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In this study, a one-step method for liquid-liquid extraction has been compared against a two-step procedure for testosterone assays in terms of accuracy, specificity, recovery, lipid removal and baseline noise, using QCs and unknown samples. The difference in accuracy was less than 5% for adult sera, while it was less than 10% for prepubescent sera. To compare specificity, the ion ratio transition of 289 → 97 to 289 → 109 was monitored for all QCs and unknown samples; no interference in the testosterone peak was observed for any tested sample prepared by either the one-step or two-step procedure. The baseline comparison of LC-MS/MS chromatograms of samples indicated that samples prepared by the one-step procedure were of the same quality as those prepared by the two-step procedure; however, recovery in unaltered serum using the one-step procedure was approximately 15% greater across the low to high concentration range. Furthermore, recovery using the one-step procedure was more consistent between stripped and unstripped serum. Lipids were removed efficiently in the two-step procedure as verified by monitoring the typical phospholipid MRM transition of m/z 496 → 184. For every sample processed by the one-step procedure, a one-minute online column wash with 95% methanol was able to remove 95% of the bound lipids, thereby providing a column life-time approximately equivalent to that for the two-step procedure. The presented data indicate that the one-step procedure could replace the two-step procedure while maintaining accuracy, saving time, increasing recovery, and minimizing the potential for errors with the fewer steps required., (© 2018 The Association for Mass Spectrometry: Applications to the Clinical Lab (MSACL). Published by Elsevier B.V.)

In the present study, the impact of the extraction solvent on the accuracy of endogenous progesterone assay in human serum has been investigated using two selective reaction monitoring (SRM) transitions (315>97 & 315>109). Higher levels of noise and more interference were observed when more polar solvents were used for extraction, thus resulting in serious bias of the measured values of progesterone in serum. This is confirmed by monitoring the ion ratio of 315>97-315>109. This issue could not be easily resolved by changes in MS/MS transitions or chromatography conditions. More bias was observed with the SRM transition 315>109 for the polar solvent extraction. Hexane and 1-chlorobutane (polarity index of 0 and 1, respectively) did provide the cleanest samples with a lower noise level in the chromatograms. Moreover, the measured values of progesterone were not changed with different SRM transitions or longer retention time in search of an improved separation. Recovery tests of progesterone have been performed with 1-chlorobutane in matrices with phosphate buffered saline (PBS) 1x, PBS 1×3% bovine serum albumin (BSA), stripped serum/H 2 O (1:1) and unstripped serum. The recovery (70%∼80%) consistency is observed not only at different levels but also in different matrices. The equivalent recovery between PBS 1x, PBS 1×3% BSA and unstripped serum shows that the impact of progesterone binding to serum proteins on the measurement accuracy can be avoided with this sample preparation procedure. No significant matrix effect on the determination of progesterone was observed with 1-chlorobutane. Within the range of 12.5-2000pg/mL, a good linearity is observed with R>0.99 and weighting factor 1/X. Bias and covariance efficiency of QCs are within 10%. With 1-chlorobutane as the extraction solvent, the concentration of progesterone was measured where the range for postmenopausal serum is 5.74∼91.7pg/mL, which is well below the reported concentrations of 314 pg/mL∼942pg/mL in postmenopausal serum by immunoassay-based techniques, while the range in premenopausal serum is 12.8 pg/mL∼18.6ng/mL., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The concentrations of allopregnanolone (Allopreg), pregnenolone (Preg) and androsterone (ADT) are very low in the circulation, especially in postmenopausal women, resulting in a considerable challenge for their accurate measurements in serum or plasma. In this report, a sensitive and reliable LC-MS/MS assay method has been developed using a simple sample preparation and the 1-Amino-4-methylpiperazine (AMP) derivatization procedure. A 5pg/ml (0.1pg on column) of low limit of quantitation has been achieved for Allopreg, Preg and ADT, with a sensitivity comparable to data obtained with the commercial reagent. The major benefit of this reagent is to limit the matrix effect since the excess amount of reagent can be removed during the reaction. Multiple reaction monitoring (MRM) from the derivatization of AMP not only increases the detection of these compounds but also provides a good resolution for Allopreg, Preg and ADT from interferences, especially for Allopreg from its isomers. Within the calibration range of 5pg/ml to 2000pg/ml, a good linearity was obtained with R>0.99 where the weighing factor is 1/X. Bias and coefficients of variance are within 15% for all QC levels. The matrix effect has been evaluated, well meeting the acceptance criteria according to the FDA guidelines. With this method, the concentrations of Allopreg, Preg and ADT in postmenopausal serum are in the range of 6.4-53.6pg/ml, 16.2-68.0pg/ml and 23.9-114.0pg/ml, respectively, while the ranges in premenopausal serum are 8.2-701.5pg/ml, 31.2-135.2pg/ml and 47.8-310.0pg/ml, respectively., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The circulating levels of 16β hydroxydehydroepiandrosterone (16β OH-DHEA) are at the limit of detection (less than 10 pg/mL), unlike the serum concentrations of 16α-hydroxydehydroepiandrosterone (16α OH-DHEA, 10-300 pg/mL) in premenopausal, postmenopausal and male serum. A major reason could be the rapid conversion of 16β OH-DHEA to 5-androstene-3beta, 17beta-diol 16 one (3β, 17β-diol 16-oxo) in serum due to the stereospecific structure of 16β OH-DHEA. In ultrapure H2O, there is no apparent conversion observed while 16β OH-DHEA (10 ng/mL) spiked in stripped or unstripped serum is quickly converted to 3β, 17β-diol 16-oxo at room temperature. During this conversion, a further converted product was observed with a difference in molecular weight of 16 Da from that of 16β OH-DHEA and 3β, 17β-diol 16-oxo, which could be their hydroxylation product, i.e. triol-ketone. Under basic conditions, further conversion occurs. The present data can explain the practically undetectable concentration of serum 16β OH-DHEA while 3β, 17β-diol 16-oxo is at the level of less than 50 pg/mL. Serum concentrations of (0.0-9.9 pg/mL for 16β OH-DHEA, 8.9-50.7 pg/mL for 3β, 17β-diol 16-oxo and 10.0-285.0 pg/mL for 16α OH-DHEA are measured in sera of premenopausal, postmenopausal women and men over 50 years of age., (Copyright © 2016 Elsevier Inc. All rights reserved.)

7alpha hydroxy-, 7beta hydroxy- and 7keto-dehydroepiandrosterone (7α OH-DHEA, 7β OH-DHEA and 7 oxo-DHEA) are oxidized metabolites of dehydroepiandrosterone (DHEA). Their concentrations are low in the circulation, especially in postmenopausal women, thus resulting in a considerable challenge for their reliable measurement. A sensitive and accurate LC-MS/MS method has been developed using a simple sample preparation procedure and a novel derivatization with 1-amino-4-methyl piperazine (MP). The derivatized metabolites are stable in high water content reagents. A 10 pg/mL (0.2 pg on column) for the low limit of quantitation (LLOQ) has been achieved for all three compounds. A proper choice of multiple reaction monitoring (MRM) transitions provides good specificity. The excess amount of reagent can be removed from the sample during the derivatization process. Within the calibration range of 10-2000 pg/mL, a good linearity was obtained with R>0.99 where the weighing factor is 1/X while the bias and coefficient of variance (CV) are within 8% for all levels of QCs and calibration curves. This method has been fully validated according to the FDA guidelines, where the results of the matrix effect meet the acceptance criteria while freeze-thaw stability, short and long term stability in matrix and solution as well as post-processed sample stability meet the requirements. With this method, the concentrations of 7α OH-DHEA, 7β OH-DHEA and 7 oxo-DHEA were measured in premenopausal and postmenopausal serum. The average concentration of 7α OH-DHEA is equivalent to that of 7β OH-DHEA in both types of sera., (Copyright © 2016 Elsevier Inc. All rights reserved.)

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The announcement of the diagnosis of cancer is difficult for doctors and patients alike. The main objective is the study of announcement's techniques used by physicians to send their patients in cancer centers. The second objective is to analyze encountered difficulties and experience of the announcement of the diagnosis. The final objective would be to provide practical ideas for GPs for a better communication with their patients in this announcement. We have conducted a qualitative study by interviewing fifteen GPs. The fifteen semi-structured interviews have been recorded and transcribed verbatim. A first analysis has been done manually to achieve a set of nodes and then in a second time using N Vivo Software 9. Most of the GPs break the news of cancer with or without pathology. They know the basics of patient-physician communication to promote the patient's expression. Some doctors have a positive experience and claim their role in this announcement. Their negative experience is linked to representations made about the disease and generated feeling. The results of this study show a need of training for physicians in order to acquire know-how and attitude at the time of cancer announcement.

Objectives: The aim of this study was to identify factors predictive of nursing home admission (NHA) over a period of 1 year among elderly subjects with dementia., Methods: The study population was drawn from the SAFES cohort that was formed within a national research program into the recruitment of emergency departments in 9 teaching hospitals. Subjects were to have been hospitalized in a medical ward in the same hospital as the emergency department to which they were initially admitted. Subjects who experienced NHA before emergency department admission were excluded. Those with a confirmed diagnosis of dementia were considered in the present analysis. NHA has been defined as the incident admission into either a nursing home or other long term care facility within the follow-up period. Data obtained from a Comprehensive Geriatric Assessment were used in a Cox model to predict 1-year NHA., Results: The 425 subjects of the study were 86 ± 6 years old, and were mainly women (63%). NHA rate was 40% (n = 172). Four factors were identified to increase NHA risk: age 85 or older (hazard ratio [HR] = 1.5; 95% confidence interval [CI] = 1.1-2.1), inability to use the toilet (HR = 2.5; 95% CI = 1.5-4.2), balance disorders (HR = 1.5; 95% CI = 1.1-2.1), and living alone (HR = 1.5; 95% CI = 1.1-2.1). Three factors decreased this risk significantly: inability to transfer (HR = 0.5; 95% CI = 0.3-0.8), increased number of children (HR = 0.88; 95% CI = 0.96-0.99), and increased initial Mini-Mental State Examination score (HR = 0.97; 95% CI = 0.8-0.9)., Conclusion: NHA determinants in dementia are strongly linked to the patient's own characteristics but also to his or her physical or social environment. Interventions should target both members of the dyad "patient-caregiver" because both are affected by the disease., (Copyright © 2012 American Medical Directors Association, Inc. Published by Elsevier Inc. All rights reserved.)

This paper describes a simple, fast and sensitive liquid chromatography-mass spectrometry method for quantification of an anti-thrombocythemic agent, anagrelide in human plasma. The samples were subjected to a liquid-liquid extraction after addition of a buffer and an internal standard. Chromatography was performed on an Inertsil ODS2 column and the extract was injected onto a HPLC system coupled with mass spectrometric detection. Linear responses for standards were observed from 50 to 7500 pg/ml. The accuracy of intra-assay and inter-assay were in the ranges 4.3-4.4% and 4.8-5.6%, respectively. The method is simple and reproducible with a run time of less than 2 min.

Introduction: Cobalamin deficiency is common in the elderly. However, most of the patients are asymptomatic or present with few symptoms. A subacute combined degeneration of the spinal cord accounts for only 10% of the neurological complications. Revealing forms of this myelopathy are exceptional, and were rarely documented by magnetic resonance imaging (MRI) study., Exegesis: We report a case of subacute combined degeneration of spinal cord in an 81-year-old woman evaluated by a spinal cord MRI. We discuss the role of the spinal cord radiographic study in the diagnosis, the etiopathogeny of cobalamin deficiency and the benefit of vitamin supplementation even at a late stage of the disease in geriatrics patients., Conclusion: The spinal cord MRI is useful in the diagnosis of late-form combined spinal cord degeneration. The high frequency of atrophic gastritis in elderly prevents the identification of a deficiency of the cobalamin etiology. The treatment relies on vitamin therapy even in the late stages. The severe disability of cobalamin deficiency neurological complications must encourage an earlier diagnosis in elderly patients.

Purpose: Diogenes syndrome is characterised by self-neglect and domestic squalor which leads to unhealthy living conditions. It seems that no single model satisfactorily explains the development of Diogenes syndrome., Methods: We report four cases of Diogenes syndrome discovered during a short-stay geriatric hospitalization. We were able to analyse them as regards social, physical, psychiatric and cognitive aspects., Results: The results showed absence of socioeconomic precariousness, psychiatric and physical pathologies which generate handicaps. A dementia characterised by a frontal dysfunction was constantly found., Conclusion: Diogenes syndrome seems to be a particular behavioural demonstration of a frontal lobe dementia. It does not correspond to a lucid life choice, which must encourage a medico-social assumption.

Purpose: In the geriatric units of the University Hospital of Saint-Etienne, 129 cases of fever (38 degrees C or more) were recorded prospectively during the 1995-1996 winter period in a population of 503 hospitalised patients (25.6%), and were investigated for the detection of a viral aetiology., Methods: In febrile patients, a standard form was used to record clinical and biological parameters, including the results of investigations for respiratory viruses from a nasal swab and dual serum specimens., Results: A clinical or radiological respiratory infection was found in 69 cases (53.5% of all cases of fever), including 14 respiratory syncytial virus (RSV) infections. In comparison to nonviral respiratory infections, the RSV infections were characterised by the prevalence of anorexia (57% vs 20%, P < 0.05) and rhinorrhea (64% vs 5%, P < 0.01). No influenza infection was recorded despite the concomitant circulation of influenza virus in the community. A nosocomial outbreak of RSV infection (nine cases, attack rate of 18.7%) was identified in a long-stay care unit., Conclusion: This study illustrates the high prevalence (10.9%) of RSV infections in elderly patients with fever during this season and the importance of hygienic measures to control the spread of nosocomial outbreaks.

Purpose: Horton disease or 'giant cell arteritis' is a known entity in its typical form; the difficulty in diagnosis is due to the atypical signs and symptoms., Methods: We review 260 medical files presenting Horton disease between 1979 and 1999 in five different departments: three internal medicine departments, one rheumatology department and one geriatric department., Results: The study shows a female domination with a mean age of 75 years. Temporal artery biopsy was done on all patients. Ten patients presented a vascular manifestation. The neurological manifestation was the first symptom in four patients. Five patients had cutaneous symptomatology, with positive temporal artery in three cases. Renal manifestation was present in two patients. Two symptoms are important to discuss because of their frequency: the cough and the peripheral arthritis. We found nine observations with arthritis affecting large joints and responding to nonsteroidal antiinflammatories with positive temporal artery biopsy in seven patients, and 21 observations manifesting by cough without radiological signs; in 57% of cases the temporal artery biopsy was positive, and the cough regressed with corticoids., Conclusion: These atypical symptoms have to be known to make a diagnosis and to begin a corticotherapy as soon as possible.

Purpose and Methods: Sixteen elderly patients with early dementia and 20 elderly patients with pain, all hospitalized in a geriatric hospital, evaluated their memory, health and mood, using a visual analog scale. Observations of their families and of the medical staff were also recorded for subsequent comparison. The patients' complaints were also compared to those of a control group including 16 healthy elderly subjects., Results: Patients with early dementia complained more often than control subjects of memory loss and health and mood disorders, while patients with pain complained more often of only health and mood disorders. However, only patients with dementia complained of memory loss. Complaints noticed by their families and medical staff were in good agreement with theirs. Regarding patients with early dementia, the medical staff underestimated their complaint of memory loss., Conclusion: Visual analog scales appear to be valuable tools regarding not only evaluation of pain but also the patients' general condition. Complaints of memory loss could be of value as they would suggest the existence of early dementia in elderly patients. However, our study emphasizes the need for training medical staff to listen to such a complaint.

We report nine cases of elderly French patients (more than 65 years old) with bronchial tuberculosis. We report the clinical features, radiological and endoscopic aspects. The symptoms are non specific and may delay the diagnostic. The chest X-ray and endoscopic aspects are tumor like. Retractile bronchial stenosis is a potential evolution.

Using explicit criteria contained in the DSM III R, we collected in a prospective cohort study clinical features, outcome and risk factors from two cohorts of delirium in hospitalized elderly patients: 138 hospitalized in geriatric department and 45 patients admitted to an acute and comprehensive care hospital. The clinical features were assessed using a quantitative scale (developed by Derouesné). Delirium was unrecognized or misdiagnosed by physicians in 34% of the cases. The onset was known only two thirds of cases. The incidence of hyperactive type, prolonged hospital stay, poor outcomes (persistent delirium leading up to dementia) were highest in subjects admitted in comprehensive hospital. The etiology of delirium is complex and multifactorial. An underlying cause was identified in 80% of patients. The length or the worsening of delirium was significantly higher in patients with psychiatric or dementia comorbidity (OR: 0.2; IC 95%: 0.1-0.5). The prognosis was better in patients without psychoactive medications (OR: 0.2; IC 95%: 0.1-0.4) or with metabolic abnormalities or acute diseases and disorders (OR: 3.3; IC 95%: 1.5-7.6). The predisposing factors to the development of dementia were prior use of psychoactive medications and signs of prior cognitive impairment. This article suggests delirium in elderly patients is associated with several outcomes. The prognosis should be improved at admission by specific scale and an evaluation of predisposing and precipitating factors.

The authors report a new case of left bundle branch block with pain during exercise, with arteriographically normal coronary arteries. Clinical findings and the course of the condition are reviewed. Pathophysiological mechanisms are discussed, with attribution of first place to an ischemic theory.

Coronary disease before the age of 40 has special clinical and pathogenic features. The authors sought evidence of the existence of abnormalities of hemostasis markers in 39 patients aged under 40, several weeks after a myocardial infarction (MI). Blood samples were drawn a mean of 8 months after the MI. These laboratory studies included assay of C and S proteins, fibrinogen, clotting factors VII and VIII and antithrombin III, as well as detection of any possible circulating anticoagulant. Plasma levels of platelet factor 4 (PT4) and of beta-thromboglobulin (BTG) were measured in the same sample, enabling determination of the BTG/PF4 ratio. Only fibrinogen and plasma levels of platelet proteins were abnormal, revealing a significant difference between patients with multi-vessel disease and those with single vessel disease or free of severe angiographic lesions. Platelet activation appeared to persist some time after the MI, chiefly in patients with multi-vessel disease, and showing no relation to either age or treatment. Conclusions require prudence in view of difficulties in interpreting plasma assays of PF4 and of BTG.

To ascertain the responsibility of renal artery thrombosis for the genesis of arterial hypertension, the methods available are not sufficiently sensitive and reproducible, and the residual revascularization maintained by a vicarious arterial network is not easy to demonstrate. Renal scintigraphy with technetium 99m-labelled mercaptoacetyltriglycine (MAG3) was performed in 4 old and severely hypertensive male patients with chronic thrombosis of one renal artery. With this tracer the thrombotic kidney was detected lately and weakly at the vascular and nephrographic stages. When the functions of both kidneys were compared, that of the affected kidney was always estimated at less than 5%. At the excretory stage a residual activity could be detected in the kidney with renal artery thrombosis. Owing to the specific biophysical behaviour of the tracer, MAG3 scintigraphy coupled with arteriography and assays of plasma renin activity in the veins contribute to the decision concerning nephrectomy.

Among the atypical forms of phaeochromocytoma the isolated inflammatory form is rare and difficult to diagnose clinically. The authors report such a case, where computerized tomography and magnetic resonance imaging contributed enormously to the diagnosis.

In a prospective study, we screened sera samples of 128 patients with glomerulonephritis (GN) for the presence of circulating immune-complexes (CIC) fixing C1q by precipitation of native C1q with 2% polyethylene glycol (PEG) in the presence of 10 mM EDTA. The amount of precipitated C1q, as measured by Mancini, is less than 27% (m +/- 2 SD) of the original value in control sera. We found 35/128 (27%) positives samples, distributed as follows: 4/17 (24%) in acute GN, 10/15 (67%) in SLE, 2/16 (13%) in membraneous GN, 13/24 (54%) in membranoproliferative GN, 3/16 (19%) in segmental focal hyalinosis, 2/10 (20%) in minimal lesions nephrotic syndrome, and 1/30 (3%) in mesangial IgA GN. We then correlated these results with clinical, serological and pathological data. Whatever the type of GN, the presence of CIC fixing C1q correlated significantly, well with : the presence of chronic renal failure (serum creatinine greater than or equal to 2 mg/dl) (X2 = 5.48, p less than 0.02), the presence of hypocomplementemia (X2 = 12.30, p less than 0.001), the presence of low serum C3 (X2 = 8.25, p less than 0.01), the activation of C3 through normal pathway (low serum C4 and/or C1q) (X2 - 18.12, p less than 0.001) and the presence of glomerular deposits of C3 (X2 = 8.52, p less than 0.01), of C4 (X2 = 7.10, p less than 0.01), and of C1q (X2 = 4.11, p less than 0.05). The technique is simple, does not require labeled C1q, and allows the further study of antigen or antibody determinants of the complexes. Its sensitivity is near that of the 125 I-C1q binding assay technique. Such routine screening is a major immunopathologic step in the investigation of human GN.

Serum levels of carcino-embryonic antigen (CEA) and beta2-microglobulin (beta2m) were assayed on 133 sera during follow-up of 31 patients with lung carcinoma (squamous cell ca. without recurrence : 2, squamous cell ca. with recurrence : 11, anaplastic cell ca. : 4, adenocarcinoma : 2, unclassifiable : 5). Normal creatinine (less than or equal to 12 mg/l) levels were found in all sera. CEA and beta2m levels showed no correlation nor in these groups, nor in the whole. The squamous cell carcinomas with recurrence showed the largest dispersion for CEA as for beta2m levels. However, the trends of serial beta2m values did not correlate with clinical features. Increasing or decreasing levels of CEA and beta2m levels showed no correlation in the whole nor in patients undergoing radiotherapy. In our experience, beta2m levels failed to correlate with clinical findings during the follow-up of lung cancer patients.