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A study on pulmonary hemorrhage experimentally produced by the Shwartzman mechanism in rabbits. Possible relationship to pulmonary hemorrhage in man.

The lung was chosen as a target organ of the univisceral Shwartzman reaction in this study. Rabbits were selected as the experimental animal, and E. coli endotoxin was used as the Shwartzman reagent. Preparative procedures were applied through the trachea into the lung in several ways; direct injection of the endotoxin solution and inhalation of the atomized endotoxin solution by natural breathing. The provocation was made by intravenous injection of the same endotoxin 24 hours later. The lung showed severe hemorrhage associated with inflammatory cell infiltration, interstitial fibrosis, macrophage accumulation, etc. The severity and extent of these changes varied, to some extent, between groups as well as between individual animals. The fundamental character was, however, common to all, and the incidence of the lesion in the lung was quite high. The relationship of the present results to idiopathic pulmonary hemorrhage and Goodpasture's syndrome is also discussed from the viewpoint of human pathology.

Animals↗

Protection against myxomatosis and rabbit viral hemorrhagic disease with recombinant myxoma viruses expressing rabbit hemorrhagic disease virus capsid protein.

Two myxoma virus-rabbit hemorrhagic disease virus (RHDV) recombinant viruses were constructed with the SG33 strain of myxoma virus to protect rabbits against myxomatosis and rabbit viral hemorrhagic disease. These recombinant viruses expressed the RHDV capsid protein (VP60). The recombinant protein, which is 60 kDa in size, was antigenic, as revealed by its reaction in immunoprecipitation with antibodies raised against RHDV. Both recombinant viruses induced high levels of RHDV- and myxoma virus-specific antibodies in rabbits after immunization. Inoculations by the intradermal route protected animals against virulent RHDV and myxoma virus challenges.

Animals↗

Massive pulmonary hemorrhage from dual circulation pulmonary arteriovenous malformations in hereditary hemorrhagic telangiectasia.

Pulmonary arteriovenous malformations (AVMs) are commonly supplied by the pulmonary arterial system and rarely by the systemic bronchial circulation. The authors outline the case of a young woman with pulmonary AVMs as part of hereditary hemorrhagic telangiectasia with the uncommon presentation of massive hemoptysis. Management of her recurrent, life-threatening pulmonary hemorrhage was complicated by pulmonary AVMs that were supplied by both the pulmonary and systemic bronchial arterial circulatory systems. Transcatheter embolotherapy of the higher pressure bronchial systemic circuit was necessary for acute hemostasis.

Adult↗

Intraventricular hemorrhage in the newborn beagle puppy. A limited model of intraventricular hemorrhage in the premature infant.

The term beagle puppy has been used extensively as an experimental model of intraventricular hemorrhage (IVH) in the preterm infant. Fourteen variables were selected which were considered theoretically important to both the model and the preterm infant, and the data were subjected to discriminant analysis. Use of only three variables in combination correctly predicted whether an animal would sustain germinal matrix hemorrhage: baseline blood pressure, Pco2, and temperature. The model does not involve ischemia, which appears to be the sentinel but not singular insult in the IVH of preterm infants.

Animals↗

Subinternal limiting lamina hemorrhages associated with sudden vascular pressure rise: yellow preretinal hemorrhages.

A group of patients with subinternal limiting lamina hemorrhages associated with the Valsalva maneuver have been described. A majority of the patients have shown a striking yellowish coloration to the globular preretinal lesions during their evolution. This unique coloration is probably due to the accumulation of bilirubin during hemoglobin disintegration. Visual prognosis is usually excellent and no retinal or vascular abnormalities have been found after the hemorrhage disappears. The unusual fundus picture presented by this lesion may pose diagnostic problems if the patient is initially seen when this yellow mass is present.

Adult↗

Use of the original, modified, or new intracerebral hemorrhage score to predict mortality and morbidity after intracerebral hemorrhage.

BACKGROUND AND PURPOSE: A simple clinical scale of intracerebral hemorrhage (ICH), comprising the Glasgow Coma Scale score, age, infratentorial origin, ICH volume, and intraventricular hemorrhage, was recently shown to predict 30-day mortality. We studied how well the original ICH Score would predict morbidity and mortality and determined whether modification would improve the predictions. METHODS: Patients admitted to a regional hospital with acute ICH in 1999 were reviewed. Independent predictors of mortality or good outcome (modified Rankin score or=3 and <3 provided the best Youden's index of diagnostic test in all ICH Scores for mortality and good outcome, respectively. The original and modified ICH Scores predict mortality equally well. The new and modified ICH Scores are slightly better for prediction of good outcome. CONCLUSIONS: All 3 ICH Scores are simple clinical grading scales. As reliable predictors of good outcome and/or mortality, they are useful in clinical research studies and standardization of clinical protocols.

Aged↗

Myosin light chain phosphorylation and contractile proteins in a canine two-hemorrhage model of subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Subarachnoid hemorrhage (SAH) impairs both contraction and relaxation response in cerebral arteries. We tested the hypothesis that cerebral vasospasm might be ATP-independent contraction, such as latch state, and protein synthesis might be substantially downregulated due to ATP consumption after long-lasting contraction. METHODS: Chronic cerebral vasospasm was induced in the canine 2-hemorrhage model of SAH. The normal and spastic basilar arteries were stabilized in Krebs-Henseleit solution, and contraction was induced by 30 micromol/L prostaglandin F2alpha (PGF2alpha) in vitro and in vivo. Before and at 15 minutes and 1 hour after the treatment with PGF2alpha, the levels of phosphorylated 20-kDa myosin light chain (MLC20) were measured. The time course of expression of contraction proteins actin and MLC20, and contraction-inhibiting proteins h-caldesmon and calponin was determined by immunoblotting techniques. RESULTS: A significant vasospasm occurred in the basilar artery during days 4 to 21, most prominently on days 7 and 14. There were no significant differences in the baseline levels of phosphorylated MLC20 between normal and spastic basilar arteries. The increase in MLC20 phosphorylation by PGF2alpha was significantly attenuated in the spastic basilar artery in vitro and in vivo (P<0.05). The immunoreactivity for actin, h-caldesmon, and calponin in the spastic basilar arteries was progressively decreased until day 14 and returned to the normal level on day 21. In contrast, protein levels of MLC20 did not significantly change during days 0 to 21. CONCLUSIONS: Chronic cerebral vasospasm closely resembles the latch state, and temporary deficiencies of contractile proteins may result from increased destruction and inhibition of protein synthesis.

Animals↗

Postnatal changes in cerebral oxygen extraction in the preterm infant are associated with intraventricular hemorrhage and hemorrhagic parenchymal infarction but not periventricular leukomalacia.

Fluctuations in cerebral hemodynamics have been implicated in the pathogenesis of acquired brain damage in babies born prematurely. This study examined the changes in cerebral fractional oxygen extraction (FOE) over the first 3 d after birth in 25 very-low-birth-weight preterm infants. Twelve infants had no major cerebral injury and 13 had acquired brain injury; cystic periventricular leukomalacia (PVL) was present in 4 and intraventricular hemorrhage (IVH) in 9, of whom 2 also had hemorrhagic parenchymal infarction (HPI). Normal values (median, 5(th)-95(th) centiles) for cerebral FOE in very-low-birth-weight infants with no cerebral injury were 0.38 (0.23-0.53) on d 1, 0.31 (0.18-0.45) on d 2, and 0.28 (0.17-0.38) on d 3. Infants who developed cystic PVL had no significant change in cerebral FOE during the first 3 d after birth. By contrast, cerebral FOE fluctuated in infants with IVH over the 3 d of measurement, decreasing from d 1 to d 2 (p = 0.03) and increasing from d 2 to d 3 (p = 0.02). The highest cerebral FOE values were seen in the two infants with HPI. The different patterns of change in cerebral FOE with HPI and cystic PVL provide additional evidence that the pathogenesis of these two conditions is different. Because high cerebral FOE is likely to be a consequence of low cerebral oxygen delivery, probably because of low cerebral blood flow, our results indicate that fluctuations in cerebral blood flow may occur when there is IVH or HPI.

Brain↗

Aneurysms in relatives of patients with subarachnoid hemorrhage: frequency and risk factors. MARS Study Group. Magnetic Resonance Angiography in Relatives of patients with Subarachnoid hemorrhage.

OBJECTIVE: To evaluate the frequency and identify risk factors of unruptured aneurysms in first-degree relatives of patients with sporadic subarachnoid hemorrhage (SAH). BACKGROUND: First-degree relatives (parents, siblings, and children) of patients with SAH have a three to seven times increased risk of SAH. METHODS: Magnetic resonance angiography (MRA) was performed in 626 first-degree relatives of a consecutive series of 193 index patients with "sporadic" SAH (participation rate, 78% of eligible relatives). The authors recorded demographic and medical data, and performed blood pressure measurements and blood tests (cholesterol, high-density lipid cholesterol, triglycerides, apoprotein A1, lipoprotein a, glucose). RESULTS: Aneurysms were found in 25 of 626 relatives (4.0%; 95% CI, 2.6 to 5.8%), and 6 relatives had multiple aneurysms. Index patients with multiple aneurysms and a younger age had a higher risk of aneurysms in relatives. Siblings of index patients had a four times higher risk than children. In screened relatives female sex, increasing age, polycystic kidney disease, hypertension, and elevated levels of cholesterol and glucose tended to be associated with a higher risk of aneurysms. No increase in risk was conferred by smoking or alcohol use, or by a previous family history of SAH or of atherosclerosis. CONCLUSIONS: First-degree relatives of index patients with sporadic subarachnoid hemorrhage have a 4.0% chance of intracranial aneurysms. Being a sibling of the index patient is the most important risk factor. Risk factors for general atherosclerosis (hypertension, smoking, hypercholesterolemia, high levels of blood triglycerides, lipoprotein a, and apoprotein A1) and use of alcohol do not increase the risk of intracranial aneurysms significantly in these relatives.

Adult↗

Time course in the development of cerebral vasospasm after experimental subarachnoid hemorrhage: clinical and neuroradiological assessment of the rat double hemorrhage model.

OBJECTIVE: The "double hemorrhage" model in the rat is frequently used to simulate delayed cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH) in humans. However, an exact neurological and angiographic characterization of the CVS is not available for this model so far and is provided in the present investigation. Additionally, perfusion weighted imaging (PWI) at 3 tesla magnetic resonance (MR) tomography was implemented to assess the reduction in cerebral blood flow (CBF). METHODS: In a prospective, randomized setting CVS was induced by injection of 0.2 ml autologous blood twice in the cisterna magna of 45 male Sprague-Dawley rats. The surviving animals were examined on Days 2, 3, 5, 7 and 9 and compared to a sham operated control group (n = 9). Rats were neurologically graded between 0 and 3, followed by MRI and selective digital subtraction angiography (DSA). The relative CBF was set in relation to the perfusion of the masseter muscle. RESULTS: The neurological state was significantly worsened on Day 2 (Grade 3), 3 (Grade 3), and 5 (Grade 2) (medians). The relative CBF/muscle BF ratio (2.5 +/- 0.8 (SAH) versus 9.2 +/- 1.3 (sham) (mean +/- SEM) and the basilar artery (BA) diameter (0.15 +/- 0.02 mm (SAH) versus 0.32 +/- 0.01 mm (sham) were significantly decreased on Day 5. Correlation between relative CBF/muscle BF ratio and BA diameter was 0.70. CONCLUSION: A valid and reproducible CVS simulation was proven by neurological score, DSA, and PWI on Day 5. Furthermore, our data demonstrate the practicability and validity of MR PWI for the monitoring of CVS in a rat SAH model.

Angiography, Digital Subtraction↗

Dynamics of intraventricular hemorrhage in patients with spontaneous intracerebral hemorrhage: risk factors, clinical impact, and effect of hemostatic therapy with recombinant activated factor VII.

OBJECTIVE: To evaluate predictors of intraventricular hemorrhage (IVH) and IVH growth, impact of IVH growth on outcome, and impact of recombinant activated factor VII (rFVIIa) in patients with intracerebral hemorrhage (ICH). METHODS: We analyzed 374 patients out of 399 who were randomized to rFVIIa (40, 80, or 160 mug/kg) or placebo for ICH (diagnosed within 3 h of symptoms). Risk factors for IVH growth (>2 ml increase in IVH volume at 24 h), and death or severe disability (modified Rankin scale score 4-6) at 3 months were identified (logistic regression). RESULTS: IVH was present in 38% (n = 141) of patients at baseline and 45% (n = 169) by 24 hours. IVH growth, by 24 hours, occurred in 17 and 10% of placebo- and rFVIIa-treated patients, respectively (P = 0.037). Risk factors for IVH growth included baseline mean arterial pressure greater than 120 mmHg, larger baseline ICH volume, IVH present at baseline, shorter time from symptom onset to baseline computed tomographic scan, and treatment (rFVIIa versus placebo) (all, P < or = 0.037). Predictors of death or severe disability included older age, lower baseline Glasgow Coma Score, larger baseline ICH volume, IVH growth greater than 2 ml, IVH present at baseline or 24 hours, and treatment (rFVIIa versus placebo) (all, P < or = 0.0405). CONCLUSION: Presence of IVH at any time and early IVH growth worsen clinical outcome and increase mortality. Elevated mean arterial pressure at baseline may be a modifiable risk factor for IVH growth. Beneficial effects of rFVIIa on ICH outcome may be mediated, at least in part, by reducing IVH growth.

Aging↗

Frameless stereotactic aspiration and thrombolysis of deep intracerebral hemorrhage is associated with reduction of hemorrhage volume and neurological improvement.

INTRODUCTION: This is a phase-2 safety trial to demonstrate the ability of frameless stereotactic aspiration and thrombolysis of ICH to safely remove blood. METHODS: Patients with ICH in the deep basal ganglia and internal capsule of > 5 cc volume were consented to undergo computed tomographic imaging for frameless stereotactic guidance registration. Using the frameless stereotactic (CT) guidance, a 4-mm diameter catheter was inserted into the body of the hematoma using a frontal burr hole approach. The catheter was aspirated and then flushed with saline and aspirated to remove unclotted blood. After a confirmatory CT scan to localize the catheter, 1 mg of recombinant tissue plasminogen activator (t-PA) was infused into the clot, permitted to bathe the clot for 30 minutes, and then drained into a closed circuit collection system. t-PA was infused every 8 hours for 48 hours. A follow up CT scan was obtained at 48 hours. RESULTS: 28 patients with ICH (mean age 67.1) were admitted and underwent the procedure. Mean initial ICH volume was 54.6 cc +/-6 37.8. Mean time from onset to aspiration was 44 hours (range 7-180). Mean initial NIH Stroke scale (NIHSS) score was 24 (range 15-33). Compared with initial CT scan, there was a mean reduction of ICH volume by 77 +/-6 13% on final CT scan (p < 0.0002). Compared with initial NIHSS, the discharge mean NIHSS (16 +/- 6) was significantly improved (p < 0.001). There were no infectious, hemodynamic or neurologic complications. There were no episodes of symptomatic hemorrhagic enlargement and one case of asymptomatic bleeding along the catheter tract. CONCLUSION: Frameless stereotactic aspiration and thrombolysis (FAST) of deep spontaneous intracerebral hemorrhage is a safe therapy that is associated with reduction in ICH volume, early improvement in NIHSS and potentially could be used to improve outcome.

Adult↗

Recurrent petechial hemorrhages and hemorrhagic vesicles of the oral mucosa.

The foregoing case is an example of amyloidosis in which biopsy of a hemorrhagic vesicle on the buccal mucosa established the diagnosis. Once the diagnosis was made, the patient's cardiomyopathy, nephrotic syndrome, hepatomegaly, GI hemorrhage, hematuria, and oral lesions readily were explained.

Amyloidosis↗

Dissecting aneurysm of the middle cerebral artery manifesting as subarachnoid hemorrhage and hemorrhagic infarctions--case report.

A 46-year-old woman presented with a dissecting aneurysm of the right middle cerebral artery manifesting as subarachnoid hemorrhage followed by hemorrhagic infarctions. The aneurysm was clipped and wrapped. However, serial angiography showed progression of the lesion, which was probably responsible for the clinical course of this patient. Intracranial dissecting aneurysms are less common, and the natural history of these lesions is unclear. Conservative management might be preferable in this patient.

Aortic Dissection↗

Retinal hemorrhages in the preterm neonate. A prospective randomized study comparing the occurrence of hemorrhages after spontaneous versus forceps delivery.

The incidence and magnitude of retinal hemorrhages (RH) in a group of 23 preterm infants (29-35 weeks) born spontaneously in vertex presentation have been compared with those of 23 others (28-35 weeks) born by gentle extraction with small forceps. Distribution to the groups was random. The overall frequency of RH in both groups together was low, 6%, with no statistically significant difference between the groups. No fundi with severe (grade III) hemorrhages were seen. Both the incidence and magnitude of RH were less in the preterm neonates when compared with previously reported figures in term infants born spontaneously or with forceps extraction. The study provides further evidence in support of the hypothesis that fetal head compression with venous congestion is the main cause of RH in the newborn.

Delivery, Obstetric↗

Transmission electron microscopic study of the hemorrhagic spots in patients with epidemic hemorrhagic fever in the early stage.

Epidemic hemorrhagic fever (EHF) virus particles were found in the squamous epithelial cells and the capillary endothelial cells of the petechial spots located on the mucous membrane of the soft palate in 3 patients with severe early-stage EHF with transmission electron microscopy. The virus particles were round or oval in shape, about 100 nm in diameter, with a two-layer lipid envelope from which spikes were protruding. The nucleocapsid of the virus appeared to be hollow microfilamentoid or dense granules. Meanwhile, budding virus particles with a diameter of 80 nm were found in the enlarged Golgi apparatus. The infected cells displayed an enlarged and proliferating Golgi apparatus. The morphological characteristics of the viron mentioned above coincided with those of the virus particles of the family Bunyaviridae. This study is the first to demonstrate that the squamous epithelial cells on the mucous membrane of the soft palate are the target cells of EHF infection and to provide subcellular morphological evidence of petechial hemorrhage at the soft palate.

Adult↗

Nosocomial outbreak of viral hemorrhagic fever caused by Crimean Hemorrhagic fever-Congo virus in Pakistan, January 1976.

This paper describes the clinical, epidemiological, and laboratory investigations undertaken to isolate and identify the etiological agent of a nosocomial cluster of hemorrhagic fever cases due to Crimean hemorrhagic fever (CHR)-Congo virus. Since this virus is usually transmitted by ticks it was surprising that the index case, in a nomadic shepherd, occurred during the winter season when ticks are relatively inactive. These are the first cases of CHF-Congo virus found in humans in Pakistan. Investigations on other biological properties, particularly strain differences and virulence, are being continued at the Islamabad laboratory.

Adult↗

Protection of turkeys from hemorrhagic enteritis with a recombinant fowl poxvirus expressing the native hexon of hemorrhagic enteritis virus.

Hemorrhagic enteritis (HE) is an economically important disease of turkeys caused by a type II aviadenovirus, hemorrhagic enteritis virus (HEV). The vaccines currently available to the commercial poultry producer are highly effective in preventing disease outbreaks; however, they are immunosuppressive. A recombinant fowl poxvirus (rFPV) expressing the native hexon of HEV has been shown to induce an anti-HEV humoral immune response in turkeys. In this study, the rFPV expressing the native hexon of HEV was compared with a commercial HEV vaccine (vxHEV) for its ability to protect turkeys from virulent HEV challenge. Complete protection from the enteritis of HE was achieved in experimental groups vaccinated with either the rFPV or the vxHEV. Lymphocyte stimulation was measured in turkeys inoculated with rFPV, vxHEV, or a sublethal dose of HEV or not inoculated. No statistically significant immunodepression was observed in turkeys receiving the rFPV.

Adenoviridae Infections↗