Calcium supplementation prevents seasonal bone loss and changes in biochemical markers of bone turnover in elderly New England women: a randomized placebo-controlled trial

Elderly women are at increased risk for bone loss and fractures. In previous cross-sectional and longitudinal studies of women residing in northern latitudes, bone loss was most pronounced during winter months and in those consuming less than 1 g calcium per day. In this study we sought to test the hypothesis that calcium supplementation by either calcium carbonate or dietary means would prevent seasonal bone loss and preserve bone mass. Sixty older postmenopausal women without osteoporosis were randomized to one of three treatment arms: Dietary milk supplementation (D-4 glasses of milk/day), Calcium carbonate (CaCO3-1000 mg/day in two divided doses), or placebo (P). After 2 yr, placebo-treated women consumed a mean of 683 mg/day of calcium and lost 3.0% of their greater trochanteric (GT) bone mineral density (BMD) (P < 0.03 vs. baseline); Dietary supplemented women averaged a calcium intake of 1028 mg/day and sustained minimal loss from the GT (-1.5%; P = 0.30), whereas CaCO3-treated women (total Ca intake, 1633 mg/day) suffered no bone loss from the GT and showed a significant increase in spinal and femoral neck BMD (P < 0.05). Femoral bone loss occurred exclusively during the two winters of the study (i.e. total loss, -3.2%; P < 0.02 in placebo-treated women) with virtually no change in GT BMD during summer. Serum 25-OH vitamin D declined by more than 20% (P < 0.001) in all groups during the winter months but returned to baseline in summer; PTH levels rose approximately 20% (P < 0.001) during winter but did not return to baseline during the summers. Urine N-telopeptide and osteocalcin levels increased significantly but only in the P-treated women and only during winter. Serum insulin growth factor binding protein 4, an inhibitory insulin growth factor binding protein, rose 15% (P < 0.03) from summer to winter, but this increase was significant only in those women consuming <1000 mg/day of calcium. By multivariate analysis, total calcium intake was the strongest predictor of bone loss from the hip. Urinary N-telopeptide also closely correlated with GT BMD but only during winter (P = 0.003). We conclude that calcium supplementation prevents bone loss in elderly women by suppressing bone turnover during the winter when serum 25-OH vitamin D declines and serum PTH increases. The precise amount of calcium necessary to preserve BMD in elderly women requires further studies, although in this study, at least 1000 mg/day of supplemental calcium was adequate prophylaxis against femoral bone loss.     

Treatment of inclusion-body myositis with IVIg: a double-blind, placebo-controlled study

The hypothesis was tested that 7-sulfooxymethylbenz[a]anthracene (7-SBA) is an ultimate electrophilic and carcinogenic form of 7-hydroxymethylbenz[a]anthracene. In conformity with this hypothesis, 7-SBA was more carcinogenic than 7-HBA in inducing sarcomas at the site of repeated subcutaneous injection. These metabolites were individually administered to female Sprague-Dawley rats, beginning at 30 days of age, in 0.2 mumol doses given three times each week for 20 doses. One year after the first injection of 7-SBA, seven of thirteen female Sprague-Dawley rats had developed sarcomas. 7-HBA, on the other hand, had induced sarcomas at the site of injection in only two of tweleve rats. No tumors developed either in the control group given sesame oil:DMSO only or in the untreated control group. It would appear from the results summarized here that the search for an ultimate electrophilic and carcinogenic form of 7-HBA has been successful.     

Bromocriptine in systemic lupus erythematosus: a double-blind, randomized, placebo-controlled study

The objective of this study was to investigate the efficacy and safety of bromocriptine (BRC) as an adjunct to conventional treatment in systemic lupus erythematosus (SLE). A prospective, double-blind, randomized, placebo-controlled study compared BRC at a fixed daily dosage of 2.5 mg with placebo. Patients were followed for 2-17 months (mean 12.5 months). Disease activity was assessed using the SLE Disease Activity Index (SLEDAI), numbers of flares were recorded, and serum prolactin (PRL) levels were obtained at intervals during the study. Patients were allowed to take prednisone and immunosuppressive drugs. Sixty-six patients with SLE entered the study. Thirty-six were treated with BRC, and 30 controls received placebo. Sixteen patients were removed from the study during the treatment period: five in each group left the study because of adverse effects, five became pregnant, and one patient who took placebo died with central nervous system lupus. Four patients in the BRC treatment group and three patients in the placebo group moved away or stopped coming for study visits for unknown reasons, and were lost to follow-up during the course. At entry, serum PRL was (mean+/-s.d.) 24.8 ng/ml+/-18.4 in the BRC treatment group. This value fell to 5.8+/-9.0 after 12 months of treatment. Corresponding PRL values in controls were 23.7+/-22.1 pretreatment and 20.3+/-14 after 12 months. PRL levels in BRC-treated subjects were significantly lower than levels in control subjects after 3, 6, 9, and 12 months of treatment. The SLEDAI score on the fifth protocol visit was decreased significantly in the BRC group vs controls: 0.9+/-1.4 vs 2.6+/-4.5 (P < 0.05). Although the absolute number of flares in each group was similar, the mean number of flares/patient/month was decreased significantly in the BRC group compared to the control group (0.08+/-0.1 vs 0.18+/-0.2, P = 0.03). Long term treatment with a low dose of BRC appears to be a safe and effective means of decreasing SLE flares in SLE patients.     

Long-term treatment of ulcerative colitis with ciprofloxacin: a prospective, double-blind, placebo-controlled study

BACKGROUND & AIMS: Although bacterial bowel flora may be one of the contributing factors in the pathogenesis of chronic mucosal inflammation, antibiotic treatment has no established role in ulcerative colitis. The aim of the study was to evaluate the role of ciprofloxacin in the induction and maintenance of remission in ulcerative colitis in patients responding poorly to conventional therapy with steroids and mesalamine. METHODS: Ciprofloxacin (n = 38; 500-750 mg twice a day) or placebo (n = 45) was administered for 6 months in a double-blind, randomized study with a high but decreasing dose of prednisone and maintenance treatment with mesalamine including follow-up for the next 6 months. Clinical assessment and colonoscopic evaluation were performed at 0, 3, 6, and 12 months. Treatment failure, the primary end point, was defined as both symptomatic and endoscopic failure to respond. RESULTS: During the first 6 months, the treatment-failure rate was 21% in the ciprofloxacin-treated group and 44% in the placebo group (P = 0.02). Endoscopic and histological findings were used as secondary end points and showed better results in the ciprofloxacin group at 3 months but not at 6 months. CONCLUSIONS: Addition of a 6-month ciprofloxacin treatment for ulcerative colitis improved the results of conventional therapy with mesalamine and prednisone.     

Pharmacokinetics and pharmacodynamics of zolmitriptan in patients with mild to moderate hypertension: a double-blind, placebo-controlled study

Zolmitriptan is a potent selective 5HT1B/1D receptor agonist for acute migraine therapy. Zolmitriptan has vasoconstrictor activity in cerebral vessels and may cause slight elevations of blood pressure in subjects without hypertension. Therefore, the pharmacokinetics and pharmacodynamics of zolmitriptan (5, 10, and 20 mg) were evaluated in 16 patients with mild to moderate hypertension (controlled by hydrochlorothiazide 50 mg once daily) and 17 healthy age- and sex-matched control subjects in a randomized, placebo-controlled, double-blind, four-period crossover study. The pharmacokinetics of zolmitriptan and its metabolites were dose proportional. Although area under the concentration-time curve (AUC0-infinity) and maximum concentration (Cmax) were slightly higher in patients with hypertension at all doses, this was only statistically significant for AUC at the 20-mg dose. Differences between subjects with and without hypertension were not clinically significant. Zolmitriptan produced a small increase in blood pressure, but this was similar in subjects with and without hypertension and was of no clinical significance. Zolmitriptan was well tolerated in both groups. Zolmitriptan plasma concentrations were higher in women than in men, with higher values of AUC and Cmax and lower total clearance in women. These results indicate that zolmitriptan can be administered for treatment of migraine in patients with controlled hypertension without dose adjustment.     

Timing of menopause, reproductive years, and bone mineral density: a cross-sectional study of postmenopausal Japanese women

Age at menopause has been found to be associated positively with bone mineral density, and age at menarche has been found to be associated negatively with bone mineral density. However, there have been few studies on the relations of timing of menopause and length of the reproductive period with bone mineral density. The purpose of this study was to examine the relations of timing of menopause and reproductive years (calculated as age at menopause minus age at menarche) with mineral density of the second metacarpal bone in postmenopausal Japanese women. The study population consisted of 1,035 naturally menopausal women aged 40-70 years who were screened in 1996-1997. Using computed x-ray densitometry, the authors measured bone mineral density by analyzing radiographic films of the right second metacarpal bone. Using the women with early menopause (age < 49 years) as the reference group and adjusting for age, subjects with late menopause were at decreased risk for low bone mineral density (odds ratio (OR) = 0.69, 95% confidence interval (CI) 0.49-0.97). After adjustment for additional covariates (grip strength, physical activity, body mass index, smoking, and calcium intake), the association was unchanged (OR = 0.70, 95% CI 0.50-0.99). Postmenopausal women with more reproductive years (> or = 40 years) were at decreased risk for low bone mineral density compared with those with fewer reproductive years, after adjustment for age (OR = 0.73, 95% CI 0.40-1.30) and potentially confounding factors (OR = 0.76, 95% CI 0.41-1.37); the p-value for trend was not statistically significant. In multiple linear regression analysis, early menopause and fewer reproductive years were independent predictors of low bone mineral density. In this study, postmenopausal Japanese women who had a late menopause and more reproductive years were at decreased risk for low bone mineral density, and may therefore be less prone to osteoporosis.     

Human leukocyte derived interferon-alpha in a hydrophilic gel for the treatment of intravaginal warts in women: a placebo-controlled, double-blind study

Persistent polychlorinated biphenyl (PCB) metabolites were studied with respect to their interaction with the human glucocorticoid receptor (GR). 3-Methylsulphonyl-2,5,6,2',4',5'-hexachlorobiphenyl (3-MeSO2-CB149) was shown to compete with 3H-dexamethasone for binding to the GR, with an IC50 (concentration that inhibits 50%) of approximately 1 microM. Using GRAF cells expressing human GR, glucocorticoid responsive element, and a reporter enzyme, we demonstrated that 3-MeSO2-CB149 functionally acts as an antagonist at the GR (IC50 = 2.7 microM). In accordance with the receptor binding, the antagonism mainly appeared to be of a competitive nature. When studying the competitive binding of 24 methylsulfonyl PCBs (relative to dexamethasone) to GR from mouse liver cytosol, seven compounds had a higher affinity to GR than 3-MeSO2-CB149. Structure-activity relationship studies indicated that the presence of three chlorine atoms in the ortho-position and chlorine and methyl sulfone groups on either end of the molecule (4 and 4'-position) increased the affinity to GR. The relevance of this finding for human health is not known, but PCB methyl sulfones are ubiquitous pollutants present in mother's milk. The results stress the need for studying endocrine disruptors that affect hormonal systems other than sex and thyroidogenic hormones.     

Adjuvant radiotherapy and chemotherapy in node-positive premenopausal women with breast cancer

BACKGROUND: Radiotherapy after mastectomy to treat early breast cancer has been known since the 1940s to reduce rates of local relapse. However, the routine use of postoperative radiotherapy began to decline in the 1980s because it failed to improve overall survival. We prospectively tested the efficacy of combining radiotherapy with chemotherapy. METHODS: From 1978 through 1986, 318 premenopausal women with node-positive breast cancer were randomly assigned, after modified radical mastectomy, to receive chemotherapy plus radiotherapy or chemotherapy alone. Radiotherapy was given to the chest wall and locoregional lymph nodes between the fourth and fifth cycles of cyclophosphamide, methotrexate, and fluorouracil. RESULTS: After 15 years of follow-up, the women assigned to chemotherapy plus radiotherapy had a 33 percent reduction in the rate of recurrence (relative risk, 0.67; 95 percent confidence interval, 0.50 to 0.90) and a 29 percent reduction in mortality from breast cancer (relative risk, 0.71; 95 percent confidence interval, 0.51 to 0.99), as compared with the women treated with chemotherapy alone. CONCLUSIONS: Radiotherapy combined with chemotherapy after modified radical mastectomy decreases rates of locoregional and systemic relapse and reduces mortality from breast cancer.     

Effect of adjuvant pindolol on the antiobsessional response to fluvoxamine: a double-blind, placebo-controlled study

In 1994, a Ph.D.-study started regarding pharmacy, organization and management (APOM) in the Netherlands. The APOM-project deals with the structuring and steering of pharmacy organization. This article describes a summary of the theoretical background of the project and the empirical results of a pilot study (n = 24). No generalization to the population of pharmacies in the Netherlands was made. Three mixes of objectives in pharmacy organization were theoretically postulated; the product mix, the process mix, and the customer mix. Mainly, the purpose of the pilot study was method selection. Additionally, it was studied if thought and action of pharmacy managers corresponded, and, if theoretical pharmacy mixes corresponded with the empirical pharmacy mixes. Two methods were selected to be applied in a survey. Thought and action did not correspond for most pharmacy managers. Thought related to customer and product mainly, and action related to process and customer mainly.     

Effect of leuprolide acetate in treatment of abdominal pain and nausea in premenopausal women with functional bowel disease: a double-blind, placebo-controlled, randomized study

Many contemporary scholars have challenged the current culture of graduate education and have suggested a need to reform nursing scholarship. The purpose of this study was to describe and analyse the common practices and shared lived experiences of nurses who are students or teachers in doctoral education. Participants recruited from across the United States included 15 nurses, five of whom were current faculty members in doctoral programmes in nursing and 10 who were currently enrolled as students in doctoral programmes. Data collected from extended, non-structured interviews were analysed hermeneutically using the interpretive phenomenology of Heidegger and Gadamer as the philosophical background. The results of this study reveal that the practices of scholarship, reading, writing, thinking and dialogue are inseparable and belong together. Analysing and describing how the practices of scholarship belong together will contribute to extending an understanding of how the practices of writing can be preserved in contemporary doctoral education. 'Preserving' refers to how teachers and students perpetuate and sustain these practices in ways that are meaningful and transformative and in ways that are oppressive. This study explores the experiences that are central to becoming a scholar and suggests how their meaningfulness can be sustained and extended into the next millennium.     

Immunotherapy with Alpare in patients with respiratory allergy to Parietaria pollen: a two year double-blind placebo-controlled study

The recent literature on the healing of tympanic membrane perforations is reviewed. Research on the migratory phenomena, epithelial migration and keratin dispersion on top of the tympanic membrane, is discussed. The etiology and pathogenesis of tympanic membrane perforations is then briefly described. The literature on the healing process of tympanic membrane on animal experiments as well as observations in humans is amply discussed. Finally different non invasive and or office procedures for tympanic membrane repair are reported.     

Clinical effects of buspirone in social phobia: a double-blind placebo-controlled study

BACKGROUND: The results of open pilot studies suggest that the serotonin-1A (5-HT1A) receptor agonist buspirone might be effective in social phobia. METHOD: In the present study, the efficacy of buspirone was investigated in patients with social phobia using a 12-week double-blind placebo-controlled design. Thirty social phobic patients (DSM-IV) were treated with either buspirone 30 mg daily or placebo. Efficacy of treatment was measured using the Social Phobia Scale (subscores anxiety and avoidance) and the Hamilton Rating Scale for Anxiety. RESULTS: Taking a reduction of 50% or more on the Social Phobia Scale as a criterion for clinically relevant improvement, only 1 patient on buspirone and 1 on placebo were classified as responder to treatment. A subjective and clinically relevant improvement was reported by 4 patients (27%) on buspirone and 2 patients (13%) on placebo. There were no statistically significant differences between buspirone and placebo on any of the outcome measures. Generally speaking, buspirone was well tolerated. CONCLUSION: The results of the study do not support the results of open studies, in which a reduction of social anxiety and social avoidance was reported in patients with social phobia treated with buspirone.     

Bathing suit delivery of 8-methoxypsoralen for psoriasis: a double-blind, placebo-controlled study

Twenty-four patients, 15 men and 9 women, aged 18-70 years with stable plaque-type psoriasis involving more than 20% of the body surface were subjected to a randomized, double-blind, age- and sex-matched, placebo-controlled study. Containers containing 25 mL of either 1% 8-MOP or a color-matched placebo were randomly numbered and stored. To 2 L of water was added 0.8 mL of 1% 8-MOP to obtain a concentration of 3.75 mg/L3, into which a bathing suit was soaked for 5 min. The suits were then gently squeezed to remove excess water and the patients were advised to put on the suit covered by a raincoat for 15 min. Immediately after removal of the raincoat and the suit, patients were irradiated with an initial dose of 4 J/cm2 UVA with increments of 0.5 J/cm2 on alternate days in a whole-body phototherapy unit obtained from the National Biological Corporation, Ohio. Erythema, scaling, and thickness (EST) of the index lesions were assessed on a 3-point scale (Table 1) and photographs were taken before and after completion of the study.     

Lymphoedema: a study of Otago women treated for breast cancer

Lymphoedema, the swollen arm that can follow treatment for breast cancer, is the build up of lymph fluid which is unable to flow normally due to the surgical removal of axillary lymph nodes or the scarring of these nodes from radiotherapy. Previous studies indicate a lack of recognition of preventative measures and treatment of lymphoedema amongst health professionals and women treated for breast cancer. There also appears to be a lack of acknowledgement of the effects that lymphoedema can have on those who develop it. Of 181 women surveyed 68 (38%) reported having developed arm swelling at some stage since their treatment, 56 (31%) of whom met the study criteria for lymphoedema. Of those with lymphoedema 21 (37%) women had not consulted anyone regarding their swollen arm; a further 10 (18%) sought advice, but were offered no treatment. Therefore, in total, 31 (55%) of the women with lymphoedema received no treatment. The remaining 25 (45%) were offered a variety of treatments. In the group of women with lymphoedema, most arm swelling occurred within the first year. For a smaller number, swelling occurred up to 25 years later. Twenty-one percent of those affected, recalled advice about its prevention, compared with 36% in the group who had not experienced lymphoedema. Lifestyles were affected in many ways, with 21 (37.5%) of the women reporting pain of varying intensity and frequency. Other effects were on dress/choice of clothing, household duties, sleep, employment and sports.     

Effect of piracetam on recovery and rehabilitation after stroke: a double-blind, placebo-controlled study

The nootropic agent piracetam has been shown to improve learning and memory, and it may, by this means, facilitate recovery and rehabilitation after a stroke. We report the results of a pilot study exploring its effects in patients undergoing rehabilitation after acute cerebral infarction in the carotid artery territory. We compared piracetam and placebo, each given for 12 weeks, in a multicenter, double-blind, randomized trial of parallel-group design; testing was performed at baseline (6-9 weeks poststroke), weeks 5 and 12, and, in fewer patients, 12 weeks after termination of treatment. Standardized tests of activities of daily living (Barthel Index, Kuriansky Test), aphasia (Aachen Aphasia Test), and perception (Rivermead Perception Assessment Battery) were the primary efficacy variables. Of 158 patients, 137 (81 males, 56 females) were studied after treatment and 88 at 24-week follow-up. Thirty patients on piracetam (45%) and 37 on placebo (53%) were aphasic on entry. Both groups, including the subgroups with aphasia, were well matched at baseline for demographic data, stroke sequelae, type and severity of aphasia, and prognostic parameters. Multivariate analysis of Aachen Aphasia subtest scores showed a significant overall improvement relative to baseline in favor of piracetam (p = 0.02) at 12 weeks. This was not seen at 24 weeks when, however, fewer patients were available for evaluation so that we could neither confirm nor deny whether improvement was maintained after cessation of piracetam. We were unable to demonstrate an effect on tests of activities of daily living and could neither confirm nor exclude an effect on perceptual deficit. We have shown an improvement in aphasia in patients undergoing rehabilitation after a stroke after 12 weeks' treatment with piracetam that requires confirmation in further studies.     

Botulinum toxin A for hyperkinetic facial lines: results of a double-blind, placebo-controlled study

Although enterotoxins have been implicated in disease states such as food poisoning and toxic shock syndrome, their role in infectious arthritis is not known. To study the arthritogenic properties of toxic shock syndrome toxin 1 (TSST-1), two pairs of S. aureus strains isogenic for TSST-1 production were injected intravenously into healthy Swiss mice. Mice injected with TSST-1-secreting staphylococcal strains developed more frequent and more severe arthritis than did mice inoculated with the isogenic TSST-1-deficient counterparts. Immunohistochemical analysis of arthritic joints revealed an equal number of infiltrating phagocytes in both groups; however, mice inoculated with TSST-1-producing staphylococci had significantly more (P < .01) interleukin-2 receptor-expressing cells in the inflamed synovium than did mice that received the isogenic counterpart. Thus, TSST-1 is a virulence determinant in S. aureus arthritis in mice. The precise mechanism by which this toxin contributes to the development and progression of arthritis needs further investigation.     

Long-term clinical effect of nilvadipine in patients with chronic heart failure: a double-blind placebo-controlled study

The long-term effect of calcium channel blockers on chronic heart failure is disappointing, probably because of reflex sympathetic activation through arterial vasodilation. However, nilvadipine may be beneficial for treatment of chronic heart failure since this drug has minimal effects on sympathetic activation. In this study, the effects of 12-week administration of nilvadipine or placebo on symptoms of heart failure and cardiac function were investigated in 23 patients with mild-to-moderate chronic heart failure in a double-blind trial. The patients were randomly assigned to either a nilvadipine group (16 mg daily) or a placebo group. Intergroup comparisons did not show significant differences in any parameters. Serious adverse effects were not observed during the study. Thus, this study failed to show any beneficial effect of nilvadipine in the long-term treatment of patients with chronic heart failure. We conclude that the long-term administration of nilvadipine (16 mg daily) is neither effective nor harmful in the treatment of patients with chronic heart failure.     

Risk factors for breast cancer in women with a breast cancer family history

For the study of the relationship of the pelviureteric system of one kidney to that of the contralateral one, bilateral cutaneous ureterostomy was performed in 14 dogs. The renal pelvis (RP) and ureter (U) of one side were distended separately with a balloon filled with saline in increments of 1 and 0.25 ml, respectively, and the pressure response of the contralateral RP and U was recorded. The test was repeated after anesthetization of the RP and U. RP distension with 1 ml of saline effected a pressure rise (P < 0.05) in the ipsilateral RP but no pressure response in the ipsilateral U or the contralateral RP or U (P > 0.05). RP distension with 2, 3, and 4 ml of saline induced a significant pressure rise in the ipsi- and contralateral RP but not in the ureters. Ureteric distension produced a pressure elevation (P < 0.05) on the ipsilateral U but had no effect on the contralateral U (P > 0.05) or on either of the renal pelves (P > 0.05). Distension of the anesthetized RP or U effected no pressure response in any of the ipsi- or contralateral RPs or Us. In conclusion, distension of the RP with large volumes led to an increase in pressure in the contralateral RP but not in the U. A reflex relationship is postulated to exist between the two renal pelves and to be mediated through a reflex we call the reno-renal pelvic reflex. It seems that this reflex acts to allow either of the kidneys to share an extra load of the other one by increasing the contractile activity of the RP, thus assumedly assisting the regulation of urine flow.