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Biomedical subjects

J B Forrest

Publications and source records attributed to J B Forrest.

At least 55 records · Page 3Linked to original sources

The effects of aspirin and methysergide on responses to clot-induced pulmonary embolism.

This study reports the effect of pretreatment of rabbits with aspirin and methysergide on pulmonary vascular and other responses to clots introduced into the lobar pulmonary artery. Pretreatment with 250 mg/kg aspirin significantly (p less than 0.01) reduced the pulmonary artery pressure, the heart rate, and the systemic blood pressure changes induced by embolization. Pretreatment with methysergide 3 mg/kg also significantly (p less than 0.005) reduced the pulmonary artery pressure rise but had no effect on heart rate, systemic blood pressure, or ventilation rate. Pretreatment with a combination of aspirin and methysergide produced an additive effect and reduced the pulmonary artery pressure rise at 2 minutes post embolization from 10 +/- 2 mm Hg in control subjects to 1.3 +/- 0.9 mm Hg. There were no significant alterations in heart rate, systemic blood pressure, or ventilation rate following combined treatment. Responses to arachidonic acid and serotonin were virtually abolished by aspirin and methysergide, respectively. These results suggest a positive role for more than one mediator in the response to clot-induced pulmonary embolism.

Animals↗

Immunoblastic sarcoma of the bladder.

We describe the first case of immunoblastic sarcoma of the bladder. Urologists should be aware of this entity arising in organs that are prone to chronic antigenic stimulation. Treatment consists of radiotherapy for localized lesions and combination chemotherapy for more advanced disease.

B-Lymphocytes↗

Morphometric study of structural changes in the mesenteric blood vessels of spontaneously hypertensive rats.

Structural changes of three categories of mesenteric arteries (representing elastic, muscular and arteriolar vessels) from 10- to 12-week-old and 28-week-old spontaneously hypertensive rats (SHR) were studied morphometrically at the light microscope level, and the results compared with age-matched Wistar-Kyoto normotensive rats. In 10- to 12-week-old SHR, hypertrophy of the vessel wall occurred only in the muscular and arteriolar vessels. At 28 weeks, further thickening of the vessel wall occurred in the muscular and arteriolar vessels, and the superior mesenteric artery (elastic vessel) was also thickened in the SHR. There was no evidence that the wall of the relaxed hypertrophied vessels encroached upon the lumen of the vessel. The structural basis for the increase in the vessel wall thickness varied with vessel type. In the superior mesenteric artery, increase in the media at 28 weeks of age would be consistent with hypertrophy of the smooth muscle cells. In the large muscular arteries, at 10-12 weeks of age, increase in medial mass occurred with increase in the number of the smooth muscle cell layers whereas at 28 weeks further increase in media could be due to hypertrophy of the smooth muscle cells. In the small arteriolar vessels, medial enlargement was due at all ages to an increase in the number of smooth muscle layers. Our results show that in the SHR hypertrophy of the media occurs not only in the small arteriolar vessels, but also in large elastic and muscular arteries.

Animals↗

Ultrastructural changes in mesenteric arteries from spontaneously hypertensive rats. A morphometric study.

Morphometric measurements at the electron microscope level were carried out on three categories of mesenteric arteries representing elastic (superior mesenteric), muscular and arteriolar vessels, from 10- to 12-week-old spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto normotensive rats (WKY). Changes were observed only in muscular and arteriolar vessels of SHR, mainly as thickening of the vessel wall due to hypertrophy of the media. In muscular arteries, hypertrophy of the endothelial cells, widening of the subendothelial space, increased volume of the internal elastic lamina (IEL), and both hyperplasia and hypertrophy of the smooth muscle cells (SMC) in the media contributed to the wall thickening. In arteriolar vessels, increase in the subendothelial space and IEL, and hyperplasia of the SMC in the media were involved in the increased thickness of the vessel wall. There was no difference in the collagen content in all vessels, but elastin was increased in the muscular and arteriolar vessels of SHR. Nerve density was also increased in arteriolar vessels of SHR. These changes, especially the increase of SMC in muscular and arteriolar vessels, may be related to the elevated blood pressure in SHR.

Animals↗

Comparison of blood vessel wall dimensions in normotensive hypertensive rats by histometric and morphometric methods.

The histometric method is often used in hypertension studies in order to reconstruct, from cross-sectional profiles of vessels in the contracted state, a hypothetical relaxed state of the vessels based on the measured length of the internal elastic lamina (IEL). In this study, the accuracy of the histometric method was tested by comparing values obtained with the histometric method from contracted vessels versus values from morphometric measurements of vessels of the same calibre but maximally relaxed. Mesenteric arteries from spontaneously hypertensive and normotensive Wistar-Kyoto rats were used. We found that the lumen size of the vessels was dependent on the methods of measurement and preparation. Lumen size, determined with the histometric method from contracted vessels, tended to be underestimated mainly because the IEL became shortened during contraction of the vessels. When vessels were prepared by perfusion fixation, a high perfusion flow rate (7.6 ml/min) caused expansion of the lumen in muscular (lumen diameter 120--250 microns) and arteriolar vessels (40--100 microns), but not in the elastic arteries (400--700 microns). The cross-sectional area of the vessel wall, however, remained unchanged when the vessels were either contracted with norepinephrine or expanded with high transmural pressure, so morphometric measurements of the vessel wall and its components can be done on both contracted and relaxed vessels. Our results suggest that the use of the histometric method for the estimation of relaxed lumen size from the contracted vessels is of very limited value. We also suggest that, for an accurate comparison of vessel wall dimensions between hypertensive and normotensive animals, cross-sectional area should be used instead of wall thickness alone.

Animals↗

Nasal cilia in normal man, primary ciliary dyskinesia and other respiratory diseases: analysis of motility and ultrastructure.

We studied the ultrastructure and function of nasal cilia from non-atopic and atopic non-smokers, smokers, patients with chronic rhinitis and cystic fibrosis, and compared these to cilia from patients with primary ciliary dyskinesia (PCD). Atypical cilia were found in normal subjects and patients with a variety of chronic respiratory tract diseases, but the proportion was small (less than 5%). Ciliary wave form, beat frequency, and mucociliary transport were normal. In patients with PCD, the proportion of atypical cilia and ultrastructural abnormalities was significantly greater than normal subjects and patients without PCD p less than 0.0001. Beat frequency was reduced, ciliary wave form was grossly abnormal, and mucociliary transport was virtually absent. These findings suggest that ciliary ultrastructural abnormalities are related to altered ciliary function and have aetiological relevance in the generalized chronic respiratory tract disease of PCD.

Cilia↗

Testicular relapse in acute childhood leukemia.

The successful induction and maintenance of hematologic remission in childhood acute leukemia has led to the recognition of extramedullary leukemia as a major clinical problem [1-6]. The central nervous system is the most common site of extramedullary relapse [1,7-12]. A more recently recognized form of extramedullary relapse is the testis [13-22]. This paper will review a series of patients with childhood acute leukemia who suffered testicular relapse. Modes of therapy for testicular relapse and research conducted into the etiology of testicular relapse will be discussed.

Acute Disease↗

Effects of glutaraldehyde fixative osmolarities on smooth muscle cell volume, and osmotic reactivity of the cells after fixation.

The contribution of glutaraldehyde (GA) to the effective osmolarity of GA fixatives, the osmotic reactivity of the cells after fixation in GA, and also the duration of fixation in GA on cell volume, were investigated using cultured smooth muscle cells (SMC) and spiral aortic strips. Four fixation procedures were studied. We found that GA contributes to the total effective osmolarity of the fixatives, and that the type of buffers used for the fixatives can also affect the cell volume differently during GA fixation. After GA fixation, the cells were still osmotically reactive, regardless of the buffer types for making up the GA fixatives, so that the osmolarity of the wash buffer after GA fixation is important. However, OsO4 eliminates osmotic responses, thus the osmolarity of OsO4 fixative and wash buffer have negligible influence on the cell volume. Longer fixation time up to 4 h had no effect of the cell volume.

Aldehydes↗

A simple method for the handling and orientation of small specimens for electron microscopy.

Cyanoacrylic glue (Eastman 910) was used to affix small pieces of nasal scrapings to lens paper immediately before fixation in the glutaraldehyde. The lens paper not only served to hold specimens together so that they were not lost during tissue processing, but also functioned as a 'landmark' for the specimens, so that specimens could be oriented in a specific manner during embedding and subsequent sectioning.

Adhesives↗

The effects of aspirin and methysergide, singly and in combination, on systemic haemodynamic responses to pulmonary embolism.

Pretreatment of anaesthetized rabbits with aspirin (A), 250 mg.kg-1, methysergide (M) 3 mg.kg-1 or a combination of both (A + M) was done before pulmonary embolism with a 1.0 ml autologous blood clot and compared with no pretreatment (C). Experiments were done until 10 survivors were present in each group. Mortality rate in controls (C) was 55 per cent (death in less than 30 minutes) compared to zero in (A) and (A + M) and nine per cent in (M). Arterial blood pressure fell to 60 per cent of pre-embolism values two minutes after embolism in (C) but had returned to 85 per cent of pre-embolism values after 60 minutes. This compares with a drop to 82 per cent at two minutes and 83 per cent at 60 minutes in (A), a drop to 70 per cent at two minutes and 90 per cent at 60 minutes in (M) and a very small drop to 92 per cent at two minutes which was unchanged at 60 minutes in (A + M). Right ventricular pressure increased by 75 per cent after two minutes compared to pre-embolism values in (C) and was still elevated by 37 per cent after 60 minutes. This compares with increases at two minutes and 60 minutes respectively of 58 and 23 per cent in (A), 65 and 35 per cent in (M) and 55 and 18 per cent in (A + M). Heart rate did not show any significant changes in any of the groups after embolism. These results show a dramatic reduction in mortality from pulmonary embolism with aspirin or methysergide pretreatment, which is associated with significant attenuation of the hypotensive response seen in controls. These agents may act by inhibiting the actions of a release of prostaglandins and serotonin. The additive effects of the combination used suggests that both mediators may play a role in the haemodynamic responses to pulmonary embolism.

Animals↗

Osmotic effects of intravenous contrast agents on renal function.

Because of renewed interest in renal insufficiency after excretory urography a set of experiments was designed to determine the effects of high dose intravenous contrast agents on renal blood flow and glomerular filtration rate. A reproducible decrease in renal blood flow and glomerular filtration rate was noted with high dose intravenous contrast agents and an osmotically similar solution without the radiographically active compound. The results are discussed in light of clinical significance.

Animals↗

Cyclophosphamide, vincristine, and the blood testis barrier.

The blood testis barrier has been implicated in the pathogenesis of testicular relapse of childhood acute leukemia by forming a "sanctuary site" for leukemic cells. Experiments were conducted to test the transport of carbon 14 cyclophosphamide and tritiated vincristine across the blood testis barrier. Both cyclophosphamide and vincristine crossed the blood testis barrier. However, other factors such as the transport of immunoglobins and leukocytes across the blood testis barrier may interact in the pathogenesis of leukemic testicular relapse.

Animals↗

Case report: malignant melanoma arising during drug therapy for vitiligo.

A 30-year-old white male developed cutaneous patches of depigmentation which were treated with Trioxsalen ingested before daily sunbathing. A darkly pigmented lesion which appeared three weeks later on his back was widely excised and classified as a low-grade malignancy. Although the treatment of vitiligo with plants containing photodynamically active compounds dates back as far as 1400 BC, the modern period of research began only in the 1930's leading to the development of oral psoralens, a coumarin derivative. In early tests, patients showed increased sunlight tolerance and repigmentation of vitiliginous areas. Although some patients have developed uveitis and vitiligo while being treated for melanoma, previous published reports deny any cutaneous malignancy arising during drug therapy of vitiligo. The associations between vitiligo and melanoma are discussed. The possible causative role of Trioxsalen in etiology of the case presented is discussed.

Adult↗