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Biomedical subjects

M Herbert

Publications and source records attributed to M Herbert.

At least 19 recordsLinked to original sources
PubMed2006

Developmental competence of human in vitro aged oocytes as host cells for nuclear transfer.

BACKGROUND: Improving human nuclear transfer (NT) efficiencies is paramount for the development of patient-specific stem cell lines, although the opportunities remain limited owing to difficulties in obtaining fresh mature oocytes. METHODS: Therefore, the developmental competence of aged, failed-to-fertilize human oocytes as an alternate cytoplasmic source for NT was assessed and compared with use of fresh, ovulation-induced oocytes. To further characterize the developmental potential of aged oocytes, parthenogenetic activation, immunocytochemical analysis of essential microtubule proteins involved in meiotic and mitotic division, and RT-PCR in single oocytes (n = 6) was performed to determine expression of oocyte-specific genes [oocyte-specific histone 1 (H1FOO), growth differentiation factor 9 (GDF9), bone morphogenetic protein 15 (BMP15), zygote arrest 1 (ZAR1)] and microtubule markers [nuclear mitotic arrest (NuMA), minus-end directed motor protein HSET and the microtubule kinesin motor protein EG5]. RESULTS: For NT, enucleation and fusion rates of aged oocytes were significantly lower compared with fresh oocytes (P < 0.05). Cleavage rates and subsequent development were poor. In addition, parthenote cleavage was low. Immunocytochemical analysis revealed that many oocytes displayed aberrant expression of NuMA and EG5, had disrupted meiotic spindles and tetrapolar spindles. One of the six oocytes misexpressed GDF9, BMP15 and ZAR1. Two oocytes expressed EG5 messenger RNA (mRNA), and HSET and NuMA were not detectable. RT-PCR of mRNA for oocyte specific genes and microtubule markers in single aged oocytes. CONCLUSIONS: Thus, aneuploidy and spindle defects may contribute to poor parthenogenetic development and developmental outcomes following NT.

Aging↗
PubMed2006

Dextran 40 (Rheomacrodex) or Polygeline (Haemaccel) as an epidural patch for post dural puncture headache: a neurotoxicity study in a rat model of Dextran 40 and Polygeline injected intrathecally.

BACKGROUND AND OBJECTIVE: Although an epidural autologous blood patch is considered the most effective treatment for post dural puncture headache, which sometimes occurs following spinal or inadvertent spinal anaesthesia, there remains a need for alternative materials for epidural patches. We investigated the potential neurotoxicity of Dextran 40 (Rheomacrodex) and Polygeline (Haemaccel) used for this purpose in a rat model. METHODS: Repeated boluses of 10% Dextran 40, 3.5% Polygeline or 0.9% saline were injected intrathecally over a period of 1 month in three groups of rats. RESULTS: No behavioural or clinical derangements were observed in any of the three groups during this period. After sacrifice of the animals at the end of the experiment, no significant differences in the histopathological appearances of the spinal cords in the three groups were observed. No toxic effects diminishing viability of spinal cord cells were evident. Similarly, viability of renal, hepatic and peripheral blood mononuclear cells remained unaffected (98% +/- 2%). CONCLUSIONS: No deleterious effects, clinical or cellular, were evident in this rat model when Dextran 40 or Polygeline were injected intrathecally. Thus, both substances can be considered as possible alternative materials for epidural patches.

Animals↗
PubMed2006

An investigation of transmission ratio distortion in the central region of the human MHC.

Transmission ratio distortion (TRD) describes a significant departure from expected Mendelian inheritance ratios that is fundamental to both the biology of reproduction and statistical genetics. The relatively high fetal wastage in humans, with consequent selection of alleles in utero, makes it likely that TRD is prevalent in the human genome. The central region of the human major histocompatibility complex (MHC) is a strong TRD candidate, as it houses a number of immune and regulatory genes that may be important in pregnancy outcome. We used a nonhaplotype-based method to select 13 tagging SNPs from three central MHC candidate regions, and analysed their transmission in 380 newborns and their parents (1138 individuals). A TRD of 54:46 was noted in favour of the common allele of a promoter SNP in the CLIC1 gene (P = 0.025), with a similar distortion using haplotypes across the same gene region (P = 0.016). We also found evidence that markers in the CLIC1 gene region may have been subject to recent selection (P < 0.001). The study illustrates the potential benefits of screening for TRD and highlights the difficulties encountered therein.

Biomarkers↗
PubMed2005

Population-specific patterns of linkage disequilibrium in the human 5q31 region.

Linkage disequilibrium across the human genome is generally lower in West Africans than Europeans. However in the 5q31 region, which is rich in immune genes, we find significantly more examples of apparent nonrecombination between distant marker pairs in West Africans. Much of this effect is due to SNPs that are absent in Europeans, possibly reflecting recent positive selection in the West African population.

Black People↗
PubMed2005

The pregnant trauma patient.

Trauma is the leading non-obstetric cause of maternal death. Optimal management of the pregnant trauma patient requires a multidisciplinary approach. The anaesthetist and critical care physician play a pivotal role in the entire continuum of fetomaternal care, from initial assessment, resuscitation and intraoperative management, to postoperative care that often involves critical care support and patient transfer. Primary goals are aggressive resuscitation of the mother and maintenance of uteroplacental perfusion and fetal oxygenation by the avoidance of hypoxia, hypotension, hypocapnia, acidosis and hypothermia. Recognizing and understanding the mechanisms of injury, the factors that may predict fetal outcome, and the pathophysiological changes that can result from trauma, will allow early identification and treatment of fetomaternal injury. This in turn should improve morbidity and mortality. A framework for the acute care of the pregnant trauma patient is presented.

Cesarean Section↗
PubMed2004

Demographic, medical and treatment characteristics associated with couples' decisions to donate fresh spare embryos for research.

BACKGROUND: Isolation of human embryonic stem cell lines has opened a promising and pioneering area of basic and applied medical research. The issues in relation to a couples' decision in donating their supernumerary embryos for research need to be investigated further. METHODS: We carried out a prospective study of 300 couples who underwent IVF/ICSI treatment cycles in our unit. We analysed various factors contributing to their decision to consent to donate spare embryos for stem cell or preimplantation genetic diagnosis research. RESULTS: The majority of couples (54%) consented to donate their surplus embryos for research. Couples of ethnic minority origin were less willing to consent for research compared to Caucasian couples. The number of ovarian follicles at pre-hCG scan and the number of embryos obtained were significantly higher in couples consenting for research. The funding source of treatment did not appear to influence the decision to donate. Couples with previous failed fertilization were less likely to consent to embryo research. CONCLUSIONS: Physical characteristics based on ovarian response during a treatment cycle may positively influence a couple's decision to donate embryos. Further studies are needed to identify those couples who are likely to agree to research so that counselling for research can be directed efficiently.

Adult↗
PubMed2002

Breast hamartomas: clinicopathological and immunohistochemical studies of 24 cases.

AIMS: The aim of our study was to investigate the clinical, pathological and immunohistochemical features of breast hamartomas, in order to obtain a detailed profile of this somewhat uncommon lesion. METHODS AND RESULTS: This study presents a clinical, pathological and immunohistochemical analysis of 24 breast hamartomas. Four cases of fibrocystic breast changes were used as a control group. The immunohistochemical panel induced oestrogen (ER) and progesterone (PR) receptors, c-erbB-2 protein, p53, Ki67, CK-MNF116, and vimentin. The patients ranged in age from 30 to 78 years (mean 48 years). All patients presented with a palpable unilateral mass. Three patients showed two hamartomas in the same breast. Tumours ranged from 20 to 50 mm in diameter. Typical macroscopic and microscopic features were noted. Immunohistochemical studies showed ER and PR receptor positivity in epithelial cells as well as in the stromal cells in all 24 cases. No c-erbB-2 protein over-expression was noted. p53 expression was not observed. Ki67 showed 2-3% positivity in epithelial cells and not in stromal cells in most cases. CONCLUSIONS: There was no association with side, ethnic origin or dietary habits. The immunohistochemistry of hamartomas is generally similar to normal breast or fibrocystic breast tissue. Ki67 together with receptor positivity may reflect some proliferative activity and explain observed faster growth of hamartoma during pregnancy and lactation.

Adult↗
PubMed2002

Time from insemination to first cleavage predicts developmental competence of human preimplantation embryos in vitro.

BACKGROUND: The absence of reliable markers for the identification of viable embryos for transfer at the early cleavage stage is likely to contribute to the generally low implantation rates and high incidence of multiple gestation in IVF treatment. In this study, we investigate the relationship between timing of first cleavage and the incidence of blastocyst formation in vitro. METHODS: Couples (n = 70) with at least one embryo remaining after transfer were included in the analyses. All embryos (n = 579) were examined for early cleavage at 25 h after insemination. Following embryo transfer, the remaining embryos (n = 426) were cultured until day 7 of development, and assessed for blastocyst formation. RESULTS: Eighty-five embryos (14.7%) cleaved to the 2-cell stage within 25 h of insemination; 26 of these were selected for transfer on day 2. Of the 59 embryos remaining in culture, 19 (32.2%) developed to the blastocyst stage; this was a significantly higher number than was observed in embryos (61/367; 16.6%) that failed to cleave within 25 h of insemination (P < 0.01). Within these two groups of embryos the proportion of hatched blastocysts was 11/59 (18.6%) and 26/367 (7.1%) respectively (P < 0.005). CONCLUSIONS: These findings indicate that early cleavage is indicative of increased developmental potential in human embryos and may be useful as an additional criterion in the selection of embryos for transfer.

Adult↗
PubMed2002

Effect of new synthetic heparin mimetics on whole blood thrombin generation in vivo and in vitro in rats.

The effect of new heparin mimetics (synthetic oligosaccharides) was studied in vitro with regard to thrombin generation (TG) in rat platelet rich plasma (PRP) and whole blood (WB) and in vivo on stasis-induced venous thrombosis in the rat. TG in PRP and in WB was highly dependent on platelet count and strongly influenced by the haematocrit. The peak of TG appeared to be significantly higher in WB than in PRP whereas the endogenous thrombin potential (ETP) was not significantly different under either condition. The effect of hirudin, the synthetic pentasaccharide SR90107/Org31540 (SP) and heparin were measured on TG in PRP and WB. We then compared the effect of two new synthetic heparin mimetics (SR121903A and SanOrg123781) with potent and comparable antithrombin (AT) mediated activity against factor Xa and thrombin. These two compounds were made of a pentasaccharide with a high affinity to AT, prolonged at the non-reducing end by an oligosaccharide chain recognised by thrombin. In SR121903A, the charge density and charge distribution was analogous to that of heparin whereas in SanOrg123781 the charges were only located on the last 5 saccharides of the non-reducing end of the molecule. In PRP and in WB, SR121903A acted on the lag time and on the AUC whereas SanOrg123781 inhibited thrombin formation with no effect on the lag time. SanOrg123781 was more potent in inhibiting TG than SR121903A. This difference was due to the structures of the compounds that differed in their ability to be neutralised by platelet factor 4. The antithrombotic effect of the two compounds was examined in a venous thrombosis model in rats. We observed that SanOrg123781 was more active than SR121903A and heparin. Taken together, these results indicate that the activity of oligosaccharides is greatly influenced by the global charge density of the molecule and show that SanOrg123781 is a potent and promising antithrombotic drug candidate.

Animals↗
PubMed2002

Beating heart surgery reduces mortality in the reoperative bypass patient.

BACKGROUND: Reoperative coronary artery bypass grafting (redo-CABG) has an increased operative morbidity and mortality compared to patients undergoing primary revascularization. In an effort to reduce the hazards of reoperative CABG, we commenced revascularizing selected patients without cardiopulmonary bypass (CPB) as an alternative to conventional approaches. METHODS: From January 1998 to Dec. 2000, 432 patients underwent reoperative CABG, 153 patients (35%) without the aid of CPB. Treatment groups were compared by means of univariate analysis for preoperative risk factors and postoperative complications. Predicted risk and risk-adjusted mortality were determined by the Society of Thoracic Surgeons risk algorithm. RESULTS: There was a significant difference in the preoperative predicted risk scores between the two treatment groups (off pump 6.5% vs. on pump 5.4%, p=0.0343). There was a significant difference in the off pump observed mortality (2.61%) versus the on pump group (9.68%, p=0.0065). Decreased morbidity in the off pump group was evidenced by a reduced need for blood products (25% vs. 67%, p<0.0001), and the incidence of prolonged ventilation (4% vs. 14%, p=0.0032). The off pump group also had shorter hospital stays (6.2 +/- 5.96 days vs. 8.0 +/- 7.82, p=0.0091). No significant differences between the two groups were seen in the prevalence of perioperative myocardial infarction, stroke, renal failure, or reoperation for bleeding. CONCLUSION: Bypass grafting without CPB significantly decreases mortality and morbidity in selected reoperative patients, and should be considered a viable alternative to conventional approaches.

Analysis of Variance↗
PubMed2001

Genetic population structure of coagulase-negative staphylococci associated with carriage and disease in preterm infants.

Coagulase-negative staphylococci (CoNS) are a leading cause of sepsis in the neonatal intensive care unit (NICU) setting. To evaluate the hypothesis that isolates of CoNS associated with disease belong to hypervirulent clones, as opposed to being drawn randomly from the neonatal unit carriage flora, we conducted a prospective, case-controlled study in a busy NICU. Using pulsed-field gel electrophoresis (PFGE), we compared the population structures of CoNS isolates associated with bacteremia with isolates from the skin of healthy and infected neonates and with blood culture contaminants. Endemic clones of CoNS were identified, but there was no difference in the distribution of the 6 species or 73 PFGE types between the carriage and disease isolate groups; this suggests that hypervirulent clones with an enhanced ability to cause disease were not present in this NICU setting.

Anti-Bacterial Agents↗
PubMed2001

Acute inflammatory myopathy with severe subcutaneous edema, a new variant? Report of two cases and review of the literature.

Acute inflammatory myopathy with severe subcutaneous edema is extremely rare and has been reported in only a handful of cases. We describe two similar patients presenting with this disorder and generalized rash. Unlike the five previously reported cases, the clinical and histologic features of our two patients are more suggestive of dermatomyositis than polymyositis. Nevertheless, scrutinizing all seven reported patients, a number of specific characteristics could be defined. All patients were adult males. Dysphagia was present in four. In six patients, acute inflammatory myopathy was idiopathic while malignancy was present in one. Two patients died despite intensive therapy, three improved on corticosteroid treatment, and two recovered spontaneously. In all patients, limb involvement with marked subcutaneous edema was present, clinically mimicking deep vein thrombosis in both our patients. The presence of severe subcutaneous edema may be a hallmark of a distinctive variant of acute inflammatory myopathy. More cases are needed to discern subtypes of this general entity and to establish guidelines for treatment and prognosis.

Acute Disease↗
PubMed2001

Granulomatous kerato-conjunctivitis as a manifestation of Hodgkin lymphoma.

PURPOSE: To report atypical kerato-conjunctivitis as a manifestation of Hodgkin disease. METHODS: Case report. RESULTS: A 19-year old woman presented with conjunctival nodules and corneal infiltrates. Diffuse lymph node enlargement occurred, but not in the preauricular or submandibular areas. Extensive microbiologic examination was negative. Conjunctival biopsy showed noncaseating granulomas. Inguinal lymph node biopsy showed Hodgkin lymphoma, and chemotherapy was instituted. Ocular signs resolved after 6 weeks, but a corneal scar remained. CONCLUSIONS: The appearance of conjunctival granulomas and corneal infiltrates may represent a clinical manifestation of Hodgkin lymphoma.

Adult↗
PubMed2001

No effect of cigarette smoking on attention or mood in non-deprived smokers.

AIM: This study aimed (a) to assess whether smoking reduces anxiety when paired with a pleasant distractor and (b) to investigate the effect of smoking a cigarette on cognitive performance in non-deprived smokers. DESIGN: Participants were allocated randomly to four conditions in a 2 x 2 factorial design: 1, Smoke + Distractor; 2, Smoke + No Distractor; 3, No Smoke + Distractor; 4, No Smoke + No Distractor. SETTING: University psychology department (University of Surrey, UK). PARTICIPANTS: Forty-five volunteer cigarette smokers (mean consumption = 16 cigarettes per day) allowed to smoke normally prior to the study. INTERVENTION: Participants were either allowed to smoke a cigarette of their choice in a manner of their choosing or not allowed to smoke, either with or without a concurrent distractor (a music video). MEASUREMENTS: Rapid Visual Information Processing (RVIP) performance was measured via computer before and after a 10-minute break (during which the interventions took place). Mood was measured by (a) State Anxiety Inventory (SAI) and (b) Feeling State Questionnaire (FSQ), before and after the first RVIP task and then immediately after the break/cigarette. FINDINGS: The RVIP task produced a significant increase in both measures of anxiety (SAI and FSQ stress subscale). Smoking, when paired with a distractor, did not decrease anxiety compared with when no distractor was present. Furthermore, smoking did not decrease anxiety or increase attentional (RVIP) performance compared with not smoking. CONCLUSION: The findings of this study failed to support the idea that smoking has anxiety-reducing or attention-enhancing properties in non-abstinent smokers.

Adolescent↗
PubMed2001

Is a NAD pyrophosphatase activity necessary for Haemophilus influenzae type b multiplication in the blood stream?

Haemophilus influenzae has an absolute requirement for factor V because it lacks all the biosynthetic enzymes necessary for the de novo synthesis of NAD. Factor V can be provided as either nicotinamide adenosine dinucleotide (NAD), nicotinamide mono-nucleotide (NMN) or nicotinamide riboside (NR) in vitro, but little is known about the source or the mechanism of uptake for factor V in vivo. Recently, a hypothetical open reading frame (ORF), termed nadN, was identified to encode a gene product essential for H. influenzae growth on NAD. Here, we report its role in the virulent H. influenzae serotype b strain Eagan. Our results indicate that NadN of type b Eagan strains is involved in NAD uptake and in processing NAD to NR, which appears to be the substrate for an as yet unidentified cytoplasmic membrane NR transport system. Furthermore, we present data showing that H. influenzae type b nadN mutants are able to survive as well as Eagan, in vivo in the five-day-old infant rat model of human invasive disease. NAD pyrophosphatase and NMN 5'-nucleotidase activities were present in rat and human serum, implying that under infection conditions H. influenzae may obtain NR directly from its host.

Animals↗
PubMed2001

Delivering health care services in the community: a multidisciplinary perspective.

The Canadian health care system has shifted away from its traditional emphasis on acute care in-patient services, to increasing dependence on community-based services. A major implication is that education for work in this new environment will need to be reconceptualized, and those already in the system will have to examine their assumptions and alter their approach to patient care. This paper reports the results of a study which examines the attitudes, educational preparation, skills sets, and perceptions of "community" among social workers, occupational therapists, nurses and physiotherapists. The results should inform social work and other health educators about relevant theoretical and practical preparation for work in an environment which increasingly emphasizes multiple skills, community partnerships and coordinated care.

Attitude of Health Personnel↗
PubMed2001

NadN and e (P4) are essential for utilization of NAD and nicotinamide mononucleotide but not nicotinamide riboside in Haemophilus influenzae.

Haemophilus influenzae has an absolute requirement for NAD (factor V) because it lacks almost all the biosynthetic enzymes necessary for the de novo synthesis of that cofactor. Factor V can be provided as either nicotinamide adenosine dinucleotide (NAD), nicotinamide mononucleotide (NMN), or nicotinamide riboside (NR) in vitro, but little is known about the source or the mechanism of uptake of these substrates in vivo. As shown by us earlier, at least two gene products are involved in the uptake of NAD, the outer membrane lipoprotein e (P4), which has phosphatase activity and is encoded by hel, and a periplasmic NAD nucleotidase, encoded by nadN. It has also been observed that the latter gene product is essential for H. influenzae growth on media supplemented with NAD. In this report, we describe the functions and substrates of these two proteins as they act together in an NAD utilization pathway. Data are provided which indicate that NadN harbors not only NAD pyrophosphatase but also NMN 5'-nucleotidase activity. The e (P4) protein is also shown to have NMN 5'-nucleotidase activity, recognizing NMN as a substrate and releasing NR as its product. Insertion mutants of nadN or deletion and site-directed mutants of hel had attenuated growth and a reduced uptake phenotype when NMN served as substrate. A hel and nadN double mutant was only able to grow in the presence of NR, whereas no uptake of NMN was observed.

Bacterial Outer Membrane Proteins↗