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Biomedical subjects

C Robertson

Publications and source records attributed to C Robertson.

At least 217 records · Page 12Linked to original sources

Synthesis of intracellular histamine in platelets is associated with activation of protein kinase C, but not with mobilization of Ca2+.

In previous reports, we have provided evidence indicating that newly formed histamine is an intracellular messenger in human platelets. The involvement of protein kinase C (PKC) and intracellular calcium (Ca2+i) in the synthesis of histamine was investigated. Human platelets were stimulated by phorbol 12-myristate 13-acetate (PMA), collagen and the Ca2+ ionophore A23187, with or without the PKC inhibitor staurosporine. Aggregation, histamine synthesis and phosphorylation of pleckstrin (47 kDa; P47) and myosin light chain (20 kDa; P20) proteins were monitored. Staurosporine inhibited PMA- and collagen-induced aggregation, histamine synthesis and phosphorylation of 47 kDa and 20 kDa proteins in a dose-dependent manner. For PMA, median inhibitory concentrations (IC50 values) for staurosporine inhibition of aggregation, histamine synthesis and phosphorylation were similar, suggesting that histamine synthesis induced by this agonist may be a consequence of PKC activation. Conversely, collagen-stimulated histamine synthesis was inhibited by staurosporine at concentrations significantly higher than those required to inhibit aggregation (P less than 0.005) or pleckstrin phosphorylation (P less than 0.01), indicating the possible involvement of non-PKC mechanism(s) in the synthesis of histamine induced by this agonist. A23187 failed to induce the synthesis of intracellular histamine in platelets, whereas staurosporine blocked A23187-induced aggregation and phosphorylation of the 20 kDa protein at significantly higher concentrations than those needed to inhibit PKC. When platelets were stimulated with a combination of A23187 and PMA, the increase in platelet histamine was less than that with PMA alone. The results provide evidence that the synthesis of intracellular histamine in platelets occurs as a consequence of PKC activation and may be down-regulated under conditions where there is a substantial rise in [Ca2+]i.

Adenosine Diphosphate↗

Identification of a platelet dense granule membrane protein that is deficient in a patient with the Hermansky-Pudlak syndrome.

Monoclonal antibodies were raised after injecting mice with isolated human dense granules. Several of these monoclonals were found to recognize a 40-Kd dense granule membrane protein. Western blot and immunofluorescent analysis confirmed the dense-granule specificity. After thrombin activation, the protein was found in patches on the external platelet membrane. By Western blot and slot blot analysis, the protein was found to be markedly deficient in a patient with the Hermansky-Pudlak syndrome. Studies of neutrophils and endothelial cells show the presence of immunologically related granule-membrane protein(s). Western blots using four anti-synaptophysin antibodies and three antibodies to the platelet 40-Kd protein suggest that the protein may share some homology with, but is not identical to, the synaptosomal membrane protein synaptophysin.

Albinism, Oculocutaneous↗

Effectiveness of a videotaped behavioral intervention in reducing anxiety in emergency oral surgery patients.

This study evaluated the effectiveness of a videotaped behavioral treatment program in reducing dental anxiety in emergency oral surgery patients. It compared a videotaped placebo program and a no-treatment control condition. Anxiety, measured for two periods during the study (an anticipatory phase just before oral surgery and a post oral surgery phase), was evaluated by means of self-report, physiological, and behavioral observation measures. Results revealed significant treatment group as well as Group X Sex interaction effects for the heart rate index of physiological arousal. Results also revealed that the treatment program was reported by subjects to be significantly more helpful than the placebo program. Overall, these results suggest that a short, videotaped behavioral intervention can have a positive effect on the oral surgery patient, and that the sex of the subject may be an important variable to be incorporated in evaluating the effectiveness of this type of treatment program.

Analysis of Variance↗

Assessment and treatment of childhood asthma.

In June 1990 a meeting of Paediatric Respiratory Physicians was held near Adelaide. The guidelines for assessing and treating asthma as prepared by the Thoracic Society of Australia and New Zealand for the management of patients with asthma was considered. Although not explicitly stated, these guidelines were designed for adult asthmatics. There was complete agreement that a companion statement was needed to take into account differences between the management of children and adults. This document fulfils that role. Further recommendations are found in a statement prepared by Australian and New Zealand respiratory paediatricians following a workshop in June 1989. This present statement should be read in association with the previous documents.

Asthma↗

Increased intestinal permeability in ankylosing spondylitis--primary lesion or drug effect?

We have found increased small intestinal permeability to 51Cr-ethylenediaminetetra acetate in patients with ankylosing spondylitis compared with controls. There is no significant difference between patients with ankylosing spondylitis and patients with rheumatoid arthritis taking non-steroidal anti-inflammatory drugs (NSAID). The increased intestinal permeability in ankylosing spondylitis is independent of disease activity. These findings suggest that the increased permeability is caused by NSAID treatment and is probably not a primary lesion of small bowel mucosa.

Adult↗

A prospective comparison of laser therapy and intubation in endoscopic palliation for malignant dysphagia.

There is little objective long-term follow-up comparing laser therapy with intubation for palliation of malignant dysphagia. In a prospective, nonrandomized two-center trial 43 patients treated with the neodymium:yttrium-aluminum-garnet laser were compared with 30 patients treated by endoscopic intubation; the two groups were comparable for mean age and tumor position, length, and histology. Dysphagia was graded from 0 to 4 (0, normal swallowing; 4, dysphagia for liquids). Pretreatment mean dysphagia grades were similar: laser-treated group, 2.9 (SD, 0.6); intubated group, 3.2 (SD, 0.55). For thoracic esophageal tumors, the percentage of patients achieving an improvement in dysphagia grade by greater than or equal to 1 grade initially and over the long term was similar (laser, 95% and 77%; intubation, 100% and 86%). For tumors crossing the cardia, intubation was significantly better (laser, 59% and 50%; intubation, 100% and 92%, respectively; P less than 0.001). In patients palliated over a long period, however, the mean dysphagia grade over the remainder of their mean dysphagia grade over the remainder of their lives (mean survival: laser, 6.1 months; intubation, 5.1 months) was better in the laser group (1.6 vs. 2.0; P less than 0.01); 33% of laser-treated and 11% of intubated patients could eat most or all solids (P less than 0.05). For long-term palliation, laser-treated patients required on average more procedures (4.6 vs. 1.4; P less than 0.05) and days in the hospital (14 vs. 9; P less than 0.05). The perforation rate was lower in the laser-treated group (2% vs. 13%; P less than 0.02); no treatment-related deaths occurred in either group. For individual patients, the best results are likely to be achieved when the two techniques are used in a complementary fashion in specialist centers.

Aged↗

Comparison of different measurements of intestinal permeability in inflammatory bowel disease.

We have compared different measurements of small intestinal permeability in 28 patients with Crohn's disease affecting the small intestine, 14 with ulcerative colitis and 17 controls. Patients and controls were given a drink containing 100 microCi (3.7 MBq) of 51Cr-ethylene diamine tetraacetic acid (51Cr-EDTA), 5 g lactulose, 5 g cellobiose, 1 g rhamnose, and 2 g mannitol. Urine was collected to 6 h after dosing, and then from 6 until 24 h. Recoveries of 51Cr-EDTA, lactulose, rhamnose, and mannitol were expressed as percentages of the amount administered. The only measurement that distinguished patients with Crohn's disease from both controls and patients with ulcerative colitis was the recovery of 51Cr-EDTA in the first 6 h after dosing. The mean recovery in patients with Crohn's disease was 1.07%; in controls, it was 0.35% (p = 0.013); in ulcerative colitis it was 0.39% (p = 0.032 compared to Crohn's; p = 0.492 compared to controls). No other measurement of permeability differentiated the three groups. Recoveries of 51Cr-EDTa and lactulose were highly correlated in each of the three groups. Recovery of rhamnose was significantly correlated with that of mannitol. In the patients with Crohn's disease, recovery of 51Cr-EDTA to 6 h was significantly correlated with some nonspecific laboratory indicators of inflammatory activity, namely, erythrocyte sedimentation rate, platelet count, white blood cell count, serum albumin, and C-reactive protein, but not with hemoglobin.

Adolescent↗

Nosocomial endophthalmitis survey. Current incidence of infection after intraocular surgery.

The authors reviewed the incidence of hospital-linked postoperative endophthalmitis at the Bascom Palmer Eye Institute between January 1, 1984 and June 30, 1989. After 30,002 intraocular surgical procedures, the following incidence of culture-proven endophthalmitis was observed: (1) extracapsular cataract extraction (ECCE) with or without intraocular lens (IOL) implantation--0.072% (17 of 23,625 cases); (2) pars plana vitrectomy--0.051% (1 of 1974 cases); (3) penetrating keratoplasty (PKP)--0.11% (2 of 1783 cases); (4) secondary IOL--0.30% (3 of 988 cases); and (5) glaucoma filtering surgery--0.061% (1 of 1632 cases). A statistically significant (P = 0.038, Fisher's exact test, two-tailed) increased incidence of endophthalmitis occurred in diabetic (0.163%, 6 of 3686 cases) compared with nondiabetic (0.055%, 11 of 19,939 cases) patients undergoing ECCE with or without IOL implantation. The authors also reviewed the incidence of postoperative endophthalmitis after intracapsular cataract extraction (ICCE) with and without IOL and observed an incidence of 0.093% (7 of 7552) in cases operated on between September 1, 1976 and December 31, 1982.

Aged↗

Inhibition of mononuclear phagocytes reduces ischemic injury in the spinal cord.

Transient ischemia to the lumbar and sacral sections of the spinal cord of rabbit leads to a deterioration in neurological function that usually worsens 24 to 48 hours after injury. This decline in movement of the hindlimbs develops simultaneously with the appearance of mononuclear phagocytes in the gray matter of injured neural tissue. Chloroquine and colchicine inhibit phagocytic and secretory functions in mononuclear phagocytes. When given up to 6 hours after an induced ischemic lesion in rabbit, this drug combination decreased the number of mononuclear phagocytes found within the gray matter of damaged spinal cord, improved the recovery of function of the hindlimbs and bladder, preserved spinal somatosensory evoked potentials, and promoted the survival of motor neurons. In contrast, the glucocorticoid dexamethasone, a weak inhibitor of mononuclear phagocytes in vivo, did not reduce the number of inflammatory cells in the spinal cord and did not improve motor and bladder functions. The suppression of mononuclear phagocytes soon after ischemic injury may offer a new approach in the treatment of vascular disease in the central nervous system.

Animals↗

Platelet storage pool deficiency: diagnosis in patients with prolonged bleeding times and normal platelet aggregation.

We evaluated 46 patients with prolonged bleeding times, and no demonstrable abnormalities of either von Willebrand factor or platelet aggregation, for possible deficiency of platelet storage pool. Studies of ATP release from thrombin-stimulated platelets and enumeration of dense granules in platelet whole mounts were performed in these patients. Seventeen patients (35%) had both decreased ATP release and decreased numbers of dense granules, suggesting the presence of a storage pool defect. Thus, storage pool deficiency may be present in the absence of the classical aggregation abnormalities. Evidence of storage pool deficiency should be considered in all patients with an isolated unexplained prolongation of the bleeding time. The methods used in this study are readily applicable to most clinical laboratories.

Adenosine Triphosphate↗

Comparison of intramuscular glucagon and intravenous dextrose in the treatment of hypoglycaemic coma in an accident and emergency department.

Hypoglycaemia remains a serious and much feared complication of insulin therapy. In this study, patients attending an accident and emergency department in hypoglycaemic coma were randomized to treatment with either intravenous dextrose (25g) or intramuscular glucagon (1mg), administered into the right thigh. Restoration of normal conscious level was slower after glucagon than dextrose (9.0 vs 3.0 min, P less than 0.01), although the average duration of hypoglycaemic coma was 120 min. Two patients in the glucagon-treated group, who failed to show satisfactory recovery after 15 min, required additional treatment with intravenous dextrose. On questioning following recovery, all except two patients reported loss of awareness of the onset of hypoglycaemia Intramuscular glucagon is valuable in the treatment of severe hypoglycaemia outwith hospital and, although the slightly slower and less predictable recovery may appear to make it a less attractive option than intravenous dextrose in the accident and emergency department, this must be balanced against the advantages of ease of administration and a lower incidence of serious adverse effects.

Diabetes Mellitus, Type 1↗

Motor set in Parkinson's disease.

Three experiments employing a five-choice button-pressing task tested the ability of Parkinsonian patients to learn and generate sequences of movement, and to switch between alternative sequences at will. It was found that patients could learn and generate individual patterns of movement normally, even complex ones involving an incompatible stimulus-response relationship. They had difficulty, however, in maintaining a sequence if two different ones had been learnt and subjects were required to switch spontaneously from one to the other within a trial. Providing external cues at the start of each sequence to guide the ordering of movements improved the stability of patients' performance. Most errors in sequencing consisted of reverting to the alternative pattern of movement. Parkinsonian subjects thus show an impairment in motor set similar to that found previously in cognitive activity.

Aged↗