Biomedical subjects

M Edwards

Publications and source records attributed to M Edwards.

At least 91 records · Page 5Linked to original sources

PubMed1999

Effect of dietary fish oil on tumor-induced hyperlipidemia and tumor growth in rats implanted with a methylcholanthrene-induced sarcoma.

Male Fischer 344 rats implanted with a methylcholanthrene-induced sarcoma (MCS), along with normal (or control) animals, were fed diets containing either 10% com oil (CO) or 2% CO + 8% fish oil (FO), designated as diets CO and FO, respectively, in a study designed to determine the effect of dietary FO on serum lipids (in the presence or absence of a tumor) and the growth and fatty acid composition of the MCS. For both diets, MCS-bearing rats had significantly (p < 0.05) higher serum levels of triglycerides, cholesterol, phospholipids, and total lipids than controls. For both controls and tumor-bearers, serum levels of all these lipids were, with the exception of cholesterol for the tumorbearers, significantly lower in rats receiving the FO diet than for the corresponding groups receiving the CO diet. Relative to rats fed the CO diet, those fed the FO diet had significantly higher serum levels of some fatty acids (e.g., 20:5n-3) but significantly lower levels of others (e.g., 18:2n-6), regardless of tumor status. For the tumor-bearers, differences in the levels of fatty acids in MCS tissue reflected differences in the fatty acid composition of total serum lipids. Sarcoma growth was unaffected by diet. Thus, feeding dietary FO resulted in changes in the lipid status of both control and tumor-bearing rats. Since sarcoma growth was unaffected by diet, the reduction in the severity of MCS-induced hyperlipidemia by FO appears to be due to an effect of the oil per se.

Animals↗

PubMed1999

A 2-year longitudinal study of myopia progression and optical component changes among Hong Kong schoolchildren.

This study investigated refractive error and optical component changes in a group of 142 Hong Kong schoolchildren from age 6 to 17 years over a 2-year period between 1991 and 1993. Subjects were refracted subjectively and corneal curvatures and ocular dimensions were measured. At the end of the 2-year study, the mean spherical equivalent refraction (SER) was -1.86 D (SD 1.99 D) and 62% of the schoolchildren were myopic. The annual incidence of myopia was 11.8%. Children aged 10 years and under had a greater change in SER toward myopia than older children. The annual rate of myopia progression for the myopic children was -0.46 D (SD 0.40 D) and the rate of progression was greatest between age 6 and 10 years old. Vitreous depth/axial length elongation was the main component contributing to the progression of myopia. Hong Kong schoolchildren develop myopia as early as 6 years old and myopia progresses at a greater rate compared with children of European extraction.

Adolescent↗

PubMed1999

New drugs for osteoporosis. Comparison of the costs and required returns with those of other drugs intended for long-term use.

Specific regulatory guidelines dictate that developing a new drug for osteoporosis will be significantly more expensive and take at least 2 years longer in comparison with other long-term therapies developed using the International Committee on Harmonisation (ICH) general guidelines. Assuming similar attrition rates, the minimal additional uncapitalised cost is $US86 million for nonestrogen osteoporosis compounds following a minimum programme designed to gain indications for both treatment and prevention. The excess expenditure is created by the size requirements for phase III fracture trials in both the European Union (EU)/US and Japan. The after-tax cash flows to the point of launch discounted at 11% are $US102 million greater, reflecting the additional effect of delayed time to market. Assuming similar lifecycles, the peak sales required to return the investment on an osteoporosis drug will be a minimum of $US95 million greater per launched compound. Many ongoing osteoporosis programmes are substantially larger than the theoretical minimum. The costs of substantially increasing the sample size in phase III trials mean that blockbuster revenues will be required to break even. However, the potential cost of a delayed launch because of fracture efficacy being incompletely proved is so substantial that fracture trials need to be powered conservatively to decrease the chances of this eventuality.

Clinical Trials as Topic↗

PubMed1999

Shipboard impact of a probable Norwalk virus outbreak from coastal Japan.

Norwalk virus has been implicated in shipboard diarrheal disease outbreaks throughout Asia. A large outbreak of suspected Norwalk virus was investigated on a U.S. Naval aircraft carrier following the clinical recognition of 450 cases of gastroenteritis over a 2-week period (September 14-28, 1997) during coastal exercises. A random sampling of 44 cases from 450 personnel who sought medical attention was compared with 19 controls. Junior enlisted sailors and marines comprised 97% of all cases. There was no evidence of shipboard geographic clustering of cases. Furthermore, no single food type was associated with illness on the basis of comparative analysis (cases versus controls). Principal case signs and symptoms reported included watery stools (89%), nausea (82%), and vomiting (77%). Anecdotal reports indicated > 50% of the cases received rehydration therapy. An absence of fever was also noted in 32% of the cases and only 5% had blood in their stools. The mean duration of illness was 37 hr, with a range of 3-96 hr. Laboratory findings based on reverse transcription-polymerase chain reaction and Southern hybridization methods showed that 21 (72%) of 29 patients had evidence of the UK2 prototype of the Norwalk virus. A cross-sectional study of 131 crew members from the ships population (n = 4,200) showed an attack rate of 44%. Attack rate is a variant of an incident rate applied to a narrowly defined population observed for a limited period of time, such as during an outbreak. The numerator is people who get sick and the denominator is people (population) at risk. An extrapolation of these findings suggests as many as 1,806 sailors may have been affected during the outbreak, of which only 26% (of the 57 outbreak related cases) where identified from sick call records. There was no difference in the mean ages between outbreak and non-outbreak affected crewmen, or geographic clustering based on berthing or work spaces. Outbreak-related cases reported signs and symptoms of watery-stools (79%), nausea (65%), and vomiting (47%). The mean duration of illness was 28 hr, ranging from 2 to 96 hr. Thirty-one percent of outbreak affected cases reported a sick call visit. Loss of work was reported by 39% of the outbreak affected population. This report documents the epidemic potential of Norwalk virus and the associated impact on fleet operational readiness. Additionally, that this outbreak occurred against a background of 3 other consecutive gastroenteritis outbreaks onboard the same ship (March 1997, February/March 1998, and June 1998), all sharing the same clinical and epidemiologic profiles, suggests possible shipboard persistence of Norwalk virus over time, despite periodic ship-wide disinfection efforts.

Adult↗

PubMed1999

The role of heat shock proteins in mammalian differentiation and development.

Heat shock proteins (HSPs) have been identified in all cells, prokaryotic and eukaryotic, to protect the cells from harmful insults and stress. Increased HSP synthesis can also result during normal cellular functions and also respond to exposure from environmental stress and infection. Although the molecular mechanisms responsible for HSP cellular protection are still not fully understood, their expression is critical for cellular survival and can be modified by cell signal transducers such as intracellular pH, cyclic AMP, Ca2+ Na+, inositol [correction of inostitol] triphosphate, protein kinase C, and protein phosphates. Most HSPs interact, assemble, fold, unfold, bind, transport, translocate and 'chaperone' other proteins in the cell and alter their function.

Animals↗

PubMed1998

APE/Ref-1 responses to ischemia in rat brain.

Cerebral ischemia and the aftermath of reperfusion form a hypoxic/hyperoxic sequence of events that can trigger oxidative stress response cascades in neurons of the central nervous system. After transient ischemia there is an increase in intracellular Ca2+ release, extracellular glutamate, reactive oxygen species (ROS) and nitric oxide, genotoxic events that stimulate DNA repair. Increased oxidative stress and interrupted blood flow in ischemia, like DNA repair, also deplete cellular ATP and commit neurons to apoptosis. We report that levels of the DNA repair enzyme apurinic/apyrimidinic endonuclease (APE/Ref-1) decreased significantly in the hippocampus but not other brain areas after 6 h of reperfusion following an induced ischemic insult. This specific inhibition of APE/Ref-1 expression may affect the extent of apoptosis after ischemia.

Animals↗

PubMed1998

APE/Ref-1 responses to oxidative stress in aged rats.

Chronic oxidative stress has been hypothesized to be a major contributor to the aging process. The continued exposure to reactive oxygen species (ROS) generated by oxidative metabolism or environmental sources can damage critical cellular structures and be responsible for some age-related pathology. The exposure of rodents to 100% oxygen, isobaric hyperoxia, increases ambient ROS levels and significantly increases apoptosis in brain. The deleterious effects of ROS also include increased lipid peroxidation, protein oxidation, and DNA damage. Although differences in the relative amounts of oxidative stress in young and old brains have been observed, the mechanisms responsible for impaired aging-associated DNA repair processes have not been characterized. We measured DNA levels of the DNA repair enzyme apurinic/apyrimidinic endonuclease (APE/Ref-1) protein by Western blot analysis in the brains of young (3-month) and old (30-month) male rats exposed to isobaric hyperoxia. Given that APE/Ref-1 is the rate-limiting enzyme in the repair pathway of apurinic/apyrimidinic sites generated in DNA by oxidative damage, we assumed that APE/Ref-1 protein levels were a good reflection of ongoing DNA base excision repair. Isobaric hyperoxia stimulated APE/Ref-1 expression in the hippocampus and basal forebrain of young rats experiencing 100% oxygen for 6 hr, while aged rats showed no significant changes in APE/Ref-1 protein levels in all brain areas at any time tested (0-48 hr) after hyperoxia. Differences in the stress-induced levels of expression of DNA repair enzymes may contribute to apoptotic increases and pathology associated with the aging process.

Aging↗

PubMed1998

A videofluoroscopic comparison of straw and cup drinking: the potential influence on dental erosion.

OBJECTIVE: Videofluoroscopy was used to compare drinking from a cup with drinking through straws of two varying bore diameters in different positions in the mouth. DESIGN: Clinical study at a single centre. SETTING: UK dental school. SUBJECTS AND METHODS: Twenty patients showing clinical signs of erosion which had necessitated advice and/or treatment. INTERVENTIONS: Subjects drank from a cup and through a narrow straw, which was then repositioned more posteriorly. A wide bore straw was used in two equivalent positions. Swallowing was viewed laterally and anteroposteriorly to assess involvement of incisors and molars respectively. MAIN OUTCOME MEASURES: Video recordings examined for presence or absence of fluid contact with teeth following each swallow. If contact occurred, the time was measured. RESULTS: Fourteen patients avoided fluid contact with both incisors and molars when using a straw. Compared with the cup, significant differences were found with the narrow straw (P = 0.03, 95% confidence interval of 22.6% to 31.6%), the narrow straw repositioned (P = 0.008, 95% confidence interval of 12.3% to 47.1%) and the wide straw repositioned (P = 0.03, 95% confidence interval of 3.1% to 37.5%). Contact time of fluid with anterior teeth was also significantly reduced. CONCLUSIONS: Drinking through a straw positioned toward the back of the mouth may reduce the erosive potential of soft drinks.

Adolescent↗

PubMed1998

Inhibition of bone resorption by 17beta-estradiol in human bone marrow cultures.

Estrogen deficiency puts individuals at risk of developing osteoporosis because it causes increased bone resorption. However, the mechanism by which this occurs is not known. We have shown, using a recently described two-phase human bone marrow culture system, that estradiol (17beta-E2) added to phase I results in inhibition of bone resorption by reducing the number of osteoclasts (identified as vitronectin receptor and/or calcitonin receptor-positive cells) formed in the cultures. The addition of 17beta-E2 in phase II was without effect, indicating that it does not interfere with the bone resorptive process. 17Beta-E2 down-regulated mRNA expression and protein synthesis of the membrane form of macrophage colony-stimulating factor (M-CSF). 17Beta-E2 did not the alter the expression of the 4.0 kb M-CSF transcript. However, it increased protein synthesis of the proteoglycan form of M-CSF, but not the 85 kDa soluble form in the same cultures. Finally, addition of M-CSF to the cultures reversed the 17beta-E2-induced inhibitory effect. These observations suggest that regulation of the synthesis of membrane-bound M-CSF plays a role in 17beta-E2-induced inhibition of bone resorption.

Actins↗

PubMed1998

Oral or vaginal misoprostol administration for induction of labor: a randomized, double-blind trial.

OBJECTIVE: To compare the efficacy and vaginal birth intervals after intravaginal or oral misoprostol for labor induction. METHODS: One hundred seventy-eight women were randomized to one of two double-blind groups: 1) oral misoprostol 200 microg and one-half tablet placebo intravaginal or 2) oral placebo tablet and one-half tablet of a 100-microg misoprostol intravaginal (dose 50 microg). Doses were repeated every 6 hours until labor was established (maximum of three doses). RESULTS: Ninety-three subjects were assigned to oral misoprostol and 85 to intravaginal administration. Oral administration was accompanied by significantly shorter intervals to the onset of uterine contractility (133+/-78 minutes versus 168+/-93, P < .01) but a higher incidence of abnormal uterine contractile activity (tachysystole 38.7% versus 20.0%, P < .01; hyperstimulation syndrome 44.1% versus 21.2%, P < .01). No adverse maternal or neonatal outcomes were noted, nor were there differences in cesarean delivery rates or total lengths of labor. CONCLUSION: Oral administration of 200 microg misoprostol has similar efficacy to intravaginal administration of 50 microg but is associated with more frequent abnormal uterine contractility.

Administration, Intravaginal↗

PubMed1998

Luminance contrast and spatial-frequency tuning of the transient-vergence system.

Vergence has transient components that are stimulated by brief presentations of stimuli at large disparities (up to several degrees). The question that we have addressed is what stimulus features are encoded by this system. A competition paradigm [Jones & Kerr, (1972)]. Vision Research, 12, 1425-1430) was used in which three gabors were presented. A single Gabor was presented to the fovea of one eye and two gabors, 2.5 deg to either side of the fovea, to the other; one of which, when paired with the single Gabor defined a convergent direction, the other a divergent direction. First we determined if increasing the luminance contrast of the Gabor pair whose disparity was opposite to the observer's response-bias direction (variable-contrast pair) relative to the remaining Gabor (reference) could alter the observer's response direction. Secondly, we determined if the contrast required for such a change in response was affected by the relative spatial frequency of the convergent and divergent Gabors. The reference Gabor was held at 2 cpd and the variable Gabor pair was varied between 5.6 and 0 (a gaussian) cpd. Results demonstrated that increasing the luminance contrast of the variable pair relative to the reference Gabor could alter the observer's response direction, even when the contrast of only one of the variable-pair Gabors was increased. The luminance contrast required for this change to occur was directly related to the spatial frequency of the variable pair over the entire frequency range tested. Vergence responses were preferentially made to lower spatial frequencies, even when a low spatial frequency was pared with a high one. We conclude that transient-vergence responses are not reduced by mixed contrasts (i.e. no contrast-paradox effect) and appear to be mediated by a system that employs a single lowpass sensitive channel.

Contrast Sensitivity↗

PubMed1998

Independent speed-tuned global-motion systems.

Several experiments were conducted to investigate the role of speed in global-motion processing; the extraction of the direction of motion of a small subset of coherently-moving (signal) dots in a stimulus in which the other (noise) dots move in random directions. The specific aim of the experiments was to determine whether multiple speed-tuned global-motion systems exist. The results of these experiments are: (1) when the signal dots were chosen from a group of dots moving at 1.2 degrees s-1, the speed of additional-noise dots had to be below 4.8 degrees s-1 for them to affect global-motion extraction; (2) the addition of static dots did not impair the extraction of a global-motion signal carried by dots moving at 1.2 degrees s-1; (3) noise dots moving at 1.2 degrees s-1 impaired the extraction of a global-motion signal from dots moving at 10.8 degrees s-1, though not to the same extent as dots moving at a higher speed; and (4) these results were dependent upon speed, not spatial-step size or luminance contrast. These results are interpreted as indicating that global-motion extraction occurs within at least two independent speed tuned systems. One of these systems is sensitive to high speeds and the other to low speeds.

Humans↗

PubMed1998

Spatial-frequency and contrast tuning of the transient-stereopsis system.

The tuning of the transient-stereopsis system to luminance contrast and spatial-frequency (SF) was investigated with narrow-band gabor targets with a constant sigma of 1 degree. They were presented for brief (140 ms) durations and subtended a large (6 degrees) disparity. When dichoptic gabor stimuli were matched in SF (0-5 cpd), transient stereo performance was either uniform across SF or greater at frequencies below 1 cpd. When dichoptic stimuli had unmatched SF (0.5 + 0-5 cpd) and matched contrast (100%), stereo performance was impaired below that of the matched SF condition. Stereo performance with matched SF at 0.5 cpd was impaired when contrast of one eye's image was reduced, demonstrating a contrast-paradox effect (i.e. contrast tuning) for transient stereopsis. Performance with three dichoptic unmatched SF conditions (0.5 and 1.0 cpd; 0.5 and 5.0 cpd; 1.5 and 3.5 cpd) was improved when the contrasts of the low SF gabor was reduced while holding the contrast of the high SF gabor constant at 100%. However stereo performance was not improved by reducing the contrast of a high SF gabor (3.5 cpd) while holding the contrast of the lower SF gabor (1.5 cpd) constant at 100%. We interpret these findings as indicating that transient-stereopsis performance is mediated by a single spatial-channel that has low-pass spatial-frequency sensitivity and which compares the ocular based signals prior to binocular combination so that signals that are not balanced in terms of their strength lead to a weaker binocular signal, as per the model proposed by Kontsevich and Tyler (Vis Res 1994; 3417:2317-2329) for sustained stereopsis.

Contrast Sensitivity↗

PubMed1998

Discrimination of global-motion signal strength.

The ability of observers to discriminate differences in global-motion-signal strength (that is the proportion of coherently moving dots in a field of randomly moving dots) was determined for both first and second-order stimuli. Observers could accurately discriminate differences in signal intensity for all reference signal levels tested; 20-100%. A similar pattern of performance was obtained for both types of stimuli. The observed first-order signal-discrimination performance is compatible with the results of electrophysiological studies that have investigated the dependence of the firing rate of V5 cells (also called the middle temporal area) upon global-motion signal intensity.

Differential Threshold↗

PubMed1998

Clinical effects of human macrophage inflammatory protein-1 alpha MIP-1 alpha (LD78) administration to humans: a phase I study in cancer patients and normal healthy volunteers with the genetically engineered variant, BB-10010.

BB-10010 is a genetically engineered variant of human macrophage inflammatory protein-1 alpha (hMIP-1 alpha) with improved pharmaceutical formulation properties. Although initially described as a pro-inflammatory cytokine, it is now recognised that hMIP-1 alpha has additional effects on haemopoietic stem cell cycling and on human immunodeficiency virus uptake by macrophages. In view of the potential clinical utility of the molecule, we have embarked on a clinical trials programme to evaluate the safety, tolerability and haematological effects of BB-10010. We now report the results of two phase I clinical studies in which 49 subjects (9 patients with advanced breast carcinoma and 40 normal healthy volunteers) received escalating doses of BB-10010, from 0.1 to 300 micrograms/kg using the subcutaneous (s.c.) or intravenous route (i.v.) of administration. Treatment was associated with a dose-related increase in monocyte count which peaked at 200% of steady-state levels and was preceded by an acute, short-lived, monocytopenia, 50-100% of baseline. no measurable effects were noted on other leucocyte subsets or on circulating progenitor cell numbers. In all cases, BB-10010 was extremely well tolerated with no significant toxicity observed at any dose level and a maximum tolerated dose was not defined. Pharmacokinetic analysis revealed that serum concentrations of BB-10010 were detectable using doses of > or = 10 micrograms/kg i.v. or > or = 30 micrograms/kg s.c., and that a single s.c. injection resulted in sustained plasma levels over a 24 h period. These preliminary studies have confirmed the safety and tolerability of BB-10010 using a dose range up to 300 micrograms/kg. Further clinical studies are ongoing to determine the biological effects and to investigate the potential myeloprotective properties using a variable dose range and schedule of BB-10010 in combination with cytotoxic chemotherapy.

Adult↗

PubMed1998

Macrophage colony-stimulating factor increases bone resorption by osteoclasts disaggregated from human fetal long bones.

Macrophage colony-stimulating factor (M-CSF) is known to play an important role in human and murine osteoclast formation. Although M-CSF has been shown to inhibit isolated neonatal rat osteoclasts from resorbing bone, its action on the mature human osteoclast has not been described. We now report that M-CSF increases osteoclastic bone resorption in a dose-responsive manner. Bone resorption by mature human fetal osteoclasts, including pit area, depth, and volume, was increased in the presence of M-CSF compared with vehicle. The number of osteoclasts in the cultures was similar after 2 and 18 h in the presence of M-CSF, whereas there was a significant reduction in osteoclast number, whether assessed as the number of tartrate-resistant acid phosphatase (TRAP)-positive or vitronectin receptor-positive cells after 18 h in M-CSF-free cultures. The number of nuclei per osteoclast after 2 or 18 h in M-CSF was also similar and there was no difference in the number of vitronectin receptor-positive mononucleate cells at 2 and 18 h. This suggests that the increased bone resorption is likely to be accounted for by enhanced osteoclast survival in M-CSF compared with controls rather than by formation of new osteoclasts.

Acid Phosphatase↗

PubMed1998

A randomized controlled trial of a "buddy" systems to improve success at giving up smoking in general practice.

AIMS: To assess the effect on abstinence rates of pairing up smokers attending a general practice smokers, clinic to provide mutual support between clinic sessions. DESIGN: Randomized controlled trial comparing a "buddy" condition with a "solo condition" in which smokers received the e same treatment but were not paired up. SETTING: A general practice smokers' clinic in London. PARTICIPANTS: One hundred and seventy-two smokers recruited by mailshot. INTERVENTION. Smokers attended a nurse-led smokers clinic 1 week prior to their quit date, on the quite date, 1 week later and 3 weeks after that. Smokers in the buddy condition were paired with another smoker trying to give up at the same time to provide mutual support between clinic sessions. MEASUREMENT: The main outcome measure was the percentage of smokers still abstinent from cigarettes at end of treatment (weeks from quite date), verified by expired air carbon monoxide concentration. FINDINGS: The percentage of smokers still abstinent at the end of treatment was significantly higher in the buddy condition than the solo condition (27% vs. 12%). CONCLUSIONS: A buddy system can provide an effective element of a smoking cessation intervention at minimal cost. Further research is needed to establish the long-term efficacy of this approach and examine the effectiveness of incorporating social support into other types of smoking cessation programmes.

Adult↗

PubMed1998

Multiple endocrine neoplasia syndrome type IIb: a case report.

Multiple endocrine neoplasia type IIb (MEN IIb) is a syndrome, part of which can involve neoplastic change in the thyroid and adrenal glands. It has unusual oro-facial manifestations including mucosal neuromata on the lips, cheeks and tongue. A child aged 3 years and 10 months presented with mucosal tags at the corners of the mouth, early eruption of permanent teeth, malocclusion and facial asymmetry. Biopsy of the excess mucosal tissue suggested a diagnosis of either MEN type IIb or neurofibromatosis. Genetic testing eventually confirmed MEN type IIb. The patient has been followed up regularly for 9 years. He has developed modular lesions on his tongue and irregular enlargement of his lower lip, but to date there have been no signs of tumour development. This report emphasizes the importance of thorough examination of the oral mucosa and follow-up of any abnormalities.

Biopsy↗