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Biomedical subjects

D Bernstein

Publications and source records attributed to D Bernstein.

At least 37 records · Page 2Linked to original sources

Effectiveness of the recombinant factor VIIa in patients with the coagulopathy of advanced child's B and C cirrhosis.

Patients with advanced liver cirrhosis have a serious disturbance in their hemostasis system that leads to increased morbidity and mortality. The vitamin K-dependent clotting factors, especially factor VII, are markedly reduced in these patients. Present treatment modalities include fresh frozen plasma (FFP), vitamin K, and desmopressin. FFP has to be given in large volume and entails the risk of transmitting infectious agents. The introduction of recombinant activated factor VII (rFVIIa) has offered another treatment option for patients with liver cirrhosis and bleeding. The clinical experience with rFVIIa is reviewed. Management seems to be effective and safe and the concern that rFVIIa might activate the hemostasis system in these patients has not materialized. Administration of rFVIIa not only corrected the abnormal clotting tests in these patients but also allowed several invasive procedures without the complication of bleeding.

Blood Coagulation↗

Suppression and recovery of GH secretion after GH injection in non-GH deficient short children.

OBJECTIVE: To identify the effect of exogenous GH on endogenous GH secretion in 48 non-GH deficient short children participating in a placebo-controlled trial of GH therapy on final adult height. DESIGN: Night GH secretion (mean of levels every 20 min from 20.00 to 08.00 h) was evaluated at baseline, 6 months before starting placebo or GH (somatotropin, 0.222 mg/kg/ week, divided into 3 doses each week). At 6 months after starting injections, blood samples for GH were obtained hourly for 24 h after an injection, and every 20 min on each of the next two nights (with no additional placebo or GH injection). RESULTS: IGF-I levels in the treatment group were elevated at 12 and 24 h but not at 36 h compared to the placebo group. Mean GH levels in the placebo group did not vary significantly among the four sampling periods. In the treatment group, the mean serum GH rose to a supraphysiological peak at an average time of 4 h after injection. Subsequently, mean GH level was significantly suppressed compared to placebo on the second night following GH injection, but returned to normal by the third night. CONCLUSION: After 6 months of a thrice weekly GH treatment regimen in non-GH deficient short children, endogenous GH secretion was reduced from 24 to 36 h after injection compared to placebo and returned to control levels by 48 to 60 h after injection.

Child↗

Targeted disruption of the beta2 adrenergic receptor gene.

beta-Adrenergic receptors (beta-ARs) are members of the superfamily of G-protein-coupled receptors that mediate the effects of catecholamines in the sympathetic nervous system. Three distinct beta-AR subtypes have been identified (beta1-AR, beta2-AR, and beta3-AR). In order to define further the role of the different beta-AR subtypes, we have used gene targeting to inactivate selectively the beta2-AR gene in mice. Based on intercrosses of heterozygous knockout (beta2-AR +/-) mice, there is no prenatal lethality associated with this mutation. Adult knockout mice (beta2-AR -/-) appear grossly normal and are fertile. Their resting heart rate and blood pressure are normal, and they have a normal chronotropic response to the beta-AR agonist isoproterenol. The hypotensive response to isoproterenol, however, is significantly blunted compared with wild type mice. Despite this defect in vasodilation, beta2-AR -/- mice can still exercise normally and actually have a greater total exercise capacity than wild type mice. At comparable workloads, beta2-AR -/- mice had a lower respiratory exchange ratio than wild type mice suggesting a difference in energy metabolism. beta2-AR -/- mice become hypertensive during exercise and exhibit a greater hypertensive response to epinephrine compared with wild type mice. In summary, the primary physiologic consequences of the beta2-AR gene disruption are observed only during the stress of exercise and are the result of alterations in both vascular tone and energy metabolism.

Animals↗

Cardiovascular and metabolic alterations in mice lacking both beta1- and beta2-adrenergic receptors.

The activation state of beta-adrenergic receptors (beta-ARs) in vivo is an important determinant of hemodynamic status, cardiac performance, and metabolic rate. In order to achieve homeostasis in vivo, the cellular signals generated by beta-AR activation are integrated with signals from a number of other distinct receptors and signaling pathways. We have utilized genetic knockout models to test directly the role of beta1- and/or beta2-AR expression on these homeostatic control mechanisms. Despite total absence of beta1- and beta2-ARs, the predominant cardiovascular beta-adrenergic subtypes, basal heart rate, blood pressure, and metabolic rate do not differ from wild type controls. However, stimulation of beta-AR function by beta-AR agonists or exercise reveals significant impairments in chronotropic range, vascular reactivity, and metabolic rate. Surprisingly, the blunted chronotropic and metabolic response to exercise seen in beta1/beta2-AR double knockouts fails to impact maximal exercise capacity. Integrating the results from single beta1- and beta2-AR knockouts as well as the beta1-/beta2-AR double knock-out suggest that in the mouse, beta-AR stimulation of cardiac inotropy and chronotropy is mediated almost exclusively by the beta1-AR, whereas vascular relaxation and metabolic rate are controlled by all three beta-ARs (beta1-, beta2-, and beta3-AR). Compensatory alterations in cardiac muscarinic receptor density and vascular beta3-AR responsiveness are also observed in beta1-/beta2-AR double knockouts. In addition to its ability to define beta-AR subtype-specific functions, this genetic approach is also useful in identifying adaptive alterations that serve to maintain critical physiological setpoints such as heart rate, blood pressure, and metabolic rate when cellular signaling mechanisms are perturbed.

Animals↗

Adult health status of women with histories of childhood abuse and neglect.

PURPOSE: Several recent studies have found associations between childhood maltreatment and adverse adult health outcomes. However, methodologic problems with accurate case determination, appropriate sample selection, and predominant focus on sexual abuse have limited the generalizability of these findings. SUBJECTS AND METHODS: We administered a survey to 1,225 women who were randomly selected from the membership of a large, staff model health maintenance organization in Seattle, Washington. We compared women with and without histories of childhood maltreatment experiences with respect to differences in physical health status, functional disability, numbers and types of self-reported health risk behaviors, common physical symptoms, and physician-coded ICD-9 diagnoses. RESULTS: A history of childhood maltreatment was significantly associated with several adverse physical health outcomes. Maltreatment status was associated with perceived poorer overall health (ES = 0.31), greater physical (ES = 0.23) and emotional (ES = 0.37) functional disability, increased numbers of distressing physical symptoms (ES = 0.52), and a greater number of health risk behaviors (ES = 0.34). Women with multiple types of maltreatment showed the greatest health decrements for both self-reported symptoms (r = 0.31) and physician coded diagnoses (r = 0.12). CONCLUSIONS: Women with childhood maltreatment have a wide range of adverse physical health outcomes.

Adult↗

Experience with staging laparoscopy in pancreatic malignancy.

BACKGROUND: The role of diagnostic laparoscopy in the staging of abdominal malignancies is not well defined. METHODS: We retrospectively reviewed the usefulness of diagnostic laparoscopy as a staging procedure in pancreatic malignancy. This experience between February 1988 and May 1997 involves 109 cases of suspected or proven pancreatic malignancy. All laparoscopies were performed with the patient under conscious sedation and local anesthesia in an endoscopy suite. RESULTS: Of the 109 patients with pancreatic cancer, 45 (42%) had metastatic disease. The use of computed tomography (CT) alone revealed the existence of liver metastases in 10 of 109 (9%) patients, which were confirmed laparoscopically. The further use of laparoscopy identified metastases in 29 more cases: hepatic, 23; hepatic and peritoneal, 3; peritoneal and mesenteric, 1; and mesenteric, 2. CT in conjunction with laparoscopy therefore revealed metastatic liver, peritoneal, or mesenteric lesions in 39 of 109 (36%) patients with pancreatic cancer. After staging laparoscopy, 67 of 69 patients underwent laparotomy. Metastatic disease was identified at laparotomy in 6 more patients; however, only 4 of these patients had metastases to the liver whereas 2 had metastases to the peripancreatic lymph nodes. Therefore, in patients with pancreatic malignancy, the negative predictive value for the diagnosis of metastases to the liver, peritoneum or mesentery was 94% (61 of 65 patients). The positive predictive value of laparoscopy alone for the detection of metastatic disease to the liver, peritoneum, or mesentery was 88% (29 of 33 patients). Laparoscopy was successfully performed without complications in all patients with pancreatic cancer; however, one had a technically unsatisfactory examination. The overall rate of resectability after staging by imaging studies and laparoscopy was 57% (35 of 61 patients). CONCLUSIONS: In patients with a negative CT for metastases, laparoscopic identification of metastases avoided unnecessary laparotomy in 29 of 99 (29%) patients with pancreatic cancer. Staging laparoscopy is indicated in all cases of pancreatic malignancy before an attempt at a surgical cure.

Aged↗

A randomized double-blind placebo-controlled trial evaluating the cost-effectiveness of droperidol as a sedative premedication for EUS.

BACKGROUND: Droperidol is a neuroleptic agent with anti-emetic properties that produces mild sedation, reduced anxiety, and a state of mental detachment and indifference to one's surroundings. Routine premedication with droperidol has been shown to improve sedation during esophagogastroduodenoscopy and endoscopic retrograde cholangiopancreatography. The purpose of this randomized double-blind placebo-controlled study was to determine whether premedication with droperidol improves sedation during routine upper endoscopic ultrasound (EUS) in a cost-effective manner. METHODS: One hundred consecutive patients referred for EUS were randomly assigned to receive either 2.5 mg or 5 mg of droperidol or placebo before the procedure. After EUS, the physician, nurse, and recovered patient scored various parameters of procedural sedation. RESULTS: In the group receiving 5 mg of droperidol there was significantly less gagging at intubation, less retching during the procedure, better patient cooperation, less need for physical restraint, and improved nurses' and physician's impression of sedation. Significantly less meperidine and less midazolam were required for sedation, making medication costs significantly lower in the group receiving 5 mg droperidol. CONCLUSIONS: A 5 mg dose of droperidol given as premedication for routine upper EUS improves sedation during the procedure while significantly decreasing the overall cost of sedation.

Adjuvants, Anesthesia↗

QT dispersion predicts ventricular arrhythmia in pediatric cardiomyopathy patients referred for heart transplantation.

BACKGROUND: QT dispersion has been used in stratifying risk for sudden death in adults with dilated cardiomyopathy, but its role in the pediatric population has not been delineated. METHODS: We reviewed electrocardiograms in pediatric patients with dilated cardiomyopathy referred for heart transplantation, to evaluate the role of QT dispersion in predicting malignant arrhythmias in these patients. Three groups were defined: Group I (n = 13) had dilated cardiomyopathy and malignant ventricular arrhythmias, Group II (n = 13) had dilated cardiomyopathy with no ventricular arrhythmias and Group III (n = 30) consisted of normals. QT dispersion was defined as the duration of the shortest QT subtracted from that of the longest. In addition, the standard deviation of the QT intervals was calculated for each ECG, using 12 leads. RESULTS: QT dispersion was significantly prolonged in Group I (97 +/- 33 msec) compared to Group II (74 +/- 19 msec) and Group III (42 +/- 17 msec). QT standard deviation was also prolonged in Group I (30 +/- 11 msec) vs Group II (22 +/- 5 msec) and Group III (13 +/- 4 msec). Using a threshold value of 90 msec for QT dispersion or 25 msec for QT standard deviation, a sensitivity of 78% and a specificity of 70% was obtained for identifying patients who would subsequently develop ventricular arrhythmias. CONCLUSIONS: In pediatric heart transplant candidates with dilated cardiomyopathy, QT dispersion and QT standard deviation identify patients at higher risk for the development of malignant ventricular arrhythmia. This simple test can be helpful in the evaluation and management of these patients awaiting transplantation.

Adolescent↗

The use of advanced-age donor hearts adversely affects survival in pediatric heart transplantation.

There is a limited supply of adequate donor hearts for cardiac transplantation. The safety of using advanced-age donor hearts has been debated in adult transplantation but has not been studied previously in pediatric recipients. In this retrospective study, survival of 79 pediatric heart transplant recipients was reviewed. Pediatric recipient groups were stratified based on donor age (group 1 donor age > 40 yr, n = 5; group 2 donor age < or = 40 yr, n = 74). Survival of 267 adolescent (ages 11-17) heart transplant recipients in the United Network for Organ Sharing (UNOS) database was also reviewed. Patients were likewise divided into two groups based on donor age (> 40 yr, n = 12; < or = 40 yr, n = 255). Survival at one yr was 20% in group 1 vs. 78% in group 2 (p < 0.005). Cause of death in all group 1 patients was graft failure secondary to acute rejection. Analysis of risk of death was only significantly attributable to the age of the donor. The increased risk attributable to advanced donor age was also supported by the UNOS data. The UNOS one and two-year Kaplan-Meier survival curves were significantly lower in adolescent patients who received donor hearts > 40 yr of age. One-year survival was 58% (older donors) vs. 85% (younger donors, p < 0.005) and two-year survival was 44% (older donors) vs. 79% (younger donors, p < 0.005). Advanced-age donor hearts should be contraindicated in pediatric transplantation with the exception of critically ill patients who may not be able to wait for a younger heart.

Acute Disease↗

The autonomy of mood disorders among cocaine-using methadone patients.

This study uses an algorithm to determine whether patients dually diagnosed with a mood disorder and cocaine dependence have either (a) an autonomous mood disorder (onset of mood disorder prior to substance use disorder (SUD) or mood disorder symptoms persist during periods of abstinence or (b) a nonautonomous mood disorder (onset of SUD preceded mood disorder and mood disorder symptoms remit during periods of abstinence). The relationship among autonomy, patient characteristics, and treatment completion is examined. The sample included 67 methadone patients with a mood disorder (87% major depression, 13% bipolar) who were enrolling in a 6-month psychosocial treatment for cocaine use. Of these subjects, 27% were rated as having an autonomous mood disorder and 73% a nonautonomous mood disorder. Mean age was 37 years; 55% were female and 82% were Hispanic or African-American. All subjects had been stabilized on methadone (mean = 70 mg). During the 30 days prior to study intake, subjects with an autonomous mood disorder, compared to subjects with a nonautonomous mood disorder, reported fewer days using cocaine (12.5 versus 21.1) and fewer days drinking four or more drinks of alcohol (1.1 versus 6. 1). Treatment completion was associated with less cocaine use, autonomy, and African-American ethnicity. However, when these variables were controlled using logistic regression, only autonomous mood disorder and ethnicity predicted treatment completion. These results suggest that autonomy may be a useful construct to measure, and that subjects with nonautonomous mood disorders may need special efforts to ensure treatment retention.

Adult↗

Abnormal regulation of the sympathetic nervous system in alpha2A-adrenergic receptor knockout mice.

alpha2-Adrenergic receptors (ARs) play a key role in regulating neurotransmitter release in the central and peripheral sympathetic nervous systems. To date, three subtypes of alpha2-ARs have been cloned (alpha2A, alpha2B, and alpha2C). Here we describe the physiological consequences of disrupting the gene for the alpha2A-AR. Mice lacking functional alpha2A subtypes were compared with wild-type (WT) mice, with animals lacking the alpha2B or alpha2C subtypes, and with mice carrying a point mutation in the alpha2A-AR gene (alpha2AD79N). Deletion of the alpha2A subtype led to an increase in sympathetic activity with resting tachycardia (knockout, 581 +/- 21 min-1; WT, 395 +/- 21 min-1), depletion of cardiac tissue norepinephrine concentration (knockout, 676 +/- 31 pg/mg protein; WT, 1178 +/- 98 pg/mg protein), and down-regulation of cardiac beta-ARs (Bmax: knockout, 23 +/- 1 fmol/mg protein; WT, 31 +/- 2 fmol/mg protein). The hypotensive effect of alpha2 agonists was completely absent in alpha2A-deficient mice. Presynaptic alpha2-AR function was tested in two isolated vas deferens preparations. The nonsubtype-selective alpha2 agonist dexmedetomidine completely blocked the contractile response to electrical stimulation in vas deferens from alpha2B-AR knockout, alpha2C-AR knockout, alpha2AD79N mutant, and WT mice. The maximal inhibition of vas deferens contraction by the alpha2 agonist in alpha2A-AR knockout mice was only 42 +/- 9%. [3H]Norepinephrine release studies performed in vas deferens confirmed these findings. The results indicate that the alpha2A-AR is a major presynaptic receptor subtype regulating norepinephrine release from sympathetic nerves; however, the residual alpha2-mediated effect in the alpha2A-AR knockout mice suggests that a second alpha2 subtype (alpha2B or alpha2C) also functions as a presynaptic autoreceptor to inhibit transmitter release.

Animals↗

Phospholamban deficiency does not compromise exercise capacity.

Deficiency of phospholamban (PLB) results in enhancement of basal murine cardiac function and an attenuated response to beta-adrenergic stimulation. To determine whether the absence of PLB also reduces the reserve capacity of the murine cardiovascular system to respond to stress, we evaluated the heart rate (HR), blood pressure, and metabolic responses of PLB-deficient (PLB-/-) mice to graded treadmill exercise (GTE). PLB-/- mice were hypertensive at rest (125 +/- 19 vs. 109 +/- 16 mmHg, P < 0.05) but had normal tachycardic and hypotensive responses to isoproterenol. The HR response to GTE was normal; however, the hypertension in PLB-/- mice normalized at peak exercise. Their exercise capacities, as measured by duration of exercise and peak oxygen consumption (VO2), were normal. The oxygen pulse (VO2/HR) curve was also normal in PLB-/- mice, suggesting an ability to appropriately increase stroke volume and oxygen extraction during GTE, despite an inability to increase beta-adrenergically stimulated cardiac contractility. Thus deficiency of PLB, although resulting in diminished beta-adrenergic inotropic reserve, does not compromise cardiac performance during exercise.

Adrenergic beta-Agonists↗

Impaired aerobic capacity in hypercholesterolemic mice: partial reversal by exercise training.

The present study assessed whether impaired aerobic capacity previously observed in hypercholesterolemic mice is reversible by exercise training. Seventy-two 8-wk-old female C57BL/6J wild-type (+, n = 42) and apolipoprotein E-deficient (-, n = 30) mice were assigned to the following eight interventions: normal chow, sedentary (E+, n = 17; E-, n = 8) or exercised (E+ex, n = 13; E-ex, n = 7) and high-fat chow, sedentary (E+chol, n = 6; E-chol, n = 8) or exercised (E+chol-ex, n = 6; E-chol-ex, n = 7). Mice were trained on a treadmill 2 x 1 h/day, 6 days/wk, for 4 wk. Cholesterol levels correlated inversely with maximum oxygen uptake (r = -0.35; P < 0. 02), which was blunted in all hypercholesterolemic sedentary groups (all P < 0.05). Maximum oxygen uptake improved in all training groups but failed to match E+ex (all P < 0.05). Vascular reactivity and nitric oxide (NO) synthesis correlated with anaerobic threshold (r = 0.36; P < 0.025) and maximal distance run (r = 0.59; P < 0.007). We conclude that genetically induced hypercholesterolemia impairs aerobic capacity. This adverse impact of hypercholesterolemia on aerobic capacity may be related to its impairment of vascular NO synthesis and/or vascular smooth muscle sensitivity to nitrovasodilators. Aerobic capacity is improved to the same degree by exercise training in normal and genetically hypercholesterolemic mice, although there remains a persistent difference between these groups after training.

Aerobiosis↗

A controlled trial of chlorofluorocarbon-free triamcinolone acetonide inhalation aerosol in the treatment of adult patients with persistent asthma. Azmacort HFA Study Group.

STUDY OBJECTIVE: To compare the dose response, efficacy, and safety of inhaled triamcinolone acetonide (TAA) with a hydrofluoroalkane (HFA) propellant (75 microg/puff), TAA with a chlorofluorocarbon propellant (dichlorodifluoromethane [P-12]; 75 microg/puff), and placebo in adult patients with persistent asthma. DESIGN: Multicenter, randomized, double-blind, placebo-controlled, parallel-group study of 514 adult patients with persistent asthma. INTERVENTIONS AND MEASUREMENTS: Patients received 8 weeks of treatment with 150, 300, or 600 microg/d of TAA HFA, the same doses of TAA P-12, or placebo following a 5- to 21-day baseline period. Efficacy was assessed by spirometry, and by daily recordings of albuterol use, peak expiratory flow (PEF), asthma symptom ratings, and nighttime awakenings throughout the study. RESULTS: Linear trend analysis showed that both formulations of TAA at all doses produced statistically significant improvements compared with placebo in spirometry, asthma symptom scores, albuterol use, and PEF. Significant improvement was seen as early as 24 h for morning PEF and as early as 1 week for FEV(1) (TAA HFA, 600 microg/d; TAA P-12, 300 and 600 microg/d) and albuterol use (all doses of both formulations). The P-12 and HFA formulations had comparable efficacy. A dose response showing greater improvement with higher doses was evident for the majority of parameters for both formulations. The incidences of adverse events were similar across all treatment groups with no dose-related trends. CONCLUSION: HFA and P-12 formulations of TAA inhalation aerosol were therapeutically equivalent and showed comparable safety and dose-related efficacy in the treatment of patients with persistent asthma.

Administration, Inhalation↗

Limb blood flow during exercise is dependent on nitric oxide.

BACKGROUND: We have recently reported that hypercholesterolemia reduces aerobic exercise capacity in mice and that this is associated with a reduced endothelium-dependent vasodilator function, endothelium-derived nitric oxide (EDNO) production, and urinary nitrate excretion. These findings led us to test the hypothesis that EDNO production contributes significantly to limb blood flow during exercise and to determine whether loss of EDNO production is responsible for the decline in exercise capacity observed in hypercholesterolemia. METHODS AND RESULTS: Twelve-week-old wild-type (E+; n=9) and apoE-deficient (E-; n=9) C57BL/6J mice were treadmill-tested to measure indices defining exercise capacity on a metabolic chamber-enclosed treadmill capable of measuring oxygen uptake and carbon dioxide excretion. Urine was collected before and after treadmill exercise for determination of vascular NO production assessed by urinary nitrate excretion. The wild-type mice were then given nitro-L-arginine (E+LNA) in the drinking water (6 mg/dL) for 4 days before undergoing a second treadmill testing and urinary nitrate measurement. An additional set of 12-week-old wild-type mice was divided into 2 groups: 1 receiving regular water (E+; n=8) and 1 administered LNA for 4 days (E+LNA; n=8). These mice, along with an additional set of E mice (n=8), underwent treadmill testing to determine maximal oxygen uptake (VO2max). The mice were then cannulated such that the tip of the tubing was positioned in the ascending aorta. Fluorescent microspheres (20000) were infused into the carotid cannula while the mice were sedentary and again while approaching VO2max. When the mice were euthanized, the running muscles were collected and fluorescence intensity was measured to determine the peak-exercise redistribution of blood flow to the running muscles (expressed as percentage of total cardiac output, %COrm) during both states. Both E+LNA and E- mice demonstrated a markedly reduced postexercise urinary nitrate excretion, aerobic capacity, and %COrm at VO2max compared with E+. CONCLUSIONS: EDNO contributes significantly to limb blood flow during exercise. Conditions that reduce EDNO production disturb the hyperemic response to exercise, resulting in a reduced exercise capacity.

Animals↗

Calcium carbonate and the premenstrual syndrome: effects on premenstrual and menstrual symptoms. Premenstrual Syndrome Study Group.

OBJECTIVE: Previous reports have suggested that disturbances in calcium regulation may underlie the pathophysiologic characteristics of premenstrual syndrome and that calcium supplementation may be an effective therapeutic approach. To evaluate the effect of calcium carbonate on the luteal and menstrual phases of the menstrual cycle in premenstrual syndrome, a prospective, randomized, double-blind, placebo-controlled, parallel-group, multicenter clinical trial was conducted. STUDY DESIGN: Healthy, premenopausal women between the ages of 18 and 45 years were recruited nationally across the United States at 12 outpatient centers and screened for moderate-to-severe, cyclically recurring premenstrual symptoms. Symptoms were prospectively documented over 2 menstrual cycles with a daily rating scale that had 17 core symptoms and 4 symptom factors (negative affect, water retention, food cravings, and pain). Participants were randomly assigned to receive 1200 mg of elemental calcium per day in the form of calcium carbonate or placebo for 3 menstrual cycles. Routine chemistry, complete blood cell count, and urinalysis were obtained on all participants. Daily documentation of symptoms, adverse effects, and compliance with medications were monitored. The primary outcome measure was the 17-parameter symptom complex score. RESULTS: Seven hundred twenty women were screened for this trial; 497 women were enrolled; 466 were valid for the efficacy analysis. There was no difference in age, weight, height, use of oral contraceptives, or menstrual cycle length between treatment groups. There were no differences between groups in the mean screening symptom complex score of the luteal (P = .659), menstrual (P = .818), or intermenstrual phase (P = .726) of the menstrual cycle. During the luteal phase of the treatment cycle, a significantly lower mean symptom complex score was observed in the calcium-treated group for both the second (P = .007) and third (P < .001) treatment cycles. By the third treatment cycle calcium effectively resulted in an overall 48% reduction in total symptom scores from baseline compared with a 30% reduction in placebo. All 4 symptom factors were significantly reduced by the third treatment cycle. CONCLUSIONS: Calcium supplementation is a simple and effective treatment in premenstrual syndrome, resulting in a major reduction in overall luteal phase symptoms.

Adolescent↗