Blunt chest trauma and the heart.

The Green Lane Hospital experience of patients presenting with cardiac damage as a result of chest trauma has been reviewed following the recent referral of a patient with tricuspid regurgitation due to trauma. A retrospective search of surgical records was made over the preceding 28 years which yielded a further nine patients. Our group has experienced a number of unusual causes of non-fatal cardiac trauma that have followed accidents. In nine out of ten cases closed chest injury resulted in damage to the heart. In some, diagnosis had been delayed for years. Echocardiography is a very useful diagnostic tool. Surgery was undertaken in all cases.

The changing epidemiology of human hookworm infection in Australia.

OBJECTIVE: To document the distribution of human hookworm infection in Australia. DESIGN: A retrospective study of published data and accessible archival records. METHODS: The core data were derived from the report of the Australian Hookworm Campaign, annual reports of various State health departments and the Queensland Institute of Medical Research, and unpublished files of the former Queensland Aboriginal Health Programme. FINDINGS: Today, hookworm infection is endemic only among Aboriginal communities of northern Western Australia and the Northern Territory, where Ancylostoma duodenale may be the sole species. Early this century, infection was also established in Queensland and northern New South Wales, in both Aboriginal and white communities, and Necator americanus predominated. The origin of these parasites is obscure. Sustained control programs seem to have eradicated hookworms from Queensland. CONCLUSIONS: Improved sanitation, hygiene and chemotherapy have eliminated hookworms from white populations of Australia. Continued anthelminthic campaigns will also clear the parasites from Aboriginal communities, but unless living conditions improve significantly infection will recur.

Immunoelectron microscopic identification of cytoplasmic and nuclear Gs alpha in S49 lymphoma cells.

The subcellular distribution of Gs alpha was characterized in S49 lymphoma cells with two polyclonal antisera directed against specific COOH- and NH2-terminal epitopes. Nonspecific binding was determined in each subcellular compartment by incubating cyc- S49 cells, known to be deficient in Gs alpha and its mRNA, with primary and secondary antisera. Small proportions of total specific binding sites were localized to the plasmalemma as well as the nuclear envelope. Because of their small size, these compartments contained a high concentration of Gs alpha. However, most of the specific binding sites were found in nonstructured cytoplasm and within the nucleus. Specific binding was abolished or significantly reduced by preincubating primary antisera with their peptide immunogens but not with an irrelevant peptide. Intracellular Gs alpha immunoreactive binding sites did not colocalize with gold-conjugated transferrin in cells preincubated with this ligand to mark a classical endocytotic pathway. The intracellular and intranuclear location of Gs alpha was confirmed with confocal microscopy of S49 cells immunostained with specific primary and fluorescently labeled secondary antibodies. Gs alpha was also detected with immunoblots of proteins extracted from purified S49 cell nuclei. Thus, Gs alpha is abundantly distributed in intracellular and intranuclear sites in S49 cells and occurs in loci distinct from organelles of the transferrin pathway. The substantial intracellular distribution of Gs alpha suggests that Gs may subserve intracellular and, perhaps, intranuclear functions that may be important in proliferating cells.

Therapeutic end points for the treatment of atrioventricular node reentrant tachycardia by catheter-guided radiofrequency current.

OBJECTIVES: The purpose of this prospective study was to test the hypothesis that the elimination of inducible repetitive atrioventricular (AV) node reentry despite the persistence of slow AV pathway conduction is a valid end point for radiofrequency catheter ablation procedures in patients with supraventricular tachycardia due to AV node reentry. BACKGROUND: Although modification of AV node physiology by radiofrequency current can eliminate AV node reentrant tachycardia, therapeutic end points that are definitive of a satisfactory result in patients undergoing modification of the slow AV pathway have not been established. Applications of radiofrequency current at selected sites may eliminate all evidence of slow pathway conduction or sufficiently modify the refractory properties of the slow pathway to preclude sustained arrhythmias. Accordingly, total abolition of dual AV node physiology may not be necessary to prevent arrhythmia recurrence. METHODS: Radiofrequency catheter ablation of the slow AV pathway was attempted in 59 patients with typical AV node reentry. Tissue ablation was performed with a continuous wave of 500-kHz radiofrequency current. Twenty-five to 35 W was applied for 60 s at the site selected for tissue destruction. RESULTS: Dual AV node physiology was eliminated completely in 35 patients (59%), persisted without inducible AV node reentry in 13 patients (22%) and persisted with inducible single AV reentrant beats in 11 patients (19%). In patients with persistent dual AV node physiology, the maximal difference between the effective refractory period of the fast and slow pathways was reduced from 104 +/- 62 ms before the procedure to 37 +/- 37 ms after AV conduction had been modified (p < 0.001). During a mean follow-up interval of 15 months (range 4 to 28), only one patient (2%) had a recurrence of the tachycardia. CONCLUSIONS: Results demonstrate that when complete elimination of dual AV node physiology is difficult, modification of slow pathway conduction to the extent that repetitive AV node reentry cannot be induced is a definitive end point that portends a good prognosis.

Diagnosis and localization of accessory pathways.

The WPW syndrome is a curable disease. The evolution of nonpharmacological methods of accessory pathway ablation has had a significant impact on management strategies in patients with arrhythmias mediated by accessory pathways. Despite an incidence of preexcitation in the general population of 0.1% to 0.3%, curative therapy is underutilized. This review has highlighted the traditional and newer methods of diagnosing and localizing accessory pathways. The number of patients benefiting from definitive therapy will parallel increased physician awareness of these methods.

Cardiac myocyte interconnections at gap junctions Role in normal and abnormal electrical conduction.

Slow conduction leading to reentrant ventricular tachycardias in patients with healed myocardial infarcts appears to depend primarily on alterations in intercellular coupling at gap junctions of myocytes bordering the infarct scar. Results of correlative morphometric and electrophysiologic studies indicate that the elongated shape of individual myocytes, their complex overlapped packing in myocardium, and the number and distribution of gap junctions that electrically couple myocytes are all important structural determinants of anisotropic patterns of current spread in normal myocardium. Alterations of these structural features likely contribute to electrophysiologic derangements critical in reentrant arrhythmogenesis. Recent observations that cardiac myocytes may be coupled by multiple gap junction channel proteins having unique electrophysiologic properties provide new insights into potential mechanisms regulating intercellular current transfer in the heart.

Remodeling of ventricular conduction pathways in healed canine infarct border zones.

Remodeling of myocyte interconnections may be an important determinant of ventricular tachycardia in regions bordering healed infarcts. We used quantitative electron microscopy to characterize the distribution of gap junctions in 10 canine left ventricles 3-10 wk after coronary occlusion. In three normal canine left ventricles analyzed ultrastructurally, myocardial gap junctions were distributed anisotropically; gap junction profile length was significantly greater in the transverse than in longitudinal planes of section. In infarct border zone tissues, the normal anisotropic distribution was completely abolished and fewer gap junctions per unit intercalated disk length were observed. Analysis of individual gap junction profile length distributions revealed selective disruption of the largest gap junctions that collectively comprised only 9.6% of total junction profiles, but encompassed nearly 40% of aggregate gap junction length in the transverse plane of section. Three-dimensional reconstructions of myocyte interconnections by high resolution quantitative light microscopy of serial sections demonstrated a reduction in the number of cells connected by intercalated disks to a single myocyte from 11.2 +/- 1.0 in normal myocardium to 6.5 +/- 1.3 in border zone tissues (P less than 0.001). Connections of cells in primarily side-to-side apposition were reduced by 75%, whereas primarily end-to-end connections were reduced by only 22% (P less than 0.05). These alterations would disproportionately enhance axial resistivity in the transverse direction, potentially contributing to development of reentrant arrhythmias.

Unidentified trematode eggs in faeces of Australian aboriginal children.

In routine surveys for intestinal parasites among Aboriginal/Torres Strait Islander populations, eggs of unidentified trematode species have been found in the faeces of three children. In two of these, the eggs appeared to belong to a schistosome, or perhaps monogenean, species, and in the third, they were most likely from a monostome of dugongs. Although these probably represent cases of spurious parasitism, one or more may have been a true infection.

Intravenous amiodarone bolus versus oral quinidine for atrial flutter and fibrillation after cardiac operations.

The safety and efficacy of amiodarone and quinidine in reverting atrial tachyarrhythmias after cardiac operations were compared in a randomized cross-over trial. Patients with sustained atrial fibrillation or flutter for more than 2 hours' duration, stable hemodynamic status, and prior digoxin therapy were randomized to receive either intravenous amiodarone, 5 mg/kg over 20 minutes (41 patients), or oral quinidine, 400 mg immediately and 400 mg in 4 hours (39 patients), with cross-over at 8 hours if reversion was not achieved. Thirty-six patients had a coronary artery operation, 35 a valvular operation, five had both, and there were four miscellaneous cases. There was a male:female ratio of 1.5:1 and a mean age of 58 years (range 23 to 75 years). Preoperative atrial fibrillation or flutter was present in nine patients, and four patients had an ejection fraction less than 40%. Twenty-five of 39 patients (64%) given quinidine first reverted to sinus rhythm, compared with 17 of 41 patients (41%) given amiodarone first (2p = 0.04). Side-effects occurred in 18 patients given quinidine and five patients given amiodarone (2p = 0.01). Two patients, both given quinidine, were withdrawn from the study. There was no correlation, with either drug, between serum levels and clinical efficacy. Multivariate analysis identified longer times from arrhythmia to treatment, preoperative atrial fibrillation, mitral valve operations, and concomitant propranolol therapy as factors predictive of failure to revert to sinus rhythm. Oral quinidine was more effective than intravenous amiodarone in reverting postoperative atrial fibrillation and flutter but caused more side-effects.

Quantitative analysis of intercellular connections by immunohistochemistry of the cardiac gap junction protein connexin43.

Polyclonal antisera directed against epitopes in the cytoplasmic domain of rat connexin43, the predominant cardiac gap junction protein, were used to delineate immunohistochemically the distribution of gap junctions in sections of canine left ventricle. Antigen-antibody binding and tissue structure were preserved after paraformaldehyde fixation and paraffin embedment of canine myocardium. Specific binding of antibody to the cytoplasmic surfaces of ultrastructurally identified gap junctions was confirmed with electron microscopy. Light microscopic morphometric analysis of immunostained sections in five separate experiments revealed a mean gap junction surface density of 0.0052 micron2/micron3 myocyte volume, which is consistent with previously reported values determined by use of quantitative electron microscopy. This new method permits quantitative determinations of gap junction surface density and distribution in relatively large heterogeneous areas of myocardium in which ultrastructural morphometry would be impractical. This approach should facilitate analysis of the relation between potential alterations in electrical coupling of myocytes and abnormalities of myocardial conduction occurring at the macroscopic scale in regions such as structurally heterogeneous infarct border zones.

Effect of temperature on rate of left ventricular pressure fall in humans.

The time constant (T) of left ventricular pressure fall is widely used as an index of ventricular "relaxation". It is not known whether its rate limiting step is deactivation, an enzymic energy consuming reaction whose rate is therefore sensitive to temperature, or elastic recoil. To distinguish between these possibilities, the time constant was measured by simple logarithmic (Tlog) and exponential (Texp) methods in 12 patients during cooling before coronary artery grafting. Ventricular loading conditions were altered by transfusion from bypass to maintain arterial and left atrial pressures constant in individual patients, though heart rate fell from 86 (8.4) to 68 (10) beats/min. Tlog increased from 49 (10) ms mean (SD), at 37 degrees C to 86 (15) ms at 31 degrees C, and Texp from 63(14) at 37 degrees C to 112 (23) ms at 31 degrees C with intermediate values at 34 degrees C. Texp proved sensitive to "noise" at low temperatures, but the overall change in Tlog with temperature was 9% per degree C--considerably less than that observed experimentally for the rate of tension decline of isolated myocardium, and possibly itself an overestimate because of the concomitant fall in heart rate. The relatively small effect of temperature on Tlog in humans, associated with a considerable load sensitivity appearing under hypothermic conditions, does not favour simple dependence on deactivation as the rate limiting step of left ventricular pressure fall, but suggests that its determinants may be complex.

Neurosarcoidosis: cerebrospinal fluid lymphocyte subpopulations.

CSF lymphocyte subpopulations of eight patients with neurosarcoidosis were examined. CSF or CT was abnormal in all. The CSF T4/T8 (helper/suppressor) ratio was elevated at 6.8 and 7.6 in two patients; in one, there were only CSF T4 cells. The ratio was normal in five patients.

Neurosarcoidosis: the long-term clinical course.

We reviewed 25 patients with neurosarcoidosis followed for at least 5 years or until death. Seventeen patients (68%) had a monophasic illness. Eight (32%) had a relapsing course, with recurrences similar to the original manifestations months later. Patients with cerebral manifestations or hydrocephalus were most likely to relapse. Seven of eight patients with relapsing disease had exacerbations while taking 10 mg prednisone or less.

Hemoglobin Milledgeville (alpha 44 (CD2) Pro leads to Leu): a new variant with increased oxygen affinity.

Hemoglobin Milledgeville, a new hemoglobin structural variant, was identified in three members of a black American family. The oxygen affinity of blood and hemoglobin samples from the affected individuals was markedly increased (p50 O2 of whole blood 11-15 mmHg at 37 degrees C, pH 7.4), and the abnormality was associated with mild erythrocytosis. The variant hemoglobin did not separate from Hb A by electrophoresis or by chromatography or isoelectric focusing, and efforts to isolate an abnormal globin chain were also unsuccessful. The Hb A2 fraction as well as Hb A from erythrocytes of affected individuals exhibited increased oxygen affinity, indicating that the altered oxygen equilibrium was the result of a hemoglobin alpha chain abnormality. Fractionation of trypsin and chymotrypsin digests of isolated alpha chains demonstrated a single abnormal peptide representing a Pro leads to Leu substitution at alpha 44 (CD2). Properties of Hb Milledgeville include low cooperativity (n = 1.1-1.4), a normal alkaline Bohr effect (delta logp50/delta pH = -0.62), and normal interaction with 2,3-diphosphoglycerate. The alpha CD2 proline residue normally participates in the formation of the alpha 1 beta 2 subunit interface in the deoxy quaternary conformation, but not in oxyhemoglobin; the leucine substitution may produce destabilization of the deoxy conformation with a resulting shift in equilibrium toward the oxy conformation.