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Biomedical subjects

G Tomkin

Publications and source records attributed to G Tomkin.

16 recordsLinked to original sources
PubMed2000

Sperm deposition site during ICSI affects fertilization and development.

OBJECTIVE: To evaluate the effects of sperm placement during ICSI relative to the M-II spindle location on fertilization and preimplantation development. DESIGN: Retrospective analysis of oocyte fertilization and embryo development with respect to sperm deposition site during ICSI. SETTING: A program of IVF-ET. PATIENT(S): Seven hundred seventy-six patients. INTERVENTION(S): Egg quality, sperm deposition site, and polar-body position were recorded during ICSI; fertilization was assessed on day 1; embryo development was evaluated on days 2 and 3. MAIN OUTCOME MEASURE(S): Fertilization, embryo development, and implantation rates. RESULT(S): Normal fertilization is not affected by polar-body orientation, with the exception of a significantly lower fertilization rate from a 9 o'clock polar-body orientation. Injections with the polar-body positioned at 7 or 11 o'clock result in the greatest number of high-quality embryos, significantly more than the adjacent 6 or 12 o'clock polar-body orientations and irrespective of oocyte anomaly frequency. Embryos originating from the 7 or 11 o'clock polar-body category implant at a higher rate, although the data are not significant. CONCLUSION(S): The placement of the sperm during ICSI relative to the presumed location of the meiotic spindle significantly impacts fertilization and high-quality embryo development. Sperm deposition in the M-II spindle area should be avoided. It appears that development, and not fertilization, is improved by decreasing the distance between the sperm cell and the spindle.

Cell Nucleus↗
PubMed2000

Cleavage anomalies in early human embryos and survival after prolonged culture in-vitro.

This study examines the relationship between common morphological anomalies of cleaving embryos and their ability to form apparently normal blastocysts in vitro. The impact of cleavage rate, fragmentation, and multinucleation on compaction, cavitation, along with inner cell mass and trophectoderm formation has been assessed. The study population consisted of 102 patients who elected or were selected to have a day 5 embryo transfer. Clinical pregnancy and implantation rates were 66.7 and 49% respectively. Slow and fast cleavage had a significant negative association with normal blastocyst formation. Only 13.8% (67/484) of embryos with <7 cells and 27.5% (25/91) of those with >9 cells on day 3 formed blastocysts with apparently normal morphology, compared to 41.9% (252/602) with 7-9 cells on day 3 (P < 0.001). Fragmentation had a negative impact on normal blastocyst formation. Embryos with >15% fragmentation formed normal blastocysts at a significantly lower rate (46/279; 16.5%) than embryos with 0-15% fragmentation (311/935; 33.3%) (P < 0. 001). Furthermore, the pattern of fragmentation was associated with blastocyst formation. Type IV fragmentation led to a significant reduction in blastocyst formation (25/170 or 14.7%), compared to types I, II and III which performed much better (38.6, 32.9 and 32.4% respectively). Only 15.9% (22/138) of embryos with one or more multinucleate cells on day 2 and/or 3 formed normal blastocysts compared with 31.9% (335/1051) (P < 0.001) of those without multinucleation. Collectively, the data suggest that cleavage anomalies, some of which do not preclude development after short-term culture, may reduce the developmental competence of embryos after prolonged culture.

Blastocyst↗
PubMed1999

Human embryo fragmentation in vitro and its implications for pregnancy and implantation.

OBJECTIVE: To evaluate the effects of fragmentation and fragment removal in day 3 human embryos on implantation and pregnancy. DESIGN: Retrospective analysis of ETs homogeneous with respect to embryo fragmentation. SETTING: A program of IVF-ET. PATIENT(S): The study population consisted of 2,410 patients. INTERVENTION(S): The degree and pattern of fragmentation were evaluated on days 2 and 3; microsurgical fragment removal was performed after assisted hatching on day 3. MAIN OUTCOME MEASURE(S): Clinical pregnancy and implantation rates. RESULT(S): The degree and pattern of fragmentation significantly impact pregnancy and implantation. With the application of microsurgical fragment removal before ET, embryos with 6%-35% fragmentation implant with similar frequency. The presence of large fragments (type IV) is detrimental to the developing embryo, whereas localized or small and scattered fragments do not significantly affect implantation. CONCLUSION(S): The potential of fragmented embryos for implantation is determined partly by the distribution of fragments. Adoption of an embryo classification system reflecting types of fragmentation is advisable. The use of microsurgical fragment removal significantly alters the course of development for some embryos and improves their implanting potential.

Adult↗
PubMed1998

Impaired development of zygotes with uneven pronuclear size.

The correlation between human zygote morphology and chromosomal anomalies after cleavage has not been well characterised. Commonly observed morphological qualities at the zygote stage have provided little insight into further development, and therefore selection for cryopreservation or transfer appears to be less specific than that at later stages of preimplantation development. The purpose of this work was to evaluate the relationship between aberrant pronuclear morphology and chromosomal anomalies after cleavage. Monospermic zygotes exhibiting two pronuclei where diameters differed by at least 4 microns were found to arrest at a significantly higher rate than zygotes with pronuclear diameters differing by less than 4 microns. In addition, a higher incidence of day 2 multinucleation was observed. Embryos deriving from zygotes with dysmorphic pronuclei that were not replaced or cryopreserved by day 3 of development were separated and fixed for fluorescence in situ hybridisation analysis of chromosomes X, Y, 13, 18 and 21. A significantly higher incidence of mosaicism was found in this group compared with others that had developed from zygotes with normal pronuclear morphology. Although the mechanism leading to this form of divergent pronuclear morphology is unclear, results suggest a correlation with oocyte cytoplasmic immaturity.

Cell Nucleus↗
PubMed1995

Embryo morphology, developmental rates, and maternal age are correlated with chromosome abnormalities.

OBJECTIVE: To determine some of the unresolved questions related to chromosome anomalies in early human embryos, such are the detection of any advanced maternal age effect; the complete assessment of mosaicism, which requires analysis of all cells; and the relationship with embryonic dysmorphism. Fluorescence in situ hybridization has been used in this study to answer these issues. DESIGN: Fluorescence in situ hybridization analysis of human embryos using simultaneously probes for three or five chromosomes. Five hundred twenty-four cleavage-stage human embryos obtained by IVF were analyzed by fluorescence in situ hybridization. Embryos were allocated into three groups according to morphological and developmental characteristics (arrested; slow and/or fragmented; morphologically and developmentally normal). The embryos also were analyzed according to maternal age. RESULTS: Dysmorphic embryos had higher rates of polyploidy and diploid mosaicism. Aneuploidy increased with maternal age in nonarrested embryos. Preimplantation genetic diagnosis successfully detected these abnormalities. CONCLUSION: This study demonstrates that, in morphologically and developmentally normal human embryos, cleavage-stage aneuploidy significantly increases with maternal age. The results suggest that implantation failure in older women largely could be due to aneuploidy.

Adult↗
PubMed1990

Cellular cholesterol metabolism in mitogen-stimulated lymphocytes--requirement for de novo synthesis.

The relationship between cholesterol synthesis and uptake in proliferating lymphocytes has been examined. [14C]Acetate incorporation into lymphocytes cultured under lipoprotein-deficient conditions increased initially in response to mitogen, decreased after 24 h, and increased rapidly between 72 and 96 h. Addition of LDL (10 micrograms/ml) to the culture during the 'trough' period caused [14C]acetate incorporation to return rapidly to baseline, while at peak periods LDL suppression of cholesterol synthesis was minimal. Lymphocytes cultured in the presence of the HMG-CoA reductase inhibitor, mevinolin, exhibited a time-dependent increase in their capacity to incorporate [14C]acetate into cholesterol, evident when mevinolin was removed by washing prior to assay. PHA enhanced 125I-labelled LDL receptor-mediated binding by lymphocytes cultured in lipoprotein-deficient medium over a 4 day period and mevinolin augmented the effect. [3H]Thymidine incorporation into mitogen-stimulated lipoprotein-deficient cultures was inhibited up to 75% by mevinolin (1 mumol/l). LDL (2.5-10 micrograms/ml) substantially reversed this inhibition in 72 h cultures, but only partially overcame inhibition in cells cultured for 96 h. Results suggest that endogenous cholesterol synthesis may be obligatory for lymphocyte proliferation after the initial round of cell division.

Acetates↗
PubMed1990

Recurrent disseminated intravascular coagulation and fulminant intra hepatic thrombosis in a patient with the anti-phospholipid syndrome.

We describe a patient with the lupus anti-coagulant who had recurrent episodes, over a 2 year period, of a severe and disseminated intravascular coagulopathy. This patient also had positive serological assays for syphilis and anti-cardiolipin antibodies. Associated with the coagulopathy were co-expressed episodes of liver disease, ultimately terminating in fulminant liver failure. At autopsy the features were characteristic of the Budd-Chiari syndrome. This is the first report to document how consumptive coagulopathy may present as a dominant feature of the anti-phospholipid syndrome. It also clearly describes an immune mediated thrombotic mechanism as a cause of hepatic veno-occlusive disorders. Furthermore, this case highlights the varied clinical spectrum of the anti-phospholipid syndrome and suggests that a high index of suspicion is required to ensure its diagnosis.

Adult↗
PubMed1990

Cellular cholesterol regulation--a defect in the type 2 (non-insulin-dependent) diabetic patient in poor metabolic control.

This study investigates the relationship between Type 2 (non-insulin-dependent) diabetes mellitus and hypercholesterolaemia with regard to delivery of cholesterol to cells and regulation of endogenous cholesterol synthesis. The ability of LDL, from hypercholesterolaemic and Type 2 diabetic patients, to suppress cellular cholesterologenesis and to enhance mitogen-stimulated lymphocyte proliferation was compared. Cholesterol synthesis was estimated by measuring [14C]-acetate incorporation into cholesterol and lymphocyte proliferation was assessed by [3H]-thymidine incorporation into mitogen-stimulated normal lymphocytes. The results indicate that LDL from both Type 2 diabetic patients in poor metabolic control and hypercholesterolaemic patients was significantly less effective (p less than 0.001) than LDL from non-diabetic normocholesterolaemic subjects in suppressing cholesterol synthesis in lymphocytes. LDL from all hypercholesterolaemic patients enhanced lymphocyte proliferation to a greater extent than LDL from normocholesterolaemic subjects and this effect was significantly increased using LDL from Type 2 diabetic, hypercholesterolaemic patients. Both suppression of [14C]-acetate incorporation and enhancement of [3H]-thymidine uptake could be related to an increased esterified/free cholesterol ratio in the LDL particle. The fact that cholesterol synthesis and cell proliferation were markedly altered by the above changes in LDL composition suggests a mechanism for cellular cholesterol accumulation in the Type 2 diabetic patient, even in the absence of elevated serum cholesterol levels.

Apolipoproteins B↗
PubMed1988

Effects of catecholamines on serum lipoproteins of normally fed and cholesterol-fed rabbits.

The effects of catecholamines on the regulation of lipoprotein metabolism have not been defined. We examined the effects of subcutaneously administered slow-release preparations of norepinephrine (2 mg/kg) and isoproterenol (0.2 mg/kg) on the serum lipoproteins of New Zealand White rabbits. Drugs or control suspension were administered daily to three groups of normally fed and three groups of cholesterol-fed rabbits, and lipoprotein analysis was performed at intervals over a 60-hour period. In the normally fed animals, norepinephrine increased the serum levels of triglyceride and phospholipid by factors of 2.4 (P less than .01) and 1.35 (P less than .05), respectively, compared with control animals at 60 hours, but had no effect on serum cholesterol. All components of serum very low density lipoproteins (VLDL: triglyceride, cholesterol, phospholipid, and protein) were significantly (P less than .01) elevated by norepinephrine in the normally fed animals. In the cholesterol-fed animals, norepinephrine at 60 hours significantly increased total serum cholesterol, triglyceride, and phospholipid concentrations by factors of 1.7 (P less than .05), 5.0 (P less than .01), and 1.6 (P less than .05), respectively, compared with controls. The norepinephrine effects in these animals was due to significant elevation of total VLDL and low density lipoproteins (LDL) and all their elemental components. Isoproterenol produced no significant effect on serum lipoprotein levels in the normally fed rabbit, but in cholesterol-fed animals it produced a rise in total serum VLDL and LDL triglyceride concentrations compared with controls at 60 hours. These data demonstrate that catecholamines are involved in the regulation of lipoprotein metabolism.

Animals↗
PubMed1987

Plasma catecholamines and lipoproteins in chronic psychological stress.

Changes in plasma catecholamines, lipoproteins and dietary intake were examined in 13 medical students during a 3-month period prior to their examinations, and in 12 controls. In the medical students mean +/- s.e.(mean) plasma cholesterol increased over the study period (3.98 +/- 0.16 v. 4.26 +/- 0.16 mmol/l, P less than 0.05) and this was reflected by a rise in low-density lipoprotein cholesterol (2.53 +/- 0.15 v. 2.71 +/- 0.17 mmol/l, P less than 0.05). Both supine adrenaline (0.45 +/- 0.05 v. 0.70 +/- 0.07 nmol/l, P less than 0.01) and noradrenaline (2.74 +/- 0.18 v. 3.40 +/- 0.31 nmol/l, P less than 0.05) increased over this period. Apart from a decline in the modest alcohol consumption (9.1 +/- 3.45 v. 2.6 +/- 1.4 g/day, P less than 0.02) there was no change in dietary intake in the medical students. There were no significant changes in plasma catecholamines, lipoproteins or dietary intake in control subjects over the study period. Changes in catecholamines and lipoproteins occurring in association with chronic psychological stress may contribute to the increased coronary heart disease mortality associated with Type A behaviour and stressful life events.

Adult↗