Cerebral Ketones Detected by 3T MR Spectroscopy in Patients with High-Grade Glioma on an Atkins-Based Diet.

BACKGROUND AND PURPOSE: Ketogenic diets are being explored as a possible treatment for several neurological diseases, but the physiologic impact on the brain is unknown. The objective of this study was to evaluate the feasibility of 3T MR spectroscopy to monitor brain ketone levels in patients with high-grade gliomas who were on a ketogenic diet (a modified Atkins diet) for 8 weeks. MATERIALS AND METHODS: Paired pre- and post-ketogenic diet MR spectroscopy data from both the lesion and contralateral hemisphere were analyzed using LCModel software in 10 patients. RESULTS: At baseline, the ketone bodies acetone and ß-hydroxybutyrate were nearly undetectable, but by week 8, they increased in the lesion for both acetone (0.06 ± 0.03 ≥ 0.27 ± 0.06 IU, P = .005) and ß-hydroxybutyrate (0.07 ± 0.07 ≥ 0.79 ± 0.32 IU, P = .046). In the contralateral brain, acetone was also significantly increased (0.041 ± 0.01 ≥ 0.16 ± 0.04 IU, P = .004), but not ß-hydroxybutyrate. Acetone was detected in 9/10 patients at week 8, and ß-hydroxybutyrate, in 5/10. Acetone concentrations in the contralateral brain correlated strongly with higher urine ketones (r = 0.87, P = .001) and lower fasting glucose (r = -0.67, P = .03). Acetoacetate was largely undetectable. Small-but-statistically significant decreases in NAA were also observed in the contralateral hemisphere at 8 weeks. CONCLUSIONS: This study suggests that 3T MR spectroscopy is feasible for detecting small cerebral metabolic changes associated with a ketogenic diet, provided that appropriate methodology is used.

Radiation-Induced Myelitis: Initial and Follow-Up MRI and Clinical Features in Patients at a Single Tertiary Care Institution during 20 Years.

Myelitis is a rare complication of radiation exposure to the spinal cord and is often a diagnosis of exclusion. A retrospective review of clinical records and serial imaging was performed to identify subjects with documented myelitis and a history of prior radiation. Eleven patients fulfilled the inclusion criteria. All patients had longitudinally extensive cord involvement with homogeneous precontrast T1 hyperintense signal in the adjacent vertebrae, corresponding to the radiation field. T2 signal abnormalities involving the central two-thirds of the cord were seen in 6/11 patients (55%). The degree of cord expansion and contrast enhancement was variable but was seen in 6 (54%) and 5 (45%) patients, respectively. On follow-up, 2 patients developed cord atrophy, while complete resolution was noted in 1. Clinical improvement was noted in 5 patients, with symptom progression in 2 patients. Our results suggest that radiation myelitis is neither universally progressive nor permanent, and some radiographic and clinical improvement may occur.

Creation of an international registry to support discovery in schwannomatosis.

Schwannomatosis is a tumor suppressor syndrome that causes multiple tumors along peripheral nerves. Formal diagnostic criteria were first published in 2005. Variability in clinical presentation and a relative lack of awareness of the syndrome have contributed to difficulty recognizing affected individuals and accurately describing the natural history of the disorder. Many critical questions such as the mutations underlying schwannomatosis, genotype-phenotype correlations, inheritance patterns, pathologic diagnosis of schwannomatosis-associated schwannomas, tumor burden in schwannomatosis, the incidence of malignancy, and the effectiveness of current, or new treatments remain unanswered. A well-curated registry of schwannomatosis patients is needed to facilitate research in field. An international consortium of clinicians and scientists across multiple disciplines with expertise in schwannomatosis was established and charged with the task of designing and populating a schwannomatosis patient registry. The International Schwannomatosis Registry (ISR) was built around key data points that allow confirmation of the diagnosis and identification of potential research subjects to advance research to further the knowledge base for schwannomatosis. A registry with 389 participants enrolled to date has been established. Twenty-three additional subjects are pending review. A formal process has been established for scientific investigators to propose research projects, identify eligible subjects, and seek collaborators from ISR sites. Research collaborations have been created using the information collected by the registry and are currently being conducted. The ISR is a platform from which multiple research endeavors can be launched, facilitating connections between affected individuals interested in participating in research and researchers actively investigating a variety of aspects of schwannomatosis. © 2016 Wiley Periodicals, Inc.

Bevacizumab treatment for symptomatic spinal ependymomas in neurofibromatosis type 2.

BACKGROUND: Neurofibromatosis type 2 (NF2) is a tumor suppressor syndrome associated with vestibular schwannomas, meningiomas, and spinal ependymomas. There have been anecdotal reports of radiographic response of spinal ependymomas in NF2 patients being treated for progressive vestibular schwannomas with bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF). AIMS: The aim of this study was to review the clinical effects of bevacizumab treatment for symptomatic, NF2-associated ependymomas METHODS: We conducted a retrospective review of all patients with NF2 treated with bevacizumab for symptomatic ependymoma at three NF2 specialty centers. Tumor size was evaluated by linear measurements; radiographic response was defined as >20% reduction in tumor size. We also performed immunohistochemical evaluation of NF2-associated symptomatic ependymomas from five patients, including two from this clinical series. RESULTS: Eight patients with NF2 and symptomatic ependymoma were treated with bevacizumab. All patients had subjective clinical improvement with bevacizumab, although only five of eight patients evaluated had radiographic response. All tumors expressed VEGF-R2. Four of five evaluated ependymomas expressed VEGF-R1; one without VEGF-R1 expression was from a patient who showed clinical but not radiographic response. CONCLUSIONS: Treatment using bevacizumab improved symptoms related to NF2-associated ependymomas, often without concurrent radiographic response. This treatment effect may be related to VEGF-R1 expression in NF2-associated ependymoma.

Conventional and functional MR imaging of peripheral nerve sheath tumors: initial experience.

BACKGROUND AND PURPOSE: Differentiating benign from malignant peripheral nerve sheath tumors can be very challenging using conventional MR imaging. Our aim was to test the hypothesis that conventional and functional MR imaging can accurately diagnose malignancy in patients with indeterminate peripheral nerve sheath tumors. MATERIALS AND METHODS: This institutional review board-approved, Health Insurance Portability and Accountability Act-compliant study retrospectively reviewed 61 consecutive patients with 80 indeterminate peripheral nerve sheath tumors. Of these, 31 histologically proved peripheral nerve sheath tumors imaged with conventional (unenhanced T1, fluid-sensitive, contrast-enhanced T1-weighted sequences) and functional MR imaging (DWI/apparent diffusion coefficient mapping, dynamic contrast-enhanced MR imaging) were included. Two observers independently assessed anatomic (size, morphology, signal) and functional (ADC values, early arterial enhancement by dynamic contrast-enhanced MR) features to determine interobserver agreement. The accuracy of MR imaging for differentiating malignant from benign was also determined by receiver operating characteristic analysis. RESULTS: Of 31 peripheral nerve sheath tumors, there were 9 malignant (9%) and 22 benign ones (81%). With anatomic sequences, average tumor diameter (6.3 ± 1.8 versus 3.9 ± 2.3 mm, P = .009), ill-defined/infiltrative margins (77% versus 32%; P = .04), and the presence of peritumoral edema (66% versus 23%, P = .01) were different for malignant peripheral nerve sheath tumors and benign peripheral nerve sheath tumors. With functional sequences, minimum ADC (0.47 ± 0.32 × 10(-3) mm(2)/s versus 1.08 ± 0.26 × 10(-3) mm(2)/s; P < .0001) and the presence of early arterial enhancement (50% versus 11%; P = .03) were different for malignant peripheral nerve sheath tumors and benign peripheral nerve sheath tumors. The minimum ADC (area under receiver operating characteristic curve was 0.89; 95% confidence interval, 0.73-0.97) and the average tumor diameter (area under the curve = 0.8; 95% CI, 0.66-0.94) were accurate in differentiating malignant peripheral nerve sheath tumors from benign peripheral nerve sheath tumors. With threshold values for minimum ADC ≤ 1.0 × 10(-3) mm(2)/s and an average diameter of ≥4.2 cm, malignancy could be diagnosed with 100% sensitivity (95% CI, 66.4%-100%). CONCLUSIONS: Average tumor diameter and minimum ADC values are potentially important parameters that may be used to distinguish malignant peripheral nerve sheath tumors from benign peripheral nerve sheath tumors.

Characterization of peripheral nerve sheath tumors with 3T proton MR spectroscopy.

BACKGROUND AND PURPOSE: The characterization of peripheral nerve sheath tumors is challenging. The purpose here was to investigate the diagnostic value of quantitative proton MR spectroscopy at 3T for the characterization of peripheral nerve sheath tumors as benign or malignant, compared with PET. MATERIALS AND METHODS: Twenty participants with 24 peripheral nerve sheath tumors underwent MR spectroscopy by use of a point-resolved sequence (TE, 135 ms). Six voxels were placed in 4 histologically proven malignant peripheral nerve sheath tumors and 22 voxels in 20 benign peripheral nerve sheath tumors (9 histologically proven, 11 with documented stability). The presence or absence of a trimethylamine signal was evaluated, the trimethylamine concentration estimated by use of phantom replacement methodology, and the trimethylamine fraction relative to Cr measured. MR spectroscopy results for benign and malignant peripheral nerve sheath tumors were compared by use of a Mann-Whitney test, and concordance or discordance with PET findings was recorded. RESULTS: In all malignant tumors and in 9 of 18 benign peripheral nerve sheath tumors, a trimethylamine peak was detected, offering the presence of trimethylamine as a sensitive (100%), but not specific (50%), marker of malignant disease. Trimethylamine concentrations (2.2 ± 2.8 vs 6.6 ± 5.8 institutional units; P < .049) and the trimethylamine fraction (27 ± 42 vs 88 ± 22%; P < .012) were lower in benign than malignant peripheral nerve sheath tumors. A trimethylamine fraction threshold of 50% resulted in 100% sensitivity (95% CI, 58.0%-100%) and 72.2% (95% CI, 59.5%-75%) specificity for distinguishing benign from malignant disease. MR spectroscopy and PET results were concordant in 12 of 16 cases, (2 false-positive results for MR spectroscopy and PET each). CONCLUSIONS: Quantitative measurement of trimethylamine concentration by use of MR spectroscopy is feasible in peripheral nerve sheath tumors and shows promise as a method for the differentiation of benign and malignant lesions. Trimethylamine presence within a peripheral nerve sheath tumor is a sensitive marker of malignant disease, but quantitative measurement of trimethylamine content is required to improve specificity.

Anatomic MR imaging and functional diffusion tensor imaging of peripheral nerve tumors and tumorlike conditions.

BACKGROUND AND PURPOSE: A number of benign and malignant peripheral nerve tumor and tumorlike conditions produce similar imaging features on conventional anatomic MR imaging. Functional MR imaging using DTI can increment the diagnostic performance in differentiation of these lesions. Our aim was to evaluate the role of 3T anatomic MR imaging and DTI in the characterization of peripheral nerve tumor and tumorlike conditions. MATERIALS AND METHODS: Twenty-nine patients (13 men, 16 women; mean age, 41±18 years; range, 11-83 years) with a nerve tumor or tumorlike condition (25 benign, 5 malignant) underwent 3T MR imaging by using anatomic (n=29), functional diffusion, DWI (n=21), and DTI (n=24) techniques. Images were evaluated for image quality (3-point scale), ADC of the lesion, tractography, and fractional anisotropy of nerves with interobserver reliability in ADC and FA measurements. RESULTS: No significant differences were observed in age (benign, 40±18 versus malignant, 45±19 years) and sex (benign, male/female=12:12 versus malignant, male/female=3:2) (P>.05). All anatomic (29/29, 100%) MR imaging studies received "good" quality; 20/21 (95%) DWI and 21/24 (79%) DTI studies received "good" quality. ADC of benign lesions (1.848±0.40×10(-3) mm2/s) differed from that of malignant lesions (0.900±0.25×10(-3) mm2/s, P<.001) with excellent interobserver reliability (ICC=0.988 [95% CI, 0.976-0.994]). There were no FA or ADC differences between men and women (P>.05). FA of involved nerves was lower than that in contralateral healthy nerves (P<.001) with excellent interobserver reliability (ICC=0.970 [95% CI, 0.946-0.991]). ADC on DTI and DWI was not statistically different (P>.05), with excellent intermethod reliability (ICC=0.943 [95% CI, 0.836-0.980]). Tractography differences were observed in benign and malignant lesions. CONCLUSIONS: 3T MR imaging and DTI are valuable methods for anatomic and functional evaluation of peripheral nerve lesions with excellent interobserver reliability. While tractography and low FA provide insight into neural integrity, low diffusivity values indicate malignancy in neural masses.

A survey of self-medication practices and perceived effectiveness of glucosamine products among older adults.

OBJECTIVES: The purpose of this study was to investigate the decision-making and self-treatment practices of older users of glucosamine products, namely (1) how do older adults decide to use glucosamine products? (2) what influences their choice? (3) how do they manage their glucosamine treatment? and (4) what is their perception of the effectiveness, side effects, and costs of glucosamine products? DESIGN: A descriptive, exploratory study using a questionnaire survey. SETTING: Province-wide. Invitations to participate were extended to all people living in a Canadian province who used/had used glucosamine products. RESULTS: Advice from friends was a major factor in the decision to take glucosamine. Cost was a major factor influencing the type and brand name of the product used. Ninety-two percent managed their own treatment. The majority (88%) used glucosamine regularly; only one-third took the recommended daily dose. Sixty-seven percent perceived the product to be helpful in relieving symptoms. CONCLUSION: Public education and further research is needed regarding the use of glucosamine products.

Evaluation of an osteoporosis workshop for women.

Osteoporosis is a serious health problem that has reached epidemic proportions among Canadian women. This disease, and its concomitant fractures, places a heavy burden on society in terms of human suffering, loss of productivity, death, and health care costs. In keeping with these concerns, a Canadian community health agency has developed a series of workshops that are designed, in part, to educate women about this disease and to encourage them to take appropriate steps to prevent it or to make informed decisions about its treatment. The present study was designed to evaluate the outcome of one of these workshops. A semi-experimental design was used to measure any changes in the participants' knowledge about osteoporosis and their prevention and treatment practices regarding this disease. The results were compared to those of a control group that consisted of members of various branches of the Women's Institute who volunteered to participate in the study. The findings indicate that the workshop was effective in increasing the participants' level of knowledge on osteoporosis, an increase that was still evident 6 months following the session. The effect of the workshop on the actual preventive and treatment practices of women who attended, however, was limited to a slight increase in the use of hormone replacement therapy (HRT) and calcium intake.

Parent satisfaction with education, support, and decision-making regarding their children's central venous access devices.

This descriptive, exploratory study assessed parents' satisfaction with the education and support they received before and after their children had central venous access devices (CVADs) inserted for cancer treatment. Decisions regarding the type of CVAD and parent satisfaction with that choice were also evaluated. Parents of children who experienced a CVAD during the six-year period 1992-1997 participated. Data were collected through telephone interviews using a questionnaire specifically designed for the purposes of the study. Results suggest that parents were satisfied with the teaching and support received both prior to and following CVAD insertion. Other findings reveal that not all parents take part in decisions about the type of device used, and that if given a choice, based on their experience, they would likely choose implanted ports over Hickman catheters.

Women's knowledge and practices regarding the prevention and treatment of osteoporosis.

Osteoporosis and related fractures are a major cause of disability, institutionalization, and death among aging women. Unless prevented or actively treated, osteoporosis will continue to limit both the quantity and quality of life for many older women and significantly add to the health care costs of this rapidly growing population group. This study was designed to assess women's knowledge and practices regarding the prevention and treatment of osteoporosis. A descriptive/exploratory design was used to survey a convenience sample of 185 women. Measures of knowledge and practices were obtained with a hand-delivered questionnaire. Data were statistically and thematically described. The results suggest that women are receiving inadequate information about osteoporosis, possess limited knowledge about the disease, and are not taking adequate measures to prevent or treat osteoporosis as they age. Implications for health education on these issues are addressed and plans for future research are briefly discussed.

Adrenergic receptor function in panic disorder. II. Neutrophil beta 2 receptors: Gs protein coupling, effects of imipramine treatment and relationship to treatment outcome.

Panic attacks are associated with increased autonomic symptoms, suggesting increased beta 2-adrenergic receptor (beta 2AR) function in PD. Tricyclic antidepressants downregulate beta AR function. Previous studies on beta AR function in PD, however, are inconsistent. We recently found increased beta AR coupling and density in neutrophils of symptomatic drug-free PD patients. This study evaluated beta AR coupling to Gs protein in 28 controls, 25 drug-free PD patients and 8 PD imipramine-treated patients. PD patients had significantly higher coupling and receptor density, particularly in the high-conformational state. Differences were more pronounced in patients with less depressive symptomatology. Treatment with imipramine was associated with decreased beta AR coupling and density in the high-conformational state. Several beta AR binding parameters were related to severity of anxiety symptoms and treatment outcome. Antidepressants downregulate beta AR density and induce uncoupling from Gs protein in PD. Future studies may investigate beta AR coupling in relationship to treatment outcome and the role of beta AR kinase in PD.

Neutrophil beta2-adrenergic receptor coupling efficiency to Gs protein in subjects with post-traumatic stress disorder and normal controls.

The symptomatology of post-traumatic stress disorder (PTSD) involves sympathetic hyperarousal. Several of these sympathetic symptoms are mediated through end-organ beta2-adrenergic receptors (beta2AR). Increased sympathetic activity in PTSD could therefore be due to increased betaAR function. This study investigated betaAR function in 30 healthy controls and 20 drug-free PTSD patients. BetaAR binding studies were conducted using antagonist-saturation and agonist-displacement experiments. Measures of beta2AR coupling to Gs protein were derived from agonist-displacement experiments. PTSD patients had significantly higher beta2AR density particularly in the high-conformational state and higher beta2AR coupling than controls, as reflected in a higher percentage of receptors in the high conformational state and a higher ratio of the agonist dissociaton constant from the receptor in the low/high-conformational state. Increased betaAR function in PTSD is consistent with the symptomatology of this disorder. Increased betaAR density and coupling may be consistent with downregulation of betaAR density and uncoupling by antidepressants and may underlie their partial efficacy in PTSD. Dysregulation in Gs protein function is postulated and, agonist-mediated regulation of betaAR expression and/or betaAR kinase activity in PTSD should be investigated in future studies.

Characteristics of norepinephrine and clonidine displacement of [3H]yohimbine binding to platelet alpha2-adrenoreceptors in healthy volunteers.

Clonidine's estimates of platelet alpha2-adrenoreceptor (alpha2AR) density are substantially lower than yohimbine's. This discrepancy could have contributed to inconsistent results from studies on the role of alpha2AR in depression. Furthermore, few studies have investigated the relative distribution of alpha2AR between the high- and low-affinity states or their Gi protein coupling. [3H]yohimbine saturable binding to platelet alpha2AR, its displacement by norepinephrine and clonidine, and the effects of Gpp(NH)p on agonist displacement curves were investigated in 11 healthy volunteers. Clonidine estimates of alpha2AR density were close to norepinephrine estimates, and both were strongly correlated. Clonidine's K(L)/K(H) ratio was lower than norepinephrine's, consistent with its partial agonist nature. Norepinephrine and clonidine displacement curves revealed two affinity states. Gpp(NH)p induced a significant rightward shift to a single low-affinity state. When used in combination with a specific antagonist, clonidine's estimates of alpha2AR density were similar to those of norepinephrine's, and both were higher than previously reported, when clonidine was used alone. Re-evaluation of previous studies on alpha2AR in depression using clonidine is needed. The combined use of antagonist-saturation and agonist-displacement experiments to examine possible dysregulation in alpha2AR coupling to Gi protein in psychiatric disorders is recommended.

Adrenergic receptor function in panic disorder. I. Platelet alpha 2 receptors: Gi protein coupling, effects of imipramine, and relationship to treatment outcome.

Various studies suggest alpha 2-adrenergic receptor (alpha 2AR) dysregulation in panic disorder (PD). Platelet alpha 2-AR exist in high- and low-conformational states as a function of their coupling to Gi protein. alpha 2AR coupling is important in signal transduction and is modulated by antidepressants. alpha 2AR density in the high- and low-conformational states, agonist affinity, and coupling efficiency were investigated in 21 healthy controls, 21 drug-free PD patients, and eight imipramine-treated patients using norepinephrine displacement of 3H-yohimbine binding. Percentage of receptors in the high-conformational state (%RH) and the ratio of the agonist dissociation constant to the receptor in the low-/high-conformational state (KL/KH), calculated from displacement experiments, were used as coupling indices. Patients had high alpha 2AR density in both conformational states. %RH and KL/KH ratio were significantly different, particularly in patients with Hamilton scale for depression (HAMD) scores > or = 15. Imipramine treatment (29 weeks) had no effect on alpha 2AR density or coupling, despite improvement in anxiety ratings. High pretreatment alpha 2AR density and coupling predicted low severity of anxiety after treatment. Increased alpha 2AR density and abnormal coupling may represent an adaptive mechanism or trait marker in PD.

Teaching community health nursing by distance methods: development, process, and evaluation.

In 1995, 23 post-RN (RN-to-BSN) students successfully completed the first clinical nursing course offered by distance methods at Memorial University of Newfoundland. Distance delivery improved access to the course for RNs dealing with conflicting work and family demands. Students rated the course favorably overall and found they had learned and applied new knowledge and skills. Community health nurses, who acted as field guides, and their supervisors were satisfied with their roles and responsibilities. However, one need identified was for detailed information about the course, and another was for more frequent communication with the course instructors during the term. Evaluation found students were able to meet their course objectives and perform as well as students who had completed a similar on-campus course.

Characteristics of agonist displacement of [3H]ketanserin binding to platelet 5-HT2A receptors: implications for psychiatric research.

Brain 5-HT(2A) receptors exist in two agonist affinity states as a function of their coupling to Gq protein. This has not yet been shown in platelets. We examined [3H]ketanserin's saturable binding to platelet 5-HT2A receptors and characteristics of agonist displacement curves of [3H]ketanserin binding in healthy control subjects. [3H]ketanserin saturation curves showed a trend for a two-site model, reflecting two independent binding sites. At low [3H]ketanserin concentrations, agonist displacement curves were flat and best fit a two-site model, indicating the existence of two agonist affinity states. Guanylyl 5'-imidotriphosphate [Gpp(NH)p] induced a significant rightward shift in agonist displacement curves to fit a one-site model. Platelet membrane 5-HT2A receptors exist in two agonist affinity states that are regulated by Gq protein. Platelet 5-HT2A receptors provide an accessible model for examining possible dysregulation in the agonist affinity or coupling efficiency to the phosphoinositide system in psychiatric disorders and their modulation by psychotropic medications.

Adrenergic receptors in premenstrual dysphoric disorder: I. Platelet alpha 2 receptors: Gi protein coupling, phase of menstrual cycle, and prediction of luteal phase symptom severity.

BACKGROUND: Abnormal alpha 2-adrenergic receptor (AR) function is implicated in anxiety and depressive disorders. Premenstrual dysphoric disorder (PMDD) is characterized by anxiety and depressive symptoms, which may be associated with changes in alpha 2AR function. Previous studies on alpha 2AR function during phases of the menstrual cycle in controls and PMDD patients are inconsistent. METHODS: alpha 2AR function was examined in 16 PMDD patients and 15 controls during the follicular phase, and in 10 PMDD patients during late luteal phase. Antagonist-measured maximum binding capacity, agonist-measured receptor density in high- and low-conformational states, and agonist affinity to both states were measured. Coupling efficiency to Gi protein was estimated. RESULTS: There were no significant differences in coupling efficiency. PMDD patients had significantly low antagonist affinity; there were no differences in other binding parameters. There were no changes in alpha 2AR binding parameters between phases of menstrual cycle in PMDD women. alpha 2AR density and symptom severity were inversely related during the follicular phase in controls and patients. During luteal phase, alpha 2AR density correlated positively with symptom severity in patients. High follicular alpha 2AR density predicted more severe luteal symptoms in PMDD patients. CONCLUSIONS: These findings are discussed in view of the molecular biology of alpha 2AR, and their role in PMDD, anxiety, and depressive disorders.

Adrenergic receptors in premenstrual dysphoric disorder. II. Neutrophil beta2-adrenergic receptors: Gs protein coupling, phase of menstrual cycle and prediction of luteal phase symptom severity.

Abnormal beta2-adrenergic receptor coupling to Gs protein is implicated in depressive disorders. Steroid hormones and antidepressants modulate beta-adrenergic receptor coupling, which may relate to the therapeutic efficacy of antidepressants. We examined beta2-adrenergic receptors in 18 patients with premenstrual dysphoric disorder (PMDD), in 15 control subjects during the follicular phase and in 12 patients during late luteal phase. Antagonist-measured receptor density, agonist-measured receptor density in the high- and low-conformational states and agonist affinity to both states were measured. Coupling indices to Gs protein were determined from agonist-displacement experiments. Follicular beta2-adrenergic receptor density was higher in patients than in control subjects, with a trend for higher receptor density in the high-conformational state. The phase of menstrual cycle had no effect on beta2-adrenergic receptor regulation in PMDD. Exploratory correlations showed that the K(L)/K(H) ratio was related to anxiety ratings in control subjects and %R(H) was correlated with symptom severity in patients. In patients, follicular beta2-adrenergic receptor binding measures were correlated with luteal symptom severity. These findings suggest abnormal beta2-adrenergic receptor regulation in PMDD. Further exploration of the role of beta-adrenergic receptor kinase, sex steroid hormones and antidepressants on beta-adrenergic receptor regulation in PMDD is warranted.