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Biomedical subjects

R Davidson

Publications and source records attributed to R Davidson.

At least 55 records · Page 3Linked to original sources
PubMed1993

Raised levels of antistreptokinase antibody and neutralization titres from 4 days to 54 months after administration of streptokinase or anistreplase.

Streptokinase and anistreplase are antigenic and their administration often leads to antibody formation. These can cause allergic reactions and/or neutralization of streptokinase with resulting suboptimal treatment. Currently, streptokinase re-administration is considered appropriate for up to 5 days and from 1 year after a previous dose. Antistreptokinase antibody and neutralization titres (NT) were measured in three groups of patients to determine if this practice is appropriate: 1. (early)--36 patients whose titres were measured for at least 5 days after thrombolysis; 2. (late)--57 patients who received thrombolysis 12-54 months previously; 3. (controls)--182 consecutive suspected myocardial infarction patients (without previous exposure to thrombolysis). Results were as follows (mean +/- SEM): 1. (early)--the antibody and/or NT were raised by day 4 in 19.4% of the patients. One patient could have neutralized 1.97 million units (MU) of streptokinase by day 4. (Day 4--antibody 1:39 +/- 11, NT 0.19 +/- 0.05 MU; day 5--1:136 +/- 41 and NT 0.7 +/- 0.43 MU respectively.) 2. (late)--23 patients (40%) had either antibody titres > or = 1:160 and/or NT > 1.5 MU. (12-23 months--antibody 1:243 +/- 43, NT 0.63 +/- 0.15 MU; 24-35 months--1:98 +/- 31 and 0.69 +/- 0.22 MU; 36-54 months--1:87 +/- 14 and 0.54 +/- 0.12 MU.) All titres were significantly higher than the controls (antibody 1:25 +/- 3, NT 0.14 +/- 0.01 MU, P < 0.01). After streptokinase or antistreplase, antibodies are raised from 4 days to at least 54 months. It would seem prudent to avoid their re-administration during this time interval.

Anistreplase↗
PubMed1993

Hypersensitivity reactions to streptokinase in patients with high pre-treatment antistreptokinase antibody and neutralisation titres.

After streptokinase or antistreplase administration, raised antibody levels can persist for many years, but it is unclear if these antibodies can cause allergic reactions following streptokinase re-administration for myocardial re-infarction. Pretreatment antistreptokinase antibody (AB) and neutralisation titres (NT) were measured in 189 consecutive patients (57 received streptokinase or anistreplase). Seven patients had previous exposure to streptokinase or anistreplase; they had high mean (SEM) antibody titres of 1:801 (332) and neutralisation titres of 3.3 (1.7) million units. The 182 patients without previous thrombolysis had mean (SD) antibody titres of 1:25 (3) and neutralisation titres of 0.14 (0.08) million units; nine patients (4.95%), however, had raised antibody titres of > or = 1:160 and neutralisation titres of > or = 0.3 million units. Of the 15 patients with antibody titres of > or = 1:160, three received streptokinase or anistreplase. Hypersensitivity reactions occurred in all three patients--neutralisation titres 0.48, 1.5 and 1.1 million units respectively. Two became severely hypotensive with systolic pressures of 70 mmHg; one developed a serum sickness-like reaction. Importantly, none of the 54 patients with antibody titres of < 1:160 who received streptokinase or antistreplase reacted adversely to the thrombolytic agents (chi 2 with Yates's correction = 38.71, P < 0.01). High antibody titres are associated with hypersensitivity reactions to streptokinase. This has important implications in reinfarction thrombolysis. In patients whose antistreptokinase antibody titres are likely to be raised the avoidance of streptokinase-related thrombolytic agents should be considered.

Adult↗
PubMed1993

A study of the Huntington's disease associated trinucleotide repeat in the Scottish population.

Accurate measurements of a specific CAG repeat sequence in the Huntington's disease (HD) gene in 337 HD patients and 229 normal controls from the Scottish population showed a range from 35 to 62 repeats in affected subjects and eight to 33 in normal subjects. A link between early onset of symptoms and very high repeat number was seen. For HD patients with the most common affected allele sizes (39 to 42 repeats) absolute repeat size was a poor index for the age at onset of symptoms. There was variability in the transmitted repeat size for both sexes in the HD size range. We observed a significant increase of repeat size for paternal transmission of the disease and greater instability for paternally transmitted CAG repeats in the HD size range.

Adult↗
PubMed1993

Presymptomatic testing for autosomal dominant spinocerebellar ataxia type 1.

Presymptomatic testing was done on four people from a large family in which an autosomal dominant form of spinocerebellar ataxia was segregating. Earlier genetic analysis had shown that in this family the disorder was tightly linked to an informative microsatellite polymorphism on chromosome 6p. Two subjects with prior risks of 50% of developing the disease had final risks after testing of 2%; the other two with prior risks of 25% had final risks of 1%. Chromosome 6p linked spinocerebellar ataxia may now be added to Huntington's disease as a late onset disorder in which genetic linkage may be used to carry out presymptomatic testing.

Adult↗
PubMed1993

Avoiding obsolescence: assessing need and shaping strategies for management development.

The purpose of this article is to focus on the goals of management development and to describe a variety of techniques that should be considered by health care executives in meeting their personal management development needs as well as the organization-wide needs of their institutions. Strategies for needs determination and resources available to accommodate those needs are discussed.

Career Mobility↗
PubMed1993

Severe prenatal infantile cortical hyperostosis (Caffey's disease).

We describe three cases of prenatal infantile cortical hyperostosis (Caffey's disease) from two families, all associated with maternal polyhydramnios. Case 1 (family 1) was an early early neonatal death after delivery at 27 weeks gestation, case 2 (family 2) an intrauterine death at 33 weeks. Case 3 (family 2) had limited skeletal involvement and followed a course typical for Caffey's disease. Only six cases of prenatal Caffey's disease with extensive skeletal involvement have previously been described. Polyhydramnios was reported in all but one and the condition was lethal unless pregnancy reached term. To our knowledge cases 2 and 3 reported here represent the first description of Caffey's disease in which the prenatal lethal form was not sporadic.

Bone and Bones↗
PubMed1991

Covalent structure, disulfide bonding, and identification of reactive surface and active site residues of human prostatic acid phosphatase.

The pairing of the half-cysteine residues of human prostatic acid phosphatase was established by proteolytic digestion and analysis of the resulting peptide mixtures by fast atom bombardment mass spectrometry (FAB-MS). An independently derived, full length cDNA clone was used as the basis for the interpretation of the FAB-MS data. The sequence of the native protein is that predicted from the present cDNA sequence, except for the carboxyl-terminal end and some possible post-translational deamidations. Isolated human prostatic acid phosphatase was found to have multiple carboxyl-terminal ends, terminating in Thr, Glu, and Asp, corresponding to residues 349-351 of the 354-residue protein that is predicted from the cDNA sequence after removal of a leader peptide. The protein contains no free sulfhydryl groups. The identical monomer chains of the dimeric native enzyme are found to contain three disulfide bonds, specifically Cys-129 to Cys-340, Cys-183 to Cys-281, and Cys-315 to Cys-319. In view of the conserved positions of cysteines in the homologous human and rat liver lysosomal acid phosphatases, an identical disulfide bonding pattern may be predicted for those proteins. The location of a potential antigenic site was established by selective labeling of proximate tyrosine residues predicted to be on the surface. A conserved RHGXRXP sequence is present in the prostatic, lysosomal, Escherichia coli, and yeast acid phosphatases and is predicted to be of mechanistic significance. In addition, residue Arg-54 is shown to be an active site residue by reaction of the enzyme with phenylglyoxal. Interestingly, this residue is present in a sequence RXRY (R,H) that is also present in lysosomal phosphatase and in recently described protein tyrosine phosphatases.

Acid Phosphatase↗
PubMed1991

Identification of the major activity derived from cultured human peripheral blood mononuclear cells, which enhances eosinophil viability, as granulocyte macrophage colony-stimulating factor (GM-CSF).

Eosinophils (EOSs) cultured in the presence of 50% peripheral blood mononuclear cell (PBMC)-derived culture supernatants remained 67% +/- 7% (mean +/- SEM; n = 5) viable for 7 days. In the absence of PBMC supernatant, only 15% +/- 7% of cells remained viable for 7 days. PBMC supernatants from six atopic individuals, with eosinophilia, and six normal subjects, with no eosinophilia, were compared for EOS viability-enhancing activity with the same target EOSs. Optimal conditions for the production of viability-enhancing activity by mononuclear cells were established as a 24-hour culture period, with a concentration of 2 x 10(6) cells per milliliter. Comparison of monocyte-enriched and lymphocyte-enriched culture supernatants for the production of the EOS viability-enhancing activity indicated that both cell types released the factor. C-18 Sep-Pak separation of the PBMC culture supernatant yielded a major EOS viability-enhancing activity in the aqueous eluent, suggesting a hydrophilic molecule. This major activity was neutralized by a specific antibody to granulocyte/macrophage colony-stimulating factor but was unaffected by specific antibodies to interleukin-3 and interleukin-5. A second, minor viability-enhancing activity was observed in the 100% methanol fraction, indicating the presence of a more hydrophobic molecule. The supernatants from the PBMCs of the atopic individuals consistently enhanced EOS survival to a greater extent than supernatants from the PBMCs of the normal, nonatopic individuals.

Cell Survival↗
PubMed1991

The cholinergic regulation of potassium (86Rb+) permeability in sweat glands isolated from patients with cystic fibrosis.

Sweat glands isolated from skin obtained from normal subjects and patients with cystic fibrosis (CF) were pre-loaded with 86Rb+ and superfused with a physiological salt solution and the rate of 86Rb+ efflux was measured as an indicator of cellular potassium permeability. Acetylcholine always evoked a permeability increase in the glands from control subjects and this response could be resolved into calcium-dependent and calcium-independent components. Sweat glands from CF patients did not show such consistent responses. In three individuals the glands were abnormally insensitive to acetylcholine but normal responsiveness was seen in a fourth case. It is proposed that CF can induce dysfunction of calcium-dependent control processes in sweat glands.

Acetylcholine↗
PubMed1991

Diagnostic usefulness of renal scanning after angiotensin converting enzyme inhibitors.

Radioisotopic renal scanning after angiotensin converting enzyme inhibition (ACEI) has proven to be an exciting area for research. The biologic activity of markers such as DTPA and hippuran, when combined with the physiological effects of ACEI, may provide noninvasive methods of diagnosing both renal artery stenosis and renovascular hypertension. Recent investigators have demonstrated that the sensitivities and specificities of these tests may vary widely; these differences are probably due to variations in study design, patient population, diagnostic criteria, and outcome measurements. We have reviewed these studies and discuss these possible sources of variation and their impact on the clinical usefulness of these diagnostic tests, especially in relation to the prevalence of disease in the population. Current results suggest that the post-ACEI DTPA scan is relatively accurate in the diagnosis of renal artery stenosis, with sensitivity generally greater than 90% and specificity around 95%. However, the best results in predicting the response to angioplasty or surgery in patients with renal artery stenosis have been with the use of post-ACEI hippuran in combination with furosemide (sensitivity, 96%; specificity, 95%). With confirmation of these findings and continued investigation, it is expected that accurate noninvasive tests will be available for widespread clinical use in the near future.

Angiotensin-Converting Enzyme Inhibitors↗