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Biomedical subjects

Daniel I Rosenthal

Publications and source records attributed to Daniel I Rosenthal.

At least 19 recordsLinked to original sources
PubMed2007

Effects of atypical anxiolytic N-phenyl-2-[1-[3-(2-pyridinylethynyl)benzoyl]-4-piperidine]acetamide (JNJ-5234801) on alcohol intake in alcohol-preferring P rats.

BACKGROUND: N-Phenyl-2-[1-[3-(2-pyridinylethynyl)benzoyl]-4-piperidine]acetamide (JNJ-5234801) is a structurally novel atypical anxiolytic with an overall in vivo profile in animals suggestive of the potential to show anxiolytic efficacy in humans at doses that will not cause CNS-related side effects. Furthermore, unlike the benzodiazepines, JNJ-5234801 does not have an adverse interaction with ethanol even at doses 20 to 40 times the minimal effective dose in the rat elevated plus maze (MED=1.0 mg/kg, p.o.). METHODS: In the present study, JNJ-5234801 was evaluated for potential efficacy in reducing alcohol intake in alcohol-preferring rats. Alcohol-preferring P rats were allowed to drink water or alcohol (10%, v/v) in a 2-bottle choice procedure. Once stable baselines were established, the acute effects of JNJ-5234801 [(10-40 mg/kg, intraperitoneally (i.p.)] were assessed. In a separate study, chronic treatment with JNJ-5234801 (40 mg/kg once daily, i.p.) for 12 consecutive days was compared with naltrexone (20 mg/kg, twice daily, i.p.). RESULTS: There was a selective dose-dependent reduction in alcohol intake in the alcohol-preferring (P) rats after acute administration of JNJ-5234801 (10-40 mg/kg, i.p.). There were no significant effects on food or water intake. When administered subchronically, both JNJ-5234801 (40 mg/kg once daily, i.p.) and naltrexone (20 mg/kg, twice daily, i.p.) considerably reduced alcohol intake, but tolerance to the alcohol-suppressing effects appeared to occur sooner in the naltrexone-treated group. While both compounds slightly but significantly reduced food intake at the beginning, only JNJ-5234801 increased water intake and decreased alcohol preference. CONCLUSIONS: The novel atypical anxiolytic JNJ-5234801 has a favorable profile effects on alcohol intake and related measures compared with naltrexone, which is recommended for the treatment of alcoholism.

Acute Disease↗
PubMed2006

Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is a complex disease entity comprised of three distinct clinical syndromes that demonstrate indistinguishable histology. These syndromes are: eosinophilic granuloma, which is predominantly osseous or pulmonary; Hand-Schûller-Christian's disease, which involves multiple organ systems and, most typically, the skull base; and Letterer-Siwe's disease, the most severe disease manifestation, which typically involves the abdominal viscera. This article reviews our current understanding of Langerhans cell histiocytosis by discussing the history, histology, etiology, and treatment of the disease. It focuses on the radiographic findings and imaging modalities that are the most useful in disease diagnosis and management.

Histiocytosis, Langerhans-Cell↗
PubMed2006

Sacral chordomas: Impact of high-dose proton/photon-beam radiation therapy combined with or without surgery for primary versus recurrent tumor.

PURPOSE: To assess the efficacy of definitive treatment of sacral chordoma by high-dose proton/photon-beam radiation therapy alone or combined with surgery. METHODS AND MATERIALS: The records of 16 primary and 11 recurrent sacral chordoma patients treated from November 1982 to November 2002 by proton/photon radiation therapy alone (6 patients) or combined with surgery (21 patients) have been analyzed for local control, survival, and treatment-related morbidity. The outcome analysis is based on follow-up information as of 2005. RESULTS: Outcome results show a large difference in local failure rate between patients treated for primary and recurrent chordomas. Local control results by surgery and radiation were 12/14 vs. 1/7 for primary and recurrent lesions. For margin-positive patients, local control results were 10 of 11 and 0 of 5 in the primary and recurrent groups, respectively; the mean follow-up on these locally controlled patients was 8.8 years (4 at 10.3, 12.8, 17, and 21 years). Radiation alone was used in 6 patients, 4 of whom received > or =73.0 Gy (E); local control was observed in 3 of these 4 patients for 2.9, 4.9, and 7.6 years. CONCLUSION: These data indicate a high local control rate for surgical and radiation treatment of primary (12 of 14) as distinct from recurrent (1 of 7) sacral chordomas. Three of 4 chordomas treated by > or =73.0 Gy (E) of radiation alone had local control; 1 is at 91 months. This indicates that high-dose proton/photon therapy offers an effective treatment option.

Adult↗
PubMed2006

Diarylacetylene piperidinyl amides as novel anxiolytics.

N-Phenyl-2-[1-[3-(2-pyridinylethynyl)benzoyl]-4-piperidine]acetamide (9) and related piperidine acetamide derivatives have good oral activity in the elevated plus maze, an animal model predictive of clinical efficacy for the treatment of anxiety. Modest affinity was observed for the neurokinin NK-1 and 2 receptors, which are known to be involved in the regulation of mood and emotion.

Acetylene↗
PubMed2006

Radiofrequency treatment.

This article discusses radiofrequency energy as a treatment of musculoskeletal tumors,focusing on osteoid osteomas. The technique has also been applied to a number of different primary musculoskeletal tumors and is increasingly being used as a palliative method in the management of painful skeletal metastases. Radiofrequency treatment of musculoskeletal tumors can be of great clinical value. When the low-power, highly limited methods are applied to small tumors such as osteoid osteomas, the technique is effective and exceptionally safe. Creation of larger thermal lesions, however, can be accompanied by significant risks, and the risk-to-benefit ratio should be carefully considered before undertaking such a treatment.

Bone Neoplasms↗
PubMed2006

Use of an arterial tourniquet to achieve complete radiofrequency ablation of a renal metastasis.

Radiofrequency (RF) coagulation of skeletal metastases is usually performed for pain relief. However, patients with solitary skeletal metastasis may benefit from more aggressive attempts to achieve local control. The authors report a case in which an arterial tourniquet was used to enhance the effectiveness of RF treatment of a calcaneal renal cell metastasis, leading to long-lasting local control with preservation of ambulation.

Bone Neoplasms↗
PubMed2005

Intramyocellular lipid quantification: repeatability with 1H MR spectroscopy.

PURPOSE: To prospectively determine the repeatability and variability of tibialis anterior intramyocellular lipid (IMCL) quantifications performed by using 1.5-T hydrogen 1 (1H) magnetic resonance (MR) spectroscopy in healthy subjects. MATERIALS AND METHODS: Institutional review board approval and written informed consent were obtained for this Health Insurance Portability and Accountability Act-compliant study. The authors examined the anterior tibial muscles of 27 healthy subjects aged 19-48 years (12 men, 15 women; mean age, 25 years) by using single-voxel short-echo-time point-resolved 1H MR spectroscopy. During a first visit, the subjects underwent 1H MR spectroscopy before and after being repositioned in the magnet bore, with voxels carefully placed on the basis of osseous landmarks. Measurements were repeated after a mean interval of 12 days. All spectra were fitted by using Java-based MR user interface (jMRUI) and LCModel software, and lipid peaks were scaled to the unsuppressed water peak (at 4.7 ppm) and the total creatine peak (at approximately 3.0 ppm). A one-way random-effects variance components model was used to determine intraday and intervisit coefficients of variation (CVs). A power analysis was performed to determine the detectable percentage change in lipid measurements for two subject sample sizes. RESULTS: Measurements of the IMCL methylene protons peak at a resonance of 1.3 ppm scaled to the unsuppressed water peak (IMCL(W)) that were obtained by using jMRUI software yielded the lowest CVs overall (intraday and intervisit CVs, 13.4% and 14.4%, respectively). The random-effects variance components model revealed that nonbiologic factors (equipment and repositioning) accounted for 50% of the total variability in IMCL quantifications. Power analysis for a sample size of 20 subjects revealed that changes in IMCL(W) of greater than 15% could be confidently detected between 1H MR spectroscopic measurements obtained on different days. CONCLUSION: 1H MR spectroscopy is feasible for repeatable quantification of IMCL concentrations in longitudinal studies of muscle metabolism.

Adult↗
PubMed2005

Automated computer-assisted categorization of radiology reports.

OBJECTIVE: The objective of our study was to create and validate an automated computerized method for the categorization of narrative text radiograph reports. MATERIALS AND METHODS: Using commercially available software with embedded Boolean logic, we created a text search algorithm to categorize reports of radiography examinations into "fracture,"normal," and "neither normal nor fracture." The algorithm was refined and optimized through repeated testing on 512 consecutive ankle radiography reports from a single clinical imaging center. The final algorithm was applied on a different set of 750 consecutive radiography reports of the spine and extremities produced at three different clinical imaging sites and interpreted by 44 different radiologists. Expert reviewers assessed the accuracy of the final classification. The chi-square test or Fisher's exact test was performed to determine the reproducibility of results across different clinical imaging sites. RESULTS: The computerized classification was highly accurate for the classification of radiography reports into "normal" (specificity, 91.6%; sensitivity, 91.3%), "neither normal nor fracture"(sensitivity, 87.8%; specificity, 94.9%), and "fracture"(sensitivity, 94.1%; specificity, 98.1%) categories. This performance showed no significant difference across the three sites (p >0.05). CONCLUSION: Computerized categorization of narrative-text radiography reports is highly sensitive and specific and can be used to classify reports from different imaging sites generated by different radiologists. This method can be an extremely powerful tool in future cost-effectiveness studies, health care policy studies, operations assessments, and quality control.

Algorithms↗
PubMed2003

Osteoid osteoma: percutaneous treatment with radiofrequency energy.

PURPOSE: To report our experience with technical success, complications, and long-term clinical success of radiofrequency (RF) ablation of osteoid osteoma. MATERIALS AND METHODS: After needle biopsy, computed tomography (CT)-guided percutaneous RF ablation was performed with general or spinal anesthesia. With an RF electrode, the lesion was heated to 90 degrees C for 6 minutes. Patient age and sex, lesion size and location, biopsy results, and complications were recorded. Clinical success was assessed at a minimum of 2 years after the procedure. Significance of patient age and sex and lesion location and size as a predictor of biopsy result was tested by means of chi2 analysis. In addition, effects of patient age and sex, lesion location and size, and biopsy results on clinical success were tested with the Fisher exact test. RESULTS: During an 11-year period, 263 patients who were suspected of having osteoid osteoma underwent 271 ablation procedures. All procedures were technically successful. There were two anesthesia-related complications (aspiration, cardiac arrest) and two minor procedure-related complications (cellulitis, sympathetic dystrophy). Results at biopsy were positive in 73% (197 of 271 biopsies). Two-year follow-up data were available for 126 procedures. The other procedures had been performed more recently or the patients could not be contacted. There was complete relief of symptoms after 112 of the 126 procedures (89%). For procedures performed as the initial treatment, the success rate was 91% (107 of 117 procedures). Procedures for recurrent lesions had a significantly lower success rate (six of 10 procedures [60%], P <.001). Clinical outcome was not dependent on biopsy result, patient age or sex, or lesion size or location. CONCLUSION: CT-guided percutaneous RF ablation of osteoid osteoma is a safe and effective technique.

Adolescent↗
PubMed2003

Neoadjuvant chemotherapy and radiotherapy for large extremity soft-tissue sarcomas.

PURPOSE: Treatment of extremity soft-tissue sarcomas yields excellent local control, but distant failure is common with large, high-grade tumors. A regimen of preoperative chemotherapy consisting of mesna, adriamycin, ifosfamide, and dacarbazine (MAID) interdigitated with radiotherapy followed by resection and postoperative chemotherapy with or without radiotherapy was designed to improve treatment outcome. We report the mature outcome data on 48 treated patients and compare them with the data of an historical matched control patient population. METHODS AND MATERIALS: Adult patients with high-grade extremity soft-tissue sarcomas >or=8 cm were treated with three cycles of preoperative chemotherapy combined with 44 Gy of radiotherapy followed by surgery. Three cycles of postoperative MAID were planned. For patients with positive surgical margins, 16 Gy was delivered postoperatively. RESULTS: All 48 patients (M0) received the MAID protocol treatment, and their outcome was superior to that of the historical control patients. The 5-year actuarial local control, freedom from distant metastasis, disease-free survival, and overall survival rate was 92% and 86% (p = 0.1155), 75% and 44% (p = 0.0016), 70% and 42% (p = 0.0002), and 87% and 58% (p = 0.0003) for the MAID and control patient groups, respectively. Acute hematologic toxicity in the MAID group included febrile neutropenia in 12 patients (25%). Wound healing complications occurred in 14 (29%) of 48 MAID patients. One MAID patient developed late fatal myelodysplasia. CONCLUSION: After aggressive chemoradiation and surgery, these patients showed a significant reduction in distant metastases, with a highly significant gain in disease-free and overall survival compared with a historical control group. On the basis of this experience, the Radiation Therapy Oncology Group conducted a multi-institutional trial.

Adult↗
PubMed2003

"Beaded" osteoid osteoma: a possible transition between solitary and multicentric tumor.

An extremely rare example of an elongated (3 cm) osteoid osteoma is presented. The tumor demonstrated three focal enlargements connected by narrow areas, suggesting a "string of beads" in appearance. The elongated shape suggested the possibility that lesional tissue was stretched in a longitudinal fashion as a result of the rapid skeletal growth. The tumor closest to the growth plate was densely ossified, while the furthest lesion was almost completely lytic, suggesting that the tumor enlarged in a centripetal direction. This case is believed to illustrate a continuum from solitary to multicentric osteoid osteoma. The tumor was treated successfully with three separate percutaneous radiofrequency ablations during a single session.

Child↗
PubMed2003

2,3-Diaryl-5-anilino[1,2,4]thiadiazoles as melanocortin MC4 receptor agonists and their effects on feeding behavior in rats.

The melanocortin-4 receptor (MC4) modulates physiological functions such as feeding behavior, nerve regeneration, and drug addiction. Using a high throughput screen based on (125)I-NDP-MSH binding to the human MC4 receptor, we discovered 2,3-diaryl-5-anilino[1,2,4]thiadiazoles 3 as potent and selective MC4 receptor agonists. Through SAR development on the three attached aryl rings, we improved the binding affinity from 174 nM to 4.4 nM IC(50). When delivered intraperitoneally, compounds 3a, 3b, and 3c induced significant inhibition of food intake in a fasting-induced feeding model in rats. When delivered orally, these compounds lost activity, mainly due to rapid metabolism to inactive imidoylthiourea reduction products.

Animals↗
PubMed2003

Osteoid osteoma: elevation of cardiac and respiratory rates at biopsy needle entry into tumor in 10 patients.

PURPOSE: To evaluate changes in cardiac and respiratory rates in a consecutive series of patients who underwent percutaneous treatment for lesions presumed to be osteoid osteoma in whom general anesthesia was established. MATERIALS AND METHODS: Changes in cardiac and respiratory rates were evaluated after establishment of stable general anesthesia in 14 patients who underwent needle biopsy and radio-frequency treatment. Cardiac and respiratory rates were recorded at penetration of skin, muscle, periosteum, cortex, and tumor. Treatment was performed before the biopsy report was available. RESULTS: Biopsy results revealed osteoid osteoma in 10 patients, chondroblastoma in one, and a herniation pit in one. Results in the two remaining patients were nondiagnostic and were excluded. Puncture of skin, muscle, and periosteum caused no detectable change. However, in the 10 patients with biopsy-proved osteoid osteoma, puncture of the tumor caused the mean cardiac rate to increase an average of 26 beats per minute (40%) to 91 (range, 62-114; P <.001) and the mean respiratory rate to increase an average of 12 breaths per minute (50%) to a mean of 37 (range, 25-52; P <.001). These changes occurred within seconds of tumor puncture and were often the first indication to the surgeon that the tumor had been entered. In the two patients with other diagnoses at biopsy, no such change was apparent. CONCLUSION: Mean cardiac and respiratory rates increase significantly at needle puncture of osteoid osteoma.

Adolescent↗
PubMed2003

Effects of growth hormone secretion on body composition in patients with Crohn's disease.

Crohn's disease is a multisystem disorder characterized by chronic intestinal inflammation. Accumulation of mesenteric fat occurs in patients with Crohn's disease, although the mechanisms underlying site-specific changes in adipose deposition are unclear. To investigate whether there are alterations in site-specific adipose deposition in patients with Crohn's disease and to determine hormonal influences that may underlie such changes, we investigated body composition and serum hormone levels in 20 men with Crohn's disease (mean age, 45 +/- 2 yr) and 20 age-, gender-, and body mass index-matched normal controls (mean age, 43 +/- 3 yr). None of the Crohn's patients was receiving glucocorticoid therapy. Subjects underwent hourly GH sampling for 12 h beginning at 2000 h and fasting serum IGF-I and testosterone measurements. Body composition was assessed by quantitative computed tomography of the abdomen and bioelectrical impedance analysis. In the Crohn's disease and control subjects, mean serum GH levels were 1.07 +/- 0.2 and 1.7 +/- 0.2 ng/ml (P = 0.06), serum IGF-I levels were 162.7 +/- 10.5 and 194.8 +/- 15.7 ng/ml (P = 0.1), and serum testosterone levels were 489 +/- 33 and 514 +/- 38 ng/ml (P = NS), respectively. Percentage body fat was significantly higher in the Crohn's patients (21 +/- 0.8% vs. 17.7 +/- 0.9%, respectively; P = 0.013). Intraabdominal fat (IAF) was significantly higher in the Crohn's subjects vs. controls (115 +/- 11 vs. 69 +/- 7 cm(2), respectively; P = 0.001). The ratio of intraabdominal to total body fat was higher in the Crohn's subjects than in the controls (0.4 +/- 0.1 vs. 0.3 +/- 0.1, respectively; P = 0.025). Subcutaneous fat area was similar in the two groups. IAF was higher in Crohn's patients even when controlling for testosterone and mean serum GH. Mean serum GH contributed independently to the differences in IAF (P = 0.001). The ratio of IAF to total body fat remained higher in the Crohn's subjects when controlling for serum testosterone, but was no longer significant in a model that also included IGF-I and mean serum GH. GH levels contributed independently to the differences in the intraabdominal to total body fat ratio (P = 0.02). In the Crohn's patients, serum GH correlated negatively with intraabdominal and total body fat and the ratio of intraabdominal to total body fat. Crohn's disease is associated with an increase in central fat accumulation, with more IAF and a higher ratio of intraabdominal to total body fat compared with controls. Although serum GH levels were similar in the two groups, GH contributed significantly to the abdominal fat measurements. These data show that GH has an important role in modulating visceral fat distribution in patients with Crohn's disease.

Adipose Tissue↗
PubMed2003

Osteoid osteoma of the glenoid: minimally invasive treatment.

Osteoid osteoma is a benign neoplasm that is often associated with a delay in diagnosis and severe pain. When indicated, surgical extirpation can be quite difficult, depending on the anatomic site of the tumor. Recent advances in radiofrequency ablation have dramatically impacted the successful treatment of these lesions. In this paper, a case report with review of the literature is presented to update all orthopedic surgeons on the use of this technique-especially important since it may obviate the need for surgery for many patients.

Adult↗