A coordinated cross-disciplinary research initiative to address an increased incidence of narcolepsy following the 2009-2010 Pandemrix vaccination programme in Sweden.

In response to the 2009-2010 influenza A(H1N1)pdm09 pandemic, a mass vaccination programme with the AS03-adjuvanted influenza A(H1N1) vaccine Pandemrix was initiated in Sweden. Unexpectedly, there were a number of narcolepsy cases amongst vaccinated children and adolescents reported. In this review, we summarize the results of a joint cross-disciplinary national research effort to investigate the adverse reaction signal from the spontaneous reporting system and to better understand possible causative mechanisms. A three- to fourfold increased risk of narcolepsy in vaccinated children and adolescents was verified by epidemiological studies. Of importance, no risk increase was observed for the other neurological and autoimmune diseases studied. Genetic studies confirmed the association with the allele HLA-DQB1*06:02, which is known to be related to sporadic narcolepsy. Furthermore, a number of studies using cellular and molecular experimental models investigated possible links between influenza vaccination and narcolepsy. Serum analysis, using a peptide microarray platform, showed that individuals who received Pandemrix exhibited a different epitope reactivity pattern to neuraminidase and haemagglutinin, as compared to individuals who were infected with H1N1. Patients with narcolepsy were also found to have increased levels of interferon-gamma production in response to streptococcus-associated antigens. The chain of patient-related events and the study results emerging over time were subjected to intense nationwide media attention. The importance of transparent communication and collaboration with patient representatives to maintain public trust in vaccination programmes is also discussed in the review. Organizational challenges due to this unexpected event delayed the initiation of some of the research projects, still the main objectives of this joint, cross-disciplinary research effort were reached, and important insights were acquired for future, similar situations in which a fast and effective task force may be required to evaluate vaccination-related adverse events.

Positive effect of parathyroidectomy on bone mineral density in mild asymptomatic primary hyperparathyroidism.

OBJECTIVES: Patients with mild primary hyperparathyroidism (pHPT) often appear asymptomatic, and have previously been regarded as not requiring treatment. However, increased cardiovascular morbidity and dyslipidaemia have also been recognized in mild pHPT, which also seem to be normalized after parathyroidectomy. The present study explores whether postmenopausal women with mild pHPT have decreased bone mineral density (BMD) compared with age-matched healthy controls, and the effects on BMD of parathyroidectomy. DESIGN, SUBJECTS AND INTERVENTION: A population-based health screening of 5202 postmenopausal women identified 87 overtly asymptomatic patients with mild pHPT as well as age-matched healthy controls. A 5-year follow-up included 49 cases who had undergone parathyroidectomy. BMD was measured with DXA at the femoral neck, the lumbar spine and the total body. RESULTS: At study entry, BMD was 5-6% lower in the lumbar spine (L2-L4) and femoral neck in cases compared with matched controls. After the 5-year follow-up, BMD increased in L2-L4 by 2.9% (P = 0.002) in the parathyroidectomized cases and remained stable in the femoral neck. However, femoral neck BMD increased 4.1% (P = 0.013) for cases <67 years old (50% of the cohort). CONCLUSION: In accordance with recent NIH guidelines for pHPT treatment, the level of BMD per se in the investigated group of patients justifies parathyroidectomy in almost half of the cases with mild pHPT. Surgery could be expected to increase BMD in L2-L4 to the level of the controls, to increase femoral neck BMD in patients <67 years of age and to preserve femoral neck BMD in the elderly population.

Graves' disease with moderate-severe endocrine ophthalmopathy-long term results of a prospective, randomized study of total or subtotal thyroid resection.

The optimal thyroid surgery to be performed in patients with Graves' disease and concomitant endocrine ophthalmopathy is a matter of debate. We randomly assigned 44 patients with moderate-severe eye signs in a trial of treatment with subtotal, leaving a small (approximately 2 g) thyroid remnant, or total thyroidectomy. At inclusion, the patients had been treated with antithyroid drugs, and corticosteroids been given to 12 (27%). All received postoperative thyroxine supplementation and were followed for 3 years at regular examinations. The eye disease improved in all cases, and throughout the study, the two groups did not differ with regard to subjective and objective eye symptoms and laboratory findings. At the study start, motility disturbances were present in 8 and 11 of the cases in the subtotal and total resection group and proptosis in 16 and 17, respectively. After 3 years, the corresponding data were 3 and 6 cases with motility defects and 16 and 15 cases with proptosis. Thyrotropin (TSH)-receptor antibody levels gradually fell and became nondetectable in 21 (49%). The surgical complication rate (permanent recurrent laryngeal nerve paresis and permanent hypoparathyroidism) was significantly higher in the total thyroidectomy group. The data indicate that in patients with Graves' disease and active endocrine ophthalmopathy, subtotal thyroidectomy, leaving a small thyroid remnant, will reduce the risk of surgical complications but not the beneficial effect of surgery.

Increased cardiovascular mortality and normalized serum calcium in patients with mild hypercalcemia followed up for 25 years.

BACKGROUND: The natural history of mild hyperparathyroidism is incompletely clarified. METHODS: Consistent hypercalcemia was found in 172 patients (aged 28-86 years) participating in population-based screenings in both 1969 and 1971. Mortality until 1994 was compared with 344 matched, normocalcemic controls from the study population. Altogether, 55 case-control pairs underwent biochemical analysis in 1992, whereas 86 patients had died, 8 were lost to follow-up, and 23 had undergone parathyroid operation. RESULTS: Mortality was higher (P = .015) in patients younger than 70 years. Cardiovascular diseases were over-represented causes of death. The hazard ratio for hypercalcemia as an independent cause of cardiovascular mortality was 1.72 (95% CI, 1.24-2.37; P < .001). The initially mild hypercalcemia in patients (2.67 +/- 0.07 mmol/L) decreased over time (P = .0001), whereas the serum calcium value remained constant in the controls. Serum calcium and serum parathyroid hormone values in patients were higher than controls at the follow-up (P < .0001, .01, respectively). All but 17 patients were normocalcemic in 1992, and only 2 (1.4%) developed a serum calcium value higher than 3 mmol/L. CONCLUSIONS: Mild hypercalcemia in patients followed up for more than 2 decades is accompanied by premature cardiovascular death despite trends to spontaneous resolution. The principal cause of hypercalcemia probably is primary hyperparathyroidism, but mechanisms contributing to its regression over time are speculative.

Endothelial vasodilatory function and blood pressure response to local and systemic hypercalcemia.

BACKGROUND: Endothelial vasodilatory dysfunction occurs in primary hyperparathyroidism. Mechanistically it could be a sign of atherosclerosis, but improvement after parathyroidectomy suggests coupling to hypercalcemia and increased parathyroid hormone levels of patients. METHOD: A total of 12 volunteers underwent forearm venous occlusion plethysmography with systemic (intravenous) and local (brachial artery) infusion of calcium. Endothelium-dependent and endothelium-independent vasodilations were evaluated at stable hypercalcemia through infusion of methacholine and nitroprusside into the brachial artery, and an endothelial function index was calculated as the ratio between them. RESULTS: Normal ionized blood calcium values rose 0.24 +/- 0.09 mmol/L in the cubital venous blood during local calcium infusion and 0.32 +/- 0.16 mmol/L during the systemic infusion. The systemic infusion raised systolic blood pressure (114 +/- 13 to 121 +/- 10 mm Hg; P < .05). It decreased the function index (1.28 +/- 0.40 to 1.00 +/- 0.14; P < .05; n = 11) due to an elevated endothelium-independent vasodilation (EIDV) (P < .05), despite the fact that serum parathyroid hormone values decreased (P< .01). A similar trend in vasodilatory responses was seen during local calcium infusion when the function index correlated inversely to the local blood calcium (r = -0.58, P < .05; n = 12). CONCLUSIONS: Acute hypercalcemia results in dose-related impairment in endothelial vasodilatory function and increased systolic blood pressure. This substantiates the importance of hypercalcemia for cardiovascular complications and prospects for normalization by active treatment in primary hyperparathyroidism.

Childbearing and the risk of parathyroid adenoma--a dominant cause for primary hyperparathyroidism.

OBJECTIVES: To explore possible associations between the reproductive history amongst women and the risk of parathyroid adenoma (PA). DESIGN: Two nationwide Swedish registries. The Fertility Register included data on more than 3.4 million livebirths between 1943 and 1992 amongst Swedish females born 1925-72. The Cancer Register encompasses more than 1800 women with a diagnosis of PA 1960 until 1992. SETTING: All women resident in Sweden 1960-92. SUBJECTS: Cases were all 1800 women born 1925-72 reported to the Swedish Cancer Registry with a histopathological diagnosis of PA. Five controls were selected at random for each case by matching for the month and year of birth. Conditional logistic regression was used to estimate relative risks of PA. MAIN OUTCOMES: Parathyroid adenoma. RESULTS: High parity (four or more live births) was associated with an increased risk of PA. Amongst women with a diagnosis of PA before menopause (i.e. the age of 50 years) there was an increased risk of PA with younger age at first childbirth. Nulliparous women were at increased risk for PA before menopause, and at decreased risk after menopause. CONCLUSIONS: There is an association between childbearing and the risk of PA, which has not previously been demonstrated, but the underlying biological mechanisms remain to be determined.

Unique clinical characteristics of primary hyperparathyroidism in India.

BACKGROUND: The features of primary hyperparathyroidism (PHPT) in developing countries have rarely been examined. This study explored the clinical characteristics of PHPT in India with the hypothesis that this may improve understanding of the pathogenesis of the disease worldwide. METHODS: Consecutive patients with PHPT (24 women, five men) were examined prospectively before and after parathyroidectomy. RESULTS: All patients had osteitis fibrosa cystica with a median symptom duration of 2.5 (range 1-26) years. Single or multiple fragility fractures were present in 14 patients (eight were bedridden); 20 had brown tumours. Mean preoperative serum calcium was 3.1 mmol/l, while mean serum intact parathyroid hormone (iPTH) and total alkaline phosphatase (ALP) levels were 17-fold and 12-fold higher than normal respectively. Nine patients had overt renal damage, mainly nephrocalcinosis. Parathyroidectomy invariably resulted in severe hypocalcaemia, necessitating long-term vitamin D treatment. The mean parathyroid gland weight was 8.6 (range 2.0-36.6) g and features of carcinoma were found in four patients. Serum calcidiol level correlated inversely (P < 0.05) with serum iPTH and ALP, and parathyroid gland weight. CONCLUSION: PHPT in Indians is a severe, symptomatic disorder with skeletal, muscular and renal manifestations at a young age. The presence of this severe variant of PHPT in vitamin D-sufficient Indians, and the lack of skeletal disease in other vitamin D-deficient populations, raises the possibility of additional pathogenetic factors.

The NeiI polymorphism in the cyclin D1 gene and sporadic primary hyperparathyroidism.

OBJECTIVES: The cell cycle regulator cyclin D1 plays an important role in parathyroid tumourigenesis. The NciI polymorphism in exon 4 has recently been associated with early onset of hereditary nonpolyposis colorectal cancer and is a prognostic indicator of nonsmall cell lung cancer and squamous cell carcinomas. Furthermore, a limited study of 28 primary hyperparathyroidism (pHPT) patients displayed a tendency of NciI influence on HPT development. We hypothesized that the NciI polymorphism may relate to a risk of developing pHPT. DESIGN, SETTING AND SUBJECTS: We genotyped 182 patients with sporadic pHPT and matched controls for the cyclin D1 polymorphism. A total of 88 pHPT patients and controls were recruited via a health-screening. RESULTS: The frequency distribution of the NciI genotypes NN, Ni, and ii were in pHPT patients and controls 22, 44 and 34%, and 26, 49 and 25%, respectively. The calculated allele frequencies were A = 0.56; G = 0.44 in cases and A = 0.49; G = 0.51 in controls. The frequency distributions did not differ comparing cases and controls when subgrouped after age and menopausal status. The NciI genotypes were not significantly associated with age of the individuals, serum (s)-calcium, s-parathyroid hormone (PTH), bone mineral density (BMD) or parathyroid tumour weight in any of the groups of pHPT patients or controls. CONCLUSIONS: No significant differences in distribution of the genotypes could be detected between the groups, suggesting that the polymorphism has minor or no pathogenic importance in the development of pHPT. Our results suggest that determination of the NciI polymorphism in the cyclin D1 gene is not a clinically useful tool for prediction of pHPT.

Left ventricular systolic and diastolic function and exercise testing in primary hyperparathyroidism-effects of parathyroidectomy.

BACKGROUND: Nontraditional manifestations of primary hyperparathyroidism (HPT) are controversial and may include morbidity, mortality, and risk factors for cardiovascular diseases. This study evaluates cardiovascular functions at rest and during exercise in HPT. METHOD: Thirty patients with HPT (mean serum calcium, 2.97 +/- 0.24 mmol/L) and 30 control people with normocalcemia, matched for age and sex, underwent symptom-limited exercise testing and echocardiography before and 13 months (mean) after having a parathyroidectomy. RESULTS: Despite similar maximal workload and blood pressures at rest in patients and healthy controls, HPT associated with higher systolic blood pressure during exercise (P =.03) and increased number of ventricular extrasystolic beats (P =.04). There was also an operatively reversible increase in ST-segment depression during exercise. Echocardiography showed an increased left ventricular (LV) isovolemic relaxation time (P =.02) and mitral deceleration time (P =.08), which indicate an LV diastolic dysfunction that could be partially reversed by operation. LV systolic function (ejection fraction and shortening fraction) tended to be elevated in HPT (P =.07 and.06, respectively) and diminished after parathyroidectomy. There was a trend toward higher LV mass, especially among the men with HPT (P =.06), which was unchanged postoperatively. CONCLUSIONS: HPT couples to reversible signs of myocardial ischemia and LV dysfunctions with a possible increased risk of life-threatening arrhythmia.

Surgical strategy for large or malignant endocrine pancreatic tumors.

Endocrine pancreatic tumors (EPTs) are rare but have a remarkably better prognosis than adenocarcinoma of the pancreas. Patients with EPTs benefit from surgical and medical therapy, which may alleviate symptoms due to hormonal excess and increase survival. Patients with large or malignant EPTs with infiltrative disease may suffer from local complications, including gastrointestinal bleeding and obstruction and involvement of the superior mesenteric (SMV) and portal (PV) veins. Among 31 patients with operable and large or malignant EPTs, 7 had hormone-producing syndromes (insulin, glucagon), and 24 had clinically nonfunctioning EPTs. Surgery in these patients included vascular reconstruction of the SMV/PV (n = 4), resection of infiltrated adjacent organs (n = 5; stomach, transverse colon), or resection of concomitant liver metastases (n = 3). Four patients with conspicuously large insulinomas, and three with glucagonoma were successfully operated on with alleviation of hormonal symptoms. Among the 24 nonfunctioning EPTs, 5 patients had been explored earlier and their tumors judged inoperable due to locally invasive disease or misdiagnosis as pancreatic adenocarcinoma. The operations were performed with no mortality and low morbidity. We conclude that large and malignant EPTs with limited spread of disease may benefit from a combination of medical and surgical therapy.

Method for dissection of mesenteric metastases in mid-gut carcinoid tumors.

With adequate medical management the midgut carcinoid tumor generally is an indolent malignancy associated with substantial life expectancy and appreciable life quality, even in the presence of liver metastases and significant tumor burden. Abdominal complications may occur in this entity of carcinoids owing to entrapment of intestines and encasement of mesenteric vessels by mesenteric metastases and associated marked mesenteric fibrosis. This may be the cause of abdominal pain, disabling diarrhea, weight loss to the extent of malnutrition, and eventually the risk of death with acute or chronic intestinal obstruction or intestinal gangrene. Operative removal of the mesentericointestinal lesion is often indicated to prevent or treat these complications but may be technically difficult when mesenteric metastases extend in the vicinity of major vessels in the mesenteric root. At laparotomy 56 patients with advanced midgut carcinoids underwent removal of the mesenteric tumor with a method for preserving the mesenteric vessels. This was feasible by mobilizing and releasing the right colon and mesenteric root from posterior adhesions, identifying the mesenteric artery below the pancreas, and free-dissecting this artery on the tumor capsule in the mobilized mesentery. Dissection was successful even with tumors initially judged inoperable unless tumor growth completely surrounded the mesenteric vessels or extended retroperitoneally. One patient was subjected to distal intestinal artery bypass. Symptom relief was been substantial and often of long duration after mesenteric tumor removal in patients who prior to surgery often had threatening intestinal ischemia. Patients with advanced midgut carcinoids may benefit markedly from dissectional removal of mesenteric tumors, which (conceivably better than conventional wedge resection) preserves the length of the remaining intestine.

Reduced parathyroid vitamin D receptor messenger ribonucleic acid levels in primary and secondary hyperparathyroidism.

Vitamin D, via its receptor (VDR), inhibits the hormone secretion and proliferation of parathyroid cells. Vitamin D deficiency and reduced parathyroid VDR expression has been associated with development of hyperparathyroidism (HPT) secondary to uremia. VDR polymorphisms may influence VDR messenger RNA (mRNA) levels and have been coupled to an increased risk of parathyroid adenoma of primary HPT. VDR mRNA relative to glyceraldehyde-3-phosphate dehydrogenase mRNA levels were determined by RNase protection assay in 42 single parathyroid adenomas of patients with primary HPT, 23 hyperplastic glands of eight patients with uremic HPT, and 15 normal human parathyroid glands. The adenomas and hyperplasias demonstrated similar VDR mRNA levels, which were reduced (42 +/- 2.8% and 44 +/- 4.0%) compared with the normal glands (P < 0.0001). Comparison of parathyroid adenoma with a normal-sized parathyroid gland of the same individual (n = 3 pairs) showed a 20-58% reduction in the tumor. Nodularly enlarged glands represent a more advanced form of secondary HPT and showed greater reduction in the VDR mRNA levels than the diffusely enlarged glands (P < 0.005). The reduced VDR expression is likely to impair the 1,25(OH)2D3-mediated control of parathyroid functions, and to be of importance for the pathogenesis of not only uremic but also primary HPT. Circulating factors like calcium, PTH, and 1,25(OH)2D3 seem to be less likely candidates mediating the decreased VDR gene expression in HPT.

Familial hypercalcemia and hypercalciuria caused by a novel mutation in the cytoplasmic tail of the calcium receptor.

Familial hyperparathyroidism (HPT), characterized by hypercalcemia and hypercalciuria, and familial benign hypocalciuric hypercalcemia (FHH) are the most common causes of hereditary hypercalcemia. The calcium-sensing receptor (CaR) regulates PTH secretion and renal calcium excretion. Heterozygous inactivating mutations of the gene cause FHH, whereas CaR gene mutations have not been demonstrated in HPT. In a kindred with 20 affected individuals, the hypercalcemic disorder segregated with inappropriately higher serum PTH and magnesium levels and urinary calcium levels than in unaffected members. Subtotal parathyroidectomy revealed parathyroid gland hyperplasia/adenoma and corrected the biochemical signs of the disorder in seven of nine individuals. Linkage analysis mapped the condition to markers flanking the CaR gene on chromosome 3q. Sequence analysis revealed a mutation changing phenylalanine to leucine at codon 881 of the CaR gene, representing the first identified point mutation located within the cytoplasmic tail of the CaR. A construct of the mutant receptor (F881L) was expressed in human embryonic kidney cells (HEK 293), and demonstrated a right-shifted dose-response relationship between the extracellular and intracellular calcium concentrations. The hypercalcemic disorder of the present family is caused by an inactivating point mutation in the cytoplasmic tail of the CaR and displays clinical characteristics atypical of FHH and primary HPT.

Hypocalcemia and parathyroid hormone secretion in critically ill patients.

OBJECTIVE: To investigate possible causes of hypocalcemia and to assess parathyroid hormone (PTH) secretion in intensive care unit (ICU) patients. DESIGN: Combined cross-sectional and prospective study. SETTING: ICU in a university hospital. PATIENTS: Thirteen patients with sepsis and 13 patients who underwent major surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Calcium metabolic indices were investigated during the first 24 hrs in the ICU and after 2 days. Eight of the surgical patients and five of the septic patients were subjected to a citrate/calcium infusion on day 1 in the ICU, to study the dynamics of PTH secretion. The blood ionized calcium (Ca2+) concentration was generally low in the septic patients (mean +/- SD, 1.03+/-0.08 mmol/L; reference value, 1.10-1.30) and increased, but not normalized, after 2 days. Hypocalcemia was only occasionally seen in the surgical patients. In the septic patients, urinary excretion of calcium was low; and, in both patient groups, elevated concentrations of two markers of bone resorption, deoxypyridinoline and ICTP (serum carboxy-terminal cross-linked telopeptide of type I collagen), were found. In cases of sepsis, the concentrations of proinflammatory cytokines were high (394+/-536 pg/mL for tumor necrosis factor-alpha and 5676+/-5190 pg/mL for interleukin-6, both normally <10-20). The Ca2+ concentration was inversely related to tumor necrosis factor-alpha and interleukin-6 (r2 = .35-.42; p<.01), as well as to procalcitonin (r2 = .71; p<.01). Despite normocalcemia in the surgical patients, serum PTH concentrations were elevated in both patient groups (97 and 109 ng/L) (reference value, <55 ng/L), both on day 1 and day 3 in the ICU. The citrate/calcium infusion revealed an increased secretory response of PTH to lowered Ca2+ concentrations in both groups of patients (p<.05), when compared with matched healthy controls. CONCLUSION: Hypocalcemia was common in septic ICU patients and was not the result of an increased urinary excretion of calcium or of an attenuated bone resorption, but seemed related to the inflammatory response. An increased PTH secretion was found in both patient groups.

PET imaging of adrenal cortical tumors with the 11beta-hydroxylase tracer 11C-metomidate.

UNLABELLED: The purpose of the study was to evaluate PET with the tracer 11C-metomidate as a method to identify adrenal cortical lesions. METHODS: PET with 11C-metomidate was performed in 15 patients with unilateral adrenal mass confirmed by CT. All patients subsequently underwent surgery, except 2 who underwent biopsy only. The lesions were histopathologically examined and diagnosed as adrenal cortical adenoma (n = 6; 3 nonfunctioning), adrenocortical carcinoma (n = 2), and nodular hyperplasia (n = 1). The remaining were noncortical lesions, including 1 pheochromocytoma, 1 myelolipoma, 2 adrenal cysts, and 2 metastases. RESULTS: All cortical lesions were easily identified because of exceedingly high uptake of 11C-metomidate, whereas the noncortical lesions showed very low uptake. High uptake was also seen in normal adrenal glands and in the stomach. The uptake was intermediate in the liver and low in other abdominal organs. Images obtained immediately after tracer injection displayed high uptake in the renal cortex and spleen. The tracer uptake in the cortical lesions increased throughout the examination. For quantitative evaluation of tracer binding in individual lesions, a model with the splenic radioactivity concentration assigned to represent nonspecific uptake was applied. Values derived with this method, however, did show the same specificity as the simpler standardized uptake value concept, with similar difference observed for cortical versus noncortical lesions. CONCLUSION: PET with 11C-metomidate has the potential to be an attractive method for the characterization of adrenal masses with the ability to discriminate lesions of adrenal cortical origin from noncortical lesions.

HandPort-assisted laparoscopic splenectomy in massive splenomegaly.

BACKGROUND: Laparoscopic splenectomy of normal-sized spleens is performed with increasing frequency. By using a handPort, which allows the intraperitoneal introduction of one surgeon's hand, massively enlarged spleens may also be extirpated via a laparoscopy-assisted technique. METHODS: Seven patients (54-80 years) with massive splenomegaly (3.5-5.8 kg) underwent handPort-assisted laparoscopic splenectomy. All patients had spleens that extended beyond the umbilicus, hypersplenism, and discomfort in the upper left quadrant due to intractable hematological malignancy. RESULTS: Both the operation and recovery were uneventful in five of the patients, but one patient had to be converted to an open procedure due to splenic damage and bleeding, and another was reoperated for hemorrhage from a trocar. The handPort allowed splenic protection while the trocars were introduced and instruments changed. It also enabled splenic mobilization, particularly prior to stapling of the hilar structures and dissection of the upper splenic pole. CONCLUSIONS: HandPort-assisted laparoscopic splenectomy seems to be a viable alternative for massive splenomegaly, but it requires further evaluation with respect to safety, efficacy, and indication.

Endothelial vasodilatory dysfunction in primary hyperparathyroidism is reversed after parathyroidectomy.

BACKGROUND: Primary hyperparathyroidism (HPT) is accompanied by hypertension and a cardiovascular mortality. Impaired endothelium-dependent vasodilatation (EDV) occurs in hypertension but has not been fully investigated in HPT despite the vasoactive influences of parathyroid hormone. METHODS: Twenty-five HPT patients and 25 normocalcemic control subjects, matched for age and gender, underwent forearm venous occlusion plethysmography. EDV and endothelium-independent vasodilatation (EIDV) were evaluated during local infusion of metacholine (2 and 4 micrograms/min) and nitroprusside (5 and 10 micrograms/min), respectively. The endothelial function index was calculated as the ratio of forearm blood flows during the high doses of metacholine and nitroprusside. Ambulatory 24-hour blood pressures and thickness of the intima-media complex of the carotid arteries were also measured; the latter is considered an early marker of atherosclerosis. RESULTS: Endothelial function index was lower in the HPT patients compared with control subjects (1.01 +/- 0.26 vs 1.27 +/- 0.31, P = .003). Reinvestigation 10 months after parathyroidectomy showed normalization of the index (1.31 +/- 0.39, P = .01) due to a numeric increase in EDV and decrease in EIDV. The carotid intima-media thickness and blood pressure were similar in the groups and unaltered postoperatively. CONCLUSIONS: Endothelial vasodilatory dysfunction is another indicator of the vascular disturbance of HPT and can be normalized by parathyroidectomy.

Abdominal US for diagnosis of pancreatic tumor: prospective cohort analysis.

PURPOSE: To elucidate the accuracy of abdominal ultrasonography (US) in the diagnosis of pancreatic tumors. MATERIALS AND METHODS: In all patients referred for pancreatic US during 1988-1990, data on malignant disease and survival were analyzed by using the Swedish Death and Cancer Registries. Nine hundred nineteen patients were entered into the analysis. In 140 of them, a clinical diagnosis of tumor in the pancreatic area was confirmed within 1 year after US. These tumors were primary pancreatic tumors (n = 102), common bile duct and duodenal cancers (n = 17), and metastases in the pancreatic area (n = 21). RESULTS: The sensitivity of US in the detection of all tumors in the pancreatic area was 88.6% (124 of 140 patients), which was similar to that for the detection of exocrine pancreatic cancer, 90% (79 of 88 patients). There were nine false-positive US examinations, for a specificity of 98.8% (770 of 779 patients). Systematic sampling of 94 investigations confirmed an association between US accuracy and presence of clinical symptoms of pancreatic cancer. Significant differences in the sensitivity (P < .05) and accuracy (P < .01) of diagnosis were observed between three experienced investigators. CONCLUSION: Study results support the use of US as a first-line diagnostic examination in patients suspected of having pancreatic tumor. Dependency on the investigator's experience with US mandates continuous evaluation of its performance.

Breathing obstruction in relation to craniofacial and dental arch morphology in 4-year-old children.

The prevalence of breathing obstruction was determined in a cohort of 4-year-old children. Craniofacial morphology was studied in obstructed children and compared with data from a control group of 4-year-old children with ideal occlusion. Dental arch morphology was compared in obstructed and non-obstructed children in the group. Parents of 95.5 per cent of the study base of 644 children answered a questionnaire concerning their child's nocturnal behaviour and related questions. The 48 children who, based on parental report, snored every night or stopped breathing when snoring (the 'snoring group'), showed a higher rate of disturbed sleep, mouth-breathing, and a history of throat infections as compared with the rest of the cohort. These children were examined by both an orthodontist and an otorhinolaryngologist and, when indicated, they were also monitored in a sleep laboratory. Twenty-eight of the children were diagnosed as having a breathing obstruction (4.3 per cent of the cohort) and six children (0.9 per cent) had sleep apnoea (mean apnoea-hypopnoea index of 17.3), using the same definition as that for adults. Cephalometric values among the obstructed children differed from those of a Swedish sample of the same age with ideal occlusion. Thy had a smaller cranial base angle and a lower ratio of posterior/anterior total face height. Small, but not significant differences were seen for NSL-ML and NL-ML. Compared with 48 asymptomatic children from the same cohort, the obstructed children had a narrower maxilla, a deeper palatal height, and a shorter lower dental arch. In addition, the prevalence of lateral crossbite was significantly higher among the obstructed children.