Clinical Characteristics of Necrotizing Enterocolitis Diagnosed by Independent Adjudication of Abdominal Radiographs, Laparotomy, or Autopsy in Preterm Infants in the "Connection Trial".

OBJECTIVE: Necrotizing enterocolitis (NEC) classically is diagnosed by radiographic demonstration of pneumatosis intestinalis/portal venous gas (PI/PVG). This study examines clinical characteristics of NEC confirmed by independent evaluation of abdominal radiographs, taken for clinical signs of NEC, or by pathologic findings at laparotomy or autopsy (confirmed NEC [cNEC]). STUDY DESIGN: The investigated cohort included 1,382 extremely low birth weight (BW) infants (BW range: 500-1,000 g) with median 27 weeks (range: 23-32) gestational age (GA) at birth. They were randomized into the placebo-controlled "Connection Trial" of the new biological drug candidate IBP-9414 with cNEC as one primary endpoint. RESULTS: Total 119 infants (8.6%) had cNEC diagnosed at median 14 days of age by confirming PI/PVG at X-ray adjudication (n = 111) and/or by surgery/autopsy (n = 21). Sixteen percent of cNEC cases died. Adverse events of NEC were reported in 8.5% of infants and 4.1% had NEC diagnosed by radiology and surgery/autopsy at the participating centers. Regression analyses showed that the risk of cNEC decreased by 11 to 30% for every 100-g increment in BW and single-week increment in GA and associated cNEC with odds ratios (ORs) > 2.0 for gastrointestinal (GI) perforation and obstruction, hypotension, hypokalemia, hypophosphatemia, and death. Comparing risks of cNEC in infants below and above 750-g BW showed higher ORs (2.7-4.3) for GI perforation, hypotension, hypokalemia, and renal complications in the smaller infants, whereas the bigger infants had higher ORs (1.9-3.2) for serious non-GI events, late-onset sepsis (LOS), and death. Predictors of cNEC (hazard ratio, HR > 1.5) included serious non-GI events (mainly infections), hyponatremia, and hyperglycemia, whereas the HR was 0.52 for intravenous antibiotics. After cNEC diagnosis, there were higher rates of GI perforation and obstruction, hypotension, hypokalemia, and LOS. CONCLUSION: Independent adjudication of abdominal radiographs increased radiological recognition of NEC and proved to be feasible in a multicenter study setting as well as able to diagnose clinically relevant NEC. KEY POINTS: · Independent adjudication of abdominal radiographs in ELBW infants increased NEC recognition.. · Risk of NEC decreased by 11 to 30% with every 100-g increment in BW and GA week.. · In infants with BW 750 to 1,000 g, the risk of death from NEC was almost twice that in infants with BW 500 to 749 g. · Infants with NEC received antibiotics during one-third and parenteral nutrition during half of the first 7 postnatal weeks..

Progression of Enteral Feeding Volumes in Extremely Low Birth Weight Infants in the "Connection Trial".

OBJECTIVE: Investigate daily feeding volumes and their association with clinical variables in the early postnatal care of premature infants of the "Connection Trial." STUDY DESIGN: A total of 641 infants of 510 to 1,000-g birth weight (BW, mean: 847 g) and mean 27 weeks' gestational age at birth (GA) were analyzed for total daily enteral (TDE) feeding volumes of 10, 20, 40, 80, and 120 mL/kg/d and their association with 24 clinical variables. Uni- and multivariable Cox regression models were used to calculate hazard ratios (HR) with 95% confidence intervals as a measure of the chance of reaching each of the TDE volumes. RESULTS: Daily feeding volumes were highly variable and the median advancement from 10 to 120 mL/kg/d was 11 mL/kg/d. Univariable analyses showed the lowest chance (HR, 0.22-0.81) of reaching the TDE volumes for gastrointestinal (GI) serious adverse events (SAEs), GI perforation, GI obstruction, and necrotizing enterocolitis, as well as respiratory SAEs, persistent ductus arteriosus, and hypotension. Each GA week, 100-g BW, and point in 5-minute Apgar score at birth associated with 8 to 20% increased chance of reaching the TDE volumes. Multivariable analyses showed independent effects for BW, GA, Apgar score, GI SAEs, abdominal symptoms/signs, respiratory SAEs, days on antibiotics, and hypotension. CONCLUSION: This observational analysis demonstrates the variable and cautious progression of enteral feedings in contemporary extremely low BW infants and the extent to which clinical variables associate with this progression. KEY POINTS: · Total feedings of 10 and 120 mL/kg/d were reached at median 4 and 14 day of age, respectively, and at a daily increase of 11 mL/kg.. · Each incremental GA week, 100-g BW, and point in 5-minute Apgar score associated with 8 to 20% increased chance of reaching enteral feedings of 10 to 120 mL/kg/d.. · Progression of enteral feeding associated with several clinical events and was slower than advocated in common feeding protocols..

Disturbances of calcium homeostasis consistent with mild primary hyperparathyroidism in premenopausal women and associated morbidity.

CONTEXT: Primary hyperparathyroidism (PHPT) and associated morbidity are comprehensively assessed in elderly females; however, less is known of the disease in younger women. OBJECTIVES: Our objectives were to estimate the prevalence of mild disturbances in calcium homeostasis, which could be analogous with early PHPT, in a premenopausal population, and determine the potential presence of associated morbidity. DESIGN: Initial results from this longitudinal study are from 2002-2004. SETTING: We conducted a population-based screening of serum (s)-calcium in conjunction with routine mammography. PARTICIPANTS: Participants included premenopausal women, 40-50 yr of age (n = 1900). Cases fulfilling previously evaluated biochemical criteria for PHPT (n=214) were matched to controls (n = 214). MAIN OUTCOME MEASUREMENTS: All participants underwent investigation, including screening of parameters of calcium homeostasis, dual x-ray absorptiometry, and body mass index assessment, and filled out extensive health and quality of life (SF-36) questionnaires. Participants were divided into four groups depending on the relation between s-calcium/intact PTH. Statistical comparisons between cases and controls as well as among the four groups were performed to evaluate morbidity. RESULTS: The prevalence of assumed mild PHPT, i.e. inappropriate intact PTH value in relation to total s-calcium, was estimated to be 5.1% (n = 96). Women with mild disturbances in calcium homeostasis had statistically significant lower bone mineral density in the proximal femur and femoral neck, higher body mass index, and lower scores for vitality and general health in the analysis of SF-36. CONCLUSIONS: Mild disturbances in calcium homeostasis in premenopausal women were more prevalent than previously thought and were associated with obesity, lower bone mineral density, and decreased quality of life.

Metabolic abnormalities in patients with normocalcemic hyperparathyroidism detected at a population-based screening.

OBJECTIVE: Dyslipidemia, hypertension, diabetes mellitus and also primary hyperparathyroidism (pHPT) are associated with an increased risk of cardiovascular diseases. Metabolic abnormalities in mild pHPT have been reported, but never in cases with normal calcium and high parathyroid hormone (PTH) levels, i.e. suffering from 'normocalcemic pHPT'. Our aim was to explore the occurrence of these metabolic abnormalities in individuals with normocalcemic pHPT identified in a population-based screening, and the effects of parathyroidectomy vs conservative treatment on metabolic variables. DESIGN AND METHODS: A population-based screening of 5202 post-menopausal women identified 30 patients with normal calcium, inappropriately high PTH and normal creatinine. A 5-year follow-up included 15 parathyroidectomized (PTx) and nine conservatively followed cases, in a non-randomized setting, together with age-matched controls. Biochemical variables and body mass index (BMI) were investigated. RESULTS: At study entry, cases had higher calcium, PTH, glucose, low-density lipoprotein (LDL)/high-density lipoprotein (HDL)-cholesterol, very low-density lipoprotein (VLDL)-cholesterol, total triglycerides, and BMI compared to controls (P = < 0.0001-0.035). The cases had a lower HDL-cholesterol value (P = 0.013) and one third of the cases had hypertriglyceridemia. During follow-up, the PTx cases decreased in calcium, PTH, LDL/HDL-cholesterol, total and LDL-cholesterol (P = 0.0076-0.022). Investigated biochemical variables remained adverse in conservatively followed cases during follow-up except a decreased LDL-cholesterol value. All surgically treated patients had parathyroid adenoma. CONCLUSIONS: Cases with normocalcemic pHPT have increased proatherogenic lipoprotein levels, BMI and glucose levels compared to age-matched controls. Parathyroidectomy has positive effects on some of these variables and reverses them to the same level as the controls, while conservative treatment fails to normalize the investigated metabolic variables.

Maintained normalization of cardiovascular dysfunction 5 years after parathyroidectomy in primary hyperparathyroidism.

BACKGROUND: Primary hyperparathyroidism (pHPT) has been associated with premature death in cardiovascular diseases. Short-term prospects for normalization of cardiovascular derangements have been described after parathyroidectomy. This study explores long-term effects of parathyroidectomy on cardiovascular functions in pHPT. METHODS: Thirty consecutive patients with pHPT were reexamined 1 and 5 years after parathyroidectomy, together with 30 matched controls, with echocardiography and a bicycle exercise test. RESULTS: Serum calcium was normal in all patients and control subjects at follow-up. The maximal blood pressure during the exercise was higher before parathyroidectomy (median 223 [range, 200-268] mm Hg vs 202 [165-277] mm Hg, P < .05) but not 5 years after (230 [155-270] mm Hg vs 219 [165-252] mm Hg. The ST-segment depression diminished from -1.4 (-8.3-0) to -0.8 (-3.3-0) mm 1 year after parathyroidectomy and further to -0.1 (-3.3-0.0) mm after 5 years but was unchanged in the control group. The number of ventricular extrasystolic beats at exercise testing in the pHPT group before parathyroidectomy was higher than in the control group (1 [0-340] vs 0 [0-3]). The isovolemic relaxation time at rest was prolonged before parathyroidectomy (mean 100 +/- 17 ms [SD] vs 89 +/- 14 ms, P < .05). CONCLUSION: Parathyroidectomy can induce long-lasting improvement in regulation of blood pressure, left ventricular diastolic function, cardiac irritability (ventricular extrasystolic beats), and other signs of myocardial ischemia, with potential implications for the postoperative life expectancy of patients with pHPT who have undergone parathyroidectomy.

Clinical presentation of primary hyperparathyroidism in Europe--nationwide cohort analysis on mortality from nonmalignant causes.

Primary hyperparathyroidism (PHPT) in developing countries is characterized by severe skeletal and renal complications and apparent mortality. This is in contrast with the Western hemisphere where research interests, rather than characteristics of PHPT, seem to differ between regions. In Europe, the "nontraditional" aspects of mild-to-moderate PHPT have attracted particular attention. These symptoms and signs include risk factors for cardiovascular disease such as hypertension, phenotype IV lipoproteinemia, insulin resistance, cardiac and vascular dysfunction, and morbidity in cardiovascular diseases. Mortality in cardiovascular diseases has been found to be increased in studies that include over 6500 European patients; this risk could not be verified in North American patients. By use of the nationwide Cancer Registry and Causes-of-Death Registry, mortality was analyzed in 10,995 Swedish patients (> 20 years of age) subjected to extirpation of single parathyroid adenoma of PHPT during 1958-1997. The Swedish population standardized for age, sex, and calendar year was used as control. The first postoperative year was excluded from the analysis. In total, the study included 102,515 observed person-years in the patients. Results verify an increased risk of dying after operation for PHPT (standard mortality ratio, 1.2; 95% CI, 1.19-1.27). The increased risk persisted far beyond 15 years postoperatively and occurred in both sexes and in all investigated age groups. Principal causes of excess mortality were cardiovascular diseases, diabetes mellitus, and urogenital diseases in all age groups. However, in patients operated on between 1985 and 1997 (n = 6386), overall mortality did not differ from that of the normal population, although there was maintained excess death in stroke, diabetes mellitus, and urogenital diseases. These findings infer that modern paradigms of surgical treatment normalize the risk of dying from PHPT. This improvement may be a late consequence of liberalized calcium screenings that were introduced about 30 years ago and indicate that operation at early disease stages may offer a survival advantage. An association between diabetes mellitus and PHPT is substantiated.

Loss of heterozygosity in parathyroid glands of familial hypercalcemia with hypercalciuria and point mutation in calcium receptor.

Development of sporadic parathyroid tumors is accompanied by loss of heterozygosity (LOH) on several chromosomes like 1p, 1q, 6q, 11q, and 15q. Here, we investigate a unique variant of familial hypercalcemia, unrelated to multiple endocrine neoplasia and hyperparathyroidism-jaw tumor syndromes, with hypercalcemia due to a point mutation in the intracellular part of the calcium receptor (CaR) gene. The hypercalcemia and hypercalciuria of the family is accompanied by age-related growth of the parathyroid glands and transition from diffuse to nodular parathyroid hyperplasia. Genome-wide screening for allelic loss was performed on nine enlarged parathyroid glands (weighing 40-680 mg) from eight parathyroidectomized members of the family (aged 22-66 yr). Using 139 fluorescent- or (32)P-labeled microsatellite markers, informative results were obtained on all examined chromosome arms and 1p, 1q, 6q, 11q, and 15q were investigated more closely. All parathyroid glands displayed allelic loss on at least one chromosomal arm (range 1-7). Most of the common loci for allelic loss corresponded to findings in sporadic parathyroid tumors, but the unique variant of familial hypercalcemia also exhibited frequent LOH on 12q (67%) and 7q (44%). LOH could not be detected at 3q, where the CaR gene is located, and additional somatic mutations in exons 2-7 of the CaR gene was not found by sequencing. The point mutation resulting in alteration of the intracellular portion of CaR seems to cause sensitivity to secondary genetic hits, with increased frequency of allelic loss (P < 0.01, r(2) = 0.66) and weight of parathyroid tumors with age in this family.

Transfection of the multiple endocrine neoplasia type 1 gene to a human endocrine pancreatic tumor cell line inhibits cell growth and affects expression of JunD, delta-like protein 1/preadipocyte factor-1, proliferating cell nuclear antigen, and QM/Jif-1.

In the absence of metastases or overgrowth to adjacent organs, the lack of reliable markers for malignancy is a well-recognized problem for clinicians managing patients with endocrine tumors. Apart from inactivation of the multiple endocrine neoplasia type 1 (MEN1) gene, the molecular mechanisms involved in tumorigenesis of the endocrine organs and MEN1-associated nonendocrine lesions are vastly unknown. To try to learn more about down-stream effects on MEN1 gene inactivation, we used the BON1 cells, showing low levels of endogenous menin, and transfected them with a MEN1 gene construct. On restoring the menin expression, we recorded inhibition of cell growth. We also performed macroarray and present data on differentially expressed genes in the transfected cells, after corroboration by Northern blots and quantitative PCR. JunD was up-regulated in menin-expressing clones, whereas delta-like protein 1/preadipocyte factor-1 (involved in differentiation and growth of the pancreatic endocrine cells), proliferating cell nuclear antigen, and QM/Jif-1 (a negative regulator of c-Jun) became down-regulated. These findings might contribute to the understanding of the tissue-specific features of MEN1. We also show that homozygous inactivation of the MEN1 gene statistically correlates to higher expression of delta-like protein 1/preadipocyte factor-1, proliferating cell nuclear antigen, and QM/Jif-1, as well as lower MEN1 expression, in a limited sample of malignant endocrine pancreatic tumors.

Mortality in sporadic primary hyperparathyroidism: nationwide cohort study of multiple parathyroid gland disease.

BACKGROUND: The risk of dying from primary hyperparathyroidism (pHPT) is controversial and has been explored mainly in single parathyroid gland disease. The present study investigates mortality in pHPT due to multiple parathyroid gland disease. METHODS: We used the nationwide Swedish In-patient Register and Cause-of-Death Registry to compare the mortality in 3485 Swedish patients subjected to parathyroidectomy during 1964 to 1999 with that of the Swedish population (standardized for age, gender, and calendar year). The patient cohort includes 36,596 person years. RESULTS: Increased risk of death beyond the first postoperative year (standardized mortality ratio, 1.4; 95% CI, 1.37-1.52) was found in both sexes and for all age intervals below 80 years. The increased risk persisted more than 15 years postoperatively and related to cardiovascular diseases, diabetes mellitus, urogenital diseases, and malignant disorders. The increased risk of dying in cardiovascular diseases normalized during 1990 to 1999. CONCLUSIONS: pHPT caused by multiple parathyroid gland enlargement is associated with an excessive mortality similar to pHPT of single parathyroid adenoma. The findings substantiate that modern modes of surgical treatment for pHPT normalize the risk of dying from cardiovascular complications and that the hyperpararthyroid state per se is the possible cause of the premature death.

Parathyroidectomy in familial hypercalcemia with clinical characteristics of primary hyperparathyroidism and familial hypocalciuric hypercalcemia.

BACKGROUND: Familial primary hyperparathyroidism is associated with tumor-susceptibility syndromes, which are unrelated to mutations in the calcium receptor gene. This study describes parathyroidectomy in a kindred with hypercalcemia due to a heterozygous point mutation in the calcium receptor gene. METHODS: Seventeen family members were studied, and postoperative follow-up averaged 5.1 years. RESULTS: Radical parathyroid resection with total parathyroid remnants of 10 to 20 mg or total parathyroidectomy with autotransplantation normalized the serum calcium and parathyroid hormone values in 12 family members. Persistent hypercalcemia was noted in 3 of 5 patients subjected to less radical procedures. Diffuse to nodular hyperplasia and microscopic findings, interpreted incorrectly as a single adenoma, were found. Weight of the parathyroid tissue increased with the age of the patients (P <.05), and almost one third of them (29%) had 1 to 3 atypically located glands. There were no patients with recurrent hypercalcemia during follow-up. CONCLUSIONS: The heterozygous inactivating mutation of the calcium receptor gene of this family is accompanied by mild increases in parathyroid gland x weight and diffuse parathyroid hyperplasia with possibly secondary genetic events causing nodule formation. Radical parathyroid resection is advocated in this hypercalcemic disorder, which may represent an intermediary stage between primary hyperparathyroidism and familial hypocalciuric hypercalcemia.

Circadian cardiac autonomic nerve dysfunction in primary hyperparathyroidism improves after parathyroidectomy.

BACKGROUND: Primary hyperparathyroidism has been associated with premature death in cardiovascular diseases, but reversibility and background mechanisms are uncertain. This study investigates autonomic nervous function in hyperparathyroidism because disturbances in this respect have been related to increased cardiovascular morbidity. METHODS: Twenty-one consecutive patients with hyperparathyroidism and 23 matched control subjects without interfering medication underwent electrocardiographic recordings and ambulatory blood pressure (ABP) determination during a 24-hour period. Patients were re-examined at normocalcemia 1 year after parathyroidectomy. Heart rate variability was analyzed in subjects with sinus rhythm and normal atrioventricular conduction; time domain measures were calculated from the RR-intervals, and frequency domain variables were obtained with an autoregressive algorithm, which expressed power distribution (high, low, or very low frequency). RESULTS: Nocturnal increase in low frequency was blunted in cases versus control subjects (103+/-128 m(2) vs 430+/-171 m(2); P=.03). Very low frequency at nighttime correlated inversely with serum parathormone (r=-0.33; P<.05) and increased postoperatively (P=.03). ABP was higher both at daytime and nighttime (P<.05) in patients and remained unchanged after surgery. Systolic ABP correlated with the parathormone (r=0.47; P<.01). CONCLUSION: Results suggest altered circadian autonomic function in hyperparathyroidism that can improve after parathyroidectomy. Despite elevated blood pressure, ABP shows retained diurnal rhythm, which indicates different pathophysiologic mechanisms behind the 2 predictors of cardiovascular death in hyperparathyroidism.

Multiple endocrine neoplasia type 1 polymorphism D418D is associated with sporadic primary hyperparathyroidism.

BACKGROUND: Sporadic primary hyperparathyroidism (pHPT) occurs separately and in several hereditary disorders including multiple endocrine neoplasia type 1. Irradiation to the neck, female gender, and age are well-identified risk factors that predispose to pHPT. The multiple endocrine neoplasia type 1 gene is the most commonly deranged gene in parathyroid adenomas and contains several polymorphisms including D418D with a prevalence of roughly 50%. METHODS: We genotyped 162 pHPT patients and control participants to evaluate if the D418D polymorphism is related to development of pHPT. One hundred fourteen of the pHPT patients and control participants were recruited from a health screening and were subjected to measurement of bone mineral density (BMD) at the lumbar spine, femoral neck, and total body. RESULTS: The prevalence of each genotype (ie, MM, Mm, and mm) was for all pHPT patients: 62%, 29%, and 9%; and for all control participants: 32%, 43%, and 25% (P <.0004). For the screening-detected pHPT patients and control participants, the genotype distribution for MM, Mm, and mm was 60%, 30%, and 10%; and 31%, 44%, and 25%, respectively (P =.009). In the screening-recruited control participants, but not in pHPT patients, the MM genotype was also associated with higher total body BMD (P =.01) and BMD at the femoral neck (P =.02), whereas it failed to be significant for BMD at the lumbar spine (P =.08). CONCLUSIONS: We report that the MM genotype was overrepresented in pHPT patients compared with control participants, suggesting a novel marker for pHPT. Furthermore, the MM genotype was associated with higher BMD at the femoral neck and in the total body in the screening-recruited control participants.

In situ RNA-RNA hybridisation of phospholipase C beta 3 shows lack of expression in neuroendocrine tumours.

BACKGROUND: Phospholipase C beta 3 (PLCB3) plays an important role in the signal transduction of the seven transmembrane receptors. The gene is located in the vicinity of the Multiple Endocrine Neoplasia type 1 (MEN1) gene on chromosome 11q13. Transfection of PLCB3 to neuroendocrine cell lines lacking expression suppresses the neoplastic phenotype and affects the gene expression of S100A3 and human mismatch repair protein, suggesting a role for PLCB3 in neuroendocrine tumorigenesis. MATERIALS AND METHODS: We used RNA-RNA in situ hybridisation for PLCB3 on a total of 82 samples including 34 from MEN1 patients. RESULTS: We show that the PLCB3 transcript is missing in 8 out of 14 MEN1-associated neoplasias as well as in 4 out of 10 bronchial carcinoids, 2 out of 10 exocrine pancreatic cancers and one sporadic adrenocortical carcinoma. CONCLUSION: Low or lack of PLCB3 expression in a subset of endocrine tumours, together with earlier published in vitro data on suppressor characteristics upon transfection, indicate that PLCB3 could be involved in the tumorigenesis in a subset of endocrine tumours.

[Management of asymptomatic primary hyperparathyroidism. New North American guidelines discussed from a Swedish perspective]. / Handläggning av asymtomatisk primär hyperparatyreoidism. Nya nordamerikanska rekommendationer diskuteras i ett svenskt perspektiv.

Primary hyperparathyroidism (HPT) is a common endocrine disease, in most cases without obvious symptoms of hypercalcemia and parathyroid hormone excess. The only curative treatment outside clinical trials is parathyroidectomy. Many patients are undiagnosed and left untreated, and the indications for curative treatment are still controversial. In 1990, NIH presented recommendations on the management of asymptomatic HPT, which was defined as HPT without symptoms and signs of renal or bone disease. Since then many studies have shed new light on mainly the cardiovascular complications and increased mortality of the disease, and the 1990 recommendations have been questioned. A workshop in 2002 revised the recommendations for handling of asymptomatic HPT in the United States. These recommendations are discussed from a Swedish perspective together with recent data on mortality in a large Swedish HPT cohort.

Multiple brown tumours of the upper extremity in a patient with secondary hyperparathyroidism as a result of chronic renal failure.

A man with chronic renal failure was referred to the hand clinic because of massive osteolytic tumours in his right arm. Secondary hyperparathyroidism and brown tumours were suggested, and he was treated by subtotal parathyroidectomy. Rapid reduction of the vast tumours was noted postoperatively.

Association of parathyroid adenoma and pregnancy with preeclampsia.

OBJECTIVE: Case reports have described associations between calcium metabolism disturbances and primary hyperparathyroidism with preeclampsia, suggesting parathyroid involvement in preeclampsia etiology. This study examines whether parathyroid adenoma, the main cause of hyperparathyroidism, diagnosed and treated before pregnancy is associated with preeclampsia. DESIGN: We conducted a register-based study to assess the association between parathyroid adenoma and subsequent preeclampsia. SETTING: Births among Sweden's general population were studied. POPULATION: The study population included 52 women with a diagnosis of parathyroid adenoma and 519 without, all of whom had a subsequent singleton pregnancy between 1973 and 1997. METHODS: We performed a conditional logistic regression investigating the association of parathyroid adenoma with subsequent preeclampsia in the first singleton pregnancy with adjustment for potential confounding factors. MAIN OUTCOME MEASURE: The main outcome was a diagnosis of preeclampsia that does not include women with prior chronic hypertension. To ensure that treatment of parathyroid adenoma was completed before pregnancy, those with a diagnosis of parathyroid adenoma made less than 2 yr before delivery (and the matched comparison women) were excluded. RESULTS: Statistically, parathyroid adenoma prior to delivery is significantly (P < 0.001) associated with preeclampsia, producing an adjusted odds ratio of 6.89 (95% confidence interval, 2.30, 20.58). CONCLUSION: A history of parathyroid adenoma should be viewed as a risk for preeclampsia.

Monoclonal Antibodies Recognizing Normal and Neoplastic Human Adrenal Cortex.

Four monoclonal antibodies (MAb) were generated by immunization of mice with dispersed cells from normal human adrenal gland (Na) and adrenocortical adenoma causing cortisol excess (Ac). Immunohistochemically reacted cryosections revealed differential labeling of the normal cortical parenchyma, and immunofluorescence on dispersed cells displayed that Ac5 alone labeled the cell surface. Immunoprecipitation demonstrated that the antibodies recognized apparently different structures of 51-88 kDa. Immunohistochemical examination of several normal human tissues substantiated restricted reactivity, especially for the Na2 and Na7 antibodies, and that the adrenal medulla was not stained by any of the antibodies. The antibodies recognized the vast majority of the parenchymal cells of cortical adenomas (n = 21). Each antibody also reacted with all adrenocortical carcinomas (n = 17), and the staining generally was most intense and extensive with Na7. Analysis of other pathological human tissues revealed highly restricted reactivity for the Na2 antibody. Na2 and Na5 failed to stain 17 renal cell carcinomas. None of the antibodies recognized pheochromocytomas. These antibodies may lead to improved histological recognition and characterization of human adrenal lesions.

Long-term survival of patients with small intestinal carcinoid tumors.

Midgut carcinoid tumors are rare and have a markedly better prognosis than adenocarcinoma in the small intestine. New diagnostic methods and medical as well as surgical therapies have evolved during the last decades, leading to more active care of these patients. Patients with small intestinal carcinoids diagnosed from 1960 to 2000 in the duodenum (n = 89) and jejunum/ileum (n = 2437) were identified in the Swedish Cancer Registry. Cases without histologic verification and autopsy cases were excluded. Overall, cause-specific and relative survival were calculated. The overall 5-, 10-, and 15 year survivals were, respectively, 60%, 46%, and 28% for duodenal tumors and 56%, 36%, and 23% for jejunal/ileal tumors. Cause-specific 5-, 10-, and 15-year survival was 94% for all three follow-up periods for duodenal tumors and 87%, 80%, and 77% for those in the jejunum/ileum. The corresponding relative survivals were, respectively, 72%, 67%, and 51% for duodenal tumors and 67%, 54%, and 44% for those in the jejunum/ileum. Sex did not influence overall or cause-specific survival. The age at diagnosis correlated inversely with overall and cause-specific survival for tumors in the jejunum/ileum. For tumors in the jejunum/ileum, the overall and cause-specific survival correlated with the time period of diagnosis, with a more favorable prognosis for those diagnosed in recent years. A multivariate Cox proportional hazards model showed similar results. We concluded that young age and diagnosis in recent years are positive predictors of survival for patients with midgut carcinoids. The divergence between cause-specific and relative survival implies the need for a more detailed analysis of the causes of death of these patients.