Late postoperative quality of life following pancreatic head resections.

BACKGROUND/AIMS: To evaluate health-related quality of life (HRQoL) in patients that have undergone pancreatic resection and compare the results with representative population samples in early and late stage evaluations. Also, this study aims to observe possible associations with postoperative complications. METHODOLOGY: Twenty-seven single-institute patients operated on during a 3-year period due to a benign or malignant process of the periampullary region. HRQoL was measured by the 15D instrument. Data were compared with those obtained from representative Finnish general population samples. RESULTS: Twenty-five patients were interviewed in the early stage (24 months postoperatively). Fifteen had a benign and 12 a malignant disease. No differences were found in the postoperative HRQoL when the nature of the disease or the postoperative complications were considered. When compared with the general population in the early stage, HRQoL was lower in the study group in whole, and also when sleep, elimination (bladder or bowel function) and sexual activity were considered separately. In the late stage evaluation (110 months postoperatively) the study group consisted of 15 surviving patients. There were no differences in comparison to the general population. Also when comparing the same patients in 2 evaluation points (24 and 110 months), we did not find any difference in any of the 15D parameters. CONCLUSIONS: Postoperative HRQoL deteriorated in comparison to general population in the early stage but there were no differences in the late stage. This study encourages us to continue the use of the 15D at least as a part of HRQoL evaluation, because it allows comparisons between different diseases and the general population.

Resection of the head of the pancreas in Finland: effects of hospital and surgeon on short-term and long-term results.

BACKGROUND: To study the effect of hospital volume and surgeon volume on postoperative hospital mortality, morbidity and long-term survival after resection of the head of the pancreas in a nationwide study (case record study), taking into a consideration risk factors found important in series based on experience in one hospital. METHOD: The case record investigation of 374 patients identified from the National Hospital Discharge Database as having undergone resection of the head of the pancreas between 1990 and 1994 in Finland. RESULTS: The records of 350 patients were obtained for analysis. Operations were performed in 33 hospitals by 98 surgeons (average 2.1/year/hospital and 0.7/year/surgeon). Hospital mortality was 36/350 (10%), increasing from 4 and 7 to 13% with decreasing hospital volume from > 10 and 5-10 to < 5 respectively (P < 0.05) and increasing from 3 and 10 to 14% with decreasing surgeon volume from > 3 and 1-3 to < 1, respectively (P < 0.05). Most deaths were caused by surgical or technical complications (31/36 = 86%). Besides hospital mortality, postoperative complications, re-operations and hospital stay were also affected by surgeon volume. In the univariate analysis, also the age of the patient had an effect on the hospital mortality, and preoperative biliary stenting on the uncomplicated recovery, but in the multivariate analysis hospital mortality was independently affected by age (OR 0.94, P = 0.004) and surgeon volume (OR 1.3, P = 0.04), re-operations by surgeon volume (OR 1.10, P = 0.05) and hospital volume (OR 1.03, P = 0.05), postoperative complications by using the preoperative stent (OR 0.45, P = 0.02). Long-term survival was dependent on the histology of the specimen and by uncomplicated recovery, but not by hospital volume or surgeon volume. CONCLUSION: To decrease postoperative morbidity, mortality and hospital stay, pancreatic head surgery needs to be concentrated to only a few hospitals and to a few surgeons.

New immunochromatographic rapid test for diagnosis of acute Puumala virus infection.

A new immunochromatographic rapid test, POC PUUMALA (Erilab Ltd., Kuopio, Finland), for detection of acute-phase Puumala virus (PUUV) infection was developed based on a highly purified baculovirus-expressed PUUV nucleocapsid protein antigen and lateral immunodiffusion techniques. After addition of sample (5 microl of serum, plasma, or fingertip blood) and buffer, PUUV-specific immunoglobulin M (IgM) antibodies, if present, together with the gold-conjugated anti-human IgM, formed a specific colored line in 5 min. The sensitivity and specificity of the test were evaluated with 200 serum samples and 30 fingertip blood samples. The reference method for the serum samples was a micro-capture enzyme immunoassay (EIA) for IgM and an immunofluorescence assay (IFA) for IgG antibodies. The analytical sensitivity and specificity of the rapid test were 100 and 99%, respectively, for unfrozen serum samples (n = 103; 12 PUUV IgM-positive samples). When freeze-thawed serum samples were used, the sensitivity and specificity were each 97.1% (n = 70; 35 PUUV IgM-positive samples). The specificity of the test was 96.2% for 27 serum samples with nonspecific IgM antibodies or rheumatoid factor (RF). The fingertip blood samples (n = 30) were negative, but they gave clear positive results when spiked with IgM-positive sera (n = 20). The results were in good agreement with the standard diagnostic methods. The rapid performance, the lack of need for refined laboratory equipment, and the high specificity with fresh serum and fingertip blood samples indicate that the developed POC PUUMALA rapid test is a useful tool for fast diagnosis of acute PUUV infection.

Bone mineral metabolism after total gastrectomy.

Gastric surgery is mostly needed for treatment of gastric malignancy. To investigate the effect of total gastrectomy on bone mineral density (BMD) and bone mineral metabolism we evaluated 18 patients after total gastrectomy. Mean interval since operation was 71 +/- 20 months. BMD results were compared with age- and gender-matched controls (n = 46) and also expressed as T and Z scores. Bone mineral density measured by dual-energy X-ray absorptiometry (DXA) was found to be significantly lower in patients after total gastrectomy compared with healthy controls in the lumbar spine (p = 0.017 for women, p = 0.002 for men), femoral neck (p = 0.004 for women, p = 0.001 for men), Ward's triangle (p = 0.031 for women, p = 0.003 for men), and greater trochanter (p = 0.001 for women, p = 0.001 for men). Z scores for lumbar spine, femoral neck, Ward's triangle, and greater trochanter were -0.83, -1.54, -1.02, and -1.19, respectively. Biochemical measurements correlated poorly with BMD and were found to be of lesser value in diagnosing reduced bone mass as well as in differential diagnosis of etiology of osteopenia. The results of our study show the deleterious effect of total gastrectomy on bone mineral status and suggest an increased fracture risk in these patients.

Regulation of immunoreactive inhibin A and B secretion in cultured human granulosa-luteal cells by gonadotropins, activin A and insulin-like growth factor type-1 receptor.

Inhibins are gonadal glycoproteins with endocrine effects on pituitary FSH secretion and para/autocrine effects on ovarian and testicular function. The purpose of this study was to investigate the endocrine and para/autocrine regulation of inhibin A and inhibin B secretion in human ovarian granulosa-luteal cells. The cells were obtained from women undergoing in vitro fertilization, and the primary cultures were treated with FSH, LH, human chorionic gonadotropin (hCG), activin A, 8-bromo cyclic AMP (8-BrcAMP), staurosporine (a protein kinase C inhibitor) and an antagonist of IGF action (type-1 IGF receptor antibody alpha IR3). The secretion of inhibins was measured by ELISA assays capable of reliably distinguishing between inhibin A and B. FSH, LH, hCG and 8-BrcAMP increased inhibin A secretion on average up to 180% (P<0.01), 192% (P<0.05), 210% (P<0.01) and 243% (P<0.01) respectively of the control level, while their stimulatory effect on inhibin B secretion was less pronounced (up to 167%, P<0.01; 139%, P<0.05; 127%, P>0.05; 133%, P>0.05 of the controls respectively). alpha IR3 decreased inhibin A and B secretion down to 70% (P<0.01) and 50% (P<0.01) respectively of the control. Staurosporine decreased inhibin B secretion down to 49% (P<0.01) of the control; its effect on inhibin A secretion was not significant. Activin A increased inhibin B secretion up to fourfold of the control (P<0.05) while its effect on inhibin A secretion was insignificant. We conclude that gonadotropins via the protein kinase A signal transduction pathway are the main positive regulators of inhibin A and B secretion in human granulosa-luteal cells. The protein kinase C signal transduction pathway seems to be important especially for inhibin B secretion. Locally produced IGFs are probably important inducers of the production of both forms of inhibin in human ovaries while activins seem to upregulate inhibin B secretion.

Suitability of collection tubes with separator gels for collecting and storing blood samples for therapeutic drug monitoring (TDM).

In this study, we present significant changes occurring in serum drug concentrations while using blood collection tubes that contain a barrier gel. This report also contains results with antidepressant drugs, which have not been studied before with human samples. The drug concentrations were measured either with high performance liquid chromatography (HPLC) or fluorescence polarization immunoassay (FPIA). The results show that gel tubes are suitable for blood collection for antiepileptic, antibiotic, asthma and cardioactive drug measurements, since only slight adsorption was seen (0-5%). However, the studied tubes are not suitable for blood collection of antidepressants nor benzodiazepines, because the adsorption can be 5-30%. The adsorption was even higher (up to 40%) when samples were stored for 24 h after centrifugation in gel tubes. When the centrifugation step was performed after storage the effect of the barrier gel was lower (only 0-13%). Antidepressant drug measurements performed from patient specimens collected in the studied gel tubes and stored for 3 h showed <10% adsorption of the studied drugs. After 24 h storage time, concentrations of all analysed drugs decreased even more: adsorbed amount of drugs were about 5-20%. The studied gel tubes are proposed to be satisfactory for blood collection for antidepressant drug measurements if separation step is performed within 3 h after blood clotting. With the spiked samples the adsorption to barrier gel was higher, so it seems that adsorption is faster when drugs are not highly bound to serum proteins.

A new biodegradable stent for the pancreaticojejunal anastomosis after pancreaticoduodenal resection: in vitro examination and pilot experiences in humans.

We sought to develop a biodegradable pancreatic stent that could be easily placed at operation into the human pancreatic duct and the degradation of which could be easily followed up. Spiral-shaped, gamma-sterilized stents were manufactured of 0.4-mm polylactide wire in which there was added 23 weight-% barium sulfate. The biodegradability of the stents was studied in vitro at two different pH values, the first resembling that of pancreatic juice and the other that of bile. The effects of enzymoactivity in the test solution and the composition of the stents (with or without barium addition) also were tested. These kinds of stents have been experimented with in two pilot patients. Degradation of the stents occurred from 24 to 52 weeks of incubation. Alkaline milieu together with the presence of pancreatic enzyme made the stents degrade twice as fast as when either alkaline milieu or enzyme was present. In the milieu resembling pancreatic juice, barium sulfate had no effect on the degradation time. Neither of the pilot patients had any postoperative complications. Biodegradable, x-ray-positive stents degrade faster in pancreatic than in biliary milieu. Their safety and efficacy in human pancreaticojejunal anastomoses need further study.

Does apolipoprotein E genotype relate to BMD and bone markers in postmenopausal women?

OBJECTIVES: Bone mineral density (BMD) and development of osteoporosis are partly determined by genetic factors. The associations between one of suggested candidate, apolipoprotein E (apo E) genotype to bone mineral density (BMD) and bone biochemical markers was studied in 464 subjects recruited from a population-based group of early postmenopausal women (n = 13100). Additionally, the influence of apo E genotype on BMD changes during a 5-year follow-up with or without hormone replacement therapy (HRT) was investigated. METHODS: Participants were randomized into two treatment groups: HRT group: Sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate with or without vitamin D3, 100-300 IU/day + calcium lactate, 500 mg/day (n = 232), and the non-HRT group: Calcium lactate, 500 mg/day alone or in combination with vitamin D3, 100-300 IU/day (n = 232). BMD was measured from the lumbar spine and proximal femur at baseline and after 5 years of treatment (n = 352). In a subgroup (n = 59), the serum concentrations of bone biochemical markers (intact osteocalcin (OC), bone-specific alkaline phosphatase (BAP) and type I collagen carboxy-terminal telopeptide (ICTP)) were measured at baseline and after 1 year of follow-up. RESULTS: At baseline, the BMDs were similar between the five apo E genotype groups (2/3, 2/4, 3/3, 3/4, 4/4). No significant differences in lumbar or femoral neck BMDs of women with the apo E4 allele were found compared with those without it. There was a statistically significant difference in 5-year BMD changes between the HRT and non-HRT groups. After 5 years, the BMD of the femoral neck had remained constant and the mean lumbar spine BMD had increased by 1.5% in the HRT group, whereas both BMDs had decreased by 4-5% in the non-HRT group. However, the apo E genotype did not modify the changes in BMD in either group. Additionally, the baseline concentrations of bone metabolic markers and their 1-year changes showed no genotype-related associations. CONCLUSIONS: The results of our population-based study indicate that apo E genotype does not modify lumbar or femoral neck BMDs or serum bone biochemical markers or their response to HRT in early postmenopausal Caucasian women.

Clinical pharmacology of eicosanoids, nicotine induced changes in man.

Smoking is an important risk factor for respiratory and cardiovascular diseases. The role of numerous chemical, partly uncharacterised compounds existing in tobacco smoke is not known. (-)-Nicotine, its stereoisomer (+)-nicotine and main metabolite cotinine are biologically active compounds influencing e.g. catecholamine and eicosanoid systems. The precise mechanisms are not well known. The purpose of the present study consisting of a PhD thesis (11) and five original papers was to investigate the in vitro effects of nicotine isomers and cotinine on eicosanoid production in polymorphonuclear leukocytes, platelets and whole blood in vitro, and to clarify the effects of smoking without and with nicotine substitution on eicosanoid production in vivo and ex vivo. It was found that all the tested compounds modulated blood cell eicosanoid synthesis. Nicotine isomers and cotinine increased PGE2 but decreased TXB2, LTB4 and LTE4 synthesis in vitro. Eicosanoid synthesis in vivo and ex vivo was higher in smokers (n = 60) than in non-smoking controls (n = 20). This may contribute to the harmful cardiovascular effects of smoking. Cessation of smoking without, but not with, nicotine substitution reduced eicosanoid synthesis measured ex vivo as whole blood production or in vivo as urinary excretion of eicosanoid metabolites after 3, 7 and 14 days. Thus long-term nicotine substitution diminishes the beneficial effects of smoking cessation.

Disturbance in bone turnover in children with a malignancy at completion of chemotherapy.

BACKGROUND: Osteoporosis and pathological fractures have been observed in children with a malignancy. The mechanisms of osteopenia in childhood malignancies have not been well established. The purpose of the present study was to evaluate changes in bone turnover and in bone hormonal metabolism in children with a malignancy at completion of their chemotherapy. PROCEDURE: Serum levels of human intact osteocalcin, type I collagen carboxyterminal propeptide (PICP), type I collagen carboxyterminal telopeptide (ICTP), 25-hydroxyvitamin D [25-(OH)-D], 1,25-dihydroxyvitamin D [1, 25-(OH)(2)-D], intact parathyroid hormone, insulin-like growth factor I (IGF-I), IGF binding protein 3 (IGFBP-3), alkaline phosphatase, calcium, and phosphate were analyzed in 22 children with acute lymphoblastic leukemia and in 26 children with other malignancies. Results were expressed as Z-scores [mean (95% confidence intervals)] relative to healthy Caucasian-children. RESULTS: The marker of collagen degradation (ICTP) was significantly increased [1.43 (1.10-1.76), P < 0.0001] compared to reference values, whereas the markers of bone formation (PICP, osteocalcin) were not changed [0.07 (-0.55 to 0.49), 0.35 (-0.05 to 0.74), respectively, NS]. Serum 25-(OH)-D, 1,25-(OH)(2)-D, and calcium were significantly reduced [-0.65 (-0.87 to -0.42), -0.68 (-0.92 to -0. 42), -1.42 (-1.80 to -1.04), P < 0.0001, respectively]. CONCLUSIONS: Disturbance in bone turnover with low serum 25-(OH)-D, 1, 25-(OH)(2)-D, and calcium was observed in children with a malignancy at completion of their chemotherapy. A controlled study determining the possible benefits of vitamin D and calcium supplementation on bone turnover could be considered in these patients.

Urinary bone resorption markers in monitoring treatment of symptomatic osteoporosis.

We have studied the clinical usefulness of urinary bone resorption markers in postmenopausal women with symptomatic osteoporosis. The study design is a randomised double-blind placebo controlled study, in which the subjects were daily treated for 24 months either with a hormone analogue (2.5 mg Livial, generic name Tibolone, Organon, Amsterdam, Holland) plus 800 mg calcium (n = 14, age 63+/-5 years, range 52-68 years), or with placebo plus 800 mg calcium (n = 19, age 66+/-7 years, range 50-75 years). The laboratory methods for urinary bone resorption markers were enzyme immunoassays (EIA) for urinary pyridoline (PYD) and deoxypyridoline crosslinks (DPD), and for cross-linked N-telopeptides of Type I Collagen (NTx), and an HPLC assay for urinary hydroxyproline (HOP). All the urine assay results were calculated per mmol creatinine. All the resorption markers decreased during the two-year study period in both groups. The Z scores (discriminating power, i.e. ability of the different tests to distinguish the hormone treated subjects from the placebo treated subjects) for HOP and PYD were rather low: 0.06-1.52 for HOP and 0.68-1.47 for PYD. The differences between the two treatment groups were statistically significant for DPD at 12 and 24 months of treatment (P = 0.0471 and P = 0.0466, respectively), the Z scores ranging 0.45-1.90. NTx showed the most prominent decrease from the beginning of the study especially in the hormone treatment group: the differences between the two treatment groups were statistically highly significant for NTx already at 6 months of treatment (P = 0.0015), and the Z scores remained high ranging 2.11-3.82 throughout the two-year study period. Dual X-ray absorptiometry (DXA) of the lumbar spine and femoral neck did not show statistically significant differences between the two treatment groups throughout the two-year study period. After 2 years there was, however, a significant increase in bone density both in the spine (+ 6.6%, P = 0.0002) and in the femoral neck (+ 3.4%, P = 0.0389) in the women with hormone treatment. In the control group a significant increase (+ 5.1%, P = 0.0012) in the spine, whereas a non-significant decrease (-1.5%, n.s.) in the femoral neck was observed. We suggest that measurement of urinary cross-linked peptides derived from Type I collagen (NTx and DPD) might be a useful biochemical method of observing the positive clinical effect (i.e. reduction in bone resorption) following hormone replacement therapy in postmenopausal fracture patients.

Is the response of serum lipids and lipoproteins to postmenopausal hormone replacement therapy modified by ApoE genotype?

Postmenopausal hormone replacement therapy (HRT) has favorable effects on the serum lipid profile, and it also decreases the risk of cardiovascular diseases. The apolipoprotein E genotype has influence on serum levels of lipids and lipoproteins; apoE allele epsilon4 (apoE4) is associated with high total and LDL cholesterol levels. Genotype also influences the lipid responses to treatment with diet and statins, but the effect of HRT in different apoE genotypes is unknown. We studied the effects of HRT on the concentrations of serum lipids in apoE4-positive early postmenopausal women (genotypes 3/4 and 4/4) compared with apoE4-negative women (genotypes 2/3 and 3/3) in a population-based, prospective 5-year study. In all, 232 early postmenopausal women were randomized into 2 treatment groups: an HRT group (n=116), which received a sequential combination of 2 mg estradiol valerate (E2Val) from day 1 to 21 and 1 mg cyproterone acetate (CPA) from day 12 to 21 (Climen), and a placebo group (n=116), which received 500 mg/d calcium lactate. Serum concentrations of total, LDL, and HDL cholesterol and triglycerides were measured at baseline and after 2 and 5 years of treatment. A total of 154 women completed the final analysis. During the follow-up period, serum total cholesterol and LDL cholesterol concentrations decreased in the HRT group in apoE4-negative women (8.1% and 17.1%, respectively; P<0.001) but did not change in the HRT group in apoE4-positive women or in the placebo group. Serum HDL cholesterol concentrations decreased in the placebo group (apoE4-negative, 3.9%, P=0.015; apoE4-positive, 8.1%, P=0.004) but did not change significantly in the HRT group. Serum triglyceride levels tended to increase in both study groups and genotypes (15.1% to 36.2%, P<0.038 to 0.001), but no differences were observed between the study groups or genotypes, respectively. Our finding was that in postmenopausal Finnish women LDL cholesterol levels in apoE4-negative subjects respond more favorably to HRT than those in apoE4-positive subjects. This finding has potential importance in postmenopausal women with hypercholesterolemia, if confirmed in other studies.

Impaired development of bone mineral density during chemotherapy: a prospective analysis of 46 children newly diagnosed with cancer.

Osteopenia and osteoporosis are becoming increasingly recognized in children with cancer, though reasons for these changes are poorly understood. The purpose of the present study was to evaluate longitudinal changes in bone mineral density (BMD) and bone turnover in newly diagnosed children with a malignancy. Lumbar spine (L2-L4) and femoral neck bone mineral density (BMDareal, g/cm2) was measured by dual-energy X-ray absorptiometry in 46 children (age 2.9-16.0, median 8.0 years; 15 leukemias, 12 lymphomas, 19 solid tumors) at diagnosis, and after 6 months from the baseline. The apparent volumetric bone mineral density (BMDvol) was calculated to minimize the effect of bone size on BMD. Serum levels of osteocalcin (OC), type I collagen carboxy-terminal propeptide (PICP), and type I collagen carboxy-terminal telopeptide (ICTP) were analyzed at diagnosis, and during a 6-month follow-up. A significant decrease in lumbar BMDvol (-2.1%, p < 0.05), and in femoral BMDareal (-9.9%, p = 0.0001) and BMDvol (-8.5%, p = 0.0001) was observed after 6 months when compared with baseline measurements. The markers of bone formation (PICP, OC) were significantly decreased, and the marker of bone resorption (ICTP) was significantly increased at diagnosis as compared with normal values. By the end the follow-up, the levels of PICP and OC were normalized, whereas the level of ICTP continued to increase indicating that there was a negative balance in bone turnover. A deficient accumulation of bone mass might predispose children with a malignancy to impaired development of peak bone mass. A controlled study determining the benefits of an early intervention on bone turnover should be considered in these patients.

Reduced bone mineral density in long-term survivors of childhood acute lymphoblastic leukemia.

PURPOSE: Osteoporosis and pathologic fractures are occasionally found in patients with childhood acute lymphoblastic leukemia (ALL). This study was performed to determine the degree of possible osteopenia in long-term survivors of childhood ALL. PATIENTS AND METHODS: Lumbar spine (L2-L4) and femoral neck bone mineral densities (BMDs) (g/cm2) were measured in 29 survivors (aged 12 to 30 years, median 17) of childhood ALL 2 to 20 (median 8) years after discontinuation of chemotherapy. These results were compared with those from 273 healthy controls and expressed as a percentage of the age- and sex-matched control values (mean +/- standard deviation). RESULTS: Lumbar and femoral BMDs were significantly reduced in survivors of childhood ALL. Particularly, male gender (lumbar: 91.7 +/- 10.4%, p = 0.008; femoral: 91.9 +/- 11.3%, p = 0.005) and a history of cranial irradiation (lumbar: 93.0 +/- 8.9%, p = 0.005; femoral: 94.4 +/- 13.3%, p = 0.03) were associated with low lumbar and femoral BMDs. CONCLUSIONS: The detected deficit in bone density in survivors of childhood ALL may predispose these patients to osteoporotic fractures later in adulthood. A follow-up of BMD in survivors of childhood ALL should facilitate the identification of patients who would require specific therapeutic interventions to prevent further decrease of their skeletal mass and preserve their BMD.

A high-stearic acid diet does not impair glucose tolerance and insulin sensitivity in healthy women.

Results in epidemiological and experimental studies suggest that a diet rich in saturated fat may affect insulin sensitivity. However, no published data are available on the effect of stearic acid in this respect. Therefore, we examined the effects of a high-stearic acid diet and a high-oleic acid diet on glucose metabolism, serum lipids and lipoproteins, and blood coagulation factors in 15 healthy female subjects. Subjects followed the two experimental diets for 4 weeks according to a randomized crossover design. Both experimental diet periods were preceded by consumption of a baseline diet for 2 weeks. The diets provided 36% of energy (E%) as fat. In the experimental diets, 5 E% stearic or oleic acid was substituted for 5 E% of saturated fatty acids in the baseline diet. After the experimental diets, no differences were found in the insulin sensitivity index (mean+/-SEM, 5.4+/-1.9 v 5.2+/-1.6 x 10(-4) min(-1) x microU(-1) x mL(-1), nonsignificant [NS]), glucose effectiveness (0.026+/-0.006 v 0.026+/-0.003 min(-1), NS), or first-phase insulin reaction ([FPIR] 368+/-57 v 374+/-66 mU/L x min, NS). The concentration of serum lipids and lipoproteins and blood coagulation factors did not differ after the diet periods. In conclusion, a diet rich in stearic acid did not deteriorate glucose tolerance or insulin action in young healthy female subjects as compared with a diet rich in oleic acid.

[HIV screening in maternity clinics]. / HIV-seulonta äitiysneuvoloissa.

With a decision of the Finnish Department of Health and Social Welfare the HIV-screenings have been extended from the beginning of the year. The most important reason for this is the development of the medical treatment. With the present treatment, the transmitting of the HIV-infection from mother to child can be prevented in most cases.

Effects of postmenopausal hormone replacement therapy with and without vitamin D3 on circulating levels of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D.

The effects of postmenopausal hormone replacement therapy (HRT) and vitamin D3 on vitamin D metabolites (25OHD and 1,25(OH)2D) were studied in a population-based prospective 1-year study. The serum concentrations of intact parathyroid hormone (PTH), calcium, and phosphate were also studied. A total of 72 women were randomized into four treatment groups: HRT group (sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate), Vit D3 group (vitamin D3 300 IU/day + calcium lactate 500 mg/day), HRT + Vit D3 group (both above) and placebo group (calcium lactate 500 mg/day). Serum samples were taken in March-April, when vitamin D formation from sunlight in Finland is minimal after the dark winter. Serum concentrations of 25OHD increased in the Vit D3 group (33.5%, P < 0. 001) and in the HRT + Vit D3 group (38.2%, P < 0.001) but had not changed significantly in the HRT and placebo groups at the 1-year follow-up examination. Serum concentrations of calcitriol (1, 25(OH)2D) increased, however, only in the HRT group (23.7%, P < 0. 05), and remained unchanged in other groups. Serum concentrations of PTH decreased by 23.2% (P < 0.05) in the placebo group, but did not change significantly in the other three groups. The concentrations of serum calcium increased in the nonhormone groups (P < 0.001), whereas serum phosphate concentrations decreased in the hormone groups (P < 0.05 and 0.001). Our results confirm the positive effect of 1 year of HRT on serum calcitriol. Vitamin D3 supplementation increased 25OHD concentrations, but did not affect calcitriol concentrations even though the initial levels were low. Interestingly, the combination of HRT and vitamin D3 did not increase serum calcitriol concentrations as much as HRT alone.

Biochemical bone markers and bone mineral density during postmenopausal hormone replacement therapy with and without vitamin D3: a prospective, controlled, randomized study.

The effects of postmenopausal hormone replacement therapy (HRT) and vitamin D on the serum concentrations of three bone biochemical markers and their associations with bone mineral density (BMD) were studied in a population-based 1-yr follow-up study. A total of 72 healthy postmenopausal women were randomized into 4 treatment groups: HRT group (sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate), D group (vitamin D3, 300 IU/day), HRT+D group (both of the above), and placebo group (calcium lactate, 500 mg/day). Serum concentrations of osteocalcin (OC) and bone-specific alkaline phosphatase (BAP) were measured as biochemical markers of bone formation, and serum type I collagen carboxy-terminal telopeptide was measured as a marker of bone resorption at baseline and after 6 and 12 months of treatment. To investigate the associations of these markers with BMD, lumbar (L2-L4) and femoral neck BMDs were determined by dual x-ray absorptiometry at baseline and after 2.5 yr of treatment. In both hormone groups, the serum concentrations of the three bone metabolic markers had decreased after 12 months. Those of OC decreased by 29.2% (P = 0.017) in the HRT group and by 37.3% (P = 0.004) in the HRT+D group, and BAP concentrations decreased by 34.4% (P < 0.001) in the HRT group and by 36.2% (P < 0.001) in the HRT+D group. Serum type I collagen carboxy-terminal telopeptide concentrations had decreased by 21.6% (P = 0.012) in HRT group and by 14.1% (P = 0.011) in the HRT+D group. In the D group, the serum concentrations of BAP had decreased by 11.7% (P = 0.040) after 12 months, but the other two markers showed no change. The only change seen in the placebo group was a 19.2% increase in OC concentrations (P = 0.041) after 6 months, but at 12 months, the mean OC level was similar to that at baseline. After 2.5 yr, both lumbar and femoral BMD had decreased in the D group [2.1% (P = 0.022) and 3.6% (P = 0.019), respectively] and in the placebo group [3.3% (P = 0.009) and 2.7% (P = 0.010), respectively], whereas no significant changes occurred in the hormone groups. There were significant inverse correlations between the changes in lumbar and femoral BMDs and changes in all three biochemical markers (r = -0.240 through -0.336; P = 0.005-0.064). Our results suggest that HRT counteracts the biochemical changes caused by increased bone turnover associated with menopause. Importantly, the changes in bone markers correlate with long term changes in BMDs of lumbar spine and femoral neck. Low dose vitamin D treatment, however, seems to have only marginal effects on bone metabolism in early postmenopausal healthy women.