Early developmental 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure decreases chick embryo heart chronotropic response to isoproterenol but not to agents affecting signals downstream of the beta-adrenergic receptor.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) causes cardiovascular toxicity in laboratory animals, including alteration in several processes in which beta-adrenergic receptor (beta-AR) signaling plays important roles. Thus, our laboratory investigated the effects of TCDD on beta-AR expression and signal transduction. Fertile chicken eggs were injected with vehicle (corn oil), 0.24 or 0.3 pmol TCDD/g egg on incubation day 0 (D0) or D5. On D10, heart function was assessed by ECG in ovo. Exposure to TCDD increased the incidence of arrhythmias and decreased the positive chronotropic responsiveness of the heart to isoproterenol. The reduced beta-AR responsiveness was, in part, independent of any overt morphological changes in the heart as chick embryos exposed to TCDD on D5 displayed an intermediate responsiveness to beta-AR agonist in the absence of the dilated cardiomyopathy observed in chick embryos exposed to TCDD on D0. TCDD did not decrease the chronotropic response of the heart to agents that stimulate signals downstream of the beta-AR. In fact, TCDD-exposed embryos were more sensitive than controls to forskolin, increasing heart rates (HR) 21.8 +/- 3.5 beats per min (bpm) above baseline versus control values at 6.3 +/- 2.7 bpm above baseline. TCDD exposure also augmented the negative chronotropic response of the heart to verapamil, decreasing HR -23.2 +/- 7.4 bpm relative to baseline versus control embryos at -12.7 +/- 5.9 bpm below baseline. Finally, the mean cardiac beta1-AR mRNA expression in D10 embryos was not significantly altered by exposure to TCDD on D0. These findings establish that a functional end point of the developing chick heart is sensitive to TCDD exposure and that the TCDD-induced reduction in beta-AR responsiveness may result from alterations in signal transduction upstream of adenylyl cyclase.     

Attenuation of hemodynamic responses to rapid sequence induction and intubation in healthy patients with a single bolus of esmolol

The effectiveness of a single preinduction intravenous (IV) bolus of esmolol in blunting hemodynamic responses to rapid sequence induction and tracheal intubation was evaluated. In a randomized double-blind study, 32 ASA I and II healthy patients scheduled for surgery were monitored with electrocardiography (EKG) lead V5, arterial cannulation, and impedance cardiography. After preoxygenation and a priming dose of vecuronium (0.01 mg/kg), patients received either saline (n = 12), esmolol 100 mg (n = 10), or esmolol 200 mg (n = 10) as an IV bolus (20 ml volume). This procedure was immediately followed by a 5 ml IV saline flush, cricoid pressure, thiopental sodium 5 mg/kg, and succinylcholine 1.5 mg/kg. Patients receiving 200 mg of esmolol had a 50% reduction in the usual tachycardia associated with induction and a greater decline in systolic blood pressure (SP) (by 50%) prior to intubation as compared with the placebo group (p less than 0.05). The increase in diastolic blood pressure (DP) and the reduction in stroke volume (SV) produced by induction and intubation were similar in all the groups. Plasma norepinephrine levels at 1.5 minutes after intubation increased in the esmolol groups about 130% above that measured in the placebo group. This finding was associated with a more gradual return of peripheral resistance to baseline following tracheal intubation. However, both doses of esmolol effectively attenuated heart rate (HR), SP, and rate pressure product (RPP) increases (p less than 0.05 vs placebo) produced by laryngoscopy and tracheal intubation.     

The prevalence of coagulation abnormalities in juvenile rheumatoid arthritis

To determine the prevalence of coagulopathy in juvenile rheumatoid arthritis, results of repeated coagulation studies obtained on 73 patients over one year were correlated with disease activity, liver function abnormalities and drug therapy. In spite of active and severe disease in the majority of these children, coagulation abnormalities developed in only 2 cases and there was no instance of clinically apparent bleeding. Although these results suggest that the development of coagulopathy is uncommon, the physician must continue to exercise vigilance for this potentially life threatening complication, especially when caring for the child with systemic disease receiving combinations of drug therapy.     

Radiographic appearance of the esophagus and stomach after laser treatment of obstructing carcinoma

Nd:YAG laser therapy is an attractive palliative treatment for carcinoma of the esophagus and gastric cardia. Twenty-five patients with these tumors underwent laser therapy over a 2-year period, receiving a total of 52 courses of therapy with 189 treatments. Treatments per course averaged 3.6, with a mean of two courses per patient. Luminal diameter is increased with this method; symptomatic improvement in dysphagia occurred in all patients after one course of therapy. Radiographic improvement also is seen. The complication rate in this series was four (2.1%) of 189 procedures, consisting of one perforation, one tracheoesophageal fistula, one pneumopericardium, and one pneumoperitoneum without leak.     

Serum glomerular binding activity is highly correlated with renal disease in MRL/lpr mice.

The pathogenesis of lupus nephritis is felt to be mediated by anti-DNA antibodies. However, the anti-DNA response and renal disease do not entirely correspond. We recently developed a new assay which detects immune elements based on their ability to bind glomeruli as an alternative approach to understanding the pathogenesis of this disorder. The glomerular binding activity (GBA) defined by this assay consists of immune elements containing IgG which interact specifically with renal tissue, the binding of which is DNase-inhibitable, but which do not bind to DNA directly. In the current study we assessed the relationship between GBA and renal disease in MRL/lpr mice (both untreated and cyclophosphamide-treated) and compared it with the anti-DNA assay. Both assays were highly correlated with renal disease in untreated mice in terms of proteinuria. In cyclophosphamide-treated mice, however, only a weak correlation between the anti-DNA assay and proteinuria was apparent. GBA, in contrast, was more strongly correlated with proteinuria in treated mice. This correlation improved substantially when the DNase-sensitive component of the GBA was used. GBA appeared related to, but not covariant with, the anti-DNA response. These results demonstrate that GBA is a better correlate of murine lupus nephritis than the anti-DNA assay, and suggest that the immune elements detected by this assay, the DNase-sensitive component in particular, may be pathogenically important.     

Comorbid disorders in hospitalized bipolar adolescents compared with unipolar depressed adolescents

This study examined comorbid psychiatric disorders in adolescents with bipolar disorder. Hospitalized bipolar adolescents (N=10) were compared to hospitalized adolescents with unipolar depression (N=33), and to adolescents with nonaffective psychiatric disorders (N=11). Results showed conduct disorder, attention-deficit hyperactivity disorder, psychosis, and having any DSM-III-R psychoactive substance use disorder were all significantly more common in the bipolar group than the unipolar depressed group. Comorbid anxiety disorder was present in 40–45% of the subjects in the unipolar and bipolar groups, but in none of the control group subjects. This study is supported in part by a grant to Dr. Borchardt from the University of Minnesota Graduate School.     

Clostridium septicum infection and associated malignancy. Report of 2 cases and review of the literature

We report 2 patients with myonecrosis due to Clostridium septicum and associated colon carcinoma and have reviewed the English language literature for all reported cases of atraumatic C. septicum infection. A total of 162 cases of C. septicum infection have been reported. Eighty-one percent of these patients had an associated malignancy. Thirty-four percent of all patients had associated colon carcinoma, while 40% had a hematologic malignancy. Thirty-seven percent of reported patients had an occult malignancy at the time of their infection with C. septicum. In many patients, the portal of entry was found in the large intestine. In a particularly lethal form (79% mortality) of C. septicum infection, known as "distant myonecrosis," infection metastatic from the initial site of infection causes severe myonecrosis, gangrene, and often death within hours of clinical detection. Overall, survival of patients with C. septicum infection is only 35%. Review of all cases of C. septicum infection suggests several conclusions. 1) Patients with malignancy, particularly colonic or hematologic, and patients with cyclic neutropenia who develop signs and symptoms of sepsis, especially with associated findings of abdominal pain or pain in an extremity, should be treated for possible clostridial infection. 2) C. septicum infection does not appear to be a result of a single specific defect in either humoral or cell-mediated immunity. Rather, it may occur in patients who are granulocytopenic and therefore prone to an enterocolitis. 3) Patients in whom an infection with C. septicum is found must undergo a vigorous search for malignancy following acute therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Collaboration--a new IT-service in the next generation of regional health care networks

During the past 10–15 years, Regional Health Care Networks (RHCN) have been established in many regions throughout the world. RHCN build on well-known techniques, methodologies and appropriate standards. Most of the European Countries today have set up IT strategic plans that focus on the establishment of RHCN. The benefits of having access to all relevant information are tremendous and contribute to cost-effective and coherent health services. By the rapid spread and use of Internet, technology has made it possible to interconnect all kinds of applications. In 2000, the most experienced regions in Europe joined PICNIC, a European project to develop the Next Generation Regional Health Care Networks and to support their new ways of providing health and social care. The previous generation of Regional Health Care Networks supported the interconnection of applications by transfer of messages. Messaging is an effective means of integration for isolated high-specialised systems that only need to exchange data. This service will continue to be one of the most important services in the future health care networks. However, tighter coupling may be desirable in some instances to avoid replicating the same functionality in several applications. In other words, certain services can be common and used by a number of applications instead of building that service inside each application. These common services are called middleware services. In PICNIC (http://www.medcom.dk/picnic), a new middleware Collaboration IT service has been identified and developed. This service allows the end users to perform real-time clinical collaboration, with exchange of text, structured data, voice and images across the limits of a single region. A clinical collaboration is associated with the shared clinical context to provide a record of relevant clinical information and facilitates synchronous as well as asynchronous collaboration. This new IT service builds on the increasing popularity of instance messaging and presence systems that facilitate smooth transition between synchronous and asynchronous interaction. The new Collaboration IT service is expected to have a strong impact on the practice of health care in the next generation of Regional Health Care Networks.