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Biomedical subjects

M Schachter

Publications and source records attributed to M Schachter.

At least 37 records · Page 2Linked to original sources
PubMed2001

Outcome of ICSI using fresh and cryopreserved-thawed testicular spermatozoa in patients with non-mosaic Klinefelter's syndrome.

BACKGROUND: Recently, intracytoplasmic sperm injection (ICSI) of testicular spermatozoa retrieved surgically from patients with non-mosaic Klinefelter's syndrome resulted in several deliveries. The aim of this study was to evaluate the outcome of ICSI using fresh and cryopreserved-thawed testicular spermatozoa in these patients. METHODS AND RESULTS: Following informed consent regarding the genetic risks of their potential offspring, mature testicular spermatozoa were found in five out of 12 (42%) patients who underwent testicular sperm extraction, and ICSI was performed while excess tissue was cryopreserved. The mean age of the patients was 28.7 +/- 3.6 (range 23-36 years). Their baseline FSH was elevated (mean 38.3 +/- 11.4; range 22-58 mIU/ml). All patients had small testicles of 2-4 ml in volume. The outcome of ICSI using fresh or cryopreserved-thawed testicular spermatozoa during five cycles in each group, was compared. No statistical significant difference was found in the two pronuclear fertilization rate (66 versus 58%), embryo cleavage rate (98 versus 90%) and embryo implantation rate (33.3 versus 21.4%) for fresh or cryopreserved sperm accordingly. The clinical outcome after using fresh testicular sperm included two singleton pregnancies (one delivered and one ongoing) and a triplet pregnancy resulting in a twin delivery (after reduction of an 47,XXY embryo). After using cryopreserved-thawed testicular spermatozoa, two pregnancies were obtained resulting in one delivery of twins and one early spontaneous abortion. CONCLUSIONS: Outcome of ICSI using cryopreserved-thawed testicular spermatozoa of patients with non-mosaic Klinefelter's syndrome is comparable with that following the use of fresh spermatozoa. The genetic implications for the future offspring should be explained to the patients.

Adult↗
PubMed2001

Monozygotic twinning after assisted reproductive techniques: a phenomenon independent of micromanipulation.

A 3 year retrospective analysis was conducted of pregnancies achieved after various assisted reproductive treatment modalities in our infertility practice, to calculate and compare the rates of monozygotic twinning (MZT). A total of 731 pregnancies achieved after various assisted reproduction treatments were reviewed. Gonadotrophin therapy for induction of ovulation and controlled ovarian hyperstimulation (COH) yielded 129 clinical pregnancies. Conventional IVF yielded 139 pregnancies. IVF and intracytoplasmic sperm injection (ICSI) with or without assisted hatching (AH) yielded 463 pregnancies, all during the same time period. The rates of multiple pregnancy (monozygotic and dizygotic) twins and triplets were recorded. MZT was found in 1.5% of ovulation induction or COH pregnancies (2/129). The incidence of MZT after conventional IVF was 0.72% (1/139). After IVF-ICSI/AH, MZT was found in 0.86% (4/463). The overall rate of MZT was 0.95% (7/731). Five cases were dizygotic triplets and two cases were monozygotic twins. We found the rate of MZT after assisted reproduction treatment increased more than two-fold over the background rate in the general population. Dizygotic triplets were found more often than monozygotic twins. The rate of MZT was consistently increased, irrespective of treatment modality or micromanipulation. This may signify that the aetiology of increased MZT after assisted reproduction is the gonadotrophin treatment rather than in-vitro conditions, micromanipulation, or multiple embryo transfer.

Adult↗
PubMed2001

Transcription factor NF kappa B expression and postsurgical organ dysfunction.

OBJECTIVE: To examine the role of neutrophil NF kappa B activation in organ dysfunction after major surgery. SUMMARY BACKGROUND DATA: NF kappa B is a transcription factor involved in the signal transduction of many stimuli that may participate in the pathogenesis of sepsis and resultant multiple organ dysfunction syndrome (MODS). It may therefore be a potential target for modulation in the reduction of postsurgical MODS. METHODS: Twenty-five patients undergoing major vascular surgery (thoracoabdominal aortic aneurysm repair) were studied. Perioperative levels of neutrophil NF kappa B, CD11b, and glutathione were measured. In vitro inhibition experiments using NF kappa B inhibitors were also performed. RESULTS: No differences in clinical parameters were apparent before surgery between the patients who subsequently developed MODS and those who did not. However, there was a significant difference in preoperative levels of NF kappa B between the patients who developed postoperative organ dysfunction and those who did not. There was also a significant preoperative difference between patients who survived surgery and those who did not. Glutathione levels were reduced both in patients who developed MODS and those who did not at the onset of surgery. NF kappa B inhibitors suppressed patient plasma-stimulated NF kappa B activation in healthy neutrophils. CONCLUSIONS: Preoperative neutrophil NF kappa B status may be a marker of postoperative outcome after major surgery, and therapy aimed at attenuating neutrophil NF kappa B activation may reduce postoperative sepsis and organ dysfunction.

Adolescent↗
PubMed2001

Action of an HMG CoA reductase inhibitor, lovastatin, on apoptosis of untransformed and ts-SV40 transformed human smooth muscle cells derived from saphenous vein.

The effect of lovastatin, an inhibitor of 3-hydroxymethyl-3-glutaryl coenzyme A (HMG CoA) reductase, was examined on human vascular smooth muscle cells (HVSMC). Untransformed HVSMC were obtained from saphenous vein and in addition an SV-40 transformed immortalized cell line (HVTs-SM1) derived from saphenous vein smooth muscle was also used. HVTs-SM1 cell proliferation and DNA synthesis were measured, and cell cycle analysis was performed by flow cytometry. Apoptosis in both cell types was assessed by a combination of flow cytometry, terminal deoxynucleotidyl transferase (TUNEL) reagent-based immunocytochemistry, DAPI staining, and DNA agarose gel electrophoresis. Lovastatin had no effect on apoptosis of HVSMC over 96 h in serum-free conditions or after stimulation with platelet-derived growth factor (PDGF-BB), although PDGF-BB increased apoptosis in HVSMC, and this was prevented by lovastatin. In HVTs-SM1 cells lovastatin inhibited cell proliferation and DNA synthesis and induced apoptosis in a time- and concentration-dependent manner. The effects of lovastatin on cell proliferation, DNA synthesis, and apoptosis were prevented by coincubation with mevalonate and geranylgeranyl pyrophosphate, but not by farnesyl pyrophosphate. Lovastatin does not induce apoptosis in saphenous vein HVSMC in culture and inhibits PDGF-BB-induced DNA synthesis and apoptosis. In contrast, in SV40 transformed immortalized HVTs-SM1 cells, lovastatin induces apoptosis and inhibits cell proliferation and DNA synthesis. The pro-apoptotic effects of lovastatin in SV40 transformed HVTs-SM1 cells may be related to the enhanced rate of proliferation or deregulation of the cell cycle in this cell line.

Apoptosis↗
PubMed2001

Hypercoagulable thrombophilic defects and hyperhomocysteinemia in patients with recurrent pregnancy loss.

PROBLEM: Placental perfusion may be compromised by increased thrombosis that leads to pregnancy complications and recurrent pregnancy loss (RPL). Since heritable thrombophilic defects and hyperhomocysteinemia are associated with increased thrombosis, their prevalence was evaluated in RPL patients with special emphasis on combinations of the above pathologies. METHODS OF STUDY: Evaluation of the prevalence of heritable thrombophilic defects (protein S, protein C, anti-thrombin III deficiency, and the mutations for factor V Leiden, methylenetetrahydrofolate reductase [MTHFR], and prothrombin gene), hyperhomocysteinemia. and combinations of these pathologies in 36 non-pregnant recurrent aborters compared with 40 parous women. RESULTS: We found a relatively high prevalence of deficiencies of plasma coagulation proteins in RPL patients compared with the controls. A non-significant different increase in factor V Leiden mutation was detected (6/36 [16%] compared with 2/40 [5%] in the control group, P = 0.14]. Hyperhomocysteinemia was found in 31% of the RPL patients. MTHFR mutation homozygosity was found in 6/36 (16%) of the aborting patients. Combinations of hyperhomocysteinemia and MTHFR mutation were found in three patients, with folate deficiency in two patients, and with B12 deficiency in three. CONCLUSIONS: Combinations of gene mutations, plasma protein deficiencies, and hyperhomocysteinemia, which are associated with an increased thrombotic risk, are more common in RPL patients compared with controls. Large-scale prevalence studies are needed in order to draw conclusions as to the causative relation of such a condition and RPL.

Abortion, Habitual↗
PubMed2001

Total antioxidant status and coronary artery calcification in type 1 diabetes.

OBJECTIVE: Type 1 diabetes is associated with a high risk of coronary heart disease (CHD), despite the absence of dyslipidemia. Oxidative modification may render LDLs more atherogenic. We aimed to assess antioxidant status in type 1 diabetes and its association with coronary artery calcification (CAC). RESEARCH DESIGN AND METHODS: Total antioxidant status (TAS) of serum was measured using the Trolox equivalent antioxidant capacity assay in 48 type 1 diabetic and 25 nondiabetic subjects. The presence of CAC was assessed in the diabetic subjects using electron beam computed tomography. RESULTS: TAS was reduced in type 1 diabetic subjects compared with nondiabetic subjects (Mann-Whitney U test, P < 0.0001). There were associations between TAS and HbA(1c) (r = -0.43; P = 0.0026) and duration of diabetes (r = -0.35; P = 0.0157). Significant CAC was considered present if the Agatston score was >10. The diabetic subjects with significant CAC were older (P < 0.0001); had longer duration of diabetes (P = 0.0002); were more likely to have high blood pressure (P = 0.040); had higher total cholesterol concentration (P = 0.039), serum creatinine concentration (P = 0.003), and urinary albumin-to-creatinine ratio (P = 0.022); and had lower serum TAS (P = 0.018) compared with those without significant calcification. In logistic regression with CAC as the dependent variable, TAS was entered as a predictor, and the effects on its predictive value of adding other explanatory variables in bivariate analyses were assessed. The power of TAS to predict CAC was independent of many of the traditional CHD risk factors. Whereas TAS as a predictor was no longer statistically significant when age or duration of diabetes were entered into the model, the odds ratio for a TAS concentration above the median value predicting significant CAC only increased from 0.19 to 0.26 and 0.32, respectively. CONCLUSIONS: TAS is reduced in type 1 diabetes and is associated with the presence of CAC.

Adult↗
PubMed2001

A randomized intervention to improve ongoing participation in mammography.

OBJECTIVE: To test the effectiveness of interventions intended to increase rates of regular breast cancer screening, according to recommended guidelines. STUDY DESIGN: A randomized controlled trial of 2 outreach interventions (a mail reminder and a telephone reminder plus appointment scheduling) compared with a routine publicity campaign to encourage continued participation in mammography screening. PARTICIPANTS AND METHODS: Participants were 1908 women aged 50 to 75 years continuously enrolled in a large group-model HMO during the study who underwent a bilateral mammogram during the first quarter of 1994 and no subsequent mammogram during the next 18 to 21 months. Data were obtained from health plan administrative data files supplemented by medical chart review. Women were randomly assigned to receive (1) a mail reminder, (2) a telephone reminder, or (3) routine publicity on mammography for all women. The outcome measure was a mammogram received after the intervention period and within 2 years of the initial mammogram date. RESULTS: Bivariate and multivariate statistical analyses showed that participation was significantly higher for women contacted by telephone than through routine publicity. Mail reminders were no more effective than a routine publicity campaign. Primary care physician and gynecologist visits increased the likelihood of a subsequent mammogram for women in all intervention groups. CONCLUSIONS: Telephone contact by regular health plan staff was more successful than publicity in encouraging continued participation in mammography screening in women enrolled in a group-model managed health care plan. Because mailings did not influence participation in mammography screening, health plans should be cautious about investing in member mailings without first evaluating their effectiveness in the context of existing outreach efforts.

Aged↗
PubMed2001

High-density lipoprotein composition and paraoxonase activity in Type I diabetes.

Type I diabetes is associated with a high incidence of coronary heart disease (CHD), despite a normal or even increased concentration of high-density lipoprotein (HDL) cholesterol. This paradox may be explained by changes in the antioxidant capacity of HDL, related to paraoxonase (PON1) activity. HDL compositional changes in subjects with Type I diabetes may result in changes in PON1 activity that are associated with a higher incidence of CHD. Single-vertical-spin density-gradient ultracentrifugation was used to isolate seven HDL fractions from serum according to density. PON1 activity was measured in serum and in the HDL fractions using phenyl acetate as substrate. The mean recovery of PON1 activity in the HDL fractions was 87% (S.D. 12%). CHD risk was assessed using B-mode ultrasound to measure carotid artery intima-media thickness (IMT). Groups of 35 subjects with Type I diabetes [duration of diabetes 18 years (12-32 years) [median (interquartile range)]; glycated haemoglobin 7.67% (1.17%)] and 24 non-diabetic control subjects were studied. Carotid IMT was greater in the diabetic subjects [0.60 (0.55-0.70) compared with 0.55 (0.45-0.64) mm; P=0.042] and HDL cholesterol concentration was higher [1.53 (0.36) compared with 1.32 (0.34) mmol/l; P=0.031]. There were qualitative differences in HDL in subjects with Type I diabetes: HDL particles were triacylglycerol-deplete, and there were greater numbers of the larger, more buoyant HDL particles. These properties were not those found to determine PON1 activity. PON1 activity increased as HDL particle density increased and particle size decreased; the increase in PON1 activity was associated with an increase in the ratio of the two HDL surface lipid components, phospholipid and unesterified cholesterol, as particle density increased. PON1 activity was similar in diabetic and non-diabetic subjects [121 (28) and 120 (36) micromol x min(-1) x ml(-1) respectively; P=0.887]. PON1 activity was not associated with carotid IMT in either group. Our results suggest that the PON1 activities of HDL particles relate to the density, size and composition of the particles. However, PON1 activity does not appear to contribute to the greater risk of CHD in subjects with Type I diabetes.

Adult↗
PubMed2000

Measurements of restricted diffusion using an oscillating gradient spin-echo sequence.

An oscillating gradient spin-echo (OGSE) pulse sequence was used to measure the apparent diffusion coefficient (D(app)) of water in the short diffusion time regime in the presence of restrictions. The diffusion coefficients of water in a simple water sample and a water and oil mixture were measured to be the same for different periods of the gradient oscillation, as expected when there are no restriction effects. The D(app) of water in the spaces between closely packed beads was also measured as a function of the gradient oscillation periods in the range 11 to 80 ms. The D(app) of water in restricted systems varies with the period of the gradient oscillation and the dispersion depends on the scale of the restriction. For a sample of packed beads of diameter 9.1 +/- 0.7 microm, the pore surface-to-volume ratio was estimated experimentally by this method to be 1.3 +/- 0.1 microm(-1), corresponding to a mean pore diameter of 6.4 +/- 0.7 microm. A Monte Carlo computer simulation of the NMR OGSE signal from the spins diffusing in a system of compartments was also implemented and the D(app) demonstrated similar behavior with gradient oscillation periods.

Computer Simulation↗
PubMed2000

Successful pregnancy after 24 consecutive fetal losses: lessons learned from surrogacy.

OBJECTIVE: To offer surrogacy as a treatment option to patients in whom maternal rather than fetal factors are responsible for high-order unexplained habitual abortions. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 36-year-old woman with 24 consecutive abortions over 11 years. INTERVENTION(S): A regular IVF procedure in the aborting woman and transfer of two good-quality embryos to the surrogate mother, who had previously received hormones. MAIN OUTCOME MEASURE(S): Ovarian response, oocytes, fertilization, and embryo quality in the aborting patient. Endometrial thickness, implantation, pregnancy, and delivery in the surrogate mother. RESULT(S): Transfer of two embryos to the surrogate mother led to a clinical pregnancy, which was uneventful until term. Cesarean section was performed for breech presentation, with delivery of a healthy male. CONCLUSION(S): Surrogacy can be offered as a treatment option to patients in whom maternal rather than fetal factors are responsible for high-order unexplained habitual abortions.

Abortion, Habitual↗
PubMed2000

Outcome of assisted reproductive technology in women over the age of 41.

OBJECTIVE: To analyze the results of ongoing pregnancies and deliveries after assisted reproductive technology (ART) in women aged >/=41 years, stratified by year of age. DESIGN: Retrospective study. SETTING: University hospital, IVF unit. PATIENT(S): A total of 431 IVF and intracytoplasmic sperm injection (ICSI) cycles were initiated in women >/=41 years of age. INTERVENTION(S): Medical files of ART patients and pregnancy outcomes were reviewed. MAIN OUTCOME MEASURE(S): Oocytes retrieved, embryos developed, and clinical pregnancy and delivery rates. RESULT(S): Of the 431 started cycles, 376 (87%) reached the oocyte retrieval stage. The mean number of oocytes aspirated per patient was 5.4 +/- 0.9 and 6.7 +/- 1.2 in the IVF and ICSI cycles, respectively, and the number of embryos obtained was 2.3 +/- 1.3 and 2.8 +/- 1.6 in the IVF and ICSI cycles, respectively. The number of transferable embryos was 2.0 +/- 1.2 and 2.5 +/- 0.8. The pregnancy rate per oocyte pickup (OPU) was 12.4%; however, the delivery rate per OPU was 4.5%. The mean delivery rate per OPU among women aged 41-43 years was 2%-7%. There were no deliveries aged >/=44 years and no pregnancies at the age of 45 years. The pregnancy and delivery rates of the ICSI and IVF patients were similar after stratification by age. CONCLUSION(S): In our studies, ART performed with homologous oocytes, whether by IVF or ICSI, yielded no clinical pregnancies among women aged >/=45 years and no deliveries aged >/=44 years. The mean delivery rate per oocyte retrieval among women aged 41-43 years varied between 2% and 7%.

Aging↗
PubMed2000

Very low sperm count affects the result of intracytoplasmic sperm injection.

PURPOSE: The aim was to examine the influence of extremely low sperm count on intracytoplasmic sperm injection (ICSI) outcome. METHODS: Over 1000 consecutive unselected ICSI cycles were divided into four groups according to sperm concentration of their patients: A, cryptozoospermia, 107 patients; B, sperm concentration of < or = 1 x 10(4), 146 patients; C, sperm count of 1 x 10(4)-1 x 10(5), 135 patients; and concentration of > 1 x 10(5) and < 10 x 10(6)/ml (control group), 688 patients. RESULTS: A significant decrease in pregnancy rate was noticed in the cryptozoospermic group in comparison to the control group (20% vs. 31%). Fertilization rate in group A was significantly lower in comparison to all other groups, respectively (46% vs. 52%, 54%, 61%). Embryo quality was inferior in group A in comparison to the control group. A higher yet not statistically significant abortion rate was observed in the cryptozoospermic group (as well as in group C) (30%, 27%) compared to the control group (15%). CONCLUSIONS: It seems that an extremely low sperm count has a negative effect on the outcome of ICSI. Nevertheless patients with cryptozoospermia should not be offered ICSI treatment with the ejaculated sperm before karyotype is established.

Adult↗
PubMed2000

Perillyl alcohol, an inhibitor of geranylgeranyl transferase, induces apoptosis of immortalized human vascular smooth muscle cells in vitro.

The isoprenoids geranylgeraniol and farnesol are required for lipid modification of several important cellular proteins. In this study the effect of perillyl alcohol (PA), an inhibitor of geranylgeranyl transferase, was examined on proliferation and apoptosis of immortalized human vascular smooth muscle cells (HVSMCs) derived from saphenous vein. PA induced a time- and concentration-dependent inhibition of cell proliferation over 3 days and 48 h exposure to PA inhibited [methyl-3H-thymidine incorporation induced by 10% fetal calf serum in a concentration-dependent manner. Flow cytometry analysis indicated that PA reduced the proportion of cells in S phase and increased apoptosis. PA-induced apoptosis was confirmed by terminal deoxynucleotidyl transferase (TdT) reagent-based immunocytochemistry. In contrast, the selective inhibitors of farnesyl transferase B581 and BZA-5B were without effect. In view of the proposed role of proliferation and apoptosis in myointimal hyperplasia, inhibitors of geranylgeranyl transferases may have therapeutic potential in cardiovascular disease.

Alkyl and Aryl Transferases↗
PubMed2000

What is a prescribing error?

OBJECTIVE: To develop a practitioner led definition of a prescribing error for use in quantitative studies of their incidence. DESIGN: Two stage Delphi technique. SUBJECTS: A panel of 34 UK judges, which included physicians, surgeons, pharmacists, nurses and risk managers. MAIN OUTCOME MEASURES: The extent to which judges agreed with a general definition of a prescribing error, and the extent to which they agreed that each of 42 scenarios represented a prescribing error. RESULTS: Responses were obtained from 30 (88%) of 34 judges in the first Delphi round, and from 26 (87%) of 30 in the second round. The general definition of a prescribing error was accepted. The panel reached consensus that 24 of the 42 scenarios should be included as prescribing errors and that five should be excluded. In general, transcription errors, failure to communicate essential information, and the use of drugs or doses inappropriate for the individual patient were considered prescribing errors; deviations from policies or guidelines were not. CONCLUSIONS: Health care professionals are in broad agreement about the types of events that should be included and excluded as prescribing errors. A general definition of a prescribing error has been developed, together with more detailed guidance regarding the types of events that should be included. This definition allows the comparison of prescribing error rates among different prescribing systems and different hospitals, and is suitable for use in both research and clinical governance initiatives.

Attitude of Health Personnel↗