bluuebunny/crossref_metadata_2025 huggingface dataset:
Intraocular Larva Migrans in Dogs
Authors: Rubin L. F. , Saunders L. Z.
Published: July 2017

The clinical and histologic features are described in 4 cases of intraocular larva migrans in dogs. Clinically, a small, raised, greyish nodule about 1/4–1/6 the diameter of the cptic disc was visible on the surface of the retina. In 3 of the cases, the lesion was recognized during ophthalmoscopic examination, and in one it was discovered histologically. The lesion is a granuloma resembling those seen in other organs of dogs affected by visceral larva migrans, and contains nematode larvae of the genus Toxocara.
Cystic Mucinous Hypertrophy of the Mucosa of the Gall Bladder in the Dog
Authors: Kovatch Robert M. , Hildebrandt Paul K. , Marcus Leonard C.
Published: July 2017

Cystic mucinous hypertrophy was observed in the gall bladder of nine mature to aged dogs that had no known clinical signs referable to the condition. The cause could not be determined.
The Lesions in Bovine Udders Shedding Hemolytic Coagulase-Positive Staphylococci
Authors: Stabenfeldt G. H. , Spencer G. R.
Published: July 2017

Coagulase-positive staphylococci occurred in the mammary tissue in a few sites of each infected quarter. Lesions varied from acute to chronic in a single quarter with neutrophilic infiltration and vacuolation of alveolar epithelial cells being associated with recent blocking of small collecting ducts by exudate. Chronic inflammatory changes were most prominent in the wall of small ducts, and fibrosis sometimes extended into the lumen or occluded it. Chronic abscesses originated in blocked areas of small mammary ducts. Ductal lesions probably contributed to focal atrophy duc to slowed drainage of milk.
Thrombocytopenic Purpura in Baby Pigs Caused by Maternal Isoimmunization
Authors: Nordstoga Knut
Published: July 2017

The pathologic findings in thrombocytopenic purpura in baby pigs, caused by maternal isoimmunization in repeated pregnancies are described. Autopsy showed the picture of a hemorrhagic diathesis. Characteristic findings were paleness of various tissues, scattered hemorrhages in the skin, subcutaneous and muscular tissues and hemorrhages in mucous membranes of the respiratory system, urogenital tract and alimentary canal. The lymph nodes were enlarged and hemorrhagic. The most outstanding histologic finding was a disappearance of the megakaryocytes from the bone marrow.
The Ocular Disease of Young Terrapins Caused by Vitamin A Deficiency
Authors: Elkan E. , Zwart P.
Published: July 2017

The histopathology of a disease is described which commonly affects young terrapins of the genera Clemmys, Pseudemys, and Graptemys kept in captivity. The first signs noticed are swelling of the eyelids and refusal to feed. Investigation of 32 terrapins revealed extensive epithelial metaplasia in the ophthalmic glands and in the excretory ducts of the liver, pancreas, and kidneys. The localization and the type of metaplasia seen are similar to those which occur in man, cattle, horses, sheep, and fowl suffering from avitaminosis A.

Occasional successes of treatment with vitamin A support the assumption that the mortality is mainly due to avitaminosis A and should be treated or prevented accordingly.
Familial Amaurotic Idiocy in Male German Shorthair Pointers
Authors: Karbe E. , Schiefer B.
Published: July 2017

Amaurotic idiocy was recognized in a family of German shorthair pointers. The disease affected only males and their familial relation indicated that this apparently sex-linked condition was probably inherited as a recessive character. The animals developed mental regression, ataxia, and impaired vision. The progressive disease started slowly at about six months and made euthanasia necessary at the age of 10 to 18 months.

One of the dogs was investigated pathologically. The characteristic lesion consisted of degeneration and enlargement of neurons throughout the central nervous system, including the retina. The cytoplasm of the neurons was engorged by a glyco-lipoid-protein complex containing neuraminic acid indicating the presence of gangliosides. The disease closely resembled late infantile familial amaurotic idiocy (Bielschowsky) in man.
Spontaneous Bilateral Renal Cortical Necrosis in Animals
Authors: Nordstoga K.
Published: July 2017

Six cases representing three species, previously diagnosed as bilateral renal cortical necrosis (BCN), were studied histologically. One horse had vascular lesions including fibrinoid necrosis and fibrinous thrombi in various organs. Intrarenally these lesions occurred in interlobular arteries, afferent arterioles, and glomeruli. Another horse had bilateral renal glomerular thrombosis but no extra-glomerular vascular lesion. Distinct fibrinous deposition in the renal vessels did not occur among the other four cases. A comparison is drawn between the characteristic lesions in the generalized Shwartzman reaction (GSR) and BCN as diagnosed in our autopsy material. The renal alterations were compatible with GSR in two horses only among the six cases.
The Generalized Shwartzman Reaction and Haemophilus Infections in Pigs
Authors: Nordstoga K. , Fj⊘lstad M.
Published: July 2017

Four pigs were injected intravenously twice at a 24-hour interval with disintegrated cells of Haemophilus parainfluenzae and killed 24 h later. Two of the pigs developed bilateral renal cortical necrosis (BCN) and renal and extrarenal vascular lesions characterized by fibrinous thrombosis and fibrinoid degeneration. The BCN is interpreted as being the result of a generalized Shwartzman reaction to bacterial endotoxin. The experiment supports the view that the vascular lesions accompanying outbreaks of Haemophilus infections in swine are due to a generalized Shwartzman reaction.
Experimental Pulmonary Talcum Granuloma and Epithelial Hyperplasia in the Chinchilla
Authors: Trautwein G. , Helmboldt C. F.
Published: July 2017

Chronic pulmonary irritation was induced in the chinchilla with talcum powder. Two effects on the pulmonary parenchyma were (1) exudative pneumonia, progressing quickly to predominantly proliferative pneumonia with formation of giant cell granulomas around talcum particles and (2) metaplasia of the alveolar epithelium in the areas adjacent to the granulomas. Early changes were hyperplasia of alveolar cells followed by their transformation into cuboidal cells to form a continuous lining in affected alveoli. In the final stage lesions approached an adenomatous appearance with tall columnar epithelium lining the affected alveoli. The experimental findings support the concept that chronic pulmonary irritation may be prerequisite to the development of adenomatous lesions in spontaneous pulmonary adenomatosis in the chinchilla.
Aortic Ring Rupture in Stallions
Authors: Rooney J. R. , Prickett M. E. , Crowe M. W.
Published: July 2017

Eight cases of acquired rupture of the aortic ring in the right coronary sinus with dissection (cardioaortic fistula) into the interventricular septum and into the right ventricle have been described in stallions. It is postulated that the ruptures are due to increased blood pressure during breeding and the direction of a recoiling column of blood against an area of anatomic weakness.
Experimental Feline Infectious Enteritis in the Germfree Cat
Authors: Johnson G. R. , Koestner A. , Rohovsky M. W.
Published: July 2017

Selected tissues from 13 germfree and 3 specific pathogen-free cats experimentally infected with feline infectious enteritis were studied electron microscopically. Intestinal lesions consisting of dilatation of intercellular spaces and of endoplasmic reticular cisternae occurred only in specific pathogen-free cats. No lesion was demonstrated in the intestine of infected germfree cats, indicating that the virus of feline infectious enteritis may not be solely responsible for the intestinal lesions described in the naturally occurring disease. The lesions in the lymph nodes were identical in specific pathogen-free and germfree cats and consisted of lymphocytic destruction within 72 hours post-inoculation and reactive proliferation of reticular cell-macrophages and plasma cells. The preferred designation of this disease in cats as feline infectious panleukopenia is supported.
Hartmannellosis in a Bull
Authors: McConnell Ernest E. , Garner F. M. , Kirk John H.
Published: July 2017

A case of Hartmannella sp. (Acanthamoeba) infection in a 1 1/2-year-old Holstein bull is reported. The disease was manifested by multifocal necrohemorrhagic nodules throughout the lung. Diagnosis was made on a morphologic basis by observing typical organisms within these nodules. The suggested mode of entry of the organism was via inhalation of the organisms or by direct extension from an inapparent nasal infection.
Cerebrale Neurofibrome beim Finnwal, Balaenoptera physalus
Authors: Pilleri G.
Published: July 2017

Two neurofibromas located at the base of the ventral paraflocculus of the cerebellum in an adult fin whale (Balaenoptera physalus) are described histologically. Both tumors were rich in collagenous fibers and related to nervous structures. There were remnants of atrophic myelinated nerve fibers, in loose arrangement, and ganglion cells within the neoplastic tissue.
Round Heart Disease of the Domestic Fowl (Gallus gallus) in Bulgaria
Authors: Shishkov N. , Obreshkov C. , Enchev St.
Published: July 2017

Clinical and pathologic methods and attempts at transmission were employed to study so-called round heart disease of the domestic fowl. These studies indicate that the disease is noninfectious. The use of old litter in poultry houses contributed to the appearance of the disease but was not the sole etiologic factor. Zinc-plated feeders were not involved. The disease could not be reproduced by inoculation or feeding of affected material. Treatment of affected fowl with selenium dioxide was ineffective. Fatty and vacuolar degeneration of the myocardium and severe renal necrosis occurred. The disease is attributed to toxic injury. Its mechanism and the factors that condition it remain unknown.

Klinische und pathologische Untersuchungsmethoden sowie Übertragungsversuche wurden zur Untersuchung der sogenannten «Kugelherz» Krankheit vom Haushuhn verwendet.
Avian Amyloidosis
Authors: Cowan Daniel F.
Published: July 2017

The incidence, staining qualities, organ distribution, age of affected individuals, and disease conditions associated with avian amyloidosis occurring in a population of 1698 zoo birds were analysed. Amyloid disease occurs in older birds, predominantly affecting the liver, spleen, and adrenals. The staining qualities and morphology are very similar to mammalian amyloid. The disease occurs mainly in exotic or poorly adapted birds, apparently related to environmental factors rather than to any specific predisposing disease.
Avian Amyloidosis
Authors: Cowan Daniel F.
Published: July 2017

The incidence and contributing factors relating to amyloidosis in the family Anatidae were analysed by genus and species. There is a striking segregation of susceptibility by species, with exotic, poorly adapted or excessively aggressive birds being the most susceptible, and indigenous, well adapted non-aggressive or domestic types least susceptible. Other associations, such as chronic disease, are inconstant. Classifications such as primary and secondary amyloidosis do not apply to avian amyloidosis.
Calcinosis Circumscripta in the Dog with Particular Reference to Lingual Lesions
Authors: Howell J. McC. , Ishmael J.
Published: July 2017

Calcinosis circumscripta of the tongue is described in 6 large, young dogs. The lingual lesions are identical with calcinosis circumscripta as described in the literature and 10 subcutaneous lesions that we examined. It is suggested that the lingual and subcutaneous lesions are part of one disease process and that the former are more frequent than is indicated in the literature. Apocrine glands were not found in association with the lingual lesions or at comparable sites in the tongues of 6 unaffected dogs; it appears that their presence is not a prerequisite for the development of the lesion. Ten calcifying epitheliomas were also examined and evidence is presented which strongly suggests that this lesion be distinct from calcinosis circumscripta.
Ein Fall von Carcinoid bei einem Elefanten
Authors: Werle E. , Haendle H. , Schmal A.
Published: July 2017

A carcinoid, metastatic in the liver, was found in an elephant in which kallikrein was demonstrated. This lends support to the hypothesis that kallikrein participates in the production of the carcinoid syndrome.
Aortic Body Tumor in a Cat
Authors: Buergelt Claus-D. , Das Krushna M.
Published: July 2017

Multicentric, moderately malignant tumors of the nonchromaffin paraganglia at the site of the aortic body, at other sites of the cardiovascular system, and in the cranial mediastinal lymph nodes were discovered incidentally at autopsy of a 7-year-old female Siamese cat. Metastases were evident grossly in the myocardium, pericardium, and cranial mediastinal lymph nodes, and histologically as tumor emboli in the stromal vessels and in epicardial, myocardial, and pulmonary lymph channels.
Ultrastructural Evidence for the Viral Etiology of Feline Infectious Peritonitis
Authors: Zook B. C. , King N. W. , Robison R. L. , McCombs H. L.
Published: July 2017

Filtration studies indicate that the causative agent of feline infectious (fibrinous) peritonitis is less than 200 m μ in smallest dimension. Viral particles 94 m μ in diameter, within and budding into the endoplasmic reticulum of the mesothelial cells in areas of inflammation, were found by electron microscopy and may be the etiologic agent. No bacterium or mycoplasma was cultured from peritoneal exudate, nor identified in affected tissues.
A Neuropathy in Goats Caused by Experimental Coyotillo (Karwinskia humboldtiana) Poisoning
Authors: Charlton K. M. , Pierce K. R.
Published: July 2017

Seven goats were poisoned with daily oral doses of coyotillo fruits and killed at various times after day 12. The distribution of lesions was studied in a sensory nerve, in short and long motor nerves, and at proximal and distal sites of a long motor nerve.

Fibers with Schwann-cell lesions (swollen Schwann cells or segmental demyelination) were widespread and outnumbered fibers with Wallerian degeneration in most sites. The percentage of fibers that were undergoing Wallerian degeneration was much greater in long motor nerves than in short ones and was much greater at a distal site of a long motor nerve than at a proximal site. The results were compatible with axonal injury being secondary to Schwann-cell injury and cumulative throughout the lengths of affected fibers, resulting in distal axonal degeneration.
A Neuropathy in Goats Caused by Experimental Coyotillo (Karwinskia humboldtiana) Poisoning
Authors: Charlton K. M. , Pierce K. R.
Published: July 2017

Lesions in peripheral nerves from 12 goats poisoned experimentally with coyotillo were studied by light and electron microscopy. The goats were poisoned with daily oral doses of the ground coyotillo fruits and killed at various times after the first day of dosing.

Lesions at a mid-femoral site of the sciatic nerve included swelling of Schwann cells, degeneration of mitochondria, depletion of glycogen, splitting of myelin, segmental demyelination, and Wallerian degeneration. The results were suggestive of primary mitochondrial injury in Schwann cells with resultant impaired active transport, intracellular edema, splitting of myelin, and segmental demyelination.
A Neuropathy in Goats Caused by Experimental Coyotillo (Karwinskia humboldtiana) Poisoning
Authors: Charlton K. M. , Pierce K. R. , Storts R. W. , Bridges C. H.
Published: July 2017

Twenty-two goats were poisoned with daily oral doses of ground coyotillo fruits and were killed at various times after the first day of dosing. The morphologic features and distribution of lesions in the central nervous system were studied by light microscopy.

An axonal dystrophy occurred in several of the goats given high daily doses. Swellings occurred along axons of Purkinje cells in the cerebellum and in the white matter of the spinal cord. There was a fairly close correlation between the occurrence of clinical signs suggestive of the neocerebellar syndrome and the occurrence and distribution of lesions in the cerebellum.
Mycobacterium abscessus Infection in an Owl Monkey (Aotus trivirgatus)
Authors: Karlson Alfred G. , Seibold Herman R. , Wolf Robert H.
Published: July 2017

Mycobacterium abscessus was isolated from the lungs of an owl monkey which died 27 days after intraperitoneal injection of herpes virus-infected Vero cells. The lungs and liver had multiple microscopic granulomas with acid-fast microorganisms. The mycobacteria also were isolated from a Vero-cell culture inoculated with a suspension of lung and liver. The same microorganism was eventually isolated from Vero cells of the same source as that used to propagate the herpes virus for the original attempt to infect the monkey.
Experimenteller Rotlauf beim Schwein
Authors: Drommer W. , Schulz L.-Cl. , Pohlenz J.
Published: July 2017

Lesions are described in the central nervous system of 35 germ-free and 6 conventional piglets after experimental infection with different strains of Erysipelothrix insidiosa, type B. As controls 12 piglets were evaluated. The predominant findings were disturbance of permeability in the form of plasmadiapedesis and erythrodiapedesis, degeneration of neurons, and swelling of endothelial cells. Malactic foci were found in the brain stem, cerebrum and the grey matter of the cervical spinal cord of piglets belonging to three different groups. The lumens of vessels often contained free bacteria and activated monocytes with phagocytosed Erysipelas bacteria. The virulence of the strains of Erysipelas for gnotobiotic piglets was very different. Only Erysipelas strain T 28, type B, caused severe lesions in the central nervous system.
Hermaphroditism in a Rat
Authors: Magnusson Göran
Published: July 2017

A case of spontaneous unilateral hermaphroditism in a Sprague-Dawley rat is reported and 10 cases from the literature summarized.
The Dr Elizabeth Casson Memorial Lecture 2015: Pushing the boundaries and leading the way
Authors: Jackson Thérèse
Published: July 2017

The Dr Elizabeth Casson Memorial Lecture 2015, given on July 1st 2015 at the 39th Annual Conference and Exhibition of the College of Occupational Therapists, held at the Brighton Centre, Brighton.
Vascular Headaches and Cerebral Circulation: An Overview
Authors: Agnoli Alessandro , De Marinis Milena
Published: July 2017

complex network of neurotransmission systems underlies the control of the cerebral circulation. Classical neurotransmitters, vasoactive peptides and receptors have been found in cerebral arteries. Central and peripheral structures are also probably involved in the neurogenic control of the cerebral circulation. Vascular and neurotransmission changes reported in vascular headaches suggest that an alteration of the neurogenic control of the brain circulation may be implicated in vascular headaches. In particular, locus coeruleus, which may control the intracerebral adrenergic pathway, can induce vascular changes similar to those of migraine. Moreover, the trigeminal ganglion, which may induce the release of substance P, can change the extracranial and intracranial vasodilator activity. The vascular theory of migraine, proposed by Wolff, is re-evaluated on the grounds of a possible mediation of the vascular responses by neurotransmitters. It is hypothesized that a deficient modulation by enkephalins may cause alterations of locus coeruleus and/or trigeminal ganglion. The problem of pain in vascular headaches is also considered: whether it is of vascular origin or whether it is due to a dysfunction of the central nociceptive pathway. Knowledge of the neurogenic control of the cerebral circulation may be useful in understanding some pathogenetic mechanisms of vascular headaches.
Headache in Transient Ischemic Attacks (Tia)
Authors: Loeb Carlo , Gandolfo Carlo , Dall'Agata Daniela
Published: July 2017

The evaluation of headache in patients with transient ischemic attacks (TIA) has various sources of difficulty, the definition of TIA being the most relevant. The classical definition needs to be supplemented with a normal CT scan if a misleading diagnostic statement is to be avoided. The clinical features of 90 patients suffering from TIA and who had contrast-enhanced CT scans are reported. (1) Headache occurred in 30% of the patients. (2) Headache prevailed in patients with vertebrobasilar TIA compared with carotid TIA ( p < 0.05). (3) Headache prevailed as a preceding (24 h) and/or concomitant sign compared with other neurological symptoms (77.8% of the patients). (4) Headache was ipsilateral, in the anterior half of the head in the carotid TIA and in the posterior half of the head in the vertebrobasilar TIA. In about 50% of the patients generalized non-localized headache occurred. Headache usually preceded the neurological symptoms in cases of arterial occlusion (20 carotid, 3 vertebral artery), usually appearing during or after the attack in cases without arterial occlusion. (5) Only 2 cases out of 20 with positive CT scan had headache. These two patients suffered from a rather large hypodense lesion. The other 18 patients showed lacunar lesions. Different hypotheses concerning the physiopathology of the headache associated with TIA are discussed.
Focal Cerebral Ischemia and Migraine
Authors: Prencipe Massimiliano , Carolei Antonio , Lenzi Gian Luigi , Fieschi Cesare
Published: July 2017

Consistent literature data on the cerebrovascular risk in migraineous patients are lacking. Available preliminary clinical data (Italian Cooperative Cross-Sectional Case-Control Study) suggest that migraine can hardly be considered a relevant pathogenetic associated risk factor of focal cerebral ischemia.
Neurogenic Control of Cerebral Circulation
Authors: Burnstock G
Published: July 2017

The cerebral vascular neuromuscular apparatus consists of a varicose perivascular nerve plexus at the adventitial-medial border and smooth muscle cells in the medial coat that are functionally connected. In addition to noradrenaline and acetylcholine, a number of putative non-adrenergic, non-cholingergic neurotransmitters have been identified in cerebral perivascular nerves, including serotonin, substance P, vasoactive intestinal polypeptide, gastrinreleasing peptide, cholecystokinin, somatostatin, neurotensin, calcitonin gene-related peptide and neuropeptide Y. The role of adenosine-5'-triphosphate as a cotransmitter with noradrenaline in some perivascular sympathetic nerves, and of endothelial cells in mediating the vasodilatation produced by some neurohumoral agents is discussed. Speculations are made about the relation between vascular neuroeffector mechanisms and migraine, including the possiblity of local vasospasm by serotoninergic nerves, reactive hyperaemia involving purine nucleotides and nucleosides, release of substance P from sensory nerve collaterals during antidromic ('axon reflex') impulses and secondary release of local agents such as prostanoids, histamine and bradykinin.
Biochemical Effects of Cerebral Ischemia: Relevance To Migraine
Authors: Welch KMA , Helpern JA , Ewing JR , Robertson WM , D'Andrea G
Published: July 2017

Although decreased CBF has now been reported during the prodrome of migraine, the cause of the decreased flow is still unknown. It is particularly unclear whether these phenomena are related to vasospasm and “steal” between the extracranial and intracranial circulation or to the spreading depression of Leao and the accompanying metabolic depression. In the present paper, metabolic changes in the brain during ischemia and reperfusion are reviewed and compared with CNS biochemical changes during migraine attack. In addition, the technique of Topical Magnetic Resonance (TMR) as applied to the in vivo study of energy phosphate metabolism in extracranial tissues and brain is described and the potential of this technique to evaluate shifts in energy metabolism and pH in stroke and migraine is discussed.
rCBF After Tia and during Migraine Attacks
Authors: Olesen Jes , Vorstrup Sissel , Lauritzen Martin
Published: July 2017

TIA is usually caused by embolism from a carotid stenosis. The stenosis has no hemodynamic significance, but recent studies of regional cerebral blood flow have indicated that this occurs in a few cases. Traditionally, TIA are not considered to cause cerebral damage, but CT-studies have revealed a number of silent infarcts and rCBF measurements have shown even more persistent abnormalities of blood flow. In classic migraine, alterations of rCBF are completely different, indicating a mechanism progressing in the cerebral cortex, probably the spreading depression of Leao. Similar blood flow changes are not seen in common migraine, where tomographic rCBF determinations have been normal.
On the Possible Relation of Spreading Cortical Depression to Classical Migraine
Authors: Lauritzen Martin
Published: July 2017

During the first 1 to 2 h of the classical migraine attack a hypoperfusion develops which starts in the posterior part of the brain and progresses anteriorly at a rate of 2-3mm/min. The hypoperfusion stops at primary sulci outlining major cortical macro-and microstructural changes, but seems not to be inhibited by other changes of the cortical architecture. The low flow regions are cortical and the low flow persists for 4–6 h, until the attack abates. Regions of hyperperfusion are either minor or non-existent. A similar behavior characterizes the velocity and mode of evolution of a cortical spreading depression, a transient perturbation of cortical neuronal function which has profound and long-lasting influence on the cortical blood flow. This paper briefly summarizes the arguments which have been put forward in recent years suggesting that spreading depression is a pathogenetic mechanism of migraine.
Visual Evoked Potentials and Brainstem Auditory Evoked Potentials in Migraine and Transient Ischemic Attacks
Authors: Benna Paolo , Bianco Chiara , Costa Paolo , Piazza Domenico , Bergamasco Bruno
Published: July 2017

A study of brainstem auditory evoked potentials (BAEPs) and pattern reversal visual evoked potentials (VEPs), recorded in intercritical phase, was carried out in 20 subjects (10 suffering from common migraine and 10 suffering from vertebrobasilar TIA) in order to obtain a comparative evaluation of cortical-subcortical functions. The data we obtained demonstrate the presence of BAEPs alterations in patients with previous vertebrobasilar TIA: no abnormalities were found in the migraine group. VEPs parameters are normal in both groups. Our data show that the study of the so-called “stimulus-related” potentials, such as BAEPs and pattern reversal VEPs, is useful in evaluating the damage produced by any noxa, while it cannot clearly emphasize individual factors predisposing to a specific pathology, as the absence of specific alterations in migraine patients demonstrates.
The Use of Retinal Fluorangiography Techniques in the Study of Cerebral Circulation
Authors: Menchini Ugo , D'Ettorre Michele , Mondelli Mauro , Moretti Luigi , Accardo Agostino , de Denaro Mario
Published: July 2017

Retinal fluorangiographic techniques can be employed in the study of cerebrovascular disorders in relation to the embryological, anatomic and functional affinities between the cerebral and retinal circulation. The techniques currently used have been improved by means of the computer analysis of the photographic image, thus allowing qualitative evaluations of the vascular dynamics and quantitative evaluations referred to remarkable variations. These improved techniques can be summed up as follows: equidensitometry with arbitrary colors, computerized fluorangiography for the evaluation of the vascular caliber, computer analysis of mean transit time (m.t.t.). A new type of qualitative evaluation not considering the fluorangiographic image has recently been introduced: the fluorophotometric analysis.
Hemorheological Factors in the Pathophysiology of Acute and Chronic Cerebrovascular Disease
Authors: Di Perri Tullio , Guerrini Maurizio , Pasini Franco Laghi , Acciavatti Angela , Pieragalli Daniela , Galigani Cinzia , Capecchi Pier Leopoldo , Orrico Alfredo , Franchi Massimo , Blardi Patrizia
Published: July 2017

The hemorheologic changes in three groups of patients suffering from acute and chronic cerebrovascular diseases were studied. Firstly, a horizontal study on 57 patients with definite stroke and on 49 patients with TIA was made. Plasma viscosity, whole blood filtration rate, fibrinogen concentration and hematocrit were evaluated as markers of the rheological property of blood. Blood samples were drawn within 6 h from the onset of vascular syndrome. The findings were compared with values obtained in 112 as controls. At the same time, washed red cell filtration rate, together with lactoferrin, betaglucuronidase and beta-thromboglobulin plasma level were assayed. In both groups the onset of the vascular storm was associated with a marked increase of plasma fibrinogen and of blood and plasma viscosity and a significant decrease of whole blood filterability. Lactoferrin, betaglucuronidase and beta-thromboglobulin levels were also significantly increased. Following this, a longitudinal study was performed on 27 patients with definite stroke and 32 patients with TIA. The clinical regression of acute stroke was associated with the progressive reduction of rheological abnormalities. Finally, 81 patients with clinical diagnosis of cerebrovascular disease due to previous stroke or repeated TIA were studied together. An increase of blood viscosity, of fibrinogen concentration and of hematocrit and a decrease of blood filtration rate together with higher levels of beta-thromboglobulin were registered. These results confirm the existence of an association between CVD and hemorheological alterations and suggest more in depth research directed towards identifying the significance of these alterations in the pathogenesis of tissue ischemia. They also serve to introduce a rationale for the pharmacological and therapeutical corrections of these syndromes.
Modification of Brain Vascular Eicosanoids After Pharmacological Treatment and Ischemia in the Rat: Drugs and Brain Vascular Eicosanoids
Authors: Galli Claudio , Petroni Anna , Borghi Alessandra
Published: July 2017

Vascular eicosanoids (E) thromboxane (measured as T×B2) and prostacyclin (measured as 6-keto-PGF1α) may modulate hemodynamic parameters in brain circulation. We have studied (a) the effects of the administration of vasoactive drugs, in the rat, on T×B2 and 6-keto-PGF1α levels and release in brain cortex, and (b) changes of brain vascular E levels during hypoxia and recovery, in the same animal species. (a) Administration of vasoactive drugs (papaverine, dipyridamole, the carbochromene derivative AD6 and nifedipine) to rats resulted in differential effects on endogenous levels and post-decapitation release of both compounds. Reduction of the T×B2/6-keto-PGF1α balance in brain cortex was obtained with papaverine and AD6, whereas nifedipine reduced 6-keto-PGF1α more than T×B2. (b) During hypoxia there was no significant modification of brain vascular E, but during recovery both compounds were decreased. Thus pharmacological treatments during recovery from hypoxia may normalize brain vascular E levels.
Correlation Between Migraine and Circulating Platelet Aggregates
Authors: Buttinelli Carla , Lazzaro Maria Pia , Lenzi Gian Luigi , Paolucci Stefano , Prencipe Massimiliano
Published: July 2017

We studied platelet aggregates, by Wu and Hoak's technique, in 73 patients (49 F and 24 M), aged 14-61 (mean age 50.4 ± 12.2) with migraine. Platelet aggregates were expressed as Platelet Aggregate Ratio (PAR). We consider as pathological PAR values lower than 86. Mean PAR value of migraine patients (78.3 ± 8.68 SD) was significantly lower ( p < 0.001) than that of 90 control subjects (95.4 ± 6.15 SD). Normal PAR values were found only in 27.4% of the migraine patients. The patients were divided according to the interval from the last attack: 17 patients were studied in the 1st week (PAR = 73.76 ± 7.6 SD; 5.8% of the values in the normal range), 15 in the 2nd week (76.6 ± 7.02 SD; 13.3% of the values in the normal range) and 41 between 15th and 30th day (80.78 ± 8.78 SD; 29.6% of the patients in the normal range). The mean PAR value of the patients studied during the first week was significantly lower ( p < 0.01) than that of the patients studied between 15th and 30th day. No significant differences were found between the patients with classical, common and complicated migraine.
Evidence of Enhanced Platelet Aggregation and Platelet Sensitivity in Migraine Patients
Authors: Lechner H , Ott E , Fazekas F , Pilger E
Published: July 2017

In fourteen untreated migraine patients with a mean age of 40 years platelet sensitivity to 5HT, EN and ADP was investigated during the prodromal phase (three patients), 12-48 h after headache (three patients) and during the headache-free period (eight patients). Platelet sensitivity was tested using an optical density method and was calculated by the percentage of disaggregation (%DA) occurring 3 min after the peak aggregation. Platelet release reaction was assessed using β-thromboglobulin (β-TG) as an indicator. Platelet sensitivity to low concentrations of 5HT, EN and ADP (0.3 × 10-9 M/ml) was most marked during the headache and prodromal phases.

The least platelet sensitivity in migraineurs was detected during the headache-free interval, but was still higher than in the control group. β-TG levels were increased during the headache phase indicating platelet release reaction. A general hyperaggregability of platelets in migraineurs has been demonstrated and in addition a varying sensibility of platelets to low concentrations of 5HT, EN and ADP has been established.
Relevance of Prostaglandins in Migraine
Authors: Parantainen J , Vapaatalo H , Hokkanen E
Published: July 2017

Prostaglandins (PG), particularly PGE, may be linked to the pathophysiology of migraine in several important ways. PGE, may “simulate” a migraine attack in healthy volunteers. PGE may be elevated in patients with migraine. In animal experiments and in human infusions, PGEs cause vasodilation and hyperalgesia, both typical reactions of inflammation. The view that vascular headache is an “inflammatory reaction” allows the best concept concerning the local role of PGs and the effectiveness of PG-inhibitors in the treatment of migraine. The local role of PGs may provide a common denominator in several hormonal, neural and other influences on vessels. The common triggers of a migraine attack like menstruation, alcohol and stress influence the PG-system and even the dietary reactions, hormonal influences, sleep and reserpine have some connections with the PG-system. A local role for PGs does not diminish the importance of other pathophysiological mechanisms operating during an attack. On the contrary, PGs may fill in gaps in our understanding of how the overt pain of attacks is produced.
Drugs and Platelet Activation in Migraine and Transient Ischemic Attacks
Authors: D'Andrea Giovanni , Cananzi Antonio , Toldo Moreno , Ferro-Milone Francesco
Published: July 2017

In order to study the role of platelets in migraine and cerebrovascular disease, beta-thromboglobulin (β-TG) and platelet factor 4 (PF4) plasma levels, indices of in vivo platelet activation, were assayed in two groups of patients suffering from migraine (common/classic and classic/complicated migraine, respectively) and in one group suffering from transitory ischemic attacks (TIAs). Plasma determinations were carried out in the absence of treatment and during the administration of aspirin (50 mg/daily) and flunarizine (10 mg/daily). Platelet activation was found in patients suffering from TIA; patients affected by classic and complicated migraine showed a high incidence of activation, in comparison with common migraine sufferers, also in headache-free periods. Administration of aspirin (ASA) was more effective than flunarizine in inducing a decrease in β-TG and PF4 plasma levels in migraineurs. Aspirin, however, did not affect platelet activation in subjects suffering from ischemic attack even though we did not observe any relapse after one year of treatment. The different effect of ASA in TIAs and migraine indicates that the platelet activation in TIA patients is due not only to cyclo-oxygenase pathway but also to other in vivo pathways.
Concluding Remarks
Authors: Buscaino Giuseppe Andrea
Published: July 2017

One of the most well-known pathophysiological phenomena in migraine is cerebral ischemia, possibly induced by vasospasm with consequent prodromic focal symptoms, followed by a reactive vasodilation associated with the pain. From a neuropharmacological point of view, the role of serotonin as a mediator of vasospasm has long dominated the scientific field, and antiserotonin drugs have, for almost as long, governed the therapeutic field. More recent approaches have implicated platelet aggregability, focal cerebral hypoxia and opioid neuropeptides in the genesis of migraine. Here I shall attempt to review the different aspects that, even though controversial, summarize the situation as it stands at the end of 1984.
Non-Vascular Central Nervous System Effects of Calcium Entry Blockers
Authors: Govoni S , Battaini F , Magnoni MS , Trabucchi M
Published: July 2017

Calcium entry blocker (CEB) use has been proposed in a variety of neurological dysfunctions. Some of the new clinical applications suggest a direct non-vascular action on neuronal activity. This view is supported by the observation that in brain CEBs bind preferentially to neuronal terminals and not to vascular elements. The data reported indicate that CEBs modify both in vitro and in vivo neurotransmitter release using brain slices and that their binding sites display some degree of plasticity in various experimental conditions altering neuronal transmission.
The Effects of Flunarizine in Experimental Models Related to the Pathogenesis of Migraine
Authors: Wauquier Albert , Ashton David , Marrannes Roger
Published: July 2017

Two new hypotheses suggest that the key pathology in migraine has a neuronal origin. A pivotal role is assigned to brain hypoxia (1) and spreading depression (SD) (neuronal depolarization spreading gradually over the cortex) (2). Flunarizine has been tested both against brain hypoxia and SD. Its potent antihypoxic properties in animal models led to its use as a prophylactic drug in migraine therapy. Earlier experiments suggested that flunarizine shortened recovery after neuronal depolarization. Recent experiments suggest that flunarizine may enhance the threshold for the elicitation of SD. Finally, it is often unclear whether the effects observed with flunarizine are due to a vascular or a direct neuronal effect. Therefore, a study was made to show whether flunarizine affected hypoxia-induced alterations in synaptic function in slices of hippocampus held in vitro. At physiological drug concentrations in brain, flunarizine improved post-hypoxic recovery of synaptic function. A direct neuronal protective effect was thus demonstrated.
Neuroendocrine and Behavioral Effects of Flunarizine in Young and Old Rats
Authors: Drago Filippo , Continella Giuseppe , Mangano Orazio , Canonico Pier Luigi , Bernardini Renato , Scapagnini Umberto
Published: July 2017

Neuroendocrine and behavioral effects following an acute or chronic treatment with the calcium antagonist, flunarizine, have been studied in young and old rats. Both in young and old rats, acute administration of flunarizine (2 mg/kg) failed to modify plasma prolactin (PRL) levels, as measured at 8.00 a.m., 4.00 p.m. and 12.00 p.m. A chronic treatment with flunarizine (0.5 mg/kg/day, for 20 days) in young rats was followed by a relevant, albeit statistically not significant, increase in plasma PRL levels, as measured at 8.00 a.m. and 4.00 p.m., and by a significant decrease at 12.00 p.m. A shift of nocturnal peak of plasma PRL levels from 12.00 p.m. to 4.00 a.m. was observed in these animals. A chronic treatment with flunarizine in old rats was followed by a significant increase in plasma PRL levels, as measured at 12.00 p.m. The acquisition of active avoidance behavior was studied in a shuttle-box test. Acute administration of flunarizine failed to change the performance of young and old rats in acquiring the behavioral response, as measured by the total number of conditioned avoidance responses (CARs) and the percentage of learners. When flunarizine was administered chronically, a decrease in CARs and learners was observed both in young and old rats. This was accompanied by a significant increase in the percentage of animals that froze during the acquisition session. No significant effect was found in young and old rats tested in a “despair” test after a chronic treatment with flunarizine.
Flunarizine in the Prevention of Classical Migraine: A Placebo-Controlled Evaluation
Authors: Mentenopoulos G , Manafi Th , Logothetis J , Bostantzopoulou S
Published: July 2017

Pharmacological data and early clinical experience have suggested that the calcium entry blocker flunarizine may be a valuable asset in the prophylaxis of migraine. This was supported by a study in twenty patients with classical migraine who were, after a drug-free running-in phase, orally treated with either placebo or flunarizine (10 mg at night) for three to four months. Flunarizine significantly reduced the frequency, duration and severity of the migraine attacks. A corrected migraine index, based on these three variables, was reduced by 82% in the drug group but increased by 66% in the control patients. Only one patient did not clearly benefit from flunarizine, and the response in another illustrated that flunarizine has to be given for at least four months before its efficacy can be judged in some cases. No side effects occurred.
Flunarizine in the Treatment of Headache With or Without Neurological Symptoms
Authors: Nattero Giovanni , Savi Lidia , De Lorenzo Cristina
Published: July 2017

Flunarizine was given in daily doses of 10 mg for periods of two to four months to 176 patients suffering from various types of headache. The symptoms were improved in 82% of the cases treated. No differences emerged among the various types of headache reported by the patients or in relation to the presence or absence of neurological involvement or its type.
Flunarizine v. Placebo in Childhood Migraine. A Double-Blind Study
Authors: Sorge Fulvio , Marano Enrico
Published: July 2017

Successful migraine prophylaxis with flunarizine has been reported in adults by several authors. We used flunarizine in a double-blind, placebo controlled, randomized trial in childhood migraine. Twenty-four children with classical or common migraine were followed by a 12-week flunarizine treatment period. Each patient took 5 mg/day of the drug before going to sleep. Twenty-four children with similar clinical characteristics were assigned to placebo treatment. Efficacy of flunarizine versus placebo was assessed on the basis of the reduction of headache frequency and duration. A statistical comparison was performed between values reported in the treatment period and those in the three months before. Children treated with flunarizine experienced a statistically significant reduction in headache (66%) and duration (51%). These results were statistically superior to those observed in the placebo group. Sixteen patients on flunarizine therapy experienced an improvement of more than 50% of both parameters. We found flunarizine is an effective agent in children's migraine prophylaxis. Moreover it is suitable for the low incidence of mild side effects.
Flunarizine in Common Migraine: Italian Cooperative Trial. I. Short-Term Results and Responders' Definition
Authors: Manzoni Gian Camillo , Bono Giorgio , Sacquegna Tommaso , Manna Vincenzo , Lanfranchi Marina , Micieli Giuseppe , Cortelli Pietro , Agnoli Alessandro
Published: July 2017

In order to assess the effects of flunarizine in long-term prophylaxis of common migraine, 120 subjects (90 female and 30 male) were treated with 10 mg at bedtime and followed-up for two years. The effectiveness of the drug was assessed by investigating the variations of the Headache Index (HI) and of the intake of analgesics. The patients considered responders were those with an at least 60% reduction of the HI compared with the baseline value. To assess side effects, on each follow-up examination the patients were weighed and submitted to the Hamilton Rating Scale for Depression, Toulouse-Pieron test for attention, and arousal test. By the third month of therapy, the average monthly HI had decreased from a baseline value of 16.5 ± 7.0 to 7.5 ± 4.2. Also by the third month, 60 subjects had proved responders and 50 non-responders; 10 had dropped out of the study because of side effects or for other reasons. The only statistically significant differences between responders and non-responders were in the baseline HI, which was higher among responders, and in the baseline intake of analgesics, which was higher in non-responders.
Flunarizine in Common Migraine: Italian Cooperative Trial. II. Long-Term Follow-Up
Authors: Bono Giorgio , Manzoni Gian Camillo , Martucci Nicola , Baldrati Anna , Farina Stefano , Cassabgi Fauzi , De Carolis Piero , Nappi Giuseppe
Published: July 2017

The effects of flunarizine administration (10 mg/day, at bed time) were studied in 120 common migraine patients who were followed for 24 months with quarterly controls. Besides headache index (HI) and analgesic use, other variables were monitored, such as arousal (Tolouse Pieron test), mood (Hamilton rating scale for depression), sleep/wake (hrs) and body weight. The study was open-type and after the 6th month control some responder (R) cases (HI reduction ≥ 60%) presenting HI scores ≤ 4 could continue the survey off-treatment. The percentage of R cases was 54.5% at the 3rd month, a figure that further increased up to 72% by the 9th month; relapses on treatment were not observed and rebound-headache occurred in 1/4 of R cases let off-treatment. Lower ( p < 0.05) baseline HI values characterized non-responders. Side-effects not requiring withdrawal were drowsiness (42% within the 1st month) and weight gain (mean 7.9 ± 6.9 kg) in 54% of the cases, while a retarded type depression was the most frequent cause of drop-out from trial (7.5%). The results, while confirming the high prophylactic activity of flunarizine in common migraine, stress the importance of clinical long-term survey of side-effects using antimigraine drugs and suggest the need for further investigations about flunarizine effects on CNS.
Erythrocyte Deformability Changes in Headache Patients Under Flunarizine Treatment
Authors: Covelli Vito , Polimeno Giuseppe , Savarese Maria A , Antonaci Fabio , Puca Franco M , Tannoia Anna
Published: July 2017

Changes in erythrocyte deformability (ED) parameters have been investigated in 36 patients suffering from different forms of headache (classic and common migraine; migraine with interval headache; chronic tension headache) and treated with flunarizine (10 mg/day at bedtime). Patients were carefully selected in order to avoid any possible interference with the parameters under study, and smoke and drug use in particular (symptomatics included) were considered as criteria for exclusion from the trial. Controls of ED parameters were planned before treatment and after 20 and 35 days. Baseline ED alterations were present only among patients with chronic tension headache, but flunarizine treatment was able to positively modify ED parameters in these patients, as well as in migraine cases that showed normal baseline ED values. No correlation was found between patients' characteristics and baseline ED values, nor between ED changes under treatment and therapeutic effects of flunarizine.