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C Christiansen

Publications and source records attributed to C Christiansen.

At least 91 records · Page 5Linked to original sources

Low doses of estradiol in combination with gestodene to prevent early postmenopausal bone loss.

OBJECTIVE: Our purpose was to study combinations of estradiol and gestodene for prevention of bone loss in early postmenopausal women. STUDY DESIGN: We randomly assigned 278 healthy, early postmenopausal women to receive either 2 mg 17beta-estradiol sequentially combined with 25 microg gestodene (group 2/25s), 2 mg estradiol sequentially combined with 50 microg gestodene (group 2/50s), 1 mg estradiol sequentially combined with 25 microg gestodene (group 1/25s), 1 mg estradiol continuously combined with 25 mg gestodene (group 1/25c), or placebo. RESULTS: After 3 years the changes in bone mineral density of the spine were as follows (mean +/- SEM): group 2/25s, 7. 41% +/- 0.72%; group 2/50s, 8.53% +/- 0.90%; group 1.25s, 6.67% +/- 0.88%; group 1/25c, 4.44% +/- 0.59%; and placebo group, -2.03% +/- 0. 64%. The changes in bone mineral density were mirrored in the biochemical bone markers. The average responses for the urinary C-terminal telopeptide fragments of type I collagen corrected for creatinine excretion were as follows (mean of baseline +/- SEM): group 2/25s, -68.8% +/- 0.03%; group 2/50s, -72.8% +/- 0.02%; group 1/25s, -60.7% +/- 0.03%; group 1/25c, -52.28% +/- 0.04%; and placebo group, 6.5% +/- 0.09%. Beneficial lipid effects were found in all active groups. The decreases in low-density lipoprotein were as follows (mean +/- SEM): group 2/25s, -13.7% +/- 3.0%; group 2/50s, -14.6% +/- 3.2%; group 1/25s, -9.28% +/- 2.2%; group 1/25c, -9.92% +/- 2.4%; and placebo group, 1.53% +/- 1.9%. CONCLUSION: These results demonstrate that estradiol therapy with 1 mg estradiol is fully protective against early postmenopausal bone loss.

Bone Density↗

Piperazine oestrone sulphate and interrupted norethisterone: effects on the postmenopausal endometrium.

OBJECTIVE: To assess the effects on the postmenopausal endometrium of two doses of oral piperazine oestrone sulphate and interrupted norethisterone in comparison with a continuously combined regimen and placebo. DESIGN: A prospective randomised trial. PARTICIPANTS: Two hundred healthy postmenopausal women. METHODS: Random assignment to two years of treatment with alternating three-day cycles of 1.5 mg piperazine oestrone sulphate and 1.5 mg piperazine oestrone sulphate + 0.7 mg norethisterone (highEP), or alternating three-day cycles of 0.75 mg piperazine oestrone sulphate and 0.75 mg piperazine oestrone sulphate + 0.35 mg norethisterone (lowEP), or 2 mg 17 beta-oestradiol continuously combined with 1 mg norethisterone acetate (E2+NETA), or placebo. MAIN OUTCOME MEASURES: Effect of treatment on endometrial histology, endometrial thickness, occurrence of uterine bleeding, endometrial oestrogen and progesterone receptor content, endometrial isocitrate dehydrogenase activity, and serum placental protein 14. RESULTS: The incidence of bleeding declined with time. In the second treatment year, the women receiving lowEP reported on average 7.3 days of bleeding, highEP 16.7 days, and E2+NETA 11.2 days. Histological assessment of endometrial biopsies revealed an atrophic or slightly secretory endometrium. Serum placental protein 14 increased slightly, but was statistically highly significant, during treatment, but no cyclical variation was observed. Endometrial isocitrate dehydrogenase was low in all three hormone groups and the same low level of endometrial oestrogen receptor and progesterone receptor was found comparable to the level in the placebo group. CONCLUSIONS: Histological and biochemical assessment of the endometrium showed that interrupted hormone replacement therapy induced the same pattern in endometrial parameters as continuous combined hormone replacement therapy.

Administration, Oral↗

Piperazine oestrone sulphate and interrupted norethisterone in postmenopausal women: effects on bone mass, lipoprotein metabolism, climacteric symptoms, and adverse effects.

OBJECTIVE: To compare the effects of two doses of piperazine oestrone sulphate combined with interrupted norethisterone, with that of oestradiol continuously combined with norethisterone acetate, and with placebo, in postmenopausal women. DESIGN: A prospective randomised trial. PARTICIPANTS: Two hundred postmenopausal women. SETTING: Monocentre study with expertise in osteoporosis. METHODS: The participants were randomly assigned to two years of treatment with alternating three-day cycles of 1.5 mg of piperazine oestrone sulphate plus 0.7 mg of norethisterone (highEP), or alternating three-day cycles of 0.75 mg of piperaine oestrone sulphate plus 0.35 mg of norethisterone (lowEP), or 2 mg of 17beta-oestradiol continuously combined with 1 mg of norethisterone acetate (E2+NETA), or placebo. MAIN OUTCOME MEASURES: Change in bone mineral density, lipoprotein metabolism, climacteric symptoms, and adverse effects. RESULTS: One hundred and twenty-one women completed the study. Spinal bone mineral density was increased about 9% over two years by E2+NETA, about 6% by highEP, 4% by lowEP, but remained unchanged in the placebo group. The same pattern was seen in the hip and forearm. All hormone regimens decreased markers of bone turnover and alleviated climacteric symptoms. Serum lipoproteins decreased by about 10% in all hormone groups. CONCLUSIONS: All hormone regimens studied prevented bone loss completely and lowered serum lipids.

Aged↗

The influence of thinness and smoking on bone loss and response to hormone replacement therapy in early postmenopausal women.

We studied the influence of thinness and smoking in 153 early postmenopausal women from a 3-yr period, comparing treatments of 1 or 2 mg estradiol with placebo. The baseline body mass index (BMI) was significantly associated with bone resorption (r = -0.26, P < 0.01 for urinary CrossLaps with 21% difference between extreme tertiles) with a consequent association between BMI and bone mineral density (BMD; r = 0.38, P < 0.001 for BMD of hip with 10% difference between extreme tertiles). A low BMI led to an increased rate of loss (r = 0.45, P < 0.01 for BMD of spine), whereas response to treatment with either 1 or 2 mg estradiol was independent of BMI. Smoking was associated with a 4% lower BMD at baseline compared with that in nonsmokers. This effect was additive with that of BMI. For smokers the increase in serum estradiol during hormone replacement therapy was only half of that in nonsmokers. For women treated with placebo or 2 mg estradiol, serum FSH levels were similar in smokers and nonsmokers, but during treatment with 1 mg estradiol, serum FSH was significantly less suppressed in smokers. This was mirrored in the BMD response, where smokers responded similarly to 2 mg estradiol and placebo as did nonsmokers, whereas smokers receiving 1 mg estradiol experienced only half the increase compared to nonsmokers. In conclusion, thinness and smoking are important risk factors for osteoporosis development, but are counteracted by hormone replacement therapy.

Body Mass Index↗

Vitamin D receptor and estrogen receptor gene polymorphisms in postmenopausal Danish women: no relation to bone markers or serum lipoproteins.

OBJECTIVE: To investigate the polymorphisms of the vitamin D receptor (VDR) and estrogen receptor (ER) genes in relation to biochemical markers of bone turnover (serum osteocalcin and urinary collagen type I degradation products (CrossLaps), and to study ER genotypes in relation to serum lipoproteins, blood pressure, or changes in these parameters after 2 years of hormone replacement therapy (HRT) in 499 Danish postmenopausal women. METHODS: The VDR gene polymorphisms were determined by means of the three restriction enzymes, i.e. BsmI, ApaI and TaqI, while the ER gene polymorphisms were determined by means of the PvuII and XbaI restriction enzymes. Serum osteocalcin, urinary CrossLaps and the lipoproteins were also assessed. Body mass index was recorded. RESULTS: The VDR or ER genotypes did not differ significantly with respect to age, age at menopause or body mass index. No significant effect of VDR or ER genotype on bone turnover was found. Furthermore, we were unable to find any relationship between ER genotype and lipoproteins or blood pressure at baseline, or changes in these parameters during HRT. CONCLUSION: A clinically significant relationship between VDR and ER genotypes and biochemical markers of bone turnover or serum lipoproteins could not be demonstrated in healthy Danish postmenopausal women.

Aged↗

Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators.

CONTEXT: Raloxifene hydrochloride, a selective estrogen receptor modulator, prevents bone loss in postmenopausal women, but whether it reduces fracture risk in these women is not known. OBJECTIVE: To determine the effect of raloxifene therapy on risk of vertebral and nonvertebral fractures. DESIGN: The Multiple Outcomes of Raloxifene Evaluation (MORE) study, a multicenter, randomized, blinded, placebo-controlled trial. SETTING AND PARTICIPANTS: A total of 7705 women aged 31 to 80 years in 25 countries who had been postmenopausal for at least 2 years and who met World Health Organization criteria for having osteoporosis. The study began in 1994 and had up to 36 months of follow-up for primary efficacy measurements and nonserious adverse events and up to 40 months of follow-up for serious adverse events. INTERVENTIONS: Participants were randomized to 60 mg/d or 120 mg/d of raloxifene or to identically appearing placebo pills; in addition, all women received supplemental calcium and cholecalciferol. MAIN OUTCOME MEASURES: Incident vertebral fracture was determined radiographically at baseline and at scheduled 24- and 36-month visits. Nonvertebral fracture was ascertained by interview at 6-month-interim visits. Bone mineral density was determined annually by dual-energy x-ray absorptiometry. RESULTS: At 36 months of the evaluable radiographs in 6828 women, 503 (7.4%) had at least 1 new vertebral fracture, including 10.1% of women receiving placebo, 6.6% of those receiving 60 mg/d of raloxifene, and 5.4% of those receiving 120 mg/d of raloxifene. Risk of vertebral fracture was reduced in both study groups receiving raloxifene (for 60-mg/d group: relative risk [RR], 0.7; 95% confidence interval [CI], 0.5-0.8; for 120-mg/d group: RR, 0.5; 95% CI, 0.4-0.7). Frequency of vertebral fracture was reduced both in women who did and did not have prevalent fracture. Risk of nonvertebral fracture for raloxifene vs placebo did not differ significantly (RR, 0.9; 95% CI, 0.8-1.1 for both raloxifene groups combined). Compared with placebo, raloxifene increased bone mineral density in the femoral neck by 2.1 % (60 mg) and 2.4% (120 mg) and in the spine by 2.6% (60 mg) and 2.7% (120 mg) P<0.001 for all comparisons). Women receiving raloxifene had increased risk of venous thromboembolus vs placebo (RR, 3.1; 95% CI, 1.5-6.2). Raloxifene did not cause vaginal bleeding or breast pain and was associated with a lower incidence of breast cancer. CONCLUSIONS: In postmenopausal women with osteoporosis, raloxifene increases bone mineral density in the spine and femoral neck and reduces risk of vertebral fracture.

Adult↗

Efficacy and acceptability of intranasal 17 beta-oestradiol for menopausal symptoms: randomised dose-response study. Aerodiol Study Group.

BACKGROUND: The benefit of oestrogen therapy for menopause symptoms is well recognised. However, the means of delivery currently available have disadvantages, including variable bioavailability, intestinal and hepatic first-pass effects, and dermatological reactions. An intranasal 17beta-oestradiol spray, S21400, which bypasses such drawbacks, has been developed. We studied the efficacy and tolerability of S21400 in the treatment of postmenopausal symptoms. METHODS: In this double-blind study, 420 postmenopausal women were randomly allocated to receive intranasal placebo or S21400 in doses of 100 microg, 200 microg, 300 microg, or 400 microg, or oral oestradiol valerate in doses of 1 mg or 2 mg, daily for 12 weeks. The primary outcomes were the Kupperman Index (KI) and the incidence of hot flushes. Tolerability assessments included rhinoscopy and ciliary function tests. FINDINGS: S21400 dose-dependently decreased KI (p<0.001), with a lowest effective dose of 300 microg/day at 4 weeks (p<0.05) and 200 microg/day at 12 weeks (p<0.01). The incidence of hot flushes decreased by a maximum of 75% (S21400 lowest effective dose 200 microg/day at 4 weeks and 100 microg/day at 12 weeks). S21400 increased serum oestradiol exposure dose-dependently, to concentrations similar to those achieved with oral oestradiol 1-2 mg, with lower intra-patient and inter-patient variability. There was no significant difference in ear, nose, and throat function or adverse events between the S21400 and the placebo or oral oestradiol groups, except for a greater incidence of sneezing and application site reaction (99% mild or moderate) in the S21400 groups. S21400 was thought to be effective and convenient by the patients, and compliance was high. INTERPRETATION: Intranasally administered 17beta-oestradiol is significantly better than placebo; its effectiveness at reducing menopausal symptoms is similar to that of oral oestradiol and is also well-tolerated. Intranasal administration avoids first-pass metabolism and provides a reproducible, easily adjustable dosing mechanism that represents a new option for hormone replacement therapy.

Administration, Intranasal↗

Natural androgens inhibit male atherosclerosis: a study in castrated, cholesterol-fed rabbits.

The effect of natural androgens on serum lipids and atherosclerosis is controversial. We therefore studied this important issue prospectively in an animal model of atherosclerosis. Eighty male rabbits were randomized to bilateral castration, and 20 animals were sham operated. The castrated rabbits were randomized to 500 mg oral dehydroepiandrosterone (DHEA) daily, 80 mg oral testosterone undecanoate (TU) daily, or 25-mg intramuscular injection of testosterone enanthate (TE) twice weekly, whereas the fourth castrated group (placebo) and the sham-operated rabbits did not receive any hormones. All animals were fed a cholesterol-rich diet during the 30-week treatment period. Average serum lipids and atherogenic lipoproteins were higher in the placebo group than in the other groups (ANOVA, P<0.0001). Aortic atherosclerosis, as evaluated by the cholesterol content (nmol/mg protein), was also highest in the placebo group (308+/-39) and lowest in the TE group (61+/-12), but was intermediate in the DHEA (155+/-30), TU (191+/-43), and sham operation (162+/-29) groups (ANOVA, P<0.0001). ANCOVA indicated that the androgen effect on aortic atherosclerosis was only in part explained by the changes in lipoproteins. Aortic estrogen receptor contents were significantly lower in the androgen-treated groups than in the control groups, whereas there was no difference in aortic androgen receptor contents between groups. Natural androgens inhibit aortic atherosclerosis in castrated male rabbits only partly through a lipid-mediated effect.

Adrenal Glands↗

Progestational effects of combinations of gestodene on the postmenopausal endometrium during hormone replacement therapy.

OBJECTIVE: The aim of the study was to assess the dose-response effects on the postmenopausal endometrium of 3 sequential combined hormone replacement regimens and 1 continuous combined hormone replacement regimen of estradiol and gestodene. STUDY DESIGN: In this 2-year double-blind, placebo-controlled study, 278 healthy postmenopausal women received either 2 mg estradiol sequentially combined with 50 microg or 25 microg gestodene, 1 mg estradiol sequentially or continuously combined with 25 microg gestodene, or placebo. RESULTS: All 4 hormone treatment regimens produced a safe endometrial histologic appearance. The regimens that were based on the lower dose of 1 mg estradiol was associated with less uterine bleeding than were those that were based on 2 mg estradiol. For sequentially opposing the 2 mg dose of estradiol, the dose of 25 microg gestodene was less efficient in producing secretory activity than was the dose of 50 microg gestodene. The measurement of placental protein 14 in serum reflected the secretory transformation of the endometrial buildup. CONCLUSION: The reduction in bleeding episodes associated with regimens with lower estradiol doses may lead to improved long-term therapy compliance by menopausal women. The potency of progestogens can be assessed by measuring the serum concentration of placental protein 14.

Dose-Response Relationship, Drug↗

Alcohol and postexercise metabolic responses in type 2 diabetes.

The objective was to investigate the impact of the combination of exercise and alcohol on the metabolic response in nonfasting and fasting type 2 diabetic subjects. In part 1, 12 untrained middle-aged type 2 diabetic subjects participated on 3 test days. On each day, they ingested a light meal (1,824 kJ) containing 48 energy percent (E%) carbohydrate, 38 E% fat, and 14 E% protein. The meal was followed by either (A) rest or (B) 30 minutes of exercise (40% of maximum O2 consumption [VO2max]) or (C) taken with alcohol (0.4 g/kg body weight) followed by 30 minutes of exercise (40% of VO2max). In part 2, 11 untrained middle-aged type 2 diabetic subjects participated on 4 test days without a meal. The subjects were either (A) resting, (B) drinking alcohol (0.4 g/kg body weight), (C) exercising 30 minutes (40% of VO2max), or (D) drinking alcohol (0.4 g/kg body weight) and exercising 30 minutes (40% of VO2max). On each test day, regular blood samples were drawn for 4 hours for analysis of glucose, insulin, lactate, triglycerides, nonesterified fatty acid (NEFA), and ethanol. Comparing exercise and rest following a light meal (part 1, no change (7%) occurred in the plasma glucose response area (642 +/- 119 v 724 +/- 109 mmol x L(-1) x 240 min, NS). However, it was significantly reduced (by 27%) in response to exercise and alcohol (509 +/- 98 v 724 +/- 109 mmol x L(-1) x 240 min; P = .03). Similar serum insulin response areas were obtained. After exercise and alcohol, plasma lactate increased compared with the resting state (2.2 +/- 0.2 v 1.6 +/- 0.1 mmol x L(-1), P = .004) and with exercise alone (2.2 +/- 0.2 v 1.8 +/- 0.2 mmol x L(-1), P = .04). Serum NEFAs were significantly reduced by exercise and alcohol compared with the resting state (0.50 +/- 0.04 v 0.65 +/- 0.06 mmol x L(-1), P = .008) and with exercise alone (0.50 +/- 0.04 v 0.61 +/- 0.05 mmol x L(-1), P = .02). Similar serum triglycerides were found. During the fasting state (part 2), similar plasma glucose response areas were obtained in the four situations. The insulin response area to exercise and alcohol increased significantly compared with the resting state (3,325 +/- 744 v 882 +/- 295 pmol x L(-1) x 240 min, P = .02) and with exercise alone (3,325 +/- 744 v 1,328 +/- 422 pmol x L(-1) x 240 min, P = .007). No difference was found compared with alcohol alone. Plasma lactate was higher after alcohol intake versus the resting state (1.9 +/- 0.1 v 1.3 +/- 0.1 mmol x L(-1), P = .003), as well as after exercise and alcohol (1.9 +/- 0.1 v 1.3 +/- 0.1 mmol x L(-1), P = .01). After exercise and alcohol serum NEFAs were significantly reduced compared with the resting state (0.43 +/- 0.02 v 0.64 +/- 0.02 mmol x L(-1), P < .001), alcohol alone (0.43 +/- 0.02 v 0.51 +/- 0.02 mmol x L(-1), P < .001), and exercise alone (0.43 +/- 0.02 v 0.64 +/- 0.02 mmol x L(-1), P < .001). Serum triglycerides were similar in the four situations. We conclude that moderate exercise with or without moderate alcohol intake does not cause acute hypoglycemia either after a light meal or in the fasting state in untrained overweight type 2 diabetic subjects.

Blood Glucose↗

Biochemical markers can predict the response in bone mass during alendronate treatment in early postmenopausal women. Alendronate Osteoporosis Prevention Study Group.

Data from the Danish cohort (n = 67) of a multicenter trial of oral alendronate in the prevention of postmenopausal osteoporosis were used to evaluate the capacity of the biochemical markers to predict changes in bone mineral density (BMD). A panel of markers were measured: serum N-terminal midfragment osteocalcin (N-MID OC); serum total osteocalcin (total OC); bone-specific alkaline phosphatase (BSAP); serum and urine C-telopeptides of type I collagen (sCL and uCL); urine N-telopeptide crosslinks of type I collagen (NTX); and deoxypyridinoline (dPyr). The correlation between change from baseline at months 3-12 in total OC, N-MID OC, sCL, uCL, and NTX and 2 year response in spine BMD ranged from r = -0.45 to r = -0.78 (p < 0.001), and from r = -0.38 to r = 0.10 (n.s. to p < 0.002) for BSAP and dPyr. Sensitivity and specificity were used to assess the accuracy of change from baseline at month 6 in the biochemical markers for predicting prevention of bone loss in the spine over 2 years. The cutpoints used were a 30% (N-MID OC) or 50% (all other markers) decrease from baseline. Sensitivity levels were 82% (N-MID OC), 98% (total OC), 78% (sCL and NTX), and 89% (uCL). Specificities were 91% (N-MID OC), 59% (total OC), 100% (sCL), 71% (uCL), and 84% (NTX). Positive predictive values were 95% (N-MID OC), 82% (total OC), 100% (sCL), 87% (uCL), and 90% (NTX). In comparison, the predictive capacities of change from baseline at year 2 in hip BMD in predicting prevention of bone loss at the spine were similar: sensitivity, 82%; specificity, 55%; and positive predictive value, 79%. In conclusion, short-term changes in biochemical markers were valid predictors of long-term changes in BMD. Short-term changes in the sensitive biochemical markers revealed a predictive capacity similar to bone densitometry at the hip measured over 2 years. The sensitive biochemical markers offered a fast and valid alternative to bone densitometry for monitoring of alendronate treatment.

Absorptiometry, Photon↗

Comparison of the effects of a monounsaturated fat diet and a high carbohydrate diet on cardiovascular risk factors in first degree relatives to type-2 diabetic subjects.

OBJECTIVE: Recent studies have demonstrated beneficial metabolic effects of dietary monounsaturated fatty acids (MUFA) in Type-2 diabetes mellitus (Type-2 DM). The question arises if dietary MUFA also has desirable effects on risk markers in subjects with high risk of developing Type-2 DM. SETTING: University department of endocrinology. SUBJECTS: Sixteen healthy, first-degree relatives (six men, 10 women, age (mean+/-s.d.): 35+/-2 years) with normal oral glucose tolerance tests. INTERVENTIONS: Randomised study with two 4-week treatment periods with either a carbohydrate-rich (CHO) diet (55 E% carbohydrate, 30 E% fat, 15 E% protein) or a diet rich in olive oil [MUFA 40 E% fat (25 E% as MUFA), 45 E% carbohydrate, 15 E% protein]. The periods were divided by a 4-week wash-out period. RESULTS: Similar lowering effects on total cholesterol, low density lipoprotein (LDL)-cholesterol, triglyceride and apoB levels were seen after the two diets. Slightly higher levels of high-density lipoprotein (HDL)-cholesterol (1.4+/-0.4 vs 1.3+/-0.4 mmol/l, P<0. 0001) and apoA-1 (1.2+/-0.3 vs 1.1+/-0.3 mmol/l, P<0.05) were found in the MUFA-diet. Furthermore, the insulin sensitivity, as assessed by Bergman's minimal model, and the first response insulin areas were similar, as were the 24-h blood pressures and the von Willebrand Factor (vWF) levels. CONCLUSIONS: Isocaloric diets rich in MUFA or rich in carbohydrate, respectively, seem to have similar effects on cardiovascular risk factors in persons at high risk of developing Type-2 DM. A potential risk, however, on body weight of high-fat diets should be kept in mind. SPONSORSHIP: This study was supported by grants from the Danish Diabetes Association, Institute of Clinical Experimental Research, Aarhus University, The Danish Heart Foundation, The Danish Medical Research Council, Velux Foundation, Poul and Erna Sehested Hansens Foundation, Mogens Svarre Mogensens Foundation.

Adult↗

The Trp64Arg mutation of the adrenergic beta-3 receptor gene impairs insulin secretion: a twin study.

AIMS: The physiological role of the adrenergic beta-3 receptor is poorly understood in man but the Trp64Arg mutation of the receptor gene has been related to the insulin resistance syndrome, an earlier onset of diabetes and rapid weight gain. This study set out to examine the effects of the mutation on glycaemic responses after an oral glucose tolerance test. METHODS: A standard oral glucose tolerance test (75 g glucose) was performed in 196 dizygotic twins. Serum insulin and glucose responses were measured at 0, 30 and 120 min. RESULTS: In the twins discordant for the mutation (21 pairs), no effects of the mutation were found on the plasma glucose responses. The insulin response given as incremental area under curve (iAUC) (median 13.8 (25-75th percentile 9.3-21.0) vs. 23.3 (14.2-29.2) mmol x l(-1) x min, P<0.021) and the insulinogenic index ((insulin30min - insulin0min)/ (glucose30min - glucose0min)), a measure of the insulin secretory capacity (44 (34-58) vs. 75 (42-124), P<0.006), were considerably lower in the variant type. The results were confirmed when using non-paired statistics on all subjects. CONCLUSION: It was concluded that the adrenergic beta-3 receptor, in addition to its already known effects, may be involved in the regulation of insulin secretion and that patients with the Trp64Arg mutation present an impaired insulin secretion.

Aged↗

Efficient identification of postdischarge surgical site infections: use of automated pharmacy dispensing information, administrative data, and medical record information.

Although most surgical site infections (SSIs) occur after hospital discharge, there is no efficient way to identify them. The utility of automated claims and electronic medical record data for this purpose was assessed in a cohort of 4086 nonobstetric procedures following which 96 postdischarge SSIs occurred. Coded diagnoses, tests, and treatments were assessed by use of recursive partitioning, with 10-fold cross-validation, and logistic regression with bootstrap resampling. Specific codes and combinations of codes identified a subset of 2% of all procedures among which 74% of SSIs had occurred. Accepting a specificity of 92% improved the sensitivity from 74% to 92%. Use of only hospital discharge diagnosis codes plus pharmacy dispensing data had sensitivity of 77% and specificity of 94%. All of these performance characteristics were better than questionnaire responses from patients or surgeons. Thus, information routinely collected by health care systems can be the basis of an efficient, largely passive, surveillance system for postdischarge SSIs.

Algorithms↗

Two-dimensional gel analysis of human endometrial proteins: characterization of proteins with increased expression in hyperplasia and adenocarcinoma.

In the search for new markers of human endometrial hyperplasia and adenocarcinoma the method of quantitative two-dimensional gel electrophoresis was applied to study the protein expression profiles of metabolically [(35)S]-methionine-labelled proteins of endometrial explants. Approximately 1700 protein spots were resolved by the two-dimensional gel electrophoresis, and the expression pattern of each of these proteins was assessed for increased expression during hyperplasia or adenocarcinoma. In total, six protein spots showed increased expression in hyperplasia, 19 in carcinoma, and eight in both hyperplasia and carcinoma. Twelve of these 33 differentially expressed proteins were identified by peptide mass mapping combined with sequence database searching. Among the identified proteins were proteins involved in cellular transport and chaperoning, i.e. heat shock protein 27 kDa protein, heat shock 70 kDa protein, heat shock cognate 71 kDa protein, and serotransferrin. Other identified proteins were: regulatory chain protein of cAMP-dependent protein kinase, prohibitin, and heterogeneous nuclear ribonucleoprotein A2/B1. Finally we identified proteins associated with the cytoskeleton, vimentin and tropomyosin isoform 3, and the glycolytic pathway, alpha enolase, and phosphoglycerate kinase. The remaining unidentified proteins were either not contained in the database and must be assumed to be novel proteins, or were present in too low amounts to allow characterization.

Adenocarcinoma↗