Search

Abstract Background The biological relevance of nuclear ErbB-2/HER2 (NuclErbB-2) presence in breast tumors remains unexplored. In this study we assessed the clinical significance of ErbB-2 nuclear localization in primary invasive breast cancer. The reporting recommendations for tumor marker prognostic studies (REMARK) guidelines were used as reference. Methods Tissue microarrays from a cohort of 273 primary invasive breast carcinomas from women living in Chile, a Latin American country, were examined for membrane (MembErbB-2) and NuclErbB-2 expression by an immunofluorescence (IF) protocol we developed. ErbB-2 expression was also evaluated by immunohistochemistry (IHC) with a series of antibodies. Correlation between NuclErbB-2 and MembErbB-2, and between NuclErbB-2 and clinicopathological characteristics of tumors was studied. The prognostic value of NuclErbB-2 in overall survival (OS) was evaluated using Kaplan-Meier method, and Cox model was used to explore NuclErbB-2 as independent prognostic factor for OS. Results The IF protocol we developed showed significantly higher sensitivity for detection of NuclErbB-2 than IHC procedures, while its specificity and sensitivity to detect MembErbB-2 were comparable to those of IHC procedures. We found 33.6% NuclErbB-2 positivity, 14.2% MembErbB-2 overexpression by IF, and 13.0% MembErbB-2 prevalence by IHC in our cohort. We identified NuclErbB-2 positivity as a significant independent predictor of worse OS in patients with MembErbB-2 overexpression. NuclErbB-2 was also a biomarker of lower OS in tumors that overexpress MembErbB-2 and lack steroid hormone receptors. Conclusions We revealed a novel role for NuclErbB-2 as an independent prognostic factor of poor clinical outcome in MembErbB-2-positive breast tumors. Our work indicates that patients presenting NuclErbB-2 may need new therapeutic strategies involving specific blockage of ErbB-2 nuclear migration.

The phrenic nerve innervates the respiratory diaphragm, the primary muscle active during ventilation. The canonical path of the phrenic nerve originates from the cervical spine at C3-C5 spinal nerves and travels inferiorly through the neck and thoracic cavity to reach the diaphragm. During a cadaver dissection, a variation of the phrenic nerve was discovered in a 93-year-old male specimen. A traditional origin of the phrenic nerve was noted; however, the nerve branched into medial and lateral components at the level of the superior trunk of the brachial plexus. The branches reconnected at the apex of the aortic arch and continued inferiorly to innervate the ipsilateral diaphragm. This case study describes a rare type of branching of the phrenic nerve and explores its potential impact on clinical procedures., (© 2024. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Monitoring of minimal residual disease (MRD) by flow cytometry (FCM) is a powerful prognostic tool for predicting outcomes in acute lymphoblastic leukemia (ALL). To apply FCM-MRD in large, collaborative trials, dedicated laboratory staff must be educated to concordantly high levels of expertise and their performance quality should be continuously monitored. We sought to install a unique and comprehensive training and quality control (QC) program involving a large number of reference laboratories within the international Berlin-Frankfurt-Münster (I-BFM) consortium, in order to complement the standardization of the methodology with an educational component and persistent quality control measures. Our QC and quality assurance (QA) program is based on four major cornerstones: (i) a twinning maturation program, (ii) obligatory participation in external QA programs (spiked sample send around, United Kingdom National External Quality Assessment Service (UK NEQAS)), (iii) regular participation in list-mode-data (LMD) file ring trials (FCM data file send arounds), and (iv) surveys of independent data derived from trial results. We demonstrate that the training of laboratories using experienced twinning partners, along with continuous educational feedback significantly improves the performance of laboratories in detecting and quantifying MRD in pediatric ALL patients. Overall, our extensive education and quality control program improved inter-laboratory concordance rates of FCM-MRD assessments and ultimately led to a very high conformity of risk estimates in independent patient cohorts.

Background: In France, general practitioners (GPs) perform out-of-hours home visits (OOH-HVs) after physician-led telephone triage at the emergency call centre. The quality of a systematic physician-led triage has not been determined in France and may affect the efficiency of the OOH-HV process. The objectives of this study were first, to evaluate the quality of reporting in the electronic patient's file after such triage and second, to analyse the factors associated with altered reporting., Methods: Cross-sectional study in a French urban emergency call centre (district of Paris area) from January to December 2015. For a random selection of 30 days, data were collected from electronic medical files that ended with an OOH-HV decision. Missing key quality criteria (medical interrogation, diagnostic hypothesis or ruled-out severity criteria) were analysed by univariate then multivariate logistic regression, adjusted on patient, temporal and organizational data., Results: Among 10,284 OOH-HVs performed in 2015, 748 medical files were selected. Reasons for the encounter were digestive tract symptoms (22%), fever (19%), ear nose and throat symptoms, and cardiovascular and respiratory problems (6% each). Medical interrogation was not reported in 2% of files (n = 16/748) and a diagnostic hypothesis in 58% (n = 432/748); ruled-out severity criteria were not reported in 60% (n = 449/748). On multivariate analysis, altered reporting was related to the work overload of triage assistants (number of incoming calls, call duration, telephone occupation rate; p < 0.03)., Conclusion: In the electronic files of patients requiring an OOH-HV by a GP in a French urban area, quality in medical reporting appeared to depend on organizational factors only, especially the triage assistants-related work factors. Corrective measures are needed to ensure good quality of triage and care.

Objective The present study compares immune and endocrine parameters between HIV-infected patients who underwent the Immune Reconstitution Inflammatory Syndrome (IRIS-P) during antiretroviral therapy (ART) and HIV-patients who did not undergo the syndrome (non-IRIS-P). Materials and methods Blood samples were obtained from 31 HIV-infected patients (15 IRIS-P and 16 non-IRIS-P) before ART (BT) and 48 ± 2 weeks after treatment initiation (AT). Plasma Interleukin-6 (IL-6) and Interleukin-18 (IL-18) were determined by ELISA. Cortisol, dehydroepiandrosterone sulfate (DHEA-S) and thyroxin concentrations were measured using chemiluminescence immune methods. Results Concentrations of IL-6 (7.9 ± 1.9 pg/mL) and IL-18 (951.5 ± 233.0 pg/mL) were significantly higher (p < 0.05) in IRIS-P than in non-IRIS-P (3.9 ± 1.0 pg/mL and 461.0 ± 84.4 pg/mL, respectively) BT. Mean T4 plasma level significantly decreased in both groups of patients after treatment (p < 0.05). In both groups cortisol levels were similar before and after ART (p > 0.05). Levels of DHEA-S in IRIS-P decreased AT (1080.5 ± 124.2 vs. 782.5 ± 123.8 ng/mL, p < 0.05) and they were significantly lower than in non-IRIS-P (782.5 ± 123.8 vs. 1203.7 ± 144.0 ng/mL, p < 0.05). IRIS-P showed higher values of IL-6 and IL-18 BT and lower levels of DHEA-S AT than in non-IRIS-P. Conclusion These parameters could contribute to differentiate IRIS-P from non-IRIS-P. The significant decrease in DHEA-S levels in IRIS-P after ART might suggest a different adrenal response in these patients, which may reflect the severity of the disease.

Objectives: To assess the prevalence, the severity and expectations regarding erectile dysfunction (ED) in diabetic patients, then to investigate how general practitioners (GP) and endocrinologists manage this disorder., Patients and Methods: A questionnaire was given during 5 weeks to every diabetic patient addressed to the endocrinology department in order to assess erectile function (IIEF5), patient's bother and expectations to be treated, and the management of ED by GP and endocrinologists and differences in management between male and female doctors., Results: One hundred and thirty questionnaires were available. Mean age was 57.5 and the mean IIEF5 score was 13.6. Twenty-two patients (16.9%) reported an IIEF5 score less than 5 and 75 patients (57,6%) reported an IIEF5 between 5 and 20. Eighty-six patients declared ED (66.2%). In these patients, 76 (88.4%) sought for a medical treatment and 11 (12.8%) received a treatment for ED. Endocrinologists were more active than GP in the screening of ED (59.5% vs 19.4%, P=0.001) but prescribed a treatment less often (14.3% vs 45.2%, P=0.008). Female doctors seemed less active in ED management (29.3% vs 13.3%, NS)., Conclusions: This study highlighted the lack of ED management by GT and endocrinologists in diabetic patients in spite of ED's frequency and patients' expectations., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

C57BL/6 mice infected with Trypanosoma cruzi, the causal agent of Chagas' disease, develop severe thymocyte depletion paralleled by an inflammatory syndrome mediated by tumor necrosis factor-alpha (TNF-alpha). The exacerbated inflammatory reaction induces the activation of hypothalamus-pituitary-adrenal (HPA) axis with the consequent release of corticosterone (CT) into the circulation as a protective response. Thymocyte apoptosis has been related to a rise in TNF-alpha and CT levels, and both mediators are increased in T. cruzi-infected C57BL/6 mice. The depletion of immature CD4(+)CD8(+) thymocytes by apoptosis following infection with the parasite was still present in mice defective in both types of TNF-receptors (double knockout). However, thymic atrophy was prevented by adrenalectomy combined with RU486 administration, demonstrating that this is a CT-driven phenomenon. Our results put emphasis on the importance of an appropriated immuno-endocrine balance during T. cruzi infection and show that functional deviations in the immuno-endocrine equilibrium have profound effects on the thymus and disease outcome.

The long-term hemodynamic and renal effects of propranolol were compared with those of propranolol plus isosorbide dinitrate in 44 portal-hypertensive alcoholic cirrhotic patients. Eight control patients, 8 patients receiving propranolol and 14 patients receiving propranolol plus isosorbide dinitrate were hemodynamically evaluated. Renal function was studied in a fourth group of 14 patients receiving propranolol plus isosorbide dinitrate. Portal pressure decreased more (p < 0.05) with combined therapy (-21.6%, from 19.5 +/- 4.8 to 15.4 +/- 4.3 mm Hg) than with propranolol alone (-12.5%, from 19.9 +/- 1.2 to 17.4 +/- 1.8 mm Hg). Serum urea and creatinine levels, plasma sodium concentration, urine volume and urinary sodium excretion showed nonsignificant changes in all groups studied. Combined therapy induced a significant (p < 0.05) decrease in plasma renin activity (from 4.42 +/- 4.7 to 1.59 +/- 1.9 ng/ml/hr) and nonsignificant reductions in plasma aldosterone concentration and creatinine clearance. None of the eight patients with ascites or history of ascites not receiving isosorbide dinitrate showed evidence of impairment in renal sodium metabolism during the study period. In contrast, 8 of the 14 patients (57%) with ascites or history of ascites receiving isosorbide dinitrate showed impairment in renal sodium metabolism (p < 0.01), as reflected by the development or worsening of ascites and the need of higher diuretic requirements. Long-term combined administration of propranolol plus isosorbide dinitrate is superior to propranolol alone in the pharmacological treatment of portal hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Testicular maldescent is one of the causes of male infertility. This paper illustrates that it was possible to determine that this pathology was present in 8.96% of the cases in 212 men who consulted for infertility at our service during 1987. When we compared clinical, hormonal and seminal studies with infertile subjects without testicular maldescent and with a group of 20 fertile patients, statistically significant differences were established, suggesting a poorer prognosis of fertility to the group with maldescent testes.

Sera of 155 chronic hepatitis (CH) patients in Argentina were tested for the presence of HBsAg, anti-HBs, anti-HBc, and anti-HAV. Our purpose was to define the role that both virus A and B might play in the etiology and pathogenesis of this condition. The patients were divided into two groups: group I (57) HBsAg-negative; group II (98) HBsAg-positive. The control group consisted of 1,209 healthy blood donors from Banco Central de Sangre de Rosario; 286/1,209 (24%) had viral markers for HBV. In group I, 38/57 (67%) had anti-HBs and/or anti-HBc, but none had anti-HBs alone. Group II showed a higher percentage of males (P less than 0.05). We found similar incidence of anti-HAV among group I, group II, and the control group.

The application of microsurgical neurolytic techniques in cases of peripheral nerve entrapments offers greater advantages than other techniques, as it allows a better understanding of the neural alterations. In most cases, a longitudinal epineurectomy is necessary to free the fascicles of the epineural fibrosis. Less frequently, internal neurolysis is needed for removal of interfascicular scarring. Fifty cases of elbow ulnar neuropathy and 58 of the carpal tunnel syndrome were treated with this technique: 72% of the results were satisfactory.

Extrahepatic and intrahepatic biliary obstruction of different etiology were studied in 62 patients, who were investigated for the presence of lipoprotein X (Lp-X). It was found present in 19 of 20 cholestasis by lithiasis, in all three primary biliary cirrhosis patients, in 2 of 4 cirrhosis, in 5 of 13 hepatitis, in all three benign recurrent intrahepatic cholestasis and in 1 of 2 recurrent juandice of pregnancy. It was found in a Dubin Johnson. Lp-X disappeared in 4 patients within two weeks after relief of the obstruction. It was found in patients with cholestatic hepatitis during the first week of jaundice. It was found in the first 48 hours in three patients with cholestasis by lithiasis. Lp-X does not help in differential diagnosis between extrahepatic and intrahepatic biliary obstruction, but the time of its appearance could contribute to it in some cases. A word of caution is raised in indicating surgery in a cholestatic patient without the presence of Lp-X.

Seventy-seven consecutive HBeAg-positive chronic hepatitis patients were studied from 1971 to 1983 to establish the seroconversion rate in the e system. Patients with less than a year of follow-up were not included in the study. Fifty-six patients with chronic active hepatitis (CAH) received immunosuppressive treatment (corticosteroids combined with azathioprine). The remaining twenty-one patients received no treatment, nine of them with chronic persistent hepatitis (CPH) and 12 with CAH. A retrospective study was performed with stored sera samples: HBeAg and anti-HBe were determined by RIA, and results were correlated with alanine aminotransferase (ALAT) levels in the same samples. The linearized seroconversion rate from HBeAg to anti-HBe was expressed as percent per patient-year. It was 9.6% in CPH patients and 8.8% in CAH patients without treatment. In CAH patients under immunosuppressive drugs it was as low as 1.1% and increased to 28.7% when treatment was withdrawn. ALAT levels were significantly lower in total seroconverted patients when compared with nonseroconverted (NS) patients, but no difference was found between partial seroconverted (PS) and NS patients. The results suggest that although immunosuppressive drug withdrawal may enhance seroconversion rate in type B CAH, delayed seroconversion and reported side effects during treatment stand against protracted usage of these drugs.

In a retrospective study, we review here the clinical presentation of patients with the biphasic form of hepatitis A, a variant of viral hepatitis characterised by an increase in ALAT levels after an initial recovery in clinical condition and laboratory tests. Twenty-one patients were diagnosed as having a biphasic form; they represent about 10% of a selected population of hepatitis A cases. Six patients were asymptomatic. Eleven patients were jaundiced, nine of them showing a "cholestatic" pattern. The second phase of the disease had a more protracted course and displayed higher ALAT levels than the first phase. The total duration of the disease was 120 +/- 28 (mean +/- SD) days, and its course was benign.

The conjugated cholic acid (glycocholic acid) (GC) in the serum and the conjugated sulfolithocholic acid (sulfolithoglycocholic acid (SLGC) in 35 aggressive chronic hepatitis (HCA), 22 cirrhosis, 11 primary biliary cirrhosis (CBP), 11 pruritus of pregnancy and in 20 normal controls were determined. The control group revealed a mean value of GC of 21 micrograms % with a dispersion of +/- 14 micrograms % and for SLGC of 36 micrograms % with a dispersion of +/- 9 micrograms %. The frequency of the alteration of GC and SLGC in the cases of chronic hepatitis was low (14% and 9%) as well as in the cirrhosis (23% and 14%). In the pruritus of pregnancy the values reached 64% and 45%. On the other hand, the values were significantly elevated in CBP (100% and 90%) (p.001 and p.006). The absolute values in the various pathologies revealed mean values which were different but with a very wide dispersion that prevented us from seeing any relation between those absolute values and the different diseases. The alteration in the metabolism of biliary acids in the hepatic pathology was manifested by the postprandial determination of GC and SLGC in 20 HCA in whom the frequency of abnormal values rose from 14% and 9% on fasting to 60% and 45% prandially.

156 patients with chronic hepatitis were studied in Rosario, Argentina. 98 patients were HBsAg positive (group I) and 58 patients were negative (group II). 209 normal volunteer blood donors served as controls (group III). In all cases the presence of anti-HAV was sought by RIA and was found in 92% of cases in group I, 91% in group II and 82% in group II patients. In groups II and III we also determined the presence of anti-HBcAg by RIA being positive in 65% and 15% respectively (p less than 0.01). There were no differences related to sex, age and type of chronic hepatitis. We conclude, firstly that the percentage of anti-HAV is similar in chronic hepatitis and healthy controls; secondly, that 65% of patients with HBsAg negative chronic hepatitis have evidence of virus B infection demonstrated by the presence of anti-HBcAg; finally we remark the greater sensitivity of RIA over hemmagglutination for the detection of anti-HBcAg.