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Peroral administration of enzymes: strategies to improve the galenic of dosage forms for trypsin and bromelain.

In this study, we investigated the presystemic metabolism of trypsin and bromelain and the influence of these proteolytic enzymes on the mucus layer covering the gastrointestinal (GI) epithelia. In vitro studies demonstrated that 77.3% +/- 4.0% (mean +/- SD, n = 3) of trypsin is autodegraded within 2 hr, whereas autodegradation of bromelain was negligible. In contrast to the metabolization of bromelain by all pancreatic serine proteases, trypsin is only degraded to some extent by elastase. Both therapeutically used enzymes remained stable after incubation with an excised porcine mucosa, demonstrating that proteolysis caused by brush border membrane-bound enzymes is negligible. Trypsin and bromelain were highly mucolytic active, thereby reducing the diffusion barrier based on the mucus gel layer. Strategies to improve the galenic of dosage forms for trypsin and bromelain include the use of bioadhesive polymers such as hydroxyethylcellulose or slightly modified chitosan-EDTA, providing strongly improved stability of these enzymes toward proteolytic degradation in vitro. The given information represents a good starting point to improve the galenic of dosage forms for orally administered proteolytic enzymes.

Administration, Oral↗

Percutaneous transvenous catheterization and embolization of vein of galen aneurysms.

Seven cases of vein of Galen aneurysms treated by percutaneous transvenous endovascular occlusion of the aneurysmal vein are presented. In one case, the approach was via the femoral vein, and in the other six cases, by the jugular vein. All of the malformations were multipedicular and, additionally, in six of the seven there was an intervening arterial-arterial network between the posterior thalamoperforating arteries and the wall of the venous aneurysm. This fistulous network was interpreted as purely arterial and not as an associated arteriovenous malformation. For this reason, the transvenous approach was considered justified, and was performed without risk of hemorrhage caused by retrograde venous hypertension. Measurement of intra-aneurysmal pressure during the course of treatment allowed better understanding of the hemodynamics of the lesions, guided the amount of occlusion to be accomplished during each treatment session, and thus may have prevented the phenomenon of normal perfusion pressure breakthrough. The percutaneous transvenous approach offers all the advantages of the transtorcular approach but avoids surgery. Because of our excellent angiographic and clinical results--five complete and two partial occlusions, with favorable outcomes and no major complications--we believe that this technique is better for the treatment of multipedicular vein of Galen aneurysms than transarterial embolization or surgery.

Basilar Artery↗

The subchoroidal approach to the third ventricle: surgical anatomy according to Galen.

THE SUBCHOROIDAL APPROACH has taken its place among the surgical access routes to the third ventricle. Eighteen centuries ago, in his major anatomic work, Galen detailed with astonishing accuracy the anatomy of the structures around the third ventricle and the procedure for exposing this cavity by entering the lateral ventricles and elevating its roof. Even more surprising is Galen's pioneering description of surgical maneuvers of the third ventricle in living animals in a way that anticipated the modern subchoroidal approach.

Anatomy↗

A newborn with cardiac failure secondary to a large vein of Galen malformation.

We report the case of a term newborn with vein of Galen aneurysm. No antenatal diagnosis was done. The infant was admitted secondary to cardiac failure, with cardiomegaly and pulmonary hypertension. Physical examination was remarkable for acrocyanosis, microcephaly, cranial bruit, bilateral neck swelling, coarse breath sounds, and a hyperdynamic precordium with continuous murmur. Head ultrasound demonstrated a large, midline venous structure. Computed tomographic scan confirmed vein of Galen malformation.

Cerebral Veins↗

Malformation of the great vein of Galen with neonatal heart failure. Report of two cases.

The clinical and patholgoical findings in two neonates with the malformation of the great vein of Galen are given. They both reported with serious neonatal heart failure suggesting congenital heart disease. In one of them cardiac catheterization revealed a foetal pattern of circulation causing cyanosis. A bruit and in one of them a thrill over the skull gave the clinical diagnosis of an intracranial arteriovenous aneurysm. They died 48 and 144 hours after birth in spite of medical treatment. The outlook for patients having malformation of the great vein of Galen and suffering neonatal heart failure treated conservatively, seems hopeless.

Abnormalities, Multiple↗

Congenital cardiac anomalies with vein of Galen malformations in infants.

Published reports and personal experience are reviewed relating to patients under 1 year of age diagnosed with a vein of Galen malformation and congenital heart disease. Including five patients from this institution, a total of 23 patients (12 neonates) with congenital heart disease and a vein of Galen malformation have been reported. Six of these had sinus venosus atrial septal defect and nine had aortic coarctation.

Angiography, Digital Subtraction↗

Clinical course and medical management of neonates with severe cardiac failure related to vein of Galen malformation.

BACKGROUND: Neonatal presentation of vein of Galen aneurysmal malformations (VGAMs) with intractable cardiac failure is considered a poor prognostic sign. Interventional neuroradiology with embolisation has been shown to control cardiac failure, but there is a perception that neurological outcome in survivors is poor. OBJECTIVE: To determine if aggressive intensive care and anaesthetic management of cardiac failure before urgent embolisation can influence morbidity and mortality. PATIENTS: Nine newborns (four boys, five girls) were diagnosed with symptomatic vein of Galen malformations in the neonatal period during the period 1996-2001. Eight developed intractable high output cardiac failure requiring initial endovascular treatment in the first week of life. RESULTS: The immediate outcome after a series of endovascular procedures was control of cardiac failure and normal neurological function in six (66%) patients, one death from intractable cardiac failure in the neonatal period, and two late deaths with severe hypoxic-ischaemic neurological injury (33% mortality). Clinical review at 6 months to 4 years of age showed five infants with no evidence of neurological abnormality or cardiac failure and one child with mild developmental delay (11%). CONCLUSIONS: Aggressive medical treatment of cardiac failure and early neurointervention combined with modern neuroanaesthetic care results in good survival rates with low morbidity even in cases of high risk VGAM presenting in the immediate perinatal period with cardiac failure. Systemic arterial vasodilators improve outcome in neonates with cardiac failure secondary to VGAM. Excessive beta adrenergic stimulation induced by conventional inotropic agents may exacerbate systemic hypoperfusion.

Cardiac Output, Low↗

Prenatal diagnosis of vein of Galen aneurysmal malformations.

Vein of Galen aneurysmal malformations are rarely seen intracranial malformations. They represent less than 1% of the cerebral arteriovenous malformations. Prenatal diagnosis of an arteriovenous fistula malformation may be achieved by real-time and Doppler sonography with color flow imaging, by identifying dilated veins and arteriovenous shunts with turbulent flow. In addition, an elevated cardiac output may be observed and correlated with the magnitude of the cerebral arteriovenous shunt. The high incidence of cardiomegaly in neonates with arteriovenous malformations also suggests that high-output cardiac failure is already present in a significant number of cases during the 3rd trimester, and, therefore, treatment in utero may need to be considered to improve the hemodynamic status. In our case, all the above cardiovascular features were present during prenatal ultrasonography. The information on outcome compiled from the literature suggests that when an arteriovenous malformation is large enough to be detected prenatally, as in our case, it is likely to lead to cardiac failure either during the antenatal period or soon after birth. In this paper, we present the management of a case of 3rd-trimester diagnosis of a vein of Galen aneurysm associated with cardiac decompensation.

Adult↗

Spontaneous thrombosis of an aneurysm of the great vein of Galen.

A case of a thrombosed aneurysm of the vein of Galen in a 9-year-old boy is reported. Previously, only ten clotted aneurysms of the vein of Galen have been described. In our case, thrombosis occurred spontaneously after birth. Clinical presentation was characterized by signs of hydrocephalus, with an abrupt deterioration after several years of satisfactory clinical evolution. The patient was successfully treated with a ventriculoperitoneal shunt.

Brain↗

In vivo comparison of two galenic forms of ampicillin-trihydrate.

In order to evaluate a new galenic form of ampicillin-trihydrate, individual blood serum levels and urine excretion of ampicillin-trihydrate were compared in a crossover study after oral absorption of 1-gram captab formulation (this being the new galenic form) versus 2x500 mg of the same product. Analyses performed by two different laboratories indicate that clinically insignificant slightly higher serum concentrations can be obtained with captabs, and that very individual absorption profiles should make one take a sceptic viewpoint as to mean serum concentrations computed from larger series of experiments. To obtain a valid blood serum level in as many patients as possible, a posology of 3-4 captabs, spaced over a 24-hour period is suggested for the treatment of infections with ampicillin-sensitive germs. For less sensitive micro-organisms, one should switch to parenteral therapy or to other antibiotics.

Administration, Oral↗

Niccolo da Reggio's translations of Galen and their reception in France.

In the first half of the fourteenth century, Niccolò da Reggio translated more than fifty works by Galen from Greek into Latin, and by mid-century most if not all of them had reached the papal court at Avignon, where Guy de Chauliac praised their accuracy and cited them regularly in his Great Surgery of 1363. Yet contemporary physicians at nearby Montpellier almost never referred to them, ordinarily preferring to quote from the older Arabic-Latin translations. Examining a particular context, the ways in which urological conditions were described in the old and new versions of Galen, suggests that medical teachers and commentators may have found it difficult to give up the familiarity of the traditional language in favor of Niccolò's new terminology.

France↗

Arteriovenous malformation of the vein of Galen in a newborn diagnosed with color Doppler examination--a case report.

A fourteen-day-old newborn infant presented with severe heart failure due to arteriovenous malformation of the vein of Galen. It was diagnosed by two-dimensional, pulsed-wave and color Doppler echocardiographic imaging. The latter method showed the afferent vessel to be the anterior cerebral artery entering an aneurysm of the vein of Galen at its posterior aspect. Information for surgical anatomic definition appears to be adequately provided by color Doppler examination, which permits avoidance of preoperative angiography.

Arteriovenous Fistula↗

The soul and the pneuma in the function of the nervous system after Galen.

Galen's teaching on anatomy and physiology was generally accepted in the Middle Ages and this applies to the part he thought was played by the pneuma in the functions of the body. In this essay I have outlined the advances made after Galen in the study of the nervous system leading eventually to a time when the soul and the pneuma were no longer thought necessary for the proper functioning of the brain and nerves.

Electrophysiology↗

Neuroradiological and pathological studies on neonatal aneurysmal dilation of the vein of Galen.

Neuroradiologic and neuropathologic findings on neonatal aneurysmal dilation of the vein of Galen are reported. Doppler echocardiography revealed a diastolic reversed Doppler signal, which suggested the presence of a cerebral arteriovenous fistula. Cerebral ultrasonography with intravenous injection of contrast medium was useful in the diagnosis. Digital subtraction cerebral angiography clearly demonstrated both the feeding and draining vessels and the aneurysmal dilation of the vein of Galen, although it failed to detect the abnormal vascular channels. Pathologic and histopathologic findings demonstrated intimal thickening of the abnormal vascular channels, which could produce higher vascular resistance and result in the detection failure with digital subtraction angiography.

Cerebral Veins↗

History of diaphragm physiology: the achievements of Galen.

Galen (129-200 AD) produced a large written output which was to remain one of the major basis of clinical medicine for centuries. His contribution to respiration, reported in his own books and in those of Oribasius, was that of a chest physician and of an experimental physiologist. He described in minute details how to perform a remarkable series of experiments by which he demonstrated the anatomy and function of the respiratory muscles. He described the actions of the diaphragm and how it moves the rib cage, in a series of spinal chord sections and muscle denervations. He investigated the passive or active nature of expiration and made fine observations of lung movements through the exposed pleural space. He described the interaction between the lungs and chest wall and developed the concept of interaction between ribcage and abdominal muscles in maintaining the position of the diaphragm, showing a clear understanding of the principle that the diaphragm can move upward during an isovolume manoeuvre as long as the ribcage is allowed to expand. A skillful clinician, Galen applied his theories of the analysis of problems at the bedside, particularly in patients affected with dyspnoea which he attributed to respiratory muscle dysfunction.

Animals↗

Vein of Galen malformation: diagnosis and management.

The vein of Galen malformation is a midline arteriovenous fistula with aneurysmal dilatation of the vein of Galen. The clinical details of diagnosis and treatment in 13 patients with such lesions together with a review of 232 cases collected from the literature are presented in this report. There were 132 males, 77 females, and 36 cases in which the sex was not stated. Eighty patients presented as neonates, 82 were 1 to 12 months old, 39 were 1 to 5 years old, 22 were 6 to 20 years old, and 22 were over the age of 20. The most common presenting symptoms were congestive cardiac failure (110 cases), raised intracranial pressure secondary to hydrocephalus (94 cases), cranial bruit (57 cases), focal neurological deficit (37), seizures (26 cases), and hemorrhage (25 cases). The most characteristic vascular supply to the midline fistula involved multiple bilateral vessels, although bilateral posterior cerebral and unilateral posterior cerebral supply was relatively common. The overall figures for treatment and outcome showed that 91 patients (37.1%) were treated by direct operation and 29 patients (11.3%) were treated by other forms of operation, predominantly shunting or remote vessel ligation. Forty-six patients (18.8%) were treated by medical means (digoxin, diuretics, and ventilatory support). In 79 patients (22.2%), there was no treatment or no details of treatment were available. There was an overall series mortality of 55.6% (no details were available in 33 cases) and a 37.4% mortality for surgically treated cases. After operation, there was a 46.3% incidence of significant morbidity in surviving patients. Neonatal patients fared worst, with an overall mortality of 64 of 70 cases (91.4%) where details were available. The outcome was equally bad for surgically and conservatively treated cases. Operation in the 1- to 12-month age group was more successful, but still carried a mortality of 31.7%, with a significant morbidity in approximately half of the surviving patients. Over the age of 1 year, the surgically treated patients had a 25.6% mortality and a 42.3% major morbidity in survivors. Consideration is given to some of the ways in which these figures may be improved, in particular a staged approach during the neonatal period, with the use of selective embolization or occlusion of vessels to reduce the volume of the arteriovenous shunt until the patient is older and better able to tolerate major operation.

Adolescent↗

Normal perfusion pressure breakthrough complicating surgery for the vein of Galen malformation: report of three cases.

Three cases are described of infants who developed malignant brain swelling (and in one case hemorrhage) after surgery for vein of Galen malformations. The cause for the brain swelling was felt to be due to hyperperfusion, or the "normal perfusion pressure breakthrough" syndrome. Although well-described for cerebral parenchymal arteriovenous malformations, cases of this complication occurring in vein of Galen malformations have not previously been reported. It is concluded from these cases that infants with large arteriovenous shunts, as attested by cardiac failure and cerebral atrophy, have an increased risk of developing this complication.

Brain Edema↗

Vein of Galen aneurysm in an adult: case report.

Vein of Galen aneurysm is a rare pathology, representing less than 1% of intracranial vascular malformations. We report on a 65-year-old man who experienced a generalized tonic-clonic seizure. Brain imaging showed a large calcified expanding mass in the pineal region, confirming the diagnosis of a vein of Galen aneurysm. Because of the spontaneous thrombosis of the malformation, there was no need for microsurgical or endovascular treatment and he has been regularly followed since that.

Aged↗