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Biomedical subjects

B J Sweetman

Publications and source records attributed to B J Sweetman.

At least 73 records · Page 4Linked to original sources
PubMed1975

Prostaglandins as mediators of hypercalcemia associated with certain types of cancer.

We investigated the role of prostaglandins in the hypercalcemia associated with neoplasia. In patients with hypercalcemia and solid tumors the excretion of the major urinary metabolite of the E prostaglandins, 7 alpha-hydroxy-5, 11-diketotetranorprostane-1, 16-dioic acid (PGE-M), was significantly greater than normal, P LESS THAN 0.01 (median of 58.4 and 7.1 ng per milligram of creatinine respectively). Slightly elevated values were seen in normocalcemic patients with solid tumors (14.3 ng per milligram). The levels of the metabolite were normal in hypercalcemic patients with either hematologic neoplasia or primary hyperparathyroidism. Immunoreactive parathyroid hormone was undetectable in the plasma of all hypercalcemic patients with solid tumors. Inhibition of prostaglandin synthesis by aspirin or indomethacin reduced excretion of both the urinary metabolite and serum calcium in six hypercalcemic patients with solid tumors and elevated excretion of the metabolite. These findings support the concept that prostaglandins are mediators of the hypercalcemia caused by certain solid tumors.

Aspirin↗
PubMed1975

Synthesis of prostaglandins by the rat renal papilla in vitro. Mechanism of stimulation by angiotensin II.

1. The biosynthesis of prostaglandins in the rat renal papilla was studied in a whole-cell preparation in vitro. Prostaglandins recovered from the incubation medium were identified by gas chromatography-mass spectrometry as prostaglandin E2 and prostaglandin F2alpha. Quantitative estimates of prostaglandin output were obtained by bioassay and confirmed by selected ion monitoring. 2. Prostaglandin biosynthesis was enhanced by exogenous arachidonic acid and also by triglyceride lipase, indicating that arachidonic acid released from papillary triglycerides is readily available for prostaglandin biosynthesis. 3. Angiotensin II (10--100 ng/ml) stimulated the biosynthesis of both prostaglandin E2 and prostaglandin F2alpha, thus increasing prostaglandin levels in both the incubation medium and the tissues. 4. The mechanism whereby angiotensin II stimulates prostaglandin biosynthesis was investigated using the isotope dilution technique. In the presence of [14-C]-arachidonic acid, angiotensin II stimulated the output of more prostaglandin that had a significantly lower specific activity than the controls. Angiotensin II therefore increased the availability of endogenous, non-labelled substrate for prostaglandin biosynthesis. This conclusion was supported by experiments in which enough arachidonic acid was added to make the kinetics of prostaglandin synthesis zero order. Under such conditions angiotensin II failed to cause any further increase in prostaglandin synthesis. 5. It is concluded that angiotensin II controls prostaglandin biosynthesis in the renal papilla by regulating the availability of free precursor. Possible mechanisms for increased levels of free arachidonic acid could be the activation of a tissue acyl hydrolase or decreased utilization of fatty acids.

Angiotensin II↗
PubMed1975

Increased arachidonate in lipids after administration to man: effects on prostaglandin biosynthesis.

Ethyl arachidonate was administered orally to 4 healthy male volunteers in a dose of 6 gm daily for a 2 to 3 wk period after 10-day control period. The increased intake of this precursor of the dienoic prostaglandins resulted in significant increases in the relative and absolute amount of arachidonate in plasma triglycerides, phospholipids, and cholesteryl esters. Similar changes in lipid composition were noted in platelets. The excretion of 7alpha-hydroxy-5,11-diketotetranoprostane-1,16-dioic acid, the major urinary metabolite of E prostaglandins in man, was increased by an average of 47% in 3 of the 4 volunteers. Platelet reactivity was assessed by determining the threshold concentration of adenosine diphosphate (ADP) necessary to induce secondary, irreversible aggregation of platelet-rich plasma. This threshold concentration dropped significantly in all volunteers (10% to 60% of control values). It is concluded that the biosynthesis and function of prostaglandins can be augmented in man by oral administration of an esterified precursor fatty acid.

Adenosine Diphosphate↗
PubMed1975

Capillary resistance and back pain.

A rapid clinical and epidemiological method of grading Capillary Resistance (CR) based on the appearance of petechiae following negative pressure on the skin of the forearm is described, and the results of testing 469 postmen aged 22 to 63 years are given. CR is shown to be increased in men who have had back pain within 24 hours of testing and no difference was found between men who had had back pain in the past and those who denied ever having had back pain. A separate series of 35 post-laminectomy patients examined at least 10 months after operation and who were shown to have disc disease at operation and/or on myelogram were found to have low CR. This work suggests that the changes involved in disc disease are not limited solely to the discs, but may involve collagen/elastic tissue or ground substance elsewhere as for example in this case when detectable in a test on the forearm. Secondly, it is suggested that CR grading could be a helpful discriminating test for 'disc disease' among those presenting with back pain of undetermined diagnosis.

Adult↗
PubMed1975

A combined flexi-rule/hydrogoniometer for measurement of lumbar spine and its sagittal movement.

A portable device is described which can record contours of the spine when standing normally and in extreme postures of flexion and extension. It can also give a numerical record of the range of lumbar movement and of the angles to the vertical in which the sacrum and upper spine are held in relation to the lordotic curve. It is felt that the device may be useful for clinical reports, ongoing assessments of therapy, and for epidemiological studies. Its use as a predictor of those at risk to develop low-back pain or for prognosis in established cases remains to be tested. The device has been used in a back-pain clinic and in an epidemiological survey, where it has been found to be assay and quick to use. Further adaptations may be found to be desirable; these would not detract from the usefulness of the device in that successive readings would still be comparable.

Adult↗
PubMed1975

Urinary prostaglandins. Identification and origin.

Human urine was analyzed by mass spectrometry for the presence of prostaglandins. Prostaglandin E2 and F2alpha were detected in urine from females by selected ion monitoring of the prostaglandin E2-methylester-methoxime bis-acetate and the prostaglandin F2alpha-methyl ester-Tris-trimethylsilylether derivative. Additional evidence for the presence of prostaglandin F2alpha was obtained by isolating from female urine an amount of this prostaglandin sufficient to yield a complete mass spectrum. The methods utilized permitted quantitative analysis. The origin of urinary prostaglandin was determined by stimulating renal prostaglandin synthesis by arachidonic acid or angiotensin infusion. Arachidonic acid, the precursor of prostaglandin E2, when infused into one renal artery of a dog led to a significant increase in the excretion rate of this prostaglandin. Similarly, infusion of angiotensin II amide led to a significantly increased ipsilateral excretion rate of prostaglandin E2 and F2a in spite of a simultaneous decrease in the creatinine clearance. In man, i.v. infusion of angiotensin also led to an increased urinary eliminiation of prostaglandin E. These results show that urinary prostaglandins may originate from the kidney, indicating that renally synthesized prostaglandins diffuse or are excreted into the tubule. Thus, urinary prostaglandins are a reflection of renal prostaglandin synthesis and have potential as a tool to delineate renal prostaglandin physiology and pathology.

Angiotensin II↗