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Biomedical subjects

N Morton

Publications and source records attributed to N Morton.

At least 37 records · Page 2Linked to original sources

Episodic memory dysfunction during sodium amytal testing of epileptic patients in relation to posterior cerebral artery perfusion.

The effect of filling of the posterior cerebral artery (PCA) on memory performance during the intracarotid sodium amytal test (IAP) was investigated in 57 patients with unilateral temporal epileptic seizure foci under consideration for surgical therapy. Memory functioning was tested following injection of the internal carotid artery contralateral and ipsilateral to the side of seizure focus. In both cases, patients with PCA filling observed using conventional angiography showed a greater memory deficit, although this effect was more robust with contralateral injections. In a subsample of patients with left hemisphere dominance for language, the effect of PCA filling on memory performance was only significant when the right hemisphere was injected. The implications of these findings are discussed in terms of the validity of the IAP test and the different factors that need to be taken into account when interpreting IAP memory performance.

Adult↗

APC intragenic haplotypes in familial adenomatous polyposis.

Genetic epidemiological studies are useful for the knowledge of the association of markers and genes involved in diseases. In the present work, we studied the frequency of four adenomatous polyposis coli intragenic RFLP markers often used in risk evaluation in a population of 10 familial adenomatous polyposis patients from 10 unrelated Portuguese familial adenomatous polyposis families not sharing the same mutation, and in a population of 55 unrelated healthy Portuguese volunteers. We compared the frequency obtained to normal and affected populations and to results already reported in other populations. We observed allelic frequencies for the Portuguese population that agree with the published ones. The intragenic polymorphisms show strong gametic disequilibrium suggesting little recombination between them. We observed haplotype frequencies significantly different in patients and controls. The gametic disequilibrium may be due to a common founder for a proportion of apparently unrelated probands.

Adenomatous Polyposis Coli↗

A role for FGF-8 in the initiation and maintenance of vertebrate limb bud outgrowth.

BACKGROUND: The outgrowth of the vertebrate limb bud is the result of a reciprocal interaction between the mesenchyme and a specialized region of the ectoderm, the apical ectodermal ridge (AER), which overlies it. Signals emanating from the AER act to maintain the underlying mesenchyme, called the progress zone, in a highly proliferative and undifferentiated state. Removal of the AER results in the cessation of limb bud growth, thus causing limb truncation. The best candidates for this AER-derived signal are members of the fibroblast growth factor (FGF) family, in particular FGF-4, which can maintain limb bud outgrowth following removal of the AER. However, FGF-4 is only expressed after considerable outgrowth has occurred and a well-developed limb bud has formed, and then only in the posterior part of the AER. Likewise, the other FGFs studied to date are not candidates for this activity. RESULTS: We report evidence that a recently identified member of this family, FGF-8, is expressed in the ectoderm of the prospective limb territory prior to morphological outgrowth of the limb bud in both mouse and chick. Thereafter, expression is maintained throughout the AER during limb development. We have produced and purified the FGF-8 protein, and shown that it will substitute for the AER in maintaining limb bud outgrowth in mouse embryos from which the AER has been surgically removed. FGF-8 does not, however, maintain expression of the sonic hedgehog gene. CONCLUSIONS: These results indicate that FGF-8 is an AER-derived mitogen that stimulates limb bud outgrowth. Moreover, our data suggest that FGF-8 may also be an ectodermally derived mitogen that stimulates the onset of limb bud outgrowth (budding) in the absence of a morphological AER, and indicate the possible involvement of FGF-8 in the establishment of the limb field.

Amino Acid Sequence↗

Positive association in the absence of linkage suggests a minor role for the glucokinase gene in the pathogenesis of type 2 (non-insulin-dependent) diabetes mellitus amongst south Indians.

Mutations of the glucokinase gene have been implicated in the development of glucose intolerance in pedigrees with maturity-onset diabetes of the young. However, the contribution of the glucokinase gene to the aetiology of common Type 2 (non-insulin-dependent) diabetes mellitus is uncertain. We have studied the role of the glucokinase gene in the pathogenesis of Type 2 diabetes in South Indians, using both population-association and linkage methodology. A pair of CA-repeat sequences (GCK(3') and GCK(5')) straddling the glucokinase gene were employed as markers, each subject being typed using the polymerase chain reaction and polyacrylamide gel electrophoresis. Comparisons of allele frequencies at these markers were made between 168 Type 2 diabetic subjects and 70 racially-matched control subjects. No differences in allele frequencies were apparent at the GCK(5') marker; however, there were significant differences in allele frequencies at the GCK(3') marker between the Type 2 diabetic subjects and control subjects (chi 2 = 11.6, df = 3, p = 0.009) with an increase of the z allele (78.0% vs 66.4%) and a decrease of the z + 2 allele (13.7% vs 25.0%) amongst the diabetic subjects. Linkage between glucose intolerance and the glucokinase gene was studied in 53 nuclear pedigrees under a variety of genetic models. Linkage was excluded (lod score < -2) at a recombination fraction of zero under five of the ten models used and highly unlikely (-2 < lod score < -1) under the others. The combination of positive association and negative linkage suggests that glucokinase acts as a minor gene influencing the development of Type 2 diabetes within this population.

Adult↗

Despite intensive efforts, egg-related salmonellosis outbreaks continue.

Reports of gastrointestinal disease, traced to bacterial contamination of foods, have recently increased in number and scope. Escherichia coli, a variety of Salmonella species and other bacterial pathogens have been isolated in many diagnoses in various parts of the country. Food trace-backs have implicated a variety of uncooked, cooked and under-cooked food sources, including cantaloupes, apple cider, ground beef, cow's milk, poultry products and even fresh, shell-in-tact table eggs. This report is intended to update the reader on control measures currently implemented for the production, processing and distribution of table eggs, specifically to control Salmonella enteritidis.

Eggs↗

Transmission of breast cancer--a controversy resolved.

The Danish breast cancer data collected by Jacobsen (1946) have been reanalysed using morbid risks which incorporate mortality due to breast cancer. A dominant gene is favoured for familial breast cancer, supporting the conclusions of Williams & Anderson (1984) and later authors. Neglect of specific mortality does not greatly alter estimates of gene frequency and displacement, but the evidence for a major gene is inflated. No evidence for heterogeneity was found. Earlier claims of non-Mendelian transmission are in error since we have discovered that transmission probabilities are not correctly implemented in the computer program POINTER. Cases with bilateral breast cancer and males with breast cancer all belonged to families favouring a major gene. Of the cancer sites frequently reported to be associated with familial breast cancer, only ovarian cancer is significant in this material.

Breast Neoplasms↗

Pharmacokinetic model driven infusion of propofol in children.

A computer controlled infusion device for propofol was used to induce and maintain general anaesthesia in 20 children undergoing minor surgical procedures. The device was programmed with an adult pharmacokinetic model for propofol. During and after anaesthesia, blood samples were taken for measurement of propofol concentrations and it was found that the values obtained were systematically overpredicted by the delivery system algorithm. New pharmacokinetic microconstants were derived from our data which reflected more accurately the elimination and distribution of propofol in a prospective study involving another 10 children.

Adult↗

Von Hippel-Lindau disease: a genetic study.

Genetic aspects of von Hippel-Lindau (VHL) disease were studied in familial and isolated cases. Complex segregation analysis with pointers was performed in 38 kindreds with two or more affected members. Dominant inheritance with almost complete penetrance in the highest age classes (0.96 at 51 to 60 and 0.99 at 61 to 70 years) was confirmed and there was no evidence of heterogeneity between families ascertained through complete and incomplete selection. The point prevalence of heterozygotes in East Anglia was 1.89/100,000 (1/53,000) persons with an estimated birth incidence of 2.73/100,000 (1/36,000) live births. Reproductive fitness was 0.83. Direct and indirect estimates of the mutation rate were 4.4 (95% CI 0.9 to 7.9) x 10(-6)/gene/generation and 2.32 x 10(-6)/gene/generation respectively. There was no significant association between parental age or birth order and new mutations for VHL disease.

Adult↗

Leukaemia and transient leukaemia in Down syndrome.

We have reviewed 215 published cases of leukaemia and transient leukaemia in Down syndrome. There is an over-representation of mosaic trisomy 21, possibly the result, at least in part, of a survival effect. The most intriguing observation is a bimodal distribution of maternal age, produced largely because cases with true leukaemia have a significantly higher maternal age than cases with transient leukaemia (33.5 versus 29.5 years). In conjunction with evidence that meiosis I nondisjunction is infrequent in transient leukaemia, this suggests different mechanisms for the etiology of leukaemia and transient leukaemia, and favours a locus predisposing to transient leukaemia proximal to the centromere on the long arm of chromosome 21.

Adolescent↗

Mode of processing and hemisphere differences in the judgement of musical stimuli.

The relationship between processing strategy and ear asymmetry was examined in two experiments in which subjects were required to make judgements about monoaurally presented musical chords. In the first experiment, subjects without musical training showed a significant left ear advantage while in those with musical training a significant shift towards a right ear advantage was observed. Performance on the Embedded Figures Test (EFT) suggested a strong relationship between analytic processing style and right ear advantage which was significant in the musician groups. The effect of musical training status on ear asymmetry continued to be significant when the scores were adjusted for analytic processing. There was also a clear relationship between self-reported listening strategies and direction of ear asymmetry, with musicians generally reporting a much greater use of analytic strategies. The second experiment failed to demonstrate a significant influence of explicit instructions in how to carry out a chords task on the direction of ear advantages in musically untrained subjects. The results partially confirm earlier studies comparing subjects with and without musical training, and extend them by demonstrating a clear relationship between ear advantage and a separate measure of processing strategy. The findings of the second experiment, however, do not support clearly the hypothesis that differences in ear asymmetry are produced through the use of different processing strategies.

Adolescent↗

Rebound hypertension after discontinuation of transdermal clonidine therapy.

Three (and possibly all four) elderly hypertensive patients who were followed sequentially after discontinuation of transdermal clonidine monotherapy manifested a rapid rise in blood pressure to levels above control (pre- and post-therapy) readings. No signs of an "overshoot" in plasma norepinephrine levels or symptoms of beta-adrenergic overactivity were seen. Such rebound hypertension suggests hypersensitivity to alpha-adrenergic receptor stimulation and could pose a heretofore unreported potential hazard to elderly or otherwise compromised patients who discontinue transdermal clonidine therapy.

Administration, Cutaneous↗

Recovery of blood and bone marrow stem cells following intense chemotherapy and autologous bone marrow transplantation.

Sixteen patients with advanced (stage III) malignant melanoma were treated with escalating doses of intravenous BCNU and melphalan starting at 400 and 35 mg/m2, respectively, and escalating to 1,000 and 110 mg/m2, respectively, combined with autologous marrow transplantation. The duration of granulocytopenia and time to granulocyte recovery was similar in all groups regardless of chemotherapy dose. Platelet recovery was delayed in patients receiving the highest doses of chemotherapy. This study showed that bone marrow colony-forming units in culture took as long as 6 months to recover. This was adequate to bring peripheral blood counts to normal but not to pretreatment levels. These studies indicate that autologous bone marrow transplantation is beneficial in enhancing short-term recovery, but may not be beneficial in the long-term hematopoietic recovery.

Agranulocytosis↗

Transdermal clonidine therapy in elderly mild hypertensives: effects on blood pressure, plasma norepinephrine and fasting plasma glucose.

Twenty patients aged 60-74 years entered a study on the effect of transdermal clonidine (Catapres-TTS) as monotherapy for mild hypertension [diastolic blood pressure (DBP) 90-104 mmHg]. Seventeen patients (85%) had a positive therapeutic response (DBP reduced to less than 90 mmHg or by greater than or equal to 5 mmHg). Patient acceptance was high and side effects mild; however, one-quarter of the patients experienced localized skin reactions. A slight increase in fasting plasma glucose level (mean delta = 20 mg/dl) was consistently observed. Transdermal clonidine led to a sustained decline in plasma catecholamine levels although this effect did not seem to be closely related to the observed decreases in blood pressure. Three out of four evaluable patients had a blood pressure 'overshoot' upon discontinuation of therapy to levels above pretreatment values. Transdermal clonidine appears to be effective and generally well tolerated in the treatment of mild hypertension in the elderly; however, more studies designed to investigate effects on glucose tolerance and the possible existence of a rebound syndrome are needed.

Administration, Topical↗

HLA antigens A, B, C and DR in hay-fever families of similar environmental conditions.

Investigation of 98 members (healthy and affected) belonging to 17 hay-fever families, for clinical picture, total and specific IgE and HLA A, B, C and DR is presented. There was no significant correlation between hay-fever, total or specific IgE and a certain HLA antigen or haplotype. There was, however, an association between hay-fever and same haplotype within 4 of the 17 families.

Adult↗

Treatment of advanced malignant melanoma with high-dose chemotherapy and autologous bone marrow transplantation. Preliminary results--Phase I study.

Thirteen patients with advanced (Stage III) malignant melanoma have been treated with high-dose chemotherapy (nitrogen mustard or a combination of BCNU and melphalan) combined with autologous, nonfrozen, bone marrow transplantation. Three patients (24%) achieved a complete remission and are currently alive and free of disease without further therapy at 26, 60, and 73 weeks. Five patients (38%) achieved partial remissions and five patients (38%) had no response. There was no difference in the response rate to nitrogen mustard and the BCNU-melphalan combination. Severe side effects to nitrogen mustard, however, precluded its further use in this study. The major cause of death in patients was intracerebral metastases, raising the question of prophylactic brain irradiation in future studies. Studies of the recovery rate of peripheral blood neutrophil, platelet, and peripheral blood and bone marrow CFU-C suggest that autologous bone marrow infusion may be of benefit in shortening hematopoietic recovery following intensive chemotherapy.

Adolescent↗