Ghada Khatib

Effect of metoprolol in acute coxsackievirus B3 murine myocarditis

Recent studies suggest that beta-adrenergic blocking agents show promise in the management of cardiomyopathies; however, their role in acute myocarditis is unknown. One hundred 3 week old mice were infected with coxsackievirus B3 and were given either metoprolol (n = 50) or normal saline solution (n = 50) intraperitoneally for 10 days. Twenty mice from each group were observed for mortality for 30 days. Of the remaining 60 mice, 10 from each group were killed on day 3, 6 or 10 and examined for heart viral titers and pathologic changes. Mortality rate in the metoprolol group was 60% compared with 0% in the saline group (p less than 0.005). Viral titers on day 10 of infection were 10(2.6 +/- 0.2) median tissue culture infective dose for the metoprolol group versus 10(2.1 +/- 0.1) for the saline group (p less than 0.05). Whereas pathologic changes at days 3, 6 and 10 of infection were similar in both groups, on day 30 of infection, inflammation, necrosis and mineralization scores (mean +/- SEM) were 1.1 +/- 0.3, 2.1 +/- 0.4, 2.2 +/- 0.5 for the metoprolol group versus 0.3 +/- 0.1, 0.4 +/- 0.3, 0.4 +/- 0.3 for the saline group, respectively (p less than 0.01). Six noninfected mice received metoprolol intraperitoneally for 10 days; there was no mortality during 30 days of observation. In conclusion, metoprolol administration exerts deleterious effects in acute coxsackievirus B3 murine myocarditis.

CD56+/CD4+ Lymphomas and Leukemias Are Morphologically, Immunophenotypically, Cytogenetically, and Clinically Diverse

CD56, a neural adhesion molecule, is a marker of natural killer (NK) lymphocytes as well as a subgroup of CD8+ T cells. Normal lymphocytes with a CD56/CD4 phenotype are scarce. Physiologic increases may occur in patients with immunosuppression, chronic inflammation, and autoimmune disorders. We report 4 cases of lymphomas/leukemias with the unusual CD56/CD4 phenotype. Two were of T-cell and 2 of true NK-cell origin. The T-cell lymphomas had large granular lymphocyte morphologic features and splenomegaly. One patients had a benign course; the other died within months of the leukemia diagnosis. The 2 NK cell lymphomas had blastic morphologic features, initially involved skin, and had a very aggressive clinical course; 1 patient died of acute leukemia, and 1 had recurrence after bone marrow transplantation. Cytogenetic analyses did not show a consistent pattern of abnormalities. The NK lymphoma with acute leukemia had a t(2;5) but was CD30- and anaplastic lymphoma kinase negative. Although CD56+/CD4+ lymphomas/leukemias are a heterogeneous group, there may be a distinct subgroup of NK lymphoblastoid lymphomas of the skin, judging from our cases, as well as those previously reported.

Correlation of bcl-2 Oncoprotein Immunohistochemical Expression with Proliferation Index and Histopathologic Parameters in Colorectal Neoplasia

Thebcl-2 oncogene plays an important role in carcinogenesis by inhibiting cell death (apoptosis). It was initially discovered in follicular B cell lymphoma with t(14, 18), and subsequently found in other malignant and premalignant lesions. Alteration of the normal controls of cell proliferation is also a significant factor in the multistep process of tumorigenesis. The proliferative activity of a given lesion is commonly evaluated by MIB1, a monoclonal antibody to Ki67 proliferation antigen. Immunohistochemical (IHC) staining expression of bcl-2 and Ki67 was retrospectively investigated in a series of 52 colorectal carcinomas and 56 adenomas according to the avidin-biotin-complex method. The aim of the study was twofold: 1) to investigate any correlation between MIB1 and bcl-2 immunostaining expression in colonic adenomas and carcinomas, 2) to identify any relationship between either marker and several histopathologic parameters including tumor size, pathologic stage, lymph node metastasis, angiolymphatic invasion, tumor grade and differentiation in colon carcinomas. Bcl-2 was consistently higher in adenomas than in carcinomas. There were 44/56 (78.6%) adenomas, and 27/52 (51.9%) carcinomas positive for bcl-2 (p=0.004). The mean Ki67 labeling index (LI) was 30.05±7.6 and 38.12±11.01 in adenomas and carcinomas, respectively (p=0.0001). Expression of bcl-2 in carcinoma was significantly associated with a lower mean Ki67 LI and with favorable histopathologic parameters. We conclude that bcl-2 oncoprotein expression is probably an early step in the process of colon carcinogenesis, and its expression may be associated with a favorable clinical course. Furthermore, an inverse relationship exists between bcl-2 and Ki67 in colonic neoplasia. Evaluation of bcl-2 and Ki67 IHC expression in colonic carcinoma should be performed prospectively to determine if their expression is of value in predicting the clinical course in these patients.

Effect of delayed captopril therapy on left ventricular mass and myonecrosis during acute coxsackievirus murine myocarditis.

The effect of captopril on coxsackievirus B3 murine myocarditis was investigated. Thirty-two, 3-week-old mice were infected with coxsackievirus B3 on day 0 of the study, then randomized into a placebo group or a captopril group starting on day 3 of infection. On day 9 of infection, the mice were put to death. Hearts were weighed and processed for light microscopic examination. Heart weight was 125 +/- 19 mg in the control group versus 102 +/- 14 mg in the captopril group (p less than 0.0003). Amount of necrosis as a percentage of left ventricular section was 3.5% (2.0% to 7.5%) in the placebo group versus 2.0% (0.0% to 5.0%) in the captopril group (p less than 0.01). The amount of dystrophic calcification was 5.0% (0.0% to 27.5%) in the placebo group versus 1.3% (0.0% to 20.0%) in the captopril group (p less than 0.01). The extent of the histopathologic involvement by planimetry was 10.2% in the placebo group versus 5.4% in the captopril group (p = 0.052). We conclude that captopril is beneficial in decreasing left ventricular mass and the amount of myocardial necrosis and calcification in the short term in the murine myocarditis model.

Prolonged Captopril Therapy in Murine Viral Myocarditis

Background: Acute myocarditis can progress to chronic heart muscle disease and cardiomyop athy. In the coxsackievirus B 3 (CB3) mouse model of myocarditis, early administration of cap topril, an angiotensin-converting enzyme (ACE) inhibitor, ameliorated histopathological changes in inflammation, necrosis, and calcification and reduced heart weight. Late administra tion of captopril reduced heart weight but did not affect the histological findings. In this study, we investigated the effects of prolonged captopril treatment in the chronic phase of this model. Methods and Results: Three-week-old male CD1 mice were infected with CB3 and then randomized to receive placebo or captopril starting on day 7 of infection. Captopril, 2 g/L, was given as the drinking water daily for up to 6 months. Autopsies were performed at 6 and 10 months. Heart-to-body weight ratios were obtained, and deaths were tallied. Myocardial fibrosis was graded according to a score system. In addition, picrosirius red stain (PSR) also was used for assessment of collagen deposition. Mean heart weights were similar in both groups. Mean body weight was significantly lower in captopril-treated mice (40.7 g) than in the untreated group (43.6 g) at 6 months (P = .0155), and mortality was higher (8.7 vs 0.87%; P = .009). At 6 months, the mean myocardial fibrosis score in treated mice (0.12) was significantly less than in untreated animals (0.35; P = .035). With PSR, the mean myo cardial fibrosis score in the captopril group (1.20) was also significantly less than in the untreated group (1.58; P = .045). At 10 months, fibrosis scores were similar in both groups. Conclusions: Chronic captopril treatment in CB3 myocarditis reduces myocardial fibrosis.

Perinatal and Neonatal Significance of Bacteria‐Related Placental Villous Edema

In a study of 82 cases of clinical chorioamnionitis in which no antibiotics were administered antenatally, significant villous edema was observed in 51 placentas (62%). Polymorphonuclear leukocyte invasion of the placental plate was found in 53 placentas (65%). the presence of SVE was significantly associated with placental bacterial recovery, occurrence of prolonged rupture of membranes, lower one minute Apgar score, the need for resuscitation and significant neonatal respiratory problems. Findings suggest that bacteria‐related placental villous edema can lead to significant perinatal and neonatal morbidities.

Focal Ventricular Thinning Caused by Indomethacin in the Late Phase of Coxsackievirus B4 Murine Myocarditis

Indomethacin has been shown to increase virus titers and to worsen cardiac injury in the acute phase of coxsackievirus B4 murine myocarditis. The authors evaluated the effects of indomethacin on the histopathologic changes in a later phase of this disease after virus clearance. Two-day old CD1 mice were infected with coxsackievirus B4. Ten days later, surviving animals were randomized to receive indomethacin or saline intraperitoneally for 10 days. They were then euthanatized, and their hearts were examined for the presence of inflammation, necrosis, scarring, and focal thinning. Mortality was slightly higher among treated animals (7/15 versus 2/12, p = 0.3). The index of inflammation (0.6 +/- 0.5 versus 0.7 +/- 0.5) necrosis and scarring (0.4 +/- 0.5 versus 0.3 +/- 0.5) among treated and control animals, respectively, was not significantly different, but the size of involved myocardium (149742 +/- 201982 versus 35300 +/- 45413 microns2) was remarkably larger (p less than 0.05), and focal ventricular thinning (5/12 versus 0/10, p = 0.03) was encountered among indomethacin recipients exclusively. These findings indicate that indomethacin treatment in the late phase of coxsackievirus B4 myocarditis enhances myocardial damage and increases the incidence of focal ventricular thinning.

Protracted necrotizing pharyngitis associated with an acquired defect of neutrophil chemotaxis in multiple myeloma

SummaryA 69-year-old man presented with protracted necrotizing pharyngitis requiring prolonged antibiotic therapy. During immunologic evaluation he was found to have IgA multiple myeloma, low complement component C1q and extrinsic defect of neutrophil chemotaxis. The severity of his pharyngitis correlated with myeloma activity implying a causal relationship. The characteristics of the illness strongly suggest that it is related to the acquired defect in neutrophil chemotaxis. This case represents a previously undescribed infectious complication of multiple myeloma.ZusammenfassungEin 69 Jahre alter Mann mußte wegen einer hartnäckigen Pharyngitis über lange Zeit mit Antibiotika behandelt werden. Bei Erhebung seines Immunstatus wurde ein multiples Myelom mit IgA-Gammopathie, eine Verminderung der Komplementkomponente C1q und ein extrinsischer Defekt der Neutrophilen-Chemotaxis festgestellt. Der Schweregrad der Pharyngitis korrelierte mit der Aktivität der Grundkrankheit, woraus eine kausale Beziehung abzuleiten war. Die Eigenschaften der Erkrankung lassen auf einen Zusammenhang mit dem erworbenen Defekt der Neutrophilen-Chemotaxis schließen. Die im vorliegenden Fall beobachtete infektiöse Komplikation bei multiplem Myelom ist bisher in der Literatur nicht beschrieben.