Interactions between cancer cells and immune cells drive transitions to mesenchymal-like states in glioblastoma

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Adjunctive therapy with bromocriptine in Parkinson's disease

Patients with moderately severe Parkinson's disease complicated by the adverse effects of chronic levodopa use benefited from the addition of bromocriptine (Parlodel; Sandoz) in doses up to 26 mg daily, which allowed an approximate 30% reduction of levodopa dose. This resulted in a significant decrease in the amount of levodopa side-effects while maintaining or improving the original parkinsonian clinical stage. Increased effectiveness in these patients was not associated with increased dosage beyond 25-30 mg daily. When the doses of bromocriptine were increased slowly, the adverse reactions were minor and usually transient.     

Regional expression of c-fos and heat shock protein-70 mRNA following hypoxia-ischemia in immature rat brain.

Cerebral ischemia induces the expression of a number of proteins that may have an important influence on cellular injury. The purpose of this study was to compare the regional effects of hypoxia-ischemia on the expression of the proto-oncogene, c-fos, and the heat shock protein-70 (HSP-70) gene in developing brain. Unilateral hypoxia-ischemia was produced in the brain of immature rats (7, 15, and 23 days after birth) using a combination of carotid artery ligation and systemic hypoxia (8% O2). After recovery for 2 and 24 h, the regional expression of c-fos and HSP-70 mRNA was determined using in situ hybridization. Littermates were permitted to recover for 1 week for assessment of histologic injury. Hypoxia-ischemia increased the expression of both c-fos and HSP-70 mRNA, but the topography of expression varied with the age of the animal as well as the mRNA species. In the 7-day-old group, expression of c-fos at 2 h increased in multiple regions of the ipsilateral hemisphere in nearly one-half of the animals, while HSP-70 mRNA was not expressed until 24 h and, then, predominantly in the hippocampus. In 15- and 23-day-old rats, expression of c-fos was increased at 2 h in the entorhinal cortex and in the dendritic field of the upper blade of the hippocampal dentate gyrus, while HSP-70 mRNA was prominently expressed in neocortex and the cell layers of the hippocampus. Interestingly, the strong expression of HSP-70 mRNA in dentate granule cells did not occur in the innermost layer of cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

Unusual metastases from a malignant melanoma. A case report.

An unusual case of malignant melanoma metastatic to the lung and to the ovaries occurred 9 and 11 years, respectively, after the initial, extragenital diagnosis. The primary lesion invaded to Clark's level IV with a thickness of greater than 4 mm, normally grave prognostic indicators. A metastatic lung nodule seen radiographically remained unchanged for two years before discovery of the intraperitoneal disease. The case illustrates the clinical variability and unpredictable biologic behavior of malignant melanoma.     

Incidental lymphocytic prostatitis. Selective involvement with nonmalignant glands.

We documented the presence of lymphocytic prostatitis in all prostate specimens received over a 4-month period. Lymphocytic prostatitis was present in 44% of biopsy specimens (n = 77), 95% of transurethral prostatic resection specimens (n = 20), and 100% of total prostatectomy specimens (n = 9). The patchiness of the prostatitis within the prostate in part explains the lower prevalence in the biopsy specimens, which sample a much smaller portion of the gland compared with the other procedures. Lymphocytic prostatitis was seen in prostates both with and without adenocarcinoma. However, in specimens containing carcinoma, the lymphocytic aggregates rarely involved malignant glands. Instead, the aggregates were either stromal or involved nonmalignant glands either adjacent to or away from the tumor, including glands with hyperplasia, atrophy, and prostatic intraepithelial neoplasia. Even when malignant and nonmalignant glands were in close proximity, there was a sharp demarcation with respect to lymphocytic inflammation. Immunohistochemical staining with B-cell and T-cell markers disclosed that the vast majority are T lymphocytes. The localization of lymphoid aggregates to nonmalignant (including prostatic intraepithelial neoplasia) glands but not frankly neoplastic glands, suggests a selective escape of immune detection by neoplastic glands.     

Correlation of radiographic and endoscopic evaluation of gastrojejunal anastomosis after Roux-en-Y gastric bypass.

BACKGROUND: Anastomotic stenosis presents as one of the most common late complications in the postoperative period after bariatric surgery. It is often diagnosed by upper gastrointestinal series (UGIS) and/or upper endoscopy (UE). The aim of this study was to determine whether a correlation exists between the Gastrografin UGIS and UE findings in the determination of gastrojejunal anastomotic strictures after Roux-en-Y gastric bypass (RYGB). METHODS: Between July 2001 and October 2003, all medical records of patients who underwent RYGB at our institution were retrospectively reviewed. The medical records of patients who underwent UE because of symptoms suggestive of gastric outlet obstruction and those of patients who were initially evaluated by Gastrografin UGIS before UE were evaluated further. RESULTS: Of 535 morbidly obese patients who underwent RYGB, 52 (9.7%) had UE and were included in this study. The mean number of UEs performed per patient was 2.67. Of these 52 patients, 30 underwent Gastrografin UGIS before UE. The mean diameter of the anastomosis on the first UE was 5.97 mm and on Gastrografin UGIS was 6.83 mm. A good correlation was found between the Gastrografin UGIS and UE findings using Pearson's correlation coefficient (0.44, P = .02) and single linear regression analysis using the endoscopic diameter as the outcome and radiographic findings as the predictor (beta = 0.27, P = .025, 95% confidence interval 0.30-0.49). CONCLUSION: In our study, the Gastrografin UGIS findings correlated positively with the endoscopic gastrojejunal anastomosis findings in patients with anastomotic stricture who had undergone RYGB.     

Functional MRI Studies of Animal Models in Epilepsy

Summary:  Functional magnetic resonance imaging (fMRI) has become a widely used imaging modality in the past decade in both human studies and animal models. Epilepsy presents unique challenges for neuroimaging due to subject movement during seizures, and the need to correlate the timing of often unpredictable seizure events with fMRI data acquisition. These challenges can readily be overcome in animal models of epilepsy. Animal models also provide an opportunity to investigate the fundamental relationships between fMRI signals and brain electrical activity through invasive studies not possible in humans. fMRI studies in animal models of epilepsy can enable us to correctly interpret fMRI signal increases and decreases in human studies, ultimately elucidating specific networks that will be targeted for improved treatment of epilepsy.     

Physicians' information needs: analysis of questions posed during clinical teaching

OBJECTIVE: To describe information requests expressed during clinical teaching. SETTING: Residents' work rounds, attending rounds, morning report, and interns' clinic in a university-based general medicine service. SUBJECTS: Attending physicians, medical house staff, and medical students in a general medicine training program. METHODS: An anthropologist observed communication among study subjects and recorded in field notes expressions of a need for information. We developed a coding scheme for describing information requests and applied the coding scheme to the data recorded. Based on assigned codes, we created a subset of strictly clinical requests. MEASUREMENTS: Five hundred nineteen information requests recorded during 17 hours of observed clinical activity were selected for detailed analysis. These requests related to the care of approximately 90 patients by 24 physicians and medical students. Sixty-five requests were excluded because they were not strictly clinical, leaving a subset of 454 clinical questions for analysis. MAIN RESULTS: On average, five clinical questions were raised for each patient discussed. Three hundred thirty-seven requests (74%) concerned patient care. Of these 337 questions, 175 (52%) requested a fact that could have been found in a medical record. Seventy-seven (23%) of these questions, motivated by the needs of patient care, were potentially answerable by a library, a textbook, a journal, or MEDLINE. Eighty-eight (26%) of the questions asked for patient care required synthesis of patient information and medical knowledge. CONCLUSIONS: Clinicians in the study settings requested information frequently. Many of these information needs required the synthesis of patient information and medical knowledge and thus were potentially difficult to satisfy. A typology is proposed that characterizes information needs as consciously recognized, unrecognized, and currently satisfied.     

Use of Vicryl mesh to support the esophageal wall after circular myotomy (Livaditis procedure) in long-gap esophageal atresia — an experimental study

Circular esophageal myotomy (CEM) is currently a well-accepted technique for elongation of the upper esophageal pouch in cases of long-gap esophageal atresia (EA). Esophageal pseudodiverticulum is a frequent and perhaps underreported sequela of this technique, characterized by ballooning or outpouching of the esophageal mucosa in the myotomized area. The present study was designed to seek a supplement for the CEM technique in order to avoid possible pseudodiverticulum formation in the myotomized area. We created an animal model to simulate the anatomic conditions present after primary repair of EA facilitated by CEM. Three groups of dogs underwent either cervical (1 group) or thoracic (2 groups) esophageal myectomy. In the cervical and first thoracic groups, the denuded mucosa was left without any support. In the second thoracic group, the denuded mucosal area was wrapped with polyglactin 910 (Vicryl) mesh. In all three groups the esophagus was narrowed by a Marlex mesh ring 3 cm distal to the myectomized zone, simulating a condition resulting from anastomotic narrowing. The dogs underwent barium swallows under fluoroscopy at different postoperative periods and were killed 4 or 6 months after surgery. The esophagi were removed for gross and radiologic investigation under maximal insufflation as well as for histologic assessment. The proposed canine model proved to be useful for study of the myectomized esophagus, mimicking the anatomy and conditions after CEM in long-gap EA repair. Wrapping the denuded mucosa with Vicryl mesh fortified the weakened esophageal wall, thus diminishing the likelihood of future pseudodiverticulum development. In light of the simplicity of the technique and the absence of any evident risk or complications, we recommend that the use of Vicryl mesh wrap be considered during CEM to reinforce the esophageal wall.Supported by the Slezak Fund for Experimental Surgery (Grant #01370791)