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Biomedical subjects

I Gordon

Publications and source records attributed to I Gordon.

At least 91 records · Page 5Linked to original sources

Dosimetry of pediatric radiopharmaceuticals: uniformity of effective dose and a simple aid for its estimation.

UNLABELLED: Formulae were investigated for predicting the effective dose to children, per unit administered activity of various pediatric radiopharmaceuticals, based only on the weight of the patient. Their influence on the uniformity of effective dose from total administered activity was also examined. METHODS: The formulae were obtained from calculations of effective dose per unit administered activity (mSv x MBq[-1]) for five anthropomorphic mathematical phantoms applicable for newborn, 1-yr-, 5-yr-, 10-yr- and 15-yr-old children, having body weights of 3.4, 9.8, 19, 32 and 57 kg, respectively, using published biokinetic models. RESULTS: In general, there was good linear correlation between effective dose per unit administered activity and inverse weight but, for some radiopharmaceuticals, logarithmic regression on weight provided a better fit to the data. An administered activity schedule based on body surface area, used with these formulae, resulted in reasonable uniformity of effective dose for children of all ages, with varying degrees of uniformity for different radiopharmaceuticals (coefficient of variation (COV) up to 20%). Individual activity schedules for separate radiopharmaceuticals gave best uniformity (COV < 7%) while a single general schedule, based on the mean results of the present study, yielded acceptable uniformity (COV < or = 10%) over the pediatric range. CONCLUSION: Effective dose per unit administered activity (mSv x MBq[-1]) of pediatric radiopharmaceuticals can be predicted from body weight alone by using simple formulae, and appropriately choosing the administered activity schedule leads to similar values of effective dose for children of all ages from a given radiopharmaceutical procedure.

Adolescent↗

Granulocyte colony-stimulating factor recruitment of CD34+ progenitors to peripheral blood: impaired mobilization in chronic granulomatous disease and adenosine deaminase--deficient severe combined immunodeficiency disease patients.

Peripheral blood (PB) CD34+ cells mobilized by granulocyte colony-stimulating factor (G-CSF) administration are potentially useful for transplantation and as a target of gene transfer for therapy of hematopoietic disorders. Efficient harvest and planning for clinical use of PB CD34+ cells ideally requires foreknowledge of the expected mobilization kinetics and yield. We developed a sensitive flow cytometric assay for accurately enumerating CD34+ cells throughout the range seen at baseline to peak mobilization. We used this assay to assess the kinetics of G-CSF-mediated mobilization of CD34+ cells to PB in normal volunteers and in patients with chronic granulomatous disease (CGD) or adenosine deaminase (ADA)-deficient severe combined immunodeficiency disease (SCID). Two dose levels of G-CSF were examined (5 and 10 micrograms/kg/d for 7 days). Both doses were well tolerated. For normal subjects and patients an increase in PB CD34+ cells was first detected only preceding the third dose of G-CSF (day 3), peaked transiently on day 5 or 6, and then decreased thereafter despite additional doses of G-CSF. With 32 normal volunteers mean peak CD34+ cell counts were 57 and 76 cells/mm2 of blood (5 and 10 micrograms doses, respectively), whereas for 18 CGD patients the mean peaks were 31 and 40 cells/mm2 of blood. For 2 ADA-deficient SCID patients studied at a G-CSF dose of 5 micrograms/kg/d, the average peak was 16 cells/mm2 of blood. For both of these patient groups mobilization of CD34+ cells to PB was impaired compared with similarly treated normal subjects (P < .05). By contrast to the kinetics of the CD34+ cell mobilization, the absolute neutrophil count (ANC) increased markedly by 6 hours after the first dose of G-CSF and then increased steadily through day 8. At days 5 and 6 (peak mobilization of CD34+ cells) the mean ANC of CGD and ADA patients was only slightly lower ( < or = 15%) than that seen with normal subjects, whereas the difference in CD34+ cell mobilization was > 48%. Thus, ANC is not a reliable surrogate to predict peak PB CD34+ cell counts and direct enumeration of PB CD34+ counts should be undertaken in decisions regarding timing and duration of apheresis to harvest a specific number of these cells. Finally, unexpected, but significant differences in the PB CD34+ cell mobilization between normal subjects and patients with inherited disorders can occur and underscores the importance of establishing the expected mobilization of PB CD34+ cells in the planning of treatment approaches using these cells.

Adenosine Deaminase↗

Derangement in stress response of apolipoprotein E-deficient mice.

Apolipoprotein E (apoE) is associated with familial and sporadic Alzheimer's disease (AD). Stress has been identified as a putative risk factor of AD. Thus, in the present study we examined the susceptibility of apoE-deficient mice to stress. The results obtained revealed that the elevation of corticosterone levels in apoE-deficient mice following restraint stress is markedly lower than in controls, and that these mice differ in their behavioral pain response to noxious stimuli in both stress and non-stress conditions. These findings suggest an interplay between apoE and the response to stressful stimuli and provide a model for elucidating the relationship between apoE and susceptibility to stress.

Alzheimer Disease↗

Modulatory effect of agents active in the presynaptic dopaminergic system on the striatal dopamine transporter.

We have investigated the effects of agents active in the presynaptic dopaminergic system on the characterization of the rat striatal dopamine transporter. The dopamine transporter was characterized by high-affinity [3H]GBR 12935 (1-[2-diphenylmethoxy)-ethyl]-4-(3-phenylpropyl)-piperazine) binding to a membrane preparation and by [3H]dopamine uptake into striatal synaptosomes. Subchronic treatment with reserpine (2.5 mg/kg, 4 days), a monoamine depletor, caused a significant decrease in both [3H]GBR 12935 binding (20%) and [3H]dopamine uptake (51%). In contrast, amantadine (a dopamine releaser) treatment (20 mg/kg, 21 days) induced an increase (28%) in the maximal number of [3H]GBR 12935 sites. Chronic levo-dopa (dopamine precursor) treatment combined with carbidopa (50 mg/kg and 5 mg/kg respectively, 21 days) as well as benztropine (dopamine uptake inhibitor) treatment (10 mg/kg, 21 days) did not affect the striatal dopamine transporter characteristics. The present results showed that the striatal dopamine transporter is sensitive to changes in dopaminergic neurotransmission caused by agents that do not interact directly with the dopamine carrier.

Amantadine↗

Pneumatic intussusception reduction via a colostomy: case report.

Intussusception is uncommon in infants with a colostomy. The authors present the first documented case of intussusception in an infant with a colostomy in which pneumatic reduction was achieved via the stomal opening. The inflated balloon of a Foley catheter was plugged against the stoma at skin level and a tight seal was obtained. Successful reduction was achieved without any adverse effects to the patient.

Catheterization↗

Long-term effects of gastric transposition in children: a physiological study.

Gastric transposition (GT) has become a reliable alternative operation for oesophageal replacement in children. The aims of this study were to assess the long-term results of the operation and to study the function of the intrathoracic stomach. Current symptoms were assessed using a questionnaire and linear analogue scales. Lung function was measured using spirometry and plethysmography, and the results were corrected for height and expressed as a percentage of the predicted values for normal children. Gastric emptying was assessed using a dual isotope radiolabelled test meal (incorporating solid and liquid phases). Full anthropometric and haematologic data also were collected. The results are expressed as medians and interquartile ranges. Seventeen children were examined at least 5 years after GT; the median age was 9 years. Two children frequently had symptoms during swallowing. Four children had significant diarrhoeal episodes, and two had significant postprandial weakness or dizziness. Unexplained breathlessness was noted by four children. All but one child had lung function values that were lower than the mean predicted value for height. For example, the total lung capacity was 68%, and forced vital capacity (FVC) was 64%. However, the ratio of forced expiratory volume in 1 second (FEV1) to FVC was normal. The gastric emptying study showed that the intrathoracic stomach in all subjects served as a conduit (rather than a reservoir) for both liquids and solids. Rapid emptying (> 50%) in both phases occurred within 5 minutes of ingestion in 82% of the group. Thirteen children were between the 3rd and 97th percentiles for height, and 11 in this range for weight. Five children were anaemic (< 11.5 g/dL). In 11 of the tested samples, the serum ferritin was low, indicating depleted iron stores. GT is compatible with an entirely normal life and has allowed satisfactory growth and nutrition for the majority of subjects in this study group.

Anastomosis, Surgical↗

Cerebral blood flow imaging in paediatrics: a review.

The ability to study regional cerebral blood flow (rCBF) is available in many institutions, especially with the spread of multi-headed gamma cameras. The use of this technique in paediatrics requires special attention to detail in the manner of data acquisition and handling the child. The interpretation of the rCBF study in a child requires knowledge of normal brain maturation. The major clinical use in paediatrics is epilepsy because of the advances in surgery and the frequency of complex partial seizures. Other indications in paediatric neurology include brain death, acute neurological loss including stroke, language disorders, cerebral palsy, hypertension due to renovascular disease, traumatic brain injury and migraine. There are paediatric psychological conditions in which rCBF assessment has been undertaken, including anorexia nervosa, autism, Gilles de la Tourette Syndrome (GTS) and attention deficit disorder-hyperactivity (ADHD). This article attempts to review all aspects of rCBF studies in paediatrics.

Adolescent↗

Investigating inflammatory bowel disease--white cell scanning, radiology, and colonoscopy.

OBJECTIVE: To evaluate different methods of examination of the bowel in suspected inflammatory bowel disease. DESIGN: Prospective investigation of all children over a three year period with suspected inflammatory bowel disease. A technetium-99m-HMPAO labelled white cell scan (Tc-WCS), barium follow through examination (Ba-FT), and colonoscopy plus biopsy were undertaken. SETTING: Great Ormond Street Hospital for Children, London. SUBJECTS: 39 children (20 male and 19 female), median age 12.1 years (range 3.9-15.1 years). MAIN OUTCOME MEASURES: There was total agreement in 21/39 cases, positive in 16, and negative in five. Of 31 histologically proved cases, positive results were obtained in 28 Tc-WCSs (sensitivity 90%), 10 of 24 Ba-FTs (sensitivity 42%), and 27 colonoscopies (sensitivity 87%). CONCLUSION: The Tc-WCS is sensitive, specific, and non-invasive and should be a first line investigation. Ba-FT with a high radiation burden and relatively low sensitivity requires its role to be redefined. Colonoscopy, with endoscopic biopsy, has a high pick-up rate where facilities and expertise exist.

Adolescent↗

Sonographic standards for a single functioning kidney in children.

OBJECTIVE: We investigated the sonographic measurements of the functioning kidney of children who were born with a single functioning kidney. MATERIALS AND METHODS: In 56 children (0-6 years old) with one multicystic dysplastic kidney and one functioning kidney, the length of the functioning kidney was correlated with the child's age, weight, and body surface area. RESULTS: The mean length of the kidney was 51.0 mm in children 2 weeks old, 56.8 mm at 9 weeks, 62.8 mm at 23 weeks, 69.6 mm at 46 weeks, 71.7 mm at 63 weeks, 78.0 mm at 112 weeks, 79.6 mm at 172 weeks, 86.7 mm at 225 weeks, and 91.0 mm at 279 weeks. When these results were compared with existing sonographic standards for bilateral functioning kidneys, the single functioning kidneys were longer by a statistically significant amount. CONCLUSION: Compensatory hypertrophy of single functioning kidneys occurs in utero. In children of the ages we investigated, the size of single functioning kidneys exceeded established standards for the size of bilateral functioning kidneys.

Age Factors↗

Biokinetic behavior of technetium-99m-DMSA in children.

UNLABELLED: After intravenous administration of 99mTc-DMSA, biokinetic data were collected from studies on 24 children aged from 5 wk to 14.8 yr (15 normal and 9 with renal pathology). METHODS: Patients were imaged with a gamma camera up to 30 hr postinjection and the absolute activities in the kidneys, liver, spleen, bladder, knees and whole body were estimated using an attenuation-corrected conjugate counting technique. Renal uptake and elimination rates and urinary excretion of radioactivity were also measured. RESULTS: In children with normal renal function, maximal kidney uptake was 42.4% +/- 5.4% and was taken up with a half-time of 1.0 +/- 0.2 hr. Renal excretion amounted to 18.0% +/- 4.4% at 24 hr and was lowest in children aged less than 1 yr. In children with abnormal renal function, apart from the expected reduction in renal uptake there was evidence of wider variations in uptake rate and increased urinary excretion. Mean uptakes in liver and spleen were approximately 5% and 2%, respectively, in all patients and uptake in knees, assumed to reside in the metaphyseal growth complexes, was 1.4%. CONCLUSION: In children with normal renal function, there was little evidence of age-dependent biokinetic factors other than reduced urinary excretion and lower uptake in knees in children aged less than 1 yr. The results therefore suggest that a single biokinetic model may suffice for radiation dosimetry purposes in normal children irrespective of age.

Age Factors↗

Radiation dosimetry of technetium-99m-DMSA in children.

UNLABELLED: Radiation dosimetry was performed on 24 children (aged 5 wk to 14.8 yr) who were undergoing routine diagnostic investigation of renal impairment with 99mTc-DMSA. METHODS: Organ doses were calculated using MIRDOSE 3 with biokinetic data obtained in previously described studies, and effective doses and effective dose equivalents were estimated. Interpolation by inverse weight between pediatric anthropomorphic phantoms was compared with age-matching to discrete phantoms. Administered activities were scaled by body surface area from the adult activity of 100 MBq and the resulting radiation doses in normal children were compared with those that would have resulted from a schedule based on body weight. RESULTS: The effective doses estimated by interpolation differed by up to 46% from those based on discrete phantoms and showed less variation. In children with normal bilateral renal function, the mean effective dose per administered activity was 0.91 +/- 0.08 mSv or 0.98 +/- 0.29 mSv by the two methods, respectively. Renal pathology reduced the effective dose, on average, by 15% of the value for normal patients. CONCLUSION: Over the pediatric age range, the uniformity of effective dose values was improved by scaling the administered activity according to body surface area rather than to body weight.

Adolescent↗

Quality of care: identification and quantification of the process of care among children undergoing nuclear medicine studies.

The aim of this study was to define indices which could be used to assess the quality of care of children undergoing an examination requiring intravenous (i.v.) access in an integrated department of radiology and to see if these indices could be quantified. A prospective study of all patients requiring an i.v. injection for a nuclear medicine examination (NME) over a period of 8 weeks was undertaken. The following indices were assessed: the waiting time of the patients in the department for a NME, the use of EMLA (a local anaesthetic cream), use of sedation, and number of attempts to achieve i.v. access. The 219 males and 174 females had a median age of 46 months. EMLA was applied to 298 children. The median times from arrival to the application of EMLA was 5 min, between EMLA to the injection 59 min, and between arrival to injection 65 min. Seventeen children had sedation. Intravenous access was achieved on the first attempt in 76.7% of cases and three or more attempts were made in 8.5% of cases. Successful injections were made in 91.5% of the children; 8.2% had partial extravasation of the radio-isotope at the injection site and in one patient the examination was abandoned due to an inability of gaining i.v. access. This study has identified and quantified indices to measure the quality of care for children undergoing an i.v. injection in an imaging department. Baseline values have been established for i.v. access, sedation and waiting times in the radiology department for various NMEs. Undertaking multiple imaging procedures on the same day requires careful scheduling and complex organization.

Adolescent↗

Memory deficits and cholinergic impairments in apolipoprotein E-deficient mice.

Apolipoprotein E-deficient mice provide a useful system for studying the role of apolipoprotein E (apoE) in the function of distinct neuronal systems. In the present study we focused on the cholinergic system of these mice. This was pursued by measurements of specific biochemical, physiological and cognitive parameters. Morris Water Maze tasks revealed impairments in working memory but not in reference memory of the apoE-deficient mice. Measurements of brain choline acetyltransferase activities revealed them to be markedly lower in the hippocampus and frontal cortex of the apoE-deficient mice than in the corresponding brain areas of the controls, but unaltered in other brain areas. In addition, hypothermia induced by the centrally acting muscarinic agonist, oxotremorine, was reduced in the apoE-deficient mice as compared to controls. These results show that apoE-deficient mice have cholinergic deficits and highlight the importance of this mouse model for studying the interactions between apoE and the cholinergic nervous system.

Animals↗

Phosphorylation of tau in apolipoprotein E-deficient mice.

It has been suggested that the deleterious effects of the allele E4 of apolipoprotein E (apoE) in Alzheimer's disease (AD) are related to its inability to interact with the microtubule associated protein tau and to thereby prevent its hyperphosphorylation. In the present study we investigated the effects of apoE on tau phosphorylation by immunoblot analysis of the levels and extents of phosphorylation of tau of apoE-deficient mice. This revealed that mAb AT8, which is directed against a phosphorylated tau epitope, labels tau of the apoE-deficient mice more intensely than that of control mice and that the opposite occurs with mAb Tau1, which is directed against dephosphorylated tau epitopes. mAb ALZ50 also labeled the tau enriched preparations of the apoE-deficient mice more intensely than those of the controls, whereas the extents of their labeling by the phosphorylation insensitive anti-tau mAb 134 were similar. These results suggest that tau of apoE-deficient mice is hyperphosphorylated.

Animals↗

Developmental and age-related alterations in rat brain presynaptic dopaminergic mechanisms.

Age-related changes in both pre- and post-synaptic components of dopamine neurons have been demonstrated in humans as well as in animals. Our study was designed to examine the effects of age on presynaptic DA neurons. To assess the developmental changes in rat striatal dopamine carrier, we used [3H]GBR 12935, which binds selectively to this transporter. In addition we monitored changes in amphetamine- and KCl-induced [3H]DA release from rat striatal slices. We were able to demonstrate age dependent changes in DA transporter density, which reached a peak at age 3 months. Amphetamine-induced released of stored DA was exactly reversed, with a nadir at age 3 months. We assumed that the combination of low DA transporter level with increased transporter-mediated DA release may have a major compensatory role with respect to the maintenance of dopaminergic transmission during normal development, aging and neuro-degenerative diseases.

Age Factors↗