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Biomedical subjects

K McDonald

Publications and source records attributed to K McDonald.

At least 55 records · Page 3Linked to original sources

Improved preservation of ultrastructure in difficult-to-fix organisms by high pressure freezing and freeze substitution: I. Drosophila melanogaster and Strongylocentrotus purpuratus embryos.

In this study, we have applied the techniques of high pressure freezing and freeze substitution to embryonic cell types which are usually difficult to fix properly for electron microscopy. In both Drosophila and Strongylocentrotus purpuratus, we see improved preservation of both membrane systems and cytoskeleton when compared to published results on the same cells using conventional electron microscope (EM) fixation methods. Finally, we have seen that postembedding labelling of sections is possible even after light osmium fixation during freeze substitution.

Animals↗

The ultrastructure of the connective tissue matrix of skin and cartilage after high-pressure freezing and freeze-substitution.

Studies designed to investigate the ultrastructure of the connective tissue matrix have historically relied on chemical fixatives to stabilize tissue microarchitecture. However, conventional fixatives are not completely effective in retaining many matrix constituents, including proteoglycans. Fixative recipes have been modified to include agents that retain proteoglycans, but they precipitate the glycosaminoglycan moiety into electron-dense granules and therefore do not preserve native microstructure. To avoid the structural artifacts introduced by aqueous fixatives, we prepared cartilage and skin by a cryostabilization procedure that included high-pressure freezing and freeze-substitution. Although similar approaches have been applied previously for study of connective tissue, our results and interpretation of matrix structure are significantly dissimilar. In optimally preserved areas of cartilage, collagen fibrils are continually surrounded by a densely staining sol. Empty fluid spaces are absent. In less optimally preserved areas, artifacts are noted and described, including a network that mimics the expected structure of proteoglycan. Similarly, the dermal matrix of human skin contains a preponderance of densely staining material that almost fills the voids commonly seen after aqueous fixation. Decorin, immunolocalized to the surface of dermal collagen fibrils, appears to be retained after this procedure.

Animals↗

Distribution of tudor protein in the Drosophila embryo suggests separation of functions based on site of localization.

Mutations in the tudor locus of Drosophila affect two distinct determinative processes in embryogenesis; segmentation of the abdomen and determination of the primordial germ cells. The distribution of tudor protein during embryogenesis, and the effect of various mutations on its distribution, suggest that tudor protein may carry out these functions separately, based on its location in the embryo. The protein is concentrated in the posterior pole cytoplasm (germ plasm), where it is found in polar granules and mitochondria. Throughout the rest of the embryo, tudor protein is associated with the cleavage nuclei. Mutations in all maternal genes known to be required for the normal functioning of the germ plasm eliminate the posterior localization of tudor protein, whereas mutations in genes required for the functioning of the abdominal determinant disrupt the localization around nuclei. Analysis of embryos of different maternal genotypes indicates that the average number of pole cells formed is correlated with the amount of tudor protein that accumulates in the germ plasm. Our results suggest that tudor protein localized in the germ plasm is instrumental in germ cell determination, whereas nuclear-associated tudor protein is involved in determination of segmental pattern in the abdomen.

Animals↗

Effects of kinesin mutations on neuronal functions.

Kinesin is believed to generate force for the movement of organelles in anterograde axonal transport. The identification of genes that encode kinesin-like proteins suggests that other motors may provide anterograde force instead of or in addition to kinesin. To gain insight into the specific functions of kinesin, the effects of mutations in the kinesin heavy chain gene (khc) on the physiology and ultrastructure of Drosophila larval neurons were studied. Mutations in khc impair both action potential propagation in axons and neurotransmitter release at nerve terminals but have no apparent effect on the concentration of synaptic vesicles in nerve terminal cytoplasm. Thus kinesin is required in vivo for normal neuronal function and may be active in the transport of ion channels and components of the synaptic release machinery to their appropriate cellular locations. Kinesin appears not to be required for the anterograde transport of synaptic vesicles or their components.

Action Potentials↗

Rehabilitation of burned patients with bilateral above-knee amputations.

Bilateral above the knee amputations occur rarely in the seriously burned population. In a 6-month interval, two patients were treated in our Burn Center whose trauma necessitated bilateral above-knee amputations. This led us to review our experience with such cases. A review of 5018 patients treated over a 28-year period identified six patients over a 20-year period who had bilateral above-knee amputations, four of whom survived. These patients were found to have large and deep burns, concomitant injuries and a number of complications. Recovery was time consuming and costly. Physical therapists were challenged to create adaptations of traditional methods to meet the rehabilitation needs of these patients. The patients who survived remain wheelchair bound and unemployed, but are socially active, appear relatively well adjusted and report themselves satisfied with their lives. During a period of time when technological advances in medicine are ensuring survival of victims of massive trauma, questions are raised concerning the advisability of resuscitation. Knowledge gained in the treatment of these patients who are both burned and have had bilateral above-knee amputations can be reassuring to care providers with limited experience with such massive injury.

Adult↗

Cardiac catheterisation with 5 French catheters.

From the beginning of November 1987 to the end of January 1989, 526 coronary arteriograms and left ventricular angiograms were performed with 5 French coronary catheters. In 448 (85%) patients diagnostic pictures were obtained with three standard types of 5 French catheters (No 4 Judkins): that is, left coronary, right coronary, and pigtail catheters. In 60 patients (11.4%) various other 5 French catheters were required to complete the study. In nine patients (1.7%), a 7 or 8 French catheter was used. Major complications causing cardiac arrest or requiring urgent operation developed in five patients. Sixty two patients (11.77%) had minor complications that required sublingual nitrates or a single bolus of atropine, or developed a haematoma that did not need intervention or had a mild reaction to the contrast material. Complications of moderate severity developed in 17 patients (3.2%): severe chest pain, arrhythmia requiring a temporary pacemaker, contrast reaction associated with hypotension, haematoma requiring blood transfusion, or a transient ischaemic episode. There were no deaths. 5 French catheters were used for routine coronary angiography and left ventriculography in 98.3% of patients. There were no major complications related to femoral artery puncture. The routine use of 5 French coronary catheters should increase the feasibility of safe coronary angiography in outpatients and should reduce the cost of this investigation.

Angina Pectoris↗

Plasma porphyrins in chronic renal failure.

Using a quantitative sensitive HPLC fluorometric assay for the measurement of plasma and urine porphyrins, we have calculated the renal clearance of uro- and coproporphyrin in normal volunteers and in patients with congenital erythropoietic porphyria and hereditary coproporphyria (HCP). In patients with porphyria cutanea tarda (PCT), only uroporphyrin clearance was calculated. Plasma porphyrin concentrations were measured in patients with chronic renal failure (CRF). All our CRF patients on haemodialysis (10) had raised plasma uroporphyrin, 4 had raised plasma heptacarboxyporphyrins and 2 had raised plasma coproporphyrin, unchanged by haemodialysis. CRF patients with raised uroporphyrins and 7-carboxyporphyrins could be distinguished from PCT in patients with normal renal function, by their higher uro/7-carboxyporphyrin ratio (8.0 vs. 1.7). Renal clearance of coproporphyrin was much greater in HCP than in any of the other groups studied. Since coproporphyrin clearance was less than creatinine clearance in most normal subjects, and because 2 patients with CRF had raised plasma coproporphyrin concentrations, we argue that the kidney is probably not a major source of coproporphyrin, as previously reported. Furthermore, the variability and degree of abnormality in plasma porphyrins in CRF would suggest caution in diagnosing chronic porphyria in patients with renal impairment.

Adult↗

Heart block as a predictor of in-hospital death in both acute inferior and acute anterior myocardial infarction.

We investigated the relationship between atrioventricular block and in-hospital mortality in 705 successive patients admitted with a first Q-wave myocardial infarction of the anterior or inferior wall. Second- or third-degree atrioventricular block developed in 61 (8.6 per cent) patients and was more frequent in inferior (12.4 per cent) than anterior infarctions (4.9 per cent). A multiple logistic regression identified three factors which were independently correlated with block: inferior infarction, older age and larger infarct size as determined by cardiac enzymes. Mortality was 27.9 per cent in patients with block and 9.3 per cent in those without; it was significantly higher in both anterior (47.0 per cent vs 11.8 per cent) and inferior (20.4 per cent vs 6.7 per cent) infarction groups. When age, infarct size, infarct site and block were analysed simultaneously as predictors of death, block was a significant independent prognostic factor. The relative risk of death, corrected for age and infarct size, in patients showing block was similar for anterior and inferior infarction. Analysis of deaths revealed a higher incidence of unheralded death in inferior infarcts associated with high-degree block.

Age Factors↗

Association of coronary artery disease in cardiac transplant recipients with cytomegalovirus infection.

Coronary artery disease (CAD) is now the major limitation to long-term survival after cardiac transplantation. Its etiology remains unclear. The possible role of viral infection in the genesis of CAD stimulated the review of 102 patients transplanted since the introduction of triple drug immunosuppression (cyclosporine, azathioprine and prednisone) to assess the importance of posttransplant cytomegalovirus infection in the development of CAD in the cardiac graft. CAD occurred in 16 patients (16%). Recipient age and sex, donor age, pretransplant diagnosis, frequency of acute rejection episodes, HLA mismatch, cytomegalovirus infection, incidence of posttransplant systemic hypertension and diabetes mellitus, and mean triglyceride, cholesterol and cyclosporine levels were analyzed to assess their influence on the development of CAD. Only the occurrence of cytomegalovirus infection was found to be a significant factor (p = 0.007): infection occurred in 62% of patients with CAD and in only 25% of those without. These data support the existence of an association between cytomegalovirus infection and CAD after cardiac transplant. It is possible that the virus contributes to the initial injury to the coronary endothelium.

Adult↗

Survival of an infant with massive thermal injury: a case report.

Survival of infants with greater than 80 per cent body surface area burns has not been well documented. Survival of a 4-month-old infant with 80 per cent full skin thickness flame injury is reported. Data from the National Burn Information Exchange showed that there were 2266 infants under 8 months of age treated for burns in reporting hospitals. Only four children of the 2266 were treated for full skin thickness thermal injury covering more than 80 per cent TBSA and none survived except for the child reported here. It was felt that early aggressive excision of the burn eschar was an important factor leading to the survival of this infant. Complex rehabilitation issues related to developmental issues as well as physical and psychosocial needs were identified and addressed throughout her time in hospital by a multidisciplinary team to ensure the best possible quality of life.

Burns↗

Familial aortic valve disease: evidence for a genetic influence?

It has been suggested that genetic factors may play a role in the aetiology of congenital bicuspid aortic valve disease. This report describes a family in which three male siblings with bicuspid aortic valves developed critical aortic stenosis. This provides further evidence that an hereditary mechanism may play a role in some patients with this condition.

Adult↗