Carvedilol Versus Metoprolol in Patients Undergoing Direct Percutaneous Coronary Interventions for Myocardial Infarction: Effects on QT Dynamicity

Beta-adrenergic blockers exert significant antiarrhythmic activity during ischemia and reperfusion. To further explore the beneficial effects conferred by alpha-1-adrenoceptor blockade on ventricular repolarization dynamicity in the acute phase of myocardial infarction (AMI), we compared carvedilol with metoprolol in the setting of primary percutaneous coronary intervention (PCI). In a prospective study, 100 consecutive patients undergoing primary PCI for AMI were randomized to metoprolol 200 mg/day versus carvedilol 25 mg/day. The first oral dose of study drug was administered and a 24-hour ambulatory electrocardiogram recorded upon hospital admission. Slopes of the linear QT/RR regression were determined before and after reperfusion. A total of 38 recordings of patients treated with metoprolol and 34 recordings of patients with carvedilol were eligible for analysis of QT/RR slopes. The two study groups were similar with respect to age, gender, TIMI perfusion grades, ventricular function, duration of ischemia, and site and size of infarction. Mean RR- and QT-intervals were similar to the metoprolol and carvedilol groups, before and after PCI. Likewise, there was no significant difference in QT/RR slopes between the metoprolol and carvedilol groups before PCI. In contrast, after PCI, there was a trend toward lower QT/RR slopes in the metoprolol group (from 0.18 ± 0.07 to 0.17 ± 0.08), and a significant decrease in QT/RR slopes in the carvedilol group (from 0.17 ± 0.07 to 0.14 ± 0.09). In patients undergoing successful direct PCI for AMI, treatment with carvedilol, in contrast to metoprolol, was associated with a significant decrease in QT–RR slopes, suggesting greater cardiac electrical stability.     

T-cell receptor gene rearrangement in T-cell large granular leukocyte leukemia: preferential V alpha but diverse J alpha usage in one of five patients

T-gamma lymphoproliferative disease (T-gamma LPD) is a chronic disorder of mature T cells that is associated with neutropenia and autoimmune phenomena. Although the progression of the lymphoproliferation is indolent, it is often associated with a monoclonal proliferation of T- cell-type large granular lymphocytes (LGL) that manifest multiple in vitro suppressor and cytotoxic activities. We considered the possibility that the granulocytopenia or anemia might represent an autoimmune disorder mediated by the monoclonal LGL via T-cell receptor (TCR) recognition of an antigen involved in hematopoiesis. Therefore, in an effort to characterize the usage of the TCR alpha- and beta-chain genes in patients with T-gamma LPD, we cloned and sequenced TCR alpha- and beta-chain mRNAs derived from the T-cell type LGL of five patients. The five patients studied did not use a common V alpha nor a common J alpha segment. However, an unusual finding was observed in one of the patients where the occurrence of a single variable-diversity-junctional (VDJ) rearrangement of the beta chain confirmed the monoclonal origin of the LGL proliferation. In accord with this evidence for monoclonality, many of the cells studied used a common V alpha (V alpha 19.1). In contrast to this common V alpha usage, there was a marked diversity of the J alpha segments and N-region addition that were associated with the V alpha 19.1 segment. This pattern of common V alpha usage associated with different N and J alpha segments suggests an immune-mediated selection process affecting the TCR alpha chain occurring after the transformation event that established the clone. We suggest that the T-cell-type LGL malignant clone might have developed autoreactivity conferred by the selected TCR alpha chain and that this autoreactivity might be implicated in this patient's anemia.     

Bezold-Jarisch-Like Phenomenon Induced by Radiofrequency Ablation of a Left Posteroseptal Accessory Pathway via the Coronary Sinus

RF Ablation-Induced Bezold-Jarisch Phenomenon. We report a case of asystole induced by radiofrequency (RF) ablation via the coronary sinus in a 35-year-old man suffering from symptomatic left posteroseptal accessory pathway. RF application provoked progressive slowing of the sinus rhythm, disappearance of the preexcitation, and an 8-second period of asystole followed by atrial fibrillation. The causal mechanism proposed is a strong stimulation of va-gal afferent pathways linked with sensory endings of the inferoposterior myocardial wall leading to a Bezold-Jarisch-like phenomenon.     

Pathology of human intestinal transplantation

BACKGROUND & AIMS: Intestinal transplantation is a developing therapeutic option for patients with irreversible intestinal failure or short bowel syndrome. The aim of this study was to delineate the histopathology of human intestinal allografts and to define the features of intestinal rejection. METHODS: The histological features of 3015 endoscopic biopsy specimens and 23 allograft specimens from 62 intestinal recipients were analyzed retrospectively and correlated with clinical findings. RESULTS: Acute allograft rejection was characterized by a varying combination of crypt injury, mucosal infiltration primarily by mononuclear cells (including blastic lymphocytes), and increased crypt cell apoptosis (more than 2 per 10 crypts). It represented a patchy, often ileal-centered process that could progress to mucosal ulceration; later episodes (more than 100 days posttransplant) tended to show lesser cellular infiltration and greater apoptosis than earlier episodes. Correlation with clinical rejection was good (false-positive rate of 9%; false-negative rate of 26%). Two resected specimens showed obliterative arteriopathy indicative of chronic rejection. In other specimens, preservation injury, cytomegalovirus infection, post-transplant lymphoproliferative disorder, and nonspecific features of active or past mucosal injury could be recognized. CONCLUSIONS: Mucosal biopsy specimens are a useful means of monitoring intestinal allografts. Based on features validated by clinical correlation, acute rejection can be identified reliably and can be differentiated from the other pathological processes affecting the intestinal allograft. (Gastroenterology 1996 Jun;110(6):1820-34)     

HIV screening and linkage to care in a health department in Valencia,Spain: Lessons learned from a healthcare quality improvement project

Spain’s rate of new human immunodeficiency virus (HIV) diagnoses exceeds that of the European Economic Area average (8.6 vs 5.6:100,000 in 2018). The country has failed to meet the first of United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 targets for HIV control by 2020, with 87.0% of people living with HIV knowing their status, and late presentation rates of 47.6% and 51.5% country-wide and in the Valencian autonomous community, respectively. Advancing screening and linkage to care (SLTC) practices is necessary to effectively control the epidemic. The Valencia Viral Screening (CRIVALVIR) project adopted the TEST model for opportunistic and systematic HIV SLTC in individuals aged 18 to 80 who required blood work for any purpose, as of February 2019. SLTC was integrated into routine clinical workflow across primary care centers serving a population of 360,000 people in Valencia, Spain. Our project successfully upscaled total HIV testing by 194% to over 32,000 patients tested in 14 months. We found an overall prevalence of 0.13% (0.08–0.21) among those screened per protocol (n = 13,061), with foreign-born citizens presenting a 12.5 times significantly higher likelihood of acquiring HIV (95% confidence interval 4.63–33.96, P < .0001). We improved late presentation by 18.2 percentage points and prevented an estimated 58 to 70 new secondary infections. HIV screening of the general population in primary care is an effective strategy for achieving timely diagnosis and preventing new infections. Opportunistic, systematic, opt-out approaches are essential to control the HIV epidemic.     

Bile duct stones: percutaneous transhepatic removal

Percutaneous transhepatic intervention for transduodenal removal of biliary stones was performed 38 times in 34 patients with obstructive jaundice, biliary colic, and cholangitis. The technique entailed the percutaneous transhepatic placement of a modified Dormia basket in the common duct with the flexible tip in the duodenum. The stones were passed into the duodenum and were crushed, or were crushed in the common duct and passed as fragments into the duodenum. In addition to the snare procedure, monooctanoin was used 18 times to dissolve remaining fragments of stone and sludge that could not be snared and passed into the duodenum. The average time for completion of the procedure was 10 days. There were no deaths from the procedure. The complication rate was 21%--probably no greater than would occur with surgery in a similar patient population. The procedure can be performed when endoscopic retrograde cholangiopancreatography and sphincterotomy with stone removal is technically impossible or refused, and in patients who have previously undergone choledochojejunostomy.     

Neonatal treatment with 192 IgG-saporin produces long-term forebrain cholinergic deficits and reduces dendritic branching and spine density of neocortical pyramidal neurons

The role of basal forebrain-derived cholinergic afferents in the development of neocortex was studied in postnatal rats. Newborn rat pups received intraventricular injections of 192 IgG-saporin. Following survival periods ranging from 2 days to 6 months, the brains were processed to document the cholinergic lesion and to examine morphological consequences. Immunocytochemistry for choline acetyltransferase (ChAT) and in situ hybridization for ChAT mRNA demonstrate a loss of approximately 75% of the cholinergic neurons in the medial septum and nucleus of the diagonal band of Broca in the basal forebrain. In situ hybridization for glutamic acid decarboxylase mRNA reveals no loss of basal forebrain GABAergic neurons. Acetylcholinesterase histochemistry demonstrates a marked reduction of the cholinergic axons in neocortex. Cholinergic axons are reduced throughout the cortical layers; this reduction is more marked in medial than in lateral cortical areas. The thickness of neocortex is reduced by approximately 10%. Retrograde labeling of layer V cortico-collicular pyramidal cells reveals a reduction in cell body size and also a reduction in numbers of branches of apical dendrites. Spine densities on apical dendrites are reduced by approximately 20-25% in 192 IgG- saporin-treated cases; no change was detected in number of spines on basal dendrites. These results indicate a developmental or maintenance role for cholinergic afferents to cerebral cortical neurons.      

Tetrahydrocannabinol vs. prochlorperazine. The effects of two antiemetics on patients undergoing radiotherapy

The authors tested the effectiveness of orally administered delta-9-tetrahydrocannabinol (THC) as compared to prochlorperazine for the alleviation of symptoms, such as vomiting and nausea, experienced by patients receiving radiotherapy. The test subjects rated the severity of their illness, as well as the extent of their subsequent moods, their level of concentration, their amount of physical activity, and their desire for social interaction. They chose the drug they preferred and recorded its side effects. The use of THC was slightly more beneficial than the use of prochlorperazine.