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OBJECTIVE The objective of this study is to study factors associated with HIV-DNA levels in chronically infected patients on long-term suppressive antiretroviral therapy (ART). DESIGN A cross-sectional, multicentre study of patients receiving ART for more than 3 years, HIV-RNA less than 50 copies/ml for more than 2 years and CD4 cell count more than 350 cells/μl. METHOD Factors associated with low ( 1000), compared with intermediate (150-1000 copies/10 PBMCs) levels of HIV-DNA were investigated using multinomial logistic regression. RESULTS Five hundred and twenty-two patients who initiated ART during the chronic phase were included (71% male; median peak HIV-RNA: 4.88 log10 copies/ml, CD4 cell count nadir: 222 cells/μl). Median ART duration was 13 years [interquartile range (IQR) 7-17], viral suppression was 5.7 years (IQR 3.9-8.5) and 66% of the patients never experienced ART failure. Median HIV-DNA was 323 copies/10 PBMCs (IQR, 129-717) with low, intermediate and high levels observed in 28.3, 55.4 and 16.3%, respectively. In multivariable analysis, women were more likely to achieve a low level of HIV-DNA. Each additional year with suppressed HIV-RNA increased the likelihood of low level and decreased the likelihood of high level of HIV-DNA. Peak HIV-RNA higher than 5log10 was always associated with a decreased risk of low and an increased risk of high HIV-DNA. For patients with peak HIV-RNA lower than 5log10, past ART failure was associated with high level of HIV-DNA. CONCLUSION Chronically HIV-infected patients with long-term suppressive ART can achieve low total HIV-DNA but one over six still presented HIV-DNA above 1000 copies/10 PBMCs despite long-term viral suppression.

International audience; Direct-Acting Antivirals (DAAs) opened a new era in HCV treatment. We report the impact of HCV treatment in French HIV-HCV coinfected patients. METHODS: All HIV-HCV patients from the Dat'AIDS cohort followed between 2012 and 2015 were included. HCV status was defined yearly as naive, spontaneous cure, sustained virological response (SVR12), failure or reinfection. RESULTS: Among 32,945 HIV-infected patients, 15.2% were positive for anti-HCV antibodies. From 2012 to 2015, HCV incidence rate increased from 0.35%PY to 0.69%PY in MSM, while median incidence was 0.08%PY in other patients. Median reinfection rate was 2.56%PY in MSM and 0.22%PY in other patients. HCV treatment initiation rate rose from 8.2% in 2012 to 29.6% (48.0% in pre-treated patients vs 22.6% in naïve patients). SVR12 rate increased from 68.7% to 95.2%. By the end of 2015, 62.7% of the patients were cured either spontaneously or following SVR. CONCLUSIONS: HCV treatment dramatically increased in HIV-HCV patients in France from 2012 to 2015 resulting in HCV cure in nearly two-thirds of the patients in this cohort. Combined with a declining HCV prevalence, the prevalence of active HCV infection among HIV patients will drastically decrease in the forthcoming years.

Given the low detection rates of CSF IgG-Oligoclonal bands (IgG-OCB) in non-European Multiple Sclerosis (MS) patients and higher specificity of the MRZH-reaction, we evaluated whether associating MRZH-reaction to CSF IgG-OCB detection improved investigation of suspected MS. Paired CSF and sera were analyzed for IgG-OCB and polyspecific viral antibodies. IgG-OCB were detected in 72% of MS patients and an MRZH-reaction in 67%. Combining IgG-OCB and MRZH raised detection of IgG abnormalities to 97% of studied MS patients. Detection of IgG-OCB and/or ≥2 MRZH antibodies showed sensitivity of 88% and specificity of 92% for MS, versus 72% and 96% for IgG-OCB alone.

International audience; Context: Maternally inherited diabetes and deafness (MIDD) is a rare form of diabetes with a matrilineal transmission, sensorineural hearing loss, and macular pattern dystrophy due to an A to G transition at position 3243 of mitochondrial DNA (mtDNA) (m.3243A>G). The phenotypic heterogeneity of MIDD may be the consequence of different levels of mutated mtDNA among mitochondria in a given tissue.Objective: The aim of the present study was thus to ascertain the correlation between the severity of the phenotype in patients with MIDD and the level of heteroplasmy in the blood leukocytes.Participants: The GEDIAM prospective multicenter register was initiated in 1995. Eighty-nine Europid patients from this register, with MIDD and the mtDNA 3243A>G mutation, were included. Patients with MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) or with mitochondrial diabetes related to other mutations or to deletions of mtDNA were excluded.Results: A significant negative correlation was found between levels of heteroplasmy and age of the patients at the time of sampling for molecular analysis, age at the diagnosis of diabetes, and body mass index. After adjustment for age at sampling for molecular study and gender, the correlation between heteroplasmy levels and age at the diagnosis of diabetes was no more significant. The two other correlations remained significant. A significant positive correlation between levels of heteroplasmy and HbA1c was also found and remained significant after adjustment for age at molecular sampling and gender.Conclusions: These results support the hypothesis that heteroplasmy levels are at least one of the determinants of the severity of the phenotype in MIDD.Heteroplasmy levels are at least one of the determinants of the severity of the phenotype of maternally inherited diabetes and deafness.

2 aberrant processes involved in the teratogenesis of round-headed sperm are focused on: acrosome development and nuclear differentiation. The spermatozoa of 1 infertile patient all appearing round-headed under a light microscope were analyzed using a scanning electron microscope a transmission microscope freeze etching cinematographic methods and electron probe analysis. Spermiogram revealed a head defect characterized by lacking acrosome and round and immature nucleoplasm occurring in nearly all cells and coiled tails in about half of the spermatozoa. Electron microscopic analysis showed an abortive development of acrosome whose primordium failed to attach the nucleus and expand regressing instead. The nuclei failed to shape and were retarded in maturing a disturbance apparently linked with the aplasia of hypolasia of the caudal manchette. Zinc appears to take a role in nuclear differentiation. The shape of the head in the movement pattern is discussed.(AUTHORS MODIFIED)

International audience; Background - Chronic kidney disease (CKD) is frequent in individuals infected with human immunodeficiency virus (HIV). Progression to end-stage renal disease can be slowed by appropriate medical management. Methods - To assess whether active promotion of guidelines improves CKD management, we conducted a cluster randomized controlled trial within the French Hospital Database on HIV (FHDH-ANRS CO4). We randomized 46 centers participating in the FHDH to either simple information on guideline availability or active promotion with a multifaceted and repeated intervention comprising reminders and audit feedback and targeting of local opinion leaders carried out between April 2009 and April 2010. Outcome measure was CKD management adequacy assessed before and 2 years after the beginning of the intervention in HIV-infected patients with moderate to severe CKD. CKD management was considered adequate in case of referral to a nephrologist or if proteinuria, blood pressure, low-density lipoprotein cholesterol level, and glycemia had been measured during the previous year and medications had been prescribed when necessary. Results - Three hundred six patients were enrolled, of whom 238 (78%) completed the 2 years of follow-up. During the study period, the percentage of patients receiving adequate CKD management improved from 64.1% to 70.4% (+6.3%) in the active arm and from 68.3% to 75.6% (+7.3%) in the control arm (adjusted mean difference, -0.7 percentage points [95% confidence interval: -9.2 to 7.9]; P = .95). The biggest impact of active promotion was on the management of proteinuria and blood pressure. Conclusions - Adequate compliance with CKD management guidelines improved slightly between 2009 and 2011, with no difference between the simple information and active promotion arms. Clinical trials registration - CCTIRS 10.150 and CNIL DR-2010-379.

In patients with maternally inherited diabetes and deafness (MIDD), due to 3 243 AG mutation of mitochondrial DNA (mtDNA), diabetes may present with variable phenotypes.To ascertain the existence of two distinct phenotypes, MIDD1 and MIDD2, in a series of patients with MIDD.Multicenter prospective study.77 patients with diabetes and the mtDNA 3243 mutation and 139 control patients with type 1 (T1D) or type 2 (T2D) diabetes, matched according to initial presentation of diabetes, age at onset, sex, and duration of diabetes (24 T1D and 115 T2D, including 55 treated with insulin).Anthropometric characteristics (height, body weight, body mass index [BMI], sex), family history of diabetes, and characteristics of diabetes (age at onset, treatment, hemoglobin A1c [HbA1c]), extrapancreatic manifestations.In 13 cases (17%, MIDD1), diabetes presented as insulin-dependent from the onset, with ketoacidosis in 6 cases. In 64 cases (83%, MIDD2), diabetes resembled T2D, and was treated with diet in 12 cases, oral hypoglycemic agents in 21 cases, or insulin in 31 cases. Compared with patients with MIDD2, patients with MIDD1 were characterized by lower age at onset of first manifestation of MIDD (25.4 +/- 9.6 vs 33.7 +/- 13.2 Years, P0.0005), lower body weight (49.1 +/- 7.4 vs 56.3 +/- 10.9 kg, P0.0025), lower BMI (18.2 +/- 2.3 vs 20.9 +/- 3.6 kg/m2, P0.0005), and higher HbA1c levels (9.5 +/- 2.0 vs 7.5 +/- 1.6%, P0.0005). Frequency of family history of diabetes and of extrapancreatic manifestations was the same in both MIDD subtypes. No difference was found within the MIDD2 subtype when comparing patients treated with or without insulin. Compared with matched controls, patients with MIDD had a lower BMI (MIDD1/T1D 18.2 +/- 2.3 vs 24.0 +/- 3.6 kg/m2 and MIDD2/T2D 20.9 +/- 3.6 vs 30.2 +/- 5.9 kg/m2, P0.0025). Lastly, male patients with MIDD had a shorter height than controls (MIDD1/T1D: 166.1 +/- 3.2 vs 177.3 +/- 6.6 cm and MIDD2/T2D: 168.4 +/- 7.2 vs 173.6 +/- 6.6 cm P0.025).These results confirm the existence of two different phenotypes in MIDD, MIDD1 and MIDD2, which may be related to the severity of the mitochondrial disease. The role of other genetic and/or environmental factors in the variable phenotype of MIDD remains to be elucidated.

Autoimmune manifestations are common both in patients chronically infected by hepatitis C virus, and in patients transplanted for non-autoimmune diseases. A correlation between interferon based treatment and autoimmune diseases or the development of autoantibodies is well established in non-transplanted patients, but few data are available about transplanted patients. It is unclear whether interferon may increase the incidence of acute cellular rejection and there are few reports on the development of atypical autoimmune manifestations during post-liver transplantation interferon or pegylated interferon treatment. We describe a case of systemic lupus erythematosus following treatment with pegylated interferon alfa-2b in a transplanted patient with recurrence of chronic hepatitis C. Our experience suggest that pegylated interferon may induce autoimmune diseases in the immunosuppressed host, different from acute cellular rejection and call for a great attention to possible autoimmune disorders development during interferon based treatments in liver transplanted patients.

In situ-perfused rat livers were infused with a single dose of 1.5 x 10(7) radiolabeled borreliae. Significant (P < 0.00005) differences in the liver uptake of the agents of Lyme borreliosis, Borrelia burgdorferi IRS, Borrelia afzelii VS461, and Borrelia garinii PBi, and that of the agents of relapsing fever, Borrelia hermsii, Borrelia parkeri, and Borrelia turicatae, were observed. The liver uptakes ranged between 65.9% for B. burgdorferi IRS and 40.5% for B. turicatae. Neither relapsing fever nor Lyme disease borreliae were recovered from infected livers when the livers were cultured in Barbour-Stoenner-Kelly II medium. The in vitro uptake of B. burgdorferi IRS by isolated rat Kupffer cells was rapid, and within 30 min of the infection, large intracellular aggregates of amorphous material were detectable by immunofluorescence with specific anti-B. burgdorferi antibody. The reculturing of B. burgdorferi IRS from Kupffer cells incubated for 24 h in RPMI medium before inoculation with bacteria was negative. The results obtained in this study indicated that borreliae are efficiently taken up and killed by rat hepatic macrophages in the absence of serum factors.

Renal biopsy specimens from 26 adult human immunodeficiency virus (HIV)-infected patients with glomerular involvement were reviewed from the files of three hospital pathology services in Northern Italy. All the patients were Italian and most (19 of 26 patients) were intravenous drug addicts. The types of glomerular lesions were as follows: minimal-change glomerulopathy (two cases), mesangial proliferative glomerulonephritis (GN) with scanty immunoglobulin deposits (four cases), and various patterns of immune complex-mediated glomerulonephritis, including postinfectious GN (six cases), membranoproliferative GN (one case), membranous GN (three cases), immunoglobulin (Ig) A nephropathy (four cases), a mixed membranous and proliferative (three cases) and diffuse proliferative lupus-like pattern with subendothelial deposits, and intraluminal thrombi (two cases) or subepithelial and subendothelial deposits (one case). None of the patients had evidence of HIV-associated nephropathy. Our study confirms previous observations on the low incidence of HIV-associated nephropathy among white HIV-infected patients in Europe, where immune complex-mediated GN seems to predominate. Apart from the frequent electron microscopic observation of endothelial tubuloreticular structures, none of the reported lesions could be distinguished on morphologic grounds from those occurring in uninfected patients. The high variability of the glomerular lesions upholds the need for accurate diagnosis for the clinician confronted with an HIV-positive patient with suspected glomerular involvement.

Of 44 pregnancies obtained at the Tenon Maternity Hospital by in vitro fertilization (IVF) using donated oocytes, 25 have already been completed by spontaneous delivery or cesarean section: 22 (88%) single; 2 (8%) twins, and 1 (4%) triple. The most frequently seen complications of pregnancy were hypertension (16%) and preterm labor in the last 3 months (12%). However, as compared to a control group of 275 pregnancies resulting from classical IVF, the only difference was a very high percentage of cesarean sections (72%). No fetal deaths or neonatal malformations were reported.

OBJECTIVE: Existing endoscopy-based data on gastro-oesophageal reflux disease (GORD) in the general population are scarce. This study aimed to evaluate typical symptoms and complications of GORD, and their associated risk factors, in a representative sample of the Italian population. METHODS: 1533 adults from two Italian villages were approached to undergo symptom assessment using a validated questionnaire and upper gastrointestinal endoscopy. Data were obtained from 1033 individuals (67.4% response rate). RESULTS: The prevalence of reflux symptoms was 44.3%; 23.7% of the population experienced such symptoms on at least 2 days per week (frequent symptoms). The prevalence rates of oesophagitis and Barrett's oesophagus in the population were 11.8% and 1.3%, respectively. Both frequent (relative risk (RR) 2.6; 95% confidence interval (CI) 1.7 to 3.9) and infrequent (RR 1.9; 95% CI 1.2 to 3.0) reflux symptoms were associated with the presence of oesophagitis. No reflux symptoms were reported by 32.8% of individuals with oesophagitis and 46.2% of those with Barrett's oesophagus. Hiatus hernia was associated with frequent reflux symptoms and oesophagitis, and was present in 76.9% of those with Barrett's oesophagus. We found no association between body mass index and reflux symptoms or oesophagitis. CONCLUSIONS: GORD is common in Italy, but the prevalence of Barrett's oesophagus in the community is lower than has been reported in selected populations. Both frequent and infrequent reflux symptoms are associated with an increased risk of oesophagitis. Individuals with oesophagitis and Barrett's oesophagus often have no reflux symptoms.

Interleukin-1α (IL-1α) and interleukin-2 (IL-2) levels were measured by radioimmunoassay in samples of conditioned medium from mononuclear cells taken from 20 normal subjects (14 adults ranging in age from 20 to 45 years and 6 children ranging in age from 3 to 11 years) and from 49 children with growth delay. Cultures were performed with 106 cells/ml in medium containing 1 % normal human serum and 4.8 g/l phytohemagglutinin M. The incubation was performed for 48 h in an atmosphere containing 5 % CO2. In normal subjects, the production of IL-lα was 38.5 ± 9.8 fmol/ml of conditioned medium (mean ± SEM) in 14 adults and 41.6 ± 3.0 fmol/ml in 6 children. The production of IL-2 was 46.9 ± 6.5 and 57.3 ± 10.5 fmol/ml, respectively. In the 16 patients with growth hormone (GH) deficiency studied before treatment, the production of ILs was significantly decreased in relation to the degree of deficiency. We observed a positive correlation between the produciton of IL-lα and the values of insulin-like growth factor I but not with serum GH values. IL-lα production was normalized after 15 days of substitutive GH therapy and IL-2 was normalized after 3 months of therapy. In 10 other patients with GH deficiency (4 with total and 6 with partial isolated GH deficiency) studied after long-term GH treatment (5 months or more), the mean of IL production was not significantly different from that of GH-deficient children treated for 3 months. In the 23 patients with constitutional delay of growth, we observed also a significant decrease in ILs compared to the control. No correlation was found between IL production and bone age ranging from 3 to 10 years. We conclude that GH is required for IL production.

Summary Background Incidence of hepatocellular carcinoma in hepatitis C virus-related cirrhosis is 4% per year. Although cost-effective, current screening could be improved. Aim To develop a statistical model including non-invasive parameters able to identify patients at high risk of developing hepatocellular carcinoma. Methods One hundred and fifty-eight patients (73F:85M) with compensated chronic hepatitis C virus liver disease underwent evaluation, including argyrophilic nucleolar organizer regions proliferation index, and were followed up for 56.18 ± 1.44 months. Results Fifty-six patients had chronic hepatitis without cirrhosis and low argyrophilic nucleolar organizer regions proliferation index (≤25%), 65 had hepatitis C virus-related cirrhosis and low argyrophilic nucleolar organizer regions proliferation index and 37 had hepatitis C virus-related cirrhosis and high argyrophilic nucleolar organizer regions proliferation index (>25%). Groups were similar for gender and viral genotype distribution. None of the patients with chronic hepatitis without cirrhosis developed hepatocellular carcinoma, compared with 6.1% of low argyrophilic nucleolar organizer regions proliferation index and 30.6% of high argyrophilic nucleolar organizer regions proliferation index (P = 0.002). By multivariable logistic regression analysis, the following parameters were independently associated with hepatocellular carcinoma development and used for the development of the statistical model: platelets (OR 0.98), γ-globulins (OR 0.111), alanine aminotransferase/aspartate aminotransferase ratio (OR 0.07), serum ferritin (OR 1.0) and ultrasonographyc pattern (coarse OR 2.9, coarse nodular OR 10.12). The statistical model properly allocated 95.9% of patients with low argyrophilic nucleolar organizer regions proliferation index and 72.2% of patients with high argyrophilic nucleolar organizer regions proliferation index. Conclusions The model, to be validated in large prospective studies, may help tailoring screening according to the risk of hepatocellular carcinoma development.

Unidimensional. Response Evaluation Criteria in Solid Tumor (RECIST) has been recently proposed in the attempt to simplify the standardized bidimensional World Health Organization (WHO) criteria. The complete accord between these two measurement systems was established in a large comparative study [J. NatL Cancer Inst. 92(3) (2000) 205] that demonstrated the validity and the good performance of RECIST criteria. We report four cases of inadequacy of RECIST criteria in the evaluation of response to chemotherapy in patients with malignant pleural mesothelioma. These four patients were enrolled in two consecutive multicenter phase II clinical trials investigating the activity of a novel chemotherapy regimen in advanced pleural mesothelioma. They were judged as having an objective response to chemotherapy according to WHO criteria. Reassessed according to both methods, we found that results obtained with RECIST criteria do not correspond to WHO underestimating response to chemotherapy. Our data raise doubts about the applicability of unidimensional RECIST response criteria to mesothelioma and, possibly, to any tumor involving the chest wall. (C) 2003 Published by Elsevier Ireland Ltd.

CD44 is a transmembrane glycoprotein involved in cell-cell and cell-substrate interactions. As a cell surface molecule, CD44 may be shed or released into the circulation by proteolytic enzymatic mechanisms. Therefore, soluble CD44 can be found in cell culture supernatants as well as in plasma. In this study we evaluated the levels of soluble total CD44 (sCD44) in serum samples of patients with breast and colorectal carcinoma as well as non-Hodgkin's lymphoma in order to correlate prognosis with sCD44 expression. Besides, we evaluated other clinical tumour markers routinely used, Cancer Antigen (CA) 15.3 and CA 19.9. We investigated 132 serological samples from breast cancer patients, 48 sera from colorectal tumours, 48 samples from stage IV non-Hodgkin's lymphoma and sera from 80 individuals without evidence of cancer or autoimmune disease. Breast cancer patients were divided into three groups: a) patients with no clinical evidence of positive nodules and no metastatic disease; b) patients with positive nodules; and c) patients with metastasis. sCD44 mean serum levels in these groups were 198+/-54 ng/ml, 221+/-78 ng/ml and 242+/-119 ng/ml, respectively, while the marker CA 15.3 values were 15.6+/-6.6 U/ml, 14.0+/-5.8 U/ml and 211.5+/-358.9 U/ml, respectively. sCD44 levels for colorectal tumour were 243+/-72 ng/ml, while CA 19.9 serum levels were 230+/-270 U/ml. Stage IV non-Hodgkin's lymphoma sCD44 levels were 398+/-160 ng/ml. sCD44, CA 15.3 and CA 19.9 values for healthy individuals without evidence of any cancer pathology were 223+/-58 ng/ml, 16.4+/-6.2 U/ml and 33+/-14 U/ml, respectively. From these results we conclude that sCD44 might be used as a reliable marker for patients with non-Hodgkin's lymphoma. However, sCD44 levels failed to correlate with prognosis, tumour burden or metastasis in breast and colorectal cancer patients. Neither was any correlation found between high CA 15.3 or CA 19.9 levels and soluble CD44 serum level.

The raised incidence of myocardial infarction and sudden death in diabetics was explained over 20 years ago by the increase in prevalence and severity of coronary atherosclerosis. Coronary angiographies of 820 consecutive patients admitted to hospital for coronary artery disease were analysed. One hundred and fifteen of these patients (14%) were diabetic. In 77.4% of diabetics and 72.6% of non-diabetics, coronary angiography showed coronary lesions which were usually distal and three vessel in diabetics. When the three coronary arteries were analysed globally, the percentage of patients with at least one mild stenosis was much higher in diabetics than in non-diabetics (50.6% vs 30.3% respectively, p0.001), but there was no statistical difference in the number of severe stenoses or occlusions. The increase in mild stenosis in the diabetic population could indicate an anatomical predisposition to future rupture of a plaque. This result could explain the increased frequency of myocardial infarction and sudden death in diabetes, not necessarily preceded clinically by angina pectoris.

The aim of this study was to evaluate the efficacy of human lymphoblastoid interferon-α treatment in chronic sporadic-type non-A, non-B hepatitis. We also aimed to determine if histological or liver function data could predict either response or relapse. Sixty patients with chronic sporadic-type non-A, non-B hepatitis were randomized in two groups of 30. One group was treated with interferon-α (3 MU thrice weekly) for one year; the other group was untreated controls. The treated group was followed for another year after interferon withdrawal. Liver function tests were performed during treatment. Liver biopsy was carried out before and a year after randomization. We evaluated rate of response [normalization of alanine aminotransferase (ALT) levels for at least three consecutive months] and rate of relapse (ALT rebound after therapy suspension). We also looked at possible predictive factors for response and relapse. In the treatment group the rate of response was 55% (16/29). No control patient exhibited ALT normalization. Among the responders, 31% (5/16) relapsed after interferon withdrawal. Low gamma GT and female sex are positive predictive factors of response (P

Summary OBJECTIVE We report clinical, biochemical, morphological and histological data of phaeochromocytoma in 40 French families and in apparently sporadic cases of multiple endocrine neoplasia (MEN) type 2 A (medullary thyroid carcinoma, phaeochromocytoma, with or without hyperparathyroidism). DESIGN This retrospective study was obtained from cases registered by the‘Groupe d'Etudes des Tumeurs a Calcitonine’ from 1968 to 1990. We analysed the cases having sufficiently precise data on phaeochromocytoma with Pigas Software. PATIENTS Characteristics of phaeochromocytoma In 100 patients with MEN 2 A were reviewed. Phaeochromocytoma was bilateral in 51 %. The disease was inherited in 94 patients from 40 families (40 probands, 54 relatives), and was apparently sporadic In six. RESULTS In this series, diagnostic circumstances were highly suggestive of phaeochromocytoma in 39.8% of the cases, whereas in 43.2%, diagnosis was made through systematic investigations of patients, either before (27.3%) or after (13.6%) thyroidectomy, or after discovery of hyperparathyroidism (2.3%). Fifteen per cent of patients were detected by family screening. Sudden death occurred in 8.9%, malignant phaeochromocytoma In 3%, and ectopic tissue in 4% of the cases. Urinary metanephrines appeared to be the most sensitive screening test. The extent of clinical symptoms was not associated with a particular hormonal pattern. Bilateral adrenalectomy was performed in 60% (in one step in 50%, in two steps in 10%). In these patients, bilateral histological lesions were observed in 92.5%. Simultaneous diagnosis for adrenal and thyroid disease was made in 73.4%, but phaeochromocytoma may be diagnosed before (9.6%) or after (17%) medullary thyroid carcinoma, with an interval greater than 2 years in 25 cases. CONCLUSION Owing to variable clinical symptoms of phaeochromocytoma in these 100 cases of MEN 2 A, systemic biological adrenal assay is required. The search for phaeochromocytoma in medullary thyroid carcinoma (and vice versa) has to be systematically performed, even in apparently sporadic cases. Screening for phaeochromocytoma must be repeated for years, owing to the frequency of bilateral adrenal disease.

The intestinal absorption of bile acids (BA) with different chemical structure has been evaluated in the rabbit, after intestinal infusion of different concentrations (025–30 mM) of BA, by mesenteric blood sampling. Cholic (CA), chenodeoxycholic (CDCA), ursodeoxycholic (UDCA) acid, free and taurine (T‐) conjugated, together with glycocholic (GCA) acid and deoxycholic acid (DCA) were studied. The apparent uptake parameters were calculated. All conjugated BA showed active transport (T max, nmol min‐1 cm‐1 int.), with Tmax values in the following order: TCA > TUDCA > TCDCA; uncon‐jugated BA showed passive uptake, with values in the following order: DCA > CDCA > UDCA > CA. GCA and CA showed both passive uptake and active transport. For all BA studied the % uptake in the ileal segment considered was less than 10%, BA uptake being thus limited by transport and/or diffusion kinetics, rather than by flow velocity. The liquid resistance to BA radial diffusion inside the lumen was evaluated, and the infusate‐to‐blood uptake parameters corrected for it, in order to get the uptake parameters from the epithelium‐to‐liquid interface to mesenteric blood: the apparent Km decreased, passive uptake coefficient increased, while Tmax was unchanged. The passive component of the uptake, corrected for the luminal resistance, correlated with the BA hydro‐phobicity (r = 0–963; P

We selected 37 cases, followed-up for more than 36 months or until death, from a series of 45 patients affected by acute renal failure due to multiple myeloma in order to identify the parameters that could allow the outcome to be predicted. The patients were allocated to group 1, consisting of 27 patients who died within one year and to group 2, consisting of 10 patients who survived for more than 36 months. Renal failure was severe enough to require dialysis in 28 patients, 16 of whom were oliguric. Renal biopsy was performed in 23 cases, whereas light chain isoelectric point and serum beta 2-microglobulin levels were evaluated in each patient. All the patients underwent chemotherapy, which was associated with plasma exchange in 16 patients. Statistical analysis of the potential prognostic factors in the 2 groups showed that the incidence of hypercalcemia, infection, irreversible renal failure and severe tubulo-interstitial damage was significantly higher in group 1. Sex, tumor load, severity of renal failure and light chain isoelectric point had no prognostic significance. Finally, the number of patients treated by plasma exchange was significantly higher in group 2. Our results underline the prognostic role of both hypercalcemia and infection and justify aggressive treatment consisting of chemotherapy, plasma exchange and dialysis, even in cases of severe renal failure and high tumor load.

We have previously shown that immunoassayable concentration of somatostatin (SRIH) was elevated in 70% of 34 consecutive medullary thyroid carcinoma (MTC) tissue samples. In the present study gastrin releasing peptide (GRP)-like immunoreactivity was measured in tissue extracts from these 34 MTC (25 inherited, 7 sporadic, 2 unclassified) and in 7 normal thyroid tissue. Plasma SRIH, calcitonin (CT) and carcinoembryonic antigen were assayed in all patients. Normal thyroid tissue contained less than 61 pmol GRP per g wet weight; in contrast GRP concentration was elevated (62-7800 pmol/g) in 32/34 tumor extracts. The distribution of tissue GRP values were similar in sporadic as well as in familial MTC. We found no significant correlation between tumor GRP concentration and plasma SRIH (r = -0.05), plasma CT (r = -0.24), or plasma carcinoembryonic antigen levels (r = -0.21). Tumor concentrations of immunoreactive GRP and SRIH were positively correlated when logarithmic transformation was used (P less than 0.01). Thus GRP, as well as SRIH, is a major product of tumoral C cells in human MTC when systematically evaluated in a large number of cases.

The local and systemic effects, as well as the repair mechanisms, of sterile absolute ethyl alcohol injection were evaluated at a range of doses (0.1-2.0 mL/kg body weight) in rabbit liver in order to confirm the feasibility and safety of local treatment of tumours in man. Saline injection was used in the control animals. The animals were killed at varying intervals (range: 1-30 days after injection), and the liver was studied by gross and microscopic examination. The ethyl alcohol injection was well tolerated and did not induce significant systemic side-effects. All doses could induce necrosis and none proved to be lethal. The alcohol injection produced an area of coagulation necrosis, the size of which appeared to be dose-related, and which was surrounded by granulation tissue, gradually repairing the necrotic lesion; the adjacent tissue was intact, or had signs of mild steatosis. However, at higher doses (1.0 and 2.0 mL/kg bodyweight), necrotic lesions were observed in the liver both near and remote from the site of injection. Fine needle percutaneous alcohol injection is effective in producing necrotic lesions which appear to be dose-related; at higher doses, however, an unpredictable intrahepatic diffusion may occur.

The intestinal absorption of bile acids has so far been studied from the measurement of the biliary secretion after their intestinal infusion. In the present investigation, the ileal absorption capacity for two different bile acids has been evaluated by means of an intestinal perfusion technique and the simultaneous blood drainage from the mesenteric vein corresponding to the isolated loop. Taurocholic acid and unconjugated cholic acid were infused at different concentrations (0.5-10.0 mM), at a flow rate of 4 ml/min/cm intest. Taurocholic acid absorption increased to a maximum with dose, then reaching a plateau, suggesting that a saturable process had taken place. Cholic acid uptake showed a saturable, possibly active, process, together with a nonsaturable one. These results are consistent with the physicochemical properties of the two bile acids. The technique seems so far suitable for the study of the intestinal absorption of substances undergoing the enterohepatic circulation, since it provides a direct measure of the absorbed fraction, without any distortion arising from the hepatic uptake and biliary secretion.

Hydroxyethyl-methacrylate (GMA)-embedded renal biopsies containing amyloid were tested by the indirect immunoperoxidase method with antibodies against the following purified amyloid fibril proteins: AA, three different A lambda preparations, Ak and AF. The anti-AA reagent was monoclonal (mc13), all the others were polyclonal. In four biopsies from cases with generalized amyloidosis, two were found to be of the AA and two of the A lambda type. Two control cases of membranous glomerulonephritis showed only a marginal reaction with anti-A lambda. These results demonstrate that GMA-embedded tissue sections are suitable for immunohistochemical classification of amyloid diseases, because proteinaceous antigenic determinants of amyloid fibril are preserved.

Fifteen patients aged 31-74 years (five male, ten female) on renal biopsy showed intense linear deposits of light chains along tubular basement membranes (TBM) by immunofluorescence, and/or granular dense deposits on electronmicroscopy. Multiple myeloma was diagnosed in ten patients. The onset of myeloma and nephropathy was simultaneous in six patients; nephropathy preceded or followed the diagnosis of myeloma in three and one patients respectively. The mode of onset of nephropathy was acute or rapidly progressive renal failure in five cases, chronic renal failure in seven, and heavy proteinuria in three. Only two patients had normal renal function at biopsy. Serum monoclonal component was kappa in five patients, IgG kappa in three, IgD kappa in one, IgG lambda in one, IgA lambda in one, absent in three, and not detected in one. On light microscopy eight cases had nodular glomerulosclerosis, three cast nephropathy and 14 TBM thickening. Immunofluorescence for monoclonal light chain(s) was positive in 11 of 13 cases. Electron microscopy showed finely granular deposits in the inner side of glomerular basement membranes (GBM) and the outer side of TBM in 11 of 11 tested cases. The evolution was towards chronic renal failure in 12 patients (six of whom required dialysis), death in two, unknown in one. Four patients died after a period of dialysis, from infections or cardiovascular complications.

The effects of long-term treatment with 25-hydroxycholecalciferol (25OHD3) and disodium ethane-1-hydroxydiphosphonate, or 25OHD3 alone on biochemical parameters, and radiographic and quantitative histomorphometry of bone tissue were evaluated in 17 dialysis patients. They all displayed evidence of bone disease consisting of osteitis fibrosa and defective mineralization of varying degree and predominance. 100 micrograms/day of 25OHD3 significantly improved the state of bone mineralization in many patients with a pronounced fall in the osteoid volume and surface and produced a small reduction in the active resorption surface. Serum parathyroid hormone (iPTH) and alkaline phosphatase levels decreased in some patients. The combination of 25OHD3 with EHDP caused the healing of bone mineralization as did 25OHD3 alone and produced a significant fall in serum alkaline phosphatase and iPTH. The mean magnitude of the reduction in iPTH was higher in patients treated with 25OHD3 and EHDP than with 25OHD3 alone. Treatment with 25OHD3 and EHDP seems more effective for the improvement of osteitis fibrosa than is 25OHD3 alone.

Twenty-five adult patients with idiopathic membranous nephropathy (IMN) and nephrotic syndrome (NS) who had participated at a long-term randomized trial with steroid and chlorambucil for six months, underwent repeated renal biopsies. The mean interval between pretreatment and the second biopsy was 41 months. Five evolutionary morphologic changes were adopted. Extensive normalization of the basement membrane (stage V) was observed in 6 of the 9 patients with complete and sustained remission. Only patients in stages I or II at admission seemed to get to reparation stage V. Persistence of NS or a partial remission was usually associated to the progression of the capillary wall lesion to stage III or IV. Our treatment schedule significantly increased the likelihood of getting to the reparation stage V.

Sixteen adult patients with Schönlein-Henoch nephritis, selected by strict inclusion criteria, were studied retrospectively. At the time of discovery of the nephropathy, 11 patients had normal plasma creatinine and 5 other patients had renal insufficiency. All patients had renal biopsies, which were studied by both light and immunofluorescence microscopy. After a mean follow-up of 90.5 +/- 59.1 months (range 16-261), 3 patients were in chronic dialysis (18.7%), 8 other patients had renal function deterioration (50%), with creatinine clearance ranging from 31 to 60 ml/min. Four other patients had mild urinary abnormalities with normal plasma creatinine (25%) and only 1 patient was in complete clinical remission (6%). No clinical features at onset were predictive for the clinical outcome of the disease, while in the biopsies the percentage of crescents was higher in patients who developed renal insufficiency. High IgA serum levels were correlated (p = 0.0242) with a favorable course. It is concluded that Schönlein-Henoch nephritis of the adult carries a high long-term risk of renal dysfunction.

To assess the influence of continuous ambulatory peritoneal dialysis (CAPD) on the evolution of renal osteodystrophy, we studied 36 adult patients with end-stage renal failure before starting dialysis and after 7-30 months. 17 patients (12 males and 5 females) were treated by CAPD as first treatment and 19 (14 males and 5 females) received maintenance hemodialysis. The two groups were age- and sex-matched and no patient received vitamin D. All patients had adequate clinical and metabolic follow-up with a radiological survey and quantitative bone histology at the start of dialysis and at the end of the study. Serum phosphate concentrations were much easier to control in CAPD than in hemodialysis patients. There was no difference in the evolutive pattern of vascular and periarticular calcifications in the two groups. The 25-hydroxyvitamin D3 levels were frequently lower in CAPD than in hemodialysis patients. In some CAPD patients, there was a significant loss of trabecular bone volume at the end of the study. The radiological and histological appearances of secondary hyperparathyroidism improved or seemed to worsen to a lesser degree in CAPD compared to hemodialysis patients.

To test whether long-term oral dosage with chenodiol (chenodeoxycholic acid) used for dissolution of cholesterol gallstones would cause impairment of small-intestinal structure or function, ten patients were studied before and after three months of oral chenodiol administration, 15 mg/kg of body weight per day. Small-intestinal structure was assessed by roentgenogram and intestinal biopsy, using both light and electron microscopy. Small-intestinal function was assessed by xylose, fat and vitamin B12, lactose, and bile-acid absorption. Bile acid metabolism was also characterized by the breath test for deconjugation using carbon dioxide labeled with radioactive carbon 14. No significant abnormalities were found. The results suggest that oral chenodiol administration does not impair intestinal structure or function in doses used for gallstone dissolution. (JAMA1981;246:2597-2601)

International audience; ObjectivesPost-exposure prophylaxis (PEP) care remains a challenge for individuals with potential sexual exposure to HIV in terms of PEP completion and ongoing risk behaviours.MethodsA retrospective analysis was carried out on data from the French Dat’AIDS prevention cohort (NCT03795376) for individuals evaluated for PEP between 2004 and 2017. A multivariable analysis was performed of predictors of both PEP completion and condom use [odds ratios (ORs)] and their associated probabilities (P, with P > 95% being clinically relevant).ResultsOverall, 29 060 sexual exposures to HIV were evaluated for PEP [36% in men who have sex with men (MSM) and 64% in heterosexuals]. Overall, 12 different PEP regimens were offered in 19 240 cases (46%). Tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) was the preferred backbone (n = 14 304; 74%). We observed a shift from boosted protease inhibitor-based regimens to nonnucleoside reverse transcriptase inhibitor- or integrase inhibitor-based regimens in recent years. Overall, 20% of PEP prescriptions were prematurely discontinued. Older age, MSM, intercourse with a sex worker, rape and intercourse with a known HIV-infected source patient were factors associated with increased rates of PEP completion (OR > 1; P > 98%). None of the 12 PEP regimens was associated with premature discontinuation. We also found 12 774 cases of unprotected sexual intercourse (48%). Condom use decreased (OR < 1; P > 99%) with the year of exposure, and was lower in MSM and rape victims. Condom use increased (OR > 1, P > 99%) with age, and was higher in those who had intercourse with a sex worker or with a female partner and in those with knowledge of the partner’s HIV status.ConclusionsWe provide new insights into how rates of condom use and PEP completion might be improved in those receiving PEP by targeting certain groups of individuals for interventions. In particular, youth and MSM at risk should be linked in a prevention-to-care continuum.