Biomedical subjects
Publications and source records attributed to D C Anderson.
A man with Nelson's syndrome developed severe associated behavioural and psychiatric problems, which completely resolved following selective resection of his pituitary tumour. It is postulated that ACTH, beta-endorphin, or related peptides may have caused these problems.
Two patients with osteoporosis circumscripta of the skull are presented who have each been treated with a 3-month course of intravenous infusions of (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD) (total dose of 185 and 375 mg), which in both cases was associated with rapid and dramatic remineralization of the porotic bone and marked clinical and biochemical remission. However, osteolytic disease reappeared (after 9 and 18 months, respectively) in both cases as an osteolytic ring showing high uptake of radiolabelled bisphosphonate on bone scan, in formerly unaffected bone just distal to the original leading edge of osteolysis. Further treatment was associated with healing of these new lesions. These cases suggest that the diseased osteoclasts entering previously normal bone are protected against the drug probably because normal bone matrix takes up relatively little APD, and that APD taken up by diseased bone behind this front confers long-term resistance to further resorption. In assessing treatment strategies with bisphosphonates for Paget's disease, the response at the leading edge of osteoporosis circumscripta may be particularly informative.
Customer service for bank tellers was defined in terms of 11 verbal behavior categories. An audio-recording system was used to track the occurrence of behaviors in these categories for six retail banking tellers. Three behavior management interventions (task clarification, performance feedback, and social praise), applied in sequence, were designed to improve overall teller performance with regard to the behavioral categories targeted. Clarification was accomplished by providing clear delineation of the various target categories, with specific examples of the behaviors in each. Feedback entailed presentation of ongoing verbal and visual information regarding teller performance. Praise consisted of verbal recognition of teller performance by branch managers. Results showed that clarification effects emerged quickly, producing an overall increase in desired behaviors of 12% over baseline. Feedback and praise effects occurred more gradually, resulting in overall increases of 6% and 7%, respectively. A suspension of all procedures led to a decline in overall performance, whereas reinstatement of feedback and praise was again accompanied by performance improvement. These findings extend the generality of behavior management applications and help to distinguish between possible antecedent and consequent effects of performance feedback.
Birth weights (BW) and weaning weights (WW) of 4,423 non-creep-fed Hereford calves were used to estimate direct and maternal sources of variation and maternal phenotypic effects (fm). Seventeen different (co)variances among relatives were estimated through Henderson's Method III and restricted estimated maximum likelihood procedures. Direct and maternal (co)variances and fm were evaluated by multiple regression procedures. Estimates of h2 for BW and WW were .28 and .28 respectively, by the paternal half-sib procedure and .45 and .88, respectively, based on full-sibs. Repeatability estimates were .21 for BW and .30 for WW. Heritabilities based on regression of offspring on dam and offspring on sire were .45 and .21 for BW and .28 and .06 for WW, respectively. Negative correlations were found between solutions for additive genetic direct and additive maternal effects (rG). Estimates of rG ranged from -.86 to -1.05 for BW and from -.57 to -.79 for WW. Estimates of heritability for direct effects (h2o), for maternal effects (h2m) and for total additive genetic effects (h2T) were .16 to .27, .18 to .63 and -.02 to .05 for BW and .26 to .32, .27 to .67 and .10 to .20 for WW. Dominance affected both direct and maternal effects for BW and WW. Values of -.15 (BW) and -.25 (WW) were found for fm (path coefficient between the maternal phenotypes of dam and daughter). These results indicated that selection response would be decreased due to the negative genetic correlation between direct and maternal effects.
Leukocyte adhesion deficiency disease is characterized by a mutation in the gene encoding the beta-subunit shared by three adhesive heterodimers, LFA-1, Mac-1 (CR3) and p150,95 expressed by leukocytes. An absent or abnormal beta-subunit leads to defective expression of the three heterodimers. Severe and moderate phenotypes of the disease are defined by absent and low surface expression of the adhesion molecules. The disease causes an inability of phagocytic cells to adhere to endothelial cells and thereafter to migrate to sites of infections. Severe widespread life-threatening bacterial and fungal infections are the consequences of this abnormality. Cure of the disease can be effected by allogeneic bone marrow transplantation. T-lymphocyte adhesion to various cells is also impaired; its consequences are, however, limited because of the existence of other T-cell-adhesive pathways. Nevertheless, haploidentical bone marrow graft rejection does not occur in the severe phenotype, an indication for possible immunotherapy with LFA-1 specific monoclonal antibodies.
Leukocyte dysfunction may contribute to infection in the elderly diabetic. Leukocyte oxidative metabolism assessed by chemiluminescence, correlates with microbicidal activity, and may be impaired with hyperglycaemia and ageing. The leukocyte chemiluminescence response to zymosan +/- luminol was assessed in 12 healthy controls (3M, 9F), aged 69 +/- 5 (mean +/- SD) years and in 23 non-insulin dependent diabetics, aged 68 +/- 5 years, before and after improving glycaemic control with sulphonylureas, when the glycosylated haemoglobin fell from 11.2 +/- 2.3 to 7.9 +/- 1.4% (p less than 0.001). The onset of maximal chemiluminescence with zymosan was similar in controls and diabetics, although the actual counts after improved glycaemic control were less in diabetic patients at all time points than initially (p range less than 0.025-less than 0.001) or when compared to the controls (p range less than 0.05-less than 0.005). Following luminal enhancement the onset and magnitude of maximum chemiluminescence was similar in all groups although an increase early response was observed in diabetics initially. We suggest that sulphonylureas may modify chemiluminescence by suppressing superoxide radical generation. Hyperglycaemic elderly non-insulin dependent diabetics may have subtle disturbances of the leukocyte oxidative burst but in general behave in a similar fashion to healthy elderly controls.
The diagnosis of cardioembolism is always based on circumstantial evidence. Echocardiography has a limited useful yield and should be reserved for young patients or older patients with clinical heart disease. Primary prophylaxis with anticoagulants appears to be reasonable for patients with acute anterior wall myocardial infarction, rheumatic valvular disease, or dilated cardiomyopathy and, possibly, for those with chronic nonvalvular atrial fibrillation. Secondary prophylaxis (after an initial embolism) is reasonable for the same conditions and, possibly, for mitral valve prolapse. Acute anticoagulation therapy is warranted when a large infarct is excluded by computed tomography 24 hours after a cerebral embolism.
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Leukocyte adhesion deficiency (LAD) is a heritable disease involving deficient expression of three related leukocyte adhesion glycoproteins: LFA-1, Mac-1, and p150,95. These proteins are alpha beta heterodimers containing identical 95,000 dalton beta subunits. Here we demonstrate that the primary defect in LAD is in the beta subunit gene. We identified five distinct beta subunit phenotypes in LAD patients: undetectable beta subunit mRNA and protein precursor; low levels of beta subunit mRNA and precursor; an aberrantly large beta subunit precursor, probably due to an extra glycosylation site; an aberrantly small precursor; and a grossly normal precursor. Mutant beta subunit precursors from LAD patients failed to associate with the LFA-1 alpha subunit. In family studies, inheritance of the aberrant precursors correlates with the known inheritance of the LAD defect.
Patients with insulin dependent diabetes mellitus who develop proteinuria may die prematurely, whereas those who do not develop this complication have a comparatively normal life span. The excess mortality in diabetics with proteinuria is from cardiovascular as well as renal disease, but the reason is unclear. Risk factors for vascular disease were therefore assessed in 22 insulin dependent diabetics with proteinuria, but not renal failure, who were matched for sex, age, duration of diabetes, and glycated haemoglobin (HbA1) values with a similar number who had normal urinary albumin excretion rates. Macrovascular disease (ischaemic heart disease and peripheral vascular disease) was present in 10 patients with proteinuria but in only three with normal albumin excretion rates, and proliferative retinopathy was detected in 11 and four patients in the two groups. There was no significant excess of smokers in the group with proteinuria. Blood pressure was, however, higher in the patients with proteinuria--mean systolic pressure 161 (SD 18) mm Hg compared with 135 (19) mm Hg (95% confidence interval of difference between means 15 to 38 mm Hg); mean diastolic pressure 90 (SD 12) mm Hg compared with 79 (15) mm Hg (confidence interval 3 to 19 mm Hg). The concentration of serum high density lipoprotein (HDL) cholesterol isolated by precipitation was lower in the patients with proteinuria (confidence interval 0.02 to 0.41 mmol/l). Their concentration of HDL2 cholesterol isolated by ultracentrifugation was also decreased (confidence interval 0.02 to 0.40 mmol/l), whereas HDL3 cholesterol tended to be increased (confidence interval -0.01 to 0.23 mmol/l). There was also a trend for serum cholesterol concentrations to be higher in the presence of proteinuria (confidence interval -0.39 to 1.20 mmol/l). The aggregation of risk factors for atherosclerosis in insulin dependent diabetes mellitus complicated by proteinuria helps to explain the increased prevalence of ischaemic heart disease and peripheral vascular disease reported in these patients. Early renal disease in insulin dependent diabetes may have an important role in hypertension and altered lipoprotein metabolism.
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Multimodal evoked potentials (EPs) were obtained serially in 57 patients with multiple sclerosis enrolled in a double-blind, controlled study of hyperbaric oxygen. We encountered drawbacks in the use of EPs in monitoring effects of a treatment for chronic multiple sclerosis. Limitations include a relatively arduous testing protocol and the significant occurrence of ambiguous and frankly unreproducible results. Test/retest variability is large in stable patients. There is poor correspondence between EP changes and changes of clinical function as well as among EP modalities. Whether EP measurements ultimately prove to be useful in testing new therapies awaits the development of a truly effective treatment, the effects of which can be shown despite these factors and limitations.
Lithium carbonate has been observed to induce neutrophilia in psychiatric patients and has been used in a number of childhood neutropenic disorders. We tried lithium carbonate in three children with glycogenosis Ib to see if the drug would alleviate the neutropenic complications of the disorder. Mean absolute neutrophil counts rose in one patient but not in the other two. Despite high-dosage schedules, serum lithium levels were highly erratic. Two patients developed potentially severe side effects, including polyuria, diarrhea, and altered mental status. One patient developed pneumonia despite a neutrophil count rise in response to therapy. Lithium carbonate is not useful in patients with glycogenosis Ib.
Sera from 10 gorillas were tested by indirect immunofluorescent antibody assay, Western blotting and ELISA to Human T-lymphotropic viruses for cross-reacting with antibodies to Simian T-lymphotropic virus I (STLV-I). Four were antibody positive. Of the 4 seropositive gorillas, one has remained healthy, while 3 have died with similar disease problems as reconstructed from clinical records. It is not known whether a causal relationship exists between these diseases and STLV-I retrovirus infection.
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