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M Page

Publications and source records attributed to M Page.

At least 37 records · Page 2Linked to original sources
PubMed2000

The role of gastro-oesophageal reflux in the aetiology of SIDS.

Gastro-oesophageal reflux (GOR) has been identified as a possible cause of SIDS. Several features of GOR unique to infants presenting with apparent life-threatening events (ALTEs) have led to its 'pathogenic' definition. One is that the life-threatening apnoea itself is initiated by GOR, another is that the ALTE relates to prolonged reflux during sleep, in a vulnerable sleep-state, and finally that the ALTE relates to excessive quantities of GOR. The presumption of GOR 'pathology' as a cause of SIDS however, is questionable in these susceptible infants for three reasons: firstly, GOR is physiological and occurs in most infants; secondly, there is no general consensus on what constitutes normal physiological reflux, and thirdly, variation in the recording technique and methods of data analysis and interpretation may account for the differences between study groups. It seems likely therefore if GOR is implicated in SIDS, additional factors are involved. Under certain circumstances, physiological GOR may trigger life-threatening apnoea in apparently healthy infants, that leads to SIDS. One mechanism that could explain such a death is reflex apnoea by stimulation of laryngeal chemoreceptors (LCR) during sleep. The conditions under which this could be fatal are the occurrence of gastric contents refluxed to the level of the pharynx during sleep, in the young infant who has depressed swallowing and arousal. That is, the occurrence of GOR to the level of the pharynx during sleep, an infrequent event that is usually innocuous, could be converted to a fatal event if swallowing is impaired and arousal depressed, by a variety of mediating factors such as prone sleeping, prematurity, sedatives, seizures or upper respiratory tract infections. The identification of LCR responses, particularly in prone sleeping and premature infants provide further evidence that this mechanism may be implicated in the aetiology of SIDS in apparently healthy infants.

Aging↗
PubMed2000

Connectionist modelling in psychology: a localist manifesto.

Over the last decade, fully distributed models have become dominant in connectionist psychological modelling, whereas the virtues of localist models have been underestimated. This target article illustrates some of the benefits of localist modelling. Localist models are characterized by the presence of localist representations rather than the absence of distributed representations. A generalized localist model is proposed that exhibits many of the properties of fully distributed models. It can be applied to a number of problems that are difficult for fully distributed models, and its applicability can be extended through comparisons with a number of classic mathematical models of behaviour. There are reasons why localist models have been underused, though these often misconstrue the localist position. In particular, many conclusions about connectionist representation, based on neuroscientific observation, can be called into question. There are still some problems inherent in the application of fully distributed systems and some inadequacies in proposed solutions to these problems. In the domain of psychological modelling, localist modelling is to be preferred.

Brain↗
PubMed2000

The role of swallowing during active sleep in the clearance of reflux in term and preterm infants.

OBJECTIVES: To investigate swallowing and peristalsis in sleep and during gastroesophageal reflux (GER) in both healthy term and preterm infants at term equivalent age. STUDY DESIGN: Multichannel recordings were made in 12 healthy term and 11 preterm infants, under the same conditions, after feeding. Sleep state, cardiorespiratory variables, esophageal pH, and pharyngeal swallowing and peristalsis were measured. GER was defined as pH <4 for > or = 15 seconds, and swallows were classified as pharyngeal only, primary peristalsis (propagated, dropped, interrupted), or secondary peristalsis. RESULTS: Spontaneous swallowing rate was not significantly different between term and preterm infants and was sleep state-related, occurring in active sleep but rarely in quiet sleep. In response to acid GER, term infants significantly increased pharyngeal swallowing from a median of 0.7 (25th-75th interquartile range, 0.5-0.9) to 1.7 (1.0-3.0) swallows/min and secondary peristalsis from a median of 0.5 (25th-75th interquartile range, 0.3-0.8) to 1.1 (0.8-2.0) waves/min (P <.05). In contrast, the preterm infants demonstrated a significantly higher proportion of fully propagated peristaltic swallows compared with the term infants (53% and 27%, respectively) (P <.05). CONCLUSION: The occurrence of swallowing is sleep state-related. In active sleep, term infants clear GER by increasing swallowing and secondary peristalsis, whereas preterm infants at term equivalent age clear GER by increasing propagated peristalsis. This method of clearance would explain the mechanism by which preterm infants have significantly shorter episodes of reflux than term infants.

Deglutition↗
PubMed2000

The effect of vanadium-contaminated commercially available albumin solutions on renal tubular function.

We report our findings in a patient with coronary heart disease who received an intravenous albumin solution that contained a significant level of vanadium on the first day after elective primary coronary revascularization. Six patients who underwent similar surgical procedures without albumin infusion were taken as a control group. After administration of the V-contaminated albumin solution, the urinary excretion rates of alpha-glutathione S-transferase, a marker of proximal tubular damage, showed a several-fold elevation above the reference value, and the mean excretion rate was significantly different from that of the control group (p < 0.05). pi-Glutathione S-transferase, a marker of distal tubular damage, only marginally exceeded the upper reference limit in two urine samples from this patient. In all urine samples from the control group the excretion rates of pi-GST were below the detection limit. No significant differences in the excretion rates of alpha1-microglobulin and N-acetyl-beta-D-glucosaminidase were found between the patient treated with the albumin infusion and the patients of the control group. The biological half-life of intravenously administered V was approximately 125 h. All commercially available albumin solutions contain traces of vanadium with the concentration varying between 1.1 and 677 microg/l. The free V fraction in the albumin solutions increased with total V concentration, the highest concentration of free V found being 299 microg/l. The data suggest that the use of albumin solutions containing high levels of vanadium can lead to renal injuries, especially in patients with existing impaired renal function, as is the case with extracorporal circulation. The contamination is believed to be a result of the commercial isolation process.

Albumins↗
PubMed1999

T-cell and antibody response characterisation of a new recombinant pre-S1, pre-S2 and SHBs antigen-containing hepatitis B vaccine; demonstration of superior anti-SHBs antibody induction in responder mice.

The incidence of non-responders to hepatitis B (HB) virus SHBs antigen (Ag) vaccines has prompted the development of pre-S containing vaccines. The aim of this study was to characterise the murine immune response to a novel recombinant particle (Hepagene) (Medeva plc) containing pre-S1, pre-S2 and SHBsAg components. Hepagene induced potent in vitro spleen T-cell proliferative responses in both BALB/c (maximum stimulation index (SI) = 38) and SWR/J (maximum SI = 43) strains of mouse, following immunisation. High concentrations of interferon-gamma and low concentrations of interleukin-10 were detected in the media of spleen cells stimulated with Hepagene. The anti-Hepagene antibody response was higher in SWR/J mice and alhydrogel adjuvant significantly improved the titres. Anti-pre-S1 antibody was detected in both strains of mouse, whereas antipre-S2 antibody was only detected in SWR/J mice. IgG subclass analysis of the anti-Hepagene response revealed a Th2-type response in BALB/c mice and a mixed Th1/Th2 response in SWR/J mice. Hepagene induced higher anti-SHBs antibody responses than Engerix-B (11097 and 1276 IU/ml, respectively) in BALB/c mice. Hepagene therefore, stimulates strong cellular and humoral immune responses in murine models. The high anti-SHBs antibody response suggests that Hepagene is an improved hepatitis B virus vaccine.

Amino Acid Sequence↗
PubMed1999

Hyperfractionated craniospinal radiation therapy for primitive neuroectodermal tumors: results of a Phase II study.

PURPOSE: To report the results of a Phase II study of hyperfractionated craniospinal radiation therapy, with and without adjuvant chemotherapy for primitive neuroectodermal brain tumors (PNETs) and malignant ependymomas. METHODS AND MATERIALS: Newly diagnosed PNET or malignant ependymomas were treated with hyperfractionated craniospinal radiation therapy. The primary tumor site was treated to a dose of 72 Gy, with 30 Gy given to the rest of the craniospinal axis. The fraction size was 1.0 Gy, given twice a day. Patients with poor risk factors also received adjuvant chemotherapy with CCNU, cisplatin, and vincristine. Patients had follow-up for survival, time to tumor progression, and patterns of relapse. RESULTS: A total of 39 patients (21 males/18 females) were treated between March 12, 1990 and October 29, 1992. The median age was 16 years (range 3-59 years). Tumor types included 25 medulloblastomas, 5 pineoblastomas, 5 cerebral PNETs, 1 spinal cord PNET, and 3 malignant ependymomas. Twenty cases were staged as poor-risk and received adjuvant chemotherapy following radiation. Three-year progression-free survival (PFS) was 60% and 63% for poor-risk and good-risk patients, respectively. Overall 3-year survival for these groups was 70% and 79%, respectively. For the 25 patients with medulloblastoma, there were 16 good-risk and 9 poor-risk patients. Three-year PFSs were 63% and 56%, respectively. The 5-year survival for good-risk medulloblastoma was 69% with 43.7% of these patients having failures outside the primary site. CONCLUSIONS: Survival in patients with good-risk medulloblastoma was no better than that seen in previous studies with single-fraction radiation, and the rate of failure outside the primary site is excessive. Those with poor-risk features had comparable survival to that seen in patients with good risk factors, but these patients were treated with chemotherapy, and the role that hyperfractionated radiation played in their outcome is uncertain.

Adolescent↗
PubMed1999

Social class and nutrition in coronary heart disease.

The UK mortality rate for coronary heart disease is higher than other industrialised countries. Inequalities in health mean people at highest risk of CHD are those least likely to be able to adopt healthy diets. Nurses responsible for nutritional health messages need to take into account people's material circumstances.

Coronary Disease↗
PubMed1998

Two erbB-4 transcripts are expressed in normal breast and in most breast cancers.

ErbB-4 is a recently described member of the epidermal growth factor receptor (EGFR) family which together with erbB-3 acts as a receptor for a group of ligands known as the neuregulins (NRGs) or heregulins (HRGs). Unlike the EGFR and erbB-2 relatively little is known about the expression of erbB-4 in human tumours. Using RT-PCR and Southern blotting analysis we have investigated the expression of erbB-4 mRNA in a range of human tumour cell lines and in normal and malignant breast tissue. Using primers which amplified a 658 base pair (bp) region corresponding to part of the cytoplasmic domain of c-erbB-4 we found the receptor was expressed in some but not all breast and ovarian tumour cell lines and also in a glioma cell line. The highest level of erbB-4 expression was found in the ovarian carcinoma OVCAR-3 and the breast carcinoma T-47D. In all cell lines where the 'full-length' erbB-4 was detected, a second previously undescribed c-erbB-4 sequence was also found as a 610 bp PCR product. The alternative PCR product was identical in sequence to c-erbB-4 except for a deletion of 48 bp which encodes a consensus phosphatidylinositol 3-kinase (PI3K) binding site. This suggested that the two forms of erbB-4 might interact with different intracellular signalling pathways and therefore influence a wider variety of cellular responses to heregulin than previously thought. Expression of both erbB-4 variants was found in 7/7 normal breast tissues but only in 9/12 breast tumours analysed. In line with the terminology of Elenius et al. (1997b) we have designated the two isoforms of the C-terminal transcripts as CT-a (full-length) and CT-b which lacks the P13K binding motif. These results identify suitable cell lines for the further investigation of erbB-4 expression and function and suggest that the role of erbB-4 in breast cancer warrants further investigation with larger numbers of normal and malignant breast tissues.

Alternative Splicing↗
PubMed1998

Sleep states and neonatal pulse oximetry.

AIM: Pulse oximetry is a quick, easy, noninvasive method widely used for monitoring oxygen saturation (SaO2) in the neonatal period. The greatest recognized problem with SaO2 readings measured from the oximeter is artifact, arising from an inability to record accurately during movement. The aim of this study was to determine the proportion of pulse oximeter readings affected by movement artifact during sleep in term and preterm infants. METHOD: Polygraphic recordings were obtained from 11 term and 6 preterm infants at postconceptional ages (SD) of 39.8 (0.8) and 39.3 (1.5) weeks respectively. The polygraphic and computer recordings were divided into epochs of 30 seconds duration and identified as active sleep (AS), quiet sleep (QS), indeterminate sleep (IS), or wakefulness (AW), using electrophysiological parameters and behavioral observations. Movement artifact was identified by visual examination of polygraphic computer recordings using strict criteria. Signal containing artifact was removed from recordings and the percentage of artifact time present per recording calculated. RESULTS: Signal artifact was present in recordings of all infants studied, comprising an average state time of 19% during quiet sleep, 49% of active sleep, 49% of indeterminate sleep and 91% of wakefulness. A significant difference in the proportion of artifact present in recordings of term and preterm was observed only during quiet sleep. CONCLUSION: Movement artifact during pulse oximetry recordings is dependent on behavioral state, and overall affects up to 50% of recorded traces. A reliable and more accurate noninvasive method of recording oxygen saturation is thus needed, for use in both neonatal nurseries and in sleep studies, to aid in accurate clinical decision-making.

Female↗
PubMed1998

Effect of proteasome inhibitors on monocytic IkappaB-alpha and -beta depletion, NF-kappaB activation, and cytokine production.

We investigated the effect of proteasome inhibitors on the lipopolysaccharide (LPS)-induced expression of several monocytic cytokines, which may be dependent on the transcription factor, nuclear factor-kappaB (NF-kappaB). Exposure of human monocytic THP-1 cells to ALLN and Mu873 prevented the LPS-induced degradation of IkappaB-alpha and -beta, as did the more potent proteasome inhibitor, PSI, whereas several calpain inhibitors were ineffective. This was accompanied by the inhibition of nuclear NF-kappaB binding activity and NF-kappaB transcriptional activation. At the mRNA level, the inhibitors blocked the expression of tumor necrosis factor (TNF) and interleukin-1beta (IL-1beta), whereas IL-8 remained unaffected by ALLN and was only partially reduced by the highest dose of PSI. The latter effect appears to be due to an increase in IL-8 mRNA stability in the presence of proteasome inhibitors. Furthermore, the production of TNF was efficiently suppressed by ALLN and PSI, less by Mu873, and not at all by calpain inhibitors. In primary human blood monocytes ALLN also prevented the LPS-induced degradation of IkappaB-alpha and -beta, efficiently blocked the production of TNF and, to a lesser extent, IL-1beta, whereas that of IL-8 was not inhibited. The expression of NF-kappaB-dependent monocytic cytokines may be selectively controlled by the proteasome, offering a potential therapeutic target in inflammatory disease.

Cell Line↗
PubMed1998

IgG purification.

Explore the source record for details and available documents.

Ammonium Sulfate↗
PubMed1998

High dose oral tamoxifen and subcutaneous interferon alpha-2a for recurrent glioma.

Chemotherapeutic regimens in present use for recurrent glioma have substantial toxicity. Activity against recurrent gliomas has been reported for both tamoxifen and interferon alpha, agents that have more acceptable toxicity profiles and that can be administered in an outpatient setting. We tested the efficacy and toxicity of the combination of high-dose tamoxifen and interferon alpha in adults with recurrent glioma in a phase II trial. Eligible patients had radiographically measurable recurrent gliomas of any grade after initial radiation therapy. Interferon-alpha [6 x 10(6) U subcutaneously three times per week] and tamoxifen (240 mg/m2/day orally) were administered continuously. Treatment response was assessed at 6 week intervals using clinical and radiographic criteria. Eighteen patients (11 males and 7 females) were enrolled. Median age was 41 years (range 23-61 years). All patients had gliomas that progressed after radiation therapy and nitrosourea chemotherapy. The histologic diagnosis of the original tumor was glioblastoma multiforme in 8 patients, anaplastic astrocytoma in 5 patients, astrocytoma in 4 patients and mixed malignant glioma in 1 patient. Reversible moderate to severe neurological toxicity manifested by dizziness and unsteady gait was seen at tamoxifen doses of 240 mg/m2/day. Although the initial tamoxifen dose was reduced to 120 mg/m2/day, moderate neurotoxicity was noted at this dose as well and the trial was closed early. The combination of oral tamoxifen (120 to 240 mg/m2/day) and subcutaneous interferon-alpha [6 x 10(6) U three times per week] was associated with significant neurotoxicity in this group of recurrent glioma patients, resulting in early study closure. Of 16 evaluable patients, 12 had progressive disease after one cycle of treatment, 3 had stable disease, and there was one minor response. Gradual dose escalation may be required if similar patients are to be treated with high dose tamoxifen in conjunction with interferon.

Administration, Oral↗
PubMed1998

Characterization of the T- and B-cell immune response to a new recombinant pre-S1, pre-S2 and SHBs antigen containing hepatitis B vaccine (Hepagene); evidence for superior anti-SHBs antibody induction in responder mice.

Hepagene is a novel recombinant particle consisting of the pre-S1, pre-S2 and small surface (SHBs) antigens (Ag) of the hepatitis B virus (HBV) and is adjuvanted with alhydrogel in the final formulation. It has been primarily developed to enhance anti-SHBs antibody titres in inadequate responders, to conventional SHBsAg vaccines. Since non-compliance is also a problem with existing HBV vaccine schedules, the ability to accelerate current immunization regimens to provide more rapid protection has also been an important objective. Here we describe the T- and B-cell responses to Hepagene in two strains of responder mouse (BALB/c and SWR/J). Hepagene induced high in vitro spleen T-cell proliferative responses in both strains (max. Stimulation Index = 43), following intraperitoneal immunization. High concentrations of interferon-gamma (max. = 5000 pg/mL) were detected in the media of spleen cells cultured with non-adjuvanted Hepagene particles. SWR/J mice showed the highest serum antibody (Ab) titres to non-adjuvanted Hepagene. The presence of alhydrogel adjuvant in the vaccine formulation significantly improved the titres. Anti-pre-S1 Ab was detected in both strains of mouse but anti-pre-S2 Ab was only detected in the SWR/J strain. In BALB/c mice, the anti-Hepagene (non-adjuvanted) IgG1 Ab subclass was predominant but in SWR/J mice IgG1, IgG2a and IgG2b subclasses were of a similar magnitude. In BALB/c mice, Hepagene induced higher anti-SHBs Ab responses than Engerix-B (11097 IU/mL and 1276 IU/mL, respectively), following two doses of vaccine (10 micrograms/mouse). The vaccine therefore, induces strong cellular and humoral immune responses and these data suggest that Hepagene is an improved hepatitis B vaccine.

Animals↗
PubMed1998

Airway protection in sleeping infants in response to pharyngeal fluid stimulation in the supine position.

This study was designed to evaluate upper airway protective mechanisms in response to pharyngeal fluid stimulation in healthy term and preterm infants at term equivalent age. Five term and seven preterm infants were studied and the following recorded: sleep state, cardiorespiratory function, and swallowing. Infusions of 0.9% saline and sterile water of volumes of 0.04, 0.2, and 0.35 mL were made during active (AS) and quiet sleep (QS). The effect of these variables on apnea (> or = 2 and > or = 5 s), swallowing, and arousal was examined. After pharyngeal infusion, apnea of > or = 2 and > or = 5 s did not change from spontaneous rates for both term and preterm infants. The most common response to pharyngeal infusion was swallowing. In AS, swallowing occurred after 65 and 73% and in QS after 40 and 64% of infusions in term and preterm infants, respectively. Swallowing was volume-related and occurred significantly more often in term infants after larger infusions of 0.35 and 0.2 mL (83 and 67%) compared with the 0.04 mL (19%) and after 0.2 mL compared with 0.04 mL for preterm infants (94 and 44%). At 0.2 mL, this was significantly higher in preterm compared with term infants (p < 0.01) and was the only significant difference between these infants. In response to pharyngeal fluid stimulation, airway defense in both full-term and preterm infants is maintained primarily by swallowing with no evidence of apnea.

Deglutition↗
PubMed1998

In situ localization of paclitaxel binding structures: Labeling with a paclitaxel fluorescent analogue.

Microtubules are a major component of cell cytoskeleton. Microtubules constitute the cellular target of paclitaxel. The interaction of paclitaxel with microtubules causes an increase in tubulin polymerization and microtubules stabilization, leading to a G2/M phase cell cycle arrest and cell death by apoptosis. Three paclitaxel fluorescent analogues were prepared by introducing fluorescein or BODIPY moiety onto the 2' of the 7-carbon. These were then used to study the interaction of paclitaxel with its cellular binding site and the microtubule network was visualized directly by fluorescence microscopy. Free paclitaxel was able to inhibit 7-FITC paclitaxel binding, demonstrating that both products bind to the same site and possess similar biological properties. Using the carbon 7 derivatives, microtubules were labeled as cytoplasmic fibers extending centripedly. A few other cellular components such as nuclear membrane, nucleoli and some other cytoplasmic structures were also labeled. The labeling intensity was reduced by preincubation with free paclitaxel. The interaction of paclitaxel with microtubules was also investigated using flow cytometry. No binding of the 2'C derivative was detected, confirming that a free 2'C is a pre-requisite for paclitaxel microtubules interaction.

Journal Article↗
PubMed1998

New active paclitaxel glucuronide derivative with improved water solubility.

Poor solubility of paclitaxel constitutes an important limitation to its administration to cancer patients. In order to increase solubility, while preserving cytotoxicity, a new paclitaxel derivative substituted at the 2' position of the side chain was prepared. The first step consisted in the introduction of a glutaryl group at the 2' position by esterification of the free hydroxyl followed by an amidation with 6-amino hexanol previously attached to a glucuronide group. The new water soluble derivative was cytotoxic in vitro against an ovarian teratocarcinoma cell line.

Antineoplastic Agents, Phytogenic↗