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Biomedical subjects

G Wallin

Publications and source records attributed to G Wallin.

At least 37 records · Page 2Linked to original sources

Expanding role of fine-needle aspiration cytology in thyroid diagnosis and management.

In non-iodine-deficient areas, 4% to 7% of the population are reported to have thyroid abnormalities. Prophylactic operations of these nodules in the thyroid are not indicated and not cost-effective, as at least four of five nodules are colloid goiter and only a few are malignant. The need for a reliable preoperative diagnosis is great, and fine-needle aspiration (FNA) is now considered the first choice during workup for thyroid nodules. The steps in the FNA procedure are clinical examination and localization of the target lesion, aspiration, preparation of smears, and collecting material for ancillary microscopy techniques. All these steps must be exercised to allow optimal use of FNA. It can also be combined with various other methods, such as immunohistochemistry of thyroglobulin and calcitonin, analysis of nuclear DNA, DNA preparation for molecular biology analyses, and magnetic resonance spectra. The accuracy of the clinical routine in our unit was evaluated by studying the 5-year outcomes of almost 4000 FNAs of the thyroid. The results were good, with only a few false-negative and false-positive results; but the problem of differentiating follicular adenoma from follicular carcinoma remains a significant problem. It is now well established that FNA biopsy and cytology is the best modality available for the workup of thyroid nodules and is widely utilized in endocrine surgical centers worldwide.

Biopsy, Needle↗

Subcutaneous versus intracutaneous injections of sterile water for labour analgesia: a comparison of perceived pain during administration.

OBJECTIVE: To investigate whether, during injections of sterile water, there is any difference in perceived pain between intracutaneous and subcutaneous injections. DESIGN: Blind controlled trial with cross-over design. SETTING: Göteborg and Skövde, Sweden. PARTICIPANTS: One hundred healthy female volunteers. METHODS: The women were randomised into two groups and subjected to two trials, within one week of each other. During the first trial one group (n = 50) received the intracutaneous injection first, followed by the subcutaneous injection. The second group (n = 50) was given the subcutaneous injection first, followed by intracutaneous injection. In both groups all the injections were given in reverse order during the second trial. MAIN OUTCOME MEASURES: Experienced pain during the administration of sterile water injections, measured by visual analogue scale. RESULTS: The analysis showed intracutaneous injections to be significantly more painful than subcutaneous injections, even after adjusting for injection day and for left/right site of injection (mean 60.8 vs 41.3, P < 0.001). CONCLUSIONS: The findings suggest that the less painful subcutaneous injection technique should be used.

Adolescent↗

Expression of RET and its ligand complexes, GDNF/GFRalpha-1 and NTN/GFRalpha-2, in medullary thyroid carcinomas.

OBJECTIVE: Mutations in the RET proto-oncogene are found in about one third of sporadic medullary thyroid carcinomas (MTCs), mostly affecting codon 918. Glial cell line derived neurotropic factor (GDNF) and its membrane-bound GDNF family receptor alpha (GFRalpha-1), as well as neurturin (NTN) and its membrane-bound receptor GFRalpha-2 form a complex with the RET product, a receptor tyrosine kinase, resulting in downstream signaling to the nucleus. DESIGN: To elucidate the role of these RET ligands in MTC tumorigenesis, their expression was determined in 15 MTC samples, one papillary thyroid carcinoma (PTC) and three normal thyroid tissue specimens. METHODS: The mRNA expression of RET, GDNF, GFRalpha-1, NTN and GFRalpha-2 was investigated by mRNA in situ hybridization, and confirmed by reverse transcription-PCR analysis. RESULTS: None of the five genes was expressed in the normal thyroids or in the PTC. All MTCs showed expression of RET, 13 expressed GDNF, 12 expressed GFRalpha-1 and 9 expressed NTN and GFRalpha-2. In 7 of the tumors RET, GDNF and GFRalpha-1 were expressed at high levels, and in five of these seven tumors NTN and GFRalpha-2 genes were also expressed at high levels. The high level of expression was preferentially seen in tumor cells adjacent to stroma and connective tissue. All MTCs without expression of the RET ligands harbored the RET codon 918 mutation. CONCLUSIONS: The results suggest that this signaling pathway is important for MTC development, and that it may be activated by expression of the RET ligand complexes by the tumor cells themselves.

Adult↗

[Amnioinfusion or not during labor? Better documentation and more trials can answer the question].

Intrapartal amnio-infusion has been described as a means of reducing the risk of fetal distress, as well as the Caesarean section rate among cases of oligohydramnios accompanied by CTG (cardiotocography) signs of cord compression. Among cases complicated by the presence of thick, meconium-stained amniotic fluid, dilution by amino-infusion has been shown to reduce the prevalence of meconium below the vocal cords, and of meconium aspiration syndrome in the newborn. A questionnaire concerning experience of the method, answered by 98% (61/62) of delivery wards in the country, showed Swedish obstetricians to be generally in favour of the procedure which they considered beneficial. However, as many of the wards had had very few cases, obstetricians answering the questionnaire felt that there was a need of guidelines and better prospective clinical studies.

Amnion↗

Sporadic follicular thyroid tumors show loss of a 200-kb region in 11q13 without evidence for mutations in the MEN1 gene.

Loss of heterozygosity (LOH) in 11q13 where the tumor suppressor gene for multiple endocrine neoplasia type 1 (MEN 1) is located has been demonstrated in several tumor types, including follicular thyroid tumors, but whether the MEN1 gene is actually involved in their tumorigenesis is not known. In the present study, the involvement of the MEN1 gene in follicular thyroid tumors was investigated. By using 14 MEN1-linked microsatellite markers, LOH was demonstrated in 12 out of 60 follicular thyroid tumors: 2/18 adenomas, 4/15 atypical adenomas, 1/6 Hürthle cell adenomas, 1/9 carcinomas, 3/6 Hürthle cell carcinomas, and 1/6 anaplastic carcinomas. In the tumors with LOH, a single minimal region of overlapping deletions was mapped to the 200-kb interval between D11S4946 and D11S4939. Tumors that showed 11q13 LOH were screened for mutations of the MEN1 gene using single-strand conformation analysis. Abnormal shifts detected in seven tumors in two exons were sequenced, which revealed two different polymorphisms present in both tumor and constitutional DNA, but without somatic mutation. Taken together, these results suggest that in this region, a tumor suppressor gene other than MEN1 might be involved in the tumorigenesis of follicular thyroid tumors. Genes Chromosomes Cancer 26:35-39, 1999.

Adenocarcinoma, Follicular↗

Value of diagnostic laparoscopy in fertile women with suspected appendicitis.

OBJECTIVE: To assess the value of diagnostic laparoscopy in women of child-bearing age with suspected appendicitis. DESIGN: Prospective, non-randomised study. SETTING: University hospital, Sweden. SUBJECTS: 94 women aged between 15 and 40 years with suspected appendicitis. INTERVENTION: Diagnostic laparoscopy. If necessary, the appendix was removed either laparoscopically or by open operation. The outcomes were compared with those during 1994, during which all appendicectomies were done through a laparotomy. MAIN OUTCOME MEASURES: Rates of unnecessary appendicectomy, operating time, and length of hospital stay. RESULTS: 77 had diagnostic laparoscopy, and 17 primary open appendicectomy. 73 appendixes were removed; 53 open and 20 laparoscopically. 12 appendicectomies (13%) were unnecessary compared with 27/80 (34%) during the year 1994. The duration of the open operation was significantly shorter (mean (SD) 35 (14) minutes) than the laparoscopic one (78 (18) minutes) (p<0.001), and there were no differences in duration of postoperative hospital stay. No patients developed complications. CONCLUSIONS: Diagnostic laparoscopy is safe and helpful in suspected cases of appendicitis and could substantially reduce the rate of unnecessary appendicectomies. However, the data suggest that laparoscopic appendicectomy offers no advantages over primary open appendicectomy in terms of postoperative course.

Adolescent↗

Modified Joel-Cohen technique for caesarean delivery.

OBJECTIVE: To investigate whether a series of changes in the current caesarean section operative routine, based on new knowledge, would be beneficial. DESIGN: A prospective controlled trial. SETTING: Labour ward with approximately 3000 deliveries annually in a suburban area of Gothenburg, Sweden. PARTICIPANTS: Seventy-two pregnant women scheduled for delivery by caesarean section were randomised to either modified Joel-Cohen technique (n = 36) or Pfannenstiel technique (n = 36). MAIN OUTCOME MEASURES: Blood loss during surgery and operating time. RESULTS: The median estimated intra-operative blood loss was 250 mL in the modified Joel-Cohen group and 400 mL in the Pfannenstiel group (P = 0.026). The proportion of women with > or = 300 mL was 16/36 in the modified Joel-Cohen group vs 28/36 in the Pfannenstiel group (OR 0.229, 95% CI 0.082-0.637). Median operating time was 20 min in the modified Joel-Cohen group compared with 28 min in the Pfannenstiel group (P < 0.001). The proportion of women with > or = 25 min was 1/36 in the modified Joel-Cohen group vs 33/36 in the Pfannenstiel group (OR 0.003, 95% CI 0.000-0.026). CONCLUSIONS: We conclude that the modified Joel-Cohen technique of caesarean delivery reduced intraoperative blood loss and operating time compared with the Pfannenstiel technique.

Adult↗

Labour pain treated with cutaneous injections of sterile water: a randomised controlled trial.

OBJECTIVE: To evaluate the relief of pain in labour with subcutaneous and intracutaneous injections of sterile water, compared with placebo. DESIGN: Randomised controlled trial. SETTING: Labour ward with approximately 3000 deliveries annually in a suburban area near Gothenburg, Sweden. PARTICIPANTS: Ninety-nine pregnant women at term, requiring pain relief for severe lower back pain during the first stage of labour. The women were randomised to receive four injections of 0.1 mL sterile water (without salt) intracutaneously (n = 33), four injections of 0.5 mL sterile water subcutaneously (n = 33) or placebo treatment (n = 33). MAIN OUTCOME MEASURES: Reduction of labour pain measured by visual analogue scale. RESULTS: The median visual analogue scale pain score for labour pain was significantly lower compared with initial values in the two study groups and compared with placebo at 10 and 45 minutes after treatment. The median reductions in visual analogue scores after 10 minutes were 5.0 cm and 4.5 cm in the intracutaneous and subcutaneous injection groups, respectively; women in the placebo group scored a median reduction of 1.7 cm. After 45 minutes the median reductions in the visual analogue scores were 4.9 cm and 4.0 cm in the intracutaneous and subcutaneous injection groups, respectively, compared with 1.0 cm for women in the placebo group. No significant differences in analgesic effect or pain experienced during administration were found between the two study groups. CONCLUSION: The new subcutaneous method of administering sterile water, as well as the earlier described intracutaneous injection method, were effective for the relief of pain in labour.

Adult↗

Low frequency of numerical chromosomal aberrations in follicular thyroid tumors detected by comparative genomic hybridization.

Follicular thyroid tumors vary from adenomas to widely invasive carcinomas, and a stepwise progression from normal thyrocyte to malignant tumor has been suggested to be due to an accumulation of genetic alterations. We have used comparative genomic hybridization to screen 21 follicular thyroid tumors (8 adenomas and 13 carcinomas) for gains and losses of DNA sequence copy numbers. In general, the tumors showed few alterations involving several different chromosomal regions. The frequency of alterations was similar in the benign (mean, 1.9) and malignant (mean, 1.5) tumors, as well as in minimally (mean, 1.5) and widely invasive carcinomas (mean, 1.6). However, specific loss of 9q13-q21.3 was detected in three tumors, which were all carcinomas showing oxyphilic changes (Hürthle cell carcinomas; P = 0.003). The fact that DNA copy number alterations were found with a similarly low frequency in both benign and malignant follicular thyroid tumors does not support the hypothesis of a multistep tumor progression in these tumors. Genes Chromosomes Cancer 25:349-353, 1999.

Adenoma↗

Anaplastic giant cell carcinoma of the thyroid gland: treatment and survival over a 25-year period.

Anaplastic giant cell carcinoma of the thyroid is a rare but highly malignant tumor. At the Karolinska Hospital in Stockholm, surgery, chemotherapy, and radiotherapy have been used separately or in various combinations in 81 patients admitted with this diagnosis during 1971-1997. In this study, we present the various multimodality treatment regimens and their changes over the years and the subsequent differences in survival and local tumor control. Overall, eight patients (10%) survived more than 2 years. All survivors were treated with combinations of chemotherapy, radiotherapy, and surgery. Among the patients who died, local tumor control was achieved by the therapy given in many cases. The results suggest that our current strategy with a combination of preoperative hyperfractionated accelerated radiotherapy, doxorubicin pre- and postoperatively, and debulking surgery whenever possible results in better local tumor control and an increased chance of survival.

Adult↗

A rapid method for DNA extraction from fine-needle aspiration biopsies of thyroid tumors, and subsequent RET mutation analysis.

The presence of germline and somatic mutations in the RET proto-oncogene (RET) in patients with hereditary and sporadic medullary thyroid carcinoma (MTC) may have important ramifications for patient management. It has been suggested that the presence of the mutation ATG-->ACG at codon 918 in sporadic MTC is associated with a worse prognosis, and hence the need for more aggressive surgical, or other, treatment. Since fine-needle aspiration biopsy (FNAB) is an important component of the preoperative management of patients with thyroid tumors, we developed a rapid (20-min) method that enables extraction of DNA from FNABs for RET mutation analysis. The method allows preoperative genetic analysis to aid in management of patients with MTC, and may be applied to other tumor types where a preoperative mutation analysis based on polymerase chain reaction amplification is desired.

Biopsy, Needle↗

Quality of life aspects and costs in treatment of Graves' hyperthyroidism with antithyroid drugs, surgery, or radioiodine: results from a prospective, randomized study.

The patients' views and costs of three different forms of treatment for Graves' hyperthyroidism were investigated. The study comprises 174 patients with Graves' hyperthyroidism who were stratified into two age groups: 20 to 34 years and 35 to 55 years. The younger group was randomly assigned to treatment with antithyroid drug plus thyroxine for 18 months or subtotal thyroidectomy, and in the older group iodine-131 was added as a third alternative. The patients' views of their therapy were based on a questionnaire formulated to identify possible differences between the three treatment forms. The costs were assessed by analyzing the official hospital reimbursement system for both outpatient and inpatient costs for a period of 2 years from the day of randomization. The results show that no significant differences in opinion were found between the five treatment groups with regard to any of the questions. Furthermore, only 10% of the patients expressed slight and 3% major hesitation to recommend the treatment form received to a friend with similar disease. Twenty percent of the patients with endocrine ophthalmopathy reported the eye problems to be much more troublesome and 14% somewhat more troublesome than the thyroid problems. The cost proportion between the medical and surgical treatment in the young group was 1:2.5 (1 = 1126 United States dollars [USD]) before and 1:1.3 (1 = 2284 USD) after inclusion of the relapse costs. The proportion between the medical, surgical, and iodine-131 treatment in the older group was 1:2.5:1.6 (1 = 1164 USD) before and 1:1.6:1.4 (1 = 1972 USD) after inclusion of the relapse costs.

Adult↗

The stress hormone adrenocorticotropin enhances sympathetic outflow to the muscle vascular bed in humans.

OBJECTIVE: To examine the role of adrenocorticotropin in the regulation of the sympathetic outflow to the muscle vascular bed in healthy female humans. DESIGN: Eight healthy, nonsmoking female subjects (aged 18-33 years) were examined before and after injection of 0.25 mg adrenocorticotropin 1-24 or placebo according to a balanced, double-blind cross-over protocol. METHODS: Muscle sympathetic nerve activity, arterial pressure, and heart rate were continuously recorded both under basal conditions and during a 50 min period after injection of each substance. Furthermore, sympathoexcitatory capacities of inspiratory apneas and cold pressure tests performed before and after injection of adrenocorticotropin were determined. RESULTS: The injection of adrenocorticotropin rapidly increased burst frequency of muscle sympathetic nerve activity (P < 0.01). The maximal effect of adrenocorticotropin, with an increase in burst frequency of 63%, occurred during the third minute after injection and waned subsequently, but muscle sympathetic nerve activity remained significantly increased during the first 10 min after injection. The stimulatory effect of adrenocorticotropin had disappeared 40 min after injection. The sympathoexcitatory capacity of a maximal inspiratory apnea and a cold pressure test, respectively, remained unchanged 10 and 45 min after the administration of adrenocorticotropin compared with control. Neither blood pressure nor heart rate was significantly affected by administration of the peptide. CONCLUSIONS: The data establish that the stress hormone adrenocorticotropin acutely increases sympathetic outflow to the muscle vascular bed in female humans. This effect is most likely mediated via central nervous system autonomic centers. The influence of adrenocorticotropin on the sympathetic nervous system might contribute to the alteration of response to stress in the course of the development of hypertension and could also add to the hypertensiogenic effects of corticosteroids and mineralocorticoids in states with excess adrenocorticotropin.

Adolescent↗

Integrins in thyroid tissue: upregulation of alpha2beta1 in anaplastic thyroid carcinoma.

OBJECTIVE: To evaluate the integrin pattern in the normal thyroid gland and in different pathological disorders including malignant tumors, because the aggressiveness of several malignant tumors correlates with alterations in the expression of one or more integrins. DESIGN: We examined the expression of integrins and E-cadherin immunohistochemically in a large and well-defined sample of normal and pathological human thyroid tissue. METHODS: Cryosections of 58 thyroid tissue specimens from normal tissue, thyrotoxicosis, nodular goiter, oxyphilic adenoma, follicular adenoma, follicular carcinoma, papillary carcinoma and anaplastic carcinoma, and three lymph node metastases were investigated immunohistochemically using monoclonal antibodies specifically recognizing the integrin beta1-, beta4-, alpha1-, alpha2-, alpha3-, alpha5- and alpha6-subunits, or E-cadherin. RESULTS: All thyroid epithelial cells expressed integrin beta1- and alpha3-subunits. Immunostaining of the beta4-subunit and the alpha6-subunits was found only in tumors. The staining pattern in the three lymph node metastases from papillary carcinomas did not differ from that in their primaries. Anaplastic carcinomas demonstrated neoexpression of the integrin alpha2-subunit. E-cadherin was detected in all tissues except anaplastic carcinomas. CONCLUSIONS: Neoexpression of alpha6beta4 was seen in most malignant tumors, whereas alpha2 was exclusively found in anaplastic carcinomas. In the latter, a loss of E-cadherin expression was also seen. These changes in cell adhesion molecule expression strongly suggest an association with the acquisition of proliferative and invasive properties.

Cadherins↗

[How much is the workload of surgeons in Scandinavia?].

According to figures presented at the Bianniul General Meeting of the Scandinavian Surgical Society, the mean number of operations performed per surgeon at some clinics of different sizes in Denmark, Finland, Iceland, Norway and Sweden ranged from 90 to 240 in 1996. This corresponds to 2.6 to 8.5 hours actual operating time, though figures are misleading since time spent assisting at operations, or on endoscopies, minor diagnostics and outpatient procedures, and essential pre- and post-operative tasks is not included. This level of operative activity is considered barely sufficient for training surgeons or for maintaining surgical skills. Surgeons could devote more time to surgery if a greater proportion of their non-surgical workload was taken over by other hospital staff, which would also reduce the number of surgeons required.

General Surgery↗

Somatic deletions and mutations in the Cowden disease gene, PTEN, in sporadic thyroid tumors.

The majority of familial medullary thyroid neoplasms are associated with germ-line mutations of the RET proto-oncogene, yet very little is known about the mechanisms involved in the pathogenesis of familial and sporadic nonmedullary thyroid tumors. A subset of thyroid tumors have loss of heterozygosity of chromosome 10q22-23, a region harboring the gene responsible for Cowden disease, an autosomal dominant hamartoma syndrome associated with thyroid and breast tumors. PTEN/MMAC1/TEP1 codes for a dual-specificity phosphatase and is likely a tumor suppressor gene. We sought to determine the PTEN status in a series of epithelial thyroid neoplasms. We studied 95 sporadic thyroid tumors, of which 39 were papillary thyroid carcinomas (PTCs), 12 were follicular carcinomas, 9 were anaplastic carcinomas, 5 were Hürthle cell carcinomas, 21 were nonfunctioning follicular adenomas, and 9 were Hürthle cell adenomas. Direct sequencing of PCR-amplified products was performed for all nine exons of PTEN. Two polymorphic markers, one located in intron 8 and another, a dinucleotide repeat marker, AFMa086wg9, located within intron 2, were analyzed in paired blood-tumor DNA samples to assess hemizygous deletions of PTEN. We found a somatic frameshift mutation in one PTC, which was expected to generate a premature stop codon 2 amino acids downstream. Twenty-six % of informative benign tumors (four follicular adenomas and three Hürthle cell adenomas) and only 3 of 49 (6.1%) informative malignant tumors (one PTC, one follicular carcinoma, and one anaplastic carcinoma) showed evidence of hemizygous deletion of PTEN (P = 0.046). We conclude that a subset of thyroid tumors have somatic deletions of the PTEN gene, predominantly the benign forms, and that small intragenic mutations of PTEN are infrequent in thyroid tumors. We speculate that other mechanisms of PTEN inactivation, rather than small intragenic mutations, might occur in the hemizygously deleted samples and act as the "Knudson second hit." Alternatively, other tumor suppressor genes mapping to chromosome 10q22-23 could be the actual targets for such deletions and thus represent the various hits in the pathway of multistep carcinogenesis.

Adenocarcinoma, Follicular↗