[Alterations of ovarian reserve tests in Human Immunodeficiency Virus (HIV)-infected women]. / Altérations des marqueurs de la réserve ovarienne chez les femmes infectées par le virus de l'immunodéficience humaine.

OBJECTIVES: Little is known about the impact of highly active antiretroviral therapy or HIV infection itself on the ovarian function. The aim of this study was to evaluate ovarian function in HIV-infected women in comparison with normal values from non-HIV infected women. PATIENTS AND METHODS: This is a prospective pilot study using markers of ovarian function: the antral follicular count (AFC) defined between cycle days 7 and 10 and follicle-stimulating hormone (FSH), inhibin B and antimüllerian hormone (AMH) for early follicular phase hormonal assessments. A descriptive analysis according to age was performed. RESULTS: Results from 78 HIV positive women are presented. AFC shows a high rate of abnormal values (63 %) occurring surprisingly early. The hormonal markers are concordant with a 36, 57 and 23 % abnormal rate for FSH, inhibin B and AMH respectively. DISCUSSION AND CONCLUSION: In our series, HIV seropositivity was associated with stigmas of premature ovarian insufficiency. This may explain impaired fertility but also suggests premature menopause in this population that should therefore be monitored early for such changes.

Oral cobalamin therapy for the treatment of patients with food-cobalamin malabsorption.

BACKGROUND: The standard treatment for cobalamin (vitamin B(12)) deficiency involves regular intramuscular cobalamin injection. It has been suggested that oral cobalamin therapy may be effective for treating patients who have food-cobalamin malabsorption. SUBJECTS AND METHODS: We prospectively studied 10 patients with cobalamin deficiency and well-established food-cobalamin malabsorption who received 3000 microg or 5000 microg of oral crystalline cyanocobalamin once a week for at least 3 months. Complete blood counts and serum cobalamin, homocysteine, and folate levels were determined at baseline and after 3 months of treatment. Patients were reexamined after 6 months. RESULTS: After 3 months of treatment, all patients had increased hemoglobin levels (mean increase, 1.9 g/dL; 95% confidence interval: 0.9 to 3.9 g/dL;P <0.01 compared with baseline) and decreased erythrocyte cell volume (mean decrease, 7.8 fL; 95% confidence interval: 0.9 to 16.5 fL;P<0.001). However, 2 patients had only minor, if any, responses. Serum cobalamin levels were increased in all 8 patients in whom it was measured. CONCLUSION: Our findings suggest that moderate doses of crystalline cyanocobalamin given orally may be an effective treatment for food-cobalamin malabsorption.

Repeated inhalation of low doses of cat allergen that do not induce clinical symptoms increases bronchial hyperresponsiveness and eosinophil cationic protein levels.

The aim of this study was to investigate whether repeated exposure to subclinical doses of cat allergens, not inducing asthma symptoms, could affect eosinophil cationic protein (ECP) levels in bronchoalveolar lavage (BAL) or in peripheral blood, without the appearance of clinical symptoms. Twelve patients with mild asthma, all sensitized to cats and not exposed to cat allergen at home, underwent a series of inhalations of cat allergen or placebo for 8 days over 2 weeks. A methacholine challenge was performed before and after the allergen and saline exposures, and BAL and blood were sampled for ECP measurements and eosinophil counts. No patients experienced asthma symptoms. However, PD20 methacholine (geometric mean) decreased significantly from 263 microg before to 126 microg after inhalation of allergen. Inhalation of saline did not induce any significant change in PD20. The change in log PD20 before and after cat allergen exposure was statistically different from the change in log PD20 before and after saline. Median ECP levels in BAL and serum increased significantly after allergen exposure, from 0.8 to 3.1 microg/l (p<0.02) and from 15.9 to 31.4 microg/l (p<0.05), respectively. No change was observed after saline inhalations. The change in BAL and serum ECP levels was statistically significant compared to that in the control group. The number of eosinophils did not change, however, nor did IL-5 and RANTES levels in BAL and serum. In conclusion, our results show that (1) exposure of asthma patients to repeated low doses of allergen, which did not provoke any clinical symptoms, is capable of inducing a local eosinophil activation associated with an increase in nonspecific bronchial hyperresponsiveness and (2) the increase in serum ECP levels due to eosinophil activation precedes the occurrence of asthma symptoms and may thus be a marker of allergen exposure in allergic asthma.

Cyfra 21-1 as a biologic marker of non-small cell lung cancer. Evaluation of sensitivity, specificity, and prognostic role.

BACKGROUND: Cytokeratins are epithelial markers whose expression is not lost during malignant transformation. Cyfra 21-1 is a cytokeratin-19 fragment that is soluble in serum and may be a useful circulating tumor marker. STUDY OBJECTIVE: The aims of this study were (1) to confirm sensitivity and specificity of Cyfra 21-1 in detecting non-small cell lung cancer (NSCLC) and especially the squamous cell subtype, (2) to assess the potential relationship between Cyfra 21-1 and disease stage of the disease in NSCLC, and (3) to evaluate prognostic effect of Cyfra 21-1 in NSCLC. METHODS: An immunoradiometric assay of serum Cyfra 21-1 was performed in 161 patients with lung cancers and 71 others with benign lung diseases. The ability of Cyfra 21-1 to detect different histologic subtypes of lung cancer vs benign lung diseases was assessed through receiver operating characteristic (ROC) curves and comparisons with other tumor markers such as carcinoembryonic antigen, neuron-specific enolase, and squamous cell carcinoma antigen. Comparisons of Cyfra 21-1 levels according to histologic subtype and disease stage were done using Kruskal-Wallis test. Independent prognostic value of Cyfra 21-1 was studied with a multivariate analysis of survival (Cox's model). RESULTS: Using a threshold of 3.3 ng/mL for Cyfra 21-1, sensitivity and specificity were, respectively, 0.59 and 0.94 in NSCLC, 0.68 and 0.94 in the subgroup of the squamous cell carcinoma, and 0.19 and 0.94 in small cell lung cancer. Cyfra 21-1 levels were significantly higher in advanced NSCLC than in early-stage disease. All 29 patients with serum concentrations > 32 ng/mL had stage IIIB-IV and only one of 14 patients with stage I-II disease had Cyfra 21-1 level > 18 ng/mL. In the multivariate analysis of survival, Cyfra 21-1 was an independent prognostic factor along with performance status and disease stage in NSCLC. CONCLUSIONS: Cyfra 21-1 is a sensitive and specific tumor marker of NSCLC, especially of squamous cell subtype. It also reflects the extent of the disease and has an independent prognostic role along with performance status and disease stage in NSCLC. IMPLICATIONS: A high level of Cyfra 21-1 in apparently early-stage NSCLC should be an indication for more extensive workup before thoracotomy. The independent prognostic role of Cyfra 21-1 level may be useful in stratifying populations with advanced NSCLC or early-stage resected NSCLC as elevated Cyfra 21-1 levels might identify those patients at high risk for treatment failure.

[High resolution autoradiographic detection of beta-gamma emitters in biological tissues: case of Indium 111]. / Détection autoradiographique à haute résolution d'émetteurs beta-gamma dans les tissus biologiques: cas de l'Indium 111.

The present paper proposes an efficient autoradiographic procedure for the microscopic localisation in biological tissues of both low energy electrons and electrons released at relatively high energy. These are emitted by radioactive tracers, decaying by electron capture and/or internal conversion, that are increasingly used in biology and medicine. A detailed inventory of the corpuscular and electromagnetic radiations has been established in the specific case of Indium-111, with emphasis placed on those presenting an autoradiographic interest. As far as the electromagnetic component is concerned, the probability for producing secondary electrons as a function of distance from the source has been calculated. The range of the electrons in the emulsion and in a tissue-like medium has also been taken into account. The comparison with experiments using isolated lymphocytes labelled with 111In-oxine confirms the feasibility to localize and quantify with a high resolution beta-gamma emitters within biological systems by autoradiographic imaging.

[Monoclonal anti-AFP immunoscintigraphy of human hepatocellular carcinoma. Influence of biological, anatomical and vascular factors]. / Immunoscintigraphie monoclonale anti-AFP du carcinome hépatocellulaire humain. Influence des facteurs biologiques, anatomiques et vasculaires.

The actual interest of immunoscintigraphy for the detection of alphafetoprotein-producing liver tumors was investigated by both visual examination and quantitative analysis in 61 patients with either hepatocellular carcinoma (39 patients, group I), secondary liver cancer (11 patients, group II), or non tumoral liver (9 cirrhosis, 2 healthy liver, group III): All patients received injections of 123I-anti-alphafoetoprotein monoclonal antibodies and planar scans were performed after 28 hours. Only 18 out of 39 hepatocellular carcinoma-bearing patients had a positive scan (46 p. 100). Such a moderate sensibility was due to a striking inhibitory influence of cirrhosis: the positivity rate was 6/24 and 12/15 respectively when hepatocellular carcinoma was and was not associated with cirrhosis (p less than 0.01). Specificity was also moderate (55 p. 100) for detection of hepatocellular carcinoma in tumor-bearing patients (group I and II). In the absence of cirrhosis, the intensity of the tumoral uptake was highly correlated with high serum alphafoetoprotein level (p less than 0.001) and tumor arterial hypervascularization (p less than 0.01). Anti-alphafoetoprotein monoclonal antibody uptake by the extratumoral liver was found to be very specific of hepatocellular carcinoma since it was high in 23 out of 39 patients of group I but in only 1 out of 22 in groups II and III (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Is anti-alphafetoprotein immunoscintigraphy a promising approach for the diagnosis of hepatoma? Implications of a quantitative study in 41 patients.

The actual interest of immunoscintigraphy for the detection of liver tumours was investigated by both visual examination and quantitative analysis in 41 patients with hepatoma (HCC, 21 cases, 13 AFP-secreting), other primary or secondary liver cancer (9 cases), testicular cancer (2 cases) and cancer free cirrhosis (9 cases). All patients were injected with 123I-anti-alphafetoprotein (AFP) monoclonal antibodies (MAbs) and scans were performed after 28 +/- 2 h. In the hepatoma-bearing patients, 11 positive anti AFP scans were found; 9 of them had an enhanced serum; besides, 3 non HCC tumours were also detected. With respect to hepatoma diagnosis, sensitivity was 52.5% and specificity 66.5%. For all hepatomas, it was striking that the positivity rate was 2/10 and 9/11, respectively, when HCC was and was not associated with cirrhosis. Among 6 patients with a positive anti AFP scan who were also injected with control anti hCG 123I-MAb, 5 positive anti hCG scans were surprisingly found, with specificity indices ranging between 1.00 and 1.75. The quantitative study also highlighted the importance for hepatoma detection of specific and non specific factors such as serum AFP, tumoural vascularization, non tumoural liver uptake and intrahepatic distribution of HCC. Anti AFP immunoscintigraphy appears as a poorly sensitive and moderately specific method for hepatoma diagnosis. In contrast, non tumoural liver uptake level could be more useful for discriminating HCC from liver metastases and perhaps to detect the early extension of HCC.