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Biomedical subjects

D Green

Publications and source records attributed to D Green.

At least 379 records · Page 21Linked to original sources

Effects of diflunisal on platelet function and fecal blood loss.

The effects of diflunisal, a nonacetylated difluorinated salicylate, on platelet function were compared with those of aspirin and placebo. In a randomized, double-blind trial, normal subjects were given diflunisal, 250, 500, or 1,000 mg twice daily; aspirin, 650 or 1,300 mg twice daily; or placebo for 8-day periods. Difunisal, 250 mg, had no effect on platelet function, whereas 500 mg induced minimal inhibition of colagen-induced release of platelet serotonin, and 1,000 mg inhibited platelet malondialdehyde production, moderately prolonged template bleeding times (P = NS), and increased fecal blood loss (P less than 0.05). In contrast, aspirin, 650 mg, markedly inhibited collagen-induced platelet aggregation and serotonin release, and 1,300 mg prolonged bleeding time (P less than 0.01) and increased fecal blood loss (P less than 0.01). The effects of aspirin lasted for up to 5 days, whereas changes induced by diflunisal had returned to baseline 24 hr after the drug was discontinued. We conclude that in doses in the same range as those of aspirin diflunisal inhibits platelet function less.

Adult↗

A semi-automated technique for assessing the microdistribution of 239 Pu deposited in bone.

A semi-automated analytical procedure is described for the localisation of 239 Pu in bone. The method is based on the use of a Quantimet 720B Image Analyser for the analysis of neutron-induced autoradiographs, and may be applied to most tissues with fissionable radionuclides. Compared with former methods the present technique offers improvements in accuracy and a considerable saving on time and manpower. These savings arise mainly from the ability of the Quantimet to be used for the automatic detection of the fission-fragment tracks and to operate directly on the neutron-induced autoradiograph without recourse to photography. Results are presented for the distribution of 239 Pu in the ilia of CBA mice at 24 h post-injection.

Animals↗

Haemorrhagic thrombocytopathy associated with dilatation of the platelet--membrane complex.

We evaluated eight patients from four families because of a history of excessive bleeding. Most patients had prolonged bleeding times, absent secondary wave of platelet aggregation in response to epinephrine, collagen and adenosine diphosphate (ADP), and defective 14C-serotonin release and platelet factor 3 availability. These findings are characteristic of a platelet release defect. Electron-microscopy examination of the platelets of seven patients revealed a common abnormality. From 30% to 70% of the platelets in any given sample exhibited a prominent membrane complex and dilated, tortuous surface-connected canalicular system ('swiss-cheese' platelet). In two patients there was coincident storage-pool disease, but the remainder had adequate dense bodies and a normal ratio of ATP to ADP. SDS-polyacrylamide gel electrophoresis of platelet proteins and glycoproteins showed no abnormalities. The patency of the canalicular system was demonstrated in one patient by the observation that dense bodies appeared in the cannaliculi and outside the platelets following collagen-induced aggregation of polylysine-treated platelets. Since platelet-aggregation responses to the calcium ionophore A23187 were normal, we conclude that the defective platelet function in these patients may be due to impaired calcium mobilization from the morphologically abnormal membrane complex.

Bleeding Time↗

Morphometric studies on mouse bone using a computer-based image-analysis system.

The morphological structure of the ilium, femur, third lumbar vertebra and a central caudal vertebra of the female CBA mouse has been studied using 5 micrometer thick, plastic embedded, transverse and longitudinal sections. The sections were analysed on a Quantimet 720, system 30, image analyser connected on-line to a PDP11 computer. Separate endosteal and periosteal surface to volume ratios were calculated for each position of sampling in each bone. For this calculation the anisotrophy of the bone was estimated from measurements of mean chord lengths in longitudinal sections of the bone using a new analytical technique. Chord length distributions in transverse sections of bone were also measured and the relevance of such measurements to the study of morphological changes in the bone and its included marrow are briefly discussed.

Animals↗

The use of radiotherapy for pelvic recurrence following abdominoperineal resection for carcinoma of the rectum: a 10-year experience.

Eighty-five patients who developed pelvic recurrence after abdominoperineal resection for carcinoma of the rectum have been reviewed. The average period of latency was 16 months, with increasing incidence of recurrence in the more advanced stages of the disease. Eighty per cent of recurrences occurred within two years of surgical treatment and a further 20% between two and five years after operation. The prominent manifestations were pelvic pain (100%) and mass (54%), which responded to palliative radiotherapy in 92% and 80% of the cases respectively. The mean duration of palliation was 6.5 months. Patients with pelvic recurrence secondary to rectal carcinoma benefit from palliative radiation therapy, and this should be given whenever possible.

Adult↗

Reliability of two-dimensional echocardiography in assessing the severity of valvular aortic stenosis.

Two-dimensional echocardiographic studies have shown that maximum long-axis systolic aortic cusp separation (MACS) represents a useful, noninvasive method for estimating severity of valvular aortic stenosis in adults. Although mean values for patients with mild, moderate, and severe aortic stenosis have been clearly separated by this method, overlap occurs among individual patients. In this study, 81 adults with aortic stenosis were studied by two-dimensional echocardiography in the long-axis view. Long-axis assessment of aortic stenosis was obtainable in 93 percent of the patients. Less than 8-mm separation was 97 percent predictive of severe stenosis and 100 percent predictive of moderate or severe stenosis. Eight- to 12-mm had a low predictive value for the severity of stenosis. Greater than 12-mm separation was 96 percent predictive of mild aortic stenosis. Short-axis scans were attempted in 61 of the 81 subjects. Short axis assessment of aortic stenosis based on patterns of leaflet motion was obtainable in 46 of the 61 patients (73 percent) and provided a valuable index of severity. When short-axis scans were included in the assessment of severity in the subgroup of patients with 8- to 12-mm MACS, the predictive value improved greatly (86 percent vs 46 percent). Direct recording of aortic valve area in short-axis was successful in only 13 percent of the subjects. The echo aortic valve area compared with the hemodynamic calculated aortic valve area yielded an r = 0.87.

Adult↗

Improvements in histological techniques for epoxy-resin embedded bone specimens.

A procedure is presented in which some of the processing difficulties with fixation, embedding and cutting whole mouse bones and large bone pieces from other species are considered. The bone specimens are fixed in acetone or by a Karnovsky-formol-saline process which preserves intact endosteal surface-to-cortex layers. After fixation the bones are embedded in a hard mixture of epoxy resin to provide blocks with face sizes up to 3.5 x 3.0 cm. Mineralized sections are cut to 4 micrometer; demineralized at 3 micrometer. Sections are fastened to gelatin-subbed slides with pressure plates which produce flat, secure sections. After removal of the plastic, an unmodified Mayer's hematoxylin and a polychromatic eosin staining method is applied to demineralized sections, and a slightly modified method to mineralized sections.

Animals↗

High does epsilon-aminocaproic acid prolongs the bleeding time and increases rebleeding and intraoperative hemorrhage in patients with subarachnoid hemorrhage.

epsilon-Aminocaproic acid (EACA) has been used to prevent rebleeding in patients with intracranial aneurysms because it crosses the blood-brain barrier and is an inhibitor of fibrinolysis. Recommended doses have ranged from 24 to 48 g/day. We now describe an inhibitory effect on platelet function at the higher dose range. In vitro, a dose-dependent inhibition of adenosine diphosphate- and collagen-induced platelet aggregation was observed with concentrations of EACA beginning at 7.6 mM. In vivo, prolongation of the template bleeding time was observed in all eight patients receiving 48 g/day (greater than 20 minutes in four), in all five on 36 g/day (greater than 20 minutes in three), and in none of seven on smaller doses. More importantly, rebleeding and excessive intraoperative bleeding (requiring more than 1 litre of blood replacement) occurred predominantly in patients receiving the larger doses of EACA. Within 48 hours of the discontinuation of EACA, the bleeding times returned to normal values in all but one patient. We conclude that EACA exerts a dose-dependent inhibitory effect on platelet function and that patients receiving doses in excess of 24 g/day may be at risk of serious bleeding. Patients receiving EACA should be monitored with serial bleeding time tests.

Adult↗

Some immunofluorescent observations on factor VIII/von Willebrand factor in dogs.

Factor VIII/von Willebrand factor (vWF) was sought by immunofluorescence in or on canine platelets and blood vessels. None was found on normal canine platelets and little was present in normal canine arteries, veins and capillaries compared with normal human blood vessels. However, free granules of vWF were scattered in platelet-rich canine plasma and occasional granules appeared on small clumps of platelets when ristocetin or collagen was added to the plasma. When the same platelets were suspended in human plasma and ristocetin or collagen was added, more clumps were formed and more vWF (human) was associated with these clumps. When thrombin was added to canine platelets in either canine or human serum, more solid, small clumps of platelets were formed and stained with anti-vWF sera. When thrombin was added to canine platelets in either canine or human plasma, a single large clot was formed which stained brightly for vWF.

Animals↗

Pulmonary alveolar proteinosis complicating chronic myelogenous leukemia.

Pulmonary alveolar proteinosis (PAP) has been reported in 5 patients with chronic myelogenous leukemia and approximately 20 patients with other hematologic malignancies. These patients have had recurrent infections, frequently by opportunistic organisms. This susceptibility suggests that they have impaired cell-mediated immunity. In the case reported, splenectomy early in the course of illness may have contributed to the susceptibility to infection and PAP. Awareness of the possibility of pulmonary alveolar proteinosis in a patient with progressive dyspnea and unexplained pulmonary infiltrates should prompt early open lung biopsy to establish the diagnosis. Therapeutic pulmonary lavage is currently the treatment of choice.

Adult↗

Variant von Willebrand's disease. A study emphasizing crossed-immunoelectrophoresis.

30 members of an Illinois kindred were studied with a battery of haemostatic tests including the template bleeding time, platelet retention by glass beads (PRGB), measurement of activities related to factor VIII, and crossed-immunoelectrophoresis (CIEP). 9 family members had a history of excessive bleeding, and all 9 had prolonged bleeding times and increased migration of their factor VIII-related antigen (VIIIR:Ag) on CIEP. Of the other tests performed, the VIII:Ristocetin Cofactor and the PRGB showed the best correlation with the bleeding time. 3 subjects who were not bleeders, but who came from a branch of the family where there were several affected members, also had an abnormal VIIIR:Ag. The pattern of inheritance of the altered VIIIR:Ag in this family was one of autosomal dominance with full penetrance. The CIEP is a valuable screening test for the detection of variant von Willebrand's disease and the recognition of silent heterozygotes.

Female↗