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Biomedical subjects

R M Bergland

Publications and source records attributed to R M Bergland.

At least 19 recordsLinked to original sources

Biodistribution of p-boronophenylalanine in patients with glioblastoma multiforme for use in boron neutron capture therapy.

OBJECTIVE: The success of boron neutron capture therapy depends on the safety and specificity of the boron delivery agent. As a preface to clinical boron neutron capture therapy of glioblastoma multiforme, a biodistribution study of intravenous p-boronophenylalanine (BPA) in patients undergoing craniotomy for resection of glioblastoma was performed. METHODS: Varying doses of intravenously administered BPA-fructose (130-250 mg BPA per kilogram of body weight) were given to patients 2 to 3 hours prior to the start of craniotomy for either suspected or known glioblastoma multiforme. Blood samples were collected over a 48-hour period for boron assay. At surgery, multiple samples of tumor, brain, and scalp were obtained for boron and histological analysis. RESULTS: Seventeen patients were studied; all but one had glioblastoma multiforme. No adverse effects from the BPA infusions were noted. The boron concentration in the blood reached a maximum at the end of the BPA infusion and was proportional to the administered dose of BPA. Normal brain concentrations of boron generally were equal to or less than that in blood. Tumor-blood boron ratios were highly variable: 1.6 +/- 0.8 (mean +/- standard deviation; n = 187; range, 0.3-3.5). The observed heterogeneity of BPA uptake in glioblastoma samples appears to correlate with the degree of cellularity observed on histological examination. CONCLUSION: Intravenous BPA administration up to a dose of 250 mg/kg is safe and well tolerated. BPA uptake in surgical samples of glioblastoma tissue is variable and may depend on the fraction of viable tumor cells in the individual sample. Further clinical studies using BPA as a boron delivery agent for boron neutron capture therapy of glioblastoma multiforme appear warranted.

Boron Compounds↗

Surgical treatment of syringomyelia based on magnetic resonance imaging criteria.

The treatment of syringomyelia includes many surgical options. We report a retrospective study of 65 patients with cavitary lesions of the spinal cord in whom the results of magnetic resonance imaging were used to develop specific treatment strategies. Intramedullary cavities were classified into three general types: 1) communicating syrinxes, which occurred with hydrocephalus and were anatomically continuous with the 4th ventricle (9 patients); 2) noncommunicating syrinxes, which were separated from the 4th ventricle by a syrinx-free segment of spinal cord (42 patients); and 3) atrophic syrinxes, which occurred with myelomalacia (14 patients). Noncommunicating syrinxes were further subdivided according to type: Chiari II malformations with hydrocephalus (5 patients), Chiari I malformations without hydrocephalus (11 patients), extramedullary compressive lesions (12 patients), spinal cord trauma (6 patients), intramedullary tumors and infections (6 patients), and multiple sclerosis (2 patients). Of the 65 patients, 39 underwent surgical treatment for progressive symptoms. Syrinxes occurring with hydrocephalus were treated empirically with a ventriculoperitoneal shunt. Excellent results were achieved in 7 of 7 patients with communicating syrinxes and in all 5 patients with Chiari II malformations. Two approaches were used in the treatment of syrinxes occurring with Chiari I malformations: Posterior fossa decompression improved symptoms but did not reduce syrinx size in 2 of 3 patients. In the third patient and in 3 patients who were not treated with decompression, shunting from the syrinx to the cerebellopontine angle cistern collapsed the cavity and resolved symptoms over the interval of follow-up (average follow-up, 1.5 years). Excision of extramedullary obstructions at the rostral end of noncommunicating syrinxes resulted in collapse or disappearance of the cavity in 6 of 7 patients. The remaining patient was treated effectively by a syringocisternal shunt. In all 4 patients with posttraumatic syringomyelia, good results were achieved by a spinal or syringocisternal shunt. Syrinxes associated with intramedullary masses were managed by biopsy or excision of the causal lesion and appropriate adjunctive therapy (6 patients). Patients with atrophic syrinxes were not operated upon except to relieve symptoms referrable to the causal lesion (4 patients). Recurrent syrinxes were not encountered in the 35 surviving patients over an average follow-up of 2.5 years. It is concluded that syringomyelia is a complex pathological disorder with several mechanisms of pathogenesis that requires a number of different treatment strategies.

Adolescent↗

Causal links between plasma and CSF endorphin levels in stress: vector-ARMA analysis.

To explore causal links between vital sign responses and immunoreactive beta-endorphin ("i-BE") rises in blood and CSF during ovine endotoxin stress, we analyzed concurrent i-BE levels in these two compartments by a "vector-ARMA" (= autoregressive moving average) method. This technique--widely used for modeling in other applications--has not to our knowledge been employed to study dynamic relationships of neuropeptides. Log-transformed i-BE levels were first "filtered" by repeated observations ANOVA to confirm significance of rises in both compartments. Next, vector-ARMA methodology was applied to derive an optimal causal model of vital sign changes and i-BE entry into plasma vs. CSF pools. The model indicated that reflux of i-BE from blood into CSF contributed to increases in CSF levels of this hormone. This novel application to neuroendocrinology of this approach illustrates its utility in evaluating changes in one or more neuropeptide levels in multiple compartments to indicate potentially causal relationships.

Animals↗

Dynamics of cortisol and endorphin responses to graded doses of synthetic ovine CRF in sheep.

Corticotropin-releasing factor (CRF), recently isolated from sheep hypothalami, has been shown to stimulate secretion of ACTH and beta-endorphin in vitro, and in vivo in rat and man. In previous reports, responses to ovine CRF were studied in heterologous bioassay systems where the ovine sequence was likely to act as a CRF analogue. We administered synthetic ovine CRF to sheep to assess the dynamics of endorphin and cortisol responses. Graded doses of CRF caused a rapid increase in immunoreactive beta-endorphin (iB-E) within 2 min of iv administration, followed by a cortisol response which was maximal 15 min after the iB-E peak. Doses of CRF in excess of 10 micrograms did not increase the magnitude of the peak iB-E response but did prolong the duration of the plasma beta-endorphin rise. Ovine CRF is an extremely potent and rapidly-acting hypothalamic peptide in vivo when assayed in a homologous system.

Animals↗

Neurosecretory bodies within the median eminence in association with pituitary tumours.

During necropsy the pituitary stalk is usually deliberately divided and the median eminence is separated from the posterior pituitary. In a series of 133 necropsies the brain was removed in a manner that preserved the integrity of the neurohypophysis and allowed histological examination of the entire neurohypophysis and the juxtaposed adenohypophysis. Neurosecretory bodies were found within the neurohypophysis in 2 patients,and in both microadenomas were found within the adenohypophysis. 2 other patients had larger tumours within the adenohypophysis but had no abnormalities within the neurohypophysis.

Adenoma, Chromophobe↗

Pituitary-brain vascular relations: a new paradigm.

Vascular casts of the pituitary gland have demonstrated a paucity of veins extending from the adenohypophysis to the systemic circulation and have suggested that some adenohypophyseal venous blood returns to the neurohypophysis. The neurohypophyseal capillary bed may function as a vascular switch and in this article a series of 14 questions are proposed regarding the vascular dynamics of the pituitary. Together these questions raise the larger question, namely, whether pituitary hormones are transported directly to the brain to modify brain function?

Animals↗

The neurohypophyseal capillary bed. II. Specializations within median eminence.

Vascular casts of the pituitary gland, median eminence and hypothalamus from several mammalian species were examined by scanning electron microscopy. These observations were correlated with light microscopic studies of injected, cleared median eminence-pituitary specimens and with light microscopic examination of serial sections of injected hypothalamic, median eminence, and pituitary specimens employing reflected lighting or epi-illumination. Transmission electron microscopy was employed to study long portal vessels on the ventral surface of the rat median eminence. In each of the species examined, the median eminence (infundibular) capillary bed is subdivided into an external and an internal plexus. The external plexus (the neurohemal contact zone) receives an arterial supply from the superior hypophyseal arteries and is continuous with the capillary bed of the infundibular stem and process. Egress from the external plexus is possible via three vascular routes: (a) by fenestrated portal vessels and capillaries to the adenohypophysis, (b) by capillary connections to the medial basilar hypothalamus and, (c) by internal plexus capillaries to the ependyma of the median eminence. Median eminence vasculature is structurally organized to deliver (1) hypothalamic and neurohypophyseal peptides to the glandular pituitary via portal vessels, (2) hypothalamic and pituitary secretions to the medial basilar hypothalamus via capillaries, and (3) hypothalamic and pituitary secretions to distant brain sites through cerebrospinal fluid via ventricular and subarachnoid routes.

Animals↗

Can the pituitary secrete directly to the brain? (Affirmative anatomical evidence).

Vascular casts of 10 rhesus monkey pituitary glands and three vascular casts of the rhesus monkey cavernous sinus were examined by scanning electron microscopy. A continuous neurohypophyseal capillary bed was found uniting the infundibulum, infundibular stem, and infundibular process. The neurophypophysis was supplied by three groups of arteries: superior hypophyseal, middle hypophyseal, and inferior hypophyseal. Numerous anastomoses were found between individual arteries, and some hypophyseal arteries formed anastomotic links between different portions of the circle of Willis. Veins located at the caudal pole of the infundibular process, capillaries linking the infundibulum to the hypothalamus, and portal vessels extending from the infundibulum to the adenohypophysis provided efferent vascular pathways from the neurohypophysis. The adenohypophysis received no direct arterial supply; its entire afferent vascular supply was provided by portal vessels. Lateral hypophyseal veins were not found; small adenohypophyseal veins joined larger neurohypophyseal veins to form confluent pituitary veins which extended to the cavernous sinus. The capacity of the venous connections draining the adenohypophysis directly to the cavernous sinus appeared small when compared to that of of the long portal vessels supplying the adenohypophysis. However, many of the short portal vessels interposed between the adenohypophysis and the infundibular stem and process were well arranged to function as alternative efferent routes from the adenohypophysis. The limited potential for venous drainage directly to the cavernous sinus suggests that blood leaves the adenohypophysis by other routes; blood carried via long portal vessels from the infundibulum to the adenohypophysis may return to the neurohypophyseal capillary bed via short portal vessels. This anatomical study suggests that hypothalamic and adenohypophyseal secretions are conveyed to the capillary bed of the neurohypohysis. These secretions may leave the neurohypophysis via any of seven potential routes: one efferent route is directed to the adenohypophysis, another route is directed to the systemic circulation, but five of the potential efferent routes are directed toward the brain.

Animals↗

Pituitary secretes to brain. Experiments in sheep.

Because vascular casts of the pituitary demonstrated that there are a few venous connections from the adenohypophysis to the juxtaposed cavernous sinus, it was predicted that some portal vessels must carry blood from the adenohypophysis back to the neurohypophysis. Physiological studies confirmed this prediction and verified earlier observations that blood-flow within the neurohypophysis can be towards the median eminence. In the present study, increased concentrations of prolactin and growth hormone were found in blood sampled from intracranial vessels (internal carotid artery and sagittal sinus). It was concluded that the neurohypophyseal capillary bed not only receives trophic hormones produced in the adenohypophysis but, under certain physiological circumstances, delivers those hormones directly to the brain.

Animals↗

The neurohypophyseal capillary bed. I. Anatomy and arterial supply.

Vascular casts of the pituitary-median eminence complex of mice,rats, dogs, sheep and monkeys were examined with the scanning electron microscope. Microfil-injected specimens of the rabbit and monkey pituitary-median eminence complex were examined by light microscopy after intracranial internal carotid artery occlusion. In each species a common neuropophyseal capillary network was found uniting infundibulum (median eminence), infundibular stem and infundibular process. This capillary bed is supplied from above by superior hypophyseal arteries and from below by inferior hypophyseal arteries. An artery to the infundibular stem was found in some species. With occlusion of the intracranial internal carotid arteries, flow through superior hypophyseal arteries did not occur. Yet the entire neurohypophyseal capillary bed filled upon injection with Microfil. These observations suggest the concept of a restricted arterial supply to the median eminence with drainage to the underlying adenohypophsis on one hand and to the infundibular process with drainage to the systemic circulation on the other must be modifed and that blood flow within the neurohypophyseal capillary bed (between infundibular process and median eminence) occurs.

Animals↗

Social and nonsocial behaviors of adult rhesus monkeys after amygdalectomy in infancy or adulthood.

At 6 yr of age six female rhesus monkeys that had sustained bilateral amygdalectomy in infancy, and five intact controls, were transferred to an observation cage where behaviors were recorded while the monkeys were (a) alone, (b) paired with unfamiliar stimulus animals, and (c) paired with familiar monkeys from the opposite experimental group. The five adult controls then underwent amygdalectomy, and all tests were repeated with the infant- and adult-operated animals. Infant-operated monkeys changed behaviors more rapidly than did intact controls in social and nonsocial situations, and their activity levels were less modified after a 24-hr period in the observation cage. They were subordinate to intact controls but expressed less fear than did controls when briefly placed with an unfamiliar aggressive animal. Adult amygdalectomy produced many changes in behavior, but these aberrations were identical to those observed in like-age monkeys that had been amygdalectomized in infancy. Infant-operated monkeys demonstrated more behavioral deficits at 6 yr than they had earlier in life.

Age Factors↗

Acute cerebellar hemorrhage. Analysis of clinical findings and outcome in 12 cases.

Although a majority of reported cases of cerebellar hemorrhage are subacute or chronic, an acute form of cerebellar hemorrhage occurs that results in coma within 48 hours of onset and is probably always fatal without surgical intervention. Our experience with 12 consecutive patients with proved acute cerebellar hemorrhage is summarized. Of three patients treated with aggressive medical therapy alone, none survived more than 48 hours. In seven of nine operated cases, emergency surgery was undertaken solely on the strength of clinical diagnosis without radiologic confirmation. Three died postoperatively. Of six survivors, two recovered fully, and two show mild and two moderate residua. The major factors influencing survival were the rate of evolution of signs and the level of consciousness at the moment of surgery.

Acute Disease↗

Scanning microscopy of pituitary vascular casts.

Vascular casts of the pituitary-median eminence complex from seventeen adult female rabbits were examined with the scanning electron microscope. The results of this study confirm the presence of a single capillary bed common to the entire neurohypophysis. Arterial supply to the rabbit pituitary is only to the neurohypophysis. A direct supply to adenohypophysis was not found. Within the median eminence there are an external and internal capillary plexus. The internal capillary plexus is directed toward the infundibular recess of the third ventricle. It does not receive a direct arterial supply but derives its blood supply from the external plexus before draining to the adenohypophysis. Vessels of the posterior median eminence are confluent with vessels of the infundibular stem. On the basis of these studies, it is proposed that the entire neurohypophysis, not simply the median eminence, serves as the final common pathway to the glandular pituitary. It is also proposed that in the median eminence, vessels are organized to deliver blood containing hypothalamic releasing and inhibiting hormones as well as posterior lobe neural hormones (antidiuretic hormone and oxytocin) to the ventricular surface for subsequent transport to cerebrospinal fluid and distribution to the brain.

Animals↗