Search PubMed⌕ Search

Biomedical subjects

S Smeds

Publications and source records attributed to S Smeds.

At least 55 records · Page 3Linked to original sources

"The low T3 syndrome" and impaired thyroid protein synthesis in experimental trauma.

The thyroid response was evaluated in the present trauma model. Trauma of varying severity was studied in 3 groups of anesthetized pigs. The animals were exposed to preparative surgery alone (n = 6) or followed by a standardized missile trauma to a hind leg (n = 10) or to the abdomen (n = 8). Post-trauma observation for 24-48 hours under continuous anesthesia included measurements of circulating T4, T3 and rT3. The serum concentrations of T4 and T3 fell significantly in all groups, the fall being exponential in the missile trauma groups. The reductions were greatest in the most severely injured group (abdominal trauma) and least in the group with preparative surgery only. The nadir of T4 concentration was reached at 24 hours in all groups. The T3 nadir occurred at 12 hours in the abdominal trauma group and at 24 hours in the groups with hind-leg trauma and preparative surgery. The rT3 concentration was significantly increased in the missile trauma groups. Thyroid protein synthesis was analysed in vitro by incubating thyroid tissue from pigs with missile trauma (n = 9) or with preparative surgery (n = 6). The 3H-leucine incorporation into the soluble thyroid proteins, measured as DPM/DNA, was 35% lower after missile trauma than after preparative surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Pathogenesis of heterogeneity in human multinodular goiter. A study on growth and function of thyroid tissue transplanted onto nude mice.

Functional and morphologic heterogeneity of human multinodular goiters was investigated in 300 samples from "cold" and "hot" regions of 20 goiters transplanted onto nude mice. Transplants were labeled with [3H]thymidine and radioiodine, while the host's thyroid-stimulating hormone (TSH) secretion was either stimulated or suppressed. Proliferation and function of follicular cells were assessed in whole follicles reconstructed from autoradiographs of serial sections. Hot transplants had a higher autonomous iodine uptake than those of cold tissue in TSH-suppressed hosts. Functional autonomy widely varied among the follicles, but even more so among individual cells. Hot grafts differed from cold ones only by a comparatively larger fraction of autonomous cells. Intercellular differences of iodinating activity were not abolished by TSH. Grafts faithfully reproduced the individual growth pattern of the original tissue. Between 0.5% and 7% of all follicular cells replicated despite suppression of TSH. Up to 70% of these cells were clustered, forming scattered foci of autonomously growing tissue. Other cells only started replicating after long-term TSH stimulation. Thus, goiters contained subsets of cells with high and others with low growth response. Progenies of replicating cells remained clustered, sometimes budding outwards to form new follicles. Autonomy of growth and autonomy of function are independent traits of epithelial cells. Epithelial cells have their individual growth pattern, replication rate, and functional capacity. These traits are passed on from a mother cell to its progeny during follicle neogenesis. To this main mechanism accounting for the morphologic and functional heterogeneity of human goiters, inheritable modifications of gene expression must probably be added.

Animals↗

Betablockers compared with antithyroid drugs as preoperative treatment in hyperthyroidism: drug tolerance, complications, and postoperative thyroid function.

Subtotal thyroid resection or hemithyroidectomy was performed for hyperthyroidism on two groups of patients: 84 treated before surgery with antithyroid drugs and thyroxin and 111 given only beta-blocking agents before surgery. These two patient groups were compared with reference to preoperative medication, operation, immediate postoperative course, and late results, with follow-up for 3 to 7 years. The advantages of beta-blockers compared with conventional antithyroid medication were lack of adverse reactions, rapid effect of treatment, considerably shortened preoperative treatment time, and fewer outpatient visits, with consequent financial benefit. No disadvantages of beta-blockers were found except that 18% of the patients required additional propranolol in the immediate postoperative period. There were no surgical complications in either group other than a mild persistent hypocalcemia in two patients from the beta-blocked group. The serum thyrotropin levels during the first 6 postoperative months were significantly higher in the patients treated with antithyroid drugs. The frequency of postoperative thyroid dysfunction showed no intergroup difference during the observation period. Signs of hypofunction, necessitating thyroxin supplementation, were observed in 28.6% of patients in the antithyroid drug/thyroxin group and in 25.7% in the beta-blocker group. Toxic recurrence occurred in 1.8% of the group that received beta-blockers and in 1.2% of the other patients. The study demonstrated that beta-adrenoceptor blockade is a safe method for preoperative treatment in hyperthyroidism, with advantages for patients and regarding costs.

Adrenergic beta-Antagonists↗

Follow-up of 102 patients operated on for gastrointestinal carcinoid.

A series of 102 patients with carcinoid tumor is reviewed. The sites of carcinoid were stomach (1 case), appendix (32), small intestine (57) and colon or rectum (12). The average age was 37 years in the patients with appendiceal carcinoid and 62 years in the others. The mean observation time was 9.2 years in appendiceal carcinoid, and none of these patients died of the tumor. Among the patients with carcinoid in other sites, the 5-year survival rate was 65%. Only patients initially free from metastases were still alive after 12 years. Multiple synchronous carcinoid tumors were found in 14 cases, all of them men. The investigation illustrated the difficulties in preoperative diagnosis of carcinoid, including the small value of laboratory tests. A positive attitude to exploratory laparotomy is therefore recommended. When no or only a few lymph-node metastases are found at intendedly curative operation, a "second look" exploration six months after the primary operation will probably reveal any recurrence and can lead to radical removal of this slow-growing tumor. When distant metastases are present, the long-term outlook is poor. The reason why only men had multiple synchronous carcinoids was not clear from our study.

Adolescent↗

Ultrastructural morphology and evidence of iodide uptake and protein synthesis in normal human thyroid transplants in nude mice.

Normal human thyroid tissue was xenotransplanted to athymic mice. Well preserved structural properties of the transplants were observed at both light and electron microscopical level. Analysis of the soluble proteins in the transplants by polyacrylamide gel electrophoresis showed that the major fractions were the 19S thyroglobulin, the 27S iodoprotein and a larger protein fraction. Protein synthesizing capacity of the transplants, as measured by in vivo 3H-leucine incorporation into the soluble transplants proteins was demonstrated. The observed 3H-leucine incorporation was in the same magnitude as that found in the original donor tissue at the time of transplantation. Four weeks after transplantation a significant 125I-iodide uptake (2.0%) was observed in the transplants. Corresponding value for the host thyroids was 6.6%. The biological half-time of the accumulated 125I-iodide in the transplants was reduced from 97 days to 38 days between 2 and 4 weeks after transplantation. The biological half-time in the host thyroid increased from 27 days to 32 days during the same period. This investigation shows that normal human thyroid tissue can be transplanted to nude mice with preserved tissue organisation and maintained cellular function.

Animals↗

Evaluation of preoperative diagnosis and surgical management of thyroid tumors.

The difficulty of obtaining an accurate diagnosis in nodules of the thyroid gland without operation and histologic examination is well documented. Surgical intervention has therefore been recommended, though opinions differ concerning the indications for surgery. Experience from 276 patients operated on for thyroid gland nodules is reported in the present paper. The decision to operate was based on a standard schedule with relatively wide indications for surgery. Complete hemithyroidectomy was performed in all surgically managed cases. The accuracy of preoperative diagnosis was evaluated against the histologic findings. Experience of hemithyroidectomy as the standard procedure is also reviewed. The incidence of malignancy with this active policy was 9% in the series as a whole and 12% in solitary adenoma of the thyroid. Total thyroidectomy was routinely performed when malignancy was demonstrated; 24% of the malignancies were bilateral. Although fine-needle biopsy and clinical evaluation were entrusted only to experienced investigators, the results confirmed earlier reports that no hitherto available diagnostic procedure can adequately distinguish malignant from benign thyroid lesions without surgery. The value of scintigraphic thyroid scan in the preoperative assessment seemed to be insufficient to warrant its use. No persistent complications arose from hemithyroidectomy. Complete hemithyroidectomy is always the operation of choice in such cases since, should be histologic examination show malignancy, the requisite additional surgery will not involve a thyroid lobe with previous surgical interference.

Adult↗

Capillary endothelial cell multiplication in adipose tissue pads on the thyroid during the feeding of thiouracil.

It has been reported that blood capillaries in adipose tissue pads on the upper and lower poles of the thyroid gland enlarge when Fischer rats are fed thiouracil (TU) in a low iodine diet. To test whether the enlargement is accompanied by proliferation of the endothelial cells, [3H]thymidine was injected into rats fed the TU-containing diet, and labeling of the endothelial cells was studied by autoradiography. Nuclear labeling of the capillary endothelial cells was observed in the mixed brown and white adipose tissue (BAT and WAT, respectively) pads on the thyroid. After a single pulse of [3H]thymidine, 10% of the nuclei were labeled at 10 days (the peak labeling), and labeling decreased thereafter. To test whether the adipose tissue was stimulated because of the poor nutritional quality of the low iodine diet, Purina Laboratory Chow (a nutritionally adequate diet) was tested and produced the same result. To test whether TU had a direct effect, 5 micrograms T4/100 g BW were given daily; there was then no response to the TU, suggesting that the effect was due to an elevated circulating concentration of TSH. The effect was generally restricted to the adipose tissue pads on the thyroid. There was no response in interscapular BAT, epididymal WAT, or sc WAT. However, there was a response in small clusters of adipocytes embedded in inguinal sc WAT. The results are consistent with the idea that the effects are directly or indirectly due to elevated circulating TSH levels.

Adipose Tissue↗

Preferential secretion of triiodothyronine in man.

The directly measured secretion rates of thyroxine (T4), 3,5,3'-triiodothyronine (T3), and 3,3',5'-triiodothyronine (rT3) were compared to the tissue concentrations of these hormones and to the distribution of follicular iodoproteins in 15 patients submitted to thyroid or parathyroid surgery. The T4/T3 and rT3/T3 ratios were higher for thyroid tissue than for the secretion rates, indicating a preferential secretion of T3. The concentrations of T4 and T3 were higher in the 27S iodoprotein fraction than in the 19S thyroglobulin fraction.

Adult↗

Evaluation of factors affecting the incidence of retained calculi in the bile ducts.

During the 4-year period (1974-1977) 1204 operations were performed for cholelithiasis. Of 139 patients who underwent choledocholithotomy, retained stones in the bile ducts were diagnosed in 22 (15.8%). Peroperative cholangiograms taken before and after exploration of the bile duct were re-examined and compared to a control material. A major factor in the occurrence of retained stones was the number of the stones on the pre-explorative cholangiogram. Among patients with retained stones 64% had five or more stones in their bile ducts on the pre-explorative cholangiogram. The corresponding frequency in controls was only 18% and this difference is statistically significant. Neither the size of stones, nor the diameter of the common duct had any bearing on the incidence of retained stones. On the post-explorative cholangiogram an interrupted passage of contrast medium into the duodenum was no proof of retained stones. False negative cholangiograms after surgical exploration of the common duct were seen in 27% and in the control group there were false positive cholangiograms in 47%. Retained stones that are undiagnosed after operation and those that are known, but cannot be removed, reflect, respectively, diagnostic and therapeutic failure. In this context, measures to improve both these areas are discussed.

Bile Duct Diseases↗

Protein composition in single follicles, homogenates and fine-needle aspiration biopsies from normal and diseased human thyroid.

The protein composition of the thyroid colloid was analysed by microgel electrophoresis and densitometry in 41 euthyroid patients. The colloid samples were obtained from single follicles by micropuncture, from homogenates of microbiopsies or from aspiration biopsies. Fourteen of the patients had morphologically normal thyroid tissue, 18 had atoxic nodular goitre and 19 of the patients had atoxic adenoma. Ten of the patients with nodular goitre had prior to the investigation received lithium therapy for psychiatric disorders. The main component of the thyroid colloid was 19S thyroglobulin (TG), but larger iodoproteins (S-TG) and smaller protein fractions, an albumin-like protein and a pre-albumin fraction, were also present in varying relative amounts. Analyses of homogenates of microbiopsies from normal thyroid tissue demonstrated the same protein composition as observed in single follicles. In colloid samples from atoxic nodular goitre the lighter protein fractions were absent in most of the samples. Analyses of homogenates or aspiration biopsies could not demonstrate this alteration in the protein composition in nodular goitre. Lithium therapy resulted in a significantly lower amount of the lighter protein fractions but unchanged amounts of the globulin fractions in atoxic nodular goitre.

Adenoma↗

Thyroid function after thermal trauma.

The thyroid function was analyzed for 4-6 weeks in a prospective study of 12 thermally injured patients. The burn size range was 15-90%. Serum concentrations of 3,5,3'-triidothyronine (T3) was suppressed and 3,3',5'-triidothyronine (rT3) was increased. The ratio T3/rT3 was subnormal on the third day after the trauma and normalized after 3 weeks. Thyroxine and the free T4-index were within the normal range. The free T3-index were within the normal range. The TSH concentration was initially low but slowly increasing during the period of study. The concentration of the thyroxine-binding globulin (TBG) varied within the normal range. The T3 resin uptake test varied inversely with the TBG concentration. The concentration of thyroxine-binding prealbumin (TBPA) was subnormal. A control experiment excluded possible interference on the hormone concentrations of administered donor blood and plasma. It is concluded that the thyroid hormones are not responsible for the posttraumatic hypermetabolism in burn injury. The present findings further indicate a depletion of metabolically active thyroid hormones at the cellular level after burn injury.

Adult↗

LCEC analysis of 5-hydroxytryptamine and norepinephrine in the human gastrointestinal tract.

The mucosal content of 5-hydroxytryptamine (5-HT) and norepinephrine (NE) in different parts of the human gastrointestinal tract has been studied. Peroperative biopsies of normal mucosa were collected during various gastrointestinal operations. The amines were extracted and assayed by liquid chromatography with electrochemical detection (LCEC). The concentration of 5-HT was generally approximately 12 times higher than the NE concentration and the highest concentration for both amines was observed in the duodenum, 14 micrograms/g and 1.5 micrograms/g wet weight for 5-HT and NE respectively.

Chromatography, Liquid↗

Protein composition of the thyroid colloid in patients with hyperthyroidism.

Analysis of the protein composition of the thyroid colloid was performed in 28 patients operated on for hyperthyroidism. Fifteen of the patients were treated before the operation with carbimazole combined with thyroxine and 13 were treated with propranolol alone. Colloid was collected by micropuncture of single follicles in peroperative thyroid biopsies. The protein composition was analysed by microgel electrophoresis and densitometry, both in the colloid samples and in the supernatant fraction of homogenates of microbiopsies from the thyroid specimens. The analyses showed that, during treatment with carbimazole and thyroxine, the relative amount of the larger thyroglobulin aggregates (S-TG) was decreased compared with the relative amount observed in the colloid from normal thyroid tissue. In the hyperfunctioning thyroid tissue from the propranolol-treated patients the protein composition of the colloid was similar to that observed in normal tissue and the relative amount of the S-TG fractions was significantly higher than in the carbimazole- and thryoxine-treated group. It may be concluded that the increased release of thyroid hormones in hyperthyroidism is not combined with changes in the protein composition of the thryoid colloid. The decreased relative amount of the S-TG fractions in the thyroid colloid from patients treated with carbomazole and thryoxine was probably due to an insufficient capacity to iodinate thyroglobulin.

Carbimazole↗

Protein synthesis in hyperfunctioning human thyroid tissue.

The rate of protein synthesis was examined in vitro in thyroid tissue slices. The material was obtained from euthyroid patients operated on for hyperparathyroidism and from hyperthyroid patients with Graves' disease pre-operatively treated with propranolol alone. The rate of protein synthesis was calculated from the incorporation of [3H]leucine radioactivity in the soluble thyroid proteins (mainly the colloid proteins), the amount of soluble protein per mg tissue and amount of DNA. Based on these figures it was observed that the rate of protein synthesis was 3.2 times higher in the hyperfunctioning thyroid tissue than in the normal tissue. A significant correlation was observed between this activity factor and the serum concentrating of thyroxine. It is concluded that the increased hormone formation in hyperthyroid Graves' disease at least partly depends on an increased rate of protein synthesis in the follicular epithelium. This could be due to stimulation by thyroid immunoglobulins, but other pathogenetic mechanisms may be responsible.

Humans↗

Depletion of colloid 27S and larger thyroid iodoproteins following treatment with propylthiouracil.

By means of a micropuncture technique and microgel electrophoresis the luminal content of single rat thyroid follicles were analyzed during PTU treatment for 4 weeks. The relative amount of aggregates of thyroglobulin (i.e. the 27S iodoprotein and larger complex) was reduced from 15 per cent to approximately 3 per cent after 48 h. The aggregates were practically absent after 2 weeks. The thyroglobulin fraction was the predominant colloid constituent. The protein concentration of the colloid was not changed at the end of the period of PTU treatment (8.9 g/100 ml). It is concluded that PTU inhibits the aggregation of thyroglobulin to a larger complex. The results further indicate that the aggregates of thyroglobulin are preferentially localized to the periphery of the lumen in the larger follicles.

Animals↗