Pegylated feline granulocyte colony-stimulating factor increases neutrophil levels in cats.

Neutropenia can often be corrected by treatment with granulocyte-colony stimulating factor (G-CSF) and off-label use of commercial human G-CSF (HuG-CSF) is a commonly used treatment for neutropenic animals. However, long-term HuG-CSF treatment can be associated with adverse effects, including neutropenia. Here, feline (Fe) G-CSF was produced in Pichia pastoris, pegylated (Peg) FeG-CSF and tested in cats. A randomized controlled clinical trial was conducted to evaluate the efficacy of PegFeG-CSF compared to FeG-CSF or HuG-CSF in FIV-infected (n=14), FIV-uninfected healthy cats (n=19), and in HuG-CSF-induced neutropenic cats (n=4). Daily FeG-CSF doses induced higher neutrophil production than HuG-CSF after the second week of treatment (P ⩽ 0.002). Weekly doses of PegFeG-CSF induced higher neutrophil counts and showed greater sustained activity than weekly doses of FeG-CSF. PegFeG-CSF provided the most therapeutic and sustainable neutrophil production (P<0.001) in both FIV-uninfected and FIV-infected cats, without the development of neutralizing antibodies. Conversely, all HuG-CSF-treated cats developed neutralizing antibodies, suggesting cross-reactive antibodies to endogenous G-CSF in a majority of the cases with severe neutropenia. Strikingly, when PegFeG-CSF was used to rescue cats with HuG-CSF-induced neutropenia, clinically normal neutrophil numbers returned. Thus, PegFeG-CSF appears to be a superior treatment for neutropenia in feline patients.

Comparison of cystatin C versus creatinine for detection of mild renal failure.

AIM: Serum cystatin C (SCyst) has been proposed as a novel indicator of GFR. PATIENTS AND METHODS: We compared SCyst, serum creatinine (SCreat) and Cockcroft and Gault's estimated clearance (CCG) using inulin clearance (Cin) as gold standard. 140 subjects (161 samples; aged 39 +/- 14; male/female: 79/82) underwent simultaneous measurements. RESULTS: A highly significant correlation r = 0.70, 0.74, 0.77 (p < 0.0001) was found between 1/SCyst, 1/SCreat, C(CG), respectively, and Cin. Receiver-operating characteristic (ROC) analysis was performed on SCyst, SCreat and C(CG) using a Cin cut-off of 90 ml/min/1.73 m2. Best fit for SCyst was 0.90 mg/l with a sensitivity of 75% and a specificity of 92%. The area under the ROC curve was not significantly greater for SCreat or C(CG) than for SCyst (p = 0.91,0.13, respectively). When relationship between Cin and SCyst was plotted, experimental data deviated from the theoretical model, suggesting that cystatin C may not be solely filtered. Additional patients were selected in our database on the basis of discordant SCreat/GFR values: false negative (n = 46 samples, 31 patients) and false positive (n = 16 samples, 9 patients). In this highly selected subgroup, 38% of the SCreat false positive had normal SCyst values and 48% of the false negative SCreat had abnormally elevated SCyst. CONCLUSION: This study suggests that SCyst is not more sensitive than SCreat or C(CG) for detecting renal failure, however, SCyst could be proposed as a confirmatory test for patients with elevated SCreat.

[Effects of amiodarone on thyroid hormonal profile. Updating based on new assay methods]. / Effets de l'amiodarone sur le profil hormonal thyroïdien. Actualisation à propos de nouvelles méthodes de dosage.

Amiodarone (A) treatment alters the levels of thyroid hormones. We investigated whether new hormonal assays are also altered by this drug. Thyroid function was determined in 21 patients chronically treated with A and in 30 controls. TSH was determined with a third generation assay. Free T3 and Free T4 levels were determined by 5 different immunoassays. Equilibrium dialysis (E.D.) was considered as the reference assay for FT3 and FT4. With this method FT3 is diminished, reverse T3 ans FT4 are increased whereas TSH remained normal. Only FT3 determined by an assay using a labelled monoclonal antibody (MAB) appears not modified by A. Other methods (chromatography, chemiluminescence and radioisotopic) give results in agreement with E.D. Some of these alterations may be explained by a marked increase in plasma levels of non esterified fatty acids. Hormonal changes induced by A are typically with all but one assays. Whatever the method used the determination of TSH remains necessary to avoid misinterpretation of the thyroid function tests in A-treated patients.

Receiver operating characteristic analysis: a useful method for a comparison of the clinical relevance of two in vitro IgE tests.

BACKGROUND: The objectives of this study were to demonstrate the usefulness of Receiver Operating Characteristic (ROC) analysis in the definition of a positive threshold in the comparison of two in vitro tests for detecting IgE antibodies and to determine the clinical relevance of specific IgE tests according to the sensitivity and specificity determined by ROC analysis. METHODS: Specific IgE levels were compared with the use of both MATRIX (Abbott Laboratories, Chicago, Ill.) and PHADEZYM (Pharmacia, Uppsala, Sweden) tests in 109 patients: 86 allergic patients and 23 control subjects. All allergic patients had a clinical history of allergy to mite, cat, grass pollen, or birch pollen and positive skin prick test results to the suspected allergen. Using various levels of specific IgE, we determined the points of the ROC curves with the best ratio of true positives to false positives for four aeroallergens (i.e., mite, cat, grass pollen, and birch pollen). RESULTS: Except for mite allergen there was no correspondence between the positive threshold values determined by ROC analysis with MATRIX and PHADEZYM tests. In terms of class, when ROC analysis was used, the threshold was class III with the MATRIX test and class II with PHADEZYM test for cat, grass pollen, and birch pollen and class III for mite. According to the threshold value, sensitivity and specificity for MATRIX and PHADEZYM tests were similar except for cat, for which the PHADEZYM test had a lower sensitivity (0.71) than the MATRIX test (0.90). With mite allergen the predictive value of only one positive MATRIX test result was 0.96. The specificities of MATRIX and PHADEZYM tests were 100% in both nonatopic and atopic control groups. CONCLUSIONS: We conclude that ROC analysis is a reliable method for comparing IgE in vitro tests and that it emphasizes the lack of correspondence between arbitrary units given for each in vitro test. ROC analysis appears to be a good method for helping to standardize IgE in vitro tests.

[A trial of stimulation with tamoxifen of progesterone nuclear receptors in patients with kidney cancer]. / Essai de stimulation par le tamoxifen des récepteurs nucléaires à la progestérone chez les patients porteurs de cancer du rein.

Stimulation of progesterone receptors synthesis by Tamoxifen was tried in 19 patients with renal cell carcinoma. No difference was found between this series and 51 controls.

Nine days post-thawing red cell conservation in a synthetic medium. Biochemical studies.

The expiration of thawed red cells (RBC) currently is 24 hours. This leads to problems in current transfusion practice, and often wastes rare and costly products. To remedy this situation, we developed a synthetic medium containing 0.085 g per l adenine, 5 g per l glucose, 48.0 g per l sucrose, 0.75 g per l NaH2PO4.H2O, 4 g per l Na2HPO4.2H2O, and 2.5 g per l NaCl, with a pH of 7.40, and an osmolarity of 320 mOsm. After 15 days post-thawing storage at 4 degrees C in our medium, the viability and function of RBC were maintained. We propose the storage of thawed RBC at 4 degrees C in our medium for up to 9 days: sterility was maintained, pH was 6.80, and 2,3-diphosphate glycerate was 50 percent, and adenosine triphosphate 100 percent of the original values. Free hemoglobin was 122 mg per unit, adenylate energy charge was 0.90, and RBC labeled 7 days after thawing showed 89 percent survival 24 hours after transfusion and a one-half disappearance of 22 days.

[Correlation between various lipid and apolipoprotein parameters and clinical severity in arteriopathy of the lower limbs]. / Corrélation entre différents paramètres lipidiques et apolipoprotéiniques et la gravité clinique dans l'artériopathie des membres inférieurs.

We have compared the serum levels of lipids (cholesterol, triglycerides, high density lipoprotein cholesterol), apolipoproteins (Apo Al and Apo B) and two ratios (HDL cholesterol/VLDL + LDL cholesterol and Apo Al/Apo B) between a population of 180 patients with atheromatous member lesions, divided into four sub-groups with respect to clinical severity, and one of 121 controls without lesions. It seems that the most discriminative values linking to the severity of atherosclerotic manifestations are levels of Apo B, ratio Apo Al/Apo B and with a lower efficiency ratio HDL cholesterol/VLDL + LDL cholesterol.

Forensic significance of postmortem estimation of the blood cerebrospinal fluid barrier permeability.

Albumin concentration in cerebrospinal fluid (CSF) and plasma was determined in 44 cadavers divided into three groups on the basis of death agony duration. The same was determined in a control group of 42 patients with no demonstrable neurological disease. Following Schuller's method, the evaluation of the blood CSF barrier permeability was based upon the rate of albumin transfer from plasma to CSF. An average increase of 9% in blood CSF barrier permeability was found in cases of a long-duration death agony but not in cases of short-duration death agony (sudden deaths) or in the control group. We consider these results to be related to the hypoxia and hypercapnia which characterize the agonic suffering period. Therefore, we conclude that the postmortem determination of the rate of albumin transfer from plasma to CSF could be a reliable indicator of the duration of the agonic process.

[Comparative study on the concentrations of steroid receptors in adenomatous and cancerous prostatic tissue]. / Rapport preliminaire d'une étude comparative des concentrations en récepteurs steroïdiens de tissus prostatiques adénomateux et cancereux.

In this preliminary study, we have determined the receptors in normal human prostatic tissue or from patients with benign prostatic hypertrophy and patients with prostatic cancer. A single point assay using a dextran-coated-charcoal treatment of cytosol is utilized. This method permits the elimination of endogenous steroids and is also useful when specimens are too small to provide the larger number of aliquots necessary for multiple steroid receptor analyses. The results are discussed in the light of several problems inherent to this assay. We conclude that adenoma-tissue contains more receptors than neoplasic tissues for the progesterones receptors but that there is no significant difference for the estrogen-receptor and the androgen-receptors. For all the adenoma tissues and some neoplasic tissues the level of the estrogen-receptors is always lower than the one for androgen-receptor which itself is lower than the one for progesterone-receptors. We think that the expression of the results as a ratio of two levels of steroid-receptors gives a better evaluation of the receptors. The ratios Progesterone-receptor Estrogen-receptor and Androgen-receptor/Estrogen-receptor are always greater than 1.5, except for some neoplasic tissues and we think that, as in breast tumors, there are perhaps two kinds of neoplastic tissues, one hormone-dependent, the other not.

[Cholesterol in serum high density lipoprotein fraction (author's transl)]. / Cholestérol de la fraction lipoprotéine de haute densité.

The risk of atheroma can be assessed and valid epidemiological surveys can be carried out by measuring cholesterol in serum high density lipoprotein fraction (HDL) and calculating the HDL cholesterol: VLDL + LDL ratio. This was done in 39 patients free from surgically confirmed atheromatous lesions and in 51 patients presenting with such lesions. Of the four different techniques used for separation in these patients (ultracentrifugation, precipitation with heparin-Mn2+, precipitation with phosphotungstate-Mg2+ and electrophoresis), precipitation with phosphotungstate-Mg/2+ seems to be the most suitable, since there is no degradation of the HDL fraction as during electrophoresis on polyacrylamide gel, and less floculation of the supernatant after separation. Contrary to ultracentrifugation, which requires sophisticated equipment and good technical skill, the technique is easily carried out.

[Are serum acid phosphatase levels of diagnostic significance in prostatic cancer? (author's transl)]. / Le dosage des phosphatases acides est-il significatif dans le bilan d'un cancer de la prostate?

The abnormal serum level of "prostatic" acid phosphatases, stresses a cellular alteration but without an own specificity allowing to certify that it is related to a prostatic affection. One could expect that during the following years thanks to the immunological and electrophoretic methods one can be able to detect in serum specific enzymes issued from a tissue which is in a definite physiopathological state.

A new method for determination of oxalate in blood serum by gas chromatography.

A method for the determination of blood oxalate by gas chromatography is described. After clarification of the serum with acetone, the oxalate was extracted, ethylated and analysed on a gas chromatograph. The concentration of oxalate in the sample was determined by comparison with the elution pattern of diethylmalonate used as an internal standard. Using this technique, the recovery of added oxalate was more than 80%. Normal subjects were found to have blood oxalate levels of 27 mumol/l or less.