p63 expression in assessment of bronchioloalveolar proliferations of the lung.

Discrimination of well-differentiated pulmonary adenocarcinoma from reactive bronchioloalveolar epithelium can be difficult on routine histology, especially with small biopsies. Ancillary studies to help in this distinction are desirable. p63, a p53-homologous nuclear protein, is a marker of reserve cells of the bronchus and terminal lobular unit. In this study, 33 cases of adenocarcinoma (20 open lung and 13 transbronchial/percutaneous biopsies) and 43 cases of benign lungs with fibrosis and metaplasia (22 open lung and 21 transbronchial/percutaneous biopsies) were studied for nuclear p63 expression by immunohistochemistry (Dako, Carpinteria, CA, USA). Five additional cases each of atypical adenomatous hyperplasia and adenosquamous carcinoma and three cases of squamous carcinoma (all open lung biopsies) were also stained. The diagnostic categories of benign lung conditions were usual interstitial pneumonia, parenchymal scar, cryptogenic organizing pneumonia and diffuse alveolar damage. In neoplastic cases, p63 positivity was calculated as percentage of all tumor cells examined. In areas of normal lung, p63 decorated the reserve cells of large and small airways and occasional cells of the distal lobular unit. In fibrotic reactive processes, an interrupted but distinct pattern of nuclear staining was present in all cases, with staining of basal cells of the airways as well as bronchiolar- and squamous-metaplastic epithelium (43/43, 100%). p63 immunoreactivity was less uniform in areas of acute lung injury within these cases. One adenocarcinoma and two cases of atypical adenomatous hyperplasia showed strong immunoreactivity (>80%), while three adenocarcinomas highlighted only rare tumor nuclei (<5% of tumor cells). Morphologic areas where p63 immunostaining was not helpful included the junction of normal lung and lepidic growth of adenocarcinoma, and retrograde spread of adenocarcinoma into small airways. Our results highlight the differential expression of p63 across various bronchioloalveolar lesions. Moreover, p63 may be helpful in distinguishing reactive from neoplastic glandular proliferations in the lung.     

EXAMINATION OF DEVELOPMENTAL NEUROTOXICITY BY THE USE OF TISSUE CULTURE MODEL SYSTEMS

1. The rotation-mediated three-dimensional reaggregate culture system is uniquely suited for studies on developmental neurotoxicity. In this system, it is possible to reconstruct central neuronal pathways and follow their development. 2. Exposure to drugs of abuse including methamphetamine and methylenedioxyamphetamine or the appetite suppressant, fenfluramine, reduces monoamines in the cultures in a dose-dependent manner and interrupts normal monoaminergic development. 3. While the monoaminergic neurones may attain normal rates of development following drug removal, the affected neurones are not capable of overcoming the drug-induced insults and a deficiency in monoamines persists throughout development. 4. In addition, the production of immortalized monoclonal hybrid cells obtained by fusion of fetal mesencephalic neurones with a neuroblastoma has yielded cell lines expressing a dopaminergic phenotype. 5. Such cells have been useful in establishing the relationship of neurotoxicity to cell lineage and can serve as models for the study of the cellular and molecular mechanisms of neurotoxicity.     

Distribution of retroperitoneal metastases after chemotherapy in patients with nonseminomatous germ cell tumors.

For patients with advanced nonseminomatous germ cell tumors a retroperitoneal lymph node dissection is routinely performed following chemotherapy if the serum tumor markers have returned to normal. Bilateral retroperitoneal lymph node dissection has been recommended because metastatic deposits may be widespread. The aim of this study was to describe the distribution of retroperitoneal metastases following chemotherapy in patients with nonseminomatous germ cell tumor and determine if the extent of the retroperitoneal lymph node dissection can be modified. We studied 113 patients who had initially bulky retroperitoneal disease and underwent retroperitoneal lymph node dissection following chemotherapy. For the purposes of this study teratoma and malignant germ cell tumor are referred to as tumor. The most common location of tumor was the para-aortic area (91%) in patients with a left primary tumor and the interaortocaval area (78%) in those with a right tumor. Tumor was located outside the boundaries of a modified retroperitoneal lymph node dissection in 14 of the 60 patients with residual disease but the tumor was present within a palpable mass in 6 of these 14 patients. If the residual mass was removed and a modified retroperitoneal lymph node dissection was performed only 9 of the 113 patients (8%) would have tumor left in the retroperitoneum. For a select group of patients with advanced nonseminomatous germ cell tumor treated with chemotherapy, resection of the residual mass combined with modified retroperitoneal lymph node dissection is appropriate.     

Ossification of the posterior longitudinal ligament: a report of nine cases in non-Oriental patients

Ossification of the posterior longitudinal ligament (OPLL) is a progressive disorder of the spine which may result in spinal cord compression and myelopathy. While prevalent among Japanese, its occurrence in non-Orientals has been infrequently reported. Nine patients with OPLL have been diagnosed and followed at the Emory Clinic Spine Center over a 5-year period. All of the patients had been misdiagnosed before presentation. Five of the nine had undergone a total of eight ineffective operations. Failure to distinguish OPLL from other more common causes of myelopathy can result in delayed or inappropriate treatment. Illustrative cases and radiographic studies are presented.     

Long-term results of dietary fenbendazole to eradicate Syphacia muris from rat colonies.

The pinworm Syphacia muris was eradicated from rats after treatment with fenbendazole-medicated chow (150 ppm) and without environmental decontamination for > 54 months. However, this regimen was successful only when the treatment was delivered and efficacy monitoring was done by personnel of the institutional animal resources program. The same pinworm elimination program failed 7 to 24 months after the cessation of treatment in a satellite colony in which animal care, including provision of medicated diet and sample collection for efficacy monitoring, was provided by research personnel. A failure to uniformly deliver adequate therapeutic doses or reinoculation of rats with pinworm eggs from the contaminated environment could not be excluded as causes of the failure. However, there were risk factors, and animal care practices unique to the satellite colony that may have facilitated the re-emergence of pinworms. These risk factors included hand-washing of cages, storage of contact bedding in areas that were not vermin-proof, and animal care provided by personnel having contact with rodents of pet-store origin.     

Comparison of risk stratification with pharmacologic and exercise stress myocardial perfusion imaging: A meta-analysis

BACKGROUND: Although pharmacologic stress myocardial perfusion imaging (MPI) and exercise stress MPI have comparable diagnostic accuracy, their comparative value for risk stratification of patients with known or suspected coronary disease is not known. METHODS AND RESULTS: The data of 14,918 patients were combined from 24 studies evaluating prognosis in patients undergoing either pharmacologic stress or exercise stress MPI. Studies were included if a 2 x 2 table for hard cardiac events (cardiac death and myocardial infarction [MI]) could be constructed from the data available. Excluded were studies performed for post-MI, post-revascularization, or preoperative risk stratification. A weighted t test was used to compare the cardiac events, and a random effects model was used to calculate summary odds ratios. Summary odds ratios for hard cardiac events were similar for pharmacologic stress and exercise stress MPI. Summary receiver operating characteristic curves also showed no difference in discriminatory power between the stressors. The cardiac event rates were significantly higher with normal and abnormal test results with pharmacologic stress MPI than with exercise stress MPI (1.78% vs 0.65% [P < .001] for normal results and 9.98% vs 4.3% [P < .001] for abnormal results). Subgroup analysis revealed that both cardiac death and nonfatal MI were significantly higher with pharmacologic stress MPI. Patients undergoing pharmacologic stress MPI had a significantly higher prevalence of poor prognostic factors, and meta-regression revealed that exercise capacity was the single most important predictor of cardiac events. CONCLUSIONS: This meta-analysis shows that exercise stress MPI and pharmacologic stress MPI are comparable in their ability to risk-stratify patients. However, patients undergoing pharmacologic stress studies are at a higher risk for subsequent cardiac events. This is true even for those with normal perfusion imaging results.     

Plasma Concentrations of Mycophenolic Acid Acyl Glucuronide Are Not Associated with Diarrhea in Renal Transplant Recipients

The aim of this study was to determine whether plasma concentrations of the acyl (AcMPAG) and phenolic (MPAG) glucuronide metabolites of mycophenolic acid (MPA) were related to diarrhoea in renal transplant patients on mycophenolate mofetil (MMF) with cyclosporine (CsA) or tacrolimus (TCL). Blood samples (0, 30, 120 min) were taken at days 3, 10, week 4, months 3, 6 and 12 for determination of MPA, MPAG and AcMPAG. MPA-AUC was estimated using validated algorithms. Two hour AUCs were calculated for MPAG and AcMPAG. Immunosuppressive therapy consisted of CsA/MMF (n= 110) and of TCL/MMF (n= 180). In 70/290 (24%) patients 86 episodes of diarrhoea were recorded during 12 months. Significantly more patients on TCL (31.1%) suffered from diarrhea compared to CsA (12.7%). MMF dose, MPA-AUC and the 2 h AUCs of MPAG and AcMPAG did not differ between patients with and without diarrhoea. Plasma AcMPAG and MPAG concentrations were substantially higher in patients on CsA compared with TCL, while MPA-AUC was lower in the former group. These data support the concept that CsA inhibits the biliary excretion of MPAG and AcMPAG, thereby potentially reducing the risk of intestinal injury through enterohepatic recycling of MPA and its metabolites.