Efficacy and toxicity of amiodarone for the treatment of supraventricular tachyarrhythmias

Amiodarone is an effective agent for all types of supraventricular tachyarrhythmias regardless of mechanism and may, in fact, control a high percentage of supraventricular tachyarrhythmias refractory to conventional antiarrhythmic agents. However, its toxicity should temper enthusiasm for the use of the medication in non-life-threatening arrhythmias. As always, when recommending specific therapies the potential benefit should be weighed in light of the related risk. In patients with life disordering, drug-refractory atrial fibrillation, it seems reasonable to attempt control with amiodarone. Likewise in patients with ectopic atrial tachycardias refractory to conventional agents, this seems reasonable as well. Other and better therapies are available for patients with life-threatening arrhythmias associated with the Wolff-Parkinson-White syndrome. While amiodarone is moderately effective in these patients, the advent of improved surgical techniques and the relatively low risk of an operation make surgery the treatment of choice. The role of IV amiodarone, acutely, in the treatment of supraventricular tachyarrhythmias remains to be defined.     

Kindling of the visual cortex in cats: comparison with amygdaloid kindling

Kindling of the primary visual cortex (VC) was compared with that of the amygdala in cats. VC kindling was basically similar to kindling of the amygdala in that daily electrical stimulation can lead to the development of a generalized convulsion in most subjects, a growth of afterdischarges in their configuration and duration, and a reduction of the afterdischarge threshold. The kindling response of the VC differed from that of the amygdala in a number of respects, i.e., a high afterdischarge threshold, a different pattern of behavioral seizure development, an abrupt growth of electroclinical seizures coincident with the onset of a generalized convulsion, an intersubject variability in seizure susceptibility, and a marked seizure instability. In VC kindling the afterdischarge propagation into the amygdala was not observed until the generalized convulsion developed, and the early involvement of afterdischarge was seen in the pulvinar, lateral geniculate body, and superior colliculus. These data suggest that a neural mechanism different from amygdaloid kindling may participate in VC kindling, and that the subcortical structures of the visual system are involved in the preferential pathway for a seizure generalization from the VC.     

Association of tuberculosis and M. tuberculosis-specific antibody levels with HLA

In the search for HLA-linked immune response genes that control susceptibility to tuberculosis, we performed HLA typing and measured antibody titers to well-defined Mycobacterium tuberculosis antigenic determinants in 101 patients with sputum smear-positive pulmonary tuberculosis and 64 healthy controls from Surabaya, Indonesia. HLA-DR2 and DQw1 were associated with sputum smear-positive pulmonary tuberculosis (attributable risk = 36% and 39%, respectively), while DQw3 was associated even more strongly with the control group (preventive fraction = 57%). Antibody titers to the TB71 and TB72 epitopes of the 38-kDa protein, present only on tubercle bacilli, were strongly associated with DR2 (Pcorr = .001 and .024, respectively). The association of both the disease and the antibody response to the 38-kDa antigen of M. tuberculosis with Class II HLA genes HLA-DR2 indicates that Ir-gene-mediated regulation of the immune response to this antigen may be of pathogenic significance for the development of sputum smear-positive tuberculosis.     

Metabolism of 3H- and 14C-labeled glutamate, proline, and alanine in normal and adrenalectomized rats using different sites of tracer administration and sampling

Alanine, glutamate and proline labeled with 14C and 3H were infused into fasted normal and adrenalectomized rats. Alanine was administered by the A-V mode (arterial administration-venous sampling), and glutamate and proline by both the A-V and V-A (venous administration-arterial sampling) modes. The kinetics of 14C alanine and 14C glutamate differed markedly from those of the tritium-labeled compounds, but there was little difference in the kinetics of 3H and 14C proline. The replacement rate calculated from the A-V mode for glutamate was about half that obtained in the V-A mode, but there was little difference with proline. The masses of the amino acids (total content of amino acids in the body) were calculated from the washout curves of the tritium-labeled compounds after the infusion of tracer was terminated. The masses for the normal rats were 407 mumol/kg for alanine, 578 mumol/kg for glutamate and 296 mumol/kg for proline. The so-called distribution spaces calculated conventionally from total masses and the amino acid concentrations in plasma are much greater than the volume of the body, reflecting the fact that amino acid concentrations in tissues greatly exceed those in plasma. Adrenalectomy markedly affected the kinetics of the three amino acids, and their replacement rates were greatly reduced. The proline and glutamate masses were reduced by at least one half, while that of alanine was unchanged. Adrenalectomy markedly reduced the conversion of proline to glutamate. The hydrocortisone regimen used in this study restored the metabolism of alanine and glutamate to normal, but had no effect on that of proline.     

Skeletal muscle blood flow and venous capacitance in patients with severe sepsis and systemic hypoperfusion

Alterations in peripheral vascular tone are presumed to contribute to circulatory failure during severe sepsis. Decreased venous tone with venous pooling may decrease effective circulatory blood volume, while decreased arterial tone with redistribution of systemic blood may compromise tissue nutrient flow. We compared forearm arterial and venous tone and forearm blood flow in ten patients with and ten patients without sepsis. The FVT, MVC, and FBF were measured by air plethysmography. In the septic patients, MCV was 1.4 +/- 0.1 ml compared with 3.1 +/- 0.2 ml in nonseptic patients (p less than 0.01). The FVT was 13.4 +/- 1.0 mm Hg/ml in septic patients versus 7.0 +/- 0.5 mm Hg/ml in nonseptic patients (p less than 0.01). The ratio of FBF to cardiac output was 0.28 +/- 0.07 percent in septic patients and 0.31 +/- 0.07 percent in nonseptic patients. These data suggest that increased peripheral venous capacitance and redistribution of skeletal muscle blood flow are not present in patients with sepsis.     

Education of patients with arterial disease. A plan for the use of Expert System in angiology via Minitel

We are presenting a computer program requiring the use of an Expert System accessible by Minitel, intended for patients with arterial disease and their attending physician. The objective is not to make a diagnosis, but to train the patients in applying health measures to the handling and prevention of his/her disease. While remaining anonymous, the patient may consult the program at home, without any time constraint. Only the patient's physician can authorize him/her to have access to the program. The Expert System may adjust the answers to the patients according to the past history and recent data. Contrary to a computer program, new knowledge does not impair the functioning of the system. The physician has access to simplified modules regarding his patient, and specific modules regarding the treatment. Such a system would help general practitioners in following his patient and would facilitate the Doctor-Patient relationship during consultations.     

Life-span development: a review of theory and practice for families with chronically ill members

While the family's primacy in the patient's adaptation to chronic illness increasingly is being recognized by health professionals and social scientists, the reverse side of the coin, that is, the impact of chronicity on the family, has received little attention. A life-span development perspective is used to enrich the more traditional frameworks employed to study family development and also as a unifying framework from which to view the impact of illness on individual family members and the family as a unit. A review of selected literature reveals a profile of families most at risk for serious disruption in situations involving chronic illness. Propositions suggesting interventions directed at patients and families experiencing chronicity are derived.     

A central mechanism of acute baroreflex resetting in the conscious dog

The role of the central nervous system in the mechanism(s) involved in acute carotid baroreflex resetting was studied in six conscious, chronically instrumented, aortic-denervated dogs. Dogs were prepared for reversible vascular isolation of the carotid sinuses. Acute baroreflex resetting was induced by holding the left carotid sinus pressure (LCcsp) at a given value for 20 minutes using a pulsatile pressure control system while at the same time keeping the right carotid sinus pressure (RCSP) at a subthreshold level (approximately 40 mm Hg). At the end of the 20 minutes, the LCcsp) was reduced to approximately 20 mm Hg, and a baroreflex (RCSP-mean arterial pressure [MAP]) curve was generated on the right carotid sinus using static-step increases in carotid sinus pressure. At the control LCcsp of 100 mm Hg, the RCSP-MAP baroreflex had a threshold pressure (Pth) of 86.6 +/- 3.1 mm Hg and a set point pressure (Psp) of 104.7 +/- 2.5 mm Hg. Increasing LCcsp) to 140 mm Hg for 20 minutes caused these parameters for the right carotid baroreflex to increase. Pth and Psp increased by 18.4 +/- 4.0 and 14.2 +/- 3.0 mm Hg, respectively (p less than 0.05). The baroreflex curve, therefore, was shifted upward and to the right. Decreasing LCcsp to 60 mm Hg caused Pth and Psp to decrease by 24.7 +/- 5.0 and 18.1 +/- 2 mm Hg, respectively (p less than 0.05). The baroreflex curve was therefore shift downward and to the left. The percent of resetting of Pth and Psp was 46 +/- 9% and 36 +/- 8%, respectively, when LCcsp was 140 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)     

Antibodies to the ADP/ATP carrier, an autoantigen in myocarditis and dilated cardiomyopathy, penetrate into myocardial cells and disturb energy metabolism in vivo

We identified the ADP/ATP carrier, located within the inner mitochondrial membrane, to be an organ- and conformation-specific autoantigen in myocarditis and dilated cardiomyopathy. We also showed that autoantibodies to the ADP/ATP carrier inhibit the nucleotide transport in vitro. Specific binding of the autoantibodies to the carrier was demonstrated by radioimmunoassay and the immunoblot technique; the inhibition of the nucleotide transport was determined by the inhibitor stop method. To establish if these autoantibodies might also affect cardiac energy metabolism in vivo, we measured whether they are capable of penetrating into myocytes and whether subcellular ATP/ADP ratios and phosphorylation potentials of ATP change in hearts of guinea pigs that have been immunized with the isolated ADP/ATP carrier. An intracellular deposition of autoantibodies was observed by direct immunofluorescence and by immunoperoxidase staining on cryosections of the myocardial tissue of animals immunized with the ADP/ATP carrier. Furthermore, binding of autoantibodies to mitochondrial membrane structures was shown by immunoelectron-microscopic methods. The cytosolic and intramitochondrial distribution of adenine nucleotides in stimulated, isolated perfused hearts of guinea pigs immunized with the ADP/ATP carrier was measured by nonaqueous fractionation. Compared with controls performing equal external heart work, the cytosolic ATP decreased in the immunized animals, whereas the mitochondrial ATP increased strongly; ADP concentrations showed an opposite change. Thus, a resultant cytosolic decrease and a marked mitochondrial increase of the ATP/ADP ratio was established. As a consequence, the cytosolic-mitochondrial phosphorylation potential of ATP was diminished. These findings demonstrate that antibodies against intracellular antigens are able to penetrate into living cells, and that autoimmunity to the ADP/ATP carrier may contribute to the pathophysiology of myocarditis and dilated cardiomyopathy by causing an autoantibody-mediated imbalance between intracellular energy delivery and demand.