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Biomedical subjects

S Pickering

Publications and source records attributed to S Pickering.

At least 19 recordsLinked to original sources
PubMed2006

Three hundred and thirty cycles of preimplantation genetic diagnosis for serious genetic disease: clinical considerations affecting outcome.

OBJECTIVE: To report on our experience with preimplantation genetic diagnosis (PGD) cycles performed for serious genetic disease in relation to the clinical factors affecting outcome. DESIGN: Retrospective review of data from a single centre. SETTING: Tertiary referral PGD centre in a London teaching hospital. METHODS: The PGD cycles included 172 cycles for chromosome rearrangements, 96 cycles for single-gene disorders and 62 cycles for X-linked disorders. In vitro fertilisation was the preferred method in chromosome rearrangement and X-linked cases, while intra cytoplasmic sperm injection was used in all single-gene disorders. Appropriate in situ hybridisation fluorescence probes were used in chromosome rearrangement and X-linked cases and polymerase chain reaction was used in single-gene disorders. All pregnancies were followed till delivery. MAIN OUTCOME MEASURE: Live birth rate per PGD cycle started. RESULTS: Eighty-six percent of cycles started (283) reached oocyte retrieval and 3743 eggs were collected, of which 2086 fertilised normally (55.7%). Two hundred and fifty cycles (76%) had embryos sutiable for biopsy on day 3 of in vitro culture, 1714 embryos were biopsied, and in 205 cycles (62%), there was at least one unaffected embryo available for transfer, resulting in 90 pregnancies, 68 clinical pregnancies and 58 live birth. The live birth rate was 18% per cycle started, 21% per egg retrieval and 28% per embryo transfer which significantly affected the live birth outcome. Woman age, number of eggs collected and achieving cryopreservation of surplus embryos had no statistically significant effect on treatment outcome. CONCLUSIONS: The live birth outcome of PGD cycles for serious genetic disorder is modest and is affected by the number of embryos genetically suitable for transfer.

Adult↗
PubMed2004

Phospholipase Czeta causes Ca2+ oscillations and parthenogenetic activation of human oocytes.

At fertilization in mammals the sperm activates development of the oocyte by inducing a prolonged series of oscillations in the cytosolic free Ca2+ concentration. One theory of signal transduction at fertilization suggests that the sperm cause the Ca2+ oscillations by introducing a protein factor into the oocyte after gamete membrane fusion. We recently identified this sperm-specific protein as phospholipase Czeta (PLCzeta), and we showed that PLCzeta triggers Ca2+ oscillations in unfertilized mouse oocytes. Here we report that microinjection of the complementary RNA for human PLCzeta causes prolonged Ca2+ oscillations in aged human oocytes that had failed to fertilize during in vitro fertilization or intracytoplasmic sperm injection. The frequency of Ca2+ oscillations was related to the concentration of complementary RNA injected. At low concentrations, PLCzeta stimulated parthenogenetic activation of oocytes. These embryos underwent cleavage divisions and some formed blastocysts. These data show that PLCzeta is a novel parthenogenetic stimulus for human oocytes and that it is unique in its ability to mimic the repetitive nature of the Ca2+ stimulus provided by the sperm during human fertilization.

Calcium↗
PubMed2003

LPA1 receptor-deficient mice have phenotypic changes observed in psychiatric disease.

Several psychiatric diseases, including schizophrenia, are thought to have a developmental aetiology, but to date no clear link has been made between psychiatric disease and a specific developmental process. LPA(1) is a G(i)-coupled seven transmembrane receptor with high affinity for lysophosphatidic acid. Although LPA(1) is expressed in several peripheral tissues, in the nervous system it shows relatively restricted temporal expression to neuroepithelia during CNS development and to myelinating glia in the adult. We report the detailed neurological and behavioural analysis of mice homozygous for a targeted deletion at the lpa(1) locus. Our observations reveal a marked deficit in prepulse inhibition, widespread changes in the levels and turnover of the neurotransmitter 5-HT, a brain region-specific alteration in levels of amino acids, and a craniofacial dysmorphism in these mice. We suggest that the loss of LPA(1) receptor generates defects resembling those found in psychiatric disease.

Animals↗
PubMed2003

Initial management of ocular hypertension and primary open-angle glaucoma: an evaluation of the royal college of ophthalmologists' guidelines.

PURPOSE: The purpose of this study was to identify any consensus of opinion among consultant ophthalmologists in Wales with respect to the initial management of glaucoma referrals based on the published guidelines of the Royal College of Ophthalmologists (RCO) and to compare consultant opinion with the practice in a typical hospital. METHOD: The RCO guidelines document was studied to identify clear statements, which could be adopted as standards for audit purposes. A questionnaire was designed and sent to all consultant ophthalmologists in Wales (n=37) to obtain their opinions. An audit was performed of 100 consecutive patients referred to our unit as glaucoma suspects with regard to initial management. Descriptive statistical analysis was performed. RESULTS: A good response rate for a postal questionnaire was obtained (81%) with 79.1% of responders finding the guidelines of at least some help. Levels of agreement with the definitions of ocular hypertension (OH) and primary open-angle glaucoma (POAG) were 76.7 and 86.7%, respectively. There was consensus of consultant opinion regarding many of the elements of the baseline clinical assessment with the significant exceptions of the necessity for dilated fundoscopy, gonioscopy, retinal nerve fibre layer assessment, and drawing of optic discs. The various 'clinical scenarios' for management of the RCO document were not all endorsed. The clinical audit results of the initial management of glaucoma referrals accurately reflected the consensus of the consultant opinion. DISCUSSION: The RCO guidelines document represents a useful contribution to the management of patients with OH and POAG. Nevertheless, considerable variation in opinion exists concerning even the most basic areas. With the advent of clinical governance, bridging the gap between the conclusions of College working parties and realities of everyday practice will assume greater importance.

Attitude of Health Personnel↗
PubMed2000

Neuropilin-2 is required in vivo for selective axon guidance responses to secreted semaphorins.

Neuropilins are receptors for class 3 secreted semaphorins, most of which can function as potent repulsive axon guidance cues. We have generated mice with a targeted deletion in the neuropilin-2 (Npn-2) locus. Many Npn-2 mutant mice are viable into adulthood, allowing us to assess the role of Npn-2 in axon guidance events throughout neural development. Npn-2 is required for the organization and fasciculation of several cranial nerves and spinal nerves. In addition, several major fiber tracts in the brains of adult mutant mice are either severely disorganized or missing. Our results show that Npn-2 is a selective receptor for class 3 semaphorins in vivo and that Npn-1 and Npn-2 are required for development of an overlapping but distinct set of CNS and PNS projections.

Age Factors↗
PubMed1999

Bilateral thalamic stimulation for the treatment of essential tremor.

OBJECTIVE: To determine the safety and efficacy of bilateral thalamic stimulation in the treatment of essential tremor (ET). METHODS: Nine ET patients with disabling tremor refractory to pharmacotherapy underwent bilateral staged implants. Tremor was assessed by the Fahn-Tolosa-Marin Tremor Rating Scale at baseline 1 (before first implant), baseline 2 (before second implant), and at 6-month and 1-year follow-up. Blinded evaluations were performed at 3 months. Associated changes in speech were evaluated in six patients. There were seven men and two women with a mean age of 73.8 years. RESULTS: There was a significant improvement in the mean total tremor score from a baseline of 66.1+/-11.6 to 28.4+/-12.8 12 months after the second surgery. Similarly, the mean motor tremor subscore was 20.1+/-5.0 before the first surgery and improved significantly to 14.1+/-3.6 before the second surgery. Motor tremor scores 6 months after the second surgery (6.0+/-3.7) and 12 months after the second surgery (7.5+/-3.9) also improved significantly relative to the preoperative scores. The mean activities of daily living (ADL) subscore at baseline was 18.2+/-2.9 and improved significantly before the second surgery to 9.0+/-3.2. These ADL scores further improved 6 months (6.2+/-5.2) and 12 months (7.9+/-5.7) following the second surgery, but these gains were not significant. Blinded evaluations also revealed a similar degree of improvement. Complications were noted in five patients: asymptomatic intracranial hematoma (1), postoperative seizures (1), a hematoma over the implanted pulse generator (IPG) (1), lead repositioning (1), and IPG malfunction (1). Adverse effects related to stimulation were mild and resolved with adjustment of the stimulation parameters. Three of the six patients demonstrated worsening of dysarthria with both stimulators on. CONCLUSIONS: Bilateral thalamic stimulation is effective in reducing tremor and functional disability in ET; however, dysarthria is a possible complication.

Activities of Daily Living↗
PubMed1998

The relationship of attributional beliefs to self-esteem.

Several studies have reported that beliefs about the causes of events (i.e., causal attributions) are related to achievement-oriented behavior. Skinner (1995) has suggested that achievement-oriented behavior is related to beliefs about successful strategies and beliefs about the capacity to enact those strategies. Based on Skinner's research, Wellborn, Connell, and Skinner (1989) developed the Students' Perception of Control Questionnaire (SPOCQ). In the present investigation, the SPOCQ was adapted for use with adolescents and adults. The SPOCQ and the Rosenberg Self-esteem Scale were administered to 147 college students. The internal consistency and the intercorrelations of the SPOCQ subscales were found to be acceptable. Additionally, SPOCQ scores were related to self-esteem and grade point average. There were statistically significant differences in the SPOCQ scores for males and females and in the relation of SPOCQ scores to self-esteem. It is suggested that the three constructs measured by the SPOCQ (control, strategies, and capacity) provide a more complete description of attributional beliefs than do previous scales.

Achievement↗
PubMed1997

The purpose of PREP.

Explore the source record for details and available documents.

Education, Nursing, Continuing↗
PubMed1996

Cost effectiveness of a single-function treatment center for cataract surgery.

PURPOSE: To compare the clinical and cost effectiveness of two models for cataract treatment: a single-function Cataract Treatment Centre (CTC) and a general ophthalmology service. SETTING: Cataract Treatment Centre and the general ophthalmology service at Sunderland Eye Infirmary, Sunderland, United Kingdom. METHODS: Two hundred patients were studied using two models of care: 100 in the CTC and 100 in the general ophthalmology service. Outcome measures were best corrected visual at 3 months postoperatively or at discharge and occurrence of surgery-related complications. All direct costs to the National Health Service were identified, measure, and assessed. RESULTS: Clinical outcomes in the two groups were similar. The average cost per patient was 496.90 pounds ($760.25) at the CTC and 566.34 pounds ($866.50) at the general ophthalmology service. The cost per patient treated as a day case in the general service group was 495.84 pounds ($758.63). Thus, treatment at the CTC was more cost effective than in the mixed service group and as cost effective as in the day case subgroup. CONCLUSIONS: Depending on local circumstances, day care must be delivered more cost effectively in a single-function center than in a general ophthalmology service. We recommend day care using local anesthesia and protocols for assessment, surgery, and follow-up.

Anesthesia↗
PubMed1995

Extracapsular cataract surgery using capsulorhexis with viscoexpression via a limbal section.

Two hundred consecutive patients had extracapsular cataract surgery by capsulorhexis and viscoexpression. Capsulorhexis, attempted in 195 eyes, was successful in 87.7%. Viscoexpression was attempted in 162 cases and successfully delivered the nucleus in 87.7%. There were five cases of zonule rupture, one of posterior capsule rupture, and two of vitreous loss. If the capsulorhexis is larger than 5 mm, viscoexpression can be safely used on all cataracts, regardless of nuclear density, and is the ideal transition to phacoemulsification.

Cataract Extraction↗
PubMed1995

Genetic diagnosis using polymerase chain reaction and fluorescent in-situ hybridization analysis of biopsied cells from both the cleavage and blastocyst stages of individual cultured human preimplantation embryos.

Cultured human preimplantation embryos have been used to develop methods which allow preimplantation genetic diagnosis (PGD) analyses by polymerase chain reaction (PCR) and fluorescent in-situ hybridization (FISH) on biopsied blastomeres and trophectoderm cells from the same embryo. An experimental design is described and experiments undertaken, which demonstrate the feasibility of extending biopsy and PGD procedures currently in use. We have shown that dual-stage biopsies are possible, and that the PCR and FISH analyses of the biopsied cell samples are effective. One to two blastomeres were biopsied from an 8- to 10-cell embryo and processed for the simultaneous PCR amplification of a beta-globin and a cytosine adenine (CA) repeat sequence, or a Y chromosome sequence. FISH procedures were also used to detect the presence of Y chromosome markers. The biopsied cleavage-stage embryo can be cultured to the blastocyst stage, where the serial biopsy of three to five mural trophectoderm cells provides two further cell samples. These can be used to repeat and/or undertake additional PGD analyses. The biopsied blastocyst is either used to confirm earlier diagnoses, or placed in culture for a further 4-24 h. Maintenance of a blastocoele cavity, hatching and formation of an outgrowth demonstrates continuing viability following the dual-stage biopsy procedures. The PCR DNA amplification procedures are effective at the cellular level for both biopsied blastomeres and mural trophectoderm cells. The FISH techniques have shown a definitive Y signal in 50% (one out of two) and 100% (two out of two) of the biopsied blastomeres and 72% (two out of three, four out of five and 7 out of 10) for the trophectoderm cell nuclei. Preliminary experiments have demonstrated that the FISH preparations can be re-amplified to improve the signal, and dual fluorescent procedures using the X and Y probes are effective. A retrospective PCR analysis has also been undertaken on preparations of biopsied cells which were previously used for PGD analysis by FISH.

Blastocyst↗
PubMed1991

Parthenogenetic activation and development of fresh and aged human oocytes.

OBJECTIVE: To develop a systematic study of the parthenogenetic activation and early development of human oocytes. DESIGN: Human oocytes (both freshly retrieved and remaining unfertilized after exposure to spermatozoa) were exposed to alcohol or calcium ionophore and examined for evidence of activation. SETTING: Academic research department of a teaching hospital. PATIENTS, PARTICIPANTS: Couples donating oocytes were undergoing therapy for infertility with in vitro fertilization or gamete intrafallopian transfer. INTERVENTIONS: Gonadotropin-releasing hormone agonist and human menopausal gonadotropin were administered at therapeutic doses. MAIN OUTCOME MEASURES: After application of activation stimuli at varying doses and durations, oocytes were examined for evidence of meiotic reactivation, pronuclear formation, deoxyribonucleic acid content, and cleavage. RESULTS: Fresh and aged human oocytes can be activated parthenogenetically using a calcium ionophore but at lower rates than seen for mouse oocytes (typically 50% to 60% versus 90% to 100%, respectively). Ethanol was a poor activating agent (maximum activation rate 16%). Human parthenotes can complete division to the eight cell stage. CONCLUSIONS: These results indicate that parthenote embryos may provide a source of material to study changes that occur during early human development. The data also raise the possibility that some early human pregnancy losses may involve oocytes that have been parthenogenetically activated spontaneously.

Calcimycin↗
PubMed1989

Cellular aspects of retention and transport of inhaled soluble and insoluble actinide compounds in the rat lung.

The binding of 241Am-hydroxide polymers (as models for readily soluble actinide compounds) to the cell components of rat lung was investigated using differential centrifugation, density gradient centrifugation, gel chromatography, carrier-free electrophoresis and electron microscopic autoradiography (with 241Pu). Irregularly shaped and spherical mixed (U, Pu)O2 particles (as models for insoluble actinide compounds) were administered to rats by inhalation and intratracheal installation and the lung and organ retention was determined. Electron microscopic studies were performed with rat lung and with rat and bovine alveolar macrophages exposed to the actinide compounds in vitro. In the case of the mixed (U, Pu)O2 particles the lung retention was independent of the particle shape and route of administration. Whereas 241Am administered as a hydroxide polymer was transferred rapidly from lung to skeleton and liver, only a few percent of the initial alveolar deposit was found in these organs after mixed oxide inhalation. It is concluded that all types of particles are stored primarily within phagolysosomes of alveolar macrophages. In the case of readily soluble compounds, the actinides are solubilized within these lysosomes and become bound to cytosolic ferritin in the alveolar macrophages. They are then released from the macrophages and probably cross the alveolar membranes as transferrin or as low-molecular-weight forms. Insoluble compounds remain within the lysosomes of alveolar macrophages, but there are indications of chemical damage to the lysosomal membranes, causing the particles to lie free in the cytoplasm.

Actinoid Series Elements↗
PubMed1989

Behaviour of spherical and irregular (U,Pu)O2 particles after inhalation or intratracheal instillation in rat lung and during in vitro culture with bovine alveolar macrophages.

Spherical and irregularly shaped mixed (U,Pu) oxide particles were administered to rats by inhalation and by intratracheal instillation. The lung retention of the particles was independent of particle shape and of the route of administration. Only a small percentage of the administered radioactivity was found in other organs. Detailed electron microscopic studies showed particles within membrane-enclosed vacuoles as well as lying free in the cytoplasm.

Administration, Inhalation↗