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Biomedical subjects

R Milner

Publications and source records attributed to R Milner.

At least 19 recordsLinked to original sources
PubMed1995

Differentiation of the O-2A progenitor cell line CG-4 into oligodendrocytes and astrocytes following transplantation into glia-deficient areas of CNS white matter.

The in vitro properties of the CG4 cell line have led to its increasing use as a cell line with which to study the behaviour of the O-2A progenitor cell. In this study we have examined the in vivo behaviour of the CG4 cell line following transplantation into areas of adult rat spinal cord white matter which have been permanently depleted of glial cells by the combination of local X-irradiation and direct injection of 0.1% ethidium bromide. Twenty-one days after transplantation, both myelin-forming oligodendrocytes and glial fibrillary acidic protein-positive astrocytes were identified within the lesion, indicating that the CG4 cell line has bipotential differentiation properties when introduced into a pathological environment consisting of demyelinated axons but devoid of oligodendrocytes or astrocytes. In this respect, the CG4 cell line resembles other glial progenitor cell lines that have been transplanted into similar lesions. In some areas of the lesion, remyelination was observed that was similar in extent to that achieved by growth factor-expanded populations of O-2A progenitor cells. The transplant origin of the cell types within the lesion was confirmed by retroviral incorporation of the lacZ marker gene, the expression of which allowed their identification by histochemistry. In conclusion, the in vivo properties of the CG4 cell line make it a highly suitable line with which to study the behaviour of O-2A progenitors following transplantation into normal and damaged CNS.

Animals↗
PubMed1995

Perichondrial arthroplasty incorporating costal cartilage.

A technique of IP joint arthroplasty is described using costal cartilage with accompanying perichondrium. All patients presented following trauma to the IP joints; their ages ranging from 15 to 45 years. Five out of six cases showed improvement of symptoms and function following reconstruction of the traumatized joint.

Adolescent↗
PubMed1994

Randomised trial of intravenous immunoglobulin G, intravenous anti-D, and oral prednisone in childhood acute immune thrombocytopenic purpura.

The most serious complication of childhood acute immune thrombocytopenic purpura (ITP), intracranial haemorrhage, occurs in about 1% of children with platelet counts below 20 x 10(9)/L. We conducted a randomised study to explore three treatment options in this high-risk group. 146 children (> 6 months and < 18 years old) with typical acute ITP and platelet counts of 20 x 10(9)/L or lower were randomised to receive high-dose intravenous immunoglobulin G (IVIgG) 1 g/kg on 2 consecutive days (n = 34), 0.8 g/kg once (n = 35), intravenous anti-D 25 micrograms/kg on 2 consecutive days (n = 38), or oral prednisone 4 mg/kg per day with tapering and discontinuation of prednisone by day 21 (n = 39). The rate of response as reflected by the number of days with platelet counts at 20 x 10(9)/L or lower and the time taken to achieve a platelet count 50 x 10(9)/L or more was significantly faster for both IVIgG groups than for the anti-D group (p < 0.05); the difference between prednisone and IVIgG was significant (p < 0.05) only for the IVIgG 0.8 g/kg group, and responses to the two IgG groups were similar. These differences in response rates were reflected in the percentages of children with platelet counts of 20 x 10(9)/L or lower at 72 hours following the start of treatment: 3% (IVIgG 0.8 g/kg x 1), 6% (IVIgG 1 g/kg x 2), 18% (anti-D), and 21% (oral prednisone 4 mg/kg/day). Treatment-associated toxicities included a fall in haemoglobin with anti-D (to less than 100 g/L in 24% of cases); weight gain with oral prednisone; and fever, nausea, vomiting, and headache with IVIgG. On the basis of these results, intravenous anti-D cannot be recommended as initial therapy for children with acute ITP and platelet counts of 20 x 10(9)/L or lower. A single dose of 0.8 g/kg IVIgG offers the fastest recovery for the least treatment; additional IgG or oral prednisone can be reserved for the one-third of children who continue to have platelet counts of 20 x 10(9)/L or less at 48-72 hours after the start of treatment.

Adolescent↗
PubMed1994

Capsaicin-induced gastric hyperemia and protection are NO- dependent.

Topical treatment of gastric mucosa with capsaicin (cap) increases gastric mucosal blood flow (GMBF) and protects the mucosa from injury by acidified bile salts. The purpose of this study was to test the hypothesis that this hyperemia related "cytoprotection" is mediated by nitric oxide. Male Sprague-Dawley rats were anesthetized and the glandular stomach (blood supply intact) was chambered between two plastic rings. Animals were divided into four groups. All groups received a 5-min topical saline exposure. Groups 1 and 2 received iv saline or nitro-L-arginine methyl ester (L-NAME, 25 mg/kg iv), a specific nitric oxide inhibitor, 5 min prior to baseline treatment, followed by a 15-min preinjury period of saline and a 15-min injury period of 10 mM acidified taurocholate (ATC, pH 1.2). Groups 3 and 4 were treated as above except topical cap (160 microM) was used during the preinjury period. GMBF was measured with a laser Doppler flowmeter (ml/min/100 g tissue). Injury was assessed grossly (grade 0-3), histologically (grade 0-3), and by measuring DNA content of a 5-min N-acetylcysteine wash (DNAE). Baseline GMBF of 30 +/- 1.5 significantly decreased to 15 +/- 1.2 in group 1 versus group 2 (P < 0.05). When topical ATC was used GMBF increased to 59 +/- 4.9 and 25 +/- 2.8, respectively. Injury by grade and DNAE was not significantly different between these groups. GMBF during cap exposure was 42 +/- 4 and 22 +/- 2 in groups 3 and 4, respectively. Graded histologic and gross injuries were significantly worse in group 4 compared to group 3 (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Blood-borne virus infections among Australian injecting drug users: implications for spread of HIV.

To describe the epidemiology of infection with hepatitis C virus (HCV), hepatitis B virus (HBV) and human immunodeficiency virus (HIV) among injecting drug users (IDUs) in Australia, in relation to the potential for further spread of HIV in IDUs, a cross-sectional analysis was performed on data from a sample of injecting drug users, correlating markers of exposure to blood-borne viruses with sex, age, sexual orientation, primary current drug injected and duration of injecting in rural and metropolitan Victoria, Australia. The subjects were currently active IDUs from a wide spectrum of age, sex, sexual orientation, geographical location and social background, contacted and recruited through their social networks and from community agencies and prisons by trained peer workers who interviewed and collected blood from them in the field. Sera were tested for antibody to HIV, HCV and hepatitis B core antigen (HBcAg), for hepatitis B surface antigen (HBsAg), and for HCV RNA using reverse transcription and polymerase chain reaction (RT-PCR). At entry to the study, 4.5% (14/311) had antibody to HIV, 47% (146/308) to HBcAg and 68% (206/303) to HCV. Prevalence of HBsAg was 1.8% overall (5/282), and 50% (84/168) were positive for HCV RNA. By multivariate analysis, HIV seropositivity was strongly associated with a history of homosexual contact in males and with exposure to HBV but not to HCV. Those who reported their current primary injected drug to be amphetamines were at greater and continuing risk of HIV infection than were current heroin injectors, while the reverse applied for HCV.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

A developmental analysis of oligodendroglial integrins in primary cells: changes in alpha v-associated beta subunits during differentiation.

We have examined the expression of integrins on primary oligodendroglial cells during the differentiation of the proliferative oligodendrocyte precursor (O-2A progenitor) cell to the postmitotic oligodendrocyte. Cells of the oligodendrocyte lineage expressed a limited repertoire of integrins: alpha 6 beta 1 and alpha v integrins including alpha v beta 1, alpha v beta 3 and alpha v beta 5, as well as a potentially novel integrin alpha v beta 80 kDa. Integrin expression was developmentally regulated; during differentiation alpha v beta 1 was reduced and alpha v beta 5 upregulated. These results suggest that laminin and vitronectin are important extracellular matrix ligands for oligodendrocytes, and provide a rational explanation for previous observations that RGD peptides inhibit the expression of myelin-specific genes. They also suggest a simple model by which switching of integrin beta subunits might regulate differentiation. As chimeric beta 1 integrins with a beta 5 cytoplasmic domain support proliferation less well than normal beta 1 integrins (Pasqualini and Hemler (1994), J. Cell Biol. 125, 447-460) the switch from alpha v beta 1 to alpha v beta 5 might play a key instructive role in the cessation of proliferation and subsequent differentiation.

Animals↗
PubMed1993

Hepatitis C virus infection among a cohort of Victorian injecting drug users.

OBJECTIVE: To describe the epidemiology of infection with hepatitis C virus (HCV) among injecting drug users (IDUs) in Victoria. DESIGN AND SUBJECTS: Subjects were current IDUs from a wide spectrum of age, sex and social background, enrolled in a prospective study of injecting drug use. They were contacted by peer workers through their social networks and through community agencies and prisons, and were regularly followed for interview and blood collection in the field. Sera were tested for presence of antibody to HCV (anti-HCV), for the presence of HCV RNA directly in serum, and for measures of liver function. The results were correlated with demographic variables. SETTING: Rural and metropolitan Victoria. MAIN OUTCOME MEASURES: Presence of anti-HCV and demonstration of HCV RNA. RESULTS: Two-thirds (68%, 206/303) of the current cohort of IDUs were seropositive for HCV, risk being particularly associated with duration of injecting, and independently for men with opiate use and prison history, and for women with a history of methadone therapy. HCV RNA was detected in 48% (76/160) by polymerase chain reaction (PCR); 61% (74/122) of these subjects were HCV seropositive and 5% (2/38) seronegative. Of 32 HCV seronegative subjects followed for a mean period of 291 days, five seroconverted to HCV, an incidence of 20 infections per 100 person-years. Those who seroconverted were older, more likely to be male, had been injecting longer, more often reported opiate use, and were more likely to be based in the country. Serum liver enzyme levels were higher and more likely to be abnormal in HCV seropositive than seronegative subjects, and were highest in those seropositive subjects in whom HCV RNA was detected. CONCLUSIONS: This population of IDUs has a very high rate of exposure to HCV, related to duration of injecting and independently to opiate use and prison history, perhaps reflecting increased risk in particular social networks. There is evidence of high rates of carriage of HCV, of continuing transmission of HCV, and of ongoing liver disease among these IDUs. If these IDUs are at all representative of all IDUs in Australia, we estimate that 80,000 current and former IDUs may be at risk of chronic liver disease from HCV, and that 8000-10,000 new infections may be occurring each year. Two subjects who were seronegative had HCV RNA detectable in sera. These data have important implications for screening programs and document the need for further measures to prevent spread of blood-borne viruses including HIV among IDUs.

Adult↗
PubMed1993

Influence of Ca2+ channel agonists and antagonists on the post-rest staircase.

It is now generally accepted that the post-rest staircase consists of two phases, an initial fast phase occurring over the first five to six beats followed by a slow phase which occurs over a period of minutes. In this study, the influence of Ca2+ channel antagonists (Cd2+ and nifedipine) and agonists (Bay K 8644 and noradrenaline) on developed tension is investigated to assess the role played by the L-type Ca2+ current (iCa) during post-rest recovery. The results show that, at a range of stimulus frequencies, exposure of guinea-pig papillary muscles to either Cd2+ or nifedipine greatly reduces the fast phase of the staircase and reduces the slow phase of the staircase compared to control (both effects being more prominent at higher stimulus frequencies). Exposure of guinea-pig papillary muscles to Bay K 8644 or noradrenaline potentiated both the fast and slow phases of the staircase with greater proportionate effects observed at higher stimulus frequencies. These results suggest that iCa plays an important role in both phases of the staircase. The first post-rest beat (the rested state contraction) proved very resistant to Ca2+ channel blockade suggesting that iCa plays little role in this contraction which may be the result of entry of Ca2+ into the cell via a relatively Cd2+ insensitive pathway, for example the Na(+)-Ca2+ exchanger.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1992

Induction of labor as compared with serial antenatal monitoring in post-term pregnancy. A randomized controlled trial. The Canadian Multicenter Post-term Pregnancy Trial Group.

BACKGROUND: The rates of perinatal mortality and neonatal morbidity are higher for post-term pregnancies than for term pregnancies. It is not known, however, whether the induction of labor results in better outcomes than does serial fetal monitoring while awaiting spontaneous labor. METHODS: We studied 3407 women with uncomplicated pregnancies of 41 or more weeks' duration. The women were randomly assigned to undergo induction of labor or to have serial antenatal monitoring and spontaneous labor unless there was evidence of fetal or maternal compromise, in which case labor was induced or cesarean section was performed. In the induction group, labor was induced by the intracervical application of prostaglandin E2. Serial antenatal monitoring consisted of counts of fetal kicks, nonstress tests, and assessments of amniotic-fluid volume. The outcomes we measured were the rates of perinatal mortality, neonatal morbidity, and delivery by cesarean section. RESULTS: Among the 1701 women in the induction group, 360 (21.2 percent) underwent cesarean section, as compared with 418 (24.5 percent) of the 1706 women in the monitoring group (P = 0.03). This difference resulted from a lower rate of cesarean section performed because of fetal distress among the women in the induction group (5.7 percent vs. 8.3 percent, P = 0.003). When two infants with lethal congenital anomalies were excluded, there were no perinatal deaths in the induction group and two stillbirths in the monitoring group (P not significant). The frequency of neonatal morbidity was similar in the two groups. CONCLUSIONS: In post-term pregnancy, the induction of labor results in a lower rate of cesarean section than serial antenatal monitoring; the rates of perinatal mortality and neonatal morbidity are similar with the two approaches to management.

Adult↗
PubMed1992

Snowmobile-related deaths in Ontario: a 5-year review.

OBJECTIVES: To investigate the demographic characteristics and circumstances surrounding fatal snowmobile accidents in Ontario, to examine the risk factors and to observe any fatality trends over the study period. DESIGN: Case series. PATIENTS: All 131 people who died accidentally while operating a snowmobile in Ontario from 1985-86 to 1989-90. Records were obtained from the chief coroner's office; registration data were obtained from the Ministry of Transportation. RESULTS: Although the absolute number of deaths increased each year, owing to a rapid increase in the number of registered snowmobiles, the risk of death from snowmobile accidents remained relatively constant. Deaths occurred most frequently in northeastern Ontario. Youths and men predominated among the victims. Fatal accidents occurred more often on lakes (in 66% of the cases in which this information was known) than on roads (in 26%) or trails (in 8%). Weekend fatalities predominated, and deaths occurred most often during times of suboptimal lighting (from 4 pm to 8 am). The driver was killed in 84% of the cases in which the person's role was known. Alcohol use before death was implicated in 69% of the cases, the level exceeding the Ontario legal limit in 59%. CONCLUSION: Snowmobile-related deaths result from factors that are generally avoidable. Strategies need to be instituted to reduce the rate of these events.

Accidents↗
PubMed1992

Effect of capsaicin on gastric mucosal injury and blood flow following bile acid exposure.

Topical bile acid at low pH stimulates gastric mucosal blood flow (GMBF), thereby limiting injury to surface epithelial cells (SEC). Capsaicin-sensitive afferent neurons (ASN) are possible mediators of the GMBF response and, therefore, of mucosal protection. In order to investigate the effect of topical capsaicin (ASN stimulant) and topical lidocaine (ASN inhibitor) on SEC exfoliation and GMBF, vascularized wedges of canine gastric corpus were mounted in lucite chambers. Mucosae were pretreated for 15 min with saline (NSS), 160 microM capsaicin (CAP), 4% lidocaine (LIDO), or CAP and LIDO, followed by a 30-min exposure to acid test solution (ATS; pH 1.2). The same mucosae were then pretreated in an identical fashion followed by a second 30-min exposure to 5 mM taurocholate (5 TC; pH 1.2). Parameters evaluated during both ATS and 5 TC periods were the luminal accumulation of DNA (DNAE, a sensitive marker of SEC exfoliation) and GMBF measured using radiolabeled microspheres. It was found that, relative to NSS pretreatment, CAP pretreatment increased GMBF and decreased DNAE during exposure to both ATS and 5 TC. LIDO blocked the CAP effect on GMBF but not on DNAE. Thus, ASN stimulation by CAP enhances GMBF and is protective. ANS inhibition blocks CAP's GMBF increase but not its protective capabilities. Therefore, augmentation of GMBF is not the only mechanism by which ASNs blunt SEC exfoliation.

Animals↗
PubMed1992

Bone ultrasonic attenuation in women: reproducibility, normal variation and comparison with photon absorptiometry.

The reproducibility of two methods of measuring broadband ultrasonic attenuation (BUA) in the calcaneus have been studied. An improvement in reproducibility in vivo from 9.6% to 2.8% between old and new techniques has been observed. Measurements of the calcaneus using BUA were correlated with measurements of bone mineral density measured by dual energy x-ray absorptiometry in the lumbar spine, femur and total body and bone mineral content in the distal and proximal forearm measured by single photon absorptiometry. For the older BUA technique the correlation coefficients ranged between r = 0.27 and r = 0.34. For the newer BUA technique the correlation coefficients ranged between r = 0.49 and r = 0.62 and were all significant (P less than 0.001).

Absorptiometry, Photon↗
PubMed1992

Bronchodilators for treatment of mild bronchiolitis: a factorial randomised trial.

A randomised double blind trial was conducted to determine the efficacy of inhaled bronchodilators, salbutamol and ipratropium bromide, compared with placebo in the treatment of bronchiolitis. Patients, who were 2 months to 2 years of age and without underlying cardiac or pulmonary disease, received drug 1 (salbutamol or saline placebo) followed one hour later by drug 2 (ipratropium bromide or placebo). Both agents were administered every four hours. The patients were allocated to one of four groups according to a factorial design. The four groups were similar in demographic characteristics, initial oxygenation, and clinical score. The change in oxygen saturation of recipients of both agents was significantly better than that of recipients of salbutamol alone or ipratropium bromide alone. This change, however, was not statistically different from that of the control group. No difference was observed in the clinical score or hospital duration. Inhaled bronchodilators did not improve the condition of hospitalised mild bronchiolitis.

Albuterol↗
PubMed1992

The physician and Down syndrome: are attitudes changing?

A survey of attitudes of pediatricians, child neurologists, and pediatric surgeons toward Down syndrome is compared with a similar study reported in 1975. A contemporary physician would be much more aggressive in treating a child with Down syndrome who has associated anomalies such as duodenal atresia or congenital heart disease. Few would recommend institutionalization of a person with Down syndrome; the majority expect that such individuals could productively spend their adult lives in group homes. Positive changes in physicians' attitudes during the past 15 years have been influenced by parent advocacy groups, court decisions, and studies showing that the ultimate intellectual and social skills of Down syndrome children are greater than was previously believed. The most prominent variable associated with attitudes was the physician's age: the older the physician, the more likely he or she would be nonsupportive of active treatment on behalf of the Down syndrome individual. These findings suggest that ongoing education of medical students and pediatric residents in the field of developmental disabilities and bioethics is required in order to promote well-informed advocacy for the mentally handicapped.

Adult↗
PubMed1991

Effects of high fat diets on hibernation and adipose tissue in Turkish hamsters.

The effects of dietary fat saturation and fat content on hibernation and several properties of white and brown adipose tissue (WAT and BAT, respectively) were investigated in Turkish hamsters (Mesocricetus brandti). Male hamsters were housed in a long photoperiod (LD 16:8) at 23 degrees C and fed one of three diets: (1) chow (6.5% fat per weight), (2) chow + 13.5% vegetable oil (OIL, 20% fat per weight [largely unsaturated fat]) and (3) chow + 13.5% vegetable shortening [(SHORTENING, 20% fat per weight (largely saturated fat)]. Five weeks later body weights had stabilized and the animals were transferred to a short photoperiod (LD 8:16) at 3 degrees C. At the peak of the hibernation season (17 weeks) the animals were sacrificed within 24 h of arousal. Chow-fed hamsters had the greatest percentage of animals hibernating and days found torpid compared with the two fat-fed groups, with no differences found between the latter two groups for these measures. There were no differences between hibernating (HIB) and non-hibernating (NON-HIB) hamsters across or within the diet groups for any of the BAT measures [uncoupling protein content, mitochondrial mass, lipoprotein lipase (LPL) activity, and in vivo lipogenesis], nor were there significant effects of the diet on these measures. CHOW- and OIL-fed HIB hamsters showed decreases in body weight. All HIB groups had decreases in each carcass component, several fat pad weights, testes weight, and food intake. No consistent differences in WAT LPL activity or in vivo lipogenesis were found between HIB and NON-HIB hamsters.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗