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Biomedical subjects

J Rastad

Publications and source records attributed to J Rastad.

At least 199 records · Page 11Linked to original sources

Ultrasound scanning for preoperative location of parathyroid tumours.

Ultrasonic examination of the parathyroid glands has been used in 50 consecutive patients with surgically verified hyperparathyroidism. It revealed 21 of 32 parathyroid adenomas located in the neck. In 16 patients with primary or secondary (uraemic) hyperplasia, 11 out of 48 hyperplastic glands in the neck were identified by ultrasound. A parathyroid adenoma was revealed in all (3) patients with hypercalcaemic crisis. Enlarged parathyroid glands were correctly located in all (5) patients with adenomas and previous explorations of the neck, whereas two out of three glands were visualized by ultrasound prior to secondary explorations in 3 patients with hyperplasia associated with the multiple endocrine neoplasia syndrome type 1. Undetected parathyroid glands were generally smaller than those visualized by ultrasonic examination. It was often difficult to unequivocally establish that identified lesions represented parathyroid glands. Irregular noduli and cysts of the thyroid as well as lymph nodes could be misinterpreted as parathyroid lesions. A nodular thyroid goitre was present in almost half of the patients with a negative ultrasonic examination of the parathyroid glands.

Adenoma↗

Ultrastructural morphology of axon terminals of an inhibitory spinal interneurone in the cat.

Axon collateral terminals of an interneurone mediating Ia reciprocal inhibition of spinal a-motoneurones have been ultrastructurally investigated after intracellular staining with horseradish peroxidase. The size of bouton profiles, the size and shape of synaptic vesicles and the characteristics of synaptic contacts were analyzed in 38 terminals. The morphology of the terminals was compared with the morphology of previously investigated terminals of excitatory spinocervical tract cells. The flatness of synaptic vesicles was only marginally greater in the terminals of the inhibitory interneurone.

Animals↗

Morphology of synaptic vesicles in axo-dendritic and axo-somatic collateral terminals of two feline spinocervical tract cells stained intracellularly with horseradish peroxidase.

Synaptic vesicles in initial collateral terminals of two feline spinocervical tract cells have been investigated after intracellular staining with horseradish peroxidase. A total of 5325 vesicles in 52 axodendritic and 26 axo-somatic terminals were analysed after aldehyde-osmium fixation. The greatest length and longest perpendicular width of each vesicle were measured, and the ratio and geometric mean of the diameters (gm-diameters) were calculated. The vesicles were divided into classes with round, elliptical and flat organelles. The variations in vesicle length, gm-diameter, and diameter ratio were statistically analysed by means of one- and two-way analyses of variance and t-tests. The diameter ratio, the length of round vesicles, and the gm-diameters of round and elliptical vesicles differed significantly between the cells. The length and gm-diameter of the elliptical vesicles differed significantly between the groups of axo-dendritic and axo-somatic terminals of each cell. Round vesicles were significantly longer in the axo-somatic than in the axo-dendritic terminals of each cell, and the gm-diameter showed this relation for both round and elliptical vesicles. It is assumed that a one-size vesicle could not account for all the measured profiles. The variability of synaptic vesicles within and between the functionally similar cells emphasize the difficulties in using the morphology of synaptic vesicles for a discrimination of axon terminals of different origin.

Animals↗

Quantitative analysis of axodendritic and axosomatic collateral terminals of two feline spinocervical tract cells.

The initial axon collaterals of two feline spinocervical tract cells have been ultrastructurally investigated after intracellular injection with horseradish peroxidase. A total of 200 axodendritic and 43 axosomatic terminals were analysed in serial section. The following variables were measured: the diameter and area of the bouton profiles, the areal densities of synaptic vesicles and mitochondria of the bouton profiles, the width and length of the synaptic clefts, the width of the postsynaptic densities, the width of the postsynaptic dendrites, and the width and length of axons between the boutons. Ten boutons were reconstructed for an investigation of the relation between measurements in two and three dimensions. All the measured variables showed wide ranges of variation. They were analysed statistically for significant differences between the cells and between the axodendritic and axosomatic boutons of each and both cells. Significant differences were mainly observed in the former comparison but they were also found between the axodendritic and axosomatic terminals of the individual cells.

Animals↗

Segmental and supraspinal input to cells of origin of non-primary fibres in the feline dorsal columns.

1. The synaptic input to ascending tract cells with axons in the dorsal columns was investigated using intracellular recording. 2. E.p.s.p.s evoked by stimulation of the lateral funiculus were analysed to test for the possibility of collateral connexions between spino-cervical tract cells and dorsal column cells. Three groups of fibres were found to contribute to such e.p.s.p.s: fibres which terminated or originated between spinal segments C3-4 and C1, or Th9 and C3-4 and cortico-spinal tract fibres. The latencies and thresholds of e.p.s.p.s evoked by stimulation of the first group of fibres were compatible with their origin via axon collaterals of spino-cervical tract cells. The occurrence of these e.p.s.p.s in dorsal column cells which were disynaptically excited from cutaneous afferents further corroborated this possibility. 3. E.P.S.P.S of specifically cervical origin were also found in some other neurones in the dorsal horn, probably segmental interneurones, but were absent in spinocervical tract cells. 4. Convergence of group I muscle afferents (possibly both group Ia and group Ib) and cutaneous afferents was found in about 50% of the dorsal column cells. The shortest latency e.p.s.p.s from cutaneous and group I afferents were evoked with segmental delays indicating monosynaptic and disynaptic coupling. 5. I.p.s.p.s were evoked from cutaneous and group I muscle afferents in either the same or different nerves as those from which the e.p.s.p.s were elicited. Excitatory potentials were, however, dominating.

Animals↗

Arborization of initial axon collaterals of spinocervical tract cells stained intracellularly with horseradish peroxidase.

The initial axon collateral arborizations of two feline spinocervical tract cells have been analysed after intracellular staining with horseradish peroxidase. The images of the cells were reconstructed in the light microscope from transverse serial sections. The cell bodies were situated in laminae IV or III of the lumbar dorsal horn. Each cell exhibited one initial collateral. These emerged from the parent axons at distances of about 310 and 580 micron, respectively, from the cell body. The collaterals branched, mainly symmetrically, in laminae III-VI and IV-VI, respectively. The total collateral lengths were about 12,000 and 10,900 micron; altogether 329 and 274 stained terminals were found per collateral in laminae III-VI and IV-VI, respectively. The great majority of boutons were found in laminae IV and V. The terminals were distributed mainly in spherically arranged groups of 3-12 boutons, usually connected to each other by thin terminal axons. The light microscopically investigated sections were 're-embedded' and processed for electron microscopy. The ultrastructural investigation showed boutons with axo-dendritic, axo-somatic or axo-axonal synapses.

Animals↗

MHC class I and II antigen expression and interferon alpha treatment of human midgut carcinoid tumors.

Cryosections of 28 primary and metastatic midgut carcinoid tumors from 12 patients with carcinoid syndrome were investigated immunohistochemically with antibodies that recognize human MHC class I (HLA-ABC) and class II (HLA-DR) antigens. The tumor parenchyma of all six patients treated with interferon alpha (IFN-alpha) during a mean 8.6 months (3 x 10(6) to 5 x 10(6) U three times weekly) exhibited unequivocal HLA-ABC immunoreactivity, with only minor discrepancies between primary lesions and metastases in mesenteric lymph nodes and liver. Class I staining was absent on the tumor cells of all 14 specimens from the patients without IFN therapy but was induced by culturing freshly dispersed tumor cells in vitro for 48 hours in the presence of recombinant IFN-alpha. The stroma of all neoplasms displayed class I and II immunostaining, as did usually a few CD4-expressing cells. The carcinoid specimens lacked parenchymal HLA-DR immunoreactivity, which is interesting considering suggestions on improved prognosis for bowel carcinomas lacking the class II expression. The study supports the idea that induction of MHC class I antigens could contribute to the beneficial clinical effect of IFN-alpha treatment in patients with midgut carcinoid tumors.

Aged↗

Surgery for sporadic primary hyperparathyroidism in the elderly.

Retrospective analysis has been performed on 108 consecutive patients operated for primary hyperparathyroidism (HPT) at 75 to 85 years of age (mean 79 years). The preoperative serum calcium value averaged 2.99 mM, and six patients had hypercalcemic crisis. Psychic disturbances were seen in 60 patients (56%), 40% of whom demonstrated dementia. Skeletal and muscular complaints were registered in 29% and 19%, respectively, and only 6% were overtly asymptomatic. Cardiovascular diseases were presented by 69% of the patients, 13% had diabetes mellitus, and 26% were institutionalized prior to surgery. Bilateral neck exploration disclosed a single adenoma in 69%, which was of the oxyphil cell type in 13%, and water-clear (n = 3) or chief cell hyperplasia in 27%. The total glandular weight averaged 1085 mg. Altogether 72 patients operated on after 1980 demonstrated a perioperative (30-day) mortality of 1.4%; the corresponding morbidity of 8.7% mainly included infections as well as a vocal cord paralysis in one patient and two incisional hematomas. Analysis for mean 3.1 years postoperatively displayed reversal of hypercalcemia in 95% of the patients; 2.8% of those operated after 1980 had persistent disease. Symptoms seemed to be alleviated in 62%, with a similar rate attained in patients with dementia. Altogether 60 patients died from mainly cardiovascular diseases mean 4.2 years after the operation. Those succumbing the first postoperative year (n = 21) showed overrepresentation of cardiac diseases and diabetes mellitus. The results demonstrate prevalent psychic disturbances, oxyphil adenomas, and multiglandular parathyroid disease in elderly patients with primary HPT and favor rather liberal application of parathyroid surgery among these individuals.

Aged↗

Surgical treatment of mid-gut carcinoid tumors.

Coincident with medical antitumor treatment of 138 patients suffering from mid-gut carcinoid tumors, 51 patients were subjected to surgery with the principal aims of removing primary tumors and debulking mesenteric or liver metastases. Sixteen patients had previously been operated with intestinal resection or, when the tumors had been considered inexcisable, with intestinal bypass or laparotomy alone. Apart from exhibiting symptoms related to the carcinoid syndrome, the majority (approximately 60%) of the 51 patients had generally intermittent, subileus-like abdominal pain and weight loss. In 18 patients, these symptoms were pronounced and associated with intestinal obstruction or severe malnutrition. Computed tomography and arteriography efficiently demonstrated mesenteric and liver metastases. At laparotomy, the primary intestinal tumors were small, mainly less than 1 cm in diameter, and they were multiple in 39% of the patients. Mesenteric metastases measuring up to 12 cm in diameter were present in 86% of the patients. These metastases were frequently associated with a pronounced mesenteric and retroperitoneal fibrosis causing fixation, angulation, and obstruction of the bowel as well as incipient intestinal gangrene in 8 patients. In all but 6 patients, the primary tumors could be removed by comparatively limited intestinal resections although bulky mesenteric metastases were often dissected from the mesenteric vessels. Liver metastases, found in 49% of the patients, were generally bilateral and multiple, and major hepatic metastases were resected in 6 patients. The results support a role for surgery also in the more compromised patients with mid-gut carcinoid tumors and that such intervention may be associated with considerable symptomatic relief and substantial periods of survival.

Adult↗

Monoclonal antibodies raised against mid-gut carcinoid tumor cells.

Three monoclonal IgG 2a antibodies were produced after immunization of mice with dispersed cells from a human mid-gut carcinoid tumor. Acetone-fixed cryosections of 57 primary and metastatic mid-gut carcinoid tumors as well as 2 hind-gut (rectal) carcinoids showed a conspicuous immunoreaction while a thymic carcinoid was essentially unstained with the antibodies. The 3 antibodies yielded a similar pattern of immunostaining. The immunoreaction comprised more than 95% of the carcinoid tumor cells, and it was more uniform and intense in primary tumors than in mesenteric, hepatic, and ovarian metastases of the mid-gut carcinoid tumors. Immunofluorescence studies on suspended carcinoid tumor cells showed that the antibodies bound to the surface membrane of the cells. The antibodies immunostained enterocytes of the small and large bowel, intestinal metaplasia of the stomach mucosa as well as colorectal adenocarcinomas. Endocrine pancreatic tumors producing vasoactive intestinal polypeptide, gastrin, somatostatin, and/or pancreatic polypeptide as well as the epithelium of pancreatic ducts were also stained with the antibodies, whereas a large number of other normal and abnormal human tissues, including benign and malignant insulinomas, were unreactive. The findings indicate that the antibodies recognize differentiation antigens on the carcinoid tumor cell surface preserved also on endocrine and nonendocrine cells of the normal bowel mucosa. The restricted tissue reactivity of the antibodies suggests that they may constitute useful tools in the histological characterization of carcinoid tumors. Further studies may reveal if they are applicable for immunolocalization and perhaps even immunotherapy of these neoplasms.

Antibodies, Monoclonal↗

Cellular physiology and pathophysiology of the parathyroid glands.

This report provides insight into parathyroid gland physiology and the pathophysiology of hyperparathyroidism (HPT). Increases in the extracellular calcium concentration constitute the primary physiological signal for inhibition of parathyroid hormone (PTH) release. Transduction of the external signal into a cellular response involves activation of a cation receptor mechanism on the plasma membrane with rapid rise in the cytoplasmic calcium concentration of the cells. This recently discovered parathyroid calcium receptor has been characterized as a glycoprotein of unusually high molecular weight, which may play a key role in calcium homeostasis since it is also expressed in the kidney and placenta. Binding of external calcium to the receptor is associated with mobilization of intracellular calcium as well as calcium influx into the cells and phosphoinositol hydrolysis. These events rapidly interfere with the release process through essentially unknown mechanisms and probably also at sustained stimulation inhibit PTH gene transcription. The relative calcium insensitivity of the PTH release in HPT is associated with a deranged regulation of cytoplasmic calcium within pathological parathyroid cells. The molecular basis for this disturbance comprises down regulation of the cation receptor, whereby external calcium is translated into abnormally low levels of cytoplasmic calcium and insufficient inhibition of PTH release. Studies on expression of the functionally important cation sensing glycoprotein and its associated cellular signal systems may provide novel means for interference with the pathophysiological derangements of HPT.

Animals↗

Primary hyperparathyroidism: epidemiology, diagnosis and clinical picture.

Primary hyperparathyroidism (HPT) is a common disorder that mainly afflicts elderly women. It can be diagnosed in at least 1% of all postmenopausal females and autopsy studies indicate an even higher frequency. Although the widespread use of automated serum calcium analyses has increased the awareness of HPT, only 10% of all cases seem to be identified. The diagnosis relies on the demonstration of an inappropriately elevated serum concentration of parathyroid hormone (PTH) relative to the serum calcium value, which need not be markedly raised. Measurements of intact PTH with immunometric methods have considerably improved the diagnostic precision but it is still difficult to evaluate patients with only marginal hypercalcemia. Few patients with diagnosed HPT are completely without symptoms. Symptoms commonly encountered are psychiatric and neuromuscular disturbances. Subclinical bone disease might be relevant but there is insufficient information about its importance in otherwise asymptomatic individuals. Various cardiovascular risk factors appear more commonly in patients with HPT and untreated disease is associated with an increased risk of premature death.

Female↗

The role of the pathologist in diagnosis and surgical decision making in hyperparathyroidism.

Hyperparathyroidism has been diagnosed with increasing frequency in recent decades. The concomitant awareness that the disease may be the cause of a concealed morbidity and even an increased mortality has resulted in more liberal indications for surgery. Many patients currently undergo surgery on the grounds of only mild hypercalcemia and in the absence of any apparent clinical symptoms. This policy of early surgical treatment has emphasized the importance of a histopathological parathyroid diagnosis, since many of these patients exhibit chief cell hyperplasia and minimal glandular enlargement. Light microscopic examination of frozen sections stained with hematoxylin-eosin and with stains for demonstration of cytoplasmic fat in the parathyroid chief cells, and appropriate weight estimates of the parathyroid glands, constitute the conventional, intra-operative basis for the diagnosis. The use of specific antiparathyroid antibodies is an important new tool in the histopathological parathyroid examination, mainly because of the ability to demonstrate the cause of increased parathyroid hormone release from the pathological parathyroid tissue. A careful histopathological examination in combination with gross inspection of the parathyroid glands by an experienced eye should contribute to adequate surgical treatment and minimize errors in operative management in patients with hyperparathyroidism.

Adenoma↗

Causes of failed primary exploration and technical aspects of re-operation in primary hyperparathyroidism.

Hypercalcemia was corrected in 62 (90%) of 69 patients after re-operation for primary hyperparathyroidism during a mean follow-up of 6.3 years. Failed primary exploration was mainly due to inadequate visualization of the pathological parathyroid glands, often in association with misleading or absent peroperative histology. Other causes included seeding of parathyroid adenoma tissue, truly recurrent adenomas, and recurrent hyperplasia, especially in patients with multiple endocrine neoplasia type 1. A considerable number of parathyroid glands missed at the primary operations were subsequently found in essentially normal positions. Ectopic superior glands were most frequently positioned para-esophageally or retro-esophageally, while abnormally placed inferior glands were generally situated within or close to the thymus. Glands in 3 patients were dissected from around the large vessels in the mediastinum. Concomitant thyroid procedures during the primary operation yielded few abnormal parathyroids and made the re-exploration considerably more difficult. We suggest a semilateral approach and caudal identification of the recurrent laryngeal nerve to reduce the hazards of difficult parathyroid re-operations. Mediastinal exploration may require total removal of the thymus and careful dissection of the middle mediastinum.

Adult↗

Pancreatic tumors in multiple endocrine neoplasia type 1: clinical presentation and surgical treatment.

Among 33 patients with endocrine pancreatic tumors due to multiple endocrine neoplasia type 1 (MEN-1), 19 (58%) patients had hypergastrinemia, 7 (21%) patients had hyperinsulinism, and 7 (21%) patients had clinically non-functioning lesions. At least one gross tumor was found in all patients undergoing pancreatic surgery, including those with negative localization studies prior to operation. The patients also had additional macroscopic tumors as well as numerous microadenomas, and the lesions frequently were positive for immunostaining with multiple hormones, mainly pancreatic polypeptide, insulin, glucagon, and somatostatin. Duodenal endocrine lesions were found in 4 of 5 investigated patients and stained with gastrin and somatostatin antibodies. Distal, mainly subtotal pancreatic resection, was performed in 18 patients, eventually combined with caput tumor enucleation or duodenotomy, while a few patients underwent only tumor enucleation or a Whipple procedure. The long-term outcome of operation was most favorable in patients with hyperinsulinism; only 1 patient had clinical recurrence. Patients with hypergastrinemia experienced only transitory lowering of serum gastrin values after pancreatic surgery and 47% of them had or developed metastases. Such tumor spread was seen in 57% of the patients with non-functioning lesions. Nine patients died from progressive tumor disease during follow-up. Consistent with previous studies, we found that surgery is indicated in MEN-1 patients with hyperinsulinism even if a lesion is not visualized by radiology. In addition, these indications should be extended to also include patients with only biochemical markers of disease, including elevations of gastrin, as these indicate the presence of gross tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Dynamics of parathyroid hormone release and serum calcium regulation after surgery for primary hyperparathyroidism.

Analysis of 14 patients with primary hyperparathyroidism (HPT) prior to and during the first year after parathyroid surgery disclosed that the operation was associated with rapid reductions of intact serum parathyroid hormone (PTH) and total serum and ionized plasma calcium values. A decreased urinary calcium excretion, a gradual elevation of renal calcium reabsorption, a transient reduction of serum calcitriol, and a late increase in 25-hydroxycholecalciferol values were also noted. Dynamic tests of parathyroid function by EDTA infusion and an oral calcium load revealed a sigmoidal relationship between serum PTH and calcium levels, and that parathyroid surgery induced considerable changes in both the position and slope of the dose-response curve. It was also apparent that PTH release was submaximally stimulated event at periods of hypocalcemia. The findings substantiate that adjustments of PTH release to acute alterations of serum calcium occur along the prevailing dose-response relationship, while stimuli being maintained for longer periods of time induce compensatory shifts in the position and slope of this curve. It is further suggested that unknown factors with PTH-like function may participate in the calcium regulation after surgery for primary HPT.

Adult↗