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Amelioration of endothelial abnormalities by prednisone in experimental thrombocytopenia in the rabbit.

Experimental thrombocytopenia results in endothelial alterations associated with bleeding. In this study prednisone was shown to prevent or reverse these changes, which supports the clinical inference that adrenocorticosteroids decrease capillary fragility in thrombocytopenia. Rabbits (3-4 kg), intraperitoneally injected with busulfan, developed 98-99% reductions in platelet count and hemorrhaged profusely. Orally administered prednisone (0.2 mg/kg or 1.0 mg/kg daily) reduced bleeding despite persistent thrombocytopenia. Tongue biopsies obtained after 3 days of prednisone treatment were examined by electron microscopy. Normal rabbits served as controls. 25 consecutive capillaries or venules from each of four animals in the control group and each of five experimental groups were examined for fenestrations, "thin spots" (<800 A thick), and mean wall thickness as determined by planimetry. Vessels from control animals had no thin spots or fenestrations, and the mean vessel wall thickness was 4,254+/-105 A SEM. The 100 vessels from the thrombocytopenic animals had a mean vessel wall thickness of 2,081+/-218 A (P < 0.001), and 42 had thin spots of fenestrations. After administration of the smaller dosage of prednisone, the mean vessel wall thickness increased to 3,556+/-40 A (P < 0.001), and only nine vessels had thin spots or fenestrations. With the larger dosage, only six vessels had thin spots or fenestrations and the mean vessel wall thickness of this group increased to 3,704+/-206 A (P < 0.005). All preparations demonstrated normal endothelial junctions. The data are consistent with the hypothesis that the bleeding of thrombocytopenia is caused by altered capillary and venule endothelium and that diminished bleeding observed with prednisone administration results from amelioration of these endothelial changes.

Animals

Familial bleeding tendency and tonsillectomy.

A retrospective study of 2,292 tonsillectomies revealed 12 cases of hereditary capillary fragility. These cases showed an increased morbidity from bleeding complications and accounted for 4.8 per cent of those with a secondary hemorrhage. When diagnosed, skin bleeding time should be carried out at the time of premedication, and, if prolonged, the procedure postponed.

Adult

[Multivariate analysis for the understanding of typical diabetic hemostasis criteria. 2. Prevalent thrombocytic markers].

Various thrombocyte functions and metabolic criteria were investigated in 309 test persons, among them 198 Patients affected with diabetes mellitus, 67 of type I and 131 of type II as well as 111 healthy control persons. From the variety of these factors an optimal amount was determined by means of the statistical method of multivariance analysis separating both types of diabetes and healthy control persons. In addition to haemoglobin A1 concentration, thrombocyte parameters have been found together with the degree of capillary fragility, adrenalin-induced aggregation, platelet aggregation test and clot retraction, which allow individuals to be assigned diagnostically to various groups of test persons. Thus, thrombocyte functions found in both types of diabetes and normal persons exhibit differences which may contribute to a diagnostic classification.

Adult

A prospective study of cerebrovascular disease in Japanese rural communities, Akabane and Asahi. Part 1: evaluation of risk factors in the occurrence of cerebral hemorrhage and thrombosis.

An epidemiological study of cerebrovascular disease in Akabane and Asahi, Japan, was made. (These cities are located near Nagoy, Japan.) The study population included 4,737 men and women aged 40 to 79 at the time of entry into the study. There were 4,186 persons who were examined and, of these, 264 cases of cerebrovascular attacks were observed between 1964 and 1970. The incidence rate of stroke in those persons not responding to the survey was 15.9 times higher than in those persons examined according to person-year observation in Akabane. The risk factors for cerebral hemorrhage and thrombosis were evaluated by age-adjusted and sex-adjusted relative risks. The predisposing factors to cerebral hemorrhage appeared to be high blood pressure, high left R wave, ST depression, T abnormality, capillary fragility counts, previous medical history of stroke and albuminuria. For cerebral thrombosis, the predisposing factors appeared to be high blood pressure, ST depression and funduscopic sclerotic findings, and those factors assumed to be significant were glycosuria and smoking habits. Ocular funduscopic abnormality was the most prominent risk factor for cerebral thrombosis, while high blood pressure and ECG abnormalities were highly related to cerebral hemorrhage. It was suggested that those subjects with a relatively higher blood pressure may have a higher relative risk of cerebral hemorrhage than those with a lower (normal range) blood pressure. A previous or family history of stroke also appeared significantly related to cerebral hemorrhage.

Adult

[Posterior fossa hemorrhage 11 years after the use of silastic dural substitute: case report].

A case of posterior fossa hemorrhage is reported. The hemorrhage occurred 11 years after posterior fossa craniotomy with closure using a graft of silastic dural substitute. This 14 year-old girl underwent suboccipital craniotomy at the age of 3 years because of traumatic posterior fossa hemorrhage. The dura mater was repaired with a piece of dural substitute. Eleven years later, she developed severe headache and vomiting. Computerized tomography scanning revealed a high density area in the right posterior fossa. At exploration, a fresh clot was evacuated between the dural graft and the fibrous scar tissue. The resected fibrous scar tissue was 1cm thick, and was adhering to the duro glial scar tissue. Her postoperative course was uneventful, and she was discharged 2 weeks after surgery. Microscopic examination of the fibrous scar tissue revealed an outer layer of loose connective tissue with numerous capillaries. The inner layer consisted of dense connective tissue. It was speculated that fragile capillaries of fibrous scar tissue caused this hemorrhage. Surgeons should not forget this complication although silastic dural substitute is less used than it used to be.

Adolescent

Capillary growth in the mesentery of normal young rats. Intravital video and electron microscope analyses.

Capillary sprouting was studied by a combination of intravital video recording and subsequent electron microscopy in the mesentery of young female rats without previous experimental manipulation. Selected segments of the mesenteric microvascular bed with capillary sprouts were carefully surveyed and mapped at a monitor magnification of 255 times and submitted to detailed in vivo analysis concerning flow pattern and cells at 2000 times magnification. The mesentery was preserved for light and electron microscopy by a superfusion of glutaraldehyde while observed and recorded on video, confirming earlier investigations that this type of fixation does preserve exceptionally well vascular topography and diameters of the mesenteric microvascular bed. Capillary sprouts originated as endothelial spurs from arteriolar-venular arcades and continued to grow in size through a bipolar rearrangement of endothelial cells, forming a solid sprout tip which progressively lengthened by alternately rapid and slow growth phases. The extended leading tip of the migrating endothelial cells displayed microspikes and pseudopodia denuded of basal lamina. The cytoplasm of the leading tip contained an array of microtubules, 75 A filaments and many small vesicles. In similarity with the situation in nerve growth cones, all these organelles probably participate in cytoplasmic streaming and cell migration. The sprout lumen arose between endothelial cells of the solid sprout. Mesenteric connective tissue fibroblasts approached and settled down on the sprouts, being converted to pericytes as the fibroblasts became enveloped by a basal lamina. The pericytes reinforced the wall of the delicate and fragile capillary sprouts, and trapped plasma, platelets and red blood cells which had leaked out temporarily, in the process assuming an umbrella shape. The arteriolar feeder of the arcades was surrounded by cells which were classified as intermediate between pericytes and true smooth muscle cells. Sprouts that presumably were on the verge of merging with other capillaries were analyzed for indications of how anastomoses are formed.

Animals

Flow-limited tracer oxygen distribution in the isolated perfused rat liver: effects of temperature and hematocrit.

We used the multiple-indicator dilution technique to examine the kinetics of tracer oxygen distribution and uptake in the rat liver perfused in a nonrecirculating fashion with blood. 51Cr-labeled 18O2-saturated erythrocytes, labeled albumin, sucrose and water (the tracers for oxygen and vascular, interstitial and cellular references) were injected simultaneously into the portal vein. Timed anaerobic samples were collected from the hepatic vein and analyzed by mass spectrometry for relative 18O2 enrichment and radioactivity. In a set of experiments performed at 32 degrees C, oxygen uptake was substantially diminished; tracer oxygen profiles approached those expected for a completely recovered, flow-limited substance. At 37 degrees C, much larger tracer oxygen sequestration occurred. Experiments were carried out at each temperature at higher and lower hematocrit, and oxygen consumption at each temperature was found to be independent of hematocrit. The tissue space of distribution for tracer oxygen relative to the total sinusoidal vascular content was influenced by the hematocrit: it was smaller at higher hematocrit and larger at lower hematocrit, as expected. The derived partition coefficient of oxygen for liver cells relative to plasma (expressed in terms of the liver and plasma water spaces) was, on average, 2.62 ml/ml; it was independent of the hematocrit. Analysis of the indicator dilution experiments indicates that the tracer oxygen is distributed into tissue in a flow-limited rather than a barrier-limited fashion, and that with this, an ongoing concomitant intracellular sequestration of tracer can be seen.

Animals

Massive pulmonary haemorrhage due to leptospirosis.

A young man with leptospirosis developed massive pulmonary haemorrhage. This was remarkable both in its severity and in its occurrence early in the clinical course - before the onset or presence of jaundice, renal failure or of a serological diagnosis. It occurred in the absence of a coagulopathy or thrombocytopenia and presumably was a consequence of the capillary fragility characteristic of the disease - perhaps precipitated in this instance by mechanical ventilation.

Adult

A review of the pathophysiology of exercise-induced pulmonary haemorrhage in the equine athlete.

In the United States, more than 75% of equine athletes are reported to suffer from exercise-related haemorrhage of the respiratory tract (Voynick and Sweeney, 1986; Sweeney et al., 1990). Fiberoptic endoscopy has traced the source of blood to beyond the bifurcation of the trachea. In 1981, the term exercise-induced pulmonary haemorrhage (EIPH) was introduced (Pascoe et al., 1981). Racehorses of all breeds, polo ponies and three-day event horses of mixed heritage, even foxhunters, may 'bleed' (Voynick and Sweeney, 1986; Pascoe et al., 1981; Sweeney and Soma, 1983; Hillidge, 1986). Any horse working at speeds greater than 240 m/min is at risk (Voynick and Sweeney, 1986). The impact of exercise-induced pulmonary haemorrhage is difficult to assess. Most attempts to demonstrate statistically a negative correlation between EIPH and performance have been unrewarding, largely due to the number of uncontrollable variables (Pascoe et al., 1981; Raphel and Soma, 1982). In racing thoroughbreds (Mason et al., 1983) and standard breeds (MacNamara et al., 1990) approximately half as many EIPH-positive as EIPH-negative horses were placed in their races. Based on extensive intrapulmonary haemorrhage, a 3-year prospective study of sudden deaths in exercising thoroughbreds concluded that 9 out of 11 deaths were attributable to EIPH (Gunson et al., 1988). By correlation of clinical signs, thoracic radiographs, ventilation/perfusion scintigraphy, gross and subgross pathology and histopathology in 26 affected thoroughbreds, EIPH has been associated with chronic small airway inflammation, proliferation of subpleural, peribronchial and septal bronchial arterioles, interstitial connective tissue fibrosis and alveolar septal disruption in the dorsocaudal lung lobes (O'Callaghan et al., 1987). From this work it was proposed that the initial insult of EIPH started as focal, dorsocaudal pulmonary peribronchial inflammation which resulted in bronchial arterial neovascularization. Haemorrhage then occurred when, during exercise, bronchial blood pressure increased in fragile capillary buds. The incidence of bronchitis/bronchiolitis, regardless of aetiology, has been estimated to be 30% in non-racing equine athletes and close to 100% in one group of racing thoroughbreds (Sweeney et al., 1989). Histological study of lungs from horses with mild, moderate and severe chronic small airway disease consistently revealed a greater density of lesions in the diaphragmatic lobes (Winder and von Fellenberg, 1988). To understand further the aetiology and/or pathophysiology of EIPH, we will first explore some aspects of general mammalian and specific equine pulmonary and bronchial vascular anatomy and physiology. Exercise-related changes in these systems in normal and EIPH-positive horses will be briefly reviewed.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Octreotide and diabetes: theoretical and experimental aspects.

Diabetes is characterized by paradoxical hypersomatotropinemia and hyperglucagonemia. The latter appears to enhance the tendency in imperfect metabolic control to reduce nitrogen balance, and the former appears to accelerate the deterioration of carbohydrate and lipid metabolism, and also to induce peripheral insulin resistance and hyperinsulinemia. In addition to direct metabolic effects, increasing evidence points to an association between hypersomatotropinemia and a number of metabolically dependent, characteristic functional abnormalities linked to the development of late diabetic manifestations. These include increased capillary fragility, lipid and hemostatic aberrations, tissue hyperperfusion, including increased cardiac output and renal plasma flow, and kidney hypertrophy. In theory, octreotide's actions could reduce these aberrations, and, in fact, this has been confirmed in recent experimental trials.

Animals

[Hematoma of the adrenal glands and heparin].

The diagnosis of adrenal haemorrhage complicating heparin therapy is often delayed, despite computed tomography (CT). Moreover, its pathogenesis is not clear. Adrenal haemorrhages are often seen in cases where there is no unduly excessive anticoagulation, and can be accompanied by a paradoxical thrombosis of the central adrenal vein. Symptoms usually occur within the first 8 to 12 days after starting heparin. The difficulty in establishing the diagnosis stems from the fact that symptoms are rather nonspecific: abdominal pain and backache, nausea, vomiting, lethargy, weakness, hypotension, hyperpyrexia. To confirm the diagnosis, both hormonal proof of adrenal failure and anatomic evidence of haemorrhage must be found. Early CT scans may show the haemorrhage. Several possible causes have been put forward to account for these adrenal haemorrhages. The degree of anticoagulation did not seem to be a prerequisite, 30 to 50% of patients showing no evidence of other bleeding or coagulation tests outside the therapeutic range. Capillary fragility of old age might be a factor. Stress would seem to be an important factor predisposing to adrenal haemorrhage. Many authors consider the paradoxical central vein thrombosis as a result of the haemorrhage rather than its cause, whereas other conclude the opposite. Unfortunately, to date coagulation studies are often incomplete; platelet counts were missing in most reports published before 1985. Since that date, a heparin induced thrombosis-thrombocytopaenia syndrome (HITTS), in which thrombosis may occur in any vascular bed, has been recognized with increasing frequency. Nine cases of adrenal haemorrhage associated with HITTS have been reported. It seems highly likely that a proportion of cases of heparin-related adrenal destruction are due to HITTS.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Gland Diseases

Blood coagulation, fibrinolysis and plasma proteins in women with normal and with excessive menstrual blood loss.

A group of women with excessive menstrual blood loss (menorrhagia) without any known local or general underlying disease was studied and compared to a group of women with normal menstrual blood loss. Blood coagulation, platelet function and fibrinolysis as well as a variety of plasma proteins were analyzed on six occasions during one menstrual cycle. Women with menorrhagia were found to have a slightly higher concentration of fibrinogen--fibrin degradation products, a higher factor V and VIII activity, higher antithrombin III, alpha 1-antitrypsin concentrations and higher antifibrinolytic activity than the normal women. The concentration of albumin, beta IE-globulin, orosomucoid, ceruloplasmin and IgG were lower in women with memorrhagia than in normals. The capillary fragility did not differ significantly between the groups. The observed differences in clotting factors between the groups could not have caused the differences in blood losses.

Adult

Assessment of calcium dobesilate in diabetic retinopathy. A double-blind clinical investigation.

In this double-blind, randomized trial, which lasted for 2 years, the authors investigated the efficacy of calcium dobesilate on diabetic retinopathy. 68 patients (51 on the active substance, 17 on placebo) participated in the study. The statistical analysis of the results indicate that calcium dobesilate acts as a potent angioprotector, capable of preventing both intra and extraretinal hemorrhages. The drug also lowers the incidence of exudate formation and improves visual acuity.

Benzenesulfonates

[Thoracic endometriosis--2 case reports and review of the literature].

Thoracic endometriosis is characterised by recurring pulmonary symptoms in association with the menstrual period. Pleural endometriosis manifests itself as recurring pneumothorax or hematothorax while pulmonary endometriosis is characterized by hemoptysis. The pathogenetic mechanism is not completely understood but it appears that hematogenous and lymphangitic embolization of endometrial tissue may play a significant part in parenchymal and pleural endometriosis respectively. Clinical symptoms begin with ovulation. Hemoptysis is explained by sloughing off of decidual tissue and an increased capillary fragility during menstruation. Rupture of pleurally based alveoli in the vicinity of endometrial tissue or necrosis of the diaphragm at the side of diaphragmatic endometrial implants might be causative for the development of a pneumothorax. Therapy of both forms of thoracic endometriosis consists in hormonal suppression but in some cases surgical intervention might become necessary.

Endometriosis

The effect of smoking and menopause on the small blood vessels.

The small blood vessels were examined in 31 premenopausal and 31 postmenopausal women. In each group there were 14 non-smokers and 17 smokers of age groups 35-45 and 45-59. The women underwent full gynecological examination. Blood pressure was normal in each. The small blood vessels were examined by capillaroscopy of conjunctivae and nailfolds, by oscillometry of the radial artery, skin thermometry of the wrist and terminal phalanx, and by capillary fragility. When all abnormalities in non-smokers were compared with those in smokers in the menopausal groups, a significant difference was found, (Table 4), to the disadvantage of the smokers.

Adult

[Hereditary hemorrhagic telangiectasia associated with von Willebrand's disease; literature review].

A 23-year-old female was admitted to our hospital in July 1987, because of cutaneous macular telangiectasia on her extremities and hypermenorrhea. In 1983, she began to notice small red spots on her palms. During next several years, these telangiectasia increased in number and spread all over her body. In 1986, she had a history of melena and prolonged bleeding after dental extraction. Her lower legs have turned red purple during the gait for a long time. Her older brother and two paternal cousins have experienced frequent epistaxis. The hemostatic laboratory data revealed prolonged IVY bleeding time and APTT, impaired capillary fragility, decreased vWf:Ag and VIII:C levels, depressed Rcof and severe decreased platelet adhesiveness, vWf mobility on two-dimensional crossed immunoelectrophoresis was normal. Platelet aggregation was reduced after addition of ristocetin and collagen. This case was diagnosed Osler-Weber-Rendu disease (Osler disease) associated with von Willebrand's disease (vW disease) type I. Previously, 28 Cases (8 families) with these two disease association have been reported. These disease seems to coexist as an inevitable consequence, because the disorder of vascular endothelial cells where von Willebrand factors are synthesized is a common pathogenetic factor in Osler disease. It is considered that such a case is secondary vW disease. Moreover, previous reports of Osler disease associated with various hemostatic defects are reviewed.

Adult