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Biomedical subjects

J McCredie

Publications and source records attributed to J McCredie.

At least 19 recordsLinked to original sources

Intravenous contrast media: use and associated mortality.

OBJECTIVE: To determine the extent of use and mortality associated with peripheral intravenous injections of radiocontrast media. DESIGN: A retrospective study of injection data was made for the three and a half year period from January 1987 to June 1990 using the Health Insurance Commission database and the records of public hospital x-ray departments. Information about deaths associated with the injections was obtained from a survey of all radiologists and from other relevant sources. SETTING AND PARTICIPANTS: The study related to the entire population of New South Wales and the Australian Capital Territory, approximately 6 million people. INTERVENTIONS: Intravenous injections of radiographic contrast medium for computed tomographic scans, intravenous pyelograms and venograms. MAIN OUTCOME: A comprehensive record of intravenous contrast usage and associated mortality in a large community. RESULTS: Between January 1987 and June 1990, 613 581 intravenous injections of radiocontrast media were administered in New South Wales and the Australian Capital Territory. The overall annual incidence of use was estimated to be 2.9% and was markedly age dependent being more than 7% in subjects over 65 years. Eight deaths were documented, representing an overall mortality of 13 per million injections (95% confidence interval [CI], 5.6-25.7). Mortality appeared to be age related being 35 per million (95% CI, 12.7-75.6) in those over 65 years compared with 4.5 per million (95% CI, 0.6-16.4) in those under 65 years. Two of the deaths involved low osmolar contrast media. CONCLUSIONS: Death after injection of intravenous contrast medium is a rare event. There was no evidence that mortality was lower with the newer, low osmolar media than with the older, high osmolar media.

Adverse Drug Reaction Reporting Systems

A spectrum of skeletal anomalies associated with pulmonary agenesis: possible neural crest injuries.

Six cases of unilateral pulmonary agenesis with skeletal and other deformities have been diagnosed in our hospitals. The various pulmonary, spinal, rib and limb anomalies with their possible inter-relationships were examined and described in detail and comparison with previously reported cases was made. It became apparent that the limb abnormalities which most constantly involved hypoplasia of the phalanges of a thumb with varying metacarpal and radial anomalies, were ipsilateral to the pulmonary agenesis in all cases. The spinal deformities involved degrees of failure of segementation of T1-T3 with other vertebrae randomly involved. Rib abnormalities also varied and did not necessarily correspond to the same side as the pulmonary agenesis. The concept of the anomalies all being part of a group of neural crest injuries was then explored.

Abnormalities, Multiple

Neurotomes and birth defects: a neuroanatomic method of interpretation of multiple congenital malformations.

It has been suggested that complexes of multiple congenital malformations, involving limbs and viscera, may be caused by embryonic neural crest injury. Structures supplied by the sensory and autonomic nerves derived from the injured zone of crest would suffer defective development through presumed impairment of neurotrophic influence. Our study aimed to examine this concept by a retrospective analysis of autopsy findings in 27 babies who died of multiple congenital malformations associated with longitudinal limb defects. Sclerotome maps of the segmental sensory innervation of the skeleton were used to analyse the limb defects in terms of their nerve supply. From a review of the literature, the approximate segmental contribution of neural crest to the autonomic innervation of internal organs was ascertained, and thus "viscerotome" diagrams were constructed. Application of sclerotomes and viscerotomes to the data derived from the autopsy reports showed a neuroanatomic correlation in 89% of cases. Interpretation of multiple malformation syndromes is proposed on the basis of neurotomes, or embryonic developmental fields with common regional innervation.

Abnormalities, Multiple

Congenital limb reduction deformities and use of oral contraceptives.

A study of congenital limb deficiencies in two Australian states indicated that use of an oral contraceptive during pregnancy by the mother was associated with an increased risk of limb defect in the child. The study included mothers of 155 children born with absence or reduction of the major long bones during a 12-year period from 1970 onward; 274 mothers with births of normal infants, matched for date of birth and area of residence, made up the control group. Compared with control infants, the case infants were more likely to have been conceived while the mother was using an oral contraceptive, especially when the deformity was a transverse or amputation type. It is too early in our state of knowledge of teratogenic mechanisms to exclude the possible existence of a biologic mechanism that would explain this statistical association.

Abnormalities, Drug-Induced

Congenital limb deficiency: maternal factors in pregnancy.

Maternal factors in pregnancy were examined in a case-control study of 155 children with limb deficiencies (longitudinal and transverse) born 1970-1981 inclusive and 274 matched normal controls. Vomiting of pregnancy was associated with an increased risk of longitudinal limb reduction defects. Gestational bleeding has long been known for its association with perinatal mortality, low birth-weight and prematurity; limb deficiencies have also been noted. In the present study the pattern of bleeding differed between women in the transverse and longitudinal groups, with the possibility of a causal role for bleeding in the aetiology of longitudinal but not transverse defects. There was a significant statistical risk associated with respiratory infections comparable with the reported association of congenital limb deficiency and influenza from Finland.

Adult

The innocent bystander. Doxylamine/dicyclomine/pyridoxine and congenital limb defects.

The antinausea drug combination, doxylamine/dicyclomine/pyridoxine (Debendox or Bendectin [US] ), has been withdrawn from the market because of litigation based upon charges that it causes congenital limb defects. To investigate this allegation, the pregnancy histories of mothers of 155 limb-deficient children, born between 1970 and 1981, have been compared with those of mothers of 273 matched normal controls. There was no significant difference between the pregnancy histories of mothers of case children and those of mothers of control children in respect of reported frequency of morning sickness, the use of doxylamine/dicyclomine/pyridoxine, the date of commencement of its intake, the duration of intake, or its dose. The relative risk of limb deficiency in children of mothers exposed to this drug is estimated to be 1.1 with confidence limits of 0.8-1.5. No risk of congenital limb defects was found to be associated with the use of this drug.

Abnormalities, Drug-Induced

Thalidomide deformities and their nerve supply.

The aim of this study was to test the hypothesis that thalidomide acts upon the embryonic peripheral nervous system rather than upon mesenchyme. Pregnant rabbits were given oral thalidomide (150 mg/kg/day) on Days 7-11 of gestation. Fetuses were removed at laparotomy, under anaesthesia, on Day 29 of gestation. Seven fetuses with partial or total absence of the tibia, five treated fetuses without deformities, and four untreated controls were photographed, radiographed, killed and fixed for histological examination. Sciatic nerves were dissected and transverse sections were taken from an identical site. Total fascicular area, myelinated fibre number, fibre density and diameter distribution were obtained. There was a significant reduction in total fascicular area, and in the number of large diameter fibres in all treated animals. There was a significant depletion of total fibre numbers in deformed fetuses compared with controls. These findings are similar to the quantitative changes described in human adult subjects with thalidomide polyneuropathy, and are consistent with primary axonal degeneration in both instances. It is concluded that thalidomide acts upon embryonic nerves rather than on mesenchyme, and that dysmelic deformities of the limbs are secondary to toxic embryonic neuropathy. It is suggested that skeletal defects result when irreversible damage to the nerves reduces the transverse fascicular area below a critical minimum threshold.

Abnormalities, Drug-Induced

Neural crest ablation and limb morphogenesis.

Left caudal neural crest was ablated by diathermy in 2-day-old chick embryos, to injure the region of sensory sciatic innervation before the appearance of the hind-limb bud. Embryos were fixed immediately, 24 hr and 14 days later, for examination of the effects of the ablation upon neural crest, neural tube, somitic mesoderm, and subsequent limb development. All embryos examined immediately and at 24 hr after ablation showed damage to the left neural crest, but the injury extended deeper into neural fold or tube, across the midline, and into somitic mesoderm. Of 17 chicks which survived to 16 days, 7 had gross deformity of the left leg and 10 had morphologically normal legs. Deformed chicks had a significant reduction in the mass of dorsal root ganglia on the operated side but no reduction in the area of the spinal cord. Operated chicks without limb deformities showed reduction of spinal cord but not of dorsal root ganglia. This suggests that limb morphogenesis may be quantitatively related to neural crest but not to neural tube. This possibility is considered in the light of previous publications. However, the experimental limitation of the diathermy method leaves the final conclusion open to interesting speculation and to future examination by improved experimental design.

Animals

Innervation of the undifferentiated limb bud in rabbit embryo.

The concept that there are no nerves in the limb bud of mammalian embryos prior to differentiation has been re-examined. Rabbit embryos were collected at 260 and 290 hours gestation, which is prior to cartilage formation in the forelimb at 320 hours. Forelimb buds and adjacent neural tube were excised, fixed and embedded for light and electron microscopy. The limb buds were sectioned in two planes by serial 1 micrometer sections and inspected by light microscopy. Bundles of nerve fibres were seen within the proximal third of the limb bud, with distal ramification into adjacent zones of condensing mesenchyme. Electron microscopy confirmed the presence of axons and associated immature Schwann cells. These results demonstrate the existence of an anatomical framework through which a neurotrophic influence might be brought to bear upon mesenchyme prior to early differentiation.

Animals

Melorheostosis and the sclerotomes: a radiological correlation.

Melorheostosis is characterised radiologically by hyperostotic linear densities in bone. These densities have a peculiarly segmental distribution which does not correspond with the anatomical course of blood vessels or mixed nerve roots of the limbs. So far this disbritubion has lacked any valid explanation, although it has been suggested to be a developmental error as a result of an embryonic metameric disturbance. Inman and Saunders in 1944 described a sensory nerve supply to skeletal structures with 'sclerotomes' representing the zones of the skeleton supplied by individual spinal sensory nerves. Radiographs of 30 cases from the Radiological Museum of the Institute of Orthopaedics, London, have been reviewed and an attempt has been made to correlate the sclerosing lesions with the sclerotomes. The investigation was handicapped by paucity of films and clinical information, but in 19 cases the skeletal abnormalities were considered to correspond with a single sclerotome or part thereof. These studies were convincing when films of an affected hand or foot were available. In the remaining 11 cases multiple sclerotomes appeared to be involved and the clinical manifestations were correspondingly more severe. It is proposed that melorheostosis may be the late result of a segmental sensory nerve lesion, to account for its sclerotomal distribution. The association with linear scleroderma is discussed, since it has been suggested that these cutaneous lesions are related to the same nerve segment. Eight cases showed paraarticular ossification of soft tissues which may be related to involvement of a corresponding myotome.

Adult