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Biomedical subjects

S Craig

Publications and source records attributed to S Craig.

At least 19 recordsLinked to original sources
PubMed2005

Admission to neonatal intensive care with respiratory morbidity following 'term' elective caesarean section.

Delaying the timing of elective caesarean section (ELCS) from 37/38 weeks to 39/40 weeks reduces the risk of respiratory morbidity in otherwise healthy neonates. The aims of this study were to clarify the number and clinical details of term infants delivered by ELCS who were admitted to neonatal intensive care (NIC) from 1st April 2001 to 31st March 2002 in Northern Ireland, to record the level of care required by these infants and to identify infants who were diagnosed with transient tachypnoea of the newborn (TTN) and/or Respiratory Distress Syndrome (RDS). Two hundred and ten (8%) of babies born by ELCS were admitted to NIC. Term infants delivered by ELCS used 343 days of level 1 & 2 care with 230 (68%) of these days being used by infants with RDS/TTN (n=105) the majority of whom were delivered at 37/38 weeks. Definitions of 'term' and clinical indications for ELCS urgently need to be debated to avoid unnecessary morbidity following ELCS in so called 'term' infants.

Cesarean Section↗
PubMed2004

GMP production and testing of Xcellerated T Cells for the treatment of patients with CLL.

BACKGROUND: Pre-clinical studies suggest Xcellerated T Cells have the potential to produce a potent anti-tumor effect, restore broad immune function and reduce the risk of infectious complications in patients with CLL. Unlike other cancer settings, T cells constitute only a small fraction of CLL patients' PBMC. To generate large numbers of Xcellerated T Cells of high purity from CLL patients' PBMC, a reproducible, streamlined and cost-effective good manufacturing process (GMP) is required. METHODS: The 10-L volume Wave Bioreactor-based Xcellerate III Process using Xcyte Dynabeads in a single custom 20-L Cellbag container was adapted, qualified and implemented for GMP operations. RESULTS: For n=17 CLL patients, starting with approximately 1.34 x 10(9) CD3+ T cells at 6.8+/-7.5% purity in the PBMC leukapheresis products, using the 10-L volume Wave Bioreactor-based Xcellerate III Process, it was feasible to manufacture 137.0+/-34.3 x 10(9) Xcellerated T Cells at 98.5+/-1.0% CD3+ T-cell purity. An average 400-fold clearance of malignant B cells was documented during the manufacturing process. The Xcellerated T Cells produced from the Xcellerate III Process exhibited high in vitro biologic activity and have their T-cell receptor repertoire restored to a normal diversity. In-process T-cell activation was reproducibly robust, as measured by increase in cell size, up-regulation of CD25 and CD154 expression and the secretion of IL-2, IFN-gamma and tumor necrosis factor (TNF)-alpha. DISCUSSION: A low-volume, high-yield bioreactor-based process has been developed, qualified and implemented for the reproducible, GMP manufacture of high purity, biologically active Xcellerated T Cells for the treatment of CLL patients in clinical trials.

B-Lymphocytes↗
PubMed2004

No deterioration after 13 years in a stability study of a rabbit brain, plain, thromboplastin, RBT 1010, in rubber-stoppered ampoules.

RBT 1010, a rabbit brain thromboplastin, plain, was prepared at the Thrombosis Reference Centre, Withington Hospital, Manchester, in 1989. The batch has been stored at -20 degrees C, in rubber-stoppered ampoules, for 13 years. The material was unchanged after this time. This was confirmed in a stability study, in which the reagent was used to test the prothrombin times of a panel of plasmas stored in liquid nitrogen, one from a normal volunteer and two from stable anticoagulated patients. RBT 1010 was also tested in calibrations, according to World Health Organization recommendations, against the reference thromboplastin preparations CRM 149S and RBT 90.

Animals↗
PubMed2001

Sialylated O-glycans and sulfated tyrosines in the NH2-terminal domain of CC chemokine receptor 5 contribute to high affinity binding of chemokines.

The chemokine receptor CCR5 plays an important role in leukocyte chemotaxis and activation, and also acts as a coreceptor for human and simian immunodeficiency viruses (HIV-1, HIV-2, and SIV). We provide evidence that CCR5 is O-glycosylated on serine 6 in the NH2 terminus. The O-linked glycans, particularly sialic acid moieties, significantly contribute to binding of the chemokine ligands. By contrast, removal of O-linked oligosaccharide exerted little effect on HIV-1 infection. Sulfation of specific tyrosine residues in the CCR5 NH2 terminus was important for efficient beta-chemokine binding. Thus, as has been observed for the binding of selectins and their ligands, O-linked carbohydrates and tyrosine sulfates play major roles in promoting the interaction of chemokines with CCR5. The resulting flexible arrays of negative charges on the CCR5 surface may allow specific, high-affinity interactions with diverse chemokine ligands. Although this is the first example of O-linked oligosaccharides and tyrosine sulfates playing a role in chemokine binding, the high density of serines, threonines and tyrosines in the N-termini of many CC chemokine receptors suggests that these posttranslational modifications may commonly contribute to chemokine binding.

Amino Acid Sequence↗
PubMed2001

Developing a service excellence system for ambulatory care pharmacy services.

A service excellence system for ambulatory care pharmacy services is described. An interview was designed to measure the needs, expectations, and priorities of a random sample of ambulatory care patients at a 964-bed county teaching hospital and its clinics to determine trends in patient service and satisfaction. The interviews were conducted by the same interviewers with the same script, and follow-up was continuous for two years. Information was summarized for each question and pharmacy site. In defining "service excellence" from a patient's perspective, it was determined that patients wanted a continuation of low-cost prescriptions, decreased waiting time, a friendlier, more caring staff, and environmental modifications. A service excellence system with key performance indicators was then designed and implemented. This effort included recruiting employees with behaviors that support service excellence, training employees to deliver service excellence, creating an environment that promotes patient satisfaction, and designing an ongoing monitoring system. Next, it was imperative to change the attitudes of staff and existing processes to meet or exceed patients' expectations. This phase addressed such issues as patient waiting time, staff-patient interaction, patients' environmental concerns, and staff ideas for service improvement. Finally, changes in service levels were measured. Overall patient satisfaction increased from 72% to 93% at the maincampus pharmacies. Satisfaction at the smaller sites rose from 85% to 95%, while turnaround time and number of pharmacist full-time-equivalents remained stable. A service excellence program was effective in addressing the service issues of ambulatory care patients at a large teaching hospital.

Ambulatory Care↗
PubMed2001

Depressive symptoms in patients with Alzheimer's disease.

OBJECTIVES: A comparison was made between the depressive symptom profiles of thirty patients with Alzheimer's disease (AD) who did not have co-existing depression and thirty patients with major depression who did not have co-existing dementia. The main objective was to identify symptoms common to both disorders and those which may be able to differentiate AD from major depression. METHOD: A sample of patients suffering from either AD (n = 30) or major depression (n = 30) were recruited from a specialist old age psychiatry service. Depressive symptoms were profiled using the Hamilton Depression Rating Scale (HDRS), the Cornell Scale for Depression in Dementia (CSDD) and the Geriatric Depression Scale (GDS). RESULTS: Depressive symptoms were present in AD in the absence of coexistent major depression. Certain depressive symptoms from all the three scales such as sadness, diurnal variation in mood and early or late insomnia were able to differentiate the two disorders with almost 90% accuracy while symptoms such as irritability, retardation and weight loss were common to both and were unable to differentiate the two. CONCLUSION: Depressive symptoms occur in AD when co-existing depression is ruled out. Their recognition has implications for the diagnosis of major depression in these patients.

Aged↗
PubMed2001

Assignment of paternity groups without access to parental genotypes: multiple mating and developmental plasticity in squid.

We present a novel approach to investigating sibling relationships and reconstructing parental genotypes from a progeny array. The Bayesian method we have employed is flexible and may be applicable to a variety of situations in addition to the one presented here. While mutation rates and breeding population allele frequencies can be taken into account, the model requires relatively few loci and makes few assumptions. Paternity of 270 veined squid (Loligo forbesi) hatchlings from three egg strings collected from one location was assigned using five microsatellite loci. Paternal and maternal genotypes reconstructed for each of the three strings were identical, strongly indicating that a single female produced the strings that were fertilized by the same four males. The proportion of eggs fertilized was not equal between males in all three strings, with male 1 siring most offspring (up to 68% in string 1), through to male 4 siring the least (as low as 2.4% in string 1). Although temperature had a profound effect on incubation time, paternity did not affect this trait at 12 degrees C or 8 degrees C.

Animals↗
PubMed2001

Laparoscopic assisted Doderlein hysterectomy: initial experience in a provincial Australian centre.

Despite the theoretical advantages that laparoscopic hysterectomy techniques offer, this is not a commonly performed operation in Australia. The laparoscopically assisted Doderlein hysterectomy is a technique that offers significant advantages in speed, ease of performance, and low cost. We describe our technique and results of the first 36 cases performed for a range of clinical indications and uterine weights, using widely available and non-disposable equipment. Operating time (including adjunctive operations) varied from 48 to 165 minutes and no significant complications were encountered.

Adult↗
PubMed2000

The heart reinnervates after transplantation.

BACKGROUND: Whether cardiac reinnervation occurs after transplantation remains controversial. If reinnervation does occur, how sympathetic and parasympathetic efferent neurons do this remains unknown. METHODS: Power spectral analysis of heart rate variability was assessed for 1 year after cardiac autotransplantation in 9 dogs. After induction of anesthesia 13 months after transplantation, cardiac and intrinsic cardiac neuronal responses elicited by both electrical stimulation of parasympathetic or sympathetic efferent neurons and systemic or local coronary artery administration of nicotine (5 microg/kg), angiotensin II (0.75 microg/kg), and tyramine (1.2 microg/kg) were studied. The transmembrane electrical properties of intrinsic cardiac neurons were studied in vitro. Ventricular tissue catecholamine content, alpha-tubulin expression, and beta-adrenergic receptor density and affinity were studied. The presence of axons crossing suture lines was sought histologically. RESULTS: Nerves were identified crossing suture lines. Electrical or chemical (ie, nicotine or angiotensin II) activation of sympathetic efferent neurons enhanced cardiodynamics, as did tyramine. Stimulating vagal efferent preganglionic axons induced bradycardia in half of the dogs. Functional reinnervation did not correlate with specific power spectra derived from rate variability in the conscious state. Responding to nicotine and angiotensin II in situ, transplanted intrinsic cardiac neurons generated spontaneous activity. These neurons displayed nicotine-dependent synaptic inputs in vitro. Ventricular tissue had normal beta-adrenergic receptor affinity and density but reduced catecholamine and alpha-tubulin contents. CONCLUSIONS: The intrinsic cardiac nervous system receives reduced input from extracardiac sympathetic efferent neurons after transplantation and inconsistent input from parasympathetic efferent preganglionic neurons. These heterogeneous neuronal inputs are not reflected in heart rate variability or ventricular beta-adrenergic receptor function. Transplanted angiotensin II-sensitive intrinsic cardiac neurons exert greater cardiac control than do nicotine-sensitive ones. The intrinsic cardiac nervous system remodels itself after cardiac transplantation, and this indicates that direct assessment of extracardiac and intrinsic cardiac neuronal behavior is required to fully understand cardiac control after transplantation.

Animals↗
PubMed2000

Sequential organ scoring as a measure of effectiveness of critical care.

We performed an observational nonrandomised study in a critical care unit of a large district general hospital in England to establish whether sequential organ scoring could be used as a measure of effectiveness of intensive care. The degree of organ dysfunction of 75 consecutive patients admitted to the critical care unit whose duration of stay exceeded 48 h was measured using the Logistic Organ Dysfunction System score. The trends in organ dysfunction of survivors and non-survivors were significantly different with function improving in survivors and remaining constant or worsening in non-survivors. In both groups, the degree of organ dysfunction decreased over the first three days of intensive care. On an individual patient basis, we achieved no change or an improvement in organ score over this period in 80% of patients. In terms of individual organ function, intensive care consistently improved scores relating to the cardiovascular, respiratory and renal systems over the first 72 h of care, but not the neurological, hepatic or haematological systems. In conclusion, daily organ scoring usefully reflects the ability of an intensive care unit to stabilise or reverse physiological dysfunction.

APACHE↗
PubMed2000

Wide-complex tachycardia: continued evaluation of diagnostic criteria.

OBJECTIVE: To evaluate the accuracy of the Brugada algorithm for analysis of wide-complex tachycardia (WCT) when applied by board-certified emergency physicians and board-certified cardiologists. METHODS: A database consisting of 157 electrocardiograms of WCTs were evaluated in a blinded fashion using the Brugada criteria to determine the presence of ventricular tachycardia (VT) or supraventricular tachycardia with aberrancy. These results were then compared with the electrophysiologically proven diagnosis for each tracing. Sensitivity and specificity of the Brugada criteria for diagnosis of VT were calculated. Two board-certified emergency physicians and two board-certified cardiologists analyzed each tracing, and interobserver agreement was determined using the kappa statistic. RESULTS: Sensitivity and specificity for the determination of VT using the Brugada algorithm were 85% [95% confidence interval (95% CI) = 79% to 91%] and 60% (95% CI = 43% to 78%) for cardiologist 1 (C 1) and 91% (95% CI = 86% to 96%) and 55% (95% CI = 37% to 72%) for C 2. Emergency physician (EP 1) achieved a sensitivity of 83% (95% CI = 78% to 91%) and a specificity of 43% (95% CI = 25% to 59%), while EP 2 attained 79% (95% CI = 73% to 87%) and 70% (95% CI = 51% to 84%), respectively. The original authors achieved a sensitivity of 98.7% and specificity of 96.5% when determining VT in their study population. Interobserver agreement for the emergency physicians and the cardiologists in determining VT was 82% and 81%, respectively. CONCLUSIONS: Neither the emergency physicians nor the cardiologists were able to achieve a sensitivity or specificity as high as that reported by the original investigators when using the Brugada algorithm to determine the presence of VT.

Adult↗
PubMed2000

The level of CD4 expression limits infection of primary rhesus monkey macrophages by a T-tropic simian immunodeficiency virus and macrophagetropic human immunodeficiency viruses.

The entry of primate immunodeficiency viruses into cells is dependent on the interaction of the viral envelope glycoproteins with receptors, CD4, and specific members of the chemokine receptor family. Although in many cases the tropism of these viruses is explained by the qualitative pattern of coreceptor expression, several instances have been observed where the expression of a coreceptor on the cell surface is not sufficient to allow infection by a virus that successfully utilizes the coreceptor in a different context. For example, both the T-tropic simian immunodeficiency virus (SIV) SIVmac239 and the macrophagetropic (M-tropic) SIVmac316 can utilize CD4 and CCR5 as coreceptors, and both viruses can infect primary T lymphocytes, yet only SIVmac316 can efficiently infect CCR5-expressing primary macrophages from rhesus monkeys. Likewise, M-tropic strains of human immunodeficiency virus type 1 (HIV-1) do not infect primary rhesus monkey macrophages efficiently. Here we show that the basis of this restriction is the low level of CD4 on the surface of these cells. Overexpression of human or rhesus monkey CD4 in primary rhesus monkey macrophages allowed infection by both T-tropic and M-tropic SIV and by primary M-tropic HIV-1. By contrast, CCR5 overexpression did not specifically compensate for the inefficient infection of primary monkey macrophages by T-tropic SIV or M-tropic HIV-1. Apparently, the limited ability of these viruses to utilize a low density of CD4 for target cell entry accounts for the restriction of these viruses in primary rhesus monkey macrophages.

Animals↗
PubMed2000

Metabolism of VLDL is increased in streptozotocin-induced diabetic rat hearts.

In streptozotocin (STZ)-induced diabetic rats, we previously showed an increased heparin-releasable (luminal) lipoprotein lipase (LPL) activity from perfused hearts. To study the effect of this enlarged LPL pool on triglyceride (TG)-rich lipoproteins, we examined the metabolism of very-low-density lipoprotein (VLDL) perfused through control and diabetic hearts. Diabetic rats had elevated TG levels compared with control. However, fasting for 16 h abolished this difference. When the plasma lipoprotein fraction of density <1.006 g/ml from fasted control and diabetic rats was incubated in vitro with purified bovine or rat LPL, VLDL from diabetic animals was hydrolyzed as proficiently as VLDL from control animals. Post-heparin plasma lipolytic activity was comparable in control and diabetic animals. However, perfusion of control and diabetic rats with heparinase indicated that diabetic hearts had larger amounts of LPL bound to heparan sulfate proteoglycan-binding sites. [(3)H]VLDL obtained from control rats, when recirculated through the isolated heart, disappeared at a significantly faster rate from diabetic than from control rat hearts. This increased VLDL-TG hydrolysis was essentially abolished by prior perfusion of the diabetic heart with heparin, implicating LPL in this process. These findings suggest that the enlarged LPL pool in the diabetic heart is present at a functionally relevant location (at the capillary lumen) and is capable of hydrolyzing VLDL. This could increase the delivery of free fatty acid to the heart, and the resultant metabolic changes could induce the subsequent cardiomyopathy that is observed in the chronic diabetic rat.

Animals↗
PubMed1999

Identification of amino acid residues critical for aggregation of human CC chemokines macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and RANTES. Characterization of active disaggregated chemokine variants.

Human CC chemokines macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and RANTES (regulated on activation normal T cell expressed) self-associate to form high-molecular mass aggregates. To explore the biological significance of chemokine aggregation, nonaggregating variants were sought. The phenotypes of 105 hMIP-1alpha variants generated by systematic mutagenesis and expression in yeast were determined. hMIP-1alpha residues Asp26 and Glu66 were critical to the self-association process. Substitution at either residue resulted in the formation of essentially homogenous tetramers at 0.5 mg/ml. Substitution of identical or analogous residues in homologous positions in both hMIP-1beta and RANTES demonstrated that they were also critical to aggregation. Our analysis suggests that a single charged residue at either position 26 or 66 is insufficient to support extensive aggregation and that two charged residues must be present. Solution of the three-dimensional NMR structure of hMIP-1alpha has enabled comparison of these residues in hMIP-1beta and RANTES. Aggregated and disaggregated forms of hMIP-1alpha, hMIP-1beta, and RANTES generally have equivalent G-protein-coupled receptor-mediated biological potencies. We have therefore generated novel reagents to evaluate the role of hMIP-1alpha, hMIP-1beta, and RANTES aggregation in vitro and in vivo. The disaggregated chemokines retained their human immunodeficiency virus (HIV) inhibitory activities. Surprisingly, high concentrations of RANTES, but not disaggregated RANTES variants, enhanced infection of cells by both M- and T-tropic HIV isolates/strains. This observation has important implications for potential therapeutic uses of chemokines implying that disaggregated forms may be necessary for safe clinical investigation.

Amino Acid Sequence↗
PubMed1999

Multilineage potential of adult human mesenchymal stem cells.

Human mesenchymal stem cells are thought to be multipotent cells, which are present in adult marrow, that can replicate as undifferentiated cells and that have the potential to differentiate to lineages of mesenchymal tissues, including bone, cartilage, fat, tendon, muscle, and marrow stroma. Cells that have the characteristics of human mesenchymal stem cells were isolated from marrow aspirates of volunteer donors. These cells displayed a stable phenotype and remained as a monolayer in vitro. These adult stem cells could be induced to differentiate exclusively into the adipocytic, chondrocytic, or osteocytic lineages. Individual stem cells were identified that, when expanded to colonies, retained their multilineage potential.

Adipocytes↗
PubMed1999

Treatment of severe postpartum hemorrhage by rectally administered gemeprost pessaries.

OBJECTIVE: To assess the efficacy of rectally administered gemeprost pessaries in the treatment of severe postpartum hemorrhage. DESIGN: Retrospective analysis of a twelve month period in which all patients having postpartum hemorrhage treated with rectal gemeprost were analyzed. SETTING: Royal Darwin Hospital, Northern Territory, Australia. POPULATION: Fourteen women with established postpartum hemorrhage not responding to oxytocine and ergometrine regimens, or not responsive to oxytocine and having contraindications to ergometrine. MAIN OUTCOME MEASURES: Per vaginum bleeding with continued postpartum hemorrhage; adverse patient reactions to gemeprost; need for operative intervention. RESULTS: All patients who were treated with rectally administered gemeprost pessaries had cessation of bleeding per vaginum. There were no adverse side effects noted from the medication and no patient required surgical treatment. CONCLUSIONS: Rectally administered gemeprost administered pessaries appear to be safe and effective method of treating severe postpartum hemorrhage in those patients in whom the standard oxytocic regimens fail. This form of treatment may avoid the need for parenteral prostaglandins or surgical intervention.

Administration, Rectal↗
PubMed1998

Genetic control of male fertility in Arabidopsis thaliana: structural analyses of postmeiotic developmental mutants.

Seven new male-sterile mutants (ms7-ms13) of Arabidopsis thaliana (L.) Heynh. (ecotype columbia) are described that show a postmeiotic defect of microspore development. In ms9 mutants, microspores recently released from the tetrad appear irregular in shape and are often without exines. The earliest evidence of abnormality in ms12 mutants is degeneration of microspores that lack normal exine sculpturing, suggesting that the MS12 product is important in the formation of pollen exine. Teratomes (abnormally enlarged microsporocytes) are also occasionally present and each has a poorly developed exine. In ms7 mutant plants, the tapetal cytoplasm disintegrates at the late vacuolate microspore stage, apparently causing the degeneration of microspores and pollen grains. With ms8 mutants, the exine of the microspores appears similar to that of the wild type. However, intine development appears impaired and pollen grains rupture prior to maturity. In ms11 mutants, the first detectable abnormality appears at the mid to late vacuolate stage. The absence of fluorescence in the microspores and tapetal cells after staining with 4',6-diamidino-2-phenylindole (DAPI) and the occasional presence of teratomes indicate degradation of DNA. Viable pollen from ms10 mutant plants is dehisced from anthers but appears to have surface abnormalities affecting interaction with the stigma. Pollen only germinates in high-humidity conditions or during in-vitro germination experiments. Mutant plants also have bright-green stems, suggesting that ms10 belongs to the eceriferum (cer) class of mutants. However, ms10 and cer6 are non-allelic. The ms13 mutant has a similar phenotype to ms10, suggesting is also an eceriferum mutation. Each of these seven mutants had a greater number of flowers than congenic male-fertile plants. The non-allelic nature of these mutants and their different developmental end-points indicate that seven different genes important for the later stages of pollen development have been identified.

Arabidopsis↗