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Biomedical subjects

A Cox

Publications and source records attributed to A Cox.

At least 19 recordsLinked to original sources

A defect of platelet aggregation associated with an abnormal distribution of glycoprotein IIb-IIIa complexes within the platelet: the cause of a lifelong bleeding disorder.

A young Italian man (A.P.) has a lifelong history of bleeding from gums and mucocutaneous tissue. Electron microscopy showed a wide diversity of platelet size including giant forms. In citrated platelet-rich plasma (PRP), platelet aggregation induced by adenosine diphosphate (ADP) and other agonists was much reduced. Both secretion and clot retraction were normal. The aggregation of washed platelets with ADP was improved but remained subnormal, as was aggregation with collagen and thrombin. Fibrinogen-binding was analyzed by flow cytometry using platelets in whole blood or PRP and was markedly decreased. Crossed immunoelectrophoresis of Triton X-100 extracts of (A.P.) platelets showed that GP IIb-IIIa levels were 40% to 50% of normal. Glycoprotein (GP) IIb and GP IIIa were of usual migration in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, but their labeling was much reduced during lactoperoxidase-catalyzed iodination. Binding to (A.P.) platelets of four different 125I-labeled monoclonal antibodies to GP IIb-IIIa complexes was reduced to 12% to 20% of normal levels. However, when the patient's platelets were stimulated with alpha-thrombin, monoclonal antibody binding showed the same increase (approximately 20,000 sites) as normal platelets. Both flow cytometry and immunocytochemical studies showed that the distribution of residual surface GP IIb-IIIa within the total (A.P.) platelet population was heterogeneous and not related to platelet size. Staining of ultrathin sections confirmed the presence of an internal pool of GP IIb-IIIa. Monoclonal antibodies to other membrane glycoproteins bound normally to (A.P.) platelets. The patient has a selective deficiency of the surface pool of GP IIb-IIIa complexes that is manifested clinically by a mild Glanzmann's thrombasthenia-like syndrome.

Adenosine Diphosphate

Ventricular dysrhythmia secondary to select environmental hazards.

Ventricular fibrillation is the mechanism of death in a number of catastrophic events related to the environment. In particular, electrical shock, organophosphate poisoning, and hypothermia are known to give rise to ventricular fibrillation either directly or by causing unstable situations in which fibrillation may be readily provoked. This article reviews these mechanisms of ventricular fibrillation and aspects of treatment unique to environmental hazards.

Critical Care

Effect of asynchronous transfer and oestrogen administration on survival and development of porcine embryos.

Results indicate that recovery of embryos on Days 11 and 13 of pregnancy was reduced for Day 5 embryos transferred to recipients on Day 6 of their oestrous cycle and was greatly reduced when embryos were transferred to recipients on Day 7 of the cycle (P less than 0.01). Administration of oestradiol-17 beta on Day 11 of the recipient's cycle did not appear to affect embryo development on Day 13. Day 6 embryos transferred to recipients on Day 8 of the oestrous cycle deteriorated rapidly within 24 h of transfer; there was no recovery of embryos from the uterus after 36 h. Treatment of pregnant gilts with 1 mg oestradiol-17 beta (i.v.) on Day 10.5 resulted in total embryonic loss by Day 23, but pregnancy rates of gilts treated with oestradiol-17 beta on Day 12 were similar to those of vehicle-treated gilts (60.6 vs. 71.4%).

Animals

Provocation tests in extrinsic allergic alveolitis in mushroom workers.

The clinical diagnosis of extrinsic allergic alveolitis can be supported by a positive provocation test. Twenty-eight common mushroom (Agaricus bisporus) workers, 4 oyster mushroom (Pleurotus ostreatus) workers and 6 Shii Take mushroom (Lentinus edodes) workers, whose medical history indicated a possible extrinsic allergic alveolitis, were examined. The provocation test consisted of a control day, an exposure day, and half a day of follow-up observation. On the control and exposure days, the body temperature, leucocyte count and lung function were measured every 2 h. The chest X-ray and arterial blood gas sample were taken once. The exposure consisted of a 1-h presence on the common mushroom farm in spawning conditions or inhaling a suspension of spores of Pleurotus or Shii-Take in the laboratory. Eighteen of the 28 people employed on the common mushroom farm, all 4 Pleurotus workers and 4 of the 6 Shii-Take workers were diagnosed as having extrinsic allergic alveolitis, according to the following criteria: a positive history and 2 or more of the following findings: increase in leucocyte count, rise in temperature and decrease in inspiratory vital capacity (IVC) and total lung capacity (TLC).

Adult

Response to dynamic exercise in cardiac transplant recipients: implications for control of the sodium regulatory hormone atrial natriuretic peptide.

1. To study the importance of cardiac innervation in the regulation of atrial natriuretic peptide, plasma atrial natriuretic peptide levels were measured during symptom-limited, graded exercise on a cycle ergometer in seven male orthotopic cardiac transplant recipients. 2. Resting plasma atrial natriuretic peptide was significantly higher in the transplant recipients than in two control groups, one matched to the transplant recipients (group I) and the other to the age of the donor heart (group II). 3. The response to exercise of the cardiac transplant recipients was compared with the response of control group II. Mean maximal work load achieved with exercise was around 40% lower in the cardiac transplant recipients. During exercise, plasma atrial natriuretic peptide levels increased in both the cardiac transplant recipients and the control subjects. The increase in plasma atrial natriuretic peptide with exercise was greater in absolute, but less in percentage, terms in transplant recipients than in the control subjects. 4. The increase in mean arterial pressure with exercise was similar in patients and in control subjects; however, heart rate increased in the patients by only 33% compared with a rise of 151% in the control group. 5. These results provide insight into the control of the sodium regulatory hormone atrial natriuretic peptide. First, factors other than a change in heart rate appear of importance in the regulation of atrial natriuretic peptide. Secondly, these findings suggest that cardiac innervation is not of dominant importance in the modulation of atrial natriuretic peptide secretion.

Atrial Function

Teaching psychiatric interview skills to medical students.

A teaching package is described for teaching interview skills to large blocks of medical students whilst on their psychiatric attachment. The aims of this package are to reduce students' concerns about interviewing psychiatric patients, to reinforce students' knowledge of basic interviewing skills and to introduce students to the particular skills required in taking a psychiatric history and mental state examination. The package emphasizes the following teaching methods: 'hands-on' experience of interviewing a patient in front of small groups of peers; peer feedback using check-lists which focus on three major aspects of interviewing; elicitation of facts, elicitation of feelings and control of the interview; facilitation of small-group discussions in the presence of senior psychiatrist. The active involvement of all students in interviewing psychiatric patients engages them in the learning process. Peer involvement increases motivation and was deemed by students as a supportive and constructive exercise. The presence of a senior psychiatrist ensures that discussion is focused on the process of interviewing rather than on patient pathology. Ideally this package would precede focused training throughout the subsequent psychiatric placement.

Clinical Clerkship

Enhancer sequences located 3' of the mouse immunoglobulin lambda locus specify high-level expression of an immunoglobulin lambda gene in B cells of transgenic mice.

In contrast to the mouse immunoglobulin heavy chain and kappa light chain genes, very little is known about the regulation of expression of the immunoglobulin lambda light chain locus. To identify elements responsible for lambda gene regulation we mapped DNaseI hypersensitive sites associated with a functionally rearranged lambda 1 gene in nuclei from the myeloma cell line J558L. Tissue-specific hypersensitive sites were identified 2.3 to 2.5 kb upstream of the CAP site of both the lambda 1 gene and the unrearranged variable (V) lambda 2 gene segments. DNA sequences flanking the lambda 1 gene were isolated and tested for their influence on expression of the lambda 1 gene after transfection into myeloma cells and after injection into fertilized mouse eggs. Two enhancer elements were identified downstream of the lambda 1 gene. A proximal element (located 4 to 10 kb 3' of the gene) enhanced expression of a lambda 1 gene in stable myeloma cell transfectants but had no effect on the expression of a heterologous reporter gene in transient assays. A second, distal element, located approximately 30 kb 3' of the gene, enhanced heterologous expression in J558L cells expressing a lambda gene but not in a non-lambda myeloma cell line (SP2/0-Ag14). Co-injection of cosmids containing the lambda 1 gene and both the proximal and distal downstream elements into fertilized mouse eggs resulted in high-level expression of the lambda 1 transgene in B cells of transgenic mice. The identification of these lambda regulatory elements, in addition to contributing to an understanding of lambda gene regulation per se, will facilitate the study of the regulation of differential expression of kappa and lambda light chain genes in the immune system.

Animals

A 6-fold difference in the half-life of immunoglobulin mu heavy chain mRNA in cell lines representing two stages of B cell differentiation.

When B cells differentiate into plasma cells, there is a large increase in the cellular content of mRNA coding for immunoglobulin. This increase cannot be fully accounted for by the increase in rate of transcription of the genes. We have investigated the possibility that the half-life of mu heavy chain mRNA increases during B cell differentiation, by measuring the rates of decay of the same endogenous mu gene in two cell lines representing the B cell and the plasma cell. Using a pulse-chase protocol, it was found that there was a significant increase in the half-life of mu mRNA between the B cell and the plasma cell, and no detectable difference in the average half-life of total poly(A)+ RNA in the two cell lines. The reduced rate of decay of mu mRNA in the more differentiated cell type is almost sufficient to account for the difference in steady state mu mRNA levels between the two cell lines.

B-Lymphocytes

Lack of anticonvulsant tolerance with RU 32698 and Ro 17-1812.

Possible development of anticonvulsant tolerance to three benzodiazepine receptor ligands was assessed in mice using an i.v. infusion of pentylenetetrazol as the convulsive stimulus. Extensive tolerance developed rapidly in the case of diazepam (0.35 mg/kg b.d. or 1.5 mg/kg b.d.). No significant tolerance was seen with the imidazopyrimidine derivative RU 32698 (9 mg/kg b.d.) or the partial agonist benzodiazepine Ro 17-1812 (1 mg/kg b.d.) These results provide further support for the hypothesis that partial agonists at the benzodiazepine receptor induce less tolerance than full agonists.

Animals

Some remarks on nasal polyposis.

After a short historical and literature review the authors present their definition of nasal polyposis. The importance of CT scanning is stressed and the results of a CT-scan study of 350 patients with nasal complaints is presented. The authors discuss the incidence of sinusitis, presence of polypi and nasal anomalies in this population. Furthermore 111 biopsies of nasal polypi were studied and the cellular content, the ducts, glands, veins, aspect of the basal membrane and epithelial layer were described. As an oral ASA provocation test can be hazardous, the authors tested a nasal provocation test with acetylsalicylic acid. Although the test showed some interesting results, the reproducibility was poor. Finally the authors conclude that endoscopy and CT-scanning enable the diagnosis of nasal polyposis in an early stage of the disease.

Aspirin

Recurrent polyposis nasi. Documentation.

After a short historical review a proposal is made for the definition of nasal polyposis. The authors studied 350 CT-scans of patients with nasal complaints. In a high percentage anatomical anomalies were observed. In 57.5% of the CT-scans sinus mucosal disease was visible. In all patients with maxillary sinus disease polyps (rounded structures) could be found; in 31% these polyps were mainly of grade 2. From a retrospective study of 111 biopsies of nasal polyposis (65 patients) it became clear that different polyps from the same patient showed substantial difference in cellular content, i.e. presence of eosinophils, neutrophils, plasma cells, glands, ducti and thickening of the basal membrane. As oral acetylsalicylic acid provocation may be hazardous in ASA-sensitive patients, the authors developed a nasal aspirin provocation test. This nasal ASA test was carried out in 10 normal test subjects, 10 patients with aspecific hyperreactivity, 10 atopic patients and 16 patients with polyposis nasi. The reproducibility of the test, however, was so poor that the nasal ASA challenge test in its present form does not appear to be of any great clinical value. Finally, the authors discuss the physiopathology of nasal polyposis.

Adult

Psychiatric interviewing techniques. A second experimental study: eliciting feelings.

The effects of two experimental interview styles, designed to differ in the extent of their use of active feeling-oriented techniques but similar in their use of active fact-oriented techniques, were compared in initial diagnostic interviews with the mothers of children referred to a psychiatric clinic. The style that employed a higher level of actively responsive feeling-oriented techniques elicited more emotional expression and more often obtained certain feelings of potential diagnostic significance. The actively responsive style was more effective in increasing the amount of feeling expressed if mothers' spontaneous rate of expression was relatively low.

Adolescent

Extrinsic allergic alveolitis caused by spores of the oyster mushroom Pleurotus ostreatus.

Four mushroom workers have developed an extrinsic allergic alveolitis, after working with the oyster mushroom (Pleurotus ostreatus). After provocation with aerosolized spores under laboratory conditions, the four patients showed the complaints of an extrinsic allergic alveolitis; a rise of body temperature, leucocytosis and changes of lung function parameters were observed. Antibodies against the spores were assessed in the blood of these patients.

Adolescent

Production of IGF-binding proteins by vascular endothelial cells.

Conditioned serum-free media from cultured human, bovine and rodent endothelial cells contained binding proteins with high affinity for the insulin-like growth factors (IGFs). After partial purifications on heparin or Multiplication Stimulating Activity (MSA)-affinity columns, 2 species of binding protein were identified, a major protein having Mr approximately 35,000 and a minor 22-28,000 protein. The binding proteins had greater affinity for IGF-I than IGF-II with no affinity for insulin or proinsulin. Substantial amounts of the binding proteins remained cell-associated, loosely bound to the outer cell surface of the endothelial cell. Binding protein(s) from human endothelial cells cross-reacted with antibodies to the 53,000 dalton acid-stable human serum binding protein. Production of endothelial binding proteins was not stimulated by growth hormone or insulin. We conclude that endothelial cells in culture produce large quantities of specific IGF binding proteins. Such binding proteins should be relevant in understanding the complex metabolism and function of the IGFs in the intact host.

Animals

Calcium carbonate is an effective phosphate binder when dialysate calcium concentration is adjusted to control hypercalcemia.

The efficacy of calcium carbonate (CaCO3) as a phosphate binder has been limited by its tendency to cause hypercalcemia. Since standard dialysate calcium concentrations (3.0-3.5 mEq/l) increase the risk of developing hypercalcemia with large doses of CaCO3 by inducing positive calcium balance during hemodialysis (HD), we compared control of hyperphosphatemia in 41 HD patients during 4 months each of aluminum hydroxide (Al(OH)3) and CaCO3 when the dialysate calcium concentration was lowered, as required, to maintain the predialysis serum calcium concentration within the normal range. Mean predialysis serum phosphorus and calcium concentrations were 5.0 +/- 0.2 mg/dl and 9.3 +/- 0.1 mg/dl, respectively, during 4 months CaCO3 (9.2 +/- 0.3 g/day) and 4.9 +/- 0.2 g/dl and 9.1 +/- 0.1 mg/dl during the previous 4 months Al(OH)3 therapy (2.9 +/- 0.2 g/day). Reducing the dialysate calcium concentration to below 3.0 mEq/l (mean 2.1 +/- 0.04) in the 11 patients who developed hypercalcemia on CaCO3 decreased serum calcium (-1.1 +/- 0.15 mg/dl) and ionized calcium (-0.3 +/- 0.04 mEq/l) during HD, enabled CaCO3 (8.8 +/- 0.4 g/day) to be continued, and maintained predialysis serum calcium and phosphorus at 10.4 +/- 0.1 mg/dl and 5.2 +/- 0.3 mg/dl, respectively. No improvement in acidosis or biochemical hyperparathyroidism was observed during CaCO3 therapy but serum aluminum was significantly decreased after CaCO3 (p less than 0.005). We conclude that CaCO3 prevents interdialytic hyperphosphatemia as effectively as Al(OH)3 without increasing the predialysis serum calcium x phosphorus product, provided serum calcium is maintained within the normal range by adjusting the dialysate calcium concentration.

Adult

Effect of thymectomy on blood T-cell subsets in myasthenia gravis.

We studied peripheral blood mononuclear T-cell subsets in 23 patients with myasthenia gravis who had undergone thymectomy at least one year before study. An increase in the T4+/T8+ (helper-inducer/suppressor-cytotoxic cell) ratio was seen, similar to that previously reported in nonthymectomized patients with myasthenia gravis. Six patients were studied before and after thymectomy and no consistent alteration in the pattern of T-cell subsets was detected. We were not able to demonstrate a quantitative effect of thymectomy on peripheral blood mononuclear T-cell subsets in patients with myasthenia gravis.

Adult