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Biomedical subjects

M Donaldson

Publications and source records attributed to M Donaldson.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1995

Atypical androgen receptor in the human melanoma cell line IIB-MEL-J.

To evaluate the presence of androgen receptors in the human melanoma cell line IIB-MEL-J, a Scatchard plot analysis was performed. Cells in culture revealed a single binding component with an apparent dissociation constant (KD) at 37 degrees C of 11 nM and a binding capacity of 326 fmol/mg protein when measured with [3H]-R1881. Competition analysis revealed an atypical relaxation of specificity, since not only androgen (testosterone, dihydrotestosterone [DHT], R1881) and antiandrogen (hydroxy-flutamide [OH-FLU]) competed for [3H]-R1881 binding, but also estradiol, progesterone, and cortisol at 500-fold excess concentration. Binding of [3H]-estradiol and [3H]-R5020 in the absence of unlabeled DHT were completely suppressed in its presence. Immunohistochemistry of androgen receptor with a monoclonal antibody showed that nuclei were vigorously stained. Different doses of flutamide (FLU) and OH-FLU tested on cultured IIB-MEL-J cells in the presence of serum inhibited significantly cell proliferation in a dose-dependent manner. When cells were incubated with 10 nM DHT and 1% charcoal-adsorbed serum, a significant stimulation of growth that was observed was inhibited by 4 microM OH-FLU. DHT stimulation was completely reversed by the antiestrogen tamoxifen. In addition, male nude mice transplanted with IIB-MEL-J tumor were treated with FLU when tumors were palpable. FLU was effective in diminishing tumor growth and increasing survival rate of the animals. As a conclusion, the presence of functional androgen receptors in these cells has been demonstrated by growth inhibition in vitro and in vivo with antiandrogens, and their atypical nature is suggested by binding cross-reactivity and competition studies.

Androgen Antagonists↗
PubMed1994

A comparison of skinfold thickness, body mass index, bioelectrical impedance analysis and dual-energy X-ray absorptiometry in assessing body composition in obese subjects before and after weight loss.

The assessment of body composition in obese subjects by anthropometric means (skinfolds), presents many difficulties. This study compares the estimates provided of fat free mass in 21 obese subjects (mean body mass index 36.6 +/- 1.2 kg/m(2)) using body mass index and skinfold thickness, with those obtained using the more recently developed techniques of bioelectrical impedance analysis and dual-energy X-ray absorptiometry. Despite highly significant correlations between some of the methods (r(2) = 0.94 for dual-energy X-ray absorptiometry versus bioelectrical impedance analysis), there was a considerable lack of agreement in the measurements, particularly when skinfold thickness was compared with dual-energy X-ray absorptiometry (limits of agreement -21.9 to -1.5 kg for fat free mass estimated from dual-energy X-ray absorptiometry and skinfold thickness) and even for dual-energy X-ray absorptiometry and bioelectrical impedance analysis (limits of agreement -10.7 to 0.4 kg). After weight loss the intermethod differences were reduced.

Journal Article↗
PubMed1994

The effects of weight loss in obese subjects on the thermogenic, metabolic and haemodynamic responses to the glucose clamp.

The aim of this work was to examine the effects of weight loss in obese subjects on the thermogenic, metabolic and cardiovascular responses to a glucose clamp. Resting measurements were made, followed by a hyperinsulinaemic (100 mU/m2/min) euglycaemic clamp (4.5 mmol/l). The subjects were six healthy, obese subjects (mean body mass index before weight loss 37.0 +/- 1.7 kg/m2 and after weight loss 31.4 +/- 2.3 kg/m2). The following measurements were made: indirect calorimetry, blood pressure, heart rate, forearm blood flow, plasma catecholamines, plasma deuterated glucose turnover before and during a glucose clamp. Glucose disposal during the clamp increased from 2.53 +/- 0.40 to 3.31 +/- 0.42 mmol/min after weight loss (P < 0.01). Glucose-induced thermogenesis rose from 0.15 +/- 0.09 to 0.50 +/- 0.12 kJ/min (P < 0.05). The apparent cost of glucose storage was not significantly different from zero prior to weight loss, but increased to 11.0 +/- 2.2% after weight loss. In response to the clamp endogenous glucose production was suppressed by 66 +/- 7% initially and this was not affected by weight loss. Weight loss was accompanied by increased peripheral insulin sensitivity and glucose-induced thermogenesis, but it did not affect hepatic insulin sensitivity.

Adult↗
PubMed1993

Hepatitis B prevalence in local authority employees.

Prevalence of hepatitis B infection was determined in 420 employees from three local authorities by testing for hepatitis B core antibody (anti-HBc). Five (1.2 per cent) were positive: this included a hepatitis BsAg carrier, three with antibody to hepatitis BsAg (anti-HBs) and one who had only anti-HBc. The prevalence of hepatitis B was not significantly different (P > 0.05) from a control group of blood donors. However, four out of five anti-HBc positive individuals worked with mentally or physically handicapped individuals or those discharged into the community after long-term institutionalized care.

Adolescent↗
PubMed1993

Computer-Assisted Retrospective Clinical Activities Statistics (CARCAS) Program.

Clinical pharmacy services have been demonstrated to have a positive impact on patient care in the hospital setting. Accurate and complete documentation of interventions aimed at improving drug use is essential to assess workload characteristics, determine the impact of pharmacist activities, justify current programs and predict future clinical staffing requirements. The need for an improved system of collecting and analyzing clinical workload statistics led to the development of a Computer-Assisted Retrospective Clinical Activities Statistics (CARCAS) Program in our department. Using a pre-defined clinical activity coding system, pharmacist activities were efficiently documented on a daily basis using an existing distributional computer system. Training requirements and data entry time were minimal. The CARCAS Program appeared to capture more clinical pharmacist activities than the earlier manual system. The flexibility of the CARCAS Program should permit adaptation to other hospitals with similar computer systems regardless of the nature of their clinical programs.

British Columbia↗
PubMed1993

[Pregnancy with spermatozoa from the head of the epididymis in spermatic duct agenesis].

From a male affected of agenesis of corpus and cauda epididymis and vas deferens, sperms were surgically obtained aspirating epididymal content with the help of a surgical microscope. Motile sperms were separated after discontinuous Percoll gradient centrifugation and used to inseminate in vitro the spouse's oocytes 8 hrs. after aspiration according to the current techniques. Twenty hours later, oocytes were checked for fertilization and transferred to fresh culture medium. From 13 preovulatory oocytes only one was fertilized and transferred to the Fallopian tube at the 6 cells stage. Fourteen days after embryo transfer, serum HCG concentration was 320 mU/ml and on day 29th a 5mm fetal sac showing heart beats was detected by transvaginal sonography. After an uneventful 38 weeks gestation a normal baby girl weighing 2,800 g was delivered.

Adult↗
PubMed1991

The pre-registration house officer year: a critical incident study.

To define the major problems faced by pre-registration house officers, 328 critical incidents from 200 house officers and related staff were collected. Each incident was analysed and key words representing the main features were abstracted. These were then aggregated into eight broad categories; personal aspects, clinical skills, communication and relationships, problem-related, organization skills, education, dying patients, and administration. Further analysis of the incidents suggested a series of conclusions which include the need for effective supervision of the house officer with feedback on performance. An induction/orientation period is necessary; there is evidence that a proportion of house officers need additional experience of practical procedures; house officers often have difficulty in setting priorities and they have little experience, prior to qualification, of organizational skills; during the year they are very busy with little time off. Facilities and accommodation may be less than adequate. They perceive a lack of support from senior staff to help with personal problems and career guidance; they are conscious that communication skills are of great importance and would like additional help with this; there is little time for formal education during the year. The range of clinical material presented is enormous, however, and the challenge for medical education is to ensure that the opportunities for learning are not missed.

Clinical Competence↗