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Biomedical subjects

M Cole

Publications and source records attributed to M Cole.

At least 19 recordsLinked to original sources

Screening for neuroblastoma in the north of England.

OBJECTIVE: To determine the feasibility of establishing a system of screening for neuroblastoma. DESIGN: Prospective study of mass screening in four clearly defined geographical areas. SETTING: Four health districts of the Northern region of England. SUBJECTS: 20,829 babies aged 6 months, 92% of target population. INTERVENTIONS: Collection of urine on filter paper for analysis of content of homovanillic and vanillylmandelic acid in relation to urinary creatinine concentrations. MAIN OUTCOME MEASURES: Derivation of reference range. Identification of babies with homovanillic or vanillylmandelic acid > 3 SD above the mean (positive cases). Investigation of positive cases for evidence of neuroblastoma. RESULTS: The upper limit of normal (3 SD above the mean) for vanillylmandelic acid was 15 mumol/mmol creatinine and for homovanillic acid 24 mumol/mmol creatinine. Of the 20,829 babies screened, 2537 (12.2%) required a second sample to be taken because the first sample was inadequate. Of these, 527 (2.5%) provided a liquid urine specimen and 10 (0.04%) had positive results for neuroblastoma. Two of them had neuroblastoma (true positives) and eight did not (false positives). A further three children from the cohort were subsequently found to have neuroblastoma; they had raised homovanillic acid or vanillylmandelic acid values, or both, but screened negative at 6 months. CONCLUSIONS: Screening for neuroblastoma is possible in the health care system of the United Kingdom. Evaluation of the efficacy of screening in reducing the mortality from neuroblastoma requires a controlled trial.

Creatinine

Thalamic amnesia: Korsakoff syndrome due to left thalamic infarction.

In order to support the concept that a lesion of the thalamus is sufficient to cause a Korsakoff syndrome, we are presenting 5 patients, all of whom developed the syndrome after sustaining a left (dominant) thalamic infarction. Two patients had pure thalamic strokes followed by a permanent Korsakoff syndrome. One of these patients was studied with neuropsychometric testing, as well as with a modern MRI scan. In 2 other patients, clinical and imaging data indicate that infarction was not limited to the thalamus. Another patient had bilateral thalamic infarcts but only a temporary Korsakoff syndrome. Neuropathological data are needed to elucidate the exact anatomical substrate of dominant thalamic Korsakoff syndrome.

Aged

A trial of the prostaglandin E1 analogue, enisoprost, to reverse chronic cyclosporine-associated renal dysfunction.

Cyclosporine (CYA) reduces the renal synthesis of prostaglandins of the E series (PGE). Analogue of PGE1 have been shown to mitigate the vasoconstriction and abnormal renal function of experimental acute CYA nephrotoxicity. We examined the hypothesis that the orally bioavailable PGE analogue enisoprost (EP) would improve renal function in renal transplant recipients chronically exposed to CYA. In a randomized double-blind study, 40 patients at two centers who were being monitored for 3 to 30 months after renal transplantation, were allocated to receive either EP 100 micrograms orally four times daily or placebo (P) for 2 weeks. CYA dosing was fixed at existing levels. There could be no evidence of concurrent acute renal injury, including that of acute rejection. Glomerular filtration rate (GFR) was measured by the clearance of radiolabeled DTPA, while effective renal plasma flow (ERPF) was measured as the clearance of p-aminohippuric acid (PAH). The acute effects of EP were examined twice, by comparing immediate postdose to predose values for GFR and ERPF on day 1 and again on day 14. Chronic effects were examined by comparing baseline (predose) values only for GFR and ERPF between days 1 and 14 and by an examination of creatinine clearances (CCR) on days 0, 14, and 21. At enrollment, patients were well matched for renal function (CCR:EP 47 +/- 5 v P 49 +/- 4 mL/min/1.73 m2; P = NS). Baseline demographics were similar, although patients treated with EP were older (46 +/- 2 v 36 +/- 3 years, mean +/- SEM, P = 0.003). CYA doses and blood levels did not change significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Intraoperative identification of a radiofrequency lesion allowing validation of catheter mapping of ventricular tachycardia with a computerized balloon mapping system.

Radiofrequency current was utilized to mark the anatomic location of earliest endocardial activation during catheter mapping of ventricular tachycardia. Intraoperative identification of the radiofrequency lesion allowed validation that the site of earliest endocardial activation determined by a catheter mapping study was the same as assessed by a computerized balloon mapping system. Radiofrequency current may be a useful method of marking areas of endocardium thought to be potential sites for ablative surgery as well as allowing correlation between different mapping techniques.

Cardiac Catheterization

Screening for neuroblastoma in the northern region of England. Laboratory aspects.

Our pilot study for neuroblastoma screening started in 1986. The study has progressed through several phases, with use of several analytical methods to a procedure based primarily on the use of automated gas chromatography mass spectrometry. The northern region of England has a relatively static population of approximately 3.5 million, with an annual birth rate of 41,000. The region consists of 16 administrative health districts. In 4 years, we have screened 20,829 infants from four health districts. In this program, we screen all children at 6 months of age. A urine sample is collected on filter paper by a health visitor, either at the time of the infant's routine clinic visit or during the health visitor's follow-up visit at home. In the laboratory, the sample is dried and processed for analysis of homovanillic acid (HVA) and vanillylmandelic acid (VMA), using a benchtop Hewlett Packard gas chromatograph mass spectrometer. The results are related to the creatinine content of the urine. Using cut-off limits of 39 micrograms/mg of creatinine for HVA and 25 micrograms/mg of creatinine for VMA, 2,537 infants (12.2%) required a second paper sample and 527 infants (2.5%) were observed with a liquid urine collection. Of these, the conditions of nine infants with elevated levels of HVA or VMA were investigated clinically for the possible presence of neuroblastoma. Two infants were found to have neuroblastoma; the other seven showed no evidence of tumor. In addition, there were three children who, when screened at 6 months of age, had normal levels of HVA and VMA but in whom neuroblastoma subsequently developed.

Biomarkers, Tumor

A pilot study of screening for neuroblastoma in the north of England.

A pilot study has been carried out to assess the feasibility of screening for neuroblastoma in 6-month-old infants in the north of England. A total of 20,829 infants were screened. Two true-positive cases were found, along with eight false-positive and three false-negative cases. It was shown that the concentrations of catecholamine metabolites in the urine are dependent on the creatinine content; centiles have been established to allow this relationship to be taken into account. Five of the eight false-positive cases would have been correctly assessed as normal if the new centiles had been used. Preliminary results lend support to the need for a well-designed study of neuroblastoma screening to be carried out, with death from this disease as the only end point.

England

max encodes a sequence-specific DNA-binding protein and is not regulated by serum growth factors.

Max and c-Myc proteins, produced in bacteria, were studied for DNA-binding activity using the electrophoretic band-shift assay (EMSA). Both Max homodimers and c-Myc-Max heterodimers selected the same sequence CA(C/T)GTG from an initial pool of 10(6) DNA molecules. From the pool of sequence-specific binding sites, the palindromic site (CACGTG) was preferentially selected over the CATGTG site using two different degenerate oligonucleotide probes. max expression is identical in myc-induced tumor cell lines relative to other cells. Furthermore, max expression is constant in both confluent and serum-stimulated A31 fibroblasts, in contrast to c-myc expression, which is barely detectable in confluent fibroblasts and induced 20-fold by serum growth factors. Based on recognition of the same DNA sequence by Max and c-Myc-Max complexes and differential expression of the two genes, we propose that Max homodimers and c-Myc-Max heterodimers may bind to a common set of cellular target genes.

Base Sequence

Locked-in syndrome: a team approach.

A person who suffers brainstem infarction resulting in quadriplegia, lower cranial nerve paralysis and mutism with intact cortical function may survive in a condition aptly termed "locked-in syndrome" (LIS). Literally a mind locked inside the body, the person remains fully aware without the ability to move or communicate. Because of the awesome nature of the condition and its likely permanent basis, family and staff may feel hopeless and incapacitated when planning care. Anatomical findings, etiologies, manifestations and outcomes are discussed in the literature but offer few suggestions for case management. Our clinical team has worked intensively with several LIS patients and has found that an interdisciplinary team approach is essential for providing creative patient care.

Adult

Neonatal meningitis.

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Bacterial Infections

A prospective study to evaluate the dose of vitamin D required to correct low 25-hydroxyvitamin D levels, calcium, and alkaline phosphatase in patients at risk of developing antiepileptic drug-induced osteomalacia.

The dose of vitamin D3 required to maintain normal serum 25-hydroxyvitamin D levels in epileptic patients was evaluated in a prospective study. Patients were divided into two groups, comprising 14 institutionalized and 18 non-institutionalized subjects; they were taking carbamazepine, phenytoin and phenobarbitone, alone or in combination. The study was divided into a dose titration stage and a further period of assessment on a fixed dose after attainment of normal serum 25-hydroxyvitamin D levels. Seventeen of the 18 non-institutionalized patients achieved normal levels over a period of 12 months; the remaining patient became normal after 15 months. The dose required to achieve normal levels ranged from 400 to 4000 IU/day; three patients required less than 2400 IU vitamin D3, 12 required 2400 IU and three required greater than 2400 IU. All institutionalized patients achieved normal levels over a period of 12 months; six patients required less than 2400 IU, six required 2400 IU and two required greater than 2400 IU vitamin D3. Raised alkaline phosphatase levels occurred in 11 patients, and reverted to normal in six patients during the initial return of 25-hydroxyvitamin D levels to normal. During the second 12 months, when patients were taking a fixed dose of vitamin D3, alkaline phosphatase increased in five patients who had achieved normal levels. During this phase normal 25-hydroxyvitamin D levels were not maintained in five patients. There was a significant seasonal variation of 25-hydroxyvitamin D levels institutionalized patients, being highest in June and lowest in December. Our findings show that while there was a wide range in the dose required to achieve normal serum 25-hydroxyvitamin D levels--between 400 and 4000 IU/day--78 per cent of patients responded to a dose of 2400 IU/day.

Adolescent

Relative growth and maturation of axon size and myelin thickness in the tibial nerve of the rat. 1. Normal animals.

Morphometric observations have been made on the medial plantar division of the tibial nerve (MPD) and on the motor branches of the tibial nerve to the calf muscles (MBC) in rats ranging in age from weaning (3 weeks) to 12 months. Axon size, assessed by measurements of circumference and cross-sectional area, increased rapidly until 3 months with further slight increases between 3 and 9 months and a slight fall between 9 and 12 months. Axon size distributions were unimodal throughout in the MPD but bimodal for the MBC except at 3 weeks. Distributions of myelin thickness were bimodal throughout for both nerves. Scatter plots of g ratios (axon diameter:total fibre diameter) confirmed the presence of two fibre populations: a group of small fibres with relatively thin myelin sheaths, and a group of larger fibres within which sheath thickness was relatively less on the larger than on the smaller axons. These two fibres populations were less easily separable in the MBC than in the MPD nerves. These results document morphometrically the normal growth changes in the rat tibial nerve and also provide control data for the analysis of the effects of experimental procedures on the growth and maturation of peripheral nerve fibres.

Aging

Relative growth and maturation of axon size and myelin thickness in the tibial nerve of the rat. 2. Effect of streptozotocin-induced diabetes.

The relative changes in the growth and maturation of axon size and myelin thickness were studied in the medial plantar division of the tibial nerve in the lower leg and in the motor branches of the tibial nerve to the calf muscles in rats in which diabetes mellitus had been induced with streptozotocin at the time of weaning. Observations were made at 6 weeks and 3, 6, 9 and 12 months of diabetes for comparison with age-matched controls. Similar changes were observed in both nerves. Growth in body weight and skeletal growth was severely retarded from the time of induction of diabetes but at the 6-week stage axon size was not reduced, suggesting that neural growth may initially be relatively protected. At later stages axon size was consistently reduced in the diabetic animals as compared with the controls and showed an absolute reduction at 12 months, as compared with 9 months, that was greater than in the controls. Myelin thickness became reduced earlier and was more severely affected than axon size so that the fibers were relatively hypomyelinated. The myelin changes were greater in larger than in smaller fibers. The index of circularity of axons was reduced in the diabetic nerves. These results show that induction of diabetes in prepubertal rats produces effects on peripheral nerve fibers which differ from those resulting from diabetes induced in adult animals. The effects also differ between large and small nerve fibres. These observations may explain some of the disparate findings obtained in previous studies on experimental diabetes in rats.

Animals