The effect of lipoic acid and vitamin E therapies in individuals with the metabolic syndrome.

The metabolic syndrome is associated with abnormal glucose and lipid metabolism, insulin resistance, increased oxidative stress and pro-inflammatory activity that increase the risk of type 2 diabetes and cardiovascular disease. The aim of this study was to investigate the effect of treatment with the antioxidant α-lipoic acid (ALA) with or without vitamin E supplementation, on markers of insulin resistance and systemic inflammation and plasma nonesterified fatty acid (NEFA) concentrations in individuals with the metabolic syndrome. In a randomized, double-blind, placebo-controlled trial, subjects with the metabolic syndrome received ALA (600 mg/day, n = 34), vitamin E (100 IU/day, n = 36), both ALA and vitamin E (n = 41), or matching placebo (n = 40) for 1 year. Fasting circulating concentrations of glucose and insulin were measure every 3 months and NEFA, markers of inflammation, adiponectin and vitamin E were measured at 6 monthly intervals. Plasma NEFA concentrations decreased [-10 (-18, 0)%] at a marginal level of significance (p = 0.05) in those who received ALA alone compared with placebo and decreased [-8 (-14, -1)% (95% CI)] significantly (P = 0.02) in participants who were randomised to ALA with and without vitamin E compared with those who did not receive ALA. Fasting glucose, insulin, homeostatic model assessment of insulin resistance, adiponectin, and markers of inflammation did not change significantly during the study. These data suggest that prolonged treatment with ALA may modestly reduce plasma NEFA concentrations but does not alter insulin or glucose levels in individuals with the metabolic syndrome.

Effects of white and red wine on endothelial function in subjects with coronary artery disease.

BACKGROUND: Levels of anti-oxidant polyphenols are higher in red than in white wine and are thought to contribute to the reduced cardiovascular risk associated with moderate consumption of wine observed in epidemiological studies. AIM: To compare the acute effects of acute ingestion of white and red wine on endothelial function in subjects with coronary artery disease (CAD). METHODS: Fourteen subjects with proven CAD were randomised to consume white and red wine with a light meal in a single blind cross-over study. Flow-mediated dilatation (FMD) of the brachial artery was measured using high-resolution ultrasonography. Endothelial function, lipid profile, plasma alcohol and polyphenols were measured at baseline, 60 and 360 min after wine consumption. RESULTS: At baseline, FMD was similar (white wine 1.6 +/- 1.9%, red wine 1.8 +/- 1.7%). At 360 min after ingestion of wine there was no difference in FMD, which improved nearly threefold after both wines (white wine 4.7 +/- 2.2%, red wine 3.4 +/- 2.9%; P = 0.002). There was no detectable change in plasma polyphenol levels after either wine. CONCLUSIONS: These data suggest that wine acutely improves endothelial function in patients with CAD. This improved endothelial function might contribute to a reduced risk of cardiovascular events.

Effect of changing from a cellulose acetate to a polysulphone dialysis membrane on protein oxidation and inflammation markers.

BACKGROUND: In vitro, synthetic dialysis membranes induce less activation of blood components to produce pro-inflammatory cytokines and reactive oxygen species compared with cellulose acetate membranes. However, the long-term effect of switching from a cellulose-based dialysis membrane to a synthetic membrane on protein oxidation and systemic inflammation in hemodialysis patients is not well defined. METHODS: Nineteen patients receiving hemodialysis were followed prospectively after changing from a low-flux cellulose acetate membrane to a low-flux polysulphone membrane for 11-17 months (n = 15) and then returning to the cellulose acetate membrane for 1 month (n = 13). Plasma markers of protein oxidation, cell activation and systemic inflammation and concentrations of soluble cell adhesion molecules were measured at baseline and at the end of each intervention period. RESULTS: Plasma levels of protein thiols (18%), IL-6 (34%), VCAM-1 (33%), ICAM-1 (21%) and beta2-microglobulin (21%) increased significantly and dityrosine fluorescence (-36%), protein lipofuscin-like fluorophores (-18%) and TNF-alpha (-20%) decreased significantly in the patients after they switched to the polysulphone membrane. After reverting to the cellulose acetate membrane for 1 month, plasma levels of protein thiols and IL-6 returned to baseline while levels of other variables were not significantly different from values at the end of the polysulphone dialysis period. There was substantial intra-individual variation between 2 baseline measurements of plasma cytokines. CONCLUSIONS: Switching from a cellulose acetate membrane to a low-flux polysulphone dialysis membrane for a year or more may decrease the level of protein oxidation suggesting a decrease in oxidant stress and greater biocompatibility of the polysulphone membrane. The effect of this change in dialysis membrane on systemic inflammation is uncertain due to increases in some but not other inflammation-sensitive molecules.

Effect of hormone replacement therapy on inflammation-sensitive proteins in post-menopausal women with Type 2 diabetes.

AIMS: To test the effect of oral hormone replacement therapy (HRT) on plasma C-reactive protein (CRP), soluble vascular cell adhesion molecule-1 (VCAM-1), soluble intercellular adhesion molecule-1 (ICAM-1) and IL-6 concentrations and leucocyte count in post-menopausal women with Type 2 diabetes. METHODS: Post-menopausal women with Type 2 diabetes (n = 61) were randomized in a double-blind fashion to receive either continuous combined hormone replacement therapy (n = 29) with conjugated equine oestrogen (0.625 mg/day) plus medroxyprogesterone acetate (2.5 mg/day) or placebo (n = 32) for 6 months. Study variables were measured at baseline and at the end of the study. RESULTS: Eight women randomized to hormone replacement therapy and four women assigned to placebo group dropped out of the study. Plasma CRP increased (2.2 mg/l, 95% confidence interval 0.3-4.1 mg/l) significantly (P = 0.02) in women treated with HRT (n = 21) compared with placebo (n = 29) taking baseline CRP, body mass index (BMI) and smoking status into account. Plasma levels of cell adhesion molecules, IL-6 and leucocyte count did not change significantly during the study. CONCLUSIONS: These findings indicate that oral HRT with conjugated equine oestrogen plus medroxyprogesterone acetate increases plasma CRP levels but not necessarily global inflammatory activity in post-menopausal diabetic women. An increase in plasma CRP may potentially increase risk of a cardiovascular event.

Normal endothelial function after meals rich in olive or safflower oil previously used for deep frying.

BACKGROUND AND AIM: Polyunsaturated fats are more susceptible to oxidation during heating than monounsaturated fats but their effects on endothelial function when heated are unknown. The aim of this study was to compare the effect of meals rich in heat-modified safflower and olive oils on postprandial flow-mediated endothelium-dependent dilation (EDD) in healthy men. METHODS AND RESULTS: Flow-mediated EDD and glyceryltrinitrate-induced endothelium-independent dilation of the brachial artery were investigated in 14 subjects before and 4 hours after meals rich in olive oil and safflower oil used hourly for deep-frying for 8 hours in a double-blind crossover study design. There were high levels of lipid oxidation products (peroxides and carbonyls) in both heated oils. Plasma triglycerides were markedly increased at 4 hours after heated olive oil (1.26 +/- 0.43 vs 2.06 +/- 0.97 mmol/L) and heated safflower oil (1.44 +/- 0.63 vs 1.99 +/- 0.88 mmol/L). There was no change in EDD between fasting and postprandial studies and the response during the postprandial period was not significantly (p = 0.51) different between the meals (heated olive oil: 4.9 +/- 2.2% vs 4.9 +/- 2.5%; heated safflower oil: 5.1 +/- 3.1% vs 5.6 +/- 3.4%). CONCLUSIONS: Meals rich in olive and safflower oils previously used for deep frying and containing high levels of lipid oxidation products increase postprandial serum triglycerides without affecting endothelial function. These findings suggest that relatively short-term use of these vegetable oils for frying may not adversely affect postprandial endothelial function when foods containing the heat-modified oils are consumed.

Vitamin C improves endothelial dysfunction in renal allograft recipients.

BACKGROUND: Endothelial function is impaired in renal allograft recipients but the effects of antioxidant vitamin therapy on endothelial function in such patients is unknown. METHODS: Thirteen renal allograft recipients were randomized to vitamin C or placebo in a double blind cross-over study design. Flow-mediated endothelium-dependent dilation and glyceryltrinitrate-induced endothelium-independent dilation of the brachial artery were assessed before and 2 h after oral administration of 2 g vitamin C or placebo. RESULTS: Plasma vitamin C levels increased from 33.5+/-17.0 micromol/l to 98.8+/-60.2 micromol/l after treatment (P=0.0001). Endothelium-dependent dilation improved (from 1.6+/-2.6 to 4.5+/-2.5%) after vitamin C administration but was unchanged after placebo (1.9+/-1.5 to 1.8+/-2.5%; P=0.003 for vitamin C vs placebo). There was no significant change in endothelium-independent dilation in response to vitamin C. Vitamin C was also associated with a significant increase in the lag time in dilute serum oxidation (P=0.001). CONCLUSIONS: Vitamin C acutely improves flow-mediated, endothelium-dependent dilation and increases the resistance of lipoproteins in dilute serum to oxidation in renal transplant recipients.

Hormone-replacement therapy increases serum paraoxonase arylesterase activity in diabetic postmenopausal women.

The paraoxonase (PON1) enzyme is associated with high-density lipoproteins (HDL) in the blood and is low in patients with type 2 diabetes. Hormone-replacement therapy (HRT) can increase HDL cholesterol levels, but its effect on serum PON1 arylesterase activity is uncertain. The aim of the present study was to determine the effect of 6 months' HRT with conjugated equine estrogen and medroxyprogesterone acetate on serum PON1 arylesterase activity in postmenopausal women with type 2 diabetes. Serum PON1 activity was measured immediately before and at the end of the second arm of a randomized, placebo-controlled, crossover with washout study originally designed to test the effect of HRT on plasma lipids in diabetic postmenopausal women. Baseline serum PON1 arylesterase activity was significantly (P <.001) lower in the postmenopausal diabetic women (149 +/- 38 micromol/mL/min; n = 47) than values in healthy postmenopausal women (173 +/- 32 micromol/mL/min; n = 51). Serum PON1 activity increased (10%) significantly (P =.009) in diabetic women treated with HRT compared with placebo. A significant (P =.02) interaction between baseline PON1 activity and treatment indicated a greater increase in PON1 activity during HRT in women with lower baseline activities. At baseline, serum PON1 arylesterase activity was correlated significantly with plasma HDL cholesterol levels in diabetic women (r = 0.333, P =.01, n = 47), and the increase in serum PON1 activity was correlated significantly with the change in plasma HDL cholesterol during HRT (r = 0.659, P =.0001, n = 28). These data suggest that serum PON1 activity is abnormally low in postmenopausal women with type 2 diabetes and increases during HRT, particularly in women with lower baseline levels and in those who show a concomitant increase in HDL cholesterol.

The effects of sequential combined oral 17beta-estradiol norethisterone acetate on insulin sensitivity and body composition in healthy postmenopausal women: a randomized single blind placebo-controlled study.

OBJECTIVE: The androgenic effect of progestogen, necessary in early postmenopausal hormone replacement therapy (HRT), may adversely affect insulin sensitivity as well as body fat distribution and thereby increase the cardiovascular risk profile. The impact of HRT with sequential combined oral 17beta-estradiol and norethisterone acetate on insulin sensitivity and body composition in early menopause has not been studied. DESIGN: A randomized single blind placebo-controlled 6-month study of sequential combined 17beta-estradiol norethisterone acetate on insulin sensitivity and body composition was carried out. Thirty fit healthy postmenopausal women were enrolled and completed this 6-month study. Body composition was measured by dual-energy x-ray absorptiometry scanning, and insulin sensitivity was measured using the euglycemic hyperinsulinemic clamp. Studies were undertaken at baseline and after 6 months of therapy. The studies were performed during the estrogen-only phase of therapy. RESULTS: All women demonstrated a degree of decreased insulin sensitivity that was not modified by 6 months of hormone replacement therapy. Body composition remained unchanged over 6 months. There was no alteration in total body fat or the distribution of body fat. The percentage of central abdominal fat (android) was not altered. CONCLUSION: Six months of HRT with sequential combined oral 17beta-estradiol norethisterone acetate does not have an adverse effect on insulin sensitivity and does not promote an increase in weight or the more android distribution of body fat, which could contribute to the increased cardiovascular risk profile that is evident in postmenopausal women.

Plasma cholesteryl ester fatty acid composition, insulin sensitivity, the menopause and hormone replacement therapy.

This study was designed to determine the effect of menopause and hormone replacement therapy (HRT) on plasma cholesteryl ester fatty acid (CEFA) composition and insulin sensitivity and the relationships between these variables in perimenopausal women (aged 40-55 years) including 49 who were premenopausal and 32 who were postmenopausal. Plasma cholesteryl ester proportions of dihomo-gamma-linolenic acid (20:3 n-6) were correlated significantly with insulin sensitivity index (r=-0.319, P=0.005), fasting serum insulin levels (r=0.230, P=0.038), body mass index (r=0.242, P=0.03) and per cent body fat (r=0.329, P=0.003) in perimenopausal women (n=81). Similar associations were observed in premenopausal women. Regression analysis suggested the relationships between 20:3 n-6 proportions and indices of insulin action may be partly mediated by levels of adiposity. In postmenopausal women, 6 months of HRT significantly (P=0.008) increased the ratio of arachidonic acid (20:4 n-6) to linoleic acid (18:2 n-6), which is an indicator of activity in the pathway of 20:4 n-6 synthesis, compared with placebo. These findings suggest that the type of fat in the diet indicated by plasma CEFA composition is linked to adiposity and insulin action. They also suggest that in postmenopausal women, HRT may increase the synthesis of 20:4 n-6, which is the precursor for eicosanoids with important cardiovascular functions.

Plasma cholesterol esterification and transfer, the menopause, and hormone replacement therapy in women.

With the onset of the menopause, plasma lipids and lipoprotein metabolism changes toward a more atherogenic profile that is improved by HRT. To determine whether cholesterol esterification rate (CER) and transfer of cholesteryl esters from high density lipoproteins to apolipoprotein B-containing lipoproteins are affected by menopause and HRT, plasma newly synthesized cholesteryl ester transfer (NCET) activity, CER and plasma lipids, lipoproteins, and apolipoprotein concentrations were measured in perimenopausal women (age range: 40-55 yr), including 49 premenopausal women and 32 postmenopausal women who were subsequently randomized to receive either placebo or 17-beta estradiol/norethisterone for 6 months. Plasma NCET (P = 0.03) and CER (P = 0.008) were significantly higher in postmenopausal women. Plasma low density lipoprotein cholesterol concentration, high density lipoprotein concentration, and body mass index were independent predictors of plasma NCET in premenopausal women, and plasma triglyceride and apolipoprotein B concentrations were corresponding predictors in postmenopausal women. When data were adjusted for plasma triglyceride, plasma NCET activity was no longer significantly different (P = 0.81) between premenopausal and postmenopausal women. Plasma NCET and CER did not change significantly in postmenopausal women during HRT. These data suggest that the determinants of plasma NCET activity after menopause and increased levels of triglyceride-rich lipoprotein acceptors of cholesteryl esters may lead to increased plasma NCET that is not reduced by HRT in postmenopausal women.

Supplementation with tomato juice increases plasma lycopene but does not alter susceptibility to oxidation of low-density lipoproteins from renal transplant recipients.

AIM: Oxidative stress and susceptibility of low-density lipoproteins (LDL) to oxidation are increased in renal transplant recipients. The aim of this study was to determine the effect of dietary supplementation with tomato juice on plasma levels of the antioxidant lycopene, serum indices of lipid peroxidation (fluorescent lipid oxidation products (FLOP) and thiobarbituric acid-reacting substances (TBARS)) and the resistance of isolated low-density lipoprotein (LDL) to oxidation (lag time) in patients with a kidney graft. SUBJECTS AND METHODS: Fifteen patients were randomized to daily consumption of either tomato juice or synthetic orange drink for 4 weeks in a crossover study. Plasma lycopene levels were significantly higher (1.57 micromol/l versus 0.91 micromol/l, p = 0.015) while serum FLOP and TBARS and resistance of LDL to oxidation were not significantly different during supplementation with tomato juice compared with orange drink. At baseline, serum levels of lycopene and FLOP were abnormally high and serum FLOP was correlated significantly with plasma cyclosporine levels (r = 0.646, p = 0.016). CONCLUSION: In conclusion, these data suggest that increased oxidative stress and susceptibility of LDL to oxidation may not be reduced by increasing plasma lycopene levels with regular consumption of tomato juice in renal transplant recipients.

Reduced postprandial serum paraoxonase activity after a meal rich in used cooking fat.

Paraoxonase is an enzyme associated with HDL in human serum that hydrolyzes oxidized phospholipids and inhibits LDL oxidation, which is an important step in atherogenesis. In animals, addition of oxidized lipids to the circulation reduces paraoxonase activity, and diets rich in oxidized fat accelerate the development of atherosclerosis. The current randomized, crossover study was designed to compare the effect of a meal rich in oxidized lipids in the form of fat that had been used for deep-frying in a fast food restaurant and a control meal rich in the corresponding unused fat on postprandial serum paraoxonase (arylesterase) activity and peroxide content of LDL and its susceptibility to copper ion catalyzed oxidation in 12 healthy men. Four hours into the postprandial period, serum paraoxonase activity had decreased significantly after the used fat meal (-17%, P=0.005) and had increased significantly after the meal rich in unused fat (14%, P=0. 005). These changes were significantly (P=0.003) different. A time-course study indicated that serum paraoxonase activity remained lower than baseline for up to 8 hours after the used fat meal. Serum apoA1 concentration tended to decrease after the unused fat meal and tended to increase after the used fat meal. These changes were different at a marginal level of significance (P=0.07). Also, a significantly (P=0.03) greater decrease in apoA1 content of postprandial HDL was recorded after the unused fat meal. The peroxide content of LDL tended to decrease after the used fat meal and tended to increase after the control meal. These changes were significantly (P=0.04) different. Susceptibility of isolated LDL to copper ion oxidation and plasma levels of malondialdehyde were unchanged during the study. These data suggest that in the postprandial period after a meal rich in used cooking fat, the enzymatic protection of LDL against accumulation of peroxides and atherogenic oxidative modification may be reduced, possibly due to factors associated with apoA1, without acutely affecting the intrinsic resistance of LDL to in vitro oxidation.

Impaired endothelial function following a meal rich in used cooking fat.

OBJECTIVES: The purpose of this study was to test the hypothesis that intake of used cooking fat is associated with impaired endothelial function. BACKGROUND: Diets containing high levels of lipid oxidation products may accelerate atherogenesis, but the effect on endothelial function is unknown. METHODS: Flow-mediated endothelium-dependent dilation and glyceryl trinitrate-induced endothelium-independent dilation of the brachial artery were investigated in 10 men. Subjects had arterial studies before and 4 h after three test meals: 1) a meal (fat 64.4 g) rich in cooking fat that had been used for deep frying in a fast food restaurant; 2) the same meal (fat 64.4 g) rich in unused cooking fat, and 3) a corresponding low fat meal (fat 18.4 g) without added fat. RESULTS: Endothelium-dependent dilation decreased between fasting and postprandial studies after the used fat meal (5.9 +/- 2.3% vs. 0.8 +/- 2.2%, p = 0.0003), but there was no significant change after the unused fat meal (5.3 +/- 2.1% vs. 6.0 +/- 2.5%) or low fat meal (5.3 +/- 2.3% vs. 5.4 +/- 3.3%). There was no significant difference in endothelium-independent dilation after any of the meals. Plasma free fatty acid concentration did not change significantly during any of the meals. The level of postprandial hypertriglyceridemia was not associated with change in endothelial function. CONCLUSIONS: Ingestion of a meal rich in fat previously used for deep frying in a commercial fast food restaurant resulted in impaired arterial endothelial function. These findings suggest that intake of degradation products of heated fat contribute to endothelial dysfunction.

IDL composition and angiographically determined progression of atherosclerotic lesions during simvastatin therapy.

Some patients with coronary artery disease experience continued progression of one or more coronary lesions despite treatment with drugs that inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and markedly lower plasma cholesterol levels. We examined relationships between the progression of coronary artery lesions and plasma lipoproteins, in particular intermediate density lipoprotein (IDL) and its composition, in 38 patients with coronary artery disease who had been treated with simvastatin for 2 years. Patients were given lipid-lowering dietary advice; 3 months later they were started on simvastatin therapy (10 mg/d) for 1 month, and after review of their plasma cholesterol levels, the dose was increased to 20 mg/d and later to 40 mg/d if the target level of plasma cholesterol had not been attained. Progression of lesions was determined by serial quantitative coronary angiography (variability of 5.5%) and was defined as an increase in percent diameter stenosis (%S)> or =10%; regression was defined as a decrease in %S > or =10%. The proportions of cholesteryl esters (CEs) and free cholesterol decreased significantly (P<.001), and proportions of protein and triglycerides increased significantly (P<.001) in IDL during simvastatin therapy. The CE content of IDL decreased significantly (-7.2 weight [wt]%, n=20, P<.001) in nonprogressors (patients who did not show progression of any lesions) and did not change significantly (-1.8 wt%, n=14, P=.36) in progressors (patients who showed progression of one or more lesions without regression of any lesion). This decrease in IDL CE content in nonprogressors was significantly (P=.01) different compared with the corresponding change in patients classified as progressors. Mean plasma cholesterol concentration tended to increase in progressors (0.47 mmol/L) and tended to decrease in nonprogressors (-0.39 mmol/L) during the initial 3-month diet period, and these changes were significantly different (P=.02). Furthermore, this change in plasma cholesterol level during the initial diet period was correlated significantly with the change in IDL CE content during the entire study (r=.348, n=38, P=.03). These data suggest that IDL CE content may be a determinant of progression of coronary lesions and may be influenced by compliance with or metabolic response to lipid-lowering dietary advice in patients with coronary artery disease during simvastatin treatment.

Diagnosis, surgical intervention, and prognosis of primary pancreatic lymphoma.

Primary pancreatic lymphoma is a rare but treatable malignancy that may present as an isolated pancreatic mass. Most of these patients are assumed to have ductal malignancies of the pancreas and are denied surgical intervention. Controversy exists concerning the method of diagnosis and the need for and extent of surgical intervention for these malignancies. Over the past 15 years, from 1976-1991, we have treated seven patients with pancreatic lymphoma who initially presented with a pancreatic mass. There were five females and two males ranging in age from 60-86 years (mean = 68). All patients were symptomatic and complained of epigastric pain, jaundice, anorexia, or early satiety. The interval between onset of symptoms and treatment averaged 6 weeks. Over half of these patients presented with an epigastric mass and/or jaundice. Abdominal CT scan was accurate in identifying and localizing the pancreatic mass in all patients. The diameter of the pancreatic mass ranged from 3-12 cm (mean = 8.1 cm) and the mass was located in the head of the pancreas in five patients. All attempted percutaneous needle biopsies of the pancreatic mass were non-diagnostic. Operative lymph node biopsy or transduodenal/wedge biopsy of the pancreatic mass was successful in demonstrating pancreatic lymphoma in all patients. Two of the seven patients underwent biliary bypass. One of the seven patients died in the postoperative period. Three of these seven patients received chemotherapy and survived an average of 6.3 years. One patient is alive 8 years after diagnosis and treatment and is currently asymptomatic. Patients who did not receive postoperative chemotherapy survived an average of 5 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Nonductal tumors of the pancreas. The importance of laparotomy.

OBJECTIVES: To delineate the incidence of nonductal pancreatic neoplasms and determine whether distinguishing clinical or radiologic characteristics exist. METHODS: From 1977 through 1990, we examined 353 patients with a pancreatic mass as demonstrated on abdominal computed tomography or ultrasonography. Patients with chronic pancreatitis or functioning neuroendocrine tumors were excluded. All patients underwent operative exploration for histopathologic diagnosis and resection when possible. RESULTS: Adenocarcinoma of the pancreas was seen in 322 patients. The remaining 31 patients (8.8%) were found to have nonductal tumors of the pancreas, including nonfunctioning islet cell tumors (15), cystadenoma (nine), lymphoma (five), lipoma (one), and mesothelioma (one). These neoplasms were evenly distributed between the head and tail of the pancreas, while most of the ductal pancreatic carcinomas were located in the pancreatic head. While abdominal computed tomography and ultrasonography accurately identified most cystic neoplasms, the remaining nonductal lesions were indistinguishable from ductal pancreatic tumors. Preoperative biochemical studies and liver function tests failed to separate ductal and nonductal pancreatic masses. Average survival for patients with nonductal lesions was significantly longer compared with ductal tumors of the pancreas. CONCLUSIONS: Because increasing reliance on advanced radiologic and invasive nonoperative diagnostic testing may deny proper surgical therapy to patients with nonductal neoplasms of the pancreas, laparotomy and histopathologic diagnosis are advisable in most patients with an isolated pancreatic mass.

Primary papillary thyroid carcinoma presenting as cervical lymphadenopathy: the operative approach to the "lateral aberrant thyroid".

In contrast to a few follicles arranged in a wedge-shaped segment at the periphery of a lymph node, a significant amount of thyroid tissue in a cervical lymph node is considered evidence of metastatic thyroid carcinoma. In a consecutive series of 243 patients with papillary carcinomas, 52 presented with lateral cervical masses that proved to be lymph nodes with metastatic thyroid carcinoma, in the absence of readily palpable thyroid nodularity. The metastatic disease was demonstrated by excisional biopsy in 40 patients and fine needle aspiration cytology in 12 patients. Thirty-two (of the 52) underwent further diagnostic work-up, consisting of radionuclide scintigraphy and ultrasonography, with the demonstration of abnormalities consistent with a thyroid neoplasm in 75 per cent (24/32) of these patients. The remaining 20 patients had no additional studies except for chemical thyroid function evaluation. The operative treatment in all 52 patients was total thyroidectomy and unilateral or bilateral modified neck dissections, when extensive cervical adenopathy was encountered. Papillary thyroid carcinoma, ranging in size from 2 to 14 mm, was found in the lobe ipsilateral to the presenting cervical node metastasis, in all specimens. In addition, contralateral cervical lymph node metastases were found in five (10%) of these patients, with no evidence of thyroid carcinoma in the corresponding thyroid lobe. With a mean follow-up period of 9 years, all patients are alive with no evidence of recurrence.(ABSTRACT TRUNCATED AT 250 WORDS)

Recurrent hyperparathyroidism due to parathyroid autografts: incidence, presentation, and management.

Recurrent hyperparathyroidism (HPT) occurs in a small percentage of patients undergoing parathyroidectomy for primary HPT and is usually due to inadequate excision of hyperfunctioning parathyroid tissue in the neck, a missed ectopic and hyperplastic parathyroid, or, less commonly, parathyroid carcinoma and parathyroid autografts. In order to determine the incidence, clinical characteristics, and outcome of patients with recurrent HPT due to parathyroid autografts, we reviewed our experience with 604 consecutive patients operated on for primary HPT between 1965 and 1989. One hundred of these patients received parathyroid autografts consisting of portions of one or more parathyroid glands. Three patients with autografts, placed in the sternocleidomastoid muscle, developed recurrent HPT due to their autografts for an incidence of 3 per cent. Recurrent disease was diagnosed between 62 and 113 months with an average of 89 months. The autotransplants in all three of these patients were from hyperplastic or adenomatous parathyroid tissue. Two patients had a history of neck irradiation. Preoperative thallium scans accurately localized the hyperfunctioning parathyroid tissue in all three patients. At operation, the hyperfunctioning autografts had grown into a discrete mass with a single vascular pedicle and were resected. Histologic examination disclosed either hyperplastic or adenomatous tissue, and corresponded to the histology and location of the original tissue transplanted in each case. Follow-up ranges from 12 to 67 months, with an average of 48 months. All patients remain cured and none require oral calcium supplementation. We conclude that graft-dependent recurrent HPT is due to the autotransplantation of hyperplastic or adenomatous parathyroid tissue and that thallium scanning is instrumental for diagnosis and localization.(ABSTRACT TRUNCATED AT 250 WORDS)

Necessity and safety of completion thyroidectomy for differentiated thyroid carcinoma.

BACKGROUND: The diagnosis of thyroid carcinoma during the course of lobectomy for a dominant nodule occasionally cannot be rendered on the basis of frozen section. Once the diagnosis of carcinoma is made, the question of completion thyroidectomy arises. The decision to perform completion thyroidectomy and the timing, safety, and efficacy of this procedure are reviewed. METHODS: During the past 25 years (1965 to 1990), we operated on 351 consecutive patients with thyroid carcinoma. One hundred of these patients (84 women and 16 men) were initially treated by unilateral thyroid lobectomy for the previously stated reasons. Histopathologic examination of the permanent sections of the initial thyroid lobectomy specimen demonstrated papillary carcinoma in 70 patients and follicular carcinoma in 30 patients. Within a few months, a completion thyroidectomy was performed. RESULTS: The completion thyroidectomy specimen contained papillary carcinoma in 33 (47%) of the 70 patients with papillary carcinoma and 10 (33%) of the 30 patients with follicular carcinoma. Overall, 43 of these 100 patients harbored thyroid carcinoma in the contralateral lobe. Complications of completion thyroidectomy were transient recurrent nerve paresis in two patients and temporary hypoparathyroidism in three patients, requiring calcium and vitamin D therapy for a few months. CONCLUSIONS: Although the significance and treatment of papillary carcinoma are debated on the basis of size and grade of the primary lesion and age and sex of the patients, once the diagnosis is made in one lobe we believe that a completion thyroidectomy should be considered, not only for papillary carcinomas but also for follicular carcinomas because 47% (papillary) to 33% (follicular) of these patients will harbor the neoplasm in the contralateral lobe.

High phosphate diet-induced primary hyperparathyroidism: an animal model.

Primary hyperparathyroidism (PHPT) is increasing in incidence and detection, primarily because of the aging of our population and the widespread use of automated serum calcium determination. As a result, a substantial number of "early" cases or "biochemical" PHPT are being detected. The indications for parathyroidectomy in such early cases of PHPT are currently under debate, primarily because of economic issues. These factors underscore the importance of research into the basic mechanisms and natural history of PHPT. We investigated an animal model of diet-induced PHPT that retains two crucial aspects of PHPT: elevation of endogenously produced parathyroid hormone (PTH), accompanied by gross and microscopic changes in the native parathyroid glands. Female Long-Evans rats were divided into six groups of 15 each and fed a control diet (Ca/P of 1:2) or a high-phosphate diet (Ca/P of 1:7) for 1-, 2-, or 3-month intervals. Compared with the control animals, serum PTH levels were elevated at all three time intervals in the experimental group, whereas serum calcium levels were decreased at all time intervals. Serum creatine levels were also elevated at all time intervals, whereas serum phosphorus levels did not change. Parathyroid histopathologic studies demonstrated no change at 1 month, whereas nine of 15 experimental animals showed mild hyperplasia at 2 months and 13 of 14 showed mild to moderate hyperplasia with gland enlargement at 3 months compared with control animals. Histopathologic examination of the kidneys showed no change at 1 month but focal parenchymal inflammation with calcium deposition at 2 and 3 months in the experimental groups. In conclusion, the high-phosphate diet successfully induced the earliest changes of PHPT: elevated PTH levels and parathyroid hyperplasia. However, because renal function was mildly compromised early on, some element of early secondary (renal) hyperparathyroidism may have supervened quickly. Because this model is simple, it may be useful to investigate this complex syndrome further, as well as its natural history and the complications it produces in other organs such as the kidneys.