Radiation Oncology Alternative Payment Model and Large Urban Academic Centers: Future Implications for Patients and Providers.

The radiation oncology alternative payment model (RO-APM) was developed by the Center for Medicare and Medicaid Innovation, a part of the Centers for Medicare & Medicaid Services, as a vehicle to optimize value for patients undergoing radiation therapy. By shifting reimbursement away from fee-for-service and toward a prospective bundled payment system, the RO-APM is intended to bend the cost curve in radiation oncology while preserving or even enhancing outcomes. As with prior large-scale policy initiatives, the nature and magnitude of the RO-APM's impact on care delivery will vary substantially depending on a host of local factors, including practice setting. Urban academic centers play a key role in radiation oncology by spearheading innovation, managing the most complicated cases, training the next generation of radiation oncologists, and often caring for vulnerable patient populations. Thus, to protect patients' access to this high-quality cancer care, it will be crucial to characterize the RO-APM's projected impact on large urban academic institutions before its implementation, including possible unintended adverse consequences. Here, we provide an overview of this seismic change in radiation oncology reimbursement and discuss its unique potential implications for large urban academic institutions as a means to facilitate necessary preparations and inform future revisions to the model.

Navigable Channel-Based Trans-Sulcal Resection of Third Ventricular Colloid Cysts: A Multicenter Retrospective Case Series and Review of the Literature.

BACKGROUND: Developments in frameless neuronavigation and tubular retractors hold the potential for minimizing iatrogenic injury to the overlying cortex and subcortical tracts, with improved access to the ventricular system. The objective of the present study was to evaluate the surgical outcomes after resection of third ventricular colloid cysts using an integrated neuronavigation and channel-based approach. METHODS: We performed a multicenter retrospective analysis of surgical Outcomes after surgical resection of third ventricular colloid cysts via a transtubular trans-sulcal approach. RESULTS: A total of 16 patients were included, with a mean age of 42 years (range, 23-62 years). The mean maximum diameter of cysts was 14 mm (range, 7-28 mm), and preoperative hydrocephalous was present in 12 patients (75%). Gross total resection was achieved in all 16 cases. Of the 12 patients, 4 (25%) had undergone septum pellucidotomy, in addition to cyst resection. No case had required conversion to open craniotomy. No perioperative mortalities occurred. Three patients (18.8%) had developed transient memory deficits, 1 of whom had also developed a pulmonary thromboembolism. The median length of hospital stay was 4 days (range, 2-18 days). All the patients reported resolution of preoperative symptoms at the 1-month follow-up examination. Only 1 patient (6.25%) had required insertion of a ventriculoperitoneal shunt. The median follow-up duration was 6.5 months (range, 3-24 months), and no recurrences were observed. CONCLUSION: Use of a channel-based navigable retractor provided a minimal trans-sulcal approach to third ventricular colloid cysts with the benefit of bimanual surgical control in an air medium for definitive resection of third ventricular colloid cysts.

Multicenter Investigation of Channel-Based Subcortical Trans-Sulcal Exoscopic Resection of Metastatic Brain Tumors: A Retrospective Case Series.

BACKGROUND: Recent advancements have aimed to optimize visualization and minimize insult to healthy cortical and subcortical tissue through the use of tubular-based retractors. OBJECTIVE: To investigate outcomes following resection of cerebral metastases using an integrated tubular retraction system with an exoscope and neuronavigation. METHODS: A multicenter retrospective analysis of surgical outcomes in consecutive patients who underwent resection of a brain metastasis using a tubular retraction system and exoscope was performed. RESULTS: Twenty-five patients were included, with a mean age of 61 yr (24-81 yr). Primary sources included lung (n = 13), breast (n = 3), renal cell (n = 3), and other (n = 6). Locations were frontal (n = 5), parietal (n = 8), cerebellar (n = 8), occipital (n = 3), and splenium (n = 1). Most lesions had a maximum diameter > 3.0 cm (n = 20) and a tumor depth > 4 cm (n = 14). Conversion to open (microscopic) craniotomy was not required in any case. Gross total resection was achieved in 20 cases (80.0%) and subtotal resection in 5 cases (20.0%). Median hospital stay was 2 d (1-12 d). All patients underwent postoperative radiation therapy. Perioperative complications developed in 1 patient (4.0%; hemiparesis and subsequent deep vein thrombosis). At 3-mo follow-up, no mortalities were observed, 19 patients (76.0%) demonstrated neurological improvements, 5 patients (20.0%) had a stable neurological exam, and 1 patient (4.0%) had a neurological decline. CONCLUSION: Utilization of a channel-based, navigable retractor and exoscope is a feasible option for surgical resection of metastatic brain lesions.

Radiosurgical Pallidotomy for Parkinson's Disease.

Deep brain stimulation (DBS) has been widely accepted as a tool for treating many symptoms of Parkinson's disease (PD); pallidotomy has been nearly abandoned. Concerns about both the safety and efficacy of pallidotomy are based on small series, isolated case reports, and techniques that would now be considered obsolete. The senior author recently reviewed long-term follow-up of a series of patients who had gamma knife pallidotomy (GKP) for advanced PD. GKP leads to durable, clinically significant benefit. Bilateral GKP adds incremental improvement. The complication rate was 4% when calculated on a per lesion basis. GKP is not quite as effective as DBS for tremor and bradykinesia; the results of GKP and DBS are equivalent for dyskinesia. GKP should be considered in patients who are not candidates for DBS. GKP is not as invasive as radiofrequency pallidotomy and avoids the problems and expenses associated with DBS. Patients on anticoagulants, with cognitive deficits or with other contraindications to DBS can be offered GKP to alleviate many of the motor symptoms of PD.

The Safety and Feasibility of Image-Guided BrainPath-Mediated Transsulcul Hematoma Evacuation: A Multicenter Study.

BACKGROUND: Subcortical injury resulting from conventional surgical management of intracranial hemorrhage may counteract the potential benefits of hematoma evacuation. OBJECTIVE: To evaluate the safety and potential benefits of a novel, minimally invasive approach for clot evacuation in a multicenter study. METHODS: The integrated approach incorporates 5 competencies: (1) image interpretation and trajectory planning, (2) dynamic navigation, (3) atraumatic access system (BrainPath, NICO Corp, Indianapolis, Indiana), (4) extracorporeal optics, and (5) automated atraumatic resection. Twelve neurosurgeons from 11 centers were trained to use this approach through a continuing medical education-accredited course. Demographical, clinical, and radiological data of patients treated over 2 years were analyzed retrospectively. RESULTS: Thirty-nine consecutive patients were identified. The median Glasgow Coma Scale (GCS) score at presentation was 10 (range, 5-15). The thalamus/basal ganglion regions were involved in 46% of the cases. The median hematoma volume and depth were 36 mL (interquartile range [IQR], 27-65 mL) and 1.4 cm (IQR, 0.3-2.9 cm), respectively. The median time from ictus to surgery was 24.5 hours (IQR, 16-66 hours). The degree of hematoma evacuation was ≥90%, 75% to 89%, and 50% to 74% in 72%, 23%, and 5.0% of the patients, respectively. The median GCS score at discharge was 14 (range, 8-15). The improvement in GCS score was statistically significant ( P < .001). Modified Rankin Scale data were available for 35 patients. Fifty-two percent of those patients had a modified Rankin Scale score of ≤2. There were no mortalities. CONCLUSION: The approach was safely performed in all patients with a relatively high rate of clot evacuation and functional independence.

Minimally Invasive Transsulcal Resection of Intraventricular and Periventricular Lesions Through a Tubular Retractor System: Multicentric Experience and Results.

BACKGROUND: Conventional approaches to deep-seated cerebral lesions range from biopsy to transcortical or transcallosal resection. Although the former does not reduce tumor burden, the latter are more invasive and associated with greater potential for irreparable injury to normal brain. Disconnection syndrome, hemiparesis, hemianesthesia, or aphasia is not uncommon after such surgery, especially when lesion is large. By contrast, the transsulcal parafascicular approach uses naturally existing corridors and a tubular retractor to minimize brain injury. METHODS: A retrospective review of patients undergoing minimally invasive transsulcal parafascicular resection of ventricular and periventricular lesions, across 5 independent centers, was conducted. RESULTS: Twenty patients with lesions located in the lateral ventricle (n = 9), the third ventricle (n = 6) and periventricular region (n = 4) are described in this report. Average age was 64 years (8 male/12 female). The average depth from cortical surface was 4.37 cm. A 13.5-mm-diameter tubular retractor (BrainPath [NICO Corporation, Indianapolis, Indiana, USA]) of differing lengths was used, aided by neuronavigation. Gross total resection was obtained in 17 patients. Pathologies included colloid cyst, subependymoma, glioma, meningioma, central neurocytoma, lymphoma, and metastasis. Three patients experienced transient morbidity: memory loss (2), hemiparesis (1). One patient died 3 months postoperatively as a result of unrelated pulmonary illness. Follow-up ranged from 6 to 27 months (average, 12 months). CONCLUSIONS: This technique is safe and effective for the treatment of intraventricular and periventricular lesions. Surgery-related morbidity is minimal and often transient. Lesions are satisfactorily resected and residuum occurs only when the neoplasm involves vital structures. The tubular retractor minimizes trauma to brain incident in the surgeon's path.

The extended supracerebellar transtentorial approach for resection of medial tentorial meningiomas.

BACKGROUND: The supracerebellar transtentorial (SCTT) approach has been established as a safe corridor to access the posteriomedial basal temporal region. Previous reports have demonstrated the efficacy of this route in the resection of intrinsic tumors and small arteriovenous malformations. Only one report in the English literature has described its use to resect a medial tentorial meningioma. METHODS: The authors discuss the relevant surgical anatomy of this approach and its advantages compared with more traditional routes, and illustrate its application to remove medial tentorial meningiomas through two operative cases with accompanying videos. RESULTS: In illustrative case one, the patient recovered from surgery with no deficits. All his preoperative symptoms had resolved at 3-month follow-up. At the 4-year follow-up, MRI did not demonstrate any growth of the residual tumor. In case two, gross total resection was achieved and the patient did not suffer any postoperative language or visual deficit. At 2-year follow-up, no tumor recurrence was present. CONCLUSION: The SCTT approach has a potential to safely access extra-axial lesions located around the medial tentorial incisura. As demonstrated in these two cases, the approach merits consideration in patients with tentorial meningiomas as an alternative to more widely utilized skull base approaches and subtemporal routes.

Effect of soy isoflavone supplementation on menopausal quality of life.

OBJECTIVE: The purpose of this study was to assess the effect of soy isoflavone supplementation on quality of life in postmenopausal women. METHODS: A multicenter, randomized, double-blind, placebo-controlled 24-month trial was conducted to assess the effect of 80 or 120 mg of daily aglycone hypocotyl soy isoflavone supplementation on quality of life in 403 postmenopausal women using a validated Menopause-Specific Quality of Life questionnaire. RESULTS: Menopause-Specific Quality of Life domain scores at 1 year and 2 years were similar to baseline. There were no differences in domain scores among treatment groups. CONCLUSIONS: Soy isoflavone supplementation offers no benefit to quality of life in postmenopausal women.

Dosimetry of a novel rotating gamma system for stereotactic radiosurgery.

This is the first report of the basic dosimetric properties of a new rotating gamma system: the RGS Vertex360™. Dosimetric properties were compared to those measured with traditional rotating gamma systems and with the Leksell Gamma Knife. The RGS Vertex360 is similar to the original rotating gamma system developed by OUR New Medical Technology Development Co., Ltd. (Shenzen, China), however, there are a few notable differences including the angular arrangement of the sources. Basic dosimetric properties of the RGS Vertex360 were measured including: absorbed dose rate, output factors, mechanical and radiation center accuracy and dose profiles. A significant discrepancy was observed for the 4 mm output measured from the RGS Vertex360 compared to those obtained from previous rotating gamma units: the 4 mm output from the RGS Vertex360 (0.807) was 32-38% higher than those measured from previous units. This is somewhat surprising considering the excellent agreement in 4 mm outputs from the RGS Vertex360, the corresponding outputs specified by the manufacturer of the original OUR unit and those measured for the Leksell Gamma Knife. The mechanical accuracy was similar to previous rotating gamma systems while the 50-90% penumbra was narrower. Dose profiles compared favorably with the Leksell Gamma Knife: in many instances the measured penumbra was narrower for the RGS Vertex360. Notwithstanding the 4 mm output factor, the dosimetric properties of the RGS Vertex360 compared favorably with those of previous rotating gamma systems. The 4 mm output discrepancy was attributed to suboptimal alignment of the primary and secondary collimators in previous studies. The dosimetric properties of the RGS Vertex360 and the Leksell Gamma Knife were similar and, taken together, the results suggest that the new rotating gamma system is well suited for stereotactic radiosurgery procedures.

Clinical outcomes of a 2-y soy isoflavone supplementation in menopausal women.

BACKGROUND: Soy isoflavones are naturally occurring phytochemicals with weak estrogenic cellular effects. Despite numerous clinical trials of short-term isoflavone supplementation, there is a paucity of data regarding longer-term outcomes and safety. OBJECTIVE: Our aim was to evaluate the clinical outcomes of soy hypocotyl isoflavone supplementation in healthy menopausal women as a secondary outcome of a trial on bone health. DESIGN: A multicenter, randomized, double-blind, placebo-controlled 24-mo trial was conducted to assess the effects of daily supplementation with 80 or 120 mg aglycone equivalent soy hypocotyl isoflavones plus calcium and vitamin D on the health of 403 postmenopausal women. At baseline and after 1 and 2 y, clinical blood chemistry values were measured and a well-woman examination was conducted, which included a mammogram and a Papanicolaou test. A cohort also underwent transvaginal ultrasound measurements to assess endometrial thickness and fibroids. RESULTS: The baseline characteristics of the groups were similar. After 2 y of daily isoflavone exposure, all clinical chemistry values remained within the normal range. The only variable that changed significantly was blood urea nitrogen, which increased significantly after 2 y (P = 0.048) but not after 1 y (P = 0.343) in the supplementation groups. Isoflavone supplementation did not affect blood lymphocyte or serum free thyroxine concentrations. No significant differences in endometrial thickness or fibroids were observed between the groups. Two serious adverse events were detected (one case of breast cancer and one case of estrogen receptor-negative endometrial cancer), which was less than the expected population rate for these cancers. CONCLUSION: Daily supplementation for 2 y with 80-120 mg soy hypocotyl isoflavones has minimal risk in healthy menopausal women. This trial was registered at clinicaltrials.gov as NCT00665860.

Complication avoidance in minimally invasive neurosurgery.

Although minimally invasive neurosurgery (MIN) holds the potential for reducing the approach-related impact on normal brain, bone, and soft tissues, which must be manipulated in more conventional transcranial microneurosurgery, the techniques necessary to perform minimally invasive, yet maximally effective neurosurgery place significant demands on the surgeon because in many ways the more limited exposure creates a number of unique ways these operations can go wrong. Safe and effective MIN requires the conscious institution of specific alterations to the surgeon's usual operative case flow, which are designed to make specific well-known mistakes impossible or at least very unlikely. Thus, it is important for the aspiring MIN surgeons to learn from the mistakes of their predecessors and to institute patterns of behavior that prevent a repetition of these mistakes. This article provides practical information regarding known pitfalls in intraventricular and transcranial neuroendoscopic surgeries and practical methods to reduce the incidence of these complications to the lowest rate possible.

Gamma Knife thalamotomy for treatment of essential tremor: long-term results.

OBJECT: The goal of this report was to describe the safety and effectiveness of nucleus ventralis intermedius (VIM) thalamotomy performed with the Leksell Gamma Knife (GK) for the treatment of essential tremor (ET). METHODS: One hundred seventy-two patients underwent a total of 214 VIM thalamotomy procedures with the Leksell GK between February 1994 and March 2007 for treatment of disabling ET. Eleven patients were lost to follow-up less than 1 year after the procedures, so that in this report the authors describe the results in 161 patients who underwent a total of 203 thalamotomies (119 unilateral and 42 bilateral). RESULTS: There were statistically significant decreases (p < 0.0001) in tremor scores for both writing and drawing. The mean postoperative follow-up duration for all patients was 44 +/- 33 months. Fifty-four patients have been followed for more than 60 months posttreatment. There were 14 patients who suffered neurological side effects that were temporary (6) or permanent (8), which accounted for 6.9% of the 203 treatments. All complications were related to lesions that grew larger than expected. CONCLUSIONS: A VIM thalamotomy with the Leksell GK offers a safe and effective alternative for surgical treatment of ET. It is particularly applicable to patients who are not ideal candidates for deep brain stimulation but can be offered to all patients who are considering surgical intervention for ET.

Distal revision of ventriculoperitoneal shunts using a peel-away sheath.

The authors describe a new technique for revision of an occluded distal ventriculoperitoneal shunt catheter that obviates the need for laparotomy or trocar insertion into the peritoneal cavity. The authors review their early experience with 34 patients suffering from a distal ventriculoperitoneal shunt failure and treated with this technique. There were no incidents of intraabdominal injury or wound complications. In 2 patients conversion to a minilaparotomy was required for safe placement of the shunt. Proper peritoneal placement was confirmed with abdominal radiographs in all cases. This technique has been safe and effective and may be considered an alternative to traditional laparotomy or laparoscopic methods.

Various doses of soy isoflavones do not modify mammographic density in postmenopausal women.

Soy isoflavones have functional similarity to human estrogens and may protect against breast cancer as a result of their antiestrogenic activity or increase risk as a result of their estrogen-like properties. We examined the relation between isoflavone supplementation and mammographic density, a strong marker for breast cancer risk, among postmenopausal women. The Osteoporosis Prevention Using Soy (OPUS) study, a multi-site, randomized, double-blinded, and placebo-controlled trial assigned 406 postmenopausal women to 80 or 120 mg/d of isoflavones each or a placebo for 2 y. Percent densities were assessed in digitized mammograms using a computer-assisted method. The mammogram reader did not know the treatment status and the time of mammograms. We applied mixed models to compare breast density by treatment while considering the repeated measures. The mammographic density analysis included 358 women, 88.2% of the OPUS participants; 303 had a complete set of 3 mammograms, 49 had 2, and 6 had only 1 mammogram. At baseline, the groups were similar in age, BMI, and percent density, but mean breast density differed by study site (P = 0.02). A model with all mammograms did not show a treatment effect on any mammographic measure, but the change over time was significant; breast density decreased by 1.6%/y across groups (P < 0.001). Stratification by age and BMI did not reveal any effects in subgroups. In this randomized 2-y trial, isoflavone supplements did not modify breast density in postmenopausal women. These findings offer reassurance that isoflavones do not act like hormone replacement medication on breast density.

Deep brain stimulation for the treatment of various chronic pain syndromes.

OBJECT: Electrical intracerebral stimulation (also referred to as deep brain stimulation [DBS]) is a tool for the treatment of chronic pain states that do not respond to less invasive or conservative treatment options. Careful patient selection, accurate target localization, and identification with intraoperative neurophysiological techniques and blinded test evaluation are the key requirements for success and good long-term results. The authors present their experience with DBS for the treatment of various chronic pain syndromes. METHODS: In this study 56 patients with different forms of neuropathic and mixed nociceptive/neuropathic pain syndromes were treated with DBS according to a rigorous protocol. The postoperative follow-up duration ranged from 1 to 8 years, with a mean of 3.5 years. Electrodes were implanted in the somatosensory thalamus and the periventricular gray region. Before implantation of the stimulation device, a double-blinded evaluation was carefully performed to test the effect of each electrode on its own as well as combined stimulation with different parameter settings. The best long-term results were attained in patients with chronic low-back and leg pain, for example, in so-called failed-back surgery syndrome. Patients with neuropathic pain of peripheral origin (such as complex regional pain syndrome Type II) also responded well to DBS. Disappointing results were documented in patients with central pain syndromes, such as pain due to spinal cord injury and poststroke pain. Possible reasons for the therapeutic failures are discussed; these include central reorganization and neuroplastic changes of the pain-transmitting pathways and pain modulation centers after brain and spinal cord lesions. CONCLUSIONS: The authors found that, in carefully selected patients with chronic pain syndromes, DBS can be helpful and can add to the quality of life.

Menopausal symptoms and treatment-related effects of estrogen and progestin in the Women's Health Initiative.

OBJECTIVE: To estimate the effects of estrogen plus progestin (E+P) therapy on menopausal symptoms, vaginal bleeding, gynecologic surgery rates, and treatment-related adverse effects in postmenopausal women. METHODS: Randomized, double-blind, placebo-controlled trial of 16,608 postmenopausal women, ages 50-79 (mean +/- standard deviation 63.3 +/- 7.1) years, with intact uterus, randomized to one tablet per day containing 0.625 mg conjugated equine estrogens plus 2.5 mg medroxyprogesterone acetate (n = 8,506) or placebo (n = 8,102), and followed for a mean of 5.6 years. Change in symptoms and treatment-related effects were analyzed at year 1 in all participants. Bleeding and gynecologic surgery rates were analyzed through study close-out. RESULTS: Baseline symptoms did not differ between the treatment groups. More women assigned to E+P than placebo reported relief of hot flushes (85.7% versus 57.7%, respectively; odds ratio 4.40; 95% confidence interval 3.40-5.71), night sweats (77.6% versus 57.4%; 2.58; 2.04-3.26), vaginal or genital dryness (74.1% versus 54.6%; 2.40; 1.90-3.02), joint pain or stiffness (47.1% versus 38.4%; 1.43; 1.24-1.64), and general aches or pains (49.3% versus 43.7%; 1.25; 1.08-1.44). Women asymptomatic at baseline who were assigned to E+P more often developed breast tenderness (9.3% versus 2.4%, respectively; 4.26; 3.59-5.04), vaginal or genital discharge (4.1% versus 1.0%; 4.47; 3.44-5.81), vaginal or genital irritation (4.2% versus 2.8%; 1.52; 1.27-1.81), and headaches (5.8% versus 4.7%; 1.26; 1.08-1.46) than women on placebo. Estrogen plus progestin treatment prevented the onset of new musculoskeletal symptoms. Vaginal bleeding was reported by 51% of women on E+P and 5% of women on placebo at 6 months; most bleeding was reported as spotting. Gynecologic surgeries (hysterectomy and dilation and curettage) were performed more frequently in women assigned to E+P (3.1% versus 2.5% for hysterectomy, hazard ratio = 1.23, P = .026; 5.4% versus 2.4% for dilation and curettage, hazard ratio = 2.23, P < .001). CONCLUSION: Estrogen plus progestin relieved some menopausal symptoms, such as vasomotor symptoms and vaginal or genital dryness, but contributed to treatment-related effects, such as bleeding, breast tenderness, and an increased likelihood of gynecologic surgery.

Resection of a non-communicating uterine horn with use of the harmonic scalpel.

BACKGROUND: Type IIA1b anomalies of the Mullerian system are rare. Traditionally, the method of treatment for such anomalies has been laparotomy. CASE: We discuss a case of this specific anomaly treated by resecting the non-communicating horn with the harmonic scalpel (Ethicon EndoSurgery, Cincinnati, Ohio) by first confirming a lack of communication with hysteroscopy, followed by chromotubation to demonstrate unilateral spill from the right side without leak from the area of dissection. CONCLUSION: Minimally invasive techniques are an excellent alternative to laparotomy for correction of problems related to Mullerian anomalies.

Effect of serum from chickens treated with clenbuterol on myosin accumulation, beta-adrenergic receptor population, and cyclic AMP synthesis in embryonic chicken skeletal muscle cell cultures.

Broiler chickens at 35 d of age were fed 1 ppm clenbuterol for 14 d. This level of dietary clenbuterol led to 5-7% increases in the weights of leg and breast muscle tissue. At the end of the 14-d period, serum was prepared from both control and clenbuterol-treated chickens, and was then employed as a component of cell culture media at a final concentration of 20% (v/v). Muscle cell cultures were prepared from both the leg and the breast muscle groups of 12-d chick embryos. Treatment groups included control chicken serum to which 10 nM, 50 nM, and 1 microM clenbuterol had been added, as well as cells grown in media containing 10% horse serum. Cultures were subjected to each treatment for 3 d, beginning on the seventh d in culture. Neither the percent fusion nor the number of nuclei in myotubes was significantly affected by any of the treatments. The quantity of myosin heavy chains (MHCs) was not increased by serum from clenbuterol-treated chickens in either breast or leg muscle cultures; however, the MHC quantity was 50-150% higher in cultures grown in control chicken serum to which 10 and 50 nM clenbuterol had also been added. The beta-adrenergic receptor (betaAR) population was 4000-7000 betaARs per cell in cultures grown in chicken serum, with leg muscle cultures having approximately 25-30% more receptors than breast muscle cultures. Receptor population was not significantly affected by the presence of clenbuterol or by the presence of serum from clenbuterol-treated chickens. In contrast, the betaAR population in leg and breast muscle cultures grown in the presence of 10% horse serum was 16,000-18,000 betaARs per cell. Basal concentration of cyclic adenosine 3':5'monophosphate (cAMP) was not significantly affected by the treatments. When cultures grown in chicken serum were stimulated for 10 min with 1 microM isoproterenol, limited increases of 12-20% in cAMP concentration above the basal levels were observed. However, when cultures grown in the presence of horse serum were stimulated with 1 microM isoproterenol, cAMP concentration was stimulated 5- to 9-fold above the basal levels. Thus, not only did cells grown in horse serum have a higher betaAR population, but also each receptor had a higher capacity for cAMP synthesis following isoproterenol stimulation. Finally, the hypothesis that clenbuterol exerts its action on muscle protein content by changes in cAMP concentration was tested. No correlation was apparent between basal cAMP concentration and MHC content.