Clindamycin phosphate 1% gel in acne vulgaris.

A 12-week study compared Clindagel, a unique water-based gel formulation of clindamycin phosphate 1%, administered once daily, and Cleocin T, a slightly different gel formulation indicated for twice-daily use, in the treatment of acne vulgaris. Clindagel was safe and effective and equivalent to Cleocin T gel, albeit with a better tolerability profile. Clindagel is a viable alternative to Cleocin T gel.

Diffuse colonic mantle cell lymphoma in a patient with presumed ulcerative colitis: detection of a precursor monoclonal lymphoid population using polymerase chain reaction and immunohistochemistry.

Primary lymphoma of the colon, a rare and typically late complication of ulcerative colitis, exhibits high-grade morphology and behavior when it occurs. Recently, several reports of colonic lymphoma masquerading as ulcerative colitis have been described. These previous reports described inflammatory mucosal changes typical of ulcerative colitis as being present in superficial biopsies, leading to the initial diagnosis of ulcerative colitis; however, further workup resulted in a diagnosis of primary colonic lymphoma within several months in these cases, and all symptoms and mucosal changes resolved after treatment of the lymphoma. Herein we report a case of mantle cell lymphoma arising in the colon and rectum in a 71-year-old woman with a 4-year history of ulcerative colitis. Immunoglobulin heavy-chain gene rearrangements were detected using the polymerase chain reaction procedure in fixed tissue in the lymphoma as well as in a prior resection specimen that histologically appeared to show only changes of severe ulcerative colitis. This finding suggests that an indolent lymphoid proliferation may have been the underlying disease in this patient and raises questions about the role of colonic lymphoma in causing mucosal injury.

Detection of low-level tumor cells in allergic contact dermatitis induced by mechlorethamine in patients with mycosis fungoides.

Two patients with histologically proven mycosis fungoides, a malignancy of phenotypically mature T cells, received a topical challenge with mechlorethamine to areas of clinically uninvolved skin to exclude possible hypersensitivity reactions to this chemotherapeutic agent. In both patients, allergic contact dermatitis (ACD) developed at the sites of the application and resolved completely after withdrawal of mechlorethamine. The lesions were biopsied and analyzed for the presence of clonal T-cell receptor (TCR)-gamma gene rearrangements using two polymerase chain reaction (PCR)-based assays involving denaturing gradient gel electrophoresis (PCR/DGGE) and ribonuclease protection analysis (PCR/RPA). The former method has a clonal detection threshold of 10(-3)-10(-2), while the latter has a sensitivity of 10(-5). In both cases, the ACD lesions were polyclonal by PCR/DGGE. In contrast, PCR/RPA detected tumor-specific TCR-gamma gene rearrangements in these same lesions. This indicates that the ACD lesions contained tumor cells at a density within the 10(-5)-10(-2) range. Analysis of peripheral blood mononuclear cells from both patients failed to detect the malignant clone and showed the same result as blood from four normal individuals. The normal skin from one skin patient also lacked detectable TCR-gamma gene rearrangements. These results indicate that mycosis fungoides tumor are present within ACD lesions induced in mycosis fungoides patients and that this phenomenon does not appear to be due to the ubiquitous presence of detectable levels of these tumor cells in the blood or skin. These findings might be explained by nonspecific recruitment of malignant T cells to sites of local inflammation mediated by non-neoplastic antigen-specific T cells. Alternatively, they might be due to the local proliferation of very rare tumor cells in apparently normal skin in response to cytokines generated during the ACD reaction. In either case, the present study offers evidence that the malignant cells in myosis fungoides retain at least some capability of responding in vivo to physiologic stimuli.

Transformation of mycosis fungoides: T-cell receptor beta gene analysis demonstrates a common clonal origin for plaque-type mycosis fungoides and CD30+ large-cell lymphoma.

It is well recognized that patients with classical mycosis fungoides (MF) may develop a large-cell lymphoma (LCL), a phenomenon known as "transformation." An unresolved issue regarding the transformation of MF is whether MF and LCL represent two separate lymphomas or whether they are derived from the same T-cell clone. We report the clinicopathologic, immunophenotypic, and immunogenotypic analysis of MF and LCL in a white male. He developed a rash at age 51 that was diagnosed at age 56 as clinical stage IA patch/plaque MF. After topical nitrogen mustard and total skin electron beam therapy for progressive generalized CD3+CD4+ patch/plaque lesions, he developed nodules of Ki-1+ (CD30+) T-LCL at age 72. Southern blot analysis of DNA digested with Bg/II or BamHI and probed with a T-cell receptor (TCR)-beta gene J beta 1/J beta 2 probe showed a single, identical rearranged band in both the MF and LCL skin lesions that had been obtained 4 years apart. V beta gene family--specific gene amplification assays demonstrated dominant V beta 6 PCR products in both types of lesions. These PCR products and lesional cDNA exhibited a monoclonal pattern when amplified with consensus TCR-beta gene VDJ joint primers and electrophoresed under conditions that allowed the resolution of small differences in size. Furthermore, sequence analysis of the V beta 6 PCR products amplified from both the MF and LCL lesions showed an identical nucleotide sequence involving V beta 6.4, D beta 1.1, J beta 1.2, and C beta 1. These findings indicate that both the MF and the LCL in this patient arose from the same T-cell clone and that these diseases developed at a stage in the clone's differentiation subsequent to rearrangement of the TCR-beta gene.

T-cell lymphoma and the virus-associated hemophagocytic syndrome.

A 20-month-old girl had a disorder that by both clinical and histologic criteria resembled the virus-associated hemophagocytic syndrome in the setting of Epstein-Barr virus infection. Subsequent investigation revealed histologic evidence of disseminated T-cell lymphoma. DNA hybridization studies displayed a monoclonal T-cell receptor beta chain rearrangement, in the absence of clonal immunoglobulin gene rearrangement, and a single band in the analysis for the fused termini of the Epstein-Barr virus genome. These results suggest the presence of a monoclonal population of T lymphocytes infected with Epstein-Barr virus. The diagnosis of lymphoma was confirmed at autopsy. The authors discuss the association of Epstein-Barr virus infection with the development of T-cell lymphoma and propose that the previous reports of virus-associated hemophagocytic syndrome include cases of unrecognized T-cell lymphoma.

Allylamine and acrolein toxicity in perfused rat hearts.

We assessed the in vitro toxicity of the cardiovascular toxicant allylamine, and its presumed in vivo metabolite, acrolein. In dose-response experiments, rat hearts perfused with allylamine (10-30 mM) or acrolein (0.01-3.0 mM) for 2 hr were assessed by standard histopathology and assay of creatine kinase (CK) in effluent. Allylamine-perfused hearts showed no grossly apparent functional abnormality except at 30 mM, but acrolein-perfused hearts beat irregularly and stopped rapidly (within 15 min at 0.01-0.3 mM, and by 5 min at 3.0 mM). Extensive contraction band necrosis and an apparently dose-dependent loss of CK were evident in allylamine-perfused hearts, whereas acrolein perfusion resulted in no morphologic lesions or CK loss. Additional experiments, however, suggest that acrolein perfusion results in denaturation of CK, making it undetectable in effluent. In hemodynamic preparations of rat hearts perfused with 10 mM allylamine, contraction band necrosis and extensive mitochondrial changes were seen by electron microscopy. Allylamine caused a marked rise in left ventricular pressure at 5 and 10 min, followed by a slow decline to a markedly depressed level at the end of 2 hr. End diastolic pressure rose steadily throughout the 2-hr perfusion. Coronary flow was similar in control and allylamine-perfused hearts for 1 hr, but then declined slowly. These experiments suggest that vascular spasm or alterations in coronary flow are not the cause of allylamine-induced myocardial damage. Allylamine's toxic effect on myocardium in this model may be mediated through its metabolism and subsequent injurious intracellular events.

Expression of bcr-abl fusion transcripts following bone marrow transplantation for Philadelphia chromosome-positive leukemia.

A modified polymerase chain reaction (PCR) procedure was used to study the expression of bcr-abl fusion transcripts following allogeneic bone marrow transplantation (BMT) for Philadelphia chromosome (Ph1) positive acute and chronic leukemias. The technique was applied to RNA preparations of peripheral blood and bone marrow cells from 10 patients with chronic myelogenous leukemia (CML) and one patient with acute lymphoblastic leukemia (ALL), all of whom had undergone allogenic BMT and were in clinical and cytogenetic remission. Pre-BMT samples available for eight of 11 patients contained detectable bcr-abl fusion products serving as a baseline for comparison to post-BMT studies. Six patients showed no PCR-detectable bcr-abl transcripts in each of several serial analyses post-BMT (1-36 months post-BMT). The remaining five patients demonstrated various patterns of bcr-abl transcript expression after transplantation. In three patients, bcr-abl transcripts persisted for up to 3 months post-BMT but subsequently were undetectable. Molecular relapse was observed 3 and 6 months post-BMT in the remaining two patients whose earlier post-BMT samples showed no bcr-abl fusion transcripts. No bcr-abl transcripts were detected in subsequent samples from both of these patients 6 months and 1 year post-BMT, respectively. These data confirm that Ph1 carrying cells expressing the bcr-abl fusion mRNA may persist or recur for several months following BMT in the absence of clinical and cytogenetic relapse. The significance of these observations is discussed with respect to results reported recently by others using similar techniques.

Use of the isolated perfused heart for evaluation of cardiac toxicity.

The isolated perfused rat heart model can be used to evaluate cardiotoxicity, and is especially useful in distinguishing direct vs indirect cardiac injury. Various perfusion systems can be used to characterize the pathophysiologic as well as morphologic changes induced by drugs or chemicals of interest. The isolated perfused heart was used in the studies described herein to characterize the mechanism of allylamine cardiotoxicity. Rat hearts were perfused with Krebs-Henseleit buffer containing 10 mM allylamine and a latex balloon was inserted into the left ventricle to monitor pressure. Coronary flow in hearts perfused with 10 mM allylamine was similar to control hearts at 5, 10, and 30 min, but was reduced by 1 hr (11.5 +/- 0.6 ml/min/g wet heart weight vs 16.0 +/- 0.7, p less than 0.01). Peak left ventricular systolic pressure increased in hearts perfused with allylamine for 5 min (156 +/- 8 mm Hg vs 103 +/- 9, p less than 0.01), but by 2 hr was decreased compared to controls (89 +/- 6 vs 105 +/- 5, p less than 0.05). End diastolic pressure was markedly increased at 2 hr (58 +/- 3 vs 4 +/- 0.8, p less than 0.01). Morphologically, allylamine perfused hearts exhibited significant contraction band changes as well as numerous cells with marked swelling of the sarcoplasmic reticulum. The findings in this study suggest that allylamine produces direct myocardial damage that appears to be independent of coronary flow. These studies demonstrate that the isolated perfused rat heart model can be used to evaluate mechanisms of acute cardiotoxicity.

Oncocytic carcinoid tumor of the lung.

We report a bronchial tumor composed of a mixture of oncocytes and carcinoid tumor cells; the latter formed ribbons and pseudoglandular structures in the fashion of a carcinoid tumor. Ultrastructurally, the oncocytic cells showed large numbers of mitochondria but no neurosecretory granules. Although the stem cell of the pulmonary K-cell is unknown, our findings support the notion that both the pulmonary endocrine cells and the oncocytes arise from it.