15-Lipoxygenase-2 is expressed in macrophages in human carotid plaques and regulated by hypoxia-inducible factor-1alpha.

BACKGROUND: Macrophages are prominent in hypoxic areas of atherosclerotic lesions and their secreted cytokines, growth factors and activity of enzymes are involved in atherogenesis. Previously, we showed that 15-lipoxygenase (LOX)-2 is expressed in human monocyte-derived macrophages and that hypoxia increases 15-LOX-2 expression and secretion of pro-inflammatory molecules. Here we investigated whether human carotid plaque macrophages express 15-LOX-2 and whether its expression in macrophages is regulated by hypoxia through hypoxia-inducible factor 1alpha (HIF-1alpha). MATERIALS AND METHODS: Carotid plaques from 47 patients with high-grade symptomatic carotid artery stenosis were analysed using immunohistochemistry, and stained areas were quantified by digital image analysis. Carotid plaque macrophages were isolated with anti-CD14 immunobeads using an immunomagnetic bead technique. Primary macrophages were transfected with HIF-1alpha siRNA or control siRNA before extraction of RNA and medium analysis. RESULTS: In paired tissue sections, the extent of staining for CD68 correlated with staining for 15-LOX-2 but not for 15-LOX-1. In carotid plaque macrophages isolated with anti-CD14 immunobeads, 15-LOX-2 mRNA was expressed at high levels. In primary macrophages, 15-LOX-2 expression was significantly increased by incubation with the HIF-1alpha stabilizer dimethyloxalylglycine. Knockdown of HIF-1alpha significantly decreased production of the 15-LOX-2 enzyme products 12- and 15-hydroxyeicosatetraenoic acid. In carotid plaques, HIF-1alpha staining correlated with staining for 15-LOX-2. CONCLUSIONS: These results demonstrate that 15-LOX-2 is highly expressed in human plaques and is correlated with the presence of macrophages and HIF-1alpha. 15-LOX-2 enzyme activity can be modulated by HIF-1alpha. Thus, increased expression of 15-LOX-2 in macrophages in hypoxic atherosclerotic plaque may enhance inflammation and the recruitment of inflammatory cells.

Drug use in patients with diabetes.

OBJECTIVE: To describe the use of pharmaceutical medications by patients with diabetes in Sweden. RESEARCH DESIGN AND METHODS: We analyzed the computerized Surveys of Living Conditions (SLC), performed regularly in Sweden, for the years 1988 and 1989, among individuals aged 16-84 years. Drug use (during a 2-week period) and the use of health services (during a 3-month period) were registered for subjects with diabetes (n = 361) and compared with age- and gender-standardized figures (using the diabetes group as the standard) in subjects with hypertension but without diabetes (n = 980), in subjects with a musculoskeletal condition but without diabetes (n = 2,187), in healthy subjects free from any medical condition (n = 6,664), and in the general population sample (n = 12,717). RESULTS: The reported use of medication was higher for subjects with diabetes compared with the general population regarding overall use (92.5 vs. 71.9%; P < 0.001), the use of cardiovascular drugs (52.2 vs. 36.3%; P < 0.001), all use of analgesics (43.8 vs. 36.5%; P < 0.05), and use of psychoactive drugs (23.5 vs. 15.3%; P < 0.01). Compared with the hypertension group, the use was lower regarding cardiovascular drugs (52.2 vs. 93.3%; P < 0.001), and compared with the musculoskeletal group, the use was lower regarding all use of analgesics (43.8 vs. 56.5%; P < 0.01) and the use of herbal products (6.8 vs. 11.8%; P < 0.05), but was higher regarding cardiovascular drugs (52.2 vs. 37.8%; P < 0.001). The use was higher compared with the healthy individuals, regarding all groups of drugs with the exception of vitamins and herbal products. CONCLUSIONS: Diabetic subjects have a higher overall use of drugs compared with the general population. Compared with other chronic illnesses, the differences are small except for disease-specific drugs (cardiovascular drugs in the hypertension group and analgesics in the musculoskeletal group). The main difference concerns the comparison with healthy subjects who had a markedly higher drug rate among diabetic subjects, thus signifying a greater impact on health.

Sympathetic outflow to muscles during treatment of hypertension with metoprolol.

Microelectrode recordings of multiunit sympathetic vasoconstrictor activity were made in muscle branches of the peroneal nerve in patients with essential hypertension before and during long-term treatment with the cardioselective beta-adrenergic receptor antagonist metoprolol. Nerve activity was quantified by counting the number of sympathetic bursts in the mean voltage neurogram. Metoprolol treatment lowered blood pressure and heart rate in all subjects. During long-term treatment, nerve activity was reduced both when compared to the level of activity after the first dose of the drug (p less than 0.01) and when compared to the control level before treatment (p less than 0.05). It is suggested that the reduction of sympathetic vasoconstrictor outflow to muscles contributed to the blood pressure reduction.

The effects of diet and zinc treatment on the fatty acid composition of serum lipids and adipose tissue and on serum lipoproteins in two adolescent patients with acrodermatitis enteropathica.

In two adolescent patients with acrodermatitis enteropathica fatty acid spectra in serum lipids and adipose tissue and serum lipoprotein concentrations were followed for about 7 yr. One patient was treated by diet and iv infusions of high amounts of linoleic acid and later by different doses of zinc. The other boy was given only varying doses of zinc. Extra supply of linoleic acid raised its concentrations in serum triglycerides, cholesterol esters, phospholipids, and adipose tissue lipids from low to normal or high levels. In both patients linoleic acid in serum lipids was sensible to the dose of zinc, decreasing when it was low and increasing when it was high. Serum triglycerides increased when the supply was low and was normalized when high doses were given. High-density lipoprotein cholesterol, however, remained low throughout the study. We conclude that in acrodermatitis enteropathica zinc thus seems to be of importance in regulating linoleic acid and serum lipoprotein metabolism.

Serum triglycerides are a risk factor for myocardial infarction but not for angina pectoris. Results from a 10-year follow-up of Uppsala primary preventive study.

At a follow-up 7-10 years after a health survey of men born in 1920-1924 in the municipality of Uppsala, 31 of the participants (n = 2322) had died from ischaemic heart disease (IHD). In response to a letter to all men alive in 1980, 106 men declared that they had had a myocardial infarction (MI) (verified or suspected). In 58 cases MI was verified from the hospital records. 28 other men had had typical central chest pain (angina pectoris) only. In another 20 men other diagnoses explained the chest pain for which they were treated in hospital. The health screening values for S-cholesterol and S-triglycerides, blood pressure and smoking habits were analysed in relation to the occurrence of IHD. In this prospective study, smoking, hypertension, S-cholesterol and S-triglycerides were identified as risk factors for fatal and non-fatal MI. The risk factor values were similar in subjects suffering from angina pectoris only to those in subjects who also developed ECG and/or transferase changes, with the exception of S-triglyceride concentration, which was normal in the group with angina pectoris. The subjects who had a fatal MI had a significantly higher blood pressure than those with non-fatal MIs, but otherwise these two groups did not differ. The results emphasize the importance of scrutinizing questionnaire data with regard to chest pain and of selection of end-points when risk factor patterns are described for cardiovascular diseases.

Metabolic effects of a change in antihypertensive treatment.

Twenty hypertensive men, aged 58 to 62 years, who had been treated with a combination of different drugs for many years, had their therapy changed in a stepwise manner to a combination of 50 mg of atenolol per day and 2 to 15 mg of prazosin per day. The effects of each change of treatment were assessed separately five to six months after the change. Serum lipids and high-density lipoprotein concentrations were determined, and an intravenous glucose tolerance test was performed at the start of the study and after each change. In the group in which therapy was changed from a diuretic to prazosin, serum cholesterol and triglyceride concentrations decreased significantly by 11 and 42 percent, respectively, but in the group in which therapy was changed from hydralazine to prazosin, there were no alterations in serum lipids or lipoproteins. The changes in therapy had no overall effects on glucose or insulin parameters evaluated with an intravenous glucose tolerance test. However, prazosin was associated with an increase in the fasting blood glucose level and a decrease in the peak insulin value after glucose injection, both of which were dose-related effects. The data indicate that the glucose turnover was at least as good after a switch from diuretic to prazosin treatment as before at lower insulin values. In those patients in whom therapy was switched from propranolol to 50 mg of atenolol per day, the serum triglyceride concentration decreased by about 10 percent, whereas in the group in which therapy was changed from 100 to 50 mg of atenolol per day, there were no serum lipid or lipoprotein alterations. The results show that a combination of 50 mg of atenolol per day and prazosin has metabolic advantages over combined diuretic and propranolol treatment. Such advantages may be of importance in the long-term treatment of hypertensive patients.

Comparative trial of felodipine and nifedipine in refractory hypertension.

The aim of this study was to compare the new vasodilator felodipine with nifedipine in 18 patients with poorly controlled hypertension. The design was a double-blind, cross-over study using a double-dummy technique. Felodipine 5mg was given 3 times daily and nifedipine 10mg 3 times daily. In case of an unsatisfactory blood pressure reduction, the drug dose was doubled. 14 patients had the higher dose of felodipine and 16 the higher dose of nifedipine. Both agents had good antihypertensive effect. After 1 week's therapy, felodipine reduced the blood pressure by 18/12 mm Hg (supine) and 18/13 mm Hg (upright), and nifedipine by 19/11 and 24/14 mm Hg, respectively. After 4 weeks' therapy, 12 hours after drug intake, felodipine reduced the blood pressure by 11/8 mm Hg (supine) and 16/8mm Hg (upright), and nifedipine by 3/2 and 6/4 mm Hg, respectively. Two patients on nifedipine withdrew from the study due to adverse reactions. In general, however, there were few side effects, with no significant difference between the drugs.

Oral contraceptives and back pain in women in a Swedish community.

BACKGROUND: Female back pain is a clinical problem-especially low back pain with symptoms from the pelvic posterior region-that is often aggravated in connection with pregnancy and childbirth. Hormones have been suggested as an aetiologic factor. This study is aimed to determine whether additional hormone preparations, i.e. oral contraceptives (OC), may contribute to the increased frequency of such pain. METHODS: A register study was conducted to investigate the use of drugs and health care use in a female population with known OC consumption. Specifically, we registered the number of primary health care visits for low back pain, comparing OC users with non-OC using age-matched women with otherwise equal circumstances. RESULTS: OC users recorded a significantly higher incidence of low back symptoms during the study period compared to non-users. Pregnancy was not found to be a confounding factor. CONCLUSIONS: The intriguing association between OC use and a higher incidence of low back pain, does not enable us to conclude that there is a causal connection, but it should lead to further studies.

PIP: The prevalence of back pain among Swedish women 16-84 years of age has increased from 6.1% in 1975 to 8.1% in 1989; no such increase has been recorded for Swedish men. To determine whether an association exists between back pain and oral contraceptive (OC) use, a register study was conducted at the major health center in Tierp, Sweden; 65% of the 45,000 physician visits made each year by the population of this municipality were to this site. The 503 women prescribed OCs in 1980 (19.08% of women 14-44 years of age in the study area) served as cases; age-matched non-users were controls. Lower back pain was recorded significantly more frequently each year during the 1981-85 follow-up period among OC users than among controls (p 0.01 in the first year and 0.05 in the fourth year). Pregnancy was not a confounding factor. However, the register did not allow analysis of life-style factors such as heavy physical work, smoking, or obesity that are also associated with back pain. Moreover, bias could have been introduced by the fact that OC users made more health center visits, increasing the potential for diagnosis. Additional studies are required to determine whether the OC-back pain association identified in this study is causal.

Functioning and well-being of patients with type 2 diabetes or angina pectoris, compared with the general population.

This study compares the health-related quality of life (HRQOL) of patients with type 2 diabetes mellitus or angina pectoris with that of a standard population sample (SPS). The HRQOL was assessed by the Swedish Health-Related Quality of Life Survey (SWED-QUAL), a generic HRQOL questionnaire adapted from the Medical Outcomes Study (MOS), with twelve scales tapping aspects of physical, mental, social and general health. Subjects between 45 and 84 years of age who answered the questionnaire were included, i.e. 266 patients with type 2 diabetes, 758 patients with mild angina pectoris (Canadian Classes I and II) and 908 with severe angina (Canadian Classes III and IV). As controls, we used 1126 subjects from the SPS. Patients with type 2 diabetes, mild angina and severe angina showed an increasing degree of health disturbance, compared with the SPS. Diabetic patients with no heart disease showed only a minor impact on the HRQOL, while the presence of a heart disease showed a considerable impact. In angina patients, the presence of diabetes also to some extent added to the decrease in HRQOL. On comparing the impact of the heart disease and diabetes on the HRQOL, the heart disease showed a stronger effect on most aspects of the HRQOL than diabetes. It is concluded that coronary heart disease is an important predictor of the impact on the HRQOL of type 2 diabetes patients.

Quality of life in relation to comorbidity among diabetic patients followed for three years in Swedish primary health care.

The aim of this study was to follow health-related quality of life (HRQOL) in diabetic subjects over a three-year period in relation to their medical situation. Forty-eight subjects 42-81 years of age in 1992 were identified as those responding to the HRQOL questionnaire on both occasions from a larger study of 341 diabetic patients in 1992 and 413 in 1995 in Stockholm County. Age- and sex-matched controls were taken from randomly collected samples of the general Swedish population. HRQOL was assessed by the SWED-QUAL (the Swedish Health-Related Quality of Life Survey). Medical data were extracted from medical records at community health centres. Pearson's correlation coefficient for SWED-QUAL results over time exceeded 0.60 for seven of the ten scales (p < 0.001). A significant difference between 1992 and 1995 was found only for "Physical functioning" (p < 0.01). The general deterioration in health seen in medical records was accompanied by a decrease in the "Sleep problems" scale. In conclusion, worse outcome was noted only for "Physical functioning", while deterioration in health according to medical records was related to a worse outcome with respect to "Sleep problems". However, as the sample was small and not randomly selected, the results should be interpreted with caution and need confirmation in further studies.

Different long-term metabolic effects of enalapril and atenolol in patients with mild hypertension. EGTA Group.

The primary objective in this multicentre, double-blind randomised, parallel study was to compare the metabolic effects of 12 months of treatment with an ACE inhibitor (enalapril) with those of a selective beta-blocker (atenolol) in patients with mild hypertension. The patients (35-69 years of age) were included if they were without antihypertensive drugs and after six months of nonpharmacological treatment had supine DBPs between 90 and 104 mmHg; 220 patients were randomised to enalapril (20 or 40 mg/day) and 218 to atenolol (50 or 100 mg/day). After 12 months of treatment, atenolol significantly increased the glucose concentrations at 60, 90 and 120 minutes after an oral intake of 75 g glucose (P < 0.01), while enalapril did not. Atenolol significantly increased fasting blood glucose and insulin concentration 120 minutes after glucose intake, while enalapril did not. Plasma total cholesterol and triglycerides increased significantly in patients having atenolol but not in those having enalapril. HDL cholesterol decreased significantly in the atenolol group but not in the enalapril group. The proportions of patients with clinical adverse experiences were similar in both treatment groups. These results indicate that enalapril does not influence either glucose tolerance or lipoprotein metabolism while atenolol does. These findings are consistent over the 12 month treatment period and confirm earlier short-term study results.

24-hour ambulatory blood pressure monitoring in elderly normotensive individuals and its reproducibility after one year.

To study ambulatory blood pressure (ABP) and its reproducibility in healthy normotensive elderly subjects, 34 individuals were randomly selected. Their ages were 65 years (n = 10), 70 years (n = 10), 75 years (n = 8) and 80 years (n = 6). SpaceLabs 90207 system was used and one initial and a follow-up measurement after one year was performed. It was found that 24h ABP easily could be recorded in elderly subjects. A mean of 97% of the measurements were successful and only two of 34 subjects dropped out because of measurement failures. Nocturnal blood pressures were lower in all age groups and in both sexes. The standard deviations of the differences between the baseline and one year measurements were for the daytime period 8/4 mmHg and for the nighttime period 12/8 mmHg. In conclusion, ABP is easily accepted as a clinical method in normotensive elderly subjects. In all subjects there is a reduction of the nocturnal blood pressure and the reproducibility of ABP after one year is good.

Quality of life in primary care asthma.

In primary care, asthma is usually assessed by means of the patients' history regarding symptoms and simple lung-function testing. These outcomes may, however, not be related to other estimates of asthma control such as quality of life. In the present study quality of life was studied in relation to symptoms (visual analogue scale, VAS) and lung function in adult patients with asthma in a primary-care setting. In a healthcare centre in Stockholm, 405 individuals diagnosed as having asthma were identified. Out of this number, 120 patients completed the study. Patients were categorized into four groups according to lung function and their response to a question regarding asthma symptoms on the VAS. Quality of life was evaluated with the Asthma Quality of Life Questionnaire (AQLQ) and current treatment was recorded. Quality of life differed significantly between the groups with regard to all domains and overall score; overall score was 6.0 (0.12)--(mean SEM) in group A (VAS < or = 2, normal FEV1), 5.4 (0.24) in group B (VAS < or = 2, low FEV1), 4.8 (0.25) in group C (VAS > 2, normal FEV1) and 4.6 (0.24) in group D (VAS > 2, low FEV1) (P < 0.0001). In general a gradient, with group A having the highest and group D the lowest score, was detected. Experience of symptoms (VAS > 2) was highly related to lower scores in the environmental domain (P < 0.0001). The correlation between FEV1 and quality of life was generally low whereas there was a fairly good correlation between VAS and quality of life (P < 0.0001 for all domains). Patients without steroid treatment had higher quality of life scores than patients treated with steroids. The majority of asthma patients in primary care have high quality of life scores, indicating a low prevalence of symptoms and only slight activity limitations. Evaluation of quality of life enables a more careful grading of asthma status. Furthermore, this measure provides information concerning asthma control that is not revealed by spirometry and simple questions regarding symptoms.

Nocturnal micturition, sleep and well-being in women of ages 40-64 years.

OBJECTIVE: To study the relationship between sleep and nocturnal micturition in women 40-64 years old. METHODS: A questionnaire study was carried out in 3669 (6000 invited) randomly selected women in the County of Jämtland in Sweden. Questions were asked about the general state of health, nocturnal micturition, sleep, menstruation and menopausal symptoms, and also about visits to doctors and the use of sleeping pills and hormone preparations. RESULTS: The subjective evaluation of the general state of health and of a feeling of contentedness and of confidence in the future worsened with increasing numbers of nocturnal voiding episodes. Sleep was more strongly correlated to the number of nocturnal voiding episodes (R2 = 0.099; P < 0.0001) than to age (R2 = 0.021; P < 0.0001) or the menopause (R2 = 0.017; P < 0.0001). Daytime sleepiness was three times more common among women with three or more nocturnal voiding episodes than among those with no nocturnal micturition. Women who voided three or more times in the night consulted a doctor twice as frequently as those without nocturnal micturition and were treated with drugs 2.5 times as often. The corresponding figures for sick-listing were 75 and 15 days per year, respectively. CONCLUSION: Frequent nocturnal micturition is common in 40-64-year-old women and impair sleep with subsequent decrease in daytime performance and general well-being.

Nocturia and health in women aged 40-64 years.

To analyse the relationship between nocturnal micturition and health in 40- to 64-year-old women. A questionnaire study was carried out in 3669 randomly selected women (out of 6000 invited) in the County of Jämtland, Sweden. Questions were asked about the general health status of health, health development during the last 5 years, nocturnal micturition, parity, menstrual status, menopausal symptoms, hormone replacement therapy, cardiac diseases, diabetes and snoring. Poor health was reported by 10.4%. In 24.1% of the women health development had been unfavourable in the last 5 years. Poor health was reported by 4.7% of women without nocturnal micturition, and by 11.2, 20.1 and 39.0% (P<0.0001) of women with one, two, and three or more nocturnal voiding episodes, respectively. In a multiple logistic regression analysis significant independent correlates of health were: one versus no nocturnal micturitions (odds ratio [OR] 2.2; confidence interval [CI] 1.5-3.3), two versus none (OR 3.2; 1.9-5.3), and three or more versus none (OR 6.5; 3.5-11.9), spasmodic chest pain (OR 6.6; CI 3.0-14.5), irregular heart beats (OR 3.0; CI 2.1-4.3), diabetes (OR 5.1; CI 2.8-9.4), leg oedema> or =6 days/month versus <6 days/month (OR 23; CI 1.6-3.3), snoring: < or =3 times/week versus never (OR 1.4; CI 1.0-2.0), snoring 4-7 times/week versus never (OR 1.6; CI 1.1-2.2), being<5 years after versus being before the menopause (OR 1.6; 95% CI 1.0-2.5), 5-9 years after versus before the menopause (OR 1.7; CI 1.0-2.9), > or =10 years after versus before the menopause (OR 2.2; CI 1.3-3.7), diuretic treatment (OR 2.8; CI 1.7-4.6). The perceived state of health in 40- to 64- year-old women is profoundly affected by nocturia, independently of heart diseases, diabetes, snoring, age and menopausal status.

Body mass index and sleep in women aged 40 to 64 years.

A questionnaire study was carried out in 6000 randomly selected women in the County of Jämtland in Sweden. The response rate was 61.2%. Questions were asked about general health, height and body weight, sleep, menstruation and menopausal complaints. There were also questions about visits to doctors and the use of sleeping pills and hormone preparations. A deterioration of the night's sleep after the age of 60 years was associated especially with a low body mass index (BMI). In the subgroup with a BMI below 20 (kg m-2), frequent awakenings were reported 4 times more often in women 60-64 years old than in those aged 40-44 years. No such difference was found with a BMI > or = 30. In the age group 60-64 years twice as many women with BMI > or = 30 as women with BMI < 20 slept without waking up at night. BMI was similar in women with and without oestrogen therapy before the menopause. After the menopause the BMI in these two groups was 25.0 +/- 3.1 (mean +/- S.D.) and 25.6 +/- 3.8, respectively (P < 0.05). Oestrogen-treated women had fewer sleep disorders than other women of the same age. Of the premenopausal women, 3.4% used sleeping pills, compared with 8.0% after the menopause. Before the menopause the use of sleeping pills was not related to BMI, but after the menopause this use was twice as common among women with BMI < 20 kg m-2 than among those with BMI > or = 30kg m-2.

Collagen metabolism markers as a reflection of bone and soft tissue turnover during the menstrual cycle and oral contraceptive use.

Two different groups of women, 23 healthy young adults and 13 women with chronic posterior pelvic pain, were studied before and during use of oral contraceptives (OC). Collagen metabolism markers-here, the amino-terminal propeptide of type I procollagen, the carboxy-terminal telopeptide of type I collagen, and the amino-terminal of procollagen type III-as well as hormones and other endocrine factors indicating the balance between androgen expression/anabolism and catabolism of the subjects (testosterone, sex-hormone binding globulin, and insulin-like growth factor I were measured. Type I procollagen, the carboxy-terminal telopeptide of type I collagen, and the amino-terminal of procollagen type III were all significantly decreased during OC use. These findings implicate OC use-induced changes in collagen type I and III turnover. A shift in the anabolic/catabolic balance was also recorded indicating a less anabolic situation during OC use.

A comparison of the hypotensive and metabolic effects of 50 and 100 mg atenolol per day.

Nine patients who had been treated for hypertension for many years with atenolol in a dose of 100 mg/day took part in this 18-month study, during which the dosage alternated between 50 and 100 mg/day for two-month periods. Blood pressure, heart rate, serum triglycerides and cholesterol and high density lipoprotein (HDL) lipids were checked at the end of each period. Altogether 27 and 32 measurements were made at the 50 and 100 mg dose levels respectively. Heart rate was lower by three beats/min (p less than 0.05) at the higher dose, but blood pressure and serum lipids and HDL cholesterol were not significantly different at the two dose levels.

Raynaud's phenomenon in a female population: prevalence and association with other conditions.

In a random sample of 3000 women of ages eighteen to fifty-nine years in the city of Västerås, Sweden, 19% of the 2705 responders to a questionnaire complained of cold and white fingers with or without numbness. On the basis of interview and examination, 79% of these women were diagnosed as having Raynaud's phenomenon (RP), giving a prevalence of 15.6%. A significantly higher rate of family members with cold, white fingers was found only in the group of women with pronounced RP (p less than 0.001). A significantly higher frequency of women with pronounced RP than of the control group had a history of recurrent muscle/joint pain (p less than 0.05). Laboratory tests that might indicate an active connective tissue disease did not, however, confirm a diagnosis of rheumatoid arthritis. All three subgroups differed significantly from the control group in terms of recurrent chest pains; subgroups 2 and N differed significantly from controls in terms of recurrent headaches.

The concentration of magnesium in erythrocytes in female patients with primary Raynaud's phenomenon; fluctuation with the time of year.

The magnesium (Mg) concentration was measured in erythrocytes of 30 women with pronounced primary Raynaud's phenomenon (PRP) and of 33 age-matched healthy control women. The measurements were made at three different times, six months apart. The mean Mg concentration in the PRP group and the control group differed significantly at each measurement. The values for the two groups were, respectively, 1.64 +/- 0.21 and 2.02 +/- 0.21 mmol/L (P < 0.001) in February, 1988; 2.16 +/- 0.21 and 1.85 +/- 0.21 mmol/L (P < 0.001) in August, 1988; and 2.01 +/- 0.21 and 2.37 +/- 0.20 mmol/L (P < 0.001) in January, 1989. The erythrocyte Mg level varied significantly with the time of year in both groups. In the PRP group the mean value was significantly higher in August than in the two winter months, but in the control group it was significantly lower in August. The authors conclude that women with PRP have a significantly lower magnesium concentration in erythrocytes during winter than the healthy controls and that this concentration varied with the season of the year in both groups.