Malakoplakia of the vagina diagnosed by fine-needle aspiration cytology.

Malakoplakia is an uncommon chronic granulomatous process that most commonly affects the urinary tract, but it may rarely recur in the female genital tract. It appears to result from a defect in macrophage function resulting in an inability to destroy ingested bacteria. We describe the fine needle aspiration cytology of malakoplakia in a 84-yr-old woman presenting with a large pelvic mass involving the apex of the vagina. The patient's history was significant for cervical squamous cell carcinoma in the remote past. CT-guided needle aspiration yielded cellular smears with large numbers of isolated histiocytes, as well as polymorphonuclear leukocytes, lymphocytes, and plasma cells. The histiocytes had central nuclei and abundant granular cytoplasm containing target-shaped, laminated bodies (Michaelis-Gutmann bodies). These bodies were PAS positive and focally von Kossa positive. Large numbers of intracellular and extracellular bacteria were also seen on the smears. The characteristic cytologic findings obtained by needle aspiration were diagnostic of malakoplakia with a rare and unusual clinical presentation.

Ethanol ingestion increases susceptibility of mice to Listeria monocytogenes.

Excessive consumption of alcohol is associated with an increase in the frequency and severity of infectious diseases. Ethanol adversely affects specific and nonspecific aspects of the immune response. We used a murine model to determine whether ethanol ingestion impairs host mechanisms of resistance to Listeria monocytogenes. Naive mice and mice immune to L. monocytogenes were pair-fed either a Leiber-DeCarli liquid diet containing 7% (v/v) ethanol or an isocaloric control diet for 7 days. Then, nonimmune mice were given a sublethal dose of L. monocytogenes and studied 2 and 5 days after infection, and immune mice were challenged with a lethal dose of L. monocytogenes and studied 5 days after infection. Multifocal liver abscesses developed in nonimmune ethanol-treated and control mice 2 days after infection. Bacterial colony counts in the spleens were similar between the two groups; however, counts in the livers were slightly higher in ethanol-treated mice as compared with those in control mice. Five days after infection the nonimmune ethanol-treated mice had large necrotizing liver granulomas and organ bacterial colony counts 100 to 1000 times higher than those in control mice. Immune ethanol-treated mice had large areas of liver necrosis and inflammation containing numerous Gram-positive bacilli, whereas immune control mice had small, well-formed granulomas and much less necrosis. Organ bacterial colony counts were about 100 times higher in immune ethanol-treated mice as compared with those in immune control mice. Liver enzyme levels and mortality were significantly higher in ethanol-treated immune and nonimmune mice as compared with those in immune and nonimmune control mice. Data support the suggestion that ethanol consumption impairs the development and expression of T cell-mediated immunity of mice to L. monocytogenes, resulting in increased susceptibility to infection with this organism.

Effects of ethanol on parameters of cellular immunity and host defense mechanisms to infectious agents.

Results of several studies have associated ethanol abuse with an increased incidence of infections, including opportunistic infections and those caused by microorganisms, as well as of certain types of cancer. Research findings from several laboratories clearly indicate that one possible mechanism in this association is an effect of ethanol on the immune system. We have developed an animal model fo ethanol ingestion in a liquid diet to study the effects of ethanol on immune responses. In most of the studies, we have used a pair-feeding design in which control animals are given a liquid diet that is isocaloric to the ethanol diet by the addition of either sucrose or dextran-maltose. Here, we discuss data obtained from in vivo studies of cellular function. We have studied the effects of ethanol on activation of T lymphocytes in vivo after intravenous injection of monoclonal antibody to CD3. The stimulation of cells in the spleen was assessed by measuring levels of cytokine RNA. We have also assessed the ability of animals to respond to a sublethal dose of Listeria monocytogenes to determine whether ethanol alters host defense mechanisms. Our findings indicate that ethanol ingestion reduced the ability of mice to respond to anti-CD3 and to resist infection with a bacterium that predominantly infects the liver.

Flow cytometric and immunohistochemical evaluation of ethanol-induced changes in splenic and thymic lymphoid cell populations.

Ethanol-induced alterations in the immune system are thought to play a major role in increasing the susceptibility of alcoholics to infections and tumors. One important change in the immune system is the noted loss of lymphoid cells from the thymus and spleen. To examine these alterations we used a model system where C57Bl/6 mice were pair-fed either a Leiber-DeCarli diet containing 7% (v/v) ethanol or an isocaloric control diet. Mice receiving ETOH for 7 days showed a loss of cells from the spleen and thymus; this loss was even more severe after withdrawal for 1 day. The most profound changes were seen after 2 weeks of ETOH. Spleen and thymus cell numbers were reduced to 36% and 6.2%, respectively compared to control mice. Staining of thymocytes with monoclonal antibodies to lymphocyte surface markers and evaluation with flow cytometry revealed that immature thymocytes (PNA+, CD4+/CD8+) were most reduced. Mature thymocytes (CD4+/CD8- or CD4-/CD8+) were depleted, and the CD4+ to CD8+ ratio was increased. Sections of thymus stained with hematoxylin and eosin or with immunohistochemical methods showed atrophy and lymphoid cell depletion. No cortex was histologically identifiable after 2 weeks of ETOH. The spleen cells most affected by ETOH were the B cells. They were reduced to 8.2 x 10(6) cells/spleen (31.5% of the lymphocytes), as compared to 38.5 x 10(6) cells/spleen (50.3% of the lymphocytes) in the control mice. The spleen was atrophic, but the immunoarchitecture was preserved. Ethanol causes a depletion of lymphocytes from the spleen and thymus with alterations in lymphocyte subpopulations.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamic effects of nitroglycerin in an experimental model of acute aortic regurgitation.

Afterload reduction is an accepted therapeutic modality for the treatment of congestive heart failure caused by chronic aortic regurgitation. However, the role of vasodilator therapy in acute aortic incompetence has not been established. To investigate this, left ventricular volume overload was produced in 18 dogs by constructing a valved conduit from the descending thoracic aorta to the left ventricular apex. The time course of aortic, pulmonary and conduit flows was analyzed in eight control studies and established stability of the experimental model. In the remaining 10 dogs, intravenous nitroglycerin, titrated to reduce mean aortic blood pressure by 40%, and placebo (ethanol) were each infused for 20 min periods. Compared with placebo, nitroglycerin significantly reduced aortic flow (3,945 +/- 324 to 3,397 +/- 362 ml/min, p less than 0.01), regurgitant flow (1,304 +/- 131 to 764 +/- 90 ml/min, p less than 0.001), septal-lateral end-diastolic diameter (47.5 +/- 1.8 to 46.5 +/- 1.8 mm, p less than 0.001), left ventricular end-diastolic pressure (6.9 +/- 0.8 to 6.0 +/- 0.6 mm Hg, p less than 0.05), left ventricular stroke work (19.0 +/- 2.6 to 10.8 +/- 1.7 g-m/beat, p less than 0.001) and systemic vascular resistance (2,253 +/- 173 to 1,433 +/- 117 dyne-s/cm5, p less than 0.001). In contrast, pulmonary flow, left anterior descending coronary flow and subendocardial pH did not change during infusion of either nitroglycerin or placebo. These data indicate that by decreasing preload and afterload, and by preserving coronary flow and tissue pH, nitroglycerin effectively reduced ventricular and regurgitant volumes in the setting of acute volume overload.(ABSTRACT TRUNCATED AT 250 WORDS)

Significance of the transmural diminution in regional hydrogen ion production after repeated coronary artery occlusions.

Previous studies have revealed that the regional accumulation of ischemic metabolites including hydrogen ion (H+) and PCO2 diminish after repeated occlusions. We postulated that this diminution reflects a blunted metabolic response that is related to the severity of ischemic injury and, hence, may be most pronounced in subendocardial (ENDO) regions. To investigate this hypothesis, the left anterior descending coronary artery was serially occluded three times in 51 dogs for a period of either 3 minutes (n = 15), 5 minutes (n = 18), or 15 minutes (n = 18). Each occlusion was separated by 45 minutes of reperfusion. Myocardial [H+] was measured in the endomyocardium and in the epimyocardium of the ischemic anterior wall by use of miniature pH glass electrodes. Accumulation of H+ during occlusion (delta [H+]) in the ENDO region was significantly less during the second occlusion when compared with the first occlusion (3-minute occlusions: 28.2 +/- 3.7 nM/l vs. 39.4 +/- 5.4 nM/l, p less than 0.002; 5-minute occlusions: 49.8 +/- 5.0 nM/l vs. 72.1 +/- 6.5 nM/l, p less than 0.0002; 15-minute occlusions: 132.3 +/- 14.6 nM/l vs. 225.6 +/- 27.7 nM/l, p less than 0.0003). A similar trend was noted for delta [H+] in the subepicardial (EPI) regions. During occlusion, the rise in [H+] occurred sooner, and delta [H+] was consistently greater in the ENDO when compared with the EPI regions (p less than 0.05). Regional myocardial blood flow did not change during the three occlusions, indicating that the diminution in H+ accumulation stemmed from a decrease in H+ production and not from an increase in collateral flow. The decrement in H+ accumulation between the first and second occlusions (delta [H+]1-delta [H+]2) 1) was greater in the ENDO than in the EPI regions (p less than 0.05); 2) correlated with the duration of occlusion (ENDO: r = 0.66, p less than 0.001; EPI: r = 0.82, p less than 0.0001); and 3) was related to the impairment of anterior wall systolic shortening after the first reperfusion period. These findings suggest that the diminution in H+ production that follows serial coronary occlusions reflects a blunted metabolic response that is related to both the duration of ischemia and the degree of systolic dysfunction. Moreover, though attenuation of ischemic metabolite production occurs transmurally, it is most pronounced in the deep ENDO regions.

Regional changes in myocardial acid production during ischemic arrest: a comparison of sanguineous and asanguineous cardioplegia.

Regional differences in myocardial acid production have not been characterized during administration of either asanguineous or sanguineous cardioplegia. To investigate this, miniature glass pH electrodes were placed in the right ventricular (RV) myocardium, the left ventricular subendocardial (LV endo) region, and the subepicardial (LV epi) region in a canine model. Multiple doses of either blood cardioplegia (Group 1; N = 11) or crystalloid cardioplegia (Group 2; N = 11) were administered during 4 hours of aortic cross-clamping. The accumulation of hydrogen ions during the cross-clamp period was greater in Group 2 than Group 1 in the LV endo region (629 +/- 79 nm/L versus 66 +/- 31 nm/L; p less than 0.001), the LV epi region (623 +/- 66 nm/L versus 72 +/- 32 nm/L; p less than 0.001), and the RV myocardium (814 +/- 296 nm/L versus 150 +/- 54 nm/L; p less than 0.05). Within each group, the time course of myocardial pH and the accumulation of hydrogen ions did not differ among the LV endo region, LV epi region, and the RV myocardium (p = not significant). These data indicate that transmural and interventricular differences in myocardial pH and hydrogen ion accumulation are not produced in the vented, arrested canine heart. In addition, when compared with asanguineous cardioplegia, blood cardioplegia globally and transmurally reduces acid accumulation during ischemic arrest.