Search PubMed⌕ Search

Biomedical subjects

M Schneider

Publications and source records attributed to M Schneider.

At least 163 records · Page 9Linked to original sources
PubMed2001

Cytogenetic analysis of human zygotes displaying three pronuclei and one polar body after intracytoplasmic sperm injection.

BACKGROUND: Digynic zygotes with three pronuclei and one polar body obtained after intracytoplasmic sperm injection (ICSI) were studied cytogenetically to elucidate the frequency and origin of chromosomal abnormalities at the earliest stage of conception. METHODS: Uncleaved, single-cell zygotes were incubated with podophyllotoxin and vinblastine and fixed by a gradual fixation air drying method. The chromosomes were stained with Giemsa. RESULTS: Twenty-two (50%) out of 44 informative zygotes revealed cytogenetic alterations, including aneuploidy (six cells, 13.6%), structural aberrations (10 cells, 22.7%) and combinations of numerical and structural abnormalities (two cells, 4.5%). In one case (2.3%), double aneuploidy or an effect of chromosomal translocation could not be distinguished and one zygote (2.3%) turned out tetraploid due to injection of a diploid spermatozoon. Two zygotes (4.5%) showed an irregular chromatid segregation between the two maternal complements. In completely analysable cells, the sex chromosome ratio XXX:XXY was 17:15. CONCLUSIONS: Digynic ICSI zygotes carry a high rate of cytogenetic abnormalities that obviously have been transmitted by the participating oocytes and spermatozoa. We also confirmed the previously reported, possibly ICSI-induced irregular oocyte chromatid segregation. The results suggest that aneuploidy in the oocytes must have been caused by predivision instead of non-disjunction.

Cell Nucleus↗
PubMed2001

Incomplete lupus erythematosus: results of a multicentre study under the supervision of the EULAR Standing Committee on International Clinical Studies Including Therapeutic Trials (ESCISIT).

OBJECTIVE: Patients characterized with antinuclear antibodies (ANA) and disease symptoms related to one organ system can be described as having incomplete systemic lupus erythematosus (SLE). The aim of this multicentre study was to describe the outcome of these so-called incomplete SLE patients. Two aspects of the outcome were studied: (i) the disease course, defined by the presence or absence of clinical symptoms; and (ii) the number of patients that eventually developed full SLE. METHODS: Outcome parameters were the ACR criteria, the SLE disease Activity Index (SLEDAI), the European Consensus Lupus Activity Measure (ECLAM) and the requirement for treatment. In 10 European rheumatology centres, patients who had been evaluated in the last 3 months of 1994 and had been diagnosed as having incomplete SLE on clinical grounds for at least 1 yr were included in the study. All 122 patients who were included in the study were evaluated annually during 3 yr of follow-up. RESULTS: Our results are confined to a patient cohort defined by disease duration of at least 1 yr, being under clinical care at the different centres in Europe. These patients showed disease activity that was related mostly to symptoms of the skin and the musculoskeletal system, and leucocytopenia. During the follow-up, low doses of prednisolone were still being prescribed in 43% of the patients. On recruitment to the study, 22 of the 122 incomplete SLE patients already fulfilled the ACR criteria for the diagnosis of SLE. In the 3 yr of follow-up only three patients developed SLE. CONCLUSIONS: A high proportion of patients in our cohort defined on clinical grounds as having incomplete SLE eventually showed disease activity defined by the SLEDAI as well as ECLAM. However, only three cases developed to SLE during the follow-up. This suggests that incomplete SLE forms a subgroup of SLE that has a good prognosis.

Adolescent↗
PubMed2001

Combination of cisplatin-doxorubicin-cyclophosphamide in adenocarcinoma of unknown primary site: a phase II trial.

The purpose of this report is to evaluate toxicity, response, and survival of the cyclophosphamide-doxorubicin-cisplatin (CAP) chemotherapy regimen in patients with adenocarcinoma of unknown primary site (ACUP). Twenty-two patients with ACUP were eligible for this study between June 1992 and April 1999. There were 13 men (59%) and 9 women (41%) with a median age of 53.5 years (range: 29--78 years). Lung (seven), liver (six), vertebral bone site (six), and abdominal nodes (six) were the most common metastatic sites. Treatment consisted of doxorubicin 50 mg/m(2), cyclophosphamide 1,000 mg/m(2), and cisplatin 100 mg/m(2) (CAP), administered every 3 weeks; a total of six courses were planned. Twenty-two patients were assessable for toxicity and 20 patients were assessable for response. Grade III to IV neutropenia was observed in 14 patients (64%); febrile neutropenia occurred in 6 patients (27%) and in 10 cycles (12.5%). Grade III to IV anemia and thrombocytopenia were found in 12 (54.5%) and 9 patients (41%), respectively. Grade III to IV nausea and vomiting was observed in 9 patients (41%). Ten patients, 50% of the assessable population, obtained an objective response, including 3 complete (15%) and 7 partial (35%) responses. The median response duration was 3.9 months (range: 0.5--13.3 months). One patient (5%) had stable disease and 5 patients (25%) had progressive disease. The median overall survival and the median time to progression were 10.7 months (range: 0.4--56.9 months) and 8.8 months (range: 6.6--16.5 months), respectively. The CAP regimen in patients with ACUP had significant activity. This chemotherapy regimen induced a high level of grade III to IV toxicities and could not be considered as a treatment of reference. However, the emergence of long-term survivors among responder patients highlighted the need to search for an active treatment for patients with ACUP.

Adenocarcinoma↗
PubMed2001

Phase II trial of a paclitaxel-carboplatin combination in recurrent squamous cell carcinoma of the head and neck.

OBJECTIVE: Twenty-seven patients with recurrent squamous cell carcinoma of the head and neck were entered in a multicenter study to determine the efficacy of the paclitaxel-carboplatin association. METHODS: Standard eligibility criteria applied, i.e. measurable disease, and chemotherapy given as induction treatment or concomitant chemoradiotherapy was allowed if completed more than 6 months prior to the study. Every 21 days, paclitaxel 175 mg/m(2) and carboplatin AUC 6 were administered. The patient group included 3 females and 24 males with a median age of 61 years (range 39-75 years). RESULTS: All patients were assessable for toxicity and 24 for responses. Main grade 3-4 toxicities were: neutropenia (62.9%), febrile neutropenia (18.5%), anemia (11.1%), thrombocytopenia (14.8%), mucositis (7.4%) and vomiting (7.4%). Among the intent-to-treat population, 29.6% of patients had an objective response, with a median response duration of 4.2 months (range 1-5.7 months). Stable and progressive disease were observed in 11.1 and 48.1% of patients, respectively. The median overall survival was 7.2 months (range 0.5-10.9 months). CONCLUSION: From these data, paclitaxel-carboplatin seems to have an activity in recurrent squamous cell carcinoma of the head and neck, but the high level of toxicity highlights the need to search for a safer chemotherapy combination.

Adult↗
PubMed2001

Clinical prognostic factors for patients with recurrent head and neck cancer: implications for randomized trials.

The purpose of our study was to determine the clinical prognostic factors for the duration of the overall survival from recurrence (OSR) in patients with recurrent head and neck squamous-cell carcinoma. We performed a retrospective analysis on 496 patients treated between 1982 and 1993 at the Antoine Lacassagne Center. The significant favorable prognostic factors for the OSR were: initial T(1-2) (p = 0.008), no initial nodal involvement (p = 0.002), no initial chemotherapy exposure (p = 0.002), induction chemotherapy response (p = 0.001), duration of disease-free interval (DFI; p = 0.0001), performance status (PS) 0-1 (p = 0.004) and local-regional recurrence (p = 0.001). In the multivariate analysis, the apparent nonsignificance of all factors apart from the DFI suggested that relevant prognostic factors could be embedded in the DFI. Multivariate analysis was performed after excluding the DFI. The results indicated that local-regional recurrence, PS 0-1 and no initial chemotherapy exposure remained significant favorable prognostic factors for the OSR. The advantages of taking into account such prognostic factors are to eliminate the patient selection bias and to ensure a fairer comparative evaluation of new or already existing agents in recurrent head and neck cancer.

Adult↗
PubMed2001

G-protein beta(3) subunit gene (GNB3) 825T allele is associated with enhanced renal perfusion in early hypertension.

The C825T polymorphism of the gene encoding the G-protein beta(3) subunit (GNB3) is associated with increased intracellular signal transduction and arterial hypertension. The aim of the study was to investigate the impact of this polymorphism on early adaptive processes of the left ventricle and renal hemodynamic changes in young normotensive to mildly hypertensive subjects. Ninety-five white male students with normal or mildly elevated blood pressure were genotyped for the GNB3 C825T polymorphism. In each participant, 24-hour ambulatory blood pressure, left ventricular structure and function (2D-guided M-mode echocardiography), renal plasma flow (para-aminohippurate clearance), glomerular filtration rate (inulin clearance), and 24-hour urinary sodium excretion were determined. The GNB3 825T allele was not associated with casual or ambulatory blood pressure, parameters of left ventricular structure or function, glomerular filtration, or 24-hour urinary sodium excretion. However, in T:-allele carriers (CT+TT), renal plasma flow was higher than in CC subjects (CT/TT: 659+/-96 versus CC: 614+/-91 mL/min, P:=0.019). ANOVA disclosed that renal plasma flow was independently influenced by both genotype and blood pressure, with hypertensives having a higher renal plasma flow than normotensive subjects. This was the fact irrespective of the criteria used for the definition of hypertension (World Health Organization or 24-hour ambulatory blood pressure criteria). The GNB3 825T variant is associated with increased renal perfusion in this study. Because early renal hemodynamic changes play a pivotal role in the pathogenesis of essential hypertension, our data suggest a relevance of increased G-protein activation in the pathogenesis of hypertension.

Adult↗
PubMed2001

The type 2 iodothyronine deiodinase is essential for adaptive thermogenesis in brown adipose tissue.

Type 2 iodothyronine deiodinase (D2) is a selenoenzyme, the product of the recently cloned cAMP-dependent Dio2 gene, which increases 10- to 50-fold during cold stress only in brown adipose tissue (BAT). Here we report that despite a normal plasma 3,5,3'-triiodothyronine (T3) concentration, cold-exposed mice with targeted disruption of the Dio2 gene (Dio2(-/-)) become hypothermic due to impaired BAT thermogenesis and survive by compensatory shivering with consequent acute weight loss. This occurs despite normal basal mitochondrial uncoupling protein 1 (UCP1) concentration. In Dio2(-/-) brown adipocytes, the acute norepinephrine-, CL316,243-, or forskolin-induced increases in lipolysis, UCP1 mRNA, and O(2) consumption are all reduced due to impaired cAMP generation. These hypothyroid-like abnormalities are completely reversed by a single injection of T3 14 hours earlier. Recent studies suggest that UCP1 is primarily dependent on thyroid hormone receptor beta (TR beta) while the normal sympathetic response of brown adipocytes requires TR alpha. Intracellularly generated T3 may be required to saturate the TR alpha, which has an approximately fourfold lower T3-binding affinity than does TR beta. Thus, D2 is an essential component in the thyroid-sympathetic synergism required for thermal homeostasis in small mammals.

Adipose Tissue, Brown↗
PubMed2001

Factor V(LEIDEN) and cardiopulmonary bypass: investigation of haemostatic parameters and the effect of aprotinin using an ex vivo model.

It has been suggested that aprotinin results in significantly increased risk for perioperative thrombotic complications in patients with Factor V(LEIDEN) (F5L) due to its ability to competitively inhibit activated protein C (APC) function in vitro. No clinical studies have been performed to assess the effect of aprotinin on APC function of F5L in vivo. We developed an ex vivo model to mimic the effects of cardiopulmonary bypass with the exclusion of the patient in order to assess APC function. Blood from normal (n = 2) and F5L heterozygous donors (n = 2) was treated with aprotinin or placebo (saline). The blood was heparinized, added to the prime and circulated at 2 l/min through a modified cardiopulmonary bypass circuit. After 60 min of circulation, the heparin was neutralized with protamine sulfate. Blood samples, drawn at specific time points, were analysed for APC ratio. Results showed a decrease in APC ratio for both F5L and normal bloods with the addition of aprotinin (18% and 40%, respectively). APC ratios also decreased with the commencement of extracorporeal circulation for all bloods, resulting in an APC ratio of 1.35 in normal placebo-treated blood and 0.67 in F5L placebo-treated blood. The combined effect of aprotinin and extracorporeal circulation resulted in APC ratios of 0.90 for normal blood and 0.63 for F5L blood, corresponding to a severe dysfunction of APC intraoperatively (reference range 1.9-4.0). The data from this model predict an increased risk of perioperative thrombosis due to inhibition of APC function in cardiac surgical patients heterozygous for the F5L mutation. Aprotinin further compounds the severity of APC dysfunction, though the effect is more severe in normal blood. The ex vivo model employed was an effective tool for the investigation of the haemostatic effect of aprotinin. This model may be exploited for other applications such as the investigation of novel or emerging haemostatic agents prior to clinical trial.

Aprotinin↗
PubMed2001

Osteoporosis screening in systemic lupus erythematosus: impact of disease duration and organ damage.

The aim of the present study was to assess the effects of disease severity and demonstrable organ damage as risk factors for the development of osteoporosis in systemic lupus erythematosus (SLE). Sixty-four SLE patients were included. Mean disease duration was 7.7 +/- 5.7 y. Thirty-two patients had persistent organ damage, defined as SLICC-ACR damage score > or = 1. Disease activity measured by SLAM-2 ranged from 3 to 27. Bone mineral density (BMD) measurements were performed with dual X-ray absorptiometry. In addition, biochemical markers of bone metabolism were studied. BMD was inversely correlated with disease duration, damage score and cumulative glucocorticoid intake, but no correlation was found for current glucocortioid use or with markers of bone metabolism. In a multivariate analysis, body weight, disease duration and damage index fitted best for the prediction of BMD at both lumbar spine and femoral neck. Seven out of 64 patients had osteoporosis according to WHO criteria. In conclusion, severe osteoporosis is uncommon in lupus patients. Disease activity and severity were no major risk factors for loss of BMD in this study, but persistent non-bone-related organ damage was significantly linked to the presence of osteoporosis measured as decreased BMD. Our data suggest that, in addition to patients receiving glucocorticoids, patients with an SLICC-ACR > or = 1 or a disease duration > or = 7 y might benefit from regular monitoring of BMD as secondary prevention of damage.

Adult↗
PubMed2001

Systemic lupus erythematosus. Disease outcome in patients with a disease duration of at least 10 years: second evaluation.

Data related to the disease course of patients with systemic lupus erythematosus (SLE) with special attention to the persistence of disease activity in the long term are scarce. At this moment reliable figures are only known about the survival rate as a measure of outcome. The aim of this multicenter study was to describe the outcome of SLE patients with a disease duration of greater than 10 y. Outcome parameters were two disease activity-scoring systems (SLEDAI and ECLAM), the end organ damage (SLICC/ACR damage index) and treatment. Our results are derived from 187 SLE patients followed at 10 different centres in Europe over a period of 1 y. Serious clinical signs or exacerbations, defined by the occurrence or detoriation of already existing symptoms of renal and cerebral nervous systems were observed in 2-11% of the patients, seizures and psychosis in 3%, proteinuria in 11% and an increase in serum creatinine in 5% of the patients. No change took place in the overall damage index. Yet, the disease course in most patients was characterized by periods of tiredness (42-60%), arthritis (20-25%), skin involvement such as malar rash (32-40%), migraine (15-20%), anaemia (15%) and leucopenia (17-19%). Summarizing these results it is shown that patients, still under care after such a long time of having this disease, do have a disease that is far from extinguished.

Adult↗
PubMed2001

Emergency contraception: pediatricians' knowledge, attitudes, and opinions.

UNLABELLED: Emergency contraception (EC) is the use of a method of contraception after unprotected intercourse to prevent unintended pregnancy. Although first described over 20 years ago, physician awareness of EC has been limited and many feel uncomfortable prescribing it. OBJECTIVE: To assess the knowledge, attitudes, and opinions of practicing pediatricians regarding the use of EC in adolescents. METHODS: An anonymous questionnaire was mailed to all 954 active members of New York Chapter 2, District II of the American Academy of Pediatrics. The questionnaire assessed basic knowledge, attitudes, and opinions regarding EC in adolescents. Data were analyzed by physician age, gender, year completed residency, and practice type. RESULTS: Two hundred thirty-three practicing pediatricians (24.4%) completed the survey. Of the respondents, 23.7% had been asked to prescribe EC to an adolescent and 49% of these cases involved a rape victim. Only 16.7% of pediatricians routinely counsel adolescent patients about the availability of EC, with female pediatricians more likely to do so. Most respondents (72.9%) were unable to identify any of the Food and Drug Administration-approved methods of EC. Only 27.9% correctly identified the timing for its initiation and only 31.6% of respondents felt comfortable prescribing EC. Inexperience with use was cited as the primary reason for not prescribing EC by 70% of respondents. Twelve percent cited moral or religious reasons and 17% were concerned about teratogenic effects. There were no differences in comfort level based on age, gender, or practice type. Twenty-two percent of respondents believed that providing EC encourages adolescent risk-taking behavior and 52.4% would restrict the number of times they would dispense EC to an individual patient. A minority of respondents (17%) believed that adolescents should have EC available at home to use if necessary and only 19.6% believed that EC should be available without a prescription. The vast majority (87.5%) were interested in learning more about EC. CONCLUSIONS: Despite the safety and efficacy of EC, the low rate of use is of concern. Pediatricians are being confronted with the decision to prescribe EC but do not feel comfortable prescribing it because of inadequate training in its use. Practicing pediatricians are aware of their lack of experience and are interested in improving their knowledge base.

Adolescent↗
PubMed2001

[Man-nature-technology. Philosophical considerations of human-animal-relations].

Man's position in nature is equivocal. Man is part of nature and through evolution is linked to other living beings. Although an "Animal among Animals", nature has provided him with capabilities that separate him from all living beings in its realm. These comprise the ability for reflection and subsequent moral behavior, but also the gift (and necessity) for using technology to shape and subjugate his natural environment. Based upon this "Dual Nature of Man" the essay focuses on the web of interactions between Man, Nature and Technology. Modern ethics of animal protection argue in favor of extending the principle of equality ("To Each His Own") to include animals as well. However, the principle of equality is a purely formal, heuristic rule for assigning morally just determinations of value. It requires normative padding as far as its content is concerned. Consequently, the content of the principle of equality ought to be more closely determined in keeping with the ideal of humanity.

Altruism↗
PubMed2001

Outpatient flexible cystoscopy in men: a randomized study of patient tolerance.

PURPOSE: We evaluate the pain of immediate versus delayed outpatient flexible cystoscopy in men after topical local anesthesia application. MATERIALS AND METHODS: A total of 100 consecutive men with superficial bladder tumors were randomized to immediate or delayed surveillance flexible cystoscopy after intraurethral instillation of lidocaine gel. Patients recorded the level of pain experienced during cystoscopy on a 4-point pain scale and on a 10-point visual linear analog self-assessment scale. RESULTS: Of the 100 patients 50 underwent immediate and 50 underwent delayed cystoscopy. The mean pain score on a scale of 1-no to 4-severe pain was 1.7 after immediate cystoscopy compared with 1.6 after delayed cystoscopy (p = 0.9). The mean linear analog self-assessment score on a scale of 1-no to 10-most pain was 2.1 after immediate cystoscopy versus 1.8 after delayed cystoscopy (p = 0.7). CONCLUSIONS: There was no difference in pain perception in men undergoing immediate or delayed outpatient flexible cystoscopy using the same local anesthetic.

Aged↗
PubMed2001

Immediate versus delayed outpatient flexible cystoscopy: final report of a randomized study.

PURPOSE: To evaluate discomfort experienced by men undergoing an immediate versus delayed outpatient flexible cystoscopy after topical local anesthesia. PATIENTS AND METHODS: Two hundred eighty eight consecutive men with superficial bladder tumors were randomized to undergo immediate or delayed surveillance flexible cystoscopy after intraurethral instillation of lidocaine jelly. The patients recorded their level of pain experienced during cystoscopy on a 4-point pain scale and on a 10-point visual analogue (VAS) scale. RESULTS: Of the 288 patients, 145 underwent immediate cystoscopy and 143 had a delayed cystoscopy. The mean pain score on a scale of 1 (no pain) to 4 (severe pain) was 1.6 after immediate cystoscopy compared with 1.5 after delayed cystoscopy (p=7). The mean VAS score on a scale of 1 (no pain) to 10 (most painful) was 1.8 after immediate cystoscopy versus 1.7 after delayed cystoscopy (p=5). CONCLUSION: There was no difference in pain perception among men undergoing an immediate or a delayed outpatient flexible cystoscopy using the same local anesthetic.

Aged↗