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Biomedical subjects

M Donaldson

Publications and source records attributed to M Donaldson.

At least 19 recordsLinked to original sources
PubMed2001

Treatment with nephrectomy only for small, stage I/favorable histology Wilms' tumor: a report from the National Wilms' Tumor Study Group.

PURPOSE: Children younger than 24 months with small (< 550 g), favorable histology (FH) Wilms tumors (WTs) were shown in a pilot study to have an excellent prognosis when treated with nephrectomy only. PATIENTS AND METHODS: A study of nephrectomy only for the treatment of selected children with FH WT was undertaken. Stringent stopping rules were designed to insure closure of the study if the true 2-year relapse-free survival rate was 90% or lower. RESULTS: Seventy-five previously untreated children younger than 24 months with stage I/FH WTs for which the surgical specimen weighed less than 550 g were treated with nephrectomy only. Three patients developed metachronous, contralateral WT 1.1, 1.4, and 2.3 years after nephrectomy, and eight patients relapsed 0.3 to 1.05 years after diagnosis (median, 0.4 years; mean, 0.51 years). The sites of relapse were lung (n = 5) and operative bed (n = 3). The 2-year disease-free (relapse and metachronous contralateral WT) survival rate was 86.5%. The 2-year survival rate is 100% with a median follow-up of 2.84 years. The 2-year disease-free survival rate (excluding metachronous contralateral WT) was 89.2%, and the 2-year cumulative risk of metachronous contralateral WT was 3.1%. CONCLUSION: Children younger than 24 months treated with nephrectomy only for a stage I/FH WT that weighed less than 550 g had a risk of relapse, including the development of metachronous contralateral WT, of 13.5% 2 years after diagnosis. All patients who experienced relapse on this trial are alive at this time. This approach will be re-evaluated in a clinical trial using a less conservative stopping rule.

Disease-Free Survival↗
PubMed2001

Effectiveness of the school dental screening programme in stimulating dental attendance for children in need of treatment in Northern Ireland.

UNLABELLED: The school dental screening programme has been in existence from the beginning of the 20th century yet its value in encouraging attendance among children with a dental health need is not fully established. OBJECTIVE: To evaluate the effectiveness of school dental screening in promoting dental attendance among children with a treatment need and to examine the relative importance of screening, social class and other factors in dental attendance. METHODS: Sixty-four participating schools were assigned to study and control groups using a stratified, blocked randomisation technique. The study group children received the standard school dental screening and the dental attendance of those with a positive screening result was assessed after 2 months by means of a questionnaire issued to the children's parents. The control group children were not, at this stage, screened, yet their parents received the same questionnaire assessing dental attendance over the 2-month period. However, only questionnaires from control group children who had a positive result at a subsequent screening were retained for analysis. RESULTS: A total of 2,321 children were screened, with 980 having a positive result. The mean dmft of those screening positive was 4.85. In all, 664 completed questionnaires were returned, giving a response rate of 67.8%. Dental attendance was reported among 45.5% of the study group (n=352) in the 2 months following screening. In the same period, 27.6% of the control group (n=312) claimed attendance. The effect was found to be significant among the high employed group (P<0.01) and the unemployed group (P<0.05). CONCLUSION: School dental screening was capable of stimulating dental attendance. The strong effect among the lowest socio-economic group shows that school dental screening may be used to decrease dental health inequalities.

Chi-Square Distribution↗
PubMed2001

Factors affecting the time of onset of resorption in avulsed and replanted incisor teeth in children.

Resorption is the main reason for loss of replanted teeth. The outcome examined in this study is the timing of the onset of resorption. The effect of dichotomised dry and wet time intervals as well as the presence of additional crown damage and of contamination were determined. Of 84 replanted teeth, 67.5% developed resorptions. Twenty-eight had detectable additional crown damage with a more rapid onset being seen in these cases (P=0.009). The critical limit for dry time was 15 min (P=0.038) and significant differences persisted for greater limits also. Serial analysis of the association between the time of onset of root resorption and dichotomised wet time variables failed to yield any significant associations. There was visible contamination detected in 32 teeth and these exhibited a more rapid onset of resorption than the other cases (P=0.030). Teeth with inflammatory root resorption (12.8%) had a more rapid onset of resorption than those that developed replacement resorption (54.7%) (P<0.001). It is concluded that the risk of early resorption is increased in teeth that have additional damage or have contamination, or are kept in dry conditions for longer than 15 min.

Adolescent↗
PubMed2001

Early spread of scrapie from the gastrointestinal tract to the central nervous system involves autonomic fibers of the splanchnic and vagus nerves.

Although the ultimate target of infection is the central nervous system (CNS), there is evidence that the enteric nervous system (ENS) and the peripheral nervous system (PNS) are involved in the pathogenesis of orally communicated transmissible spongiform encephalopathies. In several peripherally challenged rodent models of scrapie, spread of infectious agent to the brain and spinal cord shows a pattern consistent with propagation along nerves supplying the viscera. We used immunocytochemistry (ICC) and paraffin-embedded tissue (PET) blotting to identify the location and temporal sequence of pathological accumulation of a host protein, PrP, in the CNS, PNS, and ENS of hamsters orally infected with the 263K scrapie strain. Enteric ganglia and components of splanchnic and vagus nerve circuitry were examined along with the brain and spinal cord. Bioassays were carried out with selected PNS constituents. Deposition of pathological PrP detected by ICC was consistent with immunostaining of a partially protease-resistant form of PrP (PrP(Sc)) in PET blots. PrP(Sc) could be observed from approximately one-third of the way through the incubation period in enteric ganglia and autonomic ganglia of splanchnic or vagus circuitry prior to sensory ganglia. PrP(Sc) accumulated, in a defined temporal sequence, in sites that accurately reflected known autonomic and sensory relays. Scrapie agent infectivity was present in the PNS at low or moderate levels. The data suggest that, in this scrapie model, the infectious agent primarily uses synaptically linked autonomic ganglia and efferent fibers of the vagus and splanchnic nerves to invade initial target sites in the brain and spinal cord.

Animals↗
PubMed2001

[Treatment with enoxaparin adapted to the fertility programs in women with recurrent abortion and thrombophilia].

Acquired and inherited thrombophilia are associated with recurrent pregnancy loss (RPL). Antithrombotic therapy could restore hemostatic balance and improve early placentation and gestational outcome. We evaluated the efficacy of enoxaparin adapted to the fertility program for prevention of pregnancy loss in 35 women (W) with early RPL and thrombophilia. Previous to the diagnosis of thrombophilia, they had had a total of 105 gestations of which 89 (85%) ended in early pregnancy loss. After diagnosis of thrombophilia, 35 subsequent pregnancies were treated with enoxaparin. In 5 cases assisted reproductive techniques were necessary to achieve pregnancy due to couple infertility. In 17 W who had had at least one preclinical pregnancy loss, enoxaparin (20 mg/d/s.c.) was started previous to conception and adapted to the fertility program. All the women continued with the gestational regime. Eighteen W with only clinical pregnancy loss started enoxaparin (20 mg twice per day s.c.) after biochemical pregnancy diagnosis. During gestations heparin dose was adjusted with anti Xa test, maintaining a range between 0.3 at 0.6 u/ml. With antithrombotic therapy, 30/35 (85%) of the pregnancies ended in live birth versus 16/105 (15%) of the pregnancies without treatment (p < 0.001). These results suggest that enoxaparin adapted to the fertility program can be effective in the prevention of preclinical and clinical abortion in women with thrombophilia.

Abortion, Habitual↗
PubMed2000

Improving clinical indicators in acute admissions to the Department of Geriatric Medicine, Royal Perth Hospital.

Clinical indicators are an important component of quality assessment of clinical services. We outline the strategies used in the department of Geriatric Medicine at Royal Perth Hospital (RPH) to report on and improve the results. The clinical indicator for assessment of cognitive function had improved from 19% in September 1998 to 64% in February 1999. The clinical indicator for assessment of physical function has been maintained at 80%. There have been revisions to the definitions of the clinical indicators for 1999. The current clinical indicators used in this department can be modified for comparison nationwide amongst geriatric units.

Acute Disease↗
PubMed2000

Dynamic assays of inhibin B and oestradiol following buserelin acetate administration as predictors of ovarian response in IVF.

The study was designed to examine whether dynamic measurements of inhibin B and oestradiol following single administration of buserelin acetate were correlated with the ovarian response to stimulation in IVF. A total of 37 patients undergoing IVF treatment was studied when the long protocol was started in the early follicular phase. Blood samples were taken twice: on day 2 of the menstrual cycle, before the first s.c. administration of buserelin acetate 0.5 mg and on day 3, 24 h later. Inhibin B and oestradiol concentrations were compared with the ovarian response to stimulation. The ovarian response was defined in two ways: 'number of oocytes/total recombinant (r) follicle stimulating hormone (FSH) dose'; and 'square-root (number of follicles/total rFSH dose)'. The following measurements were highly correlated with the ovarian response to stimulation: increase in oestradiol (day 3-day 2 oestradiol concentration) [correlation coefficient (r) = 0.68, P: < 0.0001] and sum of inhibin B (day 2 + day 3 inhibin B concentrations) (r = 0.6, P: < 0.0001). Age and basal concentrations of FSH and inhibin B were inferior to the above measurements in terms of correlation with the ovarian response. In conclusion, dynamic measurements of inhibin B and oestradiol following single administration of buserelin acetate were highly correlated with the ovarian response to stimulation for IVF treatment.

Adult↗
PubMed1999

Glycosylation of a recombinant protein in the Tn5B1-4 insect cell line: influence of ammonia, time of harvest, temperature, and dissolved oxygen.

Glycosylation is both cell line and protein dependent. Culture conditions can also influence the profile of glycoforms produced. To examine this possibility in the insect cell/baculovirus system, structures of N-linked oligosaccharides attached to SEAP (human secreted alkaline phosphatase), expressed under various culture conditions in BTI Tn5B1-4 cells, were characterized using FACE (fluorescence-assisted carbohydrate electrophoresis). Parameters varied were time of harvest, ammonia added during infection, dissolved oxygen, and temperature. It was found that glycosylation in the insect cell/baculovirus expression system is a robust, stable system that is less perturbed by variations in culture conditions than the level of protein expression. Addition of ammonia and low oxygen conditions affected SEAP expression, but not the oligosaccharide profile of SEAP. Time of SEAP harvest increased the amount of alpha-mannosidase resistant structures from 4.1% at 34 hours postinfection (h pi), to 5.0% at 100 h pi, and to 7.5% at 120 h pi. These structures were primarily sensitive to N-acetylhexosaminidase digest, although a small amount was insensitive to both mannosidase and N-acetyl-hexosaminidase digests. Lowering the temperature from 28 degrees C to 24 degrees C or even 20 degrees C, resulted in a twofold increase in oligosaccharides containing terminal alpha(1,3)-mannose residues. This condition did not affect the amount of mannosidase-resistant structures. However, this could result in more complete glycosylation of recombinant proteins in the BTI Tn5B1-4 cell line, because more structures with the potential for further processing would be produced.

Alkaline Phosphatase↗
PubMed1998

Reduced energy expenditure in preobese children treated for acute lymphoblastic leukemia.

Children with acute lymphoblastic leukaemia (ALL) typically gain weight at excessive rates during and after therapy, and a high proportion of young adult survivors are obese. Previous studies have failed to identify the abnormalities in energy balance that predispose these children to obesity. The aim of this study was to determine the cause of excess weight gain in children treated for ALL by testing the hypothesis that energy expenditure is reduced in these patients. Twenty children [9 boys, 11 girls; mean age 10.9 (3.2) y] treated for ALL who had shown excess weight gain, but were not obese [mean body mass index SD score 0.70 (1.04)], were closely and individually matched with 20 healthy control children [9 boys, 11 girls; mean age 10.7 (3.0) y; mean body mass index SD score 0.27 (0.91)]. In each child we measured total energy expenditure by doubly-labeled water method, resting energy expenditure, energy expended on habitual physical activity, and energy intake. Total energy expenditure was significantly higher in control subjects than in patients: mean paired difference 1185 kJ/d (282 kcal/d), 95% confidence interval (CI) 218-2152. This difference was largely due to reduced energy expended on habitual physical activity in the patients. Resting energy expenditure was lower in the patients: mean paired difference 321 kJ/d (76 kcal/d), 95% CI 100-541. Energy intake was also lower in the patients: mean paired difference 1001 kJ/d (238 kcal/d), 95% CI 93-1909. Children treated for ALL are predisposed to excess weight gain, and subsequently obesity, by reduced total energy expenditure secondary to reduced habitual physical activity. Prevention of obesity in ALL should focus on modest increases in habitual physical activity, modest restriction of dietary intake, and monitoring of excess weight gain.

Adult↗
PubMed1997

Body mass index as a correlate of postoperative complications and resource utilization.

PURPOSE: To describe the relationship of body mass index (BMI) with postoperative complications and resource utilization. PATIENTS AND METHODS: Two thousand nine hundred and sixty-four patients 50 years or older undergoing elective noncardiac surgery with an expected length of stay > or = 2 days were enrolled in a prospective cohort study to measure major cardiac complications, noncardiac complications, length of stay, and costs. The setting was an urban teaching hospital. A preoperative history, physical, electrocardiogram (ECG), and chart review were performed by study personnel. Postoperative complications were detected by ECGs, creatine kinase and creatine kinase MB levels, and daily chart review. Total costs were obtained from the hospital's computerized database. RESULTS: Complication rates were not different among BMI groups (underweight < 20, normal 20 to 29, overweight 30 to 34, most overweight > 34), but patients with BMI 30 to 34 and > 34 who underwent abdominal or gynecologic procedures had significantly higher wound infection rates (11% each) than normal weight patients (4.7%) or the underweight (0%). After adjusting for age, race, gender, smoking history, comorbid diseases, procedure type, and insurance status, there were nonsignificant trends toward increased resource utilization by the most overweight patients (BMI > 34). These patients stayed 0.8 days longer (P = 0.13) and had total costs that were $843 higher (P = 0.17) than patients of normal weight (BMI 20 to 29). The underweight patients stayed 0.9 days longer (P = 0.23) and had total costs that were $3,150 higher (P = 0.04) than patients of normal weight. Quadratic models to test for a U-shaped relationship found no correlation between BMI and length of stay, but did find that BMI was significantly correlated with total costs (P = 0.04). This relationship persisted when patients who had complications were excluded from the analysis. CONCLUSIONS: Overall, BMI was not significantly correlated with postoperative complications or length of stay. However, overweight patients who underwent abdominal or gynecologic procedures had higher wound infection rates, and patients with the highest and lowest BMIs had significantly higher adjusted total costs.

Age Distribution↗
PubMed1997

Effects of inotropes on human leucocyte numbers, neutrophil function and lymphocyte subtypes.

We have investigated the effects of inotropes with different adrenergic receptor specificity on differential white cell count, lymphocyte subtypes and neutrophil function in healthy volunteers. Six healthy, male volunteers were enrolled into this randomized, placebo-controlled pilot study. Each volunteer was studied on four separate occasions during a 2-h infusion of various agents, and for 2 h after stopping the infusion. The agents investigated were adrenaline 0.1 microgram kg-1 min-1, dobutamine 5 micrograms kg-1 min-1, dopexamine 2 micrograms kg-1 min-1 and 5% glucose 0.5 ml kg-1 h-1. Venous blood was sampled at 0, 30, 120 and 240 min. Haemodynamic monitoring was continued throughout the study. Full blood count, white cell differential count and enumeration of lymphocyte subtypes were performed. Neutrophil function tests included chemoluminescence, and assessment of neutrophil chemotaxis, phagocytosis and adhesion. The Wilcoxon signed rank test was used to compare differences between placebo and active drugs at each time compared with baseline. There was a significant increase in white cell count, lymphocyte count and neutrophil count with adrenaline, and a small but significant decrease in these variables with dobutamine and dopexamine. These changes were also apparent for absolute CD3+, CD4+ and CD8+ lymphocyte counts. Neutrophil respiratory burst in response to f-methionyl-leucyl-phenylalanine increased significantly only with adrenaline at 30 min (P = 0.046). There were no other significant changes in tests of neutrophil function. Infusion of inotropes was associated with changes in white cell numbers, lymphocyte subtypes and neutrophil respiratory burst. In healthy volunteers, adrenaline had effects different from those of dobutamine and dopexamine. The clinical relevance of such effects requires further investigation in critically ill patients.

Adrenergic beta-Agonists↗
PubMed1996

Resting metabolic rate and obesity in childhood acute lymphoblastic leukaemia.

The present study described excess weight gain in children with acute lymphoblastic leukaemia (ALL) treated without cranial radiotherapy, and tested the hypothesis that reduced resting metabolic rate (RMR) predisposes children with ALL to excess weight gain. Changes in relative weight in 35 children were expressed as BMI standard deviation (s.d.) scores from diagnosis to 2 y post diagnosis. RMR was measured by ventilated hood indirect calorimetry in 27 patients who had been in positive energy balance and 27 healthy control children matched pairwise for gender and fat free mass (FFM). Mean change in BMI s.d. score to 2 y was +1.0 (s.d. 1.3), 95% CI +0.5 to +1.5 (paired t, P < 0.01). No significant differences in RMR were observed between patients and controls (paired t-test; analysis of covariance). We conclude that excess weight gain occurs during ALL therapy, even in the absence of cranial radiotherapy. Children with ALL who have been in positive energy balance do not appear to show abnormalities in RMR.

Antineoplastic Combined Chemotherapy Protocols↗