Mortality in primary and secondary myocarditis

Background

Lymphocytic myocarditis presents as a primary disorder or in association with a systemic disease. Whether primary and secondary myocarditis have the same prognosis is unknown.

Methods

Patients (n = 171) referred to the Johns Hopkins Cardiomyopathy service from 1984 to 1998 with newly diagnosed cardiomyopathy were observed for an average of 5.9 years after an original diagnosis of biopsy-proven myocarditis or until reaching the end point of death. Giant-cell myocarditis was excluded from this study. Myocarditis was classified as secondary when a systemic disease was present at the time of presentation; otherwise, myocarditis was classified as primary. Survival rates among patients with primary and secondary myocarditis were compared with Kaplan-Meier analysis and Cox proportional hazard models incorporating clinical variables, including baseline hemodynamics and treatment with immunosuppressive therapy.

Results

The mortality rate associated with secondary myocarditis varied substantially depending on the underlying systemic disorder. Peripartum myocarditis, when compared with idiopathic myocarditis, had a reduced mortality rate (relative hazard, 0.23 [0.06-0.98]; P <.05), which was attenuated after controlling for confounding variables (relative hazard, 0.62 [0.13-2.98]; P = .55). In contrast, human immunodeficiency virus myocarditis had a particularly poor prognosis (relative hazard, 6.70 [3.51-12.79]; P <.05), even after controlling for confounding variables. Myocarditis associated with systemic inflammatory disorders showed a trend toward increased mortality rate (relative hazard, 2.46 [0.65-9.38]; P = .19). For both primary and secondary myocarditis, advanced age and pulmonary hypertension were important clinical predictors of death.

Conclusions

The prognosis of patients with secondary myocarditis, when compared with patients with idiopathic myocarditis, seems most affected by the primary disease process.     

Expression of inducible nitric oxide synthase and cyclooxygenase-2 in pancreatic adenocarcinoma： Correlation with microvessel density

AIM: Cyclooxygenases (COX) are key enzymes for conversion of arachidonic acid to prostaglandins. Nitric oxide synthase (NOS) is the enzyme responsible for formation of nitric oxide. Both have constitutive and inducible isoforms. The inducible isoforms (iNOS and COX-2) are of great interest as regulators of tumor angiogenesis, tumorigenesis and inflammatory processes. This study was to clarify their role in pancreatic adenocarcinomas. METHODS: We investigated the immunohistochemical iNOS and COX-2 expression in 40 pancreatic ductal adenocarcinomas of different grade and stage. The results were compared with microvessel density and clinicopathological data. RESULTS: Twenty-one (52.5%) of the cases showed iNOS expression, 15 (37.5%) of the cases were positive for COX-2. The immunoreaction was heterogeneously distributed within the tumors. Staining intensity was different between the tumors. No correlation between iNOS and COX-2 expression was seen. There was no relationship with microvessel density. However, iNOS positive tumors developed more often distant metastases and the more malignant tumors showed a higher COX-2 expression. There was no correlation with other clinicopathological data. CONCLUSION: Approximately half of the cases expressed iNOS and COX-2. These two enzymes do not seem to be the key step in angiogenesis or carcinogenesis of pancreatic adenocarcinomas. Due to a low prevalence of COX-2 expression, chemoprevention of pancreatic carcinomas by COX-2 inhibitors can only achieve a limited success.     

Gemcitabine, vinorelbine and prednisone for refractory or relapsed aggressive lymphoma,results of a phase II single center study

The optimum therapy for patients with relapsed or refractory aggressive non-Hodgkin’s lymphomas (NHL) not qualifying for platinum-based and/or high-dose chemotherapy is not known. We conducted a prospective phase II study evaluating a regimen consisting of gemcitabine (1 g/m², days 1 and 8), vinorelbine (30 mg/m², days 1 and 8) and prednisone (100 mg/day, days 1–8) (GVP) given every 21 days. Fifteen patients with a median age of 68 years and a median of three previous therapies were enrolled. Diagnoses included B lymphoblastic (n=1), diffuse large B cell (n=10), anaplastic large T cell (n=2) and peripheral T-cell NHL (n=2). The median international prognostic index score was 3 (six patients with a score of 4 or 5). Five patients achieved a complete remission and three patients a partial remission. The median overall survival was 13.8 months, and the median time to next treatment was 4.4 months. Haematological toxicities of World Health Organisation grades 3/4 were leucopenia in 58%, thrombocytopenia in 33% and anaemia in 17% of all courses. Three patients had grade 3 infections. There was no treatment-related mortality. GVP shows substantial activity in poor prognosis relapsed or refractory aggressive lymphomas and is generally well tolerated, but haematological toxicity is dose limiting.     

Carrier detection in hemophilia A: a cooperative international study. I. The carrier phenotype

Eight laboratories in six countries cooperated to clarify several issues concerning the phenotypes of heterozygous carriers of hemophilia "A." Plasma levels of factor VIII (F.VIII:C, formerly VIII:C) and von Willebrand factor (VWF:Ag, formerly VIIIR:Ag) of carriers and normal women were determined by various "in-house" methods; a single lyophilized plasma standard was used for all assays. Analysis of the collated data from 336 carriers (296 obligatory carriers and 40 sporadic carriers) and 137 normal women showed that there was no difference in the F.VIII:C levels of "paternal" carriers (women who had obtained the abnormal gene from their fathers) and "maternal" carriers. Neither was there a difference in the VWF:Ag levels of normal women and either type of carrier. Age was found to have a significant effect on both F.VIII:C and VWF:Ag, values being higher at very young and very old ages, the minima occurring in the 25- to 30-year range. ABO blood type had a striking effect. Women of types A, B, and AB (designated non- O in the study), both normals and carriers, had significantly higher levels of both factors than did women of type O. Analysis by laboratories showed that differences in mean levels of both factors between laboratories were highly significant. It was concluded that age, ABO blood type, and laboratory variation should be taken into account in carrier detection.     

Antipsychotic Augmentation of Serotonin Reuptake Inhibitors in Treatment-Resistant Obsessive-Compulsive Disorder: An Update Meta-Analysis of Double-Blind,Randomized, Placebo-Controlled Trials

Background:

Many patients with obsessive-compulsive disorder do not respond adequately to serotonin reuptake inhibitors. Augmentation with antipsychotic drugs can be beneficial in this regard. However, since new relevant randomized controlled trials evaluating new antipsychotics were conducted, a recalculation of the effect sizes appears necessary.

Methods:

We meta-analyzed all double-blind, randomized, placebo-controlled trials comparing augmentation of serotonin reuptake inhibitors with antipsychotics to placebo supplementation in treatment-resistant obsessive-compulsive disorder. The primary outcome was mean change in the Yale-Brown Obsessive–Compulsive Scale total score. Secondary outcomes were obsessions, compulsions, response rates, and attrition rates. The data collection process was conducted independently by 2 authors. Hedges’s g and risks ratios were calculated as effect sizes. In preplanned meta-regressions, subgroup analyses, and sensitivity analyses, we examined the robustness of the results and explored reasons for potential heterogeneity.

Results:

Altogether, 14 double-blind, randomized, placebo-controlled trials (n=491) investigating quetiapine (N=4, n=142), risperidone (N=4, n=132), aripiprazole (N=2, n=79), olanzapine (N=2, n=70), paliperidone (N=1, n=34), and haloperidol (N=1, n=34) were incorporated. Augmentation with antipsychotics was significantly more efficacious than placebo in Yale-Brown Obsessive–Compulsive Scale total reduction (N=14, n=478; Hedges’s g=-0.64, 95% CI: -0.87 to -0.41; P=<.01). Aripiprazole (Hedges’s g=-1.35), haloperidol (Hedges’s g=-0.82), and risperidone (Hedges’s g=-0.59) significantly outperformed placebo. Antipsychotics were superior to placebo in treating obsessions, compulsions, and achieving response. There was no between-group difference concerning all-cause discontinuation. The nonsignificant meta-regressions suggest no influence of the antipsychotic dose or baseline symptom severity on the meta-analytic results.

Conclusions:

According to our findings, antipsychotic augmentation of serotonin reuptake inhibitors can be regarded as an evidence-based measure in treatment-resistant obsessive-compulsive disorder.     

Distinguishing between acute and subacute massive pulmonary embolism by conventional and Doppler echocardiography.

OBJECTIVE--To determine the ability of conventional and Doppler echocardiography to distinguish between minor, acute massive, and subacute massive pulmonary embolism in patients with confirmed pulmonary embolism. DESIGN--Prospective study of a consecutive series of 47 patients with confirmed pulmonary embolism. SETTING--Department of internal medicine, university clinic. PATIENTS--11 patients (23%) had minor, 23 patients (49%) had acute massive, and 13 patients (28%) had subacute massive pulmonary embolism. RESULTS--Dilatation of the right ventricular cavity (33 (92%)) and asynergy of the right ventricular free wall (29 (81%)) were seen only in patients with acute and subacute massive pulmonary embolism (n = 36). 23 (64%) with pulmonary hypertension had tricuspid regurgitation. The velocity of the tricuspid regurgitant jet correlated with the pulmonary arterial pressure (r = 0.88, SEE = 11.6 mm Hg) and was significantly lower in patients with acute massive pulmonary embolism (3.0 (0.4) m/s, n = 12) than in patients with subacute massive pulmonary embolism (4.2 (0.6) m/s; n = 11) (p < 0.001). The use of predefined indices (right ventricular free wall thickness > 5 mm; tricuspid regurgitant jet velocity > 3.7 m/s; and the occurrence of both a dilated right ventricular cavity with normal interventricular septal motion, or an inspiratory collapse of the inferior vena cava, or both) correctly identified 11 of 13 patients (85%) with subacute massive pulmonary embolism. CONCLUSION--Conventional and Doppler echocardiography were successful in evaluating the haemodynamic consequences of pulmonary embolism.     

Induction of cross-reactive antibodies by immunization of healthy adults with types Ia and Ib group B streptococcal polysaccharide-tetanus toxoid conjugate vaccines

Types Ia and Ib group B streptococcal (GBS) capsular polysaccharides (PSs) are structural isomers but are antigenically distinct. Immunization of healthy adults with GBS type Ia PS-tetanus toxoid (Ia-TT) or Ib-TT glycoconjugate vaccines induced > or = 4-fold increases in specific immunoglobulin G to the heterologous PS in more than two-thirds of subjects. Ib-TT vaccine-induced IgG bound with substantially higher affinity to homologous (Ib) than to heterologous (Ia) PS and promoted opsonophagocytic killing of GBS type Ib but not type Ia organisms. The failure of the Ib-TT- and Ia-TT-induced human antibodies to kill bacteria of the cross-reactive serotype contrasts with the results of previous studies in animals. Inhibition enzyme-linked immunosorbent assays demonstrated that Ib-TT-induced IgG to the homologous PS bound mainly to native Ib PS, whereas the cross-reactive antibodies recognized both native and derivative PSs. These results indicate that GBS Ia and Ib PSs should be included in a multivalent conjugate vaccine to prevent GBS disease.     

Diagnosis of dissecting aortic aneurysm with suprasternal echocardiography

A 33 year old woman with Marfan's syndrome and aortic root dissection was studied with precordial and suprasternal echocardiography. The precordial approach revealed some typical features of aortic root dissection. With suprasternal echocardiography it was possible to visualize the characteristic diagnostic feature of this disease: within the aortic lumen an m-shaped pattern--the aortic intimal flap--moving downward to the posterior aortic wall during systole. The diagnosis was confirmed with aortic cineangiography and intraoperative findings. Thus, suprasternal echocardiography can be a useful method of detecting aortic root dissection, especially in patients with aortic arch dissection alone.