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Biomedical subjects

M D Tilson

Publications and source records attributed to M D Tilson.

At least 73 records · Page 4Linked to original sources
PubMed1990

Morphometric analysis of reticular and elastin fibers in the cerebral arteries of patients with intracranial aneurysms.

Elastin and reticular fibers were identified using standard histological strains in middle cerebral arteries taken from patients who had died from aneurysmal subarachnoid hemorrhage and control patients who did not have cerebral aneurysms. Examination of cerebral arteries from normal individuals revealed a dense network of fine reticular fibers in the arterial media that were uniformly distributed. Computerized morphometric analysis indicated that reticular fibers in the arterial media of cerebral arteries were significantly decreased in patients with aneurysms. In addition, these fibers were irregularly distributed and shortened when compared to those seen in control arteries. In both patients with aneurysms and control patients, elastin fibers were limited almost exclusively to the internal elastin lamina. No differences were observed in the appearance or content of elastin fibers in control patients and patients with aneurysm. Although other explanations cannot be excluded, these observations are consistent with the hypothesis that "intrinsic" abnormalities in the walls of cerebral arteries lead to conditions that favor the formation and rupture of cerebral aneurysms.

Aged↗
PubMed1989

Propranolol stimulates the crosslinking of matrix components in skin from the aneurysm-prone blotchy mouse.

Propranolol prevents or delays the formation of aortic aneurysms in both the lathyritic turkey and the Blotchy mouse models. This finding in the turkey is reported to be a direct effect on crosslinking of aortic collagen and elastin, independent of effects on pulse and blood pressure. The present work was performed to evaluate this hypothesis in the mouse model by studying the effect of propranolol on the insolubility of matrix proteins of skin, which would isolate the phenomenon from direct hemodynamic effects. Eight 6- to 8-week-old Blotchy mice were fed a diet containing 0.10% (w/w) propranolol for 12 weeks, and six Blotchy controls ate regular chow. At sacrifice the skins were extracted with 8 M urea, and the soluble and insoluble fractions were analyzed for hydroxyproline to determine the collagen contents. The elastin was estimated by subtracting the collagen from the insoluble fraction. There was a 147% increase in insoluble elastin with propranolol and a lesser increase of 54% in insoluble collagen. These results suggest that propranolol has a direct effect on crosslinking of matrix components.

Animals↗
PubMed1989

Incidence and etiology of abdominal aortic aneurysms.

Unlike coronary artery disease and cerebrovascular disease, the incidence of abdominal aortic aneurysms has increased dramatically over the past three decades. There appears to be a correlation between both hypertension and smoking and the development of aneurysms, and there is a substantial predominance of white men among the patients. Recent studies have also documented a strong genetic component to this disease. Several biochemical abnormalities have been noted in those with aortic aneurysms, including increased proteolysis (elastolysis and collagenolysis). At present, the precise etiology of aneurysmal disease remains unclear, but it will most likely turn out to be a heterogenous disease with several molecular forms.

Aorta, Abdominal↗
PubMed1988

Histochemistry of aortic elastin in patients with nonspecific abdominal aortic aneurysmal disease.

Histochemical studies of nine aneurysmal aortas revealed a conspicuous deficiency of iron hematoxylin-reactive elastin in four specimens, in comparison with eight atherosclerotic control specimens. A fibrillar matrix that morphologically resembled elastin was demonstrated in these same specimens under ultraviolet light. The phenomenon of substantial preservation of features of medial architecture suggests that, if the pathogenetic mechanism is enzymatic destruction, the process is highly selective. Comparisons with differences in human fetal vs newborn aortas and in Blotchy mouse vs normal mouse aortas suggest superficial similarities. These latter observations suggest that a hypothesis of maturation arrest might be considered as an alternative to enzymatic destruction. Definitive experiments to test the relative importance of maturation arrest vs enzymatic destruction in the pathogenesis of aneurysmal disease will require further studies.

Adult↗
PubMed1988

Effect of beta-adrenergic blockade on the growth rate of abdominal aortic aneurysms.

We retrospectively identified 136 patients with abdominal aortic aneurysms (AAAs) who were initially evaluated as outpatients. Twenty-seven of these patients met the following criteria for eligibility in the study: (1) roentgenographic documentation of an AAA larger than 3 cm, (2) at least two serial ultrasound size determinations over a minimum six-month interval, and (3) a documented medication history. Of these 27 patients, 12 received long-term beta-blockade, while 15 received no beta-blockade. The two groups were comparable with respect to age, sex, initial aneurysm size, mean systolic and diastolic blood pressure, and duration of follow-up (mean, 34 months). Among patients with beta-blockade, the mean growth rate was 0.17 cm/y. The rate for the controls was 0.44 cm/y. One patient of 12 (8%) in the beta-blocker group had a rate that exceeded the mean for the overall group compared with eight patients of 15 (53%) in the group with no beta-blockade. This difference was statistically significant. Thus, beta-blockade may be associated with a decreased AAA growth rate in this small, retrospective study.

Adrenergic beta-Antagonists↗
PubMed1988

Molecular diversity in the abdominal aortic aneurysm phenotype.

Abnormalities of collagenous peptides were detected among a group of 20 patients with abdominal aortic aneurysms, studied by high-performance liquid chromatography/NaDodSO4-PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis) analysis of the cyanogen bromide (CB) cleavage products of insoluble skin protein. Three abnormal patterns were identified as follows: (1) relative deficiency of a peptide with a relative molecular mass of approximately 58 kilodaltons (four patients); (2) relative decrease in the ratio of alpha-2 to alpha-1 (I) CB peptides (seven patients); and (3) decreased detection of all collagenous CB and pepsin cleavage products (one patient, who was also heterozygous for the Z allele of alpha 1-antitrypsin). The "minimal hypothesis" to explain these findings is that most of the observed abnormalities can be explained by collagenolysis in vitro, although a mutation in the primary structure of collagen has not been ruled out in all patients. Molecular heterogeneity appears to occur within the aneurysm phenotype, and the findings in the patient in group 3 allow identification of one possible risk factor in abdominal aortic aneurysmal disease that has a genomic assignment.

Amino Acids↗
PubMed1988

Propranolol delays the formation of aneurysms in the male blotchy mouse.

Propranolol has been reported to prevent aortic aneurysms in the beta-aminoproprionitrile-fed broad-breasted white turkey model. The purpose of this investigation was to determine the effect of propranolol in another animal model of aortic aneurysms, the spontaneously aneurysm-prone Blotchy (BLO) mouse. One hundred fourteen male BLO mice were fed control chow or a diet supplemented with 0.10% (w/w) propranolol. Groups were sacrificed at monthly intervals and the presence of aneurysms was determined after latex injection into the left ventricle. Aortic diameter was also measured at the widest point in a subset of mice from each group sacrificed at 4-5 months of age. At 4 months 86% of control and 32% of propranolol-fed animals had aneurysms (P less than 0.001). The difference in mean aortic diameter was also decreased by 33% in the propranolol-fed group (P less than 0.01). This study suggests that propranolol delays the formation of aneurysms in this spontaneous, genetically determined animal model.

Animals↗
PubMed1988

Vascular complications associated with spontaneous aortic dissection.

Three hundred twenty-five cases of spontaneous aortic dissection seen at two institutions between 1965 and 1986 were reviewed to assess the incidence, morbid sequelae, and specific management of aortic branch compromise. Noncardiac vascular complications occurred in 33% of the study group, and in these patients the overall mortality rate (51%) was significantly (p less than 0.001) higher than in patients without (29%) such complications. Although aortic rupture was the strongest correlate of mortality (90%), death specifically related to vascular occlusion was common when such occlusion occurred in the carotid, mesenteric, and renal circulation. There was a strong correlation between stroke and carotid occlusion (22/26 cases), yet specific carotid revascularization was only used during the chronic phase of the disease. Similarly, peripheral operation was ineffective in reducing the mortality rate in the setting of mesenteric (87%) and renal (50%) ischemia. Fifteen patients required either fenestration or graft replacement of the abdominal aorta for acute obstruction, rupture, or chronic aneurysm development. Thirty-eight patients (12%) demonstrated some degree of lower extremity ischemia, and one third of these required a direct approach on the abdominal aorta or iliofemoral segments to restore circulation. Selected patients with acute aortic dissection may require peripheral vascular operation in accordance with a treatment strategy that directs initial attention to the immediate life-threatening complications.

Aged↗
PubMed1988

Age of onset, pattern of distribution, and histology of aneurysm development in a genetically predisposed mouse model.

The blotchy mouse has an X chromosome mutation affecting crosslinking of collagen and elastin, which results in aneurysmal dilatation of the aorta. The age of onset, patterns of distribution, and histologic features of these lesions have not been characterized in detail in previous studies. Male normal and blotchy mice 1 to 8 months of age were killed and latex was injected into the left ventricles to facilitate exposure, examination, histologic sampling, and photography of the aorta. Aneurysms were not detected in any normal animals but the affected animals had a progressive increase in the incidence of aneurysms with age, reaching 100% by 6 months. Most aneurysms occurred in the ascending aorta, with some also present in the descending thoracic and abdominal segments. Some animals had multiple aneurysms. Histologically the blotchy mice aortas exhibited disrupted elastic lamellae and thickening of the interlamellar spaces. These spaces contained conspicuously pleomorphic smooth muscle cells, confirmed by electron microscopy. These changes occurred as early as 21 days, when there was no gross evidence of aneurysmal development. Aortic aneurysms develop in blotchy mice in a consistent fashion, with characteristic gross and histologic changes. These animals provide a practical model for further studies of aneurysmal disease, including possible therapeutic interventions to prevent aneurysm development.

Age Factors↗
PubMed1987

Percutaneous angioplasty for peripheral arterial occlusive disease. Correlates of clinical success.

We reviewed 142 percutaneous transluminal angioplasties (PTAs) in the iliac (n = 94) and femoropopliteal (n = 48) positions of 107 patients. Emphasis was placed on the ultimate clinical outcome, which was determined from a pool of clinical, hemodynamic, and angiographic data. Limb-threatening ischemia was the indication for intervention in 53% of the cases. The median follow-up interval was 17 months. Overall success was achieved in 50% of cases in both iliac and femoral positions at one year after PTA. The following factors were found to correlate with a successful clinical outcome: PTA for claudication vs limb-threatening ischemia (P less than .001); focal as opposed to diffuse stenosis or occlusion (P less than .02); immediate return of distal pulses (P less than .001); the absence of diabetes (P less than .05); and the presence of a patent outflow tract (P less than .001). Treatment results with PTA will vary widely according to the nature of the patient population and the criteria for determining success.

Aged↗
PubMed1985

Partial characteristics of an analog of pyridinoline isolated from human skin.

The most abundant amine in acid hydrolysates of human skin, eluting in the crosslink region of a reversed-phase HPLC chromatogram, has the same retention time as pyridinoline standard. This amine is not pyridinoline, since it is a weak fluorophore and its U/V spectrum does not agree with that of pyridinoline. The unknown amine was isolated and characterized by fast atom bombardment mass spectrometry and its structure is consistent with a deoxy-analogue of pyridinoline. It may be a crosslink component of some biological importance, since it is not detectable in skin from a patient with Marfan's Syndrome.

Amines↗
PubMed1985

Further studies of a putative cross-linking amino acid (3-deoxypyridinoline) in skin from patients with abdominal aortic aneurysms.

A recent report claimed that an amine in human skin (believed to be pyridinoline) was deficient in specimens from patients with abdominal aortic aneurysms (AAA). Further studies suggest that this work was erroneous in two respects. First, the amine has been isolated and partially characterized; the major component of the peak of interest is a deoxyanalogue of pyridinoline. It may be a collagen cross-link of some biologic importance, because it is not detectable in skin from a patient with Marfan's syndrome. Second, further studies in an additional 19 patients with AAA and an additional 13 controls suggest that this amine is abnormally abundant in skin from patients with AAA. This difference cannot be accounted for by any potential source of artifact that has been traceable. The effects of age, diabetes, sex, race, site of biopsy, and source of specimen (autopsy versus surgery) have been studied; none of these variables can account for the high ratio of pyridinolines to hydroxylysine found in skin from patients with AAA.

Adolescent↗
PubMed1984

Malignant neoplasia in patients with abdominal aortic aneurysms.

Thirty-eight percent of 69 patients with abdominal aortic aneurysms were on record for having malignant neoplasms with the Connecticut State Tumor Registry five to ten years following aneurysm repair. Thirteen percent of 61 patients with atherosclerotic occlusive disease were on record for having malignant neoplasms as a contemporaneous case-control group. The crude and adjusted odds-ratios for this difference in patients with aneurysms v patients with atherosclerotic disease were statistically significant. There are several theoretical explanations for these observations, spanning the gamut from possible immunologic mechanisms to hypothetical disturbances in the relationship of epithelia to connective-tissue matrix in the patients with aneurysms.

Adult↗
PubMed1984

Human genetics of the abdominal aortic aneurysm.

The results of recent studies suggest that genetic factors may be important in the pathogenesis of abdominal aortic aneurysms. In the present report, the apparent mechanisms of inheritance in 16 families with a total of 41 affected individuals are summarized. The results suggest that there may be both X-linked and autosomal dominant forms of the disease, with the X-linked variant as the more common type. A multifactorial mechanism cannot be ruled out from the results of the present data.

Aged↗
PubMed1983

Deficiencies of copper and a compound with ion-exchange characteristics of pyridinoline in skin from patients with abdominal aortic aneurysms.

A spontaneously aneurysm-prone mouse has a mutation on the X chromosome, which results in an abnormality of copper metabolism. A deficiency of the copper metalloenzyme, lysyl oxidase, results in a deficiency of lysyl-derived cross-linkages in collagen and elastin. Homology of the X chromosome suggests that this model may be relevant to the human abdominal aortic aneurysm (AAA). The present studies on skin from eight AAA patients suggest that copper deficiency occurs in humans, by comparison to skin of paired control subjects with atherosclerotic occlusive disease of the aorta. The lysyl-derived cross-linkage pyridinoline (or some compound with similar ion exchange elution characteristics) is also deficient in patients with AAA; while there is an excess of one of the cross-linkage precursors, hydroxylysine. In addition, the fluorescent properties of hydrolysates of skin from the patients with AAA differ from those of the controls, suggesting that simple biochemical markers might be defined on the basis of these differences in the future. These experiments support the hypothesis that the mouse model is relevant to the disease as it occurs in humans.

Amino Acids↗
PubMed1982

Embolization of bleeding esophageal varices via umbilical vein. An alternative approach.

Embolization of bleeding esophageal varices via the umbilical vein can be used as an alternative technique to percutaneous transhepatic coronary vein occlusion (PTCVO). Both techniques can stop acute bleeding from esophageal varices and allow the cirrhotic patient with portal hypertension to be prepared for an elective rather than an emergency shunt. Embolization via the umbilical vein can be performed with a patient under local anesthesia, can be effective when other methods fail, and can be done safely in the presence of both ascites and a bleeding diathesis, which are two contraindications to PTCVO.

Acute Disease↗