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P Lindblom

Publications and source records attributed to P Lindblom.

At least 19 recordsLinked to original sources
PubMed2001

Hemithyroidectomy: long-term effects on parathyroid function--preliminary report.

Early hypocalcemia after thyroid surgery has frequently been reported, whereas data regarding long-term effects on calcium homeostasis are scarce. We have previously studied patients after hemithyroidectomy with an oral calcium load test and found normal parathyroid hormone (PTH) suppression. However, the 1,25-dihydroxyvitamin D concentration was decreased and the phosphate concentration increased, implying parathyroid insufficiency. We therefore proceeded to investigate PTH secretion and suppression in 10 euthyroid patients subjected to hemithyroidectomy due to benign thyroid disease before and at 1 year after surgery. In addition, biochemical variables known to influence calcium homeostasis were analyzed. Basal, maximal, and total PTH secretion were unaltered 1 year postoperatively. However, maximal PTH secretion was reached at a lower serum level of ionized calcium, and there was a tendency toward increased parathyroid sensitivity to ionized calcium. Furthermore, compared to preoperative, total serum calcium, 1,25-dihydroxyvitamin D, and free thyroxine (T4) concentrations were decreased at follow-up. Total serum calcium and 1,25-dihydoxyvitamin D concentrations were decreased 1 year after hemithyroidectomy. These changes were not due to parathyroid insufficiency. Instead, our results imply increased parathyroid sensitivity to calcium and possibly reduced peripheral sensitivity to PTH.

Adult↗
PubMed2001

Urate and arteriosclerosis in primary hyperparathyroidism.

OBJECTIVE: An increased mortality due to cardiovascular disease has been reported in patients with primary hyperparathyroidism (pHPT). An association between urate and cardiovascular disease has been suggested. Metabolic abnormalities in pHPT may include urate. We therefore evaluated the metabolic arteriosclerotic risk profile in pHPT with special focus on the role of urate. DESIGN: Retrospective analysis of data before and 1 year after surgery for pHPT. PATIENTS: 130 consecutive patients, over the age of 44 years, who underwent surgery for pHPT. MEASUREMENTS: Biochemical variables known to reflect risk of arteriosclerotic disease (AD) and renal function tests including measurement of glomerular filtration rate (GFR) were investigated before and 1 year after surgery. RESULTS: pHPT patients with AD (n = 40) were older and had higher serum levels of urate and triglyceride, and more impaired renal function in comparison with patients without AD. PTH and calcium values did not differ. Multiple logistic regression analysis indicated that urate was an independent risk factor for AD in pHPT (P < 0.01). Three variables were shown to be positively associated with urate; male gender (P < 0.01), fasting blood glucose (P < 0.05) and serum level of triglyceride (P < 0.05). CONCLUSIONS: Urate was found to be an independent risk factor for arteriosclerotic disease in primary hyperparathyroidism. Serum level of urate could (in addition to gender) be associated with a metabolic disorder comprising increased glucose and triglyceride levels.

Adult↗
PubMed2001

Peripheral effects of PTH are not altered after thyroid surgery in euthyroid patients.

BACKGROUND: We have previously found decreased serum levels of both ionized calcium and 1,25(OH)2D and an increase in serum phosphate levels at 1 year after hemithyroidectomy. However, basal and stimulated parathyroid hormone (PTH) secretions were not altered. To investigate whether the observed biochemical changes after unilateral thyroid surgery may be due to a relative end-organ resistance to PTH, we studied the peripheral effects of infused hPTH-(1-34) in 6 patients preoperatively and 3 months after hemithyroidectomy. METHODS: Serum levels of TSH, FT4 and FT3 were measured pre- and postoperatively. hPTH-(1-34) was infused at 0.9 IU/kg/h during 6 h. Blood samples for analysis of ionized calcium, intact PTH, phosphate, 25(OH)D, 1,25(OH)2D and urinary samples for calcium, phosphate and nephrogenous(n)-cAMP analysis were taken at baseline, when the infusion was discontinued after 6 h and at 24 h. RESULTS: Three months after hemithyroidectomy, serum levels of FT3 were decreased and TSH levels increased. Pre- and postoperative hPTH-(1-34) infusions induced increased serum levels of ionized calcium, 1,25(OH)2D, increased urinary excretion of phosphate and elevated n-cAMP levels. The changes in the studied biochemical variables during the hPTH-(1-34) infusions did not differ between the two study occasions. CONCLUSION: By using a 6-hour hPTH-(1-34) infusion protocol, we have shown that the peripheral PTH effect is not altered by a slight reduction in thyroid hormone levels at 3 months after hemithyroidectomy.

Adult↗
PubMed2001

Decreased levels of ionized calcium one year after hemithyroidectomy: importance of reduced thyroid hormones.

BACKGROUND: Previously we have found reduced levels of total serum calcium and 1,25(OH)2D3 despite an unaltered stimulated parathyroid hormone (PTH) secretion 1 year after hemithyroidectomy. The present study was undertaken to elucidate the possible relationship between calcium homeostasis, thyroid hormones and bone resorption in a group of 45 consecutive patients subjected to hemithyroidectomy because of a solitary nodule. All patients had free T4 and T3 levels within normal range preoperatively. METHODS: Thyroid hormones, bone mineral and biochemical variables known to reflect calcium homeostasis were studied. Patients were divided into three separate groups depending on their pre- and postoperative thyroid hormone status. RESULTS: One year postoperatively, serum levels of free T4 were decreased and that of thyrotropin (TSH) increased in the entire group of patients. The concentration of ionized calcium was reduced from 1.25 +/- 0.05 to 1.22 +/- 0.04 (p < 0.001) despite an unaltered PTH value (2.8 +/- 1.0 vs. 3.1 +/- 1.5, p = 0.50). A significant reduction in C-terminal telopeptide type 1 collagen (1CTP) indicated decreased bone resorption 1 year after surgery (p < 0.05). Subgroup analysis showed that a reduction in ionized calcium was seen only among patients with a postoperative decrease in free T4. Patients with subclinical hyperthyroidism preoperatively presented the lowest postoperative levels of ionized calcium, significantly reduced levels of 1CTP and increased levels of phosphate and creatinine. Multiple linear regression analysis showed that age (p < 0.05) and postoperatively changed serum levels of TSH (p < 0.05), creatinine (p < 0.05), phosphate (p < 0.001) and FT4 (p < 0.01) were independently associated with altered levels of ionized calcium. CONCLUSION: We conclude that the reduction in ionized calcium 1 year after hemithyroidectomy was not due to PTH deficiency. Instead our results suggest that the reduced effects of thyroid hormones on bone and kidney function is essential.

Adult↗
PubMed2000

Risk factors for postoperative hypocalcemia after surgery for primary hyperparathyroidism.

HYPOTHESIS: A variety of clinical and biochemical variables may be associated with hypocalcemia after surgery for parathyroid adenoma. DESIGN: A prospective study of patients who underwent surgery for solitary parathyroid adenoma. SETTING: A university hospital department of surgery. PATIENTS: Eighty-six consecutive patients who underwent surgery for solitary parathyroid adenoma. INTERVENTION: Parathyroidectomy according to the principles of unilateral neck exploration. MAIN OUTCOME MEASURES: Clinical and biochemical risk factors for early (< or =4 days after surgery) and late (1 year after surgery) postoperative symptomatic and biochemical hypocalcemia. RESULTS: Twenty-two patients developed early symptomatic hypocalcemia. The difference in total serum calcium levels between patients, with and without early symptomatic hypocalcemia, was evident on the third and fourth postoperative days. Serum level of osteocalcin greater than 6.0 microg/L, bilateral neck exploration, and history of cardiovascular disease were risk factors for symptomatic hypocalcemia (odds ratios [95% confidence intervals]: 4.4 [1.4-14.1], 3.8 [1.3-11.6], and 0.1 [0.02-0.60], respectively). Patients with up to 1 risk factor had a possibility of only 7% to develop early symptomatic hypocalcemia. One year after surgery, 16 patients had low levels of total serum calcium (late biochemical hypocalcemia) and were asymptomatic. Preoperative intermittent hypercalcemia was associated with an increased risk for late biochemical hypocalcemia (odds ratio, 3.9; 95% confidence interval, 1.0-16.3). CONCLUSIONS: Clinical and biochemical risk factors for early and late postoperative hypocalcemia in patients who underwent surgery for solitary parathyroid adenoma were found. A clinically useful prognostic index for early symptomatic hypocalcemia was constructed using these risk factors.

Adenoma↗
PubMed2000

Microsatellite instability as a predictor of a mutation in a DNA mismatch repair gene in familial colorectal cancer.

Germline alterations in human DNA mismatch repair genes are associated with hereditary nonpolyposis colorectal cancer (HNPCC). Mutation analysis of the genes reveals carriers with a high risk of colorectal cancer, who will benefit from surveillance. We wanted to find the best predictive parameter of a germline mutation in those genes among patients with familial colorectal cancer. Affected members from a total of 83 unrelated colorectal cancer families previously analyzed for mutations in MSH2 and MLH1 were used to evaluate different parameters' ability to predict a germline mutation. We studied various clinical criteria such as family structure, age of onset, and prevalence of endometrial cancer, as well as microsatellite instability in the tumors from the families. In total, 124 tumors from 59 of the families were tested for microsatellite instability (MSI) using PCR-based mono- and dinucleotide markers to establish whether the families could be scored as MSI-positive or -negative. The finding of MSI-positive tumors in a family was the best predictor of a germline mutation, and was found in 73% of the MSI-positive, but in less than 3% of the MSI-negative families (P < 0.0001). In contrast, MSI in unselected colorectal cancer is not as useful, since most of these MSI-positive tumors are sporadic. The finding of microsatellite instability in colorectal tumors seems efficient enough even to select those with germline mutations among families fulfilling HNPCC Amsterdam criteria, once used in identification of the DNA mismatch repair genes. Genes Chromosomes Cancer 27:17-25, 2000.

Adult↗
PubMed2000

Postoperative elevated serum levels of intact parathyroid hormone after surgery for parathyroid adenoma: sign of bone remineralization and decreased calcium absorption.

Increased levels of intact parathyroid hormone (PTH) have been documented after surgery for primary hyperparathyroidism (pHPT) despite normocalcemia. The pathogenesis remains to be elucidated. Seventeen consecutive patients operated on for solitary parathyroid adenoma were investigated before and at 8 weeks and 1 year after surgery with serum levels of intact PTH, biochemical variables known to reflect PTH activity, and bone mineral content (BMC). In addition, an oral calcium loading test was performed 8 weeks after the operation. All patients had low or normal serum calcium levels during follow-up. Eight weeks after operation six patients (35%) had an increased serum PTH level. These patients (group I) preoperatively had higher serum levels of PTH and alkaline phosphatase than patients with normal PTH levels (group II). They also had lower BMC and larger parathyroid adenomas. They did not differ in renal function. At 8 weeks after operation group I showed higher mean serum levels of osteocalcin and propeptide of type I procollagen but lower urinary calcium excretion. In contrast to patients in group II, they also showed a lower calciuric response and a trend to a lower calcemic response during the oral calcium load. The two groups showed similar parathyroid sensitivity for calcium. Patients in group I demonstrated a significant increase in BMC the first year after the operation. Increased serum PTH 8 weeks after surgery for sporadic parathyroid adenoma was not due to persistent pHPT or impaired renal function. Instead, the results imply there is diminished calcium absorption and increased bone turnover with cortical bone remineralization.

Absorptiometry, Photon↗
PubMed1999

Hyperthyroidism after surgery for primary hyperparathyroidism.

BACKGROUND: The coexistence of hyperthyroidism and primary hyperparathyroidism (pHPT) has been reported. We have questioned whether hypercalcemia or surgical trauma contribute to transient hyperthyroidism following parathyroid surgery. METHODS: Twenty-six pHPT and eleven breast cancer patients were compared regarding pre-, peri- and postoperative thyrotropin (TSH), free thyroxine (T4) and free triiodothyronine (T3) concentrations. Thyroglobulin concentration, occurrence of autonomous thyroid nodules, and variables reflecting surgical trauma were compared in pHPT patients with and without postoperative hyperthyroidism. RESULTS: Postoperatively, eleven pHPT patients demonstrated T4 and T3 concentrations above normal, and nine developed symptoms of mild thyrotoxicosis. A parallel rise in TSH and T4 concentrations was seen during both parathyroid and breast cancer surgery. Compared with patients with no postoperative hyperthyroidism, patients with postoperative hyperthyroidism showed a parallel rise in mean thyroglobulin and T4/T3 concentrations as well as higher thyroglobulin concentrations. However, there was no difference in variables assessing surgical trauma nor in occurrence of autonomous thyroid nodules. The peri-operative rise in TSH was preceded by a decrease in calcium. CONCLUSION: Transient hyperthyroidism after parathyroid surgery is not infrequent. The condition seems to be self-limiting, since symptoms invariably subsided without treatment. Manipulation of the thyroid gland is most likely the major contributing factor to postoperative hyperthyroidism. However, it may not be the sole explanation, since our data suggest a more multifactorial scenario.

Aged↗
PubMed1999

Various mutation screening techniques in the DNA mismatch repair genes hMSH2 and hMLH1.

Germline alterations in one of five human DNA mismatch repair genes (hMSH2, hMLH1, hPMS1, hPMS2, and hMSH6) cause hereditary nonpolyposis colorectal cancer. Mutation analyses of these genes reveal gene carriers with a high risk for colorectal cancer, who benefit from surveillance to prevent disease. Equally important, presymptomatic testing allows nondisposed individuals to discontinue surveillance. We tested different mutation screening methods to optimize mutation detection in hMSH2 and hMLH1. Affected members from a total of 142 unrelated colorectal cancer families were analyzed. Denaturant gradient gel electrophoresis (DGGE), RT-PCR, and the protein truncation test (PTT) were used to screen for mutations on a DNA or RNA basis, respectively. In addition, a mutation-specific test on genomic DNA was used to find the Finnish mutation no. 1, a deletion of hMLH1 exon 16. DGGE identified most of the mutations in the mismatch repair genes hMLH1 and hMSH2. The RNA-based techniques were used to identify large deletions; however, these were rare in our materials. We describe our compiled results and experience from all our mutation screening studies, as well as unpublished data from our last DGGE screening of 58 patients and RT-PCR and PTT screening of 73 patients.

Adaptor Proteins, Signal Transducing↗
PubMed1998

The role of ataxia-telangiectasia heterozygotes in familial breast cancer.

The role of ataxia-telangiectasia (AT) heterozygotes in breast cancer has been controversial. We have found previously an overrepresentation (3.4%) of ATM mutations in a subset of 88 selected breast cancer patients with a family history of breast cancer, leukemia, and lymphoma. This prevalence is comparable to the estimated value (3.8%) from epidemiological study. To further examine the possibility that ATM is correlated to breast cancer, we screened for ATM germ-line mutations in another 100 breast cancer patients with a family history of breast cancer. We used the protein truncating test and found one new germ-line mutation. This figure (1%) is consistent with the observed 0.2-1% carrier frequency for AT. We also studied breast tumors from ATM mutants, and three showed retention of both alleles, whereas the fourth showed loss of the mutant allele. We conclude that the contribution of heterozygous ATM mutations to familial breast cancer is minimal. Even if the ATM gene were causative in these cases, it is not likely to act as a tumor suppressor.

Ataxia Telangiectasia↗
PubMed1998

Measurement of parathyroid hormone in patients with primary hyperparathyroidism undergoing first and reoperative surgery.

BACKGROUND: The distinction between solitary parathyroid adenoma and hyperplasia can sometimes be difficult during surgery for primary hyperparathyroidism (pHPT), especially in patients who have undergone previous thyroid or parathyroid surgery. The use of intraoperative parathyroid hormone (PTH) monitoring as a possible diagnostic tool was therefore investigated. METHODS: Intraoperative levels of PTH were measured in 119 patients during 121 operations (including 14 reoperations) for pHPT. The mean(s.d.) preoperative serum calcium level was 2.79(0.21) mmol/l. Blood samples were drawn before, and at 5 and 15 min after, excision of the first enlarged parathyroid gland. PTH was analysed electively in 61 patients and on-line by a modified assay for intact PTH in 48 patients. Both procedures were used in ten patients. RESULTS: The mean(s.d.) decline in PTH concentration in 101 patients with primary exploration due to solitary adenoma was 63(17) per cent after 5 min (n=84) and 83(10) per cent after 15 min. The patients with primary exploration because of multiglandular disease (n=6) were correctly predicted not to have parathyroid adenoma. CONCLUSION: Measurement of PTH levels during surgery for pHPT is a highly sensitive method for differentiating between single and multiple gland disease. The on-line monitoring of PTH is clinically useful in patients who have undergone previous neck surgery. Its role in pHPT surgery at primary exploration should be evaluated in prospective trials.

Adenoma↗
PubMed1998

Metabolic abnormalities related to cardiovascular risk in primary hyperparathyroidism: effects of surgical treatment.

OBJECTIVES: Untreated primary hyperarathyroidism (pHPT) is accompanied by an excessive morbidity in circulatory disorders, associated with blood pressure and diabetes. The aim of the present study was to further penetrate the impact of pHPT on glucose, urate, lipid and lipoprotein concentrations, known to be interrelated metabolic cardiovascular risk factors. DESIGN: Longitudinal study of patients with pHPT before and 1 year after surgical treatment. SETTING: Departments of Internal Medicine and Surgery, Lund University Hospital. SUBJECTS: One hundred and seventeen consecutive patients with pHPT referred to surgical treatment. At presentation. 11 patients had previously diagnosed diabetes mellitus. INTERVENTION: All patients were successfully operated for pHPT. MAIN OUTCOME MEASURES: Fasting blood glucose and serum concentrations of cholesterol, triglyceride and urate were determined before and 1 year after surgery. The concentration of LDL- and HDL-cholesterol was separately analyzed in 21 cases. These data as well as the systolic and diastolic blood pressure were related to intact PTH and ionized calcium at presentation. Glomerular filtration was separately measured pre-operatively and related to the urate values. RESULTS: While the mean value for glucose remained unchanged among 11 patients with previously diagnosed diabetes at presentation, a significant decrease of glucose from 5.03+/-0.13 to 4.71+/-0.08 mmol/L (P < 0.05) was found among patients without known diabetes. Out of these patients, eight had diabetic glucose values at presentation, decreasing from 8.35+/-0.54 to 5.10+/-0.35 mmol/L (P < 0.05), and 12 had glucose values indicating impaired glucose tolerance, decreasing from 5.94+/-0.06 to 5.10 +/-0.38 mmol/L (P < 0.05) after surgery. Total cholesterol and trigylceride concentrations were not changed. However, male patients had significantly lower triglyceride levels at follow-up, 1.16+/-0.09 mmol/L compared to 1.57+/-0.14 mmol/L before surgery (P < 0.05). Significantly lower triglyceride values were also found among patients with glucose values indicating impaired glucose tolerance at presentation. The LDL/HDL cholesterol ratio remained normal. The serum level of urate decreased in both male and female patients after surgery, and was positively correlated to the PTH and ionized calcium values and inversely correlated to renal function before treatment. There was no significant correlation between calcium or PTH and the other metabolic variables studied.

Adult↗
PubMed1997

Sestamibi versus thallium subtraction scintigraphy in parathyroid localization: a prospective comparative study in patients with predominantly mild primary hyperparathyroidism.

BACKGROUND: Technetium 99m sestamibi was recently introduced for the preoperative localization of abnormal parathyroid glands in patients with primary hyperparathyroidism with promising results. However, the sensitivity of sestamibi and thallium to detect abnormal parathyroid glands is partly dependent on the gland size. In this study we compared the sensitivity of sestamibi subtraction scintigraphy with thallium subtraction scintigraphy in patients with predominantly mild increase in serum calcium level. METHODS: Thirty-nine patients with primary hyperparathyroidism were included. The mean (+/-SD) serum level of calcium was 2.75 +/- 0.17 mmol/L. In 28 (72%) of the patients the serum level of calcium was less than 2.85 mmol/L. These patients were classified as having mild abnormalities in serum calcium. All patients were investigated before operation with both sestamibi and thallium subtraction scintigraphy. RESULTS: In two patients autonomous thyroid adenomas precluded subtraction scintigraphy. Sestamibi subtraction scintigraphy correctly localized 31 (86%) of 36 parathyroid adenomas compared with only 17 (47%) of 36 by thallium subtraction scintigraphy (p < 0.001). There was one false-positive result in the sestamibi group because of a thyroid adenoma, and two of the scans were negative. Both the sestamibi and the thallium subtraction scintigraphy localized one single enlarged gland in all three patients with multiple gland involvement. In no case was multiglandular disease predicted. CONCLUSIONS: Sestamibi subtraction scintigraphy is superior to thallium subtraction scintigraphy and has a high sensitivity to localize a solitary parathyroid adenoma in patients with mild increase in serum calcium level. The sensitivity decreases in patients with multiglandular parathyroid disease and concomitant thyroid nodular abnormalities.

Adenoma↗
PubMed1995

Participatory design of computer-supported organizational learning in health care: methods and experiences.

This paper outlines a Computer-Supported Co-operative Work (CSCW) system for primary care and presents from its participatory design process time consumption, costs, and experiences. The system integrates a hypermedia environment, a computerized patient record, and an electronicmessage system. It is developed to coordinate organizational learning in primary care from micro to macro levels by connecting strategic planning to monitoring of patient routines. Summing up design experiences, critical issues for making CSCW systems support cost-effectiveness of health care are discussed.

Community Health Centers↗
PubMed1992

Developing a clinical hypermedia corpus: experiences from the use of a practice-centered method.

This paper outlines a practice-centered method for creation of a hypermedia corpus. It also describes experiences with creating such a corpus of information to support interprofessional work at a Primary Healthcare Center. From these experiences, a number of basic issues regarding information systems development within medical informatics will be discussed.

Hospital Information Systems↗