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Biomedical subjects

J Doyle

Publications and source records attributed to J Doyle.

At least 19 recordsLinked to original sources
PubMed1992

Characterization and molecular analysis of nondisjunction in 18 cases of trisomy 21 and leukemia.

We recently began a cytogenetic and molecular study of nondisjunction in leukemic Down syndrome individuals to determine whether the mechanism by which the extra chromosome 21 originates predisposes the individual to leukemia. In the present report, we summarize our observations on 18 patients with trisomy 21 and acute or transient leukemia, including 11 patients with acute lymphocytic leukemia, three with acute myeloid leukemia, one with B-cell lymphoma, one with acute megakaryoblastic leukemia, and two with transient leukemia. Results of DNA marker studies of the parental origin of the extra chromosome 21 indicated that 16 of the 18 cases (89%) were maternally derived, a percentage similar to that seen among nonleukemic Down syndrome patients. We noted that most leukemic Down syndrome patients had one locus or more in which parental heterozygosity was maintained in the trisomic individual, indicating a meiotic rather than a mitotic origin for the trisomy.

Adolescent↗
PubMed1992

Augmentation of the accuracy of percutaneous electrode implantation by using a modified arthroscope to guide insertion.

Using a clear polyvinyl fluoride sheath over an arthroscope, inserted through a 1-cm stab incision, we have demonstrated the feasibility of visualizing the sciatic nerve and its branches in the feline model. The purpose of this technique is to allow visual control, without a large surgical incision, of the exact site of implantation of electrodes used for functional neuromuscular stimulation. Currently, we determine the optimum site for percutaneous electrode implantation by stimulating the target nerve or muscle with a 26-gauge probe needle until maximal response is obtained. This method lacks accuracy because there is no direct visualization of the location of the tip of the probe or the electrode. With the new technique, we identified nerves by their distinctive vascular markings and we followed the nerves with minimal disruption of the soft tissues. In this way, individual branches were identified and targeted for instrumentation, allowing selective stimulation of specific muscle groups.

Animals↗
PubMed1992

Candoxatril, a neutral endopeptidase inhibitor: efficacy and tolerability in essential hypertension.

OBJECTIVE: To examine the efficacy and tolerability of the neutral endopeptidase inhibitor, candoxatril (UK 79,300) as monotherapy in essential hypertension. DESIGN: Double-blind, placebo-controlled, parallel-group study of 28 days' duration. SETTING: Three hospital outpatient departments participating in the Glasgow Blood Pressure Clinic (Glasgow, UK). PATIENTS: Forty patients with essential hypertension with diastolic blood pressure 95-114 mmHg after a 2-4 week placebo run-in period. INTERVENTIONS: Twenty-eight days' treatment with candoxatril 200 mg twice daily or matching placebo capsules. MAIN OUTCOME MEASURES: Changes in supine and erect blood pressure, and volunteered side effects during double-blind treatment. RESULTS: When measured at the end of the dose interval, the fall in supine blood pressure following candoxatril was not significantly greater than that after placebo. Compared with placebo, a significant effect for candoxatril was seen only for systolic blood pressure in the erect posture; the fall in erect diastolic blood pressure attributable to candoxatril was insignificant. Median plasma atrial natriuretic peptide concentration increased in candoxatril-treated patients and decreased in the placebo group. No stimulation of the renin-aldosterone axis was seen. There was a non-significant trend towards greater urinary excretion of cyclic guanosine monophosphate after candoxatril. Mean plasma concentration of candoxatril at (UK 73,967--the active metabolite of candoxatril) reached a peak of 1010 +/- 437 ng/ml after acute dosing, and 1328 +/- 405 ng/ml after chronic dosing; time to maximum concentration was 2 h in each case. Candoxatril was well-tolerated; numbers of adverse events did not differ between active treatment and placebo. CONCLUSIONS: Although atrial natriuretic peptide levels were significantly increased, candoxatril 200 mg twice daily for 28 days did not produce a clinically relevant fall in blood pressure. Our results cast some doubt upon the role of neutral endopeptidase inhibition in the treatment of unselected hypertensive patients.

Antihypertensive Agents↗
PubMed1992

Their future in your hands. Infant heart transplantation.

Recent advances in techniques have meant that infant heart transplant programmes are more assured of success. This article describes one such programme in America, and highlights the ethical and nursing dilemmas involved.

Academic Medical Centers↗
PubMed1992

Effect of functional neuromuscular stimulation on anterior tibial compartment pressure.

Intramuscular pressures in the anterior tibial compartment were measured in five paraplegic subjects who used functional neuromuscular stimulation (FNS) by percutaneous intramuscular electrodes for exercise and walking. Effects of two types of stimulation pattern were tested: continuous stimulation for 15 minutes and cyclic stimulation for 60 minutes, with duty cycle and stimulation levels similar to that used in walking. Resting compartment pressure levels before stimulation were less than 7 mm Hg in all subjects. Continuous stimulation at maximum parameters produced compartment pressure levels up to 116 mm Hg, but these were not sustained. They decreased to below 40 mm Hg within one minute in all except one subject, who was having repeated spasms. Cyclical stimulation raised mean muscle pressure to between 70 and 80 mm Hg in two patients. Muscle contraction pressure increased to 153 mm Hg in one patient, but was below 100 mm Hg in all patients after two minutes, except during spasms. Muscle relaxation pressure stayed below 30 mm Hg in four subjects. After stimulation, the pressure returned to prestimulation levels within 15 minutes. These results suggest that FNS subjects are not in danger of developing compartment syndrome. Nevertheless, occasional testing of compartment pressures is recommended, especially when activity levels rise significantly.

Adult↗
PubMed1991

Atrial natriuretic peptide: a vasodilator of the fetoplacental circulation?

Paired maternal and fetal atrial natriuretic peptide concentrations were measured in 62 percutaneous umbilical blood samplings performed principally for the assessment and treatment of rhesus isoimmunization. Pretransfusion fetal atrial natriuretic peptide levels were significantly higher than maternal atrial natriuretic peptide levels (median 117 pg/ml vs median 32 pg/ml; p less than 0.001); paired pretransfusion fetal and maternal atrial natriuretic peptide samples showed a weak correlation with each other (R2 = 17%; p = 0.002). Fetal atrial natriuretic peptide levels correlated inversely with hematocrit (R2 = 14%; p = 0.003), but not with albumin or gestational age. Paired pretransfusion and posttransfusion (median = 134 pg/ml) fetal atrial natriuretic peptide levels (n = 38) showed a significant rise after transfusion (p less than 0.001); this rise was related to the percentage of fetoplacental blood volume transfused (R2 = 33%; p = 0.035). In a subgroup of 26 procedures, change in fetal atrial natriuretic peptide levels was weakly correlated with transient reductions in the Doppler systolic/diastolic ratio of the umbilical artery (R2 = 14%; p = 0.07). These data support work in animals that indicate a role for atrial natriuretic peptide in the human fetus, but these data do not confirm that atrial natriuretic peptide modulates fetoplacental vascular impedance in the human fetus.

Atrial Natriuretic Factor↗
PubMed1991

Lentinginous dysplastic naevi in the elderly: a potential precursor for malignant melanoma.

Seventy-seven skin biopsies diagnosed histologically as lentiginous junctional naevi from individuals aged over 60 years were reviewed. Seventy-three specimens showed a primarily nested pattern with disordered arthitecture concentrated within the rete ridges conforming to the pathology of a lentiginous dysplastic naevus. In 28 biopsies this was combined with a melanoma in situ. The latter was reflected by a focal loss of the rete ridge system, confluent melanocytic hyperplasia and single cell invasion of the epidermis by atypical malanocytes. Four biopsies showed lentiginous junctional naevi with only isolated naevus cell nests without a disordered architecture or cellular atypia. Thirty-seven of the 57 naevi in men were located on the back in contrast to 5 of the 20 women. In women the lower limb was the most frequent site with 8 of the 20 lesions originating at this site in contrast to 1 of the 57 men. The pathological diagnosis of dysplastic lentiginous naevi in the elderly needs to be recognised as having a high association of melanoma-in-situ changes.

Aged↗
PubMed1991

Four different mutations in codon 28 of alpha spectrin are associated with structurally and functionally abnormal spectrin alpha I/74 in hereditary elliptocytosis.

Hereditary elliptocytosis (HE) Sp alpha I/74 is a disorder associated with defective spectrin (Sp) heterodimer self-association and an abnormal tryptic cleavage of the 80-kD alpha I domain of Sp resulting in increased amounts of a 74-kD peptide. The molecular basis of this disorder is heterogeneous and mutations in codons 28, 46, 48, and 49 (codons 22, 40, 42, and 43 in the previous nomenclature which did not include the six NH2-terminal amino acids) have been reported. In this study we present data on seven unrelated HE Sp alpha I/74 kindred from diverse racial backgrounds in whom we identified four different mutations all occurring in exon 2 of alpha Sp at codon 28. Utilizing the polymerase chain reaction we established a CGT----CTT; Arg----Leu 28 mutation in one kindred of Arab/Druze origin. In two unrelated white kindred of English/European origin the substitution is CGT----AGT; Arg----Ser 28 and in two apparently unrelated white kindred from New Zealand, the mutation is CGT----TGT; Arg----Cys 28. Finally, in one American black kindred and in a black kindred from Ghana the mutation involves CGT----CAT; Arg----His 28. Allele specific oligonucleotide hybridization confirmed that the probands are heterozygous for the respective mutant alleles. All four point mutations abolished an Aha II restriction enzyme site which allowed verification of linkage of the mutation with HE Sp alpha I/74. Our results imply that codon 28 of alpha Sp is a "hot spot" for mutations and also indicate that Arg 28 is critical for the conformational stability and functional self association of Sp heterodimers.

Base Sequence↗
PubMed1990

The atriopeptidase inhibitor UK 69,578 increases atrial natriuretic factor and causes a natriuresis in normal humans.

The endopeptidase EC 3.4.24.11 (atriopeptidase) degrades atrial natriuretic factor (ANF). Intravenous administration of UK 69,578 (0.025 to 10.0 mg/kg), a new specific atriopeptidase inhibitor, in 16 normal volunteers produced a two- to three-fold rise in endogenous ANF. Peak levels were reached within 2 h declining to control values by 8 h. The rise in ANF was associated with an increase in urine volume and mean urinary sodium excretion rose from 64.9 mmoles/8 h after placebo to 116.1 mmoles/8 h after 10 mg/kg UK 69,578. Despite the natriuresis, plasma active renin concentration was suppressed for up to 8 h. We conclude that inhibition of the endopeptidase EC 3.4.24.11 in humans elevates endogenous ANF and causes a natriuresis and may offer a novel therapeutic approach to the treatment of hypertension and cardiac failure.

Adult↗
PubMed1977

Preserved scleral allografts in periodontal defects in man. II. Histological evaluation.

1. The scleral grafts appeared to be well accepted as there were no signs of antigenicity or untoward reactions. 2. The gingival connective tissue, periodontal ligament and the periosteum were observed intertwined with sclera at the interface. 3. Sclera was invaded by host fibroblasts, capillaries, and appeared in some areas to be raplaced by a dense connective tissue. 4. Areas of cementogenesis could be observed in all specimens. 5. There were no signs of osteogenesis within the scleral grafts. 6. The alveolar crest appeared relatively nonreactive to sclera. 7. There were no signs of external root resorption or ankylosis. 8. Sclera may be able to be used to fill in osseous craters, other periodontal defects and as a scaffolding in conjunction with osseous grafts. This requires further investigation. 9. Sclera may possibly be used in areas where there was loss of gingival contour or need for ridge augmentation.

Alveolar Process↗
PubMed1976

Dermatology in hospital practice.

Modern hospital facilities have proved of great value in the management of the more difficult problems presenting to dermatologists. In a series of 100 consecutive patients admitted to hospital, four died, at least one out of every three was found to have undiagnosed internal disease and the average time to gain a remission was three weeks after outpatient treatment had proved unsuccessful over an average of six months.

Hospitalization↗