Research: a process essential to nursing practice.
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Biomedical subjects
Publications and source records attributed to D Blake.
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Measurement of uroporphyrinogen decarboxylase (UROD; EC 4.1.1.37) activity in erythrocytes is useful in distinguishing between familial porphyria cutanea tarda (PCT), in which UROD activities are low, and acquired PCT, in which UROD activity is normal. In this method for measuring UROD, pentacarboxylic acid porphyrinogen I (PPI) is used as substrate. A sample of the patient's whole blood is incubated with PPI at 37 degrees C for 30 min at pH 6.0. The reaction is stopped by adding trichloroacetic acid/dimethyl sulfoxide containing mesoporphyrin (internal standard). The coproporphyrin so produced is measured directly by high-performance liquid chromatography, with fluorescence detection. Our values by this method for healthy subjects and non-PCT patients ranged from 1.8 to 4.0 U/L. The CV for the assay was 10% at 1.1 U/L and 9% at 2.4 U/L. Twelve of 42 patients with PCT had low erythrocyte UROD activities. In each of six families of patients with low UROD activity we found at least one other family member with a low UROD activity in erythrocytes.
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Questionnaires were sent to 1025 female board-certified obstetricians, and information was retrieved about pregnancy outcome. A total of 454 pregnancies, one third of which occurred during residency, were evaluated, and the relationship between pregnancy outcome and residency was assessed. Children of primiparous women who were delivered during or after residency had significantly lower mean birth weights than those who were delivered before residency (p less than 0.001 and p less than 0.005, respectively), whereas birth weights of infants born to multiparous women were not significantly different. The low birth weight rate (less than 2500 gm) was significantly increased during residency (p less than 0.002), and infants born during residency were 7.5 times more likely to be growth retarded than those born outside residency (p less than 0.002). The incidence of other pregnancy complications was not found to be increased during residency. Our data suggest a potentially negative impact of residency on the birth weights of infants born to female obstetricians in training.
Speed of injection of bupivacaine was assessed in 73 women who received epidural analgesia in labour. Rapid injection was shown to produce quicker onset of epidural block and more reliable perineal anaesthesia than slow injection, but there was no difference in the final extent of the block.
1. Changes in plasma atrial natriuretic peptide (ANP) were examined in conscious rabbits in response to a 33% blood volume expansion in intact animals and after blockade of cardiac nerve activity. 2. Blood volume expansion by one-third markedly increased right atrial pressure and resulted in a four-fold increase in plasma ANP. 3. Cardiac nerve blockade with intrapericardial procaine had no effect on resting plasma ANP levels. The ANP responses to volume expansion in the presence of cardiac nerve blockade were similar to those seen in intact animals. 4. Release of ANP from its cardiac stores in response to volume expansion is not influenced by cardiac nerve activity.
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1 The pharmacokinetics of isoxicam have been compared in 57 volunteers with an average age of 31.3 years and 48 elderly subjects with an average age of 71.9 years. 2 Isoxicam was given in a single daily dose of 200 mg for up to 22 days. Similar plasma concentrations were obtained in the two age groups, average maximum concentrations being 39.7 mg l-1 in those under 65 and 38.1 mg l-1 in the elderly. There were no significant differences in the half-life which averaged 30.4 and 32.1 h respectively. 3 Approximately 9% of all those studied had half-life values in excess of 50 h. The results are consistent with the possibility of genetic polymorphism of isoxicam hydroxylation. 4 It is concluded that isoxicam is suitable for use in once daily dosage and that there are no clinically significant differences in its pharmacokinetics between young and elderly subjects.
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Activated phagocytic cells produce superoxide (O2-) and hydrogen peroxide (H2O2); their production is important in bacterial killing by neutrophils and has been implicated in tissue damage by activated phagocytes. H2O2 and O2- are poorly reactive in aqueous solution and their damaging actions may be related to formation of more reactive species from them. One such species is hydroxyl radical (OH.), formed from H2O2 in the presence of iron- or copper-ion catalysts. A major determinant of the cytotoxicity of O2- and H2O2 is thus the availability and location of metal-ion catalysts of OH. formation. Hydroxyl radical is an initiator of lipid peroxidation. Iron promoters of OH. production present in vivo include ferritin, and loosely bound iron complexes detectable by the 'bleomycin assay'. The chelating agent Desferal (desferrioxamine B methanesulphonate) prevents iron-dependent formation of OH. and protects against phagocyte-dependent tissue injury in several animal models of human disease. The use of Desferal for human treatment should be approached with caution, because preliminary results upon human rheumatoid patients have revealed side effects. It is proposed that OH. radical is a major damaging agent in the inflamed rheumatoid joint and that its formation is facilitated by the release of iron from transferrin, which can be achieved at the low pH present in the micro-environment created by adherent activated phagocytic cells. It is further proposed that one function of lactoferrin is to protect against iron-dependent radical reactions rather than to act as a catalyst of OH. production.
To delineate the efficacy of continuous intravenous 5-fluorouracil (5-FU) infusion therapy for advanced colorectal adenocarcinoma, a study of 36 patients with measurable metastatic disease was conducted. Patients received a daily intravenous infusion of 300 mg/m2 5-FU over a 24-h period utilizing portable infusion devices and central venous catheters. In a population characterized by substantial pretreatment exposure to radiotherapy, chemotherapy, and other indicators of poor prognosis, 13/36 (36%) patients achieved an objective response. An additional 10/36 (28%) patients manifested stable disease (no change) and experienced survival comparable to that of patients with objective response. Toxicity was minimal; patients were able to continue 5-FU infusions 95% of the total time on protocol. There were no adverse hematologic effects or catheter complications. Because previously untreated patients benefited more frequently (positive response, 50%), continuous intravenous infusion should be evaluated further as a primary modality option when 5-fluorouracil antitumor chemotherapy is contemplated.
A randomised control trial was carried out on support measures given to parents with a subsequent child after previously suffering a cot death. Apnoea monitors were used in one group and weighing scales in the other. General support measures given to both groups included the keeping of symptom charts and weekly visits by health visitors. Many alarms occurred which were presumed to be false. Eleven per cent fewer symptoms were reported by parents of children on monitors than parents of children being weighed daily. Both systems were acceptable and gave parents confidence. Sixty per cent of parents were reluctant to give up using the monitor compared with 26% of parents using scales. Virtually all parents commented on the great value of the weekly home visit of the health visitor and the symptom diary.
Exposure of human caeruloplasmin, an acute phase protein with antioxidant properties, to a mixture of xanthine/hypoxanthine and xanthine oxidase as a source of reactive oxygen intermediates decreased its ferroxidase and ascorbate oxidase activities and its ability to inhibit lipid peroxidation. Immunological reactivity was also altered. Exposure to hydrogen peroxide mimicked these effects. Exposure to low-intensity u.v. irradiation depressed caeruloplasmin's ability to inhibit iron-catalysed hyaluronic acid degradation. The results may explain the mechanism of the observed inactivation of caeruloplasmin within human rheumatoid synovial fluid.
Thiobarbituric acid (TBA)-reactive material is present in serum and knee joint synovial fluid from rheumatoid patients, consistent with lipid peroxidation occurring in vivo. The amount of TBA-reactive material in synovial fluid correlates with the concentration of iron salts present as determined by the bleomycin method, presumably because iron is an important catalyst of radical reactions in vivo. There appear to be significant correlations between the contents of TBA-reactive material and bleomycin-detectable iron in synovial fluid and the activity of rheumatoid arthritis as assessed with a clinical index of local inflammation and with various laboratory parameters.
Ferritin-containing fractions with different degrees of iron loading were prepared. All ferritin fractions stimulated the peroxidation of bovine brain phospholipid liposomes, as measured by the formation of thiobarbituric acid-reactive material. This stimulation was increased in the presence of ascorbate. Iron salts of equivalent concentration to those of the ferritin fractions were more stimulatory to lipid peroxidation at the higher iron concentrations. None of the fractions inhibited ascorbate-dependent peroxidation in the presence of added iron salts.
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Anti-lipid-A, anti-endotoxin, antibodies have been measured by a passive haemolysis test using antigen from an E. coli Re mutant. Titres in the normal population are low but do rise in situations in which there has been gram-negative sepsis. Absence of raised titres in other situations has profound implications.
Details of two patients with regional enteritis, whose condition was complicated by renal amyloidosis, are presented. The literature relating to the association is reviewed with special reference to the diagnosis, treatment and prognosis of renal amyloidosis.