Subconjunctival gentamicin induction of extraocular toxic muscle myopathy.

Subconjunctival injection of commercially available gentamicin, delivered in one of several protocols, caused an acute toxic reaction myopathy of the extraocular muscles. The response began as a small focal infiltrate of polymorphonuclear leukocytes, and as the lesion progressed it assumed a mononuclear cell predominance accompanied by muscle fiber degeneration. The injection of individual components of the commercial preparation (gentamicin, methylparaben, ethylenediaminetetraacetic acid (EDTA) and sodium bisulfite), each at the same concentration as in the parent solution, gave no response except for gentamicin alone. Gentamicin caused acute toxic myopathy when injected away from the muscles and when given as an isotonic solution in saline compared to the hypotonic commercial solution. Solutions at acidic pH not containing gentamicin did not initiate myopathy. Several factors that have been inferred as participating in the toxic response to gentamicin have been eliminated. Gentamicin alone is responsible for the induction of the extraocular muscle myopathy.

Differential expression of c-myc and H-ras oncogenes in Barrett's epithelium. A study using colorimetric in situ hybridization.

To determine the role of c-myc and H-ras in progressive, dysplastic Barrett's mucosa (BM), and the usefulness of these oncogenes as markers for dysplastic lesions at high risk for malignant transformation, sequential formaldehyde solution-fixed, paraffin-embedded biopsy specimens that were obtained from 12 patients with BM were evaluated by in situ hybridization with the use of biotinylated complimentary DNA probes. Nine of the patients were taken from a previous prospective study. Four of these nine patients had dysplasia, and adenocarcinoma had developed in two of them; five had nondysplastic BM only. Two additional patients had adenocarcinoma, but their initial biopsy specimens had revealed dysplasia. One additional patient had intermediate-grade dysplasia. The intensity of oncogene expression was quantified by computerized color-image analysis. Enhanced c-myc expression of approximately equal intensity was consistently observed in all grades of dysplasia and carcinoma. H-ras was also consistently expressed in higher grades of dysplasia and carcinoma but not in low-grade dysplasia. Neither c-myc nor H-ras expression was detected in nondysplastic BM. The expression of H-ras in dysplastic BM appears to be a helpful marker for identifying which dysplastic lesions will progress to carcinoma.

Chlamydia trachomatis in chronic abacterial prostatitis: demonstration by colorimetric in situ hybridization.

Twenty-three transurethral resected prostate specimens with histologic evidence of chronic abacterial prostatitis were evaluated by colorimetric in situ hybridization for evidence of Chlamydia trachomatis. Intracellular chlamydia bodies were detected in seven of 23 cases (30.4%). In five of seven positive cases, chlamydia inclusion bodies were present within both epithelial cells and intraluminal histiocytes. In two of seven positive cases, extracellular chlamydia bodies were identified in conjunction with intraepithelial inclusions. In only one case were extraductal, extraacinar, intrahistiocytic inclusion bodies observed. Our study confirms previous reports implicating C trachomatis as an etiologic agent in chronic abacterial prostatitis, and underscores the applicability of DNA probes for the detection and identification of C trachomatis in routinely fixed, paraffin-embedded tissues.

Enhanced expression of c-myc and H-ras oncogenes in Letterer-Siwe disease. A sequential study using colorimetric in situ hybridization.

Tissues from two patients with disseminated histiocytosis X (Letterer-Siwe disease) in which histiocytosis X cells exhibited histologic and cytologic features of malignancy were evaluated by in situ hybridization with the use of biotinylated nucleic acid probes to c-myc and H-ras oncogenes. Enhanced expression of these oncogenes was observed in mononucleated and multinucleated cells of histiocytosis X in the terminal proliferative phase but not in the early quiescent phase of Letterer-Siwe disease in both patients. Our findings indicate that deregulation of c-myc and H-ras in histiocytosis X are late events that likely confer a selective growth advantage to histiocytosis X cells.

Fatty change in the human temporomandibular joint disc. Light and electron microscopy study.

Joint pain has been associated with fatty infiltration of the knee articulation. The purpose of this study is to report on the histopathological findings, especially fatty changes, that are seen in surgical specimens from the temporomandibular joints (TMJ) of patients that had persistent pain after non-surgical therapy. Forty plicated TMJ retrodiscal samples from 25 patients were used in this study. The patients were previously treated with splints for variable periods but not less than 2 months. The specimens were obtained by 2 surgeons using standard TMJ plication techniques. Control disc specimens were obtained from normal appearing cadaveric TM joints. Samples were immediately immersed in glutaraldehyde and processed for light and electron microscopic examination. The specimens were composed mainly of moderately dense tissue with cells that appeared fibroblastic and intermittent chondrocytic type cells. Fatty change, exclusively in association with the perivascular areas, was observed in 27 of 40 specimens. Electron microscopy showed fibroblasts, as well as large fat inclusions adjacent to elastin macroglobules. Fatty infiltration of the TMJ has been interpreted as a degenerative change. It is postulated that kinins and prostaglandins generated in the fat pads can pass freely in tissue fluid to adjacent, highly innervated structures thus leading to joint pain. It is further postulated that the finding of associated elastin with fatty deposition is similar to the atherosclerotic changes encountered in large blood vessels and the aorta.

Malignant fibrous histiocytoma and malignant melanoma: the role of immunohistochemistry and electron microscopy in the differential diagnosis.

Malignant fibrous histiocytoma (MFH) and malignant melanoma (MM) occur together often in the differential diagnosis of poorly differentiated neoplasms. They differ, however, in their biologic behavior and recommended treatment. Investigators have therefore explored a variety of special techniques, including electron microscopy (EM) and immunoperoxidase (IP), to classify these tumors accurately and to separate them from each other. To determine the usefulness of IP and EM in the classification of these tumors, we applied a Fontana-Masson stain and IP probes for vimentin, alpha-1-antitrypsin (alpha-1-A), human melanoma black (HMB)-45, and S-100 protein to twelve MMs and nine MFHs, all of which had available EM studies. Three of twelve MMs were amelanotic. All tumors contained vimentin. Eight of twelve MMs and six of nine MFHs contained alpha-1-A. Ten of twelve MMs and no MFHs contained HMB-45. Eleven of twelve MMs and, surprisingly, two of nine tumors classified by light and EM as MFHs contained S-100 protein. When problems arose with either IP negativity or potentially misleading cross-reactivity, careful EM study allowed definitive classification.