acquired type II) were infused on 13 occasions including a pharmacokinetic study. Satisfactory haemostasis was achieved in all cases, including the treatment of spontaneous haemorrhages and the prevention of bleeding following surgery. The bleeding time was corrected for 6-12 h in 6/9 patients and shortened in the others. Furthermore, it was shown that the plasma vWF multimeric pattern of types II and III patients was greatly improved. When measured in eight patients 1 h after infusion, the vWF:RCo recovery was 77.3 (+/- 10.7)% while the F VIII:C recovery was strikingly higher (876 +/- 906%). This high recovery is likely related to the predominant 'pseudo-synthesis' of FVIII following the restoration of normal vWF levels. Maximum levels of FVIII:C occurred 6-12 h after the first infusion and normal levels of FVIII:C were maintained throughout the treatments with a dosage of 26-39 IU/kg vWF:RCo and only 0.2-5 IU/kg FVIII:C. The half-lives of the vWF-related parameters determined in a type III vWD patient were 20.6 h for vWF antigen, 17.8 h for vWF:RCo, 14 h for the high molecular weight multimers of vWF, 55.3 h for FVIII:Ag and 74 h for FVIII:C. In conclusion, it does not appear necessary that vWF concentrates intended for the treatment of vWD should contain FVIII in addition to vWF to be clinically effective in most patients.
OBJECTIVE: Diagnostic classification and reliability are critical in genetic linkage studies of schizophrenia and bipolar disorder. To establish an optimal diagnostic procedure, the authors drew 13 methodological elements from 38 major linkage studies and workshop reports. They determined reliability for a consensus best-estimate diagnostic method based on these 13 features. METHOD: Each of 59 subjects from several large multiplex pedigrees, densely affected by either schizophrenia or bipolar disorder, received a best-estimate diagnosis from unblind diagnosticians in the field and also from a panel of four research psychiatrists who were blind to the proband's and relatives' clinical status. The best estimate was based on personal diagnostic interviews, all available medical records, and family history data. RESULTS: The diagnostic concordance between the field team and the blind psychiatric board yielded 78% to 90% agreement for the whole sample (kappa = 0.83-0.88) and 71% to 87% agreement for the subjects given field diagnoses (kappa = 0.76-0.83). The diagnoses made by the unblind field diagnosticians were biased toward a greater severity (or certainty) level in the diagnostic hierarchy (schizophrenic or bipolar) and more consistency with the most prevalent diagnosis affecting the pedigree. CONCLUSION: Since several previous linkage studies used diagnoses made by diagnosticians who were not blind to the status of the probands and the relatives or did not use a consensus best-estimate diagnosis, further reliability studies of different aspects of the best-estimate method and of its effect on linkage studies are needed. Such research is imperative given the serious impact of diagnostic misclassifications on genetic linkage results.
STUDY OBJECTIVE: Our aim was to document the following in patients with septic shock and disseminated intravascular coagulation (DIC): (1) the influence of DIC in the mortality rate and the occurrence of organ failure; (2) the comparative prognostic value of initial antithrombin III (ATIII), protein C (PC), and protein S (PS) levels; and (3) the compared pattern of sequential ATIII, PC, and PS levels according to clinical outcome. DESIGN: Demographic data, criteria of severity, mortality in ICU, frequency of organ failure, hemodynamic and oxygenation parameters, and laboratory findings were compared in patients with septic shock according to the occurrence of DIC. Initial and sequential levels of ATIII (activity), PC (antigen and activity), PS (total and free), and C4b binding protein (C4bBP) were compared according to the outcome in patients with DIC. PATIENTS: Sixty patients with septic shock were studied. Forty-four entered the group DIC+; 16 entered the group DIC-. RESULTS: Simplified acute physiologic score (SAPS), frequency of acquired organ failure, blood lactate, and transaminase values were significantly higher in the group DIC+. The mortality rate reached 77 percent in group DIC+ vs 32 percent in DIC- (p less than 0.001). In patients with DIC, a fatal outcome was associated with higher bilirubin and transaminase levels, lower PaO2/FIo2 ratio, Vo2, Do2 and O2 extraction. In the group DIC+, all patients but two had severe deficiencies in ATIII and PC levels. Significant correlations were found between initial ATIII and PC levels, PC and free PS levels, and free PS and C4bBP levels. Initial ATIII levels had the best prognostic value for prediction of subsequent death. Serial measurements were consistent with a prolonged ATIII and PC deficiency with significantly different levels between survivors and nonsurvivors. CONCLUSIONS: DIC is a strong predictor of death and multiple organ failure in patients with septic shock. Sequential ATIII, PC, and PS measurements were consistent with prolonged consumption or inhibition that might account for a sustained procoagulant state and inhibition of fibrinolysis. The initial ATIII level was the best laboratory predictor of death in these patients.
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This study was conducted to test the effects of Concept Graphics on learning in clinical nephrology. Second-year medical students were exposed to summaries of the major renal pathologies presented as text with, or without Concept Graphics for 30 minutes, followed by a quiz. Concept Graphics summarize diagnoses using icons that are metaphors of objects or processes. Of nine quiz questions, five were classified as correlation questions and four as memorization questions. The experimental group (n = 39) performed better than the controls (n = 33) in answering the correlation questions (p = 0.018). The experimental group mentioned more frequently than the controls two pathogonomic criteria of the nephritic syndrome (p = 0.02). Results of an opinion poll of the students, comparing sources used in their studies of nephrology were treated by correspondence analysis; the Concept Graphics ranked closest to the classification "very useful".
The plasma levels of several haemostatic and fibrinolytic parameters were measured before and after delivery in 61 hypertensive pregnant women of whom 22 developed preeclampsia, and compared to the results obtained in 42 normal pregnant women. In the two last weeks before delivery (D less than or equal to -15) tPA antigen, PAI-1 activity, vWF:Ag/FVIII:C ratio, ATIII activity and platelet count were found to be significantly different in the hypertensive pregnant women with and without preeclampsia. Combined all together, an association of three of these five parameters were found to be pathological (i.e.:tPA:Ag greater than or equal to 19 ng/ml, PAI-1 activity greater than or equal to 58 IU/ml, vWF:Ag/FVIII:C ratio greater than or equal to 2.6, ATIII activity less than or equal to 73%) in none of the hypertensive women without preeclampsia and in only 35% of the preeclamptic group. A positive correlation was demonstrated between vWF:Ag/FVIII:C ratio and tPA:antigen levels suggesting that both tPA and vWF:Ag could be considered as early indicators of a possible micro angiopathy occurring in preeclampsia. However, due to the high dispersion of the results, it appears that the investigated haemostatic and/or fibrinolytic criteria give only presumptive arguments before assigning risk for preeclampsia development among hypertensive pregnant women.
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Epidemiological data show that the co-occurrence of two or more supposedly separate child (and adult) psychiatric conditions far exceeds that expected by chance (clinic data cannot be used for this determination). The importance of comorbidity is shown and it is noted that it is not dealt with optimally in either DSM-III-R or ICD-9. Artifacts in the detection of comorbidity are considered in terms of referral and screening/surveillance biases. Apparent comorbidity may also arise from various nosological considerations; these include the use of categories where dimensions might be more appropriate, overlapping diagnostic criteria, artificial subdivision of syndromes, one disorder representing an early manifestation of the other, and one disorder being part of the other. Possible explanations of true comorbidity are discussed with respect to shared and overlapping risk factors, the comorbid pattern constituting a distinct meaningful syndrome, and one disorder creating an increased risk for the other. Some possible means of investigating each of these possibilities are noted.
This is a retrospective study of 37 patients with endometrial carcinoma and presence of tumor on endocervical curettage (clinical Stage II). We intended to correlate the presence or absence of endocervical stromal invasion with the clinical behavior and other prognostic factors. Based on the endocervical curettage, three categories (CAT) were defined: CAT I: tumor fragments only (seven cases); CAT II: endocervical tissue and free-floating tumor fragments (13 cases); and CAT III: endocervical tissue and tumor with evidence of stromal invasion (17 cases). Five tumors were partly of clear cell and/or papillary serous types and three of them belonged to CAT I. Six of seven tumors with a nuclear Grade 3 were in CAT III (p less than 0.05). Nine patients had local recurrence, metastases, or died of their disease (median follow-up: 56 mo) and seven of them were in the CAT III (p less than 0.05). We conclude that despite the presence of tumor on the endocervical curettage, the lack of endocervical tissue invasion is associated with a lower nuclear grade and a less aggressive behavior. These tumors should be regarded and treated as Stage I disease. Special attention must be paid to staging of clear cell and papillary serous adenocarcinomas because of the tendency for these tumors to contaminate the endocervical curettage.
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In patients with cerebrospinal fluid internal shunts, immune complex glomerulonephritis sometimes develops. Of two new cases the first was classic, while the second was in an adult who had had a ventriculoatril shunt for 8 years; furthermore, the patient had acute renal failure and is the first to have been reported to have Peptococcus septicemia. Shunt glomerulonephritis is characterized by the following: (a) its occurrence following, most often, Staphylococcus albus infection in a patient who usually has a ventriculoatrial shunt; (b) transitory improvement of the symptoms by antibiotherapy only; and (c) full recovery if the prosthesis is removed. Laboratory studies show a low serum concentration of the C3 component of complement, the presence of cryoglobulins and a positive rheumatoid factor test. These abnormalities are reversible with removal of the prosthesis. Optical microscopy of a renal biopsy specimen in the two cases showed cellular proliferation of the glomerular tuft, electron microscopy demonstrated subepithelial deposits and immunofluorescent studies revealed intramembranous and intramesangial immune complexes. These features are similar to those observed in experimental nephritis induced in animals by foreign protein.
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Although glucose intolerance occurs as a consequence of chronic renal failure, improvement of a diabetic state by deterioration of renal function is a well known phenomenon. Recently occasional cases of spontaneous hypoglycemia in patients with chronic renal failure have been reported; two such cases and the results of metabolic studies are described in this paper. Pituitary, thyroid and adrenal function appeared to be normal. The results of an oral glucose tolerance test were normal; an appropriate insulin response was demonstrated in one patient, and a slightly elevated basal insulin value with a delayed insulin response to oral administration of glucose was demonstrated in the other. An insulin tolerance test did not support the hypothesis of increased insulin sensitivity as a factor, and the growth hormone response to hypoglycemia was normal. An intravenous glucagon test caused a subnormal increase in plasma glucose concentration, and the intravenous administration of tolbutamide produced hypoglycemia without an increase insulin sensitivity as a factor, and the growth hormone response to hypoglycemia was normal. An intravenous glucagon test caused a subnormal increase in plasma glucose concnetration, and the intravenous administration of tolbutamide produced hypoglycemia without an increase in insulin values. The plasma alanine concentration was low and the proinsulin/insulin ratio was increased. The origin of this hypoglycemia is not clear but is probably multifactorial. However, low hepatic glycogen stores and inadequate gluconeogenesis due to substrate deficiency seem to be involved.
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A 22-year-old male patient was seen with vasculitis and subcutaneous nodules on arms and legs. Discret thoracic venous dilations were noticed and venography demonstrated obstruction of the superior vena cava. Clinical and biological examination, roentgenograms revealed no sign of immunological disease but led to the diagnosis of mediastinal and retroperitoneal idiopathic fibrosis. No drug could be incriminated. Right hydronephrosis obliged to a surgical bilateral ureterolysis combined with systemic steroid therapy. Histological and ultrastructural examinations on retroperitoneal biopsies showed dense collagenous fibrosis, with vasculitis. Perivascular infiltrate was mainly composed of extravased erythrocytes and lymphocytes. Fibrin deposits were seen around implicated vessels. Direct immunofluorescence investigations were negative. These morphological features seem to be in agreement with the physiopathological hypothesis of sclerosis. No retroperitoneal or mediastinal fibrosis extension occurred three years after surgical procedure, and under corticosteroid therapy. Similar vasculitis with mediastinal and retroperitoneal idiopathic fibrosis have previously been reported in only one case by R. W. Carton and R. Wrong. Multifocal fibrosclerosis is the generic term currently used, since Comings et al. (1967), to describe a group of fibrosing conditions which affect separate organ systems. Findings suggest that retroperitoneal fibrois, mediastinal fibrosis, sclerosing cholangitis, Riedel's thyroiditis and pseudotumors of the orbit may be different manifestations of a single disease whose pathogenesis remains obscure.