Hepatitis G virus RNA is common in AIDS patients'' plasma but is not associated with abnormal liver function tests or other clinical syndromes

OBJECTIVE: To determine whether postmenopausal oestrogen replacement therapy affects carotid artery pulsatility index. DESIGN: A prospective double-blind placebo controlled trial. SETTING: University associated teaching hospital. PARTICIPANTS: Twenty-eight postmenopausal women who were more than 12 months postmenopausal and who had not taken exogenous oestrogen. INTERVENTIONS: Independent randomisation to receive oral oestradiol (2 mg daily) or placebo for 20 to 24 weeks. MAIN OUTCOME MEASURES: Internal carotid artery Doppler pulsatility index, measured within one centimetre of the carotid bifurcation. RESULTS: Replicate data were available from 27 women. The mean pulsatility index decreased by -0.11 in 15 women receiving oestradiol, compared with a mean rise of 0.05 in the 12 women who received placebo (P = 0.006, 95% CI for treatment difference 0.06-0.31). CONCLUSIONS: Oestrogen replacement decreases postmenopausal carotid artery pulsatility index, probably reflecting decreased peripheral vascular resistance. This is a further mechanism whereby hormone replacement therapy may impart cardiovascular protection.     

Comparison of tacrolimus absorption in transplant patients receiving continuous versus interrupted enteral nutritional feeding

1. The obese gene product leptin, secreted exclusively from adipocytes, was discovered to serve as a satiety factor and to play an important role in regulating body weight. In adults, the serum leptin level reportedly increases with the degree of obesity. Leptin receptors are expressed in various tissues, and recent in vitro studies suggest a role for leptin in haematopoiesis. 2. The present study was designed to clarify the relationship between serum leptin and body mass index, peripheral blood cell counts, serum cholesterol, high-density lipoprotein-cholesterol, insulin and cortisol levels in 299 Japanese male adolescents aged 15-16 years. 3. With simple linear correlation, log [serum leptin] showed a strong correlation with body mass index (r = 0.56), log [insulin] (r = 0.36) and leucocyte count (r = 0.22) (P < 0.001 for all). There were also correlations with systolic blood pressure, erythrocyte count, haematocrit and high-density lipoprotein-cholesterol (P < 0.01 for all). Even after adjustment for body mass index and log [insulin], log [leptin] correlated with leucocyte (P = 0.004) and erythrocyte (P = 0.057) counts. Stepwise multiple regression analyses revealed log [leptin] to correlate significantly with body mass index, log [insulin] and the leucocyte count (P < 0.005 for all, r2 = 0.399). 4. To our knowledge, this is the first clinical study to show the possible association of serum leptin level with blood cell counts, independent of body mass index and serum insulin. We conclude that these data further support a role for leptin in haematopoiesis.     

Bisphosphonate risedronate prevents bone loss in women with artificial menopause due to chemotherapy of breast cancer: a double-blind, placebo-controlled study

PURPOSE: To determine the effectiveness and safety of the bisphosphonate risedronate in preventing bone loss in young women with breast cancer and early menopause induced by chemotherapy who are at major risk for the development of postmenopausal osteoporosis. PATIENTS AND METHODS: Fifty-three white women, aged 36 to 55 years, with breast cancer and artificially induced menopause were stratified according to prior tamoxifen use. Thirty-six patients received tamoxifen (20 mg/d). Within each stratum, patients were randomly assigned to receive risedronate (n = 27) or placebo (n = 26). Treatment consisted of eight cycles oral risedronate 30 mg/d or placebo daily for 2 weeks followed by 10 weeks of no drug (12 weeks per cycle). Patients were monitored for a third year without treatment. RESULTS: Main outcomes of the study were changes in lumbar spine and proximal femur (femoral neck, trochanter, and Ward's triangle) bone mineral density (BMD), and biochemical markers of bone turnover. In contrast to a significant decrease of BMD at the lumbar spine and hip in the placebo group, there was an increase in BMD in the risedronate group. On treatment withdrawal, bone loss ensued, which suggests that treatment needs to be continuous to maintain a protective effect on bone mass. At 2 years, the mean difference (+/- SEM) between groups was 2.5% +/- 1.2%, (95% confidence interval [CI], 0.2 to 4.9) at the lumbar spine (P = .041) and 2.6% +/- 1.1%, (95% CI, 0.3 to 4.8) at the femoral neck (P = .029). Similar results were observed at the hip trochanter. Results by stratum indicate a beneficial, although partial, effect of tamoxifen in reducing bone loss. Risedronate was well tolerated and showed a good safety profile, with no evidence of laboratory abnormalities. CONCLUSION: Risedronate appears to be a safe treatment that prevents both trabecular and cortical bone loss in women with menopause induced by chemotherapy for breast cancer.     

Tamoxifen and bone metabolism in postmenopausal low-risk breast cancer patients: a randomized study

PURPOSE: This trial was undertaken to evaluate the effect of adjuvant tamoxifen on bone metabolism in postmenopausal women undergoing surgery for low-risk breast cancer. PATIENTS AND METHODS: In an open trial, 25 women were randomized to receive tamoxifen 30 mg/d for 2 years, and 25 women constituted the control group. Twenty women treated with tamoxifen and 23 women in the control group provided data for the analysis. Inclusion criteria were operation for low-risk breast cancer and cessation of menstruations for more than 1 year. Exclusion criteria were presence of metastases, disorders of bone metabolism, contraindications against tamoxifen, use of drugs with influence on bone metabolism, ailments that made bone mineral measurements impossible, and age greater than 65 years. Repeated measurements of bone mineral density and content at the lumbar spine and forearms, serum alkaline phosphatase, phosphate, and ionized calcium were performed in all patients. RESULTS: Lumbar spine bone mineral density increased during the first year in women treated with tamoxifen and then stabilized, compared with decreased bone mineral density in the control group (P = .00074). Bone mineral content at the forearms remained almost stable in tamoxifen-treated women compared with a decrease in the control group (P = .024). Serum alkaline phosphatase, phosphate, and ionized calcium decreased in the tamoxifen group (P < .00001, P = .002, and P = .002, respectively). CONCLUSION: Tamoxifen has estrogen-like effects on bone metabolism that result in an increase and stabilization of bone mineral density in the axial skeleton and a stabilization of bone mineral content in the appendicular skeleton.     

P300 and allocation of attention in dual-tasks

The performance of the CELL-DYN 1700 (Abbott Diagnostics, Abbott Park, IL, USA) was evaluated in a tertiary care hospital laboratory using the guidelines proposed by the German Society of Clinical Chemistry. Precision, accuracy, linearity, background counts, and carry-over were satisfactory for all measured standard parameters including haemoglobin concentration, haematocrit, red blood cell count, mean corpuscular volume (MCV), red cell distribution width (RDW), white blood cell count and platelet count. With 259 selected normal and abnormal blood samples the results of the CELL-DYN 1700 (CD1700) compared very well (r > 0.96 for all parameters with exception of RDW) with those obtained with the Bayer Diagnostic H-1 and the Hoffmann-La Roche Cobas Argos systems. This study considered in particular the performance of the CD1700 three-part leucocyte differential. For those samples without instrument-generated suspect flags, the neutrophil and lymphocyte percentages were highly correlated with the results of the H-1 blood cell counter (r = 0.97 and 0.98, respectively) and with manual 400-cell differentials (r = 0.91 and 0.88, respectively). In contrast, the CD1700 mid-fraction which comprised the composite total of monocytes, eosinophils, basophils and precursor white cells (when present) could not be directly compared to the differentials from the H-1 system or from manual microscopy. For those samples with CD1700 instrument suspect flags, the neutrophil and lymphocyte differential results also compared well with both the H-1 (r = 0.93 and 0.93, respectively) and manual estimates (r = 0.89 and 0.87, respectively). In conclusion, the CD1700 is an accurate haematology analyser for cellular blood counts and three-part leucocyte differentiation.     

Early histopathologic and ultrastructural changes in the heart of Sprague-Dawley rats following administration of soman

Anaemia of prematurity, a postnatal fall in haemoglobin concentration and haematocrit, is particularly common in those born at less than 32 weeks of gestation. Experimental and clinical data implicate inadequate erythropoietin production as an important reason. In this study recombinant human erythropoietin (r-HuEpo) was used in an attempt to treat or prevent this anaemia and thereby provide an alternative to erythrocyte transfusions. Premature infants (birth weight < or = 1250 g and gestational age < or = 32 weeks), who were likely to need transfusions, were randomly assigned to receive 4 weeks of treatment with either subcutaneously administered r-HuEpo (200 U; n = 12) or placebo (n = 12), three times weekly. All patients had oral supplements of elemental iron at a dose of 3 mg/kg/day. Treatment was started in the third week of life. Reticulocyte counts were significantly raised (P < 0.05) in the group treated with r-HuEpo at the end of treatment. The neonates in the group treated with r-HuEpo needed fewer erythrocyte transfusions than those in the placebo group during treatment. There were no toxic effects attributable to r-HuEpo. The results indicate that treatment of infants with very low birth weights with r-HuEpo will reduce their need for erythrocyte transfusions.     

Haematological variables in prostatic carcinoma patients

Routine laboratory tests of the red, white and platelet blood cell systems were performed in 49 patients with benign prostatic hyperplasia (BPH), in 24 hormonally treated patients with metastatic prostatic carcinoma, in 17 patients with untreated prostatic carcinoma without metastases and in 14 patients with untreated metastatic prostatic carcinoma. Significantly lower erythrocyte counts, haemoglobin levels and haematocrit values were found in the hormonally treated cancer group compared to all three other groups. The untreated metastatic cancer group had significantly lower haemoglobin levels and haematocrit values compared to the untreated non-metastatic cancer group. These results indicate that patients with metastases were developing anaemia and that this development was not influenced by palliative hormonal therapy. The results of this study showed that abnormal platelet counts in patients with prostatic carcinoma were rare and that the white blood cell system did not seem to be affected in patients with prostatic carcinoma.     

Flexibility in the boiling method of extracting plasmid DNA directly from cell culture

To investigate the possibility of correcting thrombocytopenia of chronic liver disease, 19 patients (6 male and 13 female) with long-term chronic liver disease and platelet count < or = 85,000/microliters were studied. Either a short-term course (7-20 days) of recombinant human erythropoietin, 4000 U daily SQ (12 patients) or placebo (7 patients) was administered. Treatment was interrupted if the platelets rose to > or = 100,000/microliters or if no significant increase was noted after 14 days. After treatment, platelets increased in the recombinant human erythropoietin group (from a baseline value of 70,000 +/- 11,184 to 101,250 +/- 37,625/microliters), while no difference was noted in the placebo group (70,714 +/- 9928 vs 70,000 +/- 10,231/microliters). The increase in the platelet count in the recombinant human erythropoietin group was significant, both compared to baseline values (paired Student's t-test, t = -3.80, p < 0.005) and to the results of treatment in the placebo group (unpaired Student's t-test, t = 2.71, p < 0.02). Eight out of 12 recombinant human erythropoietin-treated patients (66%) reached > or = 100,000/microliters platelets while four (33%) did not. In comparison to responders, non-responders had a significantly lower baseline platelet count (58,500 +/- 7937 vs 75,750 +/- 7498/microliters, t = -3.69, p = 0.004) and failed more frequently than responders to improve their haematocrit in response to recombinant human erythropoietin (Pearson chi 2 = 4.687, p = 0.03). When treatment was discontinued, the platelet count reverted to baseline in a few weeks. In conclusion, recombinant human erythropoietin treatment transiently corrected mild thrombocytopenia in patients with chronic liver disease.(ABSTRACT TRUNCATED AT 250 WORDS)     

Randomized, double-blind, placebo-controlled study of the effects of raloxifene and conjugated equine estrogen on plasma homocysteine levels in healthy postmenopausal women

OBJECTIVE: To investigate the long-term effects of raloxifene on fasting plasma homocysteine levels in postmenopausal women compared with conjugated equine estrogen (CEE). DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Outpatient department of a university hospital. PATIENT(S): Fifty-two hysterectomized, healthy postmenopausal women. INTERVENTION(S): Oral raloxifene in two dosages (60 mg/d [n=13] and 150 mg/d [n=13]), oral CEE (0.625 mg/d [n=13], and placebo (n=13) were given for 24 months. MAIN OUTCOME MEASURE(S): Fasting plasma homocysteine concentrations. RESULT(S): Plasma homocysteine levels were not altered in the placebo group. After 12 months, a significant reduction versus baseline in the mean plasma homocysteine level (-16%) was found only in the raloxifene 150-mg group. The mean change in plasma homocysteine levels within this group also was significantly different from the changes versus baseline found in the placebo group (+2%) and the raloxifene 60-mg group (-2%), but not different from those found in the CEE group (-8%). After 24 months, plasma homocysteine levels were decreased significantly in the raloxifene 150-mg and CEE groups compared with both baseline (-13% and -10%, respectively) and placebo values (-15% and -11%, respectively). No significant change in plasma homocysteine levels was observed in the raloxifene 60-mg group. CONCLUSION(S): Raloxifene has a favorable, dose-related effect on plasma homocysteine levels in postmenopausal women.     

Short-term oestrogen replacement therapy improves insulin resistance, lipids and fibrinolysis in postmenopausal women with NIDDM

Oestrogen replacement therapy is associated with a decreased risk of cardiovascular disease in postmenopausal women. Patients with non-insulin-dependent diabetes mellitus (NIDDM) have an increased cardiovascular risk. However, oestrogen replacement therapy is only reluctantly prescribed for patients with NIDDM. In a double blind randomized placebo controlled trial we assessed the effect of oral 17 beta-estradiol during 6 weeks in 40 postmenopausal women with NIDDM. Glycated haemoglobin (HbA1c), insulin sensitivity, suppressibility of hepatic glucose production, lipoprotein profile and parameters of fibrinolysis were determined. The oestrogen treated group demonstrated a significant decrease of HbA1c and in the normotriglyceridaemic group a significantly increased suppression of hepatic glucose production by insulin. Whole body glucose uptake and concentrations of non-esterified fatty acids did not change. LDL-cholesterol- and apolipoprotein B levels decreased, and HDL-cholesterol, its subfraction HDL2-cholesterol and apolipotrotein A1 increased. The plasma triglyceride level remained similar in both groups. Both the concentration of plasminogen activator inhibitor-1 antigen and its active subfraction decreased. Tissue type plasminogen activator activity increased significantly only in the normotriglyceridaemic group. Oestrogen replacement therapy improves insulin sensitivity in liver, glycaemic control, lipoprotein profile and fibrinolysis in postmenopausal women with NIDDM. For a definite answer as to whether oestrogens can be more liberally used in NIDDM patients, long term studies including the effect of progestogens are necessary.     

Ticlopidine improves dialysis clearance of solutes in uremic patients by reducing blood clotting in dialyser fibers

Ticlopidine, a platelet aggregation inhibitor was tested, in a double blind comparative cross-over study versus placebo, in 51 dialysed uremic patients who had increased dialyser blood clotting (> 25 fibers clotted/dialyser). At the end of a 7-day treatment period with 250 mg daily, the clearance of urea, creatinine and phosphate was determined at 30 and 210 minutes of dialysis, as well as the number of fibers clotted at the end of dialysis. Ticlopidine improved dialyser clearances for urea, creatinine and phosphate from 165 +/- 41 to 182 +/- 35 (p < 0.01), 135 +/- 37 to 143 +/- 35 (p < 0.05), and 120 +/- 36 to 130 +/- 35 (p < 0.05) ml/min, respectively, at 30 min of HD and a similar effect was seen after 210 min of dialysis. The number of dialyser fibers clotted after dialysis was reduced by ticlopidine therapy from 110 +/- 48 to 15 +/- 8 (p < 0.01). Ticlopidine reduced the initial dialysis-induced drop in leucocyte count by 20% (p < 0.05); no change in platelet or erythrocyte count was observed. Two out of 51 patients experienced an adverse reaction from ticlopidine (cutaneous haematoma and minor gingival bleeding). We conclude that ticlopidine is an efficient and safe drug for dialysed uremic patients since it can reduce blood clotting and thereby increase dialysis efficiency.     

A randomized trial of long term adjuvant tamoxifen plus postoperative radiation therapy versus radiation therapy alone for patients with early stage breast carcinoma treated with breast-conserving surgery. Stockholm Breast Cancer Study Group

BACKGROUND: The use of adjuvant tamoxifen to treat postmenopausal breast carcinoma patients as an adjunct to primary surgery is well established. The current study reports the long term results for a low risk stratum in a randomized trial of adjuvant tamoxifen. The main focus of this analysis was to determine whether tamoxifen would result in a reduced local failure rate for lymph node negative, postmenopausal patients treated with breast-conserving surgery and postoperative radiotherapy. METHODS: The study population included 432 lymph node negative, postmenopausal patients with invasive breast carcinoma (classified as T1-T2) who underwent breast-conserving surgery followed by radiotherapy in Stockholm during the period 1976-1990. The patients constituted a separate stratum of the Stockholm Adjuvant Tamoxifen Trial, which included a total of 2729 patients. Of 432 patients, 213 received 40 mg of tamoxifen daily for either 2 or 5 years. The median follow-up time was 8 years (range, 5-19 years). RESULTS: At 10 years, the overall survival was 90% for the tamoxifen group and 88% for the control group. The event free survival at 10 years was 80% for the tamoxifen group and 70% for the control group (P=0.03). Tamoxifen reduced the overall rate of ipsilateral (hazard ratio=0.4, 95% confidence interval [CI]=0.2-0.9, P=0.02) and contralateral breast tumor recurrences (hazard ratio=0.4, 95% CI=0.1-1.1, P=0.06). Trends toward a reduced number of distant metastases (hazard ratio=0.6, 95% CI=0.3-1.2, P=0.1) and deaths due to breast carcinoma (hazard ratio=0.5, 95% CI=0.2-1.2, P=0.1) also were observed. CONCLUSIONS. The addition of tamoxifen to radiotherapy for postmenopausal, lymph node negative breast carcinoma patients treated with breast-conserving surgery resulted in a reduced rate of ipsilateral and contralateral breast tumor recurrences. The avoidance of salvage mastectomies, reexcisions, and new contralateral malignancies justifies the use of tamoxifen even in the treatment of patients with a 10-year survival rate of 90%.     

T- and B-cell responses of malaria immune individuals to synthetic peptides corresponding to non-repeat sequences in the N-terminal region of the Plasmodium falciparum antigen Pf155/RESA

OBJECTIVE: This study was conducted in order to determine whether the effects of tamoxifen in elderly, frail nursing home residents are similar to those that have been previously reported for younger postmenopausal women. DESIGN: A chart review study. SETTING: The Jewish Home and Hospital for Aged (JHHA), a subacute long-term care facility. PARTICIPANTS: One hundred fifty-eight women who had been at the JHHA at any time since 1986. One hundred ten had a history of breast cancer; 43 of these had been treated with tamoxifen while at the JHHA (Group I), and 66 had not (Group II). The remaining 49 women had no history of breast cancer (Group III). MEASUREMENTS: Data were collected from the time of admission to the JHHA through August, 1994 on: chemistry profiles, bone fractures apparently not a consequence of metastasis, gynecological parameters, and thromboemboli. RESULTS: The lack of pre-admission clinical information presented problems regarding research design and the interpretation of our findings. Nevertheless, compared to women who had not been treated with tamoxifen, treated women had a significantly elevated incidence of vaginal discharge (P = 0.01) and a lower prevalence of elevated total cholesterol (P = 0.04). Although not statistically significant, they also had decreased levels of low density lipoprotein cholesterol and an increased incidence of thromboemboli and bone fractures. CONCLUSIONS: While some of the effects of tamoxifen in elderly, frail women are similar to those observed in younger, postmenopausal women, others may be different. Our results suggest a need for further innovative studies that focus on the consequences of tamoxifen treatment in the elderly, frail population.     

Interim analysis of the incidence of breast cancer in the Royal Marsden Hospital tamoxifen randomised chemoprevention trial

BACKGROUND: Tamoxifen, a drug with antioestrogenic effects, is predicted to prevent the occurrence of breast cancer. We have undertaken a trial of tamoxifen in healthy women who are at increased risk of breast cancer because of family history. We report a planned interim analysis. METHODS: Between October, 1986, and April, 1996, we accrued 2494 healthy women aged between 30 and 70 with a family history of breast cancer. They have been randomised (double blind) to receive tamoxifen 20 mg per day orally or placebo for up to 8 years. Follow-up included clinical assessment, annual mammography, and assessment of toxicity and compliance. The primary endpoint was the occurrence of breast cancer, which was analysed on an intention-to-treat basis with a survival curve. FINDINGS: With a median follow-up of 70 months, 2471 women (tamoxifen 1238, placebo 1233) were suitable for analysis. The groups were evenly matched at baseline, and compliance was good. The overall frequency of breast cancer is the same for women on tamoxifen or placebo (tamoxifen 34, placebo 36, relative risk 1.06 [95% CI 0.7-1.7], p=0.8). Participants who were already on hormone-replacement therapy when they entered the study had an increased risk of breast cancer compared with non-users. Those participants who started such therapy while on trial had a significantly reduced risk. The safety profile of tamoxifen was as expected. INTERPRETATION: We have been unable to show any effect of tamoxifen on breast-cancer incidence in healthy women, contrary to the report from the NSABP-P1 study showing a 45% reduction in healthy women given tamoxifen versus placebo. Differences in the study populations for the two trials may underlie these conflicting findings: eligibility in our trial was based predominantly on a strong family history of breast cancer whereas in the NSABP trial was mostly based on non-genetic risk factors. The importance of oestrogen promotion may vary between such populations.     

Effect of recombinant human erythropoietin on platelet production in dialysis patients

Two hundred forty-four anemic hemodialysis patients were randomized into recombinant erythropoietin and placebo-treated groups during a 12-wk double-blind phase, followed by a 24-wk open-label period. Mean platelet count rose from the baseline value of 242 x 10(9)/L to 264 x 10(9)/L on day 5 of epoetin therapy (P < 0.001, paired t test). Mean platelet count peaked at 290 x 10(9)/L on day 40 and remained at a significantly elevated level below the peak thereafter. The peak platelet count did not exceed the normal range in a majority of cases. Platelet count was unaffected by placebo. Patients without an erythropoietic response during the first few weeks of therapy exhibited a rise in platelet count comparable to that in patients with a satisfactory erythropoiesis. Patients with low initial serum ferritin concentrations had baseline platelet counts comparable to those with normal or high ferritin values and showed a similar rise in platelet count during therapy. As a group, patients with baseline platelet counts above 400 x 10(9)/L showed no rise in platelet count, whereas those with normal or reduced platelet counts showed a marked thrombopoietic response to epoetin. Erythropoietin therapy did not significantly alter the incidence of blood access thrombosis when compared with placebo treatment.     

Paradoxical influence of estrogenic hormones on platelet-endothelial cell interactions

Controversies abound in the literature about the safety and efficacy of tamoxifen and estrogen. We studied the effect of these 2 hormonal agents on factors involved in in vitro thrombogenesis: platelets and endothelial cells. Endothelial cells were derived from human umbilical veins and platelets were obtained from premenopausal and postmenopausal women, women on oral contraceptives, postmenopausal women on hormone replacement therapy, men, and patients with breast cancer who had been taking adjuvant tamoxifen for more than 1 year. The interaction of platelets with endothelial cell matrix was measured in 2 systems: 1) in a flow chamber at low shear rate and, 2) with 51Cr labeled platelets in a "static" culture system. In the static system, platelets from women on tamoxifen exhibited decreased platelet adherence to endothelial cell matrix whether they were grown in tamoxifen or control conditions, when compared to platelets from premenopausal women. When flow (25 sec-1) was added these differences were negated. Neither tamoxifen nor 17 beta estradiol had an effect on endothelial cell proliferation or platelet aggregation. Adhesion of platelets at low shear was not altered when platelet rich plasma was incubated with tamoxifen nor when endothelial cells were grown in tamoxifen. In contrast, incubation of platelets in 17 beta estradiol decreased platelet adhesion at low shear rate, however, there was no effect on platelet adhesion when endothelial cells were grown in 17 beta estradiol. We conclude that in early stages of thrombus formation as measured in vitro, tamoxifen may not have a detrimental effect and estrogen may be protective.     

Continuous, low dosage estradiol administration with a vaginal ring: a placebo-controlled study

Estrogen replacement therapy is used in postmenopausal women with symptoms of urogenital atrophy. The aim of this study was to detect differences in efficacy of a low-dose estradiol-releasing vaginal ring and a placebo ring in the relief of symptoms of estrogen deficiency and reduction of urogenital atrophy (pH and vaginal mucosal maturation) in postmenopausal women. DESIGN: This was a multicentre double-blind, placebo-controlled study. PATIENT SAMPLE: 84 postmenopausal women, of whom 67 completed the full 24 weeks of treatment. RESULTS: Vaginal pH decreased significantly (p = 0.0006) in the estradiol group compared with the placebo group. Similarly, in the estradiol group the mean maturation value increased significantly (p = 0.0004), while incidence of pallor and friability were significantly reduced. Patients in the estradiol group reported significantly greater relief of dyspareunia. CONCLUSION: The results indicate that the estradiol-releasing vaginal ring is effective and well tolerated in the treatment of local estrogen deficiency.     

Increased autologous blood donation in rectal cancer by recombinant human erythropoietin (rhEPO)

A randomised, placebo-controlled trial was conducted to study whether the subcutaneous administration of recombinant human erythropoietin (rhEPO) increases the donated red cell blood volume in patients with rectal cancer. Patients with resectable rectal cancer and a haemoglobin (Hb) level > or = 12.5/ > 12 g/dl (males/females) were scheduled to receive pre-operatively either erythropoietin (200 U/kg body weight daily) (n = 28) or placebo (n = 26) subcutaneously for 11 days. During this period autologous blood was collected. No serious adverse events were attributed to erythropoietin. 20 of 28 patients treated with rhEPO were able to donate > or = 3 units (71%) compared with 11 of 26 control patients (42%). The mean cumulative volume of red cells donated was 29% higher in the patients who received rhEPO (571 versus 444 ml, P = 0.02). The change in the mean reticulocyte value from baseline to the last pre-operative value was significantly higher in the rhEPO group (10.4 to 61.6/1000 versus 11.0 to 20.1/1000, P = 0.0001). The fall in the mean haematocrit from baseline to the last pre-operative value was significantly lower in the rhEPO group (41.4 to 37.6% versus 41.8 to 34.8%, P = 0.0004). rhEPO increases the ability of cancer patients to donate autologous blood during a short pre-operative period and enhances the restoration of haematological values after the donation period.     

Effects of estrogen replacement therapy on the lipoprotein profile in postmenopausal women with ESRD

BACKGROUND: Patients with ESRD have excessive cardiovascular morbidity and mortality. In postmenopausal women with normal renal function, estrogen replacement therapy decreases cardiovascular mortality by 50%, in part because of their beneficial effects on the lipoprotein profile. Because of similarities in the lipoprotein profile between healthy, postmenopausal women, and women with ESRD, we examined the effects of estrogen replacement on lipoproteins in 11 postmenopausal women with ESRD. METHODS: In a randomized, placebo-controlled crossover study (8 week treatment arms) using 2 mg daily of oral, micronized estradiol, 11 postmenopausal women with ESRD were treated. Neither baseline lipid nor lipoprotein abnormalities were used as entry criteria for study participation. RESULTS: Blood estradiol levels were 19 +/- 4 with placebo and 194 +/- 67 pg/ml (P = 0.024) with estradiol treatment. Total HDL cholesterol concentrations increased from 52 +/- 19 mg/dl to 61 +/- 20 mg/dl (16%), with placebo and estradiol treatments, respectively (P = 0.002). Apolipoprotein A1 increased by 24.6% (P = 0.0002) with estradiol intervention. HDL2 concentrations were 19 +/- 13 with placebo and 24 +/- 16 with estradiol treatment (P = 0.046). There were no differences in total or LDL cholesterol, other lipoprotein fractions including Lp(a), and triglycerides with 2 mg daily estradiol treatment. No significant side effects were observed. CONCLUSIONS: Therefore, using standard dosage regimens for estrogen replacement therapy in postmenopausal women with ESRD, HDL cholesterol is increased to an extent that would be expected to improve their cardiovascular risk profile. Further studies are needed to assess whether estrogen replacement therapy decreases the incidence or severity of cardiovascular disease in ESRD patients to a similar degree compared with other women.     

Intermittent etidronate therapy to prevent corticosteroid-induced osteoporosis

BACKGROUND AND METHODS: Osteoporosis is a recognized complication of corticosteroid therapy. Whether it can be prevented is not known. We conducted a 12-month, randomized, placebo-controlled study of intermittent etidronate (400 mg per day for 14 days) followed by calcium (500 mg per day for 76 days), given for four cycles, in 141 men and women (age, 19 to 87 years) who had recently begun high-dose corticosteroid therapy. The primary outcome measure was the difference in the change in the bone density of the lumbar spine between the groups from base line to week 52. Secondary measures included changes in the bone density of the femoral neck, trochanter, and radius and the rate of new vertebral fractures. RESULTS: The mean (+/-SE) bone density of the lumbar spine and trochanter in the etidronate group increased 0.61 +/- 0.54 and 1.46 +/- 0.67 percent, respectively, as compared with decreases of 3.23 +/- 0.60 and 2.74 +/- 0.66 percent, respectively, in the placebo group. The mean differences between the groups after one year were 3.72 +/- 0.88 percentage points for the lumbar spine (P = 0.02) and 4.14 +/- 0.94 percentage points for the trochanter (P = 0.02). The changes in the femoral neck and the radius were not significantly different between the groups. There was an 85 percent reduction in the proportion of postmenopausal woman with new vertebral fractures in the etidronate group as compared with the placebo group (1 of 31 patients vs. 7 of 32 patients, P = 0.05), and the etidronate-treated postmenopausal women also had significantly fewer vertebral fractures per patient (P = 0.04). CONCLUSIONS: Intermittent etidronate therapy prevents the loss of vertebral and trochanteric bone in corticosteroid-treated patients.