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Biomedical subjects

D Blake

Publications and source records attributed to D Blake.

At least 91 records · Page 5Linked to original sources

Atrial natriuretic peptide release in the rabbit is independent of cardiac nerve activity.

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.

Animals↗

A comparison of isoxicam pharmacokinetics in young and elderly subjects.

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.

Adolescent↗

Metal ions and oxygen radical reactions in human inflammatory joint disease.

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.

Arthritis, Rheumatoid↗

Long-term ambulatory treatment of metastatic colorectal adenocarcinoma by continuous intravenous infusion of 5-fluorouracil.

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.

Adenocarcinoma↗

Apnoea monitors compared with weighing scales for siblings after cot death.

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.

Apnea↗

Action of free radical generating systems upon the biological and immunological properties of caeruloplasmin.

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.

Ascorbate Oxidase↗

Lipid peroxidation in rheumatoid arthritis: thiobarbituric acid-reactive material and catalytic iron salts in synovial fluid from rheumatoid patients.

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.

Arthritis, Rheumatoid↗

Effect of ferritin-containing fractions with different iron loading on lipid peroxidation.

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.

Ascorbic Acid↗

Anti-endotoxin (anti-lipid-A) antibodies.

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.

Animals↗

Transrectal ultrasonography in the evaluation of cervical carcinoma.

Transrectal ultrasonography has proved useful in the evaluation of genitourinary disease. Experience with prostate scans has shown that such conditions as prostate carcinoma and benign prostatic hyperplasia can be diagnosed and assessed with a high degree of accuracy. In patients with carcinoma of the bladder this method is useful in determining the degree of tumor invasion within the bladder wall. Our experience with scans of the uterus is in its early stages. We have studied 30 patients with documented cervical carcinoma and are studying 1) the presence and extent of parametrial involvement, 2) the ability to distinguish benign from malignant lesions, and 3) the identification of bladder invasion.

Adult↗

Radiation therapy in the treatment of superior vena caval obstruction.

The obstruction of the superior vena cava by tumor is recognized as an acute or subacute oncologic emergency. Rapid high-dose irradiation to the mediastinum is shown to be effective therapy for a superior vena caval obstruction. In our series 35 patients have been treated with rapid high-dose irradiation between January 1971 and July 1977. The present treatment consists of 400 rad given in a daily midplane dose for 3 days, and then slowing to 150 rad midplane per day to a total dose of 3000 rad over 15 fractions. There have been no instances of exacerbations of symptoms or severe complications from this treatment. There have been 2 failures of the 35 patients treated with this regimen. Both were shown at autopsy to have massive thrombi obstructing the superior vena cava. Six years of experience using this regimen has proven to be a safe and effective means of treatment for superior vena caval obstruction.

Adult↗