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Biomedical subjects

D Blake

Publications and source records attributed to D Blake.

At least 37 records · Page 2Linked to original sources

Vasoconstriction in the renal vascular bed during exercise: studies in control and heart failure rabbits.

1. The effects of graded treadmill exercise on renal blood flow (RBF) were examined in seven rabbits, in which congestive heart failure (CHF) was produced by the administration of doxorubicin, 1 mg/kg, twice weekly for 8 weeks, and in seven controls. A third group of five rabbits underwent doxorubicin treatment with the addition of surgical section of the left renal sympathetic nerve. 2. During submaximal exercise, there was a small reduction in RBF in controls, which was greatly exaggerated in CHF. 3. In both control and heart failure rabbits, there was a precipitous fall in RBF as exercise fatigue developed. 4. Renal sympathectomy ablated these changes in RBF during exercise. 5. It is concluded that in heart failure there is an exaggerated, sympathetically mediated, diversion of blood flow away from the kidney. The onset of exercise fatigue in both normal and heart failure rabbits is accompanied by a marked intensification of this process.

Animals

An unusual case of variegate porphyria with possible homozygous inheritance.

We report an unusual case of variegate porphyria in a young girl with epilepsy, mental retardation and premature adrenarche. Symptoms of porphyria commenced about the age of 12 years and death occurred about 18 months later. The patient had very low protoporphyrinogen oxidase activity in her cultured fibroblasts. Both parents had half the normal activity of this enzyme in lymphocytes and are heterozygous for the abnormal gene for variegate porphyria. Therefore, it is possible that the patient was a homozygous variant. Anticonvulsant therapy and low hepatic 5 alpha reductase activity were probably other contributing factors to the severity of the condition in this patient.

Animals

Role of immunity to mycobacterial stress proteins in rheumatoid arthritis.

'Stress Proteins in Inflammation' provided a forum for the discussion of topical issues in this rapidly moving field. The mycobacterial 65 kDa stress proteins play a key role in certain animal models of inflammatory arthritis. However, the impression emerging is that the mechanism probably involves more than a simple cross-reaction between mycobacterial SP65 and either the host SP65 or a cartilage antigen, and that evidence for a primary role in human rheumatoid arthritis is lacking. A realistic role for immune responses against stress proteins might be the amplification or perpetuation of inflammation. If so, this is unlikely to be limited to arthritis.

Animals

Effect of ingestion of hemoproteins on fecal excretion of hemes and porphyrins.

Stools from asymptomatic volunteers on diets containing red meat, whole blood, or high fiber were analyzed for their content of hemes and dicarboxylic (heme-derived) porphyrins by the "HemoQuant" assay, the "Hemoccult" test, and "high-performance" liquid chromatography (HPLC). In 49 subjects, ingestion of red meat increased HemoQuant-determined combined fecal heme plus dicarboxylic porphyrins by an average 375%; the contribution of heme-derived porphyrins to total fecal porphyrins increased from 37% to 78%. Of subjects on a red-meat diet, 27% passed stools with a porphyrin content suggestive of a porphyria, compared with only 4% on a red-meat-free diet. These increases were due largely to protoporphyrin and its derivatives pemptoporphyrin and deuteroporphyrin, all of which were present in feces as iron-free porphyrins and iron-ligated (heme) forms. Ingestion of blood had an effect similar to that of red meat, but ingestion of fiber had no effect. These effects of dietary and endogenous hemoproteins must be considered when such methods are used to test feces for occult blood or to test for excess fecal porphyrins as an indicator of a porphyria.

Adolescent

An assay of uroporphyrinogen decarboxylase in erythrocytes.

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.

Adult

Pregnancy among obstetricians: a comparison of births before, during, and after residency.

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.

Birth Weight

Speed of injection and spread of bupivacaine in the epidural space.

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.

Anesthesia, Epidural

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