Polymorphisms in candidate obesity genes and their interaction with dietary intake of n-6 polyunsaturated fatty acids affect obesity risk in a sub-sample of the EPIC-Heidelberg cohort

Summary. Background, aim: In several genes coding for molecules involved in the regulation of body weight (fat mass) and thermogenesis, polymorphisms have been reported which possibly modify human obesity risk. The aim of this study was a) to reproduce these observations with data and biological material from the Heidelberg cohort of EPIC, a large European prospective investigation into diet and cancer, and b) to investigate potential effects of interactions between dietary fatty acid intake and allelic variants on obesity risk. Subjects and methods: Within EPIC-Heidelberg, 154 subjects with a body mass index > 35 kg/m² and 154 age- and sex-matched normal-weight controls were selected and genotypes determined for 11 candidate genes. Dietary intake was assessed by a validated food frequency questionnaire. Odds ratios (OR) were computed by means of unconditional logistic regression and different adjustment models. Genotyping was performed by PCR-RFLP and allele-specific PCR. Results: For most of the investigated genes (PPARA, PPARG2, UCP1, UCP2, UCP3, BAR-2, APM1, leptin, SORBS1, HSL, and TNFA) an indication for a minor effect on obesity risk was found. Indication of a risk-increasing effect was strongest for the homozygous form of leptin −2548AA with an adjusted OR of 3.53 (p < 0.009). Additionally, for the polymorphic sites of BAR-2 (Arg16Gly and Gln27Glu) a significant effect on obesity risk was seen. Importantly, the results of the analysis of gene-diet interactions suggest that the allelic variants of candidate genes (leptin, TNFA, PPARG2) might strongly affect diet-related obesity risk. Conclusions: The results support some but not all previous reports about a risk-modulating effect of polymorphisms in genes affecting obesity risk. The most important finding is an indication of substantial interaction between allelic variants of particular genes and fatty acid intake-related obesity risk. These observations suggest that future studies on polymorphisms in obesity genes should take data on dietary habits into account. Received: 3 May 2002, Accepted: 21 August 2002 Correspondence to: Dr. A. Nieters     

A cohort mortality study of construction workers

This report presents a mortality study among the 17,344 members of the Construction Workers' Health Insurance Society of Mie Prefecture in Japan. The study period was between 1973 and 1993. During this period, 480 members died. Age-specific mortality rates of Mie Prefecture were used as comparison standards. Significantly elevated standardized mortality ratio (SMR) and proportionate mortality ratio (PMR) were observed for “accidents and adverse effects.” In addition, the PMRs of all cancers and “cancers of trachea, bronchus and lung” were also significantly elevated. The job classifications were reorganized into three groups, according to the frequency of asbestos exposure the workers experienced on the construction sites. The asbestos exposure was based on job classifications among 7,411 workers who had completed a self-administered survey questionnaire. In the frequent-exposure group, the PMR was significantly elevated for all cancers. In the medium-exposure group, the SMRs were significantly elevated for all cancers and “cancer of trachea, bronchus and lung.” The PMR was significantly elevated for “cancer of trachea, bronchus and lung.” In the less-exposure group, the PMR was significantly elevated for “accidents and adverse effects.” This study provided support for the hypothesis that working in the construction industry might be associated with high risks for asbestos-associated cancers and accidental deaths. Am. J. Ind. Med. 32:35-41, 1997. © 1997 Wiley-Liss, Inc.     

Plasma levels of antioxidant vitamins and cholesterol in a large population sample in Central-Northern Italy

Background: In a population-based multicenter case-control study of diet, life-style, and gastric cancer a large series of adults, aged 30–75 years (mean 58.9 yearss), were randomly sampled from the general population in 3 areas of Central-Northern Italy. Aim of the study: To evaluate the relationship between plasma levels of antioxidant vitamins and cholesterol, and sociodemographic characteristics, life-style factors, and dietary intake of selected nutrients in a sample of the Italian population. Methods: A fasting blood sample was available for 945 subjects (553 men, 392 women). The plasma concentrations of ascorbic acid, carotene, retinol, alpha-tocopherol, and cholesterol were determined by a centralized laboratory. All participants answered to a detailed questionnaire collecting information on sociodemographic and anthropometric characteristics, smoking, alcohol drinking, and dietary habits. Covariance analysis models, with post hoc Dunnett tests, including terms for age, sex, study center, and period of blood drawing, were used for selected multiple-way comparisons of mean values of plasma nutrients. Results: Mean plasma values of retinol were higher among men while women had higher levels of plasma carotene, ascorbic acid, alpha-tocopherol, and cholesterol. Plasma carotene levels showed an inverse association with body mass index, alcohol consumption, and smoking and a positive association with social class. Carotene concentrations were higher in plasma samples obtained in spring/summer, while ascorbic acid levels were higher in autumn/winter. Partial correlation coefficients between carotene and ascorbic acid (0.69 in men; 0.74 in women), between carotene and alpha-tocopherol (0.44; 0.37), and between alpha-tocopherol and ascorbic acid (0.45; 0.41). Plasma alpha-tocopherol and retinol correlated with plasma cholesterol. On the other hand, plasma carotene and ascorbic acid were correlated with their estimated dietary intakes, while the intakes of other nutrients, as expected, correlated rather poorly with the respective plasma concentrations. Conclusions: Socio-economic factors, life-style, and specific nutrient intake, in addition to gender, are related to nutrient plasma levels in Italian adults and may provide specific suggestions for the prevention of chronic diseases. Received: 8 December 1998, Accepted: 25 February 1999     

Use of BMI as a measure of overweight and obesity in a field study on 5-7 year old children

Summary Objective The present field study examines the use of BMI in comparison with estimates of percent fat mass to screen for overweight and obesity in children. Design Cross-sectional field study. Setting Four waves of children 1996–1999 at Kiel, North West Germany. Subjects A representative large sample of 2286 5–7 year old children representing 40 % of the total child population examined by school physicians within the same period in Kiel. Main outcome measures BMI was compared with anthropometric measures (TSF, BSF, SIF, SSF) and bioelectrical impedance analysis (BIA). The 90^th and 97^th BMI percentiles were used as cut offs for overweight and obesity, respectively. Results BMI reached a low sensitivity to identify overweight children when compared with the two estimates of % FM (0.60 to 0.78 for girls, 0.71 to 0.82 for boys, respectively). The specificity of BMI was 93 to 95 %. By contrast, BMI reached higher sensitivity to screen for obese children of 0.83 to 0.85 for boys and 0.62 to 0.80 for girls at a concomitant specificity of 0.95 to 0.98 for boys and 0.96 to 0.97 for girls as defined by assessment of body fat mass. Comparing nutritional status of overweight children classified as overweight or non overweight by BMI shows that BMI only identified obese but not-overweight children. Conclusion BMI can be used to screen for obese children. In contrast BMI has a poor sensitivity to screen for overweight children. Body composition analysis should be used to screen for children at risk of becoming obese. Received: 10 October 2001, Accepted: 21 December 2001     

Metalworking fluids and cancer mortality in a US autoworker cohort (1941–2015)

Objectives:This report describes the extended follow-up (1941–2015) of a cohort of 38 549 automobile manufacturing workers with potential exposure to metalworking fluids (MWF). The outcomes of interest were mortality from cancers of the esophagus, stomach, intestine, rectum, bladder, liver, pancreas, larynx, lung, skin, prostate, brain, and female breast, as well as leukemia. This report includes 5472 deaths from cancer, more than ten times the numbers of deaths in our last summary report published 20 years ago.Methods:Standardized mortality ratios were computed for the entire study period. Adjusted hazard ratios (HR) were estimated in Cox proportional hazard models with categorical variables for cumulative exposure to each type of MWF.Results:Exposure–response patterns are consistent with prior mortality reports from this cohort. We found increased risk of skin and female breast cancer with straight fluids. For the first time, we found elevated risk of stomach cancer mortality. Overall, many of the exposure–response results did not suggest an association with MWF.Conclusions:Mortality is a poor proxy for cancer diagnosis for treatable cancers and not the optimal outcome measure in etiological studies. Although the HR presented here handle bias from the healthy worker hire effect and left truncation, they do not handle bias from healthy worker survivor effect, which likely results in underestimates of the health impacts of MWF. Although this updated summary provides some information on the risk of cancer from MWF, targeted future analyses will help clarify associations.     

Cancer mortality among a cohort of chromium pigment workers

A study of mortality among 1,879 male workers employed in a New Jersey chromium pigment factory was carried out, with follow-up from 1940 to 1982. Vital status of 1,737 (92%) of the eligible cohort members was determined. For all malignant neoplasms, 101 deaths were observed while 108.8 were expected, SMR = 93 (standardized mortality ratio; n.s.). For the entire study group, no significant excess was observed for respiratory cancer or cancer at other sites. However, the total number of years of employment in the factory and the total number of years of exposure to chromate dusts were both statistically significantly (p less than .05, for trend) associated with an increased risk for lung cancer. The excess risk for lung cancer associated with duration of exposure to chromate dusts was, however, only clearly apparent for subjects followed for 30 years or more after initial employment. For this group, the SMRs were 81, 139, 201, and 321 for the subjects with 0 years, less than 1 year, 1-9 years, and 10+ years of exposure to chromate dusts (p less than .01, for trend), respectively. The risk for digestive cancer was only weakly associated with exposure to chromate dusts.     

Effect of 24-h food deprivation on lipoprotein composition and oleoyl-estrone content of lean and obese Zucker rats

BACKGROUND: Food deprivation induces the mobilization of fat reserves and, consequently, the transport of lipids in plasma. Zucker obese rats are grossly hyperlipidemic and do not use lipids as an efficient energy substrate. They also have lower circulating levels of acyl-estrone than expected because of their large fat stores. AIM OF THE STUDY: To measure the effect of 24 h food deprivation on hyperlipidemia and acyl-estrone distribution in plasma in Zucker obese rats. METHODS: The plasma lipoprotein distribution and composition of Zucker lean (Fa/?) and obese (fa/fa) rats was determined after 24 hours of food deprivation. Lipid classes: phospholipid, free and esterified cholesterol and triacylglycerols, and protein and total (mainly acyl-) estrone were also measured in total plasma and lipoprotein fractions. RESULTS: Food-deprived rats showed lower triacylglycerol levels than fed rats, but obese rats maintained high lipid levels, mainly in the VLDL fraction. The ratio of total plasma free-to-esterified cholesterol was lower in fed lean rats (0.29) than in the obese (0.61); the situation improved slightly after 24-h starvation, since the corresponding ratios were 0.30 and 0.41. Acyl estrone levels changed little with 24-h food deprivation. The chylomicra + VLDL total estrone compartment was essentially unchanged in lean and obese fed and starved groups, but the HDL pool decreased with food deprivation in the obese. CONCLUSION: Short-term starvation helped to enhance the differences between lean and obese Zucker rats in the handling of lipoprotein lipids, the latter showing a marked impairment in their ability to dispose of circulating lipids. The different pace of plasma lipid utilization may compound the problems of cholesterol transfer, partly explaining the dyslipemia that characterizes this animal model of obesity. The differences in acyl-estrone distribution also indicate that fat mass is preserved more effectively in obese rats even after food deprivation.     

Short- and long-term mortality after an acute illness for elderly whites and blacks

Objective. To estimate racial differences in mortality at 30 days and up to 2 years following a hospital admission for the elderly with common medical conditions.
Data Sources. The Medicare Provider Analysis and Review File and the VA Patient Treatment File from 1998 to 2002 were used to extract patients 65 or older admitted with a principal diagnosis of acute myocardial infarction, stroke, hip fracture, gastrointestinal bleeding, congestive heart failure, or pneumonia.
Study Design. A retrospective analysis of risk-adjusted mortality after hospital admission for blacks and whites by medical condition and in different hospital settings.
Principal Findings. Black Medicare patients had consistently lower adjusted 30-day mortality than white Medicare patients, but the initial survival advantage observed among blacks dissipated beyond 30 days and reversed by 2 years. For VA hospitalizations similar patterns were observed, but the initial survival advantage for blacks dissipated at a slower rate.
Conclusions. Racial disparities in health are more likely to be generated in the posthospital phase of the process of care delivery rather than during the hospital stay. The slower rate of increase in relative mortality among black VA patients suggests an integrated health care delivery system like the VA may attenuate racial disparities in health.     

Plasma levels of advanced glycation end products in healthy, long-term vegetarians and subjects on a western mixed diet

Summary Background Evidence indicates that food-derived Maillard's reaction products are absorbed and yet can be detected in the circulation. Aim of the study We postulated that consumption of the heat-treated food by omnivores could be reflected by higher plasma levels of advanced glycation end products (AGEs) in comparison with vegetarians, who in cooking (by keeping away from meat) use lower temperatures and less time for heating. Methods Plasma fluorescent AGEs (350/450 nm) and Ne-(carboxymethyl)lysine (CML, competitive ELISA) levels were investigated in 3 groups of healthy vegetarians (9 vegans-V, 19 lacto-ovo-vegetarians – VLO and 14 semi-vegetarians – VS) and compared with those of age-matched omnivores (O, n=19). Mean duration of vegetarian diet was V: 7.2±1.0, VLO: 8.2±0.8 and VS: 7.9±1.1 years. Results Both fluorescent AGE (O: 9.9±0.5; V: 10.8±0.7, LO: 13.1±0.8* and SV: 11.6±1.2 ×10³ AU), and CML levels (O: 427.1±15.0, V: 514.8±24.6*, LO: 525.7±29.5**, SV: 492.6±18.0* ng/ml) were significantly lower in omnivores than in vegetarians. Plasma glucose, parameters of renal function (plasma concentration of creatinine and cystatin C, calculated glomerular filtration rate – GFR) as well as C-reactive protein levels were within the normal range and did not differ significantly between the groups. Thus, neither decline of kidney function nor inflammatory processes contributed to the rise in plasma AGEs. Conclusion Enhanced plasma AGE levels in vegetarians in comparison to omnivores are herein presented for the first time. Mechanisms of AGE elevation and potential pathophysiological relevance of this finding are to be elucidated in prospective studies. Received: 18 June 2001, Accepted: 7 November 2001     

A cohort mortality study of leather tanners in Tuscany, Italy

BACKGROUND: Work in leather tanning may involve exposure to a wide range of chemicals. Some of these are carcinogens or suspected carcinogens. Increased risk for a number of cancers have been reported, although there are considerable inconsistencies between studies. The present study investigates the mortality of leather tanners in Tuscany, Italy. METHODS: Tanneries were selected from the 1996 Valdarno Inferiore Tanneries Census and were in operation since December 31, 1970. Employees were followed until December 31, 1998 through company records, and the National and Regional Death Index. Demographic and work history data were abstracted from company payrolls. Regional mortality rates were used to calculate Standardized Mortality Ratio (SMR). Analyses were completed for the overall cohort (men and women) and for men who ever worked as of finisher, chrome tanners, and vegetable tanner (only men). RESULTS: The cohort consisted of 4,874 workers (4,150 males and 724 females) employed in 92 tanneries active in 1996 and operating on December 31, 1970. Ascertainment of vital status and cause of death were completed for all individuals by the end of follow-up, December 31, 1998. Males showed increases for cancer of the endocrine glands (SMR 5.67, 4 observed (obs), 90% Confidence Intervals (CI) 195-1,308), blood diseases (SMR 3.29, 4 obs, 90% CI 112-753), mental disorders (SMR 1.95, 6 obs, 90% CI 85-385), violence and accidents (SMR 1.30, 54 obs, 90% CI 102-163). Mortality from myeloid leukemia was increased in males (SMR 2.08, 5 obs, 90% CI 82-437) and in females (SMR 5.99, 2 obs, 90% CI 106-1,887). One death from nasal cancer was observed versus 0.2 expected. Mortality from lung cancer was increased among finishers (SMR 1.45, 19 obs, 90% CI 95-212), an increase was observed also for bladder cancer (SMR 1.25, 2 obs, 90% CI 22-393) and pancreatic cancer (SMR 1.20, 2 obs, 90% CI 21-379). CONCLUSIONS: The study confirms previous observations among tanners of increased mortality from lung, bladder, and pancreatic cancer. Noteworthy are the increased mortality from myeloid leukemia together with the new findings of an increased mortality from endocrine glands tumors, blood diseases, and psychiatric disorders which should be considered with caution because of the small number of cases and the novelty of the observation.     

New approaches in the pharmacological treatment of obesity

Summary Many new substances are currently being investigated for their usefulness in the pharmacotherapy of obesity. Most drugs interfere with monoamine neurotransmitter (serotonin, noradrenalin, dopamine and histamine) effects and act as an appetite suppressant. Other approaches are to primarily increase thermogenesis (e.g. β₃-adrenoceptor agonists), or to decrease fat absorption by inhibiting the pancreatic lipase (orlistat). New promising agents are substances that increase the effect of corticotropin releasing factor (CRF) or urocortin in the brain (CRF-binding protein ligand inhibitor) and a neuropeptide Y (NPY) Y₅ receptor antagonist. The clinical relevance of leptin in the therapy of obesity is probably limited, but can not be fully evaluated at the moment. As obesity has a multifactorial basis, all these substances have in common the fact that they can not cure obesity. They should only be used as an adjunct to classical strategies like diet and exercise in severe obesity. For developing new, perhaps even more specific pharmacological agents, further research is needed to understand the individually different genetic and physiological basis of obesity. Received: 31 August 1998, Accepted: 10 November 1998     

Adaption of Sprague Dawley rats to long-term feeding of high fat of high fructose diets

Summary Background Present animal models used to emulate type 2 diabetes may not accurately reflect the metabolic changes that occur in humans. Aims of the study The purpose of this research was to evaluate diets reported to induce insulin resistance and impaired glucose metabolism in rats as a potentially useful model for studying type 2 diabets. Methods Three groups of male Sprague Dawley rats (n=7) were fed either a control diet, based on AIN recommendations (53% cornstarch, 10% sucrose and 7% soybean oil), a high fat diet (25% soybean oil, 35% cornstarch) or a high fructose diet (53% fructose, 10% sucrose) for a 3 month period. Glucose tolerance tests were carried out in week 3 and week 9 of the experiment. At the termination of the experiment, serum insulin, glucose, cholesterol and triacylglycerols were measured. Glucose incorporation into glycogen and glycogen synthase activity were measured in soleus muscles. Results Similar weight gain was observed for all three groups of rats. Glucose tolerance curves and fasting glucose levels were not significantly different at any time point in the experiment. Insulin levels were unchanged for the controls (171±21 pM), high fructose (164±16 pM) and high fat (181±30 pM) diets. Fasting serum triacylglycerols and cholesterol levels were not significantly elevated by dietary treatment. In soleus muscles, rats on all three diets had a significant increase in glycogen synthesis in response to insulin, but synthesis was similar in all three groups. Glycogen synthase activity was also not significantly affected by long-term dietary intervention. Conclusions In this study, healthy Sprague Dawley rats fed high fat or high fructose diets for 3 months adapted to the nutritional intervention without developing classical signs of insulin resistance and impaired glucose tolerance. Received: 17 May 2000, Accepted: 31 August 2000     

医院标准化死亡比指标建设及应用的国际经验与启示

死亡类指标是反映医疗质量和安全的重要指标,医院标准化死亡比指标已被很多国家作为重要的质量工具以衡量医院的医疗质量。本文通过文献综述,系统梳理和对比了苏格兰、英格兰、美国马萨诸塞州、澳大利亚、荷兰和加拿大6个国家/地区的医院标准化死亡比指标构建经验及其应用情况,并对我国建设该指标的可行性、建设方法以及指标应用方面提出建议。     

Five year changes in waist circumference, body mass index and obesity in Augsburg, Germany

Summary Aims To assess temporal changes in body fat distribution, body mass index and obesity in Augsburg, Germany. Methods Waist circumference, weight and height were measured in two independent samples of 4804 and 4792, men and women, aged 25–74 years, in the MONICA Augsburg surveys 1989/90 and 1994/95. Abdominal obesity was defined as waist circumference greater than the 80^th gender-specific percentile (men:103, women: 92 cm) in the 1989/90 population. Obesity was defined as a body mass index (BMI) ≥ 30 kg/m². Results Age-standardized mean waist circumference increased by more than 1 cm (p-value < 0.00003) in both men and women while BMI increased by 0.3–0.4 kg/m² (p-value < 0.01). We observed both a shift to higher values in the waist circumference distribution plus – particularly in women older than 45 years – a substantial right shift in the top of the distribution. Moreover, survey participants in 1994/95 who were at the higher end of the BMI distributions were disproportionately more obese than their respective peers in 1989/90. The prevalence of abdominal obesity rose by 3.3 % in men and 3.6 % in women, while the prevalence of obesity rose by 2 % from 17 % in men and by 2.5 % from 19 % in women. Conclusions While changes in the Augsburg population may not be as alarming as in other countries, the secular increase in waist circumferences in both men and women occurring over a short time period indicates a need for prevention given the already high absolute weight, BMI and waist circumference levels in the population. Received: 8 August 2001, Accepted: 14 November 2001     

Effects of non-esterified stanols in a liquid emulsion on cholesterol absorption and synthesis in hypercholesterolemic men

Summary Background Background Numerous studies have shown that dietary plant sterols (phytosterols and phytostanols) and their esters can decrease cholesterol absorption. However, few researchers have examined the effects of plant sterols on cholesterol absorption and synthesis using stable isotope tracers, instead of relying on endogenous pathway precursors. Further, we have worked with non-esterified lecithin-solubilized stanols as opposed to the more frequently studied esterified sterols and stanols. The vehicle was an oil-in-water liquid emulsion rather than the more common spread vehicle typically employed. Aim of the study To determine the effects of relatively low doses of lecithin-solubilized non-esterified stanols in liquid emulsions on cholesterol absorption and synthesis in mildly hypercholesterolemic subjects. Methods In a randomized, double blind crossover design, 12 mildly hypercholesterolemic men received either a free phytostanol supplement (3 g/d in 3 servings) or a control treatment for 3 days. Cholesterol endogenous synthesis rate was determined using the rate of incorporation of deuterium from body water into newly formed cholesterol molecules. Cholesterol absorption at the intestinal level was determined using the dual isotope method using ¹³C cholesterol injected intravenously and ¹⁸O cholesterol given orally. Results Cholesterol absorption was 55.7 ± 6.5 % for the control and 33.5 ± 5.3 % for the phytostanol treatment. This massive reduction of the cholesterol absorption did not induce, on average, a difference in cholesterol endogenous synthesis which was measured at 0.074 ± 0.0015 pool/d for plant sterols and 0.0736 ± 0.0015 pool/d for controls (p > 0.05). Conclusions The results demonstrated that lecithin-solubilized stanols administrated during a short period of time (3 days) in an oil-in-water emulsion can dramatically decrease cholesterol absorption, without a consistent, concomitant increase in synthesis, which is highly suggestive of effective LDL cholesterol lowering. The effects of synthesis should be verified in a longer study with more subjects. Received: 17 September 2001, Accepted: 17 December 2001     

Comparison of the mortality of a cohort with the mortality of a reference population in a prognostic study

It is standard practice in epidemiological studies to compare the observed mortality of a cohort to the mortality expected in a reference population of the same age and sex distributions computed from national statistics. The same methods can be used in a prognostic study where the effects on survival of potential prognostic factors are studied in a cohort of patients with a given disease. Writing the hazard function in the cohort as the product of the hazard function in the reference population and a function of some characteristics of the patients, one can derive simple estimates and statistical tests of the standardised mortality ratios (Breslow et al.). The study of a cohort of patients with thyroid cancer will provide an example.     

The effects of calcium supplementation to patients with primary hyperparathyroidism and a low calcium intake

Summary. Background: In patients with primary hyperparathyroidism (PHPT) a low calcium intake might cause increased bone loss and thus aggravate osteoporosis, and a high intake might increase serum calcium level and the risk of nephrolithiasis. Aim of the study: Generally, guidelines recommend a normal calcium intake, and accordingly, those with a low intake might benefit from a modest calcium supplementation. This hypothesis was tested in the present study. Methods: Thirty-one patients with asymptomatic PHPT were recruited from an epidemiological study (The Troms? study 1994/95). Those with a daily calcium intake below 450 mg were given calcium supplementation (500 mg Ca²⁺), and those with an intake above 450 mg were followed without supplementation. The study was open and lasted 1 year. Serum levels of calcium, PTH, 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D, urinary calcium excretion, blood pressure, and bone mineral density (BMD) were measured. Results: Three subjects dropped out without reason, 1 developed abdominal discomfort from the calcium supplementation, and 3 had an increase in serum calcium of more than 0.2 mmol/L and were therefore excluded. The latter three did not differ from the rest of the group at baseline. Of the remaining 24 that completed the study, 17 were given calcium. In this group there was a non-significant increase in serum calcium and urinary calcium excretion, a significant decrease in PTH after 4 weeks (13.2 (6.0) vs 9.4 (3.0) pmol/L, P < 0.05), and a significant increase in BMD at the femoral neck at the end of the study (0.849 (0.139) vs 0.870 (0.153) g/cm², P < 0.05). The blood pressure was not significantly affected. Conclusions: Most patients with mild PHPT and a low calcium intake tolerate a moderate calcium supplement. This may have beneficial effects on the bones, but the patients must be followed carefully. Received: 30 April 2002, Accepted: 17 September 2002 Correspondence to: R. Jorde