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Biomedical subjects

R Milner

Publications and source records attributed to R Milner.

At least 55 records · Page 3Linked to original sources

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

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

Leukotriene receptor blockade reduces bile acid-induced superficial gastric mucosal injury.

Leukotriene C4 and D4 are putative mediators of the severe gastric mucosal injury caused by a variety of topical irritants. The purpose of this present study was (1) to investigate the effect of pretreatment with topical leukotriene C4 and D4 on the more superficial injury caused by low concentrations of bile acid and (2) to determine the effect of leukotriene receptor blockade, alone and during leukotriene pretreatment, on this injury. Prior to injury with topical 5 mM acidified taurocholate (pH 1.2) rat stomachs were pretreated with either normal saline, leukotriene C4 or D4, SKF-104353 (a leukotriene receptor antagonist), SKF-104353/LTC4, or SKF-104353/LTD4. Injury was assessed by measuring hydrogen ion flux and DNA efflux, a marker of gastric mucosal cell exfoliation. Both LTC4 and LTD4 significantly increased bile acid-induced luminal hydrogen ion loss and DNA efflux. Leukotriene receptor blockade not only blocked this effect, but also significantly decreased the injury from bile acid alone. Thus, both LTC4 and LTD4 exacerbate the superficial gastric mucosal injury caused by physiologic concentrations of bile acids. Leukotriene receptor blockade with SKF-104353 completely blocks these effects and reduces injury from bile acid alone.

Animals

White cell depletion of red cell and pooled random-donor platelet concentrates by filtration and residual lymphocyte subset analysis.

This study comparing the relative white cell (WBC)-depleting efficiency of single and double filtration used two filters and new, sensitive, and reliable methods for performing WBC counts on WBC-depleted blood products. A single filtration of red cell (RBC) concentrates with a cotton-wool filter reduced WBC content by 98.64 percent, but the range of residual WBCs was wide, and many filtered units still contained more than the theoretical immunizing dose of 5 to 10 x 10(6) WBCs. A second filtration, however, always produced RBC units that had less than 5 x 10(6) WBCs. Although the degree of WBC depletion observed after a single filtration of a 6-unit pool of random-donor platelet concentrates was greater with a polyester filter than with the cotton-wool filter (98.92 vs. 98.14% reduction, respectively, when mean prefiltration WBC count was less than 600 x 10(6], in both cases, 25 percent of filtered products still contained greater than 5 x 10(6) WBCs; a second filtration (with the cotton-wool filter), however, produced units that were always below the immunizing dose. All double-filtered platelet concentrates had less than 10(6), and one-half had less than 10(4) residual WBCs. Platelet loss was similar with both filters (+/- 16% loss with one filtration). The effectiveness of the filters in producing products that were WBC-depleted below the immunizing dose was dependent on the prefiltration WBC content (but not on the age of the units), and it may be worthwhile to employ methods to ensure that total prefiltration WBC count of the product is less than 400 x 10(6).(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, CD

Hepatitis B and human immunodeficiency virus infection in street youths in Toronto, Canada.

Hepatitis B and human immunodeficiency virus are transmitted by venereal contact or by the sharing of used needles during drug use. A questionnaire was administered to street youths admitting to prostitution and to a group denying prostitution, as well as to sexually active adolescents who lived with their family and were attending an adolescent medical clinic. The age, gender, race, number of sexual partners, condom use, illicit drug use, anal intercourse and admission to prostitution were recorded for each of the subjects. Serology was obtained for hepatitis B markers and human immunodeficiency virus antibody. Multiple regression analysis was performed to determine the factors which might predict hepatitis B serologic status. A single subject, who admitted to prostitution, was found to be human immunodeficiency virus-seropositive. Seven of 43 (16%) admitted prostitutes compared with 1 of 44 (2%) other street youth and none of 27 controls demonstrated anti-hepatitis B surface antibodies. The higher rate of seropositivity in admitted prostitutes was statistically significant (P less than 0.0097). Two seropositive prostitutes had IgM hepatitis B core antibody suggesting recent infection. Two factors, number of partners (P less than 0.0007) and practice of anal intercourse (P less than 0.05), were identified in the multiple regression analysis as predictive of seropositivity. Thus adolescents who live on the street are at increased risk for becoming infected with hepatitis B virus. The difficulty in ensuring vaccine coverage in this population would support calls for including hepatitis B vaccination as part of childhood immunization.

Adolescent

Failure of supplementation with vitamin E to prevent bronchopulmonary dysplasia in infants less than 1,500 g birth weight.

In a randomized trial to determine whether oral vitamin E reduced stages III and IV bronchopulmonary dysplasia (BPD) by 50%, 268 infants were randomly allocated, after stratification by birth weight and severity of disease, to receive vitamin E 25 units or an indistinguishable placebo. The experimental (E) group and the control (C) group were similar in weight, gestational ages, Apgar scores, severity of illness, and initial oxygen and ventilator exposure. Serum vitamin E levels were significantly different within 48 h of administration and remained well above normal adult levels from the first week of life in the experimental group. There was no difference in the rates of early death, BPD at 28 days, or mortality from BPD. Severity was similar and no difference was seen in the incidence of necrotizing enterocolitis or sepsis. There was no evidence that vitamin E supplementation offered protection against chronic lung disease in infants less than 1,500 g birth weight.

Bronchopulmonary Dysplasia

The demography of primary biliary cirrhosis in Ontario, Canada.

The demographics of primary biliary cirrhosis in Ontario, Canada, are described. Two hundred and twenty-five primary biliary cirrhosis patients were identified by 85 of 502 gastroenterologists (or internists) practicing in Ontario acute care hospitals that have 150 or more beds. Two hundred and six patients were verified as being antimitochondrial antibody-positive, resulting in an incidence of 3.26 per million per year and a prevalence of 22.39 per million. Questionnaire data were obtained on 88.5% of these patients. Twenty-nine percent of the patients were found to be asymptomatic. Geographical clustering and racial predisposition were not seen. No increase in breast cancer prevalence was noted. By the time the diagnosis of primary biliary cirrhosis was established, the patients had consulted a median number of 3.5 physicians. Fatigue was reported as the most disabling symptom. The diagnosis of primary biliary cirrhosis in patients referred from across the province of Ontario was independently confirmed by us, using standard criteria (antimitochondrial antibody testing and liver biopsy), and was found to be reliable.

Autoantibodies

Percutaneous ablation of gallstones.

The purpose of this study was to determine if gallstones could be safely and effectively ablated in the pig using a proprietary percutaneous rotor-tipped catheter, the Kensey-Nash Lithotrite (KNL). All gallstones in a single human gallbladder were defined as a gallstone set. Human gallstone sets not meeting current treatment criteria for extracorporeal shock wave lithotripsy (ESWL) were placed in the gallbladder (GB) of male pigs (N = 8; 80-100 kg). A percutaneous transhepatic guide wire was put into the GB and the abdomen closed. The KNL was then introduced under fluoroscopy using the Seldinger technique and activated. Gallstone ablation was monitored by tactile and auditory feedback to the operator and by fluoroscopy. Once completed the device was withdrawn, the GB irrigated, and the 9F sheath removed. Animals were sacrificed immediately (Group 1, N = 4) and at 28 +/- 5 days (Group 2, N = 4). Gallstones were ablated in 26 +/- 8 min. No pig had significant hemorrhage, GB perforation, or pancreatitis. One acute animal had stone fragments greater than 2 mm in the gallbladder. No other animals had any fragments greater than 1 mm present in the GB, cystic duct, common duct, ampulla, or duodenum. Histologic examination of the GB showed acute hemorrhagic mucosal injury in Group 1 and extensive mucosal regeneration with some stone fragment granulomata and mural fibrosis in Group 2. We conclude that percutaneous gallstone ablation with the KNL is safe and effective in this short-term pig model and appears to be a safe procedure for gallstone ablation. Long-term safety and effectiveness remain to be demonstrated. This device should be useful for treatment of symptomatic gallstones in patients not treatable by ESWL.

Animals

Decreased disability rate among 3-year-old survivors weighing 501 to 1000 grams at birth and born to residents of a geographically defined region from 1981 to 1984 compared with 1977 to 1980.

In this article we report the survival and morbidity rates for all live-born infants weighing 501 to 1000 gram at birth and born to residents of a defined geographic region from 1977 to 1980 (n = 255) compared with 1981 to 1984 (n = 266). During these periods, there were no changes in the proportion of infants delivered at the tertiary care center or community hospitals (171/84 vs 194/72); use of the tertiary care center increased only slightly, from 84% to 91%; and changes in neonatal management were mainly in improvements in diagnostic and monitoring techniques. When infants were grouped according to birth weights in 100 gm increments, survival improved significantly only for infants weighing between 501 and 600 gm at birth (2% vs 20% p less than 0.001). There were no differences in the overall survival rates to hospital discharge (46% vs 48%). The prevalence of neurosensory impairments was 24% in period 1 and 17% in period 2. There was a significant improvement in the proportion of infants considered to have disabilities by a functional classification assigned at 3 years corrected age (50% vs 27%, p less than 0.001), but only for infants weighing more than 800 gm at birth (49% vs 22%, p less than 0.001). Infants delivered at the community hospitals had a higher prevalence of neurosensory impairments compared with infants delivered at the tertiary care center (period 1, 35% vs 21%, not significant; period 2, 37% vs 14%, p less than 0.05). These data are encouraging; further efforts should be directed toward assessing which, if any, components of perinatal care are contributing to the improvement in morbidity rates.

Academic Medical Centers

Evaluation of a new method of detection of nosocomial infection in the pediatric intensive care unit: the Infection Control Sentinel Sheet System.

To improve the efficiency of nosocomial infection detection, a highly structured system combining initial reporting by the bedside night nurse of symptoms possibly related to infection with follow-up by the infection control nurse (ICN) was developed: The Infection Control Sentinel Sheet System (ICSSS). Between July 1, 1987 and February 28, 1988, a prospective comparison of results obtained through ICSSS and daily bedside observation/chart review by a full-time trained intensivist was undertaken in the pediatric intensive care unit (PICU). Ratios of nosocomial infections and nosocomially-infected patients were 15.8 and 7.0 respectively among 685 admissions; included are seven infections identified only through the ICSSS so that the "gold standard" became an amalgamation of the two systems. The sensitivity for detection of nosocomially-infected patients by bedside observation/chart review and ICSSS was 100% and 87% respectively. The sensitivity for detection of standard infections (blood, wound and urine) was 88% and 85% respectively. The sensitivity for detection of nosocomial infections at all sites was 94% and 72% respectively. Missed infections were minor (e.g., drain, skin, eye), required physician diagnosis (e.g., pneumonia), were not requested on the sentinel sheet (SS) (e.g., otitis media), related to follow-up of deceased patients or were minor misclassifications or failures to associate with device (e.g., central-line related). Daily PICU surveillance by the ICN required only 20 minutes a day. The ICSSS appears highly promising and has many unmeasured benefits.

Bias

Epidemiologic study of 4684 hospital-acquired infections in pediatric patients.

During a 4-year period 4684 nosocomial infections occurred in a university pediatric hospital which admitted 78,120 patients (nosocomial infection rate (NIR) = 6.0). NIR varied from 0.17 to 14.0 on different wards or services; the highest rates (greater than or equal to 5.6) were found in the Neonatal Intensive Care Unit, infant neurosurgery, hematology/oncology, neonatal surgery, cardiology/cardiovascular surgery, Pediatric Intensive Care Unit and infant/toddler medicine areas. Infections were most common in patients less than or equal to 23 months (NIR = 11.5), were less common in the 2- to 4-year age group (NIR = 3.6) and occurred least frequently in patients greater than or equal to 5 years (NIR = 2.6). The median day of onset of infections was 15.3 days. The proportional frequencies of infections were: 35% gastrointestinal; 21% bacteremia; 16% respiratory (10% upper, 6% lower); 7% postoperative wound; 6% urinary tract; 5% skin (32% of these skin infections were related to intravascular lines); 5% eye; 3% cerebrospinal fluid; and 2% other. A similar proportional frequency of 379 infections in patients hospitalized for more than 100 days was observed. The etiologic agents were Gram-positive bacteria (50%), viruses (23%), Gram-negative bacteria (18%), fungi (4%) and mixed/other (5%).

Adolescent

An epidemiological study of children's attitudes toward disability.

In this epidemiological study the authors recorded the attitudes of children in Hamilton, Ontario, to physically disabled and mentally handicapped children. Univariate analyses confirmed the importance of female gender, friendship and contact with handicapped persons as determinants of more accepting attitudes. Type of disability and the presence or absence of disabled children in respondents' schools were not found to influence attitudes in a systematic manner. Correlations between attitudes and children's self-esteem or sociometric ratings were not significant, nor were parent-child attitude correlations. Maternal language of origin was found to influence children's attitudes, in favour of children of English-speaking mothers. These results are discussed with reference to their practical applications by community and educational systems seeking to foster integration of disabled children.

Attitude

[Two immunologically differing forms of p53 oncoprotein from B-lymphocytes of mice are coded with identical mRNA].

The detailed analysis of mRNA structure coding for p53 protein from the intact and KonA stimulated lymphocytes from mouse spleen has shown both matrices to be identical. mRNAs have been analyzed by S1 mapping. Both mRNAs directed in vitro the synthesis of p53 protein reacting with monoclonal antibodies PAb421 and PAb248 both of which are specific for one of p53 forms synthesized by lymphocytes in vivo. Thus, the phenomenon of epitopes exclusion on p53 surface from intact or activated B-lymphocytes might be explained by peculiarities of posttranslational step of protein synthesis.

Animals

Human nasal polyp epithelial basophil/mast cell and eosinophil colony-stimulating activity. The effect is T-cell-dependent.

We have previously reported highly potent basophil/mast cell (BMC) and basophil/eosinophil (Eo) colony-stimulating activities (CSA) in conditioned medium derived from cultured human nasal polyp epithelial scrapings (NP-CM). We now have examined the involvement of peripheral blood T-cells in the NP-CM stimulation of colony-forming units (cfu) from the blood of atopic and nonatopic subjects. Because the number of BMC- and Eo-cfu was significantly higher in cultures of peripheral blood from subjects with out-of-season ragweed allergic rhinitis than from control subjects (23.8 +/- 4.1 versus 9.0 +/- 2.4, p less than 0.01), we asked whether the observed colony stimulation could be a T-cell-dependent effect. Indeed, peripheral blood target cells consisting of a reconstituted mixture of T-cells and T-cell-depleted peripheral blood mononuclear cells (non-T-cells) yielded a significantly higher number of colonies in the presence of NP-CM than the non-T-cells alone. NP-CM did not stimulate colony formation by isolated T-cells. These observations point to interactions among nasal epithelial growth and differentiation factors, blood-borne progenitors and T-cells in the local accumulation of basophils, mast cells, and eosinophils in nasal polyps.

Basophils

Laminar flow air cleaner bed attachment: a controlled trial.

Thirteen house dust mite-allergic young asthmatics were entered into a double-blind, crossover clinical trial to compare "in use" with "non-use" of a laminar flow air cleaner bed attachment. The study design encouraged maintenance of symptom control by adjustment of the dose of medications used. There was a significant reduction in the amount of medications required by the patients during the trial period that the air cleaner was in use. Histamine airway responsiveness was significantly decreased for a group of eight of the subjects tested at the end of a 3-month open trial.

Adolescent

Development of the human coagulation system in the healthy premature infant.

This study was designed to determine the postnatal development of the human coagulation system in the healthy premature infant. Consecutive mothers of healthy premature infants born at either St Joseph's Hospital or McMaster University Medical Centre in Hamilton were asked for consent. One hundred thirty-seven premature infants (30 to 36 weeks of gestational age) entered the study. The premature infants did not have any major health problems and did not require ventilation or supplemental oxygen. Demographic information and a 20-mL blood sample were obtained in the postnatal period on days 1, 5, 30, 90, and 180. Between 40 and 96 premature infants were studied on each day for each of the following tests: prothrombin time, activated partial thromboplastin time, thrombin clotting time, plasminogen; 13 factor assays [fibrinogen, II, V, VII, VIII, IX, X, XI, XII, XIII, high-mol-wt kininogen (HMWK), prekallikrein (PK), von Willebrand factor (vWF)] and eight inhibitors [antithrombin III (AT-III), heparin cofactor II, alpha 2-antiplasmin, alpha 2-macroglobulin, alpha 1-antitrypsin, C1 esterase inhibitor, protein C (PC), and protein S (PS)]. A combination of biologic and immunologic assays were used. Between 30 to 36 weeks there was a minimal effect of gestational age for levels of AT-III, PC, and factors II and X only; therefore, the entire data set was used to generate reference ranges for these components of the coagulation system for premature infants. Next, the results for the premature infants were compared with those of a previously published study in 118 fullterm infants and with those for adults. An effect of gestational age was shown for plasminogen, fibrinogen, factors II, V, VIII, IX, XI, XII, HMWK, and all eight inhibitors. In general, the postnatal maturation towards adult levels was accelerated in premature infants as compared with the fullterm infants. By 6 months of age, most components of the coagulation system in premature infants had achieved near adult values.

Age Factors