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Biomedical subjects

M Albert

Publications and source records attributed to M Albert.

At least 19 recordsLinked to original sources

[Long-term effects of environmental endocrine disruptors on male fertility].

Several epidemiologic studies have demonstrated during the last 50 years an increased incidence in testis cancer, male genital tract malformations (cryptorchidism and hypospadias) and a decrease in sperm quality in men. These three pathologies seem to be linked and to belong to the testicular dysgenesis syndrome (TDS). It was suggested that TDS is a consequence of intra-uterine exposure to environmental compounds that disrupt the metabolism of native hormones. Such substances are so called endocrine disruptors (EDs). EDs are present in our daily environment such as food and water (through the use of pesticides), cosmetics, house-care products etc. Experimental models have been carried out to (i) establish a link between EDs exposure and SDT and (ii) identify the mechanisms that are involved in. After a brief definition of EDs and having underlined the importance of the window of exposure to EDs, several mechanisms will be described such as (i) intergenerational transmission (epigenetic), (ii) programmed cell death of testicular cells, (iii) modification of the androgenic signal and (iv) role of the germ cells-nourishing cells. To conclude, we will try to propose some biomarkers that would be useful to identify the potential link between fetal exposure to anti-androgenic EDs and male testicular pathology.

Androgen Antagonists↗

[Late paternity: spermatogenetic aspects].

The effect of maternal age on the risk of meiotic abnormality is well documented. In contrast little is known about the effect of the paternal age. The question of the risk related to paternal age is raised because of the increased demand of Assisted Reproduction Techniques for older men. This review focuses on the alterations of male semen parameters, testis histology and genetic risks related to age. The motility, vitality and morphology of spermatozoa and semen volume are found decreasing with age. Histomorphometric studies reveal various alterations including a thickening of the basal membrane when spermatogenesis is arrested. The number of germinal and Sertoli cells decreases with increased age. Up to 95 years old, we could find subjects with complete spermatogenesis. Chromosomal analyses in different studies have provided controversial results. Our investigation on subjects aged from 29 to 102 showed that the rate of aneuploidy in the group of aged subjects with preserved spermatogenesis was not statistically different from the young control group. However the incidence of postmeiotic aneuploidy was increased when spermiogenesis had stopped. On the other hand from epidemiological studies, autosomal dominant diseases are known to be associated with paternal age. However, in the case of achondroplasia and Apert syndrome, direct DNA sperm analysis did not reveal significant increase in the mutation frequency with paternal age.

Adult↗

Longitudinal study of effects of patient characteristics on direct costs in Alzheimer disease.

OBJECTIVES: To estimate long-term trajectories of direct cost of caring for patients with Alzheimer disease (AD) and examine the effects of patients' characteristics on cost longitudinally. METHODS: The sample is drawn from the Predictors Study, a large, multicenter cohort of patients with probable AD, prospectively followed up annually for up to 7 years in three university-based AD centers in the United States. Random effects models estimated the effects of patients' clinical and sociodemographic characteristics on direct cost of care. Direct cost included cost associated with medical and nonmedical care. Clinical characteristics included cognitive status (measured by Mini-Mental State Examination), functional capacity (measured by Blessed Dementia Rating Scale [BDRS]), psychotic symptoms, behavioral problems, depressive symptoms, extrapyramidal signs, and comorbidities. The model also controlled for patients' sex, age, and living arrangements. RESULTS: Total direct cost increased from approximately 9,239 dollars per patient per year at baseline, when all patients were at the early stages of the disease, to 19,925 dollars by year 4. After controlling for other variables, a one-point increase in the BDRS score increased total direct cost by 7.7%. One more comorbid condition increased total direct cost by 14.3%. Total direct cost was 20.8% lower for patients living at home compared with those living in an institutional setting. CONCLUSIONS: Total direct cost of caring for patients with Alzheimer disease increased substantially over time. Much of the cost increases were explained by patients' clinical and demographic variables. Comorbidities and functional capacity were associated with higher direct cost over time.

Aged↗

Clinical features associated with costs in early AD: baseline data from the Predictors Study.

BACKGROUND: Few studies on cost of caring for patients with Alzheimer disease (AD) have simultaneously considered multiple dimensions of disease costs and detailed clinical characteristics. OBJECTIVE: To estimate empirically the incremental effects of patients' clinical characteristics on disease costs. METHODS: Data are derived from the baseline visit of 180 patients in the Predictors Study, a large, multicenter cohort of patients with probable AD followed from early stages of the disease. All patients initially lived at home, in retirement homes, or in assisted living facilities. Costs of direct medical care included hospitalizations, outpatient treatment and procedures, assistive devices, and medications. Costs of direct nonmedical care included home health aides, respite care, and adult day care. Indirect costs were measured by caregiving time. Patients' clinical characteristics included cognitive status, functional capacity, psychotic symptoms, behavioral problems, depressive symptoms, extrapyramidal signs, comorbidities, and duration of illness. RESULTS: A 1-point increase in the Blessed Dementia Rating Scale score was associated with a $1,411 increase in direct medical costs and a $2,718 increase in unpaid caregiving costs. Direct medical costs also were $3,777 higher among subjects with depressive symptoms than among those who were not depressed. CONCLUSIONS: Medical care costs and unpaid caregiving costs relate differently to patients' clinical characteristics. Poorer functional status is associated with higher medical care costs and unpaid caregiving costs. Interventions may be particularly useful if targeted in the areas of basic and instrumental activities of daily living.

Aged↗

Bone marrow Th2 cytokine expression as predictor for relapse in childhood acute lymphoblastic leukemia (ALL).

The immunological environment of leukemic blasts in the bone marrow might play a decisive role in determining an individual's risk for relapse. In order to identify potential predictors of relapse and to elucidate the mechanisms of immune control of leukemic blasts we examined the expression of cytokines, costimulatory molecules and members of the TNF family in leukemic marrow samples in a prospective study. Samples from 49 consecutive pediatric patients with B cell precursor acute lymphocytic leukemia (BCP ALL) were analyzed by semiquantitative RT-PCR. We identified interleukin (IL)-10 expression as a significant adverse prognostic indicator in childhood BCP-ALL. The event free survival (EFS) of patients expressing IL-10 mRNA in high quantity was significantly lower compared with patients expressing low IL-10 mRNA. Taqman RT-PCR of sorted cell populations showed that IL-10 mRNA was synthetized almost exclusively by NK or T cells. In addition, we found an increased expression of IL-1, IL-4, CD86 and VEGF mRNA in patients with late relapses. Possibly, ALL cells mediate a Th2 shift through increased expression of CD86 and thereby influence the individual relapse risk. These findings emphasize the role of the immune system for the outcome of childhood ALL.

Adolescent↗

Motor signs predict poor outcomes in Alzheimer disease.

OBJECTIVE: To examine whether the presence of motor signs has predictive value for important outcomes in Alzheimer disease (AD). METHODS: A total of 533 patients with AD at early stages (mean Folstein Mini-Mental State Examination [MMSE] 21/30 at entry) were recruited and followed semiannually for up to 13.1 years (mean 3) in five University-based AD centers in the United States and European Union. Four outcomes, assessed every 6 months, were used in Cox models: cognitive endpoint (Columbia Mini-Mental State Examination < or = 20/57 [ approximately MMSE < or = 10/30]), functional endpoint (Blessed Dementia Rating Scale > or = 10), institutionalization equivalent index, and death. Using a standardized portion of the Unified PD Rating Scale (administered every 6 months for a total of 3,149 visit-assessments, average 5.9 per patient), the presence of motor signs, as well as of individual motor sign domains, was examined as time-dependent predictor. The models controlled for cohort, recruitment center, sex, age, education, a comorbidity index, and baseline cognitive and functional performance. RESULTS: A total of 39% of the patients reached the cognitive, 41% the functional, 54% the institutionalization, and 47% the mortality endpoint. Motor signs were noted for 14% of patients at baseline and for 45% at any evaluation. Their presence was associated with increased risk for cognitive decline (RR, 1.72; 95% CI, 1.24 to 2.38), functional decline (1.80 [1.33 to 2.45]), institutionalization (1.68 [1.26 to 2.25]), and death (1.38 [1.05 to 1.82]). Tremor was associated with increased risk for reaching the cognitive and bradykinesia for reaching the functional endpoints. Postural-gait abnormalities carried increased risk for institutionalization and mortality. Faster rates of motor sign accumulation were associated with increased risk for all outcomes. CONCLUSIONS: Motor signs predict cognitive and functional decline, institutionalization, and mortality in Alzheimer disease. Different motor sign domains predict different outcomes.

Aged↗

Neuropsychological predictors of dependency in patients with Alzheimer disease.

OBJECTIVE: To determine whether specific cognitive deficits can predict the progression of Alzheimer disease (AD). METHODS: Two hundred fifty-two patients with AD enrolled in the Predictors Study were followed at 6-month intervals for up to 4.5 years with neurologic, cognitive, and psychiatric examinations. Neuropsychological functions were assessed by the Modified Mini-Mental State Examination (mMMSE). Items of mMMSE were divided into five cognitive domains: temporospatial orientation, short-term memory, long-term memory, language, and visuoconstructive functions. Loss of autonomy was assessed by both the Dependency Scale (DS) and the Equivalent Institutional Care (EIC) rating. Cox proportional hazards models, adjusted for age, sex, estimated duration of illness at entry into the study, and presence of extrapyramidal signs and behavioral disturbances, were used to determine the predictive value of each neuropsychological domain on dependency outcomes. RESULTS: Global mMMSE, temporospatial orientation, and short-term memory scores were associated with a greater relative risk of moderate or severe dependency. The visuoconstructive score predicted the development of severe dependency. Long-term memory and language scores were not predictive of the EIC or DS endpoints. CONCLUSIONS: The presence of certain neuropsychological deficits at a patient's initial visit, such as short-term memory, temporospatial orientation, and constructive apraxia, predict more rapid dependency in patients with Alzheimer disease. Neuropsychological items have different weights in term of predictive power, and these effects are independent of the influence of age and disease duration at baseline.

Age Distribution↗

Medicines and psychoactive agents in traffic users--the medico-legal problem in Poland.

The increasing number of traffic accidents connected with rapid development of motorization makes us think of their causes. Regulations by law binding in Poland demand traffic users to be checked up on the presence of agents similar ethyl alcohol. Commonly abused medicines, especially sedative and psychotropic but also hypnotic and analgesic are a great traffic problem. Up to the present analytical procedures and a model medico-legal opinion on the influence of medicines on psychophysical efficiency have not been standardised. In the paper the authors have presented the results of their research on agents negatively influencing the human psychophysical efficiency carried out in the Forensic Medicine Department, Silesian University of Medicine, Katowice. The research comprised individuals involved in both traffic crashes and accidents who (as checked) either where not under the influence of ethyl alcohol or the concentration of ethanol was low (1 per thousand). Positive cases most often showed only one sort of medicines (barbiturates, benzodiazepines or opiates). In other cases barbiturates and benzodiazepines, benzodiazepines and opiates as well as derivatives of benzodiazepine and tricyclic antidepressants were determined. Blood concentrations of all these substances were in a wide range of therapeutic doses.

Accidents, Traffic↗

No indication for a defect in toll-like receptor signaling in patients with hyper-IgE syndrome.

Hyper-IgE syndrome is a rare primary immunodeficiency of unknown etiology characterized by recurrent infections of the skin and respiratory system, chronic eczema, elevated total serum IgE, and a variety of associated skeletal symptoms. Recent reports about susceptibility to pyogenic bacterial infections and high IgE levels in patients and animals with defects in toll-like receptor (TLR) signaling pathways prompted us to search for TLR signaling defects as an underlying cause of hyper-IgE syndrome. Blood samples from six patients with hyper-IgE syndrome were analyzed for serum cytokine levels, intracellular cytokine production in T cells after stimulation with PMA/ionomycin, and cytokine production from peripheral blood mononuclear cells stimulated by TLR ligands and bacterial products including LPS (TLR4), peptidoglycan (TLR2), PolyIC (TLR3), R848 (TLR7/8), CpG-A, and CpG-B (TLR9), zymosan and heat killed Listeria monocytogenes. All results were compared to data from healthy controls. A reduction in IFN-gamma, IL-2, and TNF-alpha producing T cells after PMA stimulation suggested a reduced inflammatory T cell response in patients with hyper-IgE syndrome. Increased serum levels of IL-5 indicated a concomitant Th2 shift. However, normal production of cytokines (TNF-alpha, IL-6, IL-10, IFN-alpha, IP-10) and upregulation of CD86 on B cells and monocytes after TLR stimulation made a defect in TLR signaling pathways highly unlikely. In summary, our data confirmed an imbalance in T cell responses of patients with hyper-IgE syndrome as previously described but showed no indication for an underlying defect in toll-like receptor signaling.

Adolescent↗

[Aging and spermatogenesis: an histologic, cytogenetic and apoptosis study].

OBJECTIVE: The increase of frequency of Assisted Reproductive Techniques (ART) for elder men raises the question of the genetic risk for the offspring. Our aim was to evaluate the influence of ageing on the testicular histology, the aneuploidy rate in testis postmeiotic cells and the DNA fragmentation in sperm. PATIENTS AND METHODS: We performed a histomorphometric study of 36 men aged from 61 to 102 years and 10 young men from 29 to 40 years. The aneuploidy rate was evaluated by fluorescent in situ hybridation (FISH X, Y, 18) and DNA fragmentation in spermatozoa was evaluated by TUNEL. RESULTS: Histomorphometry showed various alterations of testicular histology with age including thickening of the basal membrane when spermatogenesis was arrested. The number of germinal cells and Sertoli cells decreased with age with important individual variations. Nevertheless spermatogenesis could be possible until 95 years. The rate of aneuploidy was not influenced by age when spermatogenesis was complete. However, we observed an increased aneuploidy rate in postmeiotic cells when spermiogenesis was arrested. On the other hand apoptosis was not increased with age. DISCUSSION AND CONCLUSION: Our study confirms that spermatogenesis is possible until a very advanced age (95 years) without any specific chromosome risk. The question of mutagenesis remains to be solved.

Adult↗

Motor signs during the course of Alzheimer disease.

BACKGROUND: Motor signs (MOSIs) are common in Alzheimer disease (AD) and may be associated with rates of cognitive decline, mortality, and cost of care. OBJECTIVE: To describe the progression and identify predictors of individual MOSIs in AD. METHODS: A cohort of 474 patients with AD at early stages was followed semiannually for up to 13.1 years (mean 3.6 years) in five centers in Europe and the United States. MOSIs were rated using a standardized portion of the Unified Parkinson's Disease Rating Scale. Overall, 3,030 visits/assessments of MOSIs (average 6.4/patient) were performed. Prevalence and incidence rates were calculated, and cumulative risk graphs were plotted for individual non-drug-induced MOSI domains. Rates of change over time taking into account potential covariates were also estimated. With use of each MOSI domain as outcome in Cox models, predictors of MOSI incidence were identified. RESULTS: At least one MOSI was detected in 13% of patients at first examination and in 36% for the last evaluation. Total MOSI score increased at an annual rate of 3% of total possible score. Rates of annual change for speech/facial expression (4%), rigidity (2.45%), posture/gait (3.9%), and bradykinesia (3.75%) were of similar magnitude, and their occurrence increased from first (3 to 6%) to last (22 to 29%) evaluation. Tremor was less frequent throughout the course of the disease (4% at first and 7% at last evaluation) and worsened less (0.75% increase/year). CONCLUSIONS: Most motor signs occur frequently and progress rapidly in Alzheimer disease. Tremor is an exception in that it occurs less frequently and advances at slower rates.

Aged↗

Characterization of honey amino acid profiles using high-pressure liquid chromatography to control authenticity.

Amino acid analysis of honey by high-performance liquid chromatography (HPLC) was used first to discriminate different botanical origins and then to combat adulteration. Pure honeys of seven selected floral varieties were examined. A principal component analysis (PCA) was carried out on the results after selection of the most discriminating parameters. Lavender honeys were thus perfectly characterized, but complete satisfaction was not obtained with the six other varieties. This method (analysis by HPLC and statistical processing by PCA) enabled us to detect the addition of sugar syrup to rape and fir honeys.

Amino Acids↗

[Infection peritonitis in patients undergoing continuous ambulatory peritoneal dialysis: microbiological review during an four-year period].

The purpose of this study was to analyse the microbiological characteristics of infectious peritonitis in patients undergoing continuous ambulatory peritoneal dialysis. This study was conducted at the CHU Nancy from 1999 to 2002. The diagnosis of peritonitis was based on cloudy peritoneal effluent (>100 cells per mm(3)) with an elevated leukocyte count (>50%), on isolation of bacteria or fungi and on symptoms such as abdominal discomfort or pain. The majority of infections associated with continuous ambulatory peritoneal dialysis were caused by Gram-positive bacteria (68%), Gram-negative bacteria (31%), and Candida (1%). The coagulase-negative staphylococci were the most common cause of peritonitis. The antibiotic sensitivity of species corresponded to community-acquired isolation.

Aged↗

Distinct gene signatures of transient and acute megakaryoblastic leukemia in Down syndrome.

Approximately 10% of newborns with Down syndrome develop Transient Leukemia (TL), a disorder that is unique to infants with constitutional trisomy 21 (or trisomy 21 mosaicism). TL blasts disappear spontaneously within the first 3 months of life in the majority of cases. Despite the resolution of TL, 20-30% of these newborns will go on to develop acute megakaryoblastic leukemia (AMKL) later in life. In this study, samples from both TL and AMKL patients were examined using cDNA microarrays to study the pathogenic progression from TL to AMKL. TL and AMKL samples partition separately by cluster analysis, and AMKL samples had substantial increases in apolipoprotein C-I, transporter 1, myosin alkali light chain 4, and spermidine/spermine N-acetyltransferase, compared to TL samples. Although these findings will require validation in an independent series of TL and AMKL samples, they indicate that TL and AMKL have distinct gene signatures, and provide a basis for studies of the different mechanisms underlying either the resolution of TL or its progression to AMKL.

Adolescent↗

The cell wall-modifying xyloglucan endotransglycosylase/hydrolase LeXTH1 is expressed during the defence reaction of tomato against the plant parasite Cuscuta reflexa.

A suppressive subtractive hybridization technique was used to identify genes, which were induced during the early phases of the interaction between dodder (Cuscuta reflexa), a phanerogamic parasite, and its incompatible host plant tomato. One of the identified genes encodes a tomato xyloglucan endotransglycosylase/hydrolase (XTH)--an enzyme involved in cell wall elongation and restructuring. The corresponding LeXTH1 mRNA accumulated 6 h after attachment of the parasite. In contrast, wounding did not influence the expression level. Subsequent to LeXTH1 mRNA accumulation, an increase in XTH activity at the infection sites as well as in adjacent tissues was observed. The effect of IAA on LeXTH1 expression was analyzed because the concentration of this phytohormone is known to increase in the tomato tissue during the interaction with the parasite. LeXTH1 mRNA accumulation was in fact induced by external application of auxin. However, in the auxin-insensitive tomato mutant diageotropica, Cuscuta induced LeXTH1-mRNA accumulated with a time course similar to wild type tomato. Thus, auxin appears not to be an essential signal for infection-induced LeXTH1 activation. Our data suggest a role for xyloglucan transglycosylation in defence reactions associated with the incompatible tomato- Cuscuta interaction.

Cell Wall↗

Mild cognitive impairment--beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment.

The First Key Symposium was held in Stockholm, Sweden, 2-5 September 2003. The aim of the symposium was to integrate clinical and epidemiological perspectives on the topic of Mild Cognitive Impairment (MCI). A multidisciplinary, international group of experts discussed the current status and future directions of MCI, with regard to clinical presentation, cognitive and functional assessment, and the role of neuroimaging, biomarkers and genetics. Agreement on new perspectives, as well as recommendations for management and future research were discussed by the international working group. The specific recommendations for the general MCI criteria include the following: (i) the person is neither normal nor demented; (ii) there is evidence of cognitive deterioration shown by either objectively measured decline over time and/or subjective report of decline by self and/or informant in conjunction with objective cognitive deficits; and (iii) activities of daily living are preserved and complex instrumental functions are either intact or minimally impaired.

Aged↗