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Biomedical subjects

D MacGregor

Publications and source records attributed to D MacGregor.

At least 19 recordsLinked to original sources
PubMed2003

An anatomical database of carpal bone measurements for intercarpal arthrodesis.

During limited intercarpal fusion it is sometimes difficult to determine correct screw length and staple size. This is because of overlap, and the shape and orientation of the carpal bones on radiography. One hundred complete sets of dry cadaver carpal bones were measured to provide an anatomical database of carpal bone measurements. This should help prevent inadvertent overpenetration of fixation devices during surgery.

Adult↗
PubMed2003

Predictive, pre-natal and diagnostic genetic testing for Huntington's disease: the experience in Canada from 1987 to 2000.

Predictive and pre-natal testing for Huntington's Disease (HD) has been available since 1987. Initially this was offered by linkage analysis, which was surpassed by the advent of the direct mutation test for HD in 1993. Direct mutation analysis provided an accurate test that not only enhanced predictive and pre-natal testing, but also permitted the diagnostic testing of symptomatic individuals. The objective of this study was to investigate the uptake, utilization, and outcome of predictive, pre-natal and diagnostic testing in Canada from 1987 to April 1, 2000. A retrospective design was used; all Canadian medical genetics centres and their affiliated laboratories offering genetic testing for HD were invited to participate. A total of 15 of 22 centres (68.2%), currently offering or ever having offered genetic testing for HD, responded, providing data on test results, demographics, and clinical history. A total of 1061 predictive tests, 15 pre-natal tests, and 626 diagnostic tests were performed. The uptake for predictive testing was approximately 18% of the estimated at-risk Canadian population, ranging from 12.5% in the Maritimes to 20.7% in British Columbia. There appears to have been a decline in the rate of testing in recent years. Of the predictive tests, 45.0% of individuals were found to have an increased risk, and a preponderance of females (60.2%) sought testing. A greater proportion of those at < or = 25% risk sought predictive testing once direct CAG mutation analysis had become available (10.9% after mutation analysis vs 4.7% before mutation analysis, p = 0.0077). Very few pre-natal tests were requested. Of the 15 pre-natal tests, 12 had an increased risk, resulting in termination of pregnancy in all but one. Diagnostic testing identified 68.5% of individuals to be positive by mutation analysis, while 31.5% of those with HD-like symptoms were not found to have the HD mutation. The positive diagnostic tests included 24.5% of individuals with no known prior family history of HD.

Adolescent↗
PubMed2002

Reproductive fitness in maternal homocystinuria due to cystathionine beta-synthase deficiency.

Early diagnosis and improved treatment are leading to the potential for increased reproductive capability in homocystinuria due to cystathionine beta-synthase (CbetaS) deficiency, but information about reproductive outcome and risk of thromboembolism in pregnancy is limited. To provide further information, clinical and biochemical information was obtained on women with maternal homocystinuria, on their pregnancies and on the offspring. This information included blood sulphur amino acids and total homocysteine, CbetaS gene mutations and developmental and cognitive scores in the offspring. The study involved 15 pregnancies in 11 women, of whom 5 were pyridoxine-nonresponsive and 6 were pyridoxine-responsive. Complications of pregnancy included pre-eclampsia at term in two pregnancies and superficial venous thrombosis of the leg in a third pregnancy. One pregnancy was terminated and two pregnancies resulted in first-trimester spontaneous abortions. The remaining 12 pregnancies produced live-born infants with normal or above-normal birth measurements. One offspring has multiple congenital anomalies that include colobomas of the iris and choroid, neural tube defect and undescended testes. He is also mentally retarded and autistic. A second offspring has Beckwith-Wiedemann syndrome. The remaining 10 offspring were normal at birth and have remained normal. There was no relationship between the severity of the biochemical abnormalities or the therapies during pregnancy to either the pregnancy complications or the offspring outcomes. The infrequent occurrences of pregnancy complications, offspring abnormalities and maternal thromboembolic events in this series suggest that pregnancy and outcome in maternal homocystinuria are usually normal. Nevertheless, a cautious approach would include careful monitoring of these pregnancies with attention to metabolic therapy and possibly anticoagulation.

Adolescent↗
PubMed2002

Impact of community neonatal services: a multicentre survey.

OBJECTIVES: To explore the impact of a community neonatal service on high risk infant survivors in the first year of life. DESIGN: Retrospective multicentre survey. Postal questionnaires were sent to selected parents. SETTING: Thirty two neonatal units in England and Wales. PATIENTS INCLUSION CRITERIA: infants over 12 months of age with birth weight < or =1500 g, or who received level I intensive care for at least 48 hours. EXCLUSION CRITERIA: multiple births, infants who had died or had severe congenital abnormalities. A total of 3367 eligible infants were selected, and their parents were sent a questionnaire; 65% responded. MAIN OUTCOME MEASURES: Length of stay on the neonatal unit from birth to initial discharge. Readmission to hospital during the first year of life. RESULTS: The median length of stay in units with a community neonatal service was 35 days compared with 37 days in units without. When adjusted for infant and parent characteristics, the median length of stay was reduced by 12.6% where a community neonatal service was provided (95% confidence interval 5.3% to 19.3%). The readmission rates were 44.6% in units with a community neonatal service and 43.5% in units without. There was no significant reduction in the adjusted odds of readmission. CONCLUSIONS: The retrospective nature of this study means that these findings cannot be definitely attributed to the presence of a community neonatal service. However, the results suggest that community neonatal services may reduce the length of stay without any subsequent increase in readmission.

Community Health Services↗
PubMed2001

Specific targeting, biodistribution, and lack of immunogenicity of chimeric anti-GD3 monoclonal antibody KM871 in patients with metastatic melanoma: results of a phase I trial.

PURPOSE: KM871 is a chimeric monoclonal antibody against the ganglioside antigen GD3, which is highly expressed on melanoma cells. We conducted an open-label, dose escalation phase I trial of KM871 in patients with metastatic melanoma. PATIENTS AND METHODS: Seventeen patients were entered onto one of five dose levels (1, 5, 10, 20, and 40 mg/m2). Patients received three infusions of KM871 at 2-week intervals, with the first infusion of KM871 trace-labeled with indium-111 (111In) to enable assessment of biodistribution in vivo. Biopsies of metastatic melanoma sites were performed on days 7 to 10. RESULTS: Fifteen of 17 patients completed a cycle of three infusions of KM871. No dose-limiting toxicity was observed during the trial; the maximum-tolerated dose was therefore not reached. Three patients (at the 1-, 5-, and 40-mg/m2 dose levels) developed pain and/or erythema at tumor sites consistent with an inflammatory response. No normal tissue uptake of 111In-KM871 was observed, and tumor uptake of 111In-KM871 was observed in all lesions greater than 1.5 cm (tumor biopsy 111KM871 uptake results: range, 0.001% to 0.026% injected dose/g). The ratio of maximum tumor to normal tissue was 15:1. Pharmacokinetic analysis revealed a 111In-KM871 terminal half-life of 7.68 +/- 2.94 days. One patient had a clinical partial response that lasted 11 months. There was no serologic evidence of human antichimeric antibody in any patient, including one patient who received 16 infusions over a 12-month period. CONCLUSION: This study is the first to demonstrate the biodistribution and specific targeting of an anti-GD3 antibody to metastatic melanoma in patients. The long half-life and lack of immunogenicity of KM871 makes this antibody an attractive potential therapy for patients with metastatic melanoma.

Adult↗
PubMed2001

Acute childhood encephalitis and Mycoplasma pneumoniae.

In a prospective 5-year study of children with acute encephalitis, evidence of Mycoplasma pneumoniae infection was demonstrated in 50 (31%) of 159 children. In 11 (6.9%) of these patients, M. pneumoniae was determined to be the probable cause of encephalitis on the basis of its detection in cerebrospinal fluid (CSF) by polymerase chain reaction (PCR) or by positive results of serologic tests for M. pneumoniae and detection of the organism in the throat by PCR. CSF PCR positivity correlated with a shorter prodromal illness (P=.015) and lack of respiratory symptoms (P=.06). Long-term neurologic sequelae occurred in 64% of probable cases. Thirty children (18.9%) who were seropositive for M. pneumoniae but did not have the organism detected by culture or PCR had convincing evidence implicating other organisms as the cause of encephalitis, suggesting that current serologic assays for M. pneumoniae are not sufficiently specific to establish a diagnosis of M. pneumoniae encephalitis.

Acute Disease↗
PubMed2001

Chickenpox and stroke in childhood: a study of frequency and causation.

BACKGROUND AND PURPOSE: The purpose of this study was to determine whether infection with varicella is causal for arterial ischemic stroke (AIS) in children. METHODS: First, a prospective cohort study was conducted in young children (aged 6 months to 10 years) with AIS at 2 institutions (cohort study). The presence of varicella infection <12 months before AIS was determined and compared with the published frequency of varicella infection in the healthy pediatric population. The clinical and radiographic features of AIS were compared between the varicella and nonvaricella study cohorts. Second, a literature search of varicella-associated AIS was conducted, and the clinical and radiographic features were compared with the study nonvaricella cohort. RESULTS: In the cohort study, 22 (31%) of 70 consecutive children with AIS had a varicella infection in the preceding year compared with 9% in the healthy population. Children in the varicella cohort were more likely to have basal ganglia infarcts (P<0.001), abnormal cerebral vascular imaging (P<0.05), and recurrent AIS or transient ischemic attacks (P<0.05) than those in the nonvaricella cohort. The pooled literature analysis of 51 cases of varicella-associated AIS showed similar findings to the varicella cohort. CONCLUSION: In young children with AIS, there is a 3-fold increase in preceding varicella infection compared with published population rates, and varicella-associated AIS accounts for nearly one third of childhood AIS. Varicella-associated AIS has characteristic features, including a 2-fold increase in recurrent AIS and transient ischemic attacks. Varicella is an important risk factor for childhood AIS.

Age Distribution↗
PubMed2000

Perforin-mediated cytotoxicity is critical for surveillance of spontaneous lymphoma.

Immune surveillance by cytotoxic lymphocytes against cancer has been postulated for decades, but direct evidence for the role of cytotoxic lymphocytes in protecting against spontaneous malignancy has been lacking. As the rejection of many experimental cancers by cytotoxic T lymphocytes and natural killer cells is dependent on the pore-forming protein perforin (pfp), we examined pfp-deficient mice for increased cancer susceptibility. Here we show that pfp-deficient mice have a high incidence of malignancy in distinct lymphoid cell lineages (T, B, NKT), indicating a specific requirement for pfp in protection against lymphomagenesis. The susceptibility to lymphoma was accentuated by simultaneous lack of expression of the p53 gene, mutations in which also commonly predispose to human malignancies, including lymphoma. In contrast, the incidence and age of onset of sarcoma was unaffected in p53-deficient mice. Pfp-deficient mice were at least 1,000-fold more susceptible to these lymphomas when transplanted, compared with immunocompetent mice in which tumor rejection was controlled by CD8(+) T lymphocytes. This study is the first that implicates direct cytotoxicity by lymphocytes in regulating lymphomagenesis.

Animals↗
PubMed2000

Comparative study of inter- and intrahemispheric somatosensory functions in children with partial and complete agenesis of the corpus callosum.

Inter- and intrahemispheric somatosensory functions were evaluated in blinded tests of 11 children with partial and complete agenesis of the corpus callosum (age range 2 years 8 months to 11 years 9 months) and compared with those of age- and sex-matched control individuals both normally developing and with neurological impairment. Tests included uni- and bimanual measures of stereognosis, haptic visual discrimination, kinaesthesis, and texture matching. Children with callosal absence displayed significant difficulties with many somatosensory functions, but most deficits were no greater than those of the children who had neurological dysfunction and an intact corpus callosum. Children with callosal absence, however, had significantly greater difficulty with bimanual texture matching, seemingly because this task required refined spatial interpretation of somatosensory input. Response times for the individuals with callosal absence were significantly greater than those for control participants with neurological impairment on several tasks in which overall accuracy of performance among groups did not significantly differ. These findings suggest that children with agenesis of the corpus callosum may have less efficient and slower processing capacity for certain types of somatosensory information. Possible compensatory mechanisms are discussed.

Agenesis of Corpus Callosum↗
PubMed2000

The development of a pig model to study fetal vesico-ureteric reflux.

OBJECTIVE: To develop a surgical protocol to induce vesico-ureteric reflux (VUR) in utero by ablating the ureteric tunnel in a fetal pig model. MATERIALS AND METHODS: Fetal surgery was conducted on nine sows, which were divided into three groups according to changes in the surgical protocol. Sows in groups 2 and 3 received different anaesthetics and antibiotics, and the operating theatre temperature was increased. In all cases, the intramural part of the ureter was unroofed in the fetuses, which were then returned to the uterus. Upon delivery, cystograms were taken in the male piglets, and the urinary tracts removed for anatomical and histological examination. RESULTS: All three sows in group 1 delivered healthy piglets, but the fetuses that had undergone surgery were mummified. In group 2 the animals survived the fetal intervention, as shown by ultrasonography after surgery, but the four sows aborted spontaneously within a week. In group 3, both sows delivered normally developed piglets, three of which had undergone ablation of the ureteric tunnel. VUR was present only in those renal units in which the ureteric tunnel was ablated, and this was associated with hydronephrosis, dilatation of the ureters and thinning of the renal parenchyma on gross pathological examination. CONCLUSIONS: The fetal pig model of VUR not only appears to be feasible, but with similarities in renal anatomy and physiology also seems to be ideal for investigating fetal VUR.

Animals↗
PubMed2000

Neurologic outcome in survivors of childhood arterial ischemic stroke and sinovenous thrombosis.

Ischemic stroke during infancy and childhood has the potential for life-long morbidity. Information on the neurologic outcome of children who survive ischemic stroke is lacking. Children surviving ischemic stroke between January 1, 1995 and July 1, 1999 were prospectively followed. Neurologic deficit severity was based on the Pediatric Stroke Outcome Measure (PSOM) developed in this study and parental response to two recovery questions. Predictor variables for poor outcome were tested. One-hundred twenty-three children with arterial ischemic stroke and 38 with sinovenous thrombosis were followed for a mean of 2.1 years (range, 0.8 to 6.6 years). The primary outcome based on PSOM assessment was: normal, 37%; mild deficit, 20%; moderate deficit, 26%; and severe deficit, 16%. The secondary outcome was full recovery in 45% of patients, based on parental response. The primary and secondary outcome measures were moderately correlated (P < .001; K = 0.5). In bivariate analysis, arterial stroke type, male gender, age of at least 28 days, presence of associated neurologic disorders, and need for rehabilitation therapy after stroke were predictors of poor outcome (P < .05). Multivariate analysis showed that only arterial ischemic stroke, associated neurologic disorders, and presence of rehabilitation therapy were independent predictors of poor outcome (P < .02). Poor outcome in children after ischemic stroke is therefore frequent and more likely in the presence of arterial stroke, rehabilitation therapy, and associated neurologic disorders, which justifies clinical trials of treatment strategies in childhood ischemic stroke.

Adolescent↗
PubMed1998

Prothrombotic disorders in infants and children with cerebral thromboembolism.

BACKGROUND: To our knowledge, the contribution of prothrombotic conditions to cerebral thromboembolism has never been prospectively studied in a large series of pediatric patients. METHODS: The Hospital for Sick Children, Toronto, Ontario, established a program in January 1992 to diagnose and treat children (term newborn to 18 years old) with arterial ischemic stroke or sinovenous thrombosis. The routine evaluation for prothrombotic conditions included plasminogen, antithrombin, protein C, free protein S, activated protein C resistance, IgG and IgM anticardiolipin antibody, and lupus anticoagulant. We analyzed samples taken within 2 years of the event. We report results on patients seen from January 1, 1992, to January 1, 1997. RESULTS: Ninety-two patients (47 males and 45 females) entered the program during the study interval. Patients ranged from newborn to 18 years in age. Arterial ischemic stroke occurred in 78% of patients while sinovenous thrombosis occurred in 22%. All were tested for prothrombotic disorders. One or more abnormal results were present in 35 (38%) of the 92 patients. The majority (21/35) had multiple abnormal test results. The abnormal test results were anticardiolipin antibody (33%), plasminogen (9.5%), activated protein C resistance (9%), protein C (7%), antithrombin (12.5%), lupus anticoagulant (8%), and free protein S (11.5%). Male sex predicted the presence of prothrombotic abnormalities (relative risk, 1.7; 95% confidence interval, 1.2-2.5), but stroke type (relative risk, 0.8; 95% confidence interval, 0.7-1.1), age group, and presence of other risk factors did not predict abnormal testing. CONCLUSIONS: A significant proportion (38%) of children with cerebral thromboembolism had evidence of prothrombotic conditions. In particular, there was a predominance of children with anticardiolipin antibody (33%). These data support a recommendation that children with cerebral thromboembolism be evaluated for prothrombotic disorders.

Adolescent↗
PubMed1998

Etiology of acute childhood encephalitis at The Hospital for Sick Children, Toronto, 1994-1995.

Of 145 patients admitted to our hospital because of encephalitis-like illness, 50 patients hospitalized for > or =72 hours underwent standardized microbiological investigations. A confirmed or probable etiologic agent was identified in 20 cases (40%), including Mycoplasma pneumoniae (9 cases). M. pneumoniae and enterovirus (2), herpes simplex virus (4), Epstein-Barr virus (1), human herpes-virus 6 (HHV-6) (1), HHV-6 and influenza virus type A (1), influenza virus type A (1), and Powassan virus (1). In 13 cases (26%), a possible pathogen was identified, including M. pneumoniae in nine cases. Presenting features included fever (80% of patients), seizures (78%), focal neurological findings (78%), and decreased consciousness (47%). The frequency of findings at the time of admission vs. later in hospitalization was as follows: pleocytosis, 59% vs. 63%; electroencephalogram abnormalities, 87% vs. 96%; and neuroimaging abnormalities, 37% vs. 69%, respectively. The outcomes at the time of discharge were as follows: normal results of physical examination, 32% (16) of the patients; death, 2% (1); motor difficulties, 26% (13); global neurological deficits, 16% (severe, 6; mild, 2); mental status changes, 14% (7); visual defects, 8% (4); and hearing impairment, 2% (1).

Acute Disease↗
PubMed1998

Cardiac failure in children with pneumonia in Papua New Guinea.

BACKGROUND: Cardiac failure is suspected of contributing to mortality from pneumonia in children in developing countries, but its role has not been clearly defined. METHODS: A convenience sample of 47 children admitted to Goroka Hospital in Papua New Guinea was studied prospectively with ultrasound, chest radiographs and assays of creatine kinase and lactate dehydrogenase. Results. Seven (15%) of the 47 children died. Of the 43 children who had a chest radiograph, 31 (72%) had severe or very severe pneumonia. No child had poor contractility of the heart on ultrasound examination or unequivocally raised cardiac isoenzymes; therefore no evidence of myocardial injury from sepsis was found. However, ultrasound examination showed dilatation of the right ventricle or hepatic veins in 12 (26%) of the children (both were dilated in 7 children) and 4 (33%) of these children died; this suggests that right ventricular cardiac failure secondary to pulmonary hypertension was present in 26% (95% confidence interval, 14 to 40%) of these children with severe pneumonia. Tachycardia was not associated with right ventricular dilatation on ultrasound, but 3 of the 4 children with more than 3 cm of liver palpable in the abdomen had right ventricular dilatation. Only 4 of the 12 children with right heart failure had hepatomegaly, tachycardia, raised jugular venous pressure or peripheral edema. CONCLUSIONS: Right ventricular failure is common in children with severe pneumonia, and it is probably caused by pulmonary hypertension rather than septic toxemia. The clinical signs of heart failure are unreliable. There is no evidence that digoxin is effective treatment for right ventricular failure secondary to pulmonary hypertension.

Cause of Death↗
PubMed1998

Tumor-specific IgE-mediated inhibition of human colorectal carcinoma xenograft growth.

Antibodies have found application in the diagnosis and therapy of cancer. These antitumor antibodies are confined to isotypes of IgG and little is known of the potential usefulness of other classes of immunoglobulin. In order to determine a possible antitumor effect of IgE antibody a tumor-specific mouse monoclonal IgE antibody was constructed. This antibody was derived from the mouse monoclonal antibody 30.6 that detects an antigenic determinant expressed on the surface of colorectal adenocarcinoma cells, including COLO 205. Mouse IgE 30.6 inhibited the growth of established COLO 205 tumor growing subcutaneously in scid mice. This effect was transient with tumor growth returning to pretreatment levels after 48 h. By contrast, a mouse IgG 30.6 and a chimeric human/mouse IgE 30.6 were without antitumor effect. This isotype-specific antitumor effect was not attributable to differences in antibody affinity, tumor localization, or serum half-life as these were essentially the same for all three isotypes of antibody. In addition, none of the 30.6 monoclonal antibodies inhibited the growth of COLO 205 cells in vitro. As little as 1 microgram per mouse of the tumor-specific mouse IgE antibody was sufficient to inhibit COLO 205 tumor growth, which is in contrast to previous results in which the comparatively weak antitumor effect of a chimeric human/mouse IgG1 required an optimum dose of 4 x 250 micrograms per mouse. This antitumor effect of mouse IgE 30.6 was specifically abrogated by prior administration of a nonspecific mouse IgE. Given this potency, and the fact that mouse Fc epsilon RI binds mouse IgE, but not human IgE, a role for Fc epsilon receptor bearing effector cells in the observed antitumor effect is discussed.

Animals↗