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J Rastad

Publications and source records attributed to J Rastad.

At least 55 records · Page 3Linked to original sources
PubMed1997

Intraoperative gamma detection reveals abdominal endocrine tumors more efficiently than somatostatin receptor scintigraphy.

BACKGROUND: [(111)In]-diethylenetriamine pentaacetic acid (DTPA)-D-[Phe1]-octreotide (OctreoScan, Mallinckrodt Medical, Petten, The Netherlands), combined with single photon emission computed tomography (SPECT), has limited possibilities to detect small abdominal endocrine tumors. This study explores the efficacy of OctreoScan and a newly developed handheld gamma detector probe (H-probe2) for the localization of neuroendocrine abdominal tumors. METHODS: Twenty-one patients with endocrine pancreatic or midgut carcinoid tumors were given 100-200 megabecquerels (MBq) [(111)In]-DTPA-D-[Phe1]-octreotide and underwent preoperative SPECT examination, after which time surgery was undertaken within 24-48 hours. Intraoperatively the radioactivity of tumors and normal tissues was measured with the H-probe2 connected to a portable personal computer. Resected intestinal specimens of ten patients with carcinoid tumors were examined by gamma camera ex vivo. Biopsies of all tumors subsequently were investigated in a wellcounter and by routine histopathology. RESULTS: Disregarding liver metastases, a total of 34 of 60 abdominal tumors were detected by SPECT; however, SPECT failed to visualize any tumor < 9 mm. The shielding of the manual probe allowed intraoperative examination despite the substantial radiation energy of (111)In. The H-probe2 detected 91% of the tumors investigated, and these included all those > 5 mm. In the wellcounter the H-probe2-detected tumors exhibited 4.7-157.7 times higher radionuclide uptake than the surrounding normal tissues. The gamma camera analysis detected 68% of tumors in the resected specimens. CONCLUSIONS: The intraoperative H-probe2 examination provided substantial improvement in the detection of small endocrine lesions accumulating [(111)In]-DTPA-D-[Phe1]-octreotide and all lesions with a size > 5 mm in greatest dimension could be identified.

Adult↗
PubMed1997

A gamma detector probe with ex vivo detection of carcinoid tumors superior to intraoperative palpation.

BACKGROUND: Despite the generally successful scintigraphic detection of endocrine tumors with [(111)In]-DTPA-D-[Phe1]-octreotide (OctreoScan, Mallinckrodt Medical, Petten, The Netherlands), its intraoperative application awaits the development of suitable gamma detectors. This study describes a novel probe (H-probe2) and its ex vivo efficacy for the detection of midgut carcinoid tumors. METHODS: The probe measures 180 mm x 24 mm, and contains a bismuth germinate crystal connected to a photomultiplicator tube, a lead shield, and a tantalum collimator with an angled, 3-mm wide opening. It was characterized in a test bench utilizing solublilized (111)In and 99mTc, and 8 fresh operative specimens containing 26 histologically verified midgut carcinoid tumors (2-40 mm) from patients exposed to OctreoScan. Measurements were made at 2.5-mm intervals over the entire specimens and presented three dimensionally. RESULTS: The test bench analysis supported efficient shielding, and a total collimation of 27 degrees for (111)In and 20 degrees for 99mTc. In addition to 18 palpable tumors, 4 of 6 surgically occult tumors (2-3 mm in dimension) could be discovered with H-probe2. Small tumors in close apposition to a large tumor could not be separated. Wellcounter examination showed that tumors detected with the H-probe2 exhibited 1.7-84.1 times higher radionuclide uptake than the surrounding normal tissue. CONCLUSION: Ex vivo analysis of H-probe2 supported detection of tumors inaccessible to surgical palpation, but its clinical efficiency awaits intraoperative evaluation.

Carcinoid Tumor↗
PubMed1997

Aberrantly expressed cytokeratin 1, a tumor-associated autoantigen in papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is a somewhat puzzling disease, combining a propensity to metastasize with an indolent clinical course. The often pronounced T cell-dominated inflammatory infiltrate seen in PTC tumors has prompted us to search for signs of a tumor-induced immune response. In previous studies, we have demonstrated large tumor-specific deposits of IgG and complement in PTC tissue and isolated a putative target antigen. This investigation examines the presence of autoantibodies to cytokeratin 1, a high m.w. cytokeratin normally expressed only in suprabasal keratinocytes, in the serum and tumor tissue of PTC patients. Using immunoprecipitation and Western blot, cytokeratin 1-reactive autoantibodies were demonstrated in 80% of the PTC sera tested, and tumor-derived antibodies were shown to precipitate cytokeratin 1. Using immunohistochemistry, cytokeratins 1 and 10 were found in a large proportion of PTC tumors (39/44) but were absent from normal thyrocytes of most PTC-bearing glands. Our results indicate that this protein is expressed aberrantly in neoplastic cells and is immunogenic in this context.

Autoantibodies↗
PubMed1997

Vitamin D receptor alleles b, a, and T: risk factors for sporadic primary hyperparathyroidism (HPT) but not HPT of uremia or MEN 1.

Polymorphisms in the vitamin D receptor (VDR) gene have been hypothezised to interfere with VDR expression. VDR alleles (Bb, Aa and Tt) were examined in 254 Caucasian patients with sporadic primary hyperparathyroidism (spHPT, n = 206), HPT of multiple endocrine neoplasia type 1 (MEN-1; n = 17), and HPT of uremia (n = 31). In comparison to age- and sex-matched controls, the b, a and T alleles were overrepresented in 100 menopausal females with spHPT (p = 0.006-0.0004), equivalent to an odds ratio of 2.6-3.4 for spHPT in homozygotes for the b, a and, T alleles. The association between VDR genotypes and spHPT was restricted to female patients and those with parathyroid adenoma (p = 0.0006-0.0001), whereas HPT of MEN 1 and uremia seemed unrelated to the VDR polymorphisms (p = 0.26-0.96). The results suggest that the VDR alleles b, a, and T are novel risk factors in the essentially uncharacterized pathogenesis of spHPT.

Alleles↗
PubMed1997

Survival and daily physical activity in patients treated for advanced midgut carcinoid tumors.

BACKGROUND: Prospects for survival and quality of life ought to influence treatment strategies in patients with midgut carcinoids. METHODS: A total of 121 patients with midgut carcinoid received a combined medical and surgical treatment from 1980 to 1993. In all, 158 operations were undertaken for removal of mesentericointestinal lesions and occasional liver metastases or as repeat intervention for abdominal complications. Survival was analyzed together with estimates of daily physical activity during follow-up. RESULTS: Cause of death (63 patients) included carcinoid heart disease (41%) and cachexia (mesentericointestinal entrapment, 35%). Median survival was 11 years in patients with irresectable mesenteric metastases, 7 years with liver metastases, and 1 year with extraabdominal spread. Extensive liver metastases or substantial weight loss (9 kg or greater) reduced survival to a median of 4 to 5.5 years, and surgically treated intestinal ischemia reduced survival to a median of 8 years. Patients with carcinoid syndrome survived a median 7 years, those with 5-hydroxyindoleacetic acid values greater than 500 mumol/24 hr or a valvular heart disease survived a median of 5 years, those with heart failure a median of 2.5 years. Most patients retained an acceptable daily physical activity; impairment occurred in cases of malnutrition, high 5-hydroxyindoleacetic acid values, or heart valve fibrosis, and activity was markedly reduced in the presence of extraabdominal metastases or overt heart disease. CONCLUSIONS: Favorable survival statistics and the maintenance of daily physical activity support active medical and surgical management in patients with advanced midgut carcinoids.

Activities of Daily Living↗
PubMed1997

Estrogen receptor gene polymorphism in postmenopausal primary hyperparathyroidism.

BACKGROUND: Estrogen and its receptor play a key role in calcium homeostasis, with implications in both the development and treatment of primary hyperparathyroidism. METHODS: Leukocyte DNA was isolated from 101 postmenopausal female patients with primary hyperparathyroidism and age-matched female control subjects (n = 101). Polymorphic estrogen receptor alleles denoted P/p and X/x were detected by polymerase chain reaction and restriction digestion with Pvu II and Xba 1 RESULTS: Allelic prevalences were similar in the patients and control subjects. In contrast to normocalcemic control subjects, patients with primary hyperthyroidism homozygous for alleles P and X displayed less elevated serum calcium concentrations (mean, 2.63 and 2.66 mmol/L) versus those with Pp and pp (2.72 mmol/L; p < 0.01) and Xx and xx (2.71; p < 0.05), respectively, as well as trends for higher intact serum parathyroid hormone values (p = 0.09). The PP genotype was accompanied by lower bone mineral density in the lumbar spine (p < 0.05). CONCLUSIONS: Estrogen receptor gene polymorphisms are presumably not directly involved in the parathyroid tumorigenesis. However, they seem to interact with the extent of biochemical derangements of primary hyperthyroidism by possible influences on both the peripheral action of parathyroid hormone and calcium regulation of its secretion.

Aged↗
PubMed1997

Population-based screening for primary hyperparathyroidism with serum calcium and parathyroid hormone values in menopausal women.

BACKGROUND: Population-based screenings for primary hyperparathyroidism have failed to systematically use intact parathyroid hormone (PTH) values for diagnosis, to explore prevalence and diagnostic criteria of normocalcemic hyperparathyroidism, and to attempt surgical verification of the disorder. METHODS: A total of 5202 women (ages, 55 to 75 years) attending a population-based mammography screening were investigated for primary hyperparathyroidism. In women lacking a family history of hypercalcemia, significant renal impairment, or low urinary calcium excretion hyperparathyroidism was diagnosed on the basis of predetermined criteria encompassing lower intact serum PTH levels in hypercalcemia (serum PTH 25 ng/L or greater; reference range, 12 to 55 ng/L) than in two intervals of normocalcemia (serum PTH 35 or greater, greater than 55 ng/L). RESULTS: Prevalence of hyperparathyroidism was 2.1% (n = 109). At diagnosis total serum calcium and serum PTH levels were 2.32 to 3.19 mmol/L and 34 to 300 ng/L, respectively, and 66% of the women exhibited normocalcemia. Repeated examination showed persistent normocalcemia in 30 patients, and all but two of them had normal ionized plasma calcium levels. Significantly higher serum calcium, serum PTH, and urine calcium--but not serum creatinine--levels were found in patients with hyperparathyroidism compared with matched control subjects from the screened population. Within an ongoing stratified treatment program, 59 of 60 patients who underwent operation exhibited pathologic parathyroid tissue (mean weight, 591 mg). CONCLUSIONS: Substantial prevalence of sporadic primary hyperparathyroidism is demonstrated in a risk group. Although criteria for hyperparathyroidism recognition included patients with truly mild biochemical derangement, operative findings suggested underdiagnosis of the disorder.

Aged↗
PubMed1997

Serum levels of parathyroid hormone are related to the mortality and severity of illness in patients in the emergency department.

Hypocalcaemia is a common finding in intensive care patients. In addition, raised levels of parathyroid hormone (PTH) have been described. The explanation and clinical importance of these findings are yet to be revealed. To investigate the occurrence of hypocalcaemia and elevated PTH levels and their relationship to morality and the severity of disease, serum levels of PTH, ionized calcium (Ca2+) and the cytokines interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-alpha) were measured on arrival in the emergency department in a broad spectrum of 140 acutely ill patients patients suffering from common diseases such as stroke, acute abdominal disorders, obstructive lung diseases, heart failure, acute myocardial infarction, angina pectoris, trauma and infectious diseases. A score (APACHE II) was calculated to assess the severity of disease. Elevated PTH levels (> 55 pg ml-1) were seen in 16% of the patients, being most frequent in patients with myocardial infarction (28%) and congestive heart failure (42%). The levels were significantly correlated with the APACHE II score (r = 0.48, P < 0.0001) and with the length of stay in hospital (r = 0.26, P < 0.002). PTH was also significantly (P < 0.03) elevated in non-survivors compared with survivors and was found to be a stronger predictor of mortality (P < 0.01) than the APACHE II score (P < 0.02) in Cox's proportional hazard analysis. No close relationships were found between the cytokine levels and the indices of calcium metabolism. In conclusion, a rise in serum levels of PTH was common and related to the severity of disease and mortality in a mixed emergency department population.

APACHE↗
PubMed1997

Tissue distribution of human gp330/megalin, a putative Ca(2+)-sensing protein.

We used riboprobes and monoclonal antibodies to characterize tissue distribution of the human 550-kD homologue to gp330/megalin, primarily identified in the rat kidney. Human gp330/megalin mRNA and protein are readily identified in human parathyroid cells, placental cytotrophoblasts, kidney proximal tubule cells, and epididymal epithelial cells. The immunoreactivity is found on the surface of the cells and is heterogeneously downregulated in parathyroid hyperplasia and adenomas. Cells of the proximal kidney tubule and epididymis express the protein on their luminal aspect. Moreover, the protein is expressed in Type II pneumocytes, mammary epithelial and thyroid follicular cells, and the ciliary body of the eye. Sequence analysis of cDNA fragments, obtained by RT-PCR, revealed identical nucleotide sequences in parathyroid, kidney, placenta, epididymis, and lung. Immunohistochemistry for parathyroid hormone-related protein (PTHrP) revealed partial co-expression with human gp330/megalin in parathyroid, placenta, and mammary gland. The findings substantiate human gp330/megalin expression in a variety of human tissues expected to possess calcium-sensing functions. It may constitute a protein of utmost importance to adult and fetal calcium homeostasis, although other important functions may also be coupled to this exceptionally large protein with highly restricted tissue distribution.

Amino Acid Sequence↗
PubMed1997

Vitamin D receptor polymorphisms correlate to parathyroid cell function in primary hyperparathyroidism.

Calcitriol acts via its receptor (VDR) and inhibits PTH secretion and parathyroid cell proliferation. Increased prevalence of the polymorphic VDR alleles b, a, and T has been demonstrated in sporadic primary hyperparathyroidism. Sixty-two patients with primary hyperparathyroidism due to parathyroid adenoma (mean age, 69.5 +/- 1.4 yr) were genotyped for these VDR polymorphisms. Dispersed cells of the adenomas were exposed to increasing concentrations of extracellular Ca2+ and analyzed for PTH release and cytoplasmic Ca2+ concentrations. Ca2+-mediated PTH inhibition exhibited higher ED50 and less suppression in the cells of patients who were homozygous for the b, a, and T alleles (P < 0.05-0.10). When analyzing haplotypes, the patients with baT demonstrated a ED50 of 1.81 +/- 0.15 vs. 1.29 +/- 0.10 for BAt (P < 0.05). As VDR alleles were unrelated to parathyroid intracellular Ca2+, influences of polymorphic VDR alleles on PTH secretion seem to involve mechanisms other than the Ca2+-sensing protein of the parathyroid cell surface.

Adenoma↗
PubMed1997

Endothelin-induced calcium signaling and secretion in chief cells and fibroblasts from pathological human parathyroid glands.

Endothelins (ETs) are 21 amino acid peptides with vasoactive and mitogenic properties. The three isopeptides (ET-1, -2, and -3) and their receptors (E1A and ETB subtypes) display expression in numerous tissues and possibly mediate autocrine/paracrine actions. The present investigation shows that ET-1 triggers biphasic increases of the concentration of cytoplasmic Ca2+ ([Ca2+]i) in pathological human parathyroid cells. Both the peak and sustained [Ca2+]i increase, as well as the proportion of responding cells, are dose-dependent in the 10(-10)-10(-7) mol/L range of ET-1. In absence of external Ca2+, the ET-1-induced [Ca2+]i peak is attenuated. ET-3 has no effect on [Ca2+]i indicating functional dominance of the ETA receptor subtype. ET-1 (10 nmol/L) lowers parathyroid hormone secretion in 0.5 mmol/L but not in higher external Ca2+ concentrations, and parathyroid cell ET release is inhibited by increases of external Ca2+. Fibroblasts overgrowing the parathyroid chief cells during monolayer culture respond to ET-1 with biphasic [Ca2+]i increases or repetitive [Ca2+]i spikes, but show no response to elevation of external Ca2+. These findings imply that ET secretion and ET receptor expression may constitute an autocrine/paracrine mechanism in the regulation of human PTH secretion.

Adenoma↗
PubMed1996

Parathyroid tissue in normocalcemic and hypercalcemic primary hyperparathyroidism recruited by health screening.

Parathyroid tissue from 57 women (mean age 65.5 years) with sporadic primary hyperparathyroidism (HPT) was analyzed mainly to clarify its characteristics versus tissue from those with normocalcemia. Patients were recruited by population-based health screening of menopausal women. Analysis of three or four total serum calcium values showed normocalcemia in 16 patients (mean 2.53 mmol/L); 20 and 21 of the women were consistently (mean 2.82 mmol/L) or intermittently (mean 2.59 mmol/L) hypercalcemic, respectively. Parathyroid operation demonstrated a single adenoma in 81% of the individuals, and these lesions were most prevalent and commonly dominated by oxyphil parathyroid cells in the persistently hypercalcemic patients. Chief cell hyperplasia (two or three abnormal glands) of the nodular type was found more often in the normocalcemic patients. Total glandular weight was the smallest (mean 270 mg) among the normocalcemic women and contributed to delicate decisions with regard to the extent of resection. Immunostaining of cryosections with a monoclonal antibody recognizing a putative Ca2+ sensor demonstrated variably heterogeneous down-regulation of the recognized glycoprotein in the pathologic parathyroid glands from all the individuals. Dose-response relations for PTH release and the cytoplasmic Ca2+ concentration ([Ca2+]i) were determined in Ca2+ 0.5-3.0 mmol/L by examining dispersed cells with radioimmunoassay and microfluorometry after fura-2 loading, respectively. ED50 for PTH release and [Ca2+]i and the [Ca2+]i concentrations at Ca2+ 3.0 mmol/L were the least deranged in cells from pathologic glands of the normocalcemic patients. The findings substantiate that the abnormal parathyroid tissue of normocalcemic HPT principally is characterized by the same, albeit less extensive, morphologic and functional derangements, which consistently have been demonstrated in patients with HPT accompanied by hypercalcemia and detected clinically.

Adenoma↗
PubMed1996

Surgery for asymptomatic pancreatic lesion in multiple endocrine neoplasia type I.

Patients with multiple endocrine neoplasia (MEN) type I underwent pancreatic surgery at presymptomatic (n = 8, mean age 33 years) or symptomatic (n = 12, mean age 51 years) stages of pancreatic endocrine involvement with the principal aim to evaluate postoperative morbidity, survival, and malignant potential of the pancreatic lesion. Radiologic signs of malignancy were not identified in any patient prior to exploration. All patients displayed multiple tumors with generally complex immunoreactivity. Normal postoperative pancreatic tumor markers were recorded in five of the asymptomatic patients, which became abnormal in three of them at a mean of 3 years after surgery. All patients remained without symptoms for a mean of 6 years after operation. In four symptomatic individuals (33%) metastases were identified at exploration, and two died with tumor; 83% of symptomatic patients displayed persistent or recurrent endocrine morbidity from the pancreatic lesion. Recognizing lead time bias, this limited and uncontrolled patient comparison suggests that exploration at the symptomatic stage of pancreatic involvement in MEN-I patients is unsatisfactory. Rather than to obtain biochemical cure, surgery in asymptomatic patients might be regarded as a means of cancer prevention. The malignancy of the pancreatic lesion may be preceded by several decades of biochemical abnormality. Extensive screening for this lesion allows diagnosis during adolescence and the timely application of primary exploration. Active management of individuals with repeated biochemical analyses followed by selective reintervention could enable satisfactorily maintained pancreatic functions and substantial duration of cancer prevention.

Adenoma↗
PubMed1996

Progression of metastases and symptom improvement from laparotomy in midgut carcinoid tumors.

A total of 121 consecutive patients with midgut carcinoid tumors underwent regular clinical control and 158 laparotomies for abdominal symptoms with 1 to 11 years (mean 5.2 years) of follow-up. Metastases were present in 93% of the patients at study inclusion and developed at initially uninvolved sites with an overall probability of 0.38. Patients without initial tumor spread developed mesenteric or liver metastases with the probability of 0.25 (mean delay 12 years), whereas those with mesenteric metastases exhibited a probability 0.56 to develop liver metastases (mean delay 6.1 years). Spread to extraabdominal sites in patients with mesenteric and liver metastases exhibited a probability of 0.22 (mean delay 4.3 years), and this spread was especially frequent (probability 0.60) in patients with only liver metastases at inclusion. Patients without the carcinoid syndrome (52%) mainly suffered from more or less episodic abdominal pain, nausea, and diarrhea. Marked mesenteric fibrosis detected at surgery (n = 59) generally was accompanied by symptoms of abdominal pain and weight loss, and it often required urgent intervention due to intestinal obstruction or ischemia. Complete or partial symptom alleviation was accomplished in 82% of the operated patients, and generally was most auspicious after primary acute or subacute procedures (n = 54). The complete or partial symptom improvements after surgery lasted for mean 5.3 years and tended to be longer after elective (n = 50) than acute operations. The findings substantiate encouraging results of laparotomy in a compromised cohort of patients with midgut carcinoid tumors. Because the patients also displayed a generally slow progression of metastases, liberal indications for laparotomy should prevail in symptomatic and possibly also asymptomatic individuals with midgut carcinoid tumors.

Abdominal Pain↗
PubMed1996

Expression and function of a CD4-like molecule in parathyroid tissue.

BACKGROUND: Parathyroid tissue expresses the T-lymphocyte antigens CD3 and CD4, and parathyroid CD3 has earlier been proposed to interact in the regulation of parathyroid hormone (PTH) release. METHODS: Anti-Leu3a, a monoclonal antibody recognizing CD4, was used to stain parathyroid tissue immunohistochemically, to influence PTH secretion from enzymatically dispersed parathyroid cells, and to immunoprecipitate parathyroid CD4. Northern blot and polymerase chain reaction were used to clarify the similarity between parathyroid and lymphocytic CD4. Serum PTH level was measured with an immunoradiometric assay in healthy control subjects and individuals with human immunodeficiency virus type 1. RESULTS: The parenchyma of normal and abnormal parathyroid tissue displayed strikingly variable CD4 expression. Immunoprecipitation showed a 56 kd molecule, and Northern blot and polymerase chain reaction confirmed the similarity with lymphocyte CD4. Anti-Leu3a inhibited preferentially low calcium-stimulated secretion of PTH from dispersed parathyroid cells, without discernible influences on the cytoplasmic calcium concentration of these cells. Individuals with human immunodeficiency virus type 1 displayed significantly lower serum PTH levels than healthy control subjects. CONCLUSIONS: The results suggest that the human parathyroid chief cell expresses a CD4 moiety, which seems to interact in the PTH release in vitro and in vivo and which seems to use another second messenger system than the structurally similar T-cell equivalent.

Blotting, Northern↗