Subtyping male alcoholics by family history of alcohol abuse and co-occurring psychiatric disorder: a bi-dimensional model

Six studies of 568 alcoholics in treatment are summonsed to illustrate the interactive effects of familial alcoholism, other forms of family psychopathology and the lifetime prevalence of additional psychiatric disorder on the onset and course of male alcoholism. A family history of alcoholism as well as additional co-occurring psychiatric syndromes were associated with (1) earlier onsets of problem drinking, (2) a more virulent course and (3) greater heterogeneity of psychopathology among first degree relatives. A bi-dimensional method of classifying male alcoholics is proposed which combines a family history of abusive drinking and the presence or absence of co-morbid psychiatric disorders. Implications for the clinical researcher and practitioner are briefly discussed.     

Reentrant Circuits and the Effects of Heptanol in a Rabbit Model of Infarction with a Uniform Anisotropic Epicardial Border Zone

Reentry in Rabbit Ventricles. Introduction: The purpose was to study reentry in a rabbit model of infarction.
Methods and Results: A model of an infarct epicardial border zone was produced in Langendorff perfused rabbit hearts by freezing the inner two thirds of the left ventricular wall, allowing only a thin epicardial muscle layer to survive. Reentrant circuits causing stable ventricular tachycardia occurred in the surviving rim of epicardial muscle as shown by mapping impulse propagation with a 196–electrode array. The circuits were functional, and reentry did not occur around an anatomical obstacle. Slow conduction in the circuits was caused by the anisotropic properties of the epicardial muscle. Activation in the circuits was slow transverse to the long axis of the fiber bundles and rapid parallel to the long axis. Other features of the circuits, including orientation of the central functional line of block parallel to the fiber long axis, and an oval shape are also characteristic of anisotropic reentry. Since the slow conduction causing reentry is a result of poor transverse intercellular coupling, we determined whether the "uncoupler" heptanol would cause block in the circuits and terminate tachycardia. Heptanol in concentrations up to 1.2 mM slowed conduction in the transverse and longitudinal directions in the circuits and sometimes extended the central line of functional block. It did not, however, stop reentry because the reentrant impulse was still able to conduct around the ends of the block line.
Conclusion: Drugs that decrease intercellular coupling may not be effective antiarrhythmic agents when uniform anisotropy causes functional reentry.     

Induction of CD4+ and CD8+ T cell responses in efferent lymph responding to Toxoplasma gondii infection: analysis of phenotype and function

The kinetics of induction of T cell responses were examined in efferent lymph from a node draining the site of a primary inoculation of Toxoplasma gondii. The numbers of T cells increased after infection, due initially to an expansion of the CD4⁺ T cell population followed by an increase in the number of CD8⁺ T cells which coincided with the peak lymphoblast response. Proliferative responses of CD4⁺ T cells to T. gondii antigen were detectable from day six after infection and immune efferent lymph cells inhibited the intracellular multiplication of T. gondii in vitro. Optimum inhibition was achieved using CD8⁺ T cells restimulated in vitro, and the effector function appeared to be directed preferentially against the autologous rather than the allogeneic infected target cell. The results provide unique information on the induction of immune responses to T. gondii in vivo and provide evidence that both CD4⁺ and CD8⁺ T cells are necessary for the development of protective immunity induced by the S48 strain of T. gondii which is used as a live vaccine in sheep.     

The H2O2-Generating Enzyme,Xanthine Oxidase,Decreases Luminal Ca2+ Content of the IP3-Sensitive Ca2+ Store in Vascular Endothelial Cells

Objective: Xanthine oxidase inhibits agonist-stimulated Ca²⁺ signaling in calf pulmonary artery endothelial cells by an H₂O₂-dependent mechanism. We investigated the effect of xanthine oxidase on luminal Ca²⁺ content of the inositol-1,4,5-trisphosphate (IP₃)-sensitive Ca²⁺ store. Methods: Luminal Ca²⁺ content was estimated from the net release of Ca²⁺ activated by 2,5-di-t-butylhydroquinone (BHQ), an inhibitor of microsomal Ca²⁺ pumps. Results: Initially, xanthine oxidase depleted the IP₃-sensitive Ca²⁺ store of releasable Ca²⁺, but with more prolonged incubation, the enzyme also depleted non-IP₃-sensitive stores. In addition, xanthine oxidase inhibited capacitative Ca²⁺ influx. Similar results were observed when thapsigargin was substituted for BHQ. Conclusions: Depletion of luminal Ca²⁺ content within the IP₃-sensitive Ca²⁺ store contributes to xanthine oxidase inhibition of Ca²⁺ signaling in vascular endothelial cells.     

Analysis of Deaths in Patients with an Implantable Cardioverter Defibrillator

The cause of death and clinical characteristics of 26 patients that died after implantable cardioverter defibrillator placement were reviewed and compared to the 145 patients still living after a mean follow-up of 17 months. Operative mortality was 4% (7/171) and resulted from postoperative ventricular arrhythmias (four patients), heart failure (two patients), and respiratory failure (one patient). Operative mortality was significantly higher (1.7% vs 9.6%, P less than 0.05) following concomitant surgical procedures. Total late mortality was 11% (18/171). Thirteen deaths (75%) occurred in-hospital from progressive deterioration of left ventricular function (nine patients), arrhythmia (two patients), and noncardiac causes (two patients). Outpatient mortality was 3.5% (6/171) and resulted from presumed sudden cardiac death in five of six patients; two of the five had devices that were inactive, one had high defibrillation thresholds, and two had suspected bradyarrhythmic deaths. One postoperative death and one late in-hospital death were also considered sudden cardiac deaths for a total of seven patients with defibrillation system failures. By multivariant analysis, preoperative clinical characteristics associated with a worse prognosis following defibrillator implantation were identified: presentation as ventricular tachycardia (P less than 0.02), induction of sustained monomorphic ventricular tachycardia (P less than 0.05), poor left ventricular performance (P less than 0.01), poor functional status (P less than 0.001), and the use of diuretics (P less than 0.01). Frequent device discharges (P less than 0.001) and concomitant antitachycardia pacing systems (P less than 0.001) were markers for greater arrhythmia recurrence and were potent predictors of a worse prognosis and particularly sudden death.     

Episodic Arthropathy in Adult Cystic Fibrosis

SUMMARY Five (8.5 per cent) of 59 adult patients with cystic fibrosisdescribed a characteristic arthropathy which was episodis, self-limitingand polyarticular, affecting large and small peripheral jointswithout evidence of progression to joint damage. The five patientswith arthropathy did not differ from the remaining 54 with respectto manifestations of cystic fibrosis. Synovial fluid obtainedfrom two patients during acute episodes was clear, viscous andcontained no cells. Biopsies of synovial membrance from thesame patietns demonstrated prominent congested blood vessleswith some synovial oedma, but no evidence of inflammation. Immunofluorescentstaining of synovial membrance demonstrated characteristic ini\timaldeposition of immunoglobulin in the vessles. In one of the twopatients acute arthropathy was accompained by transient cutaneousvasculities, circulating immune complexes and lowered serumcomplement levels, which suggests that the episodic arthropathyin at least some patients with cystic fibrosis is mediated byan immune mechanism.     

Alternative Locations for Internal Defibrillator Electrodes

Successful defibrillation is described in two patients in whom the defibrillating electrode was positioned in the coronary sinus and right ventricular outflow tract as alternative sites. Internal cardiac defibrillation has been successful with single or multiple endocardial electrodes, epicardial patch electrodes, and subcutaneous surface electrodes (patch, array) in varying combinations and recently with an active can electrode. While the traditional location of the endocardial electrode has been the right ventricular apex, we describe two patients in whom defibrillation was successful in alternate locations, the coronary sinus and the right ventricular outflow tract.     

IL-10 deficit correlates with chronic, hypersplenomegaly syndrome in male CBA/J mice infected with Schistosoma mansoni

Twenty weeks after moderate level infections with Schistosoma mansoni, approximately 20% of male CBA/J mice develop hypersplenomegaly syndrome (HSS) while the rest present with moderate splenomegaly syndrome (MSS). HSS and MSS mice differ pathophysiologically (degree of splenomegaly, anaemia, ascites, periportal fibrosis, portal hypertension) and immunologically with regard to antibodies (idiotypic expression, isotype levels) to schistosome soluble egg antigens (SEA), and spleen cell phenotypic profiles. This study compared in vitro proliferative responses and IL-2, IFNγ, IL-4, and IL-10 production by spleen cells from uninfected mice and mice with acute (8 wk), MSS or HSS schistosomiasis mansoni, upon exposure to anti-CD3_ε or SEA. Spleen cells from uninfected mice produce IL-2 to anti-CD3_ε, but exposure of cells from all three groups of infected mice to anti-CD3_ε or SEA led to only very low levels of supernatant IL-2. Anti-CD3_ε- or SEA-stimulated production of IFNγ or IL-4, and anti-CD3_ε-stimulated production of IL-10, displayed similar patterns: highest cytokine production by cells from mice with acute infections and lower levels of production that did not differ between the two chronic groups. In contrast, while SEA-stimulated IL-10 production was again highest with cells from mice with acute infections, spleen cells from mice with MSS produced significantly more IL-10 than did those from mice with HSS. This association of low levels of antigen-induced IL-10 with severe pathology is consistent with the theory that IL-10 plays a role in the immunoregulation that occurs in chronic schistosomiasis .     

OCULAR TRAUMA FROM LEAD-ACID VEHICLE BATTERY EXPLOSIONS

Ocular trauma caused by lead-acid car battery explosions has been seen in a number of cases presenting to the major teaching hospitals in Adelaide. Injuries range from superficial acid burns to penetrating eye injury and retinal haemorrhage. The cause of the explosions has been ignition of the hydrogen-oxygen gas mixture generated by lead-acid batteries. The risk of explosion is known to battery manufacturing and distributing bodies and methods of avoiding explosions are well known to the industry. It is suggested that efforts should be made to design safe car batteries, and that there is an urgent need to educate the public to the risks involved with the present batteries.