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Biomedical subjects

G Wallin

Publications and source records attributed to G Wallin.

At least 73 records · Page 4Linked to original sources

Prognostic significance of serum concentration of squamous cell carcinoma antigen in anal epidermoid carcinoma.

The prognostic significance of pre-treatment serum concentration of squamous cell carcinoma antigen (SCCAg) was investigated in a population of 60 patients with anal epidermoid cancer. Serum concentration was determined during the period 1985-90. The patients were followed until December 1991. An antigen level above 2.0 ng/ml was classified as elevated. Thirty-eight patients had T1-2 tumours, while 22 had T3-4 tumours. Sixteen of the 20 patients (80%) with an elevated SCCAg concentration relapsed or had residual tumour after conclusion of primary therapy, compared to 8 of 40 (20%) with a normal concentration (P = 0.00001). Six patients of 40 (15%) with a normal SCCAg had died at the end of follow-up compared to 10 of 20 (50%) with an elevated value (P = 0.006). For patients with T1-2 tumours 2 of 29 (7%) with a normal SCCAg had died with or from their cancer compared to 3 of 9 (33%) with an elevated value (P = 0.14); for T3-4 tumours these figures were 3 of 11 (P = 0.14); for T3-4 tumours these figures were 3 of 11 (27%) and 7 of 11 (64%) respectively (P = 0.009). Actuarial survival analyses for patients with normal vs elevated SCCAg concentration showed that the projected five year overall survival was 81% for those with a normal level and 43% for those with an elevated level (P = 0.004). For tumour specific survival the figures were 83% vs 45% (P = 0.004).(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗

Occurrence of ophthalmopathy after treatment for Graves' hyperthyroidism. The Thyroid Study Group.

BACKGROUND: Ophthalmopathy caused by Graves' disease may first appear or worsen during or after treatment for hyperthyroidism. It is not known, however, whether choosing to treat hyperthyroidism with antithyroid drugs, iodine-131, or surgery affects the development or aggravation of Graves' ophthalmopathy. METHODS: We studied 168 patients with hyperthyroidism caused by Graves' disease, stratified into two age groups--20 to 34 years (54 patients, group 1) and 35 to 55 years (114 patients, group 2). The patients in group 1 were randomly assigned to treatment with methimazole for 18 months or subtotal thyroidectomy, and those in group 2 to either of these two treatments or to iodine-131 therapy. All the patients received thyroxine to avert hypothyroidism, except those treated with iodine-131, who received thyroxine only if hypothyroidism developed. The duration of follow-up was at least 24 months. RESULTS: Twenty-two patients (13 percent) had infiltrative Graves' ophthalmopathy at randomization. During follow-up, ophthalmopathy developed for the first time in 22 patients (13 percent) and worsened in 8 patients (5 percent). The frequency of the development or worsening of ophthalmopathy was similar among the patients in group 1 (medical therapy, 4 of 27 patients [15 percent]; and surgery, 3 of 27 patients [11 percent]). In group 2, ophthalmopathy developed or worsened in 4 of the 38 patients (10 percent) treated medically, 6 of the 37 patients (16 percent) treated surgically, and 13 of the 39 patients (33 percent) given iodine-131 (P = 0.02 for the comparison between the iodine-131 subgroup and the others combined). The risk of the development or worsening of ophthalmopathy increased as pretreatment serum triiodothyronine concentrations increased. CONCLUSIONS: As compared with other forms of antithyroid therapy, iodine-131 is more likely to be followed by the development or exacerbation of Graves' ophthalmopathy.

Adult↗

Expression of the thyroid hormone receptor, the oncogenes c-myc and H-ras, and the 90 kD heat shock protein in normal, hyperplastic, and neoplastic human thyroid tissue.

Expression of the thyroid hormone receptor (TR beta), the 90 KD heat shock protein (HSP 90), and the oncogenes H-ras and c-myc mRNA in normal hyperplastic, and neoplastic human thyroid tissue was investigated by Northern blot and slot blot analyses. The TR beta mRNA was present in all normal and neoplastic thyroid tissue samples. The levels were significantly higher in normal and hyperplastic tissues (7.91 +/- 0.48 and 7.60 +/- 0.68 arbitrary units, respectively) than in neoplastic tissues (3.82 +/- 0.67) (p < 0.001). H-ras and c-myc mRNA were also detected in glandular tissue specimens, but no significant difference was observed in their expression levels. Furthermore, there was a tendency to a negative correlation between the level of TR beta and c-myc mRNA (p = 0.06). In normal thyroid tissue, HSP 90 mRNA levels were significantly higher than in hyperplastic and papillary carcinoma tissue specimens (p < 0.001). These results indicate that mRNA of TR beta and HSP 90 (the latter only in papillary thyroid carcinoma) are expressed in relation to the degree of cellular differentiation. Furthermore, the presence of TR beta in normal thyroid tissue implies that T3 and T4 may be involved in the regulation of their own production via TR beta activated feedback mechanism(s).

Adult↗

Nuclear protein content and Ki-67 immunoreactivity in nonneoplastic and neoplastic thyroid cells.

The nuclear DNA content in thyroid tumor cells has been shown to be closely related to the malignant potential of the neoplasm. Besides DNA, nuclear protein (NP) constitutes the major mass of the nucleus. The NP content may vary significantly in relation to the proliferative stage in growing as compared to growth-arrested cells. The increase in NP content associated with the transition from G0 to G1 occurs before the onset of DNA synthesis and may be used to assess growth activity. The nuclear DNA and NP contents were analyzed in 90 nonneoplastic lesions and 75 benign and 62 malignant thyroid tumors. All nonneoplastic specimens were euploid, and 1 of 90 was growth activated. In the group of benign tumors, 59 were euploid, and 16 were aneuploid. Among these there were 5 (9%) of 59 and 6 (38%) of 16 growth-activated specimens, respectively. In the group of malignant tumors 57 of 62 were classified as euploid, and in this group 12 (21%) showed growth activity according to the NP content. Five of 62 were aneuploid, and 3 (60%) of these 5 tumors were growth activated. Evaluation of the growth activity by means of monoclonal antibody Ki-67 was performed on a subgroup of 32 thyroid specimens, both nonneoplastic and neoplastic lesions. Ki-67 immunoreactivity was observed in 0-1.1% cells of 6 nonneoplastic lesions, in 0-3.1% cells of 14 benign cells and in 0.2-3.9% cells of 12 malignant thyroid tumors. Growth activity, as reflected by the NP/DNA ratio and Ki-67 immunoreactivity, appears to be low both in nonneoplastic thyroid lesions and thyroid tumors.

Adenoma↗

Addition of nuclear DNA content to the AMES risk-group classification for papillary thyroid cancer.

BACKGROUND: The purpose of this study was to prospectively assess whether nuclear DNA content added prognostic value to existing risk factors in patients with papillary thyroid cancer. METHODS: Nuclear DNA content was measured both on the fine needle aspiration material and the surgical specimen in 73 patients with primary or recurrent papillary thyroid cancer. We modified the existing age of patient, presence of distant metastases, extent and size of the tumor (AMES) risk-group classification to include DNA ploidy with AMES (DAMES). Patients with euploid tumors that were AMES low risk were considered to be DAMES low risk; patients with euploid tumors that were AMES high risk became intermediate risk, and patients with aneuploid tumors that were AMES high risk became DAMES high risk. RESULTS: Forty-eight patients were in the DAMES low-risk group. Recurrences and/or distant metastases developed in only four (8%) of these patients. Twenty-two patients were in the DAMES intermediate-risk group. Twelve (55%) of the intermediate-risk group had residual, recurrent, or distant metastatic disease, with one death from cancer at 120 months. Three patients were in the DAMES high-risk group. Distant metastases developed in all three patients, who died within 24 months from thyroid cancer. A statistically significant difference existed in the development of recurrence/metastases or death from cancer in the DAMES high-risk group compared with the other risk groups combined. CONCLUSIONS: Nuclear DNA content adds prognostic value to the existing AMES risk-group classification. Because DNA analysis on fine needle aspiration correlated well with the surgical specimen DNA analysis, this modified classification can be used perioperatively to further individualize the treatment of patients with papillary thyroid cancer.

Adult↗

Yield and grain quality of spring wheat (Triticum aestivum L., cv. Drabant) exposed to different concentrations of ozone in open-top chambers.

Spring wheat (Triticum aestivum L., cv. Drabant) was exposed to different concentrations of ozone in open-top chambers for two growing seasons, 1987 and 1988, at a site located in south-west Sweden. The chambers were placed in a field of commercially grown spring wheat. The treatments were charcoal-filtered air (CF), non-filtered air (NF) and non-filtered air plus extra ozone (NF(+)). In 1988, one additional ozone concentration (NF(++)) was used. Grain yield was affected by the ozone concentration of the air. Air filtration resulted in an increase in grain yield of about 7% in both years, compared to NF. The addition of ozone (NF(+), NF(++)) reduced grain yield and increased the content of crude protein of the grain in both years. Filtration of the air had no significant effect on the content of crude protein, compared to NF. The results showed a strong positive chamber effect on grain yield in the cold and wet summer of 1987. In 1988, there was no net chamber effect on grain yield. The relative differences between the CF, NF and NF(+) treatments with respect to grain yield were of the same magnitude in the two years, despite the very different weather conditions.

Journal Article↗

Reflexogenic neuronal and humoral responses to selective stimulation of low-pressure cardiopulmonary receptors in man.

This study was conducted to determine the relative importance of efferent muscle sympathetic nerve activity (MSA), vasopressin (ADH) and atrial natriuretic peptide (ANP) in the short-term neurohumoral response to moderate changes in low-pressure cardiopulmonary receptor activity. The low-pressure receptors were stimulated and unloaded, respectively, by autotransfusion of blood (450 ml) and the application of lower body negative pressure (LBNP, -20 mmHg), and in 11 healthy men we measured MSA in the left peroneal nerve, indirect blood pressure, ECG, central venous pressure (CVP) and venous plasma concentrations of ANP and ADH (radioimmunoassay). Total MSA rose by 30% during LBNP and decreased during a rapid autotransfusion of blood, and the changes in MSA were significantly related to changes in CVP. The plasma concentrations of ADH and ANP were not significantly affected by either procedure. It is suggested that during moderate short-term changes in venous return, MSA responded more rapidly and/or at a lower threshold than the ADH and ANP systems.

Adult↗

Effects of desipramine on sympathetic nerve firing and norepinephrine spillover to plasma in humans.

In isolated organs, or when given in low dose intra-arterially, tricyclic antidepressant drugs are known to block reuptake of norepinephrine into sympathetic nerve varicosities, with a resultant increased norepinephrine washout. On the other hand, systemic administration of such drugs in humans reduces norepinephrine spillover to plasma. To clarify these seemingly contradictory findings, we have measured concurrently muscle sympathetic activity in the peroneal nerve (microneurography) and rates of norepinephrine spillover to plasma for the body as a whole and for the heart, the kidneys, and the forearm (radiotracer technique), both before and after intravenous infusion of desipramine, 0.5 mg/kg. Desipramine lowered the overflow of norepinephrine to plasma for the body as a whole and from the forearm and the kidneys (by 30-50%) but increased cardiac norepinephrine spillover by 25%. Both the number of sympathetic bursts per min in the peroneal nerve and their mean voltage amplitudes were markedly reduced after desipramine; total activity (bursts/min x mean burst amplitude) fell by approximately 90%. The effects of desipramine on norepinephrine spillover are explicable in terms of inhibition of central sympathetic outflow, balanced against the local blockade of transmitter reuptake. In most sites, the predominant effect is a reduction of norepinephrine overflow. For the heart, where reuptake is so important in transmitter disposition, the net effect is increased overflow.

Adult↗

Analysis of the DNA content in the management of thyroid tumours.

Thyroid carcinoma is rare and constitutes about 1% of all malignant tumours. For some time it has been known that age, sex, histology, and tumour grade are factors of importance for prognosis. In Stockholm we have analyzed the amount of nuclear DNA in thyroid tumours for the last 10 years. In our studies and those of other nuclear DNA-analysis has given important prognostic information for differentiated thyroid tumours in addition to that provided by histopathology, and may be of value preoperatively for treatment planning. DNA-analysis is well established in our clinical work and is one of the factors considered in a prospective randomized study concerning patients with papillary carcinoma in the Stockholm-Uppsala area. Tumours with diploid nuclear DNA pattern are randomized between lobectomy and total thyroidectomy in this study.

Aneuploidy↗

Anaplastic thyroid carcinoma. Doxorubicin, hyperfractionated radiotherapy and surgery.

Sixteen consecutive patients with anaplastic carcinoma of the thyroid were prospectively treated according to a combined regimen consisting of hyperfractionated radiotherapy, doxorubicin and debulking surgery. The radiotherapy was preoperatively administered to a target dose of 30 Gy in 3 weeks, and postoperatively to an additional dose of 16 Gy in 1.5 weeks. Radiotherapy was administered twice daily, 5 days a week, with a target dose of 1 Gy per fraction and with a minimum interval of 6 hours. A dose of 20 mg doxorubicin was administered intravenously 1 to 2 hours before the first radiotherapy session every week. Debulking surgery was feasible in 9 patients. Local complete remission was achieved in 5 patients and 3 of these are still alive disease-free at 10, 30, and 30 months respectively after diagnosis. Only 6 patients succumbed to a local failure. This combination regimen was well tolerated despite the patients' high age and advanced disease.

Aged↗

Chemotherapy and multimodality treatment in thyroid carcinoma.

With the combination of pre- and postoperative chemotherapy and radiotherapy, the majority of patients with anaplastic giant cell thyroid carcinoma will achieve local tumor control. A few patients may even be cured by this treatment. Only few patients with differentiated thyroid carcinoma respond to chemotherapy treatment. However, at present it is not possible to discern these few. Chemotherapy for advanced thyroid carcinoma cannot as yet be routinely recommended. Doxorubicin, cisplatin, and VP16 are the drugs currently considered most effective. Side effects may be severe. Multimodality treatment may be an alternative.

Antineoplastic Combined Chemotherapy Protocols↗

Co-release of neuropeptide Y and noradrenaline from pig spleen in vivo: importance of subcellular storage, nerve impulse frequency and pattern, feedback regulation and resupply by axonal transport.

The importance of subcellular storage, nerve impulse rate and pattern, and feedback regulation, as well as resupply by axonal transport for the release of noradrenaline and neuropeptide Y-like immunoreactivity, was studied in the blood perfused pig spleen in vivo. Vasoconstrictor responses were recorded as perfusion pressure changes. Subcellular fractionation experiments using sucrose density gradients showed a bimodal distribution of noradrenaline (peak concentrations at 0.8 and 1.1 M sucrose) while only one main peak of neuropeptide Y was present (at 1.1 M sucrose). Overflow suggesting release of noradrenaline and neuropeptide Y-like immunoreactivity could be detected after 10 s stimulation at 10 Hz. The ratio for the output of noradrenaline and neuropeptide Y upon continuous nerve stimulation in control animals decreased with frequency. After inhibition of noradrenaline reuptake by desipramine the vasoconstrictor response and noradrenaline output were enhanced while the corresponding overflow of neuropeptide Y was reduced by 50% at 0.5 Hz. Stimulation with the irregular or regular bursting patterns at high frequencies caused larger perfusion pressure increase and relative enhancement of neuropeptide Y output compared to noradrenaline than a continuous stimulation both before and after desipramine treatment. A similar fractional release per nerve impulse was calculated both for [3H]noradrenaline (5.6 +/- 1.0 x 10(-5) and neuropeptide Y (7.3 +/- 0.3 x 10(-5). After reserpine treatment combined with preganglionic denervation the vasoconstrictor responses were more long-lasting, neuropeptide Y release was enhanced while noradrenaline content and release were reduced by 99%. The difference in neuropeptide Y overflow between continuous and bursting types of stimulation was smaller after reserpine treatment. After prolonged intermittent stimulation with regular bursts (20 Hz) for 1 h the splenic content of neuropeptide Y was reduced by 58%, while no change was observed for noradrenaline. The maximal perfusion pressure increase upon prolonged nerve stimulation after reserpine was similar in control and reserpine-treated animals, but after reserpine the vasoconstrictor response and neuropeptide Y release were subjected to fatigue. Ligation experiments of the splenic nerves revealed the splenic neuropeptide Y content was resupplied by axonal transport with a calculated total tissue turnover time of 11 days. In contrast, axonal transport contributed only to a marginal extent for the resupply of noradrenaline.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Nuclear DNA content in anaplastic giant-cell thyroid carcinoma.

The nuclear DNA content was measured in 36 cases of anaplastic giant-cell thyroid carcinoma registered at Radiumhemmet, Karolinska Hospital, Sweden, between November 1973 and December 1985. The DNA content was measured in morphologically identified single tumor cells by image cytometry. Either fine needle aspirate material or histologic sections from primary tumors, recurrences, or metastases were studied. All tumors were aneuploid. Aneuploidy decreased in four of seven tumors studied sequentially. Analysis of the nuclear DNA content did not provide additional prognostic information and did not explain why occasional patients enjoy longer survival than expected.

Adult↗

Co-existent anaplastic and well differentiated thyroid carcinomas: a nuclear DNA study.

Clonal transformation of well differentiated follicular or papillary carcinomas has been suggested as a mechanism by which anaplastic carcinomas of the thyroid might arise. Of 126 cases of anaplastic (giant cell) carcinomas, 17 (13.5%) contained histologically well differentiated tumour foci within or adjacent to the high grade malignant anaplastic tumour. Cytophotometric DNA analysis after Feulgen staining was performed on 11 cases in order to evaluate ploidy of the anaplastic and the well differentiated tumour cells. The majority of these co-existent carcinomas (9/11) were papillary. All 11 anaplastic carcinomas demonstrated an aneuploid DNA pattern which correlated with a poor clinical outcome (7 of 11 died of disease in less than 6 months). In contrast six co-existent papillary and one co-existent follicular tumours were diploid. These data show that the co-existence of anaplastic and well differentiated carcinoma occurs only rarely and when it occurs only one third of the well differentiated tumours contain aneuploid tumour cells. This suggests that in the majority of cases of anaplastic thyroid carcinoma the malignant cells arise de novo rather than through clonal transformation of well differentiated carcinomas.

Adenocarcinoma↗

Adrenaline infusion in man increases muscle sympathetic nerve activity and noradrenaline overflow to plasma.

This study was conducted to determine if muscle sympathetic nerve activity (MSA) and/or the neuronal release of noradrenaline per impulse are modulated by adrenaline in the physiological plasma concentration range. We gave step-wise infusions of adrenaline (0.05-0.6 nmol/kg per min) to 10 healthy young men and measured: intra-arterial blood pressure; heart rate; central venous pressure (CVP); efferent MSA (microneurography in the peroneal nerve); arterial (brachial artery) and femoral venous plasma concentrations of noradrenaline, and the spillover of noradrenaline to arterial and venous plasma (radiotracer infusion). The infusion of adrenaline caused a fall in diastolic blood pressure and tachycardia, and was associated with increases in MSA and noradrenaline spillover. These observations suggest that part of the adrenaline-induced increase in transmitter release is due to enhanced nerve impulse activity, but such a conclusion rests on the absence of diffusion limitations from the site of noradrenaline infusion into the blood stream. After termination of adrenaline infusion the tachycardia and elevated plasma noradrenaline levels persisted, but these changes were probably due mainly to a profound increase in nerve activity. Concurrently, there was a reduction in CVP which may have triggered the increase in efferent sympathetic nerve activity. Infusions of adrenaline did not influence the clearance of noradrenaline from arterial plasma, but the fractional extraction over the leg was moderately reduced, indicating that more arterial noradrenaline is recovered in venous plasma during adrenaline infusion. The present data suggest that the reasons for the adrenaline-induced increase in noradrenaline release are complex, but they are consistent with the hypothesis that stress levels of adrenaline enhance sympathetic nerve activity, and that circulating adrenaline may modulate both haemodynamic and neural responses to stress.

Adult↗

Nuclear DNA measurements in follicular thyroid adenomas.

The nuclear DNA content was measured retrospectively in histologically confirmed follicular adenomas in 20 patients, and prospectively in 25 patients. In the retrospective group two of the adenomas, and in the prospective group three of the adenomas were classified as atypical due to high cellularity and nuclear atypia, but with no sign of micro-invasive growth. In the group of patients studied retrospectively, the two patients with atypical adenoma had an aneuploid DNA pattern. One of these died 11 years after diagnosis with generalized disease. The other patient in this group with an aneuploid atypical adenoma is alive, as are all the remaining 18 patients with diploid adenomas. In the prospective group there were five aneuploid tumours. The atypical adenomas were aneuploid in two cases and polyploid in one case. No patient in the prospective group has shown any evidence of recurrence so far. Although DNA measurements are of value in distinguishing between low and high malignant potential in invasive tumors, the prognostic information if no invasion is found is uncertain. The importance of examining an adequate number of tissue blocks from the capsular region is emphasized.

Adenoma↗

Molecular forms of katacalcin, calcitonin gene-related peptide and gastrin-releasing peptide, in a human medullary thyroid carcinoma.

Peptides synthesized by a human medullary thyroid carcinoma were purified to homogeneity by reverse-phase high performance liquid chromatography and structurally characterized by determination of amino acid composition, amino acid sequence, and fast atom bombardment mass spectra. The katacalcin-related material in the tumor extract was heterogeneous. Katacalcin (1-21) represented the predominant molecular form but metabolites, identified as katacalcin (1-20), (1-19), (1-15) and (1-13), were also identified in high concentration. Calcitonin gene-related peptide-I was isolated from the tumor but calcitonin gene-related peptide-II was absent. A minor component of calcitonin gene-related peptide-like immunoreactivity was of higher molecular weight and may represent an incompletely processed form of the prohormone. Gastrin-releasing peptide (1-27) and gastrin-releasing peptide (18-27) (neuromedin C) were isolated from the tumor but gastrin-releasing peptide (14-27) and bombesin were absent.

Adult↗