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We reviewed 202 biopsies performed on patients with suspected vasculitic neuropathy, of which 24 Churg-Strauss cases are studied separately. Specimens from the superficial peroneal nerve and peroneus brevis muscle were taken simultaneously by one incision. Without taking into account constitutional signs, systemic involvement was present in 131 patients, whereas the remaining 47 corresponded to non-systemic patients with lesions limited to peripheral nervous system and adjoining muscles. Diagnosis of panarteritis nodosa or microscopic polyangiitis, according to the size of involved vessels, was attested by an infiltration of vessel walls by inflammatory cells associated with fibrinoid necrosis or sclerosis. Microvasculitis was diagnosed when inflammatory infiltration concerned small vessels with few or no smooth-muscle fibers and without any necrosis. Microvasculitis was present in 11 of 46 non-systemic cases, and this predominance is statistically significant. Isolated perivascular cell infiltrates in the epineurium were considered not significant but allowed the diagnosis of 'probable vasculitis' if associated with at least one of the following features: regenerating small vessels, endoneurial purpura, asymmetric nerve fiber loss, and/or asymmetric acute axonal degeneration. Necrotizing vasculitis was visible in 60 cases: in nerve (16 cases), in muscle (19 cases), and both (25 cases). Microvasculitis was present in 25 cases: in nerve (19 cases), muscle (four cases), or both (two cases). Moreover, granulomatous vasculitis was found in the nerve of one non-systemic patient presenting also sarcoid granulomas in muscle. There were 24 'probable vasculitis' and 68 negative cases. Muscle biopsy improved the yield of definite vasculitis by 27%.

We examined nerve biopsies from 24 patients with Charcot-Marie-Tooth disease type 1A (CMT1A) and proven 17p11.2-12 duplication. There were seven males and 17 females with a mean age of 27.85 +/- 18.95 years at the time of nerve biopsy. A family history consistent with dominant inheritance was present in 17 patients. Clinical features were classical in 16 patients and were atypical in the other eight: one had calf hypertrophy; two had Roussy-Levy syndrome; one had had a subacute inflammatory demyelinating polyneuropathy 11 years earlier and presented a relapse on the form of a chronic inflammatory demyelinating polyneuropathy; one had carpal tunnel syndrome; one had a recent painful neuropathy in both legs; and two had chronic inflammatory demyelinating polyneuropathy. Onion bulb formations (OMFs) were present in every case and most of them were characteristic, whereas burnt-out or cluster-associated OMFs were less common. Depletion of myelinated fibers was severe in 20 cases (169-2927/mm2) and varied from 5187 to 3725/mm2 in three children (4-9 years old). In addition, features of macrophage-associated demyelination were observed in the last four atypical cases. Known for more than 20 years, inflammatory demyelination superimposed in the course of CMT1A has been reported in a few cases in the past few years, mainly concerning asymptomatic or atypical patients. Such an association deserves to be better known because corticotherapy improves weakness in most of these patients.

We performed a retrospective study of 35 peripheral nerve biopsies (PNBs) with amyloid deposits in the endoneurium. In every case, nerve lesions were studied on paraffin-embedded fragments (PEFs) and by ultrastructural examination (USE). In addition, muscle fragments were taken and embedded in paraffin. Immunohistochemistry was performed with anti-transthyretin (TTR) serum on 19 nerve and 15 muscle PEFs. Direct immunofluorescence with anti-light-chain sera was performed on frozen nerve fragments in 19 cases. Endoneurial amyloid deposits were easily identified on routine PEF in 26 cases, after Congo red or thioflavine staining in three, and by USE in six. A dramatic myelinated fiber loss was evidenced in 34 cases (77-2970 per mm2), and features of axonal degeneration were present in every case. Segmental demyelination was observed in 10 cases. A mutation in the TTR gene was present in 14 cases, with Met30 mutation in 10 and Ala49 in four members of the same family. Amyloid deposits were strongly marked by the anti-TTR serum in 11 other cases, twice in the endoneurium, five around muscle fibers, and four in both locations. In eight patients, light-chain positivity was evidenced in endoneurial deposits, lambda in six and kappa in two. Two other patients with monoclonal gammopathy did not present any light-chain fixation. In 17 cases, amyloidosis was disclosed by PNB and 13 had a TTR pathology; eight of them, over 65 years old, correspond to a late-onset form of familial amyloid polyneuropathy which is an underdiagnosed condition.

In most cases of hereditary neuropathy with liability to pressure palsy (HNPP) the diagnosis is now assessed by molecular detection of 17p11.2 deletion. However, the family history may be missing and the clinical presentation is not always informative. In such cases, a peripheral nerve biopsy showing the characteristic focal myelin sheath thickening ("tomaculae") may be helpful. We present a retrospective study of peripheral nerve biopsies performed in 19 patients suffering from either a mononeuropathy or a generalized sensory-motor polyneuropathy, and for whom the finding of tomaculae led to a search for 17p11.2 deletion, which was confirmed secondarily. Tomaculae and other coexisting neuropathological lesions such as uncompacted myelin, "onion bulb" formations, and axonal degeneration are described and discussed in the view of previously reported data. It appears that demyelinating lesions with tomaculae are strongly suggestive of HNPP but are not specific as they may be observed in other conditions. Moreover, these features may be overlooked if axonal degeneration is marked.

The pathogenesis of Crow-Fukase (POEMS) syndrome is not well known, and in some cases, a definite diagnosis is difficult to establish. Nerve fibers have been studied in about 120 peripheral nerve biopsies (PNBs), and a mixture of axonal and demyelinating lesions were found in most of them. We report five new cases of Crow-Fukase (POEMS) syndrome with ultrastructural examination of their PNBs. In every case, there were features of axonal degeneration and primary demyelination. Interestingly, uncompacted myelin lamellae (UMLs) were present in every case at a percentage of 1-7. The association of UML and Crow-Fukase (POEMS) syndrome was described 20 years ago but was only reported in a few studies and found in 31 of 41 cases. In fact, this association is very significant because apart from Crow-Fukase (POEMS) syndrome, UMLs can only be found with such a frequency in rare cases of Charcot-Marie-Tooth disease type 1B. UML was also reported in acute and chronic inflammatory demyelinating polyneuropathies but at a much lower percentage. Moreover, in our five cases, UML was frequently associated with a decrease in the number of intra-axonal filaments, and this finding raises the problem of relationships between myelin formation and neurofilaments. So far, glomeruloid hemangiomas present in the dermis of some patients are considered as the only specific criteria of Crow-Fukase (POEMS) syndrome, but we think UML can also be regarded as highly suggestive of this entity on condition that a thorough ultrastructural examination of a PNB is performed.

Since 1979, the authors have studied 49 peripheral nerve biopsies presenting uncompacted myelin lamellae (UML). Based on the ultrastructural pattern of UML they propose a 3-category classification. The first category includes cases displaying regular UML, which was observed in 43 cases; it was more frequent in 9 cases with polyneuropathy organomegaly endocrinopathy m-protein skin changes (POEMS) syndrome as well as in 1 case of Charcot-Marie-Tooth 1B with a novel point mutation in the P0 gene. The second category consists of cases showing irregular UML, observed in 4 cases with IgM monoclonal gammopathy and anti-myelin-associated glycoprotein (MAG) activity. This group included 1 benign case and 3 B-cell malignant lymphomas. The third category is complex UML, which was present in 2 unrelated patients with an Arg 98 His missense mutation in the P0 protein gene. Irregular and complex UML are respectively related to MAG and P0, which play a crucial role in myelin lamellae compaction and adhesion.

The authors recently reexamined the peripheral nerve biopsies from 42 patients with chronic inflammatory demyelinating polyneuropathy (CIDP). There were 27 males and 15 females, aged from 9 to 84 years, and 13 had relapses. No patient had vasculitis, monoclonal gammopathy, tumor, diabetes mellitus, Lyme disease, familial neuropathy, HIV, or any other immune deficiency. In the endoneurium, perivascular inflammatory cell infiltrates were present in only one case, but scattered histiocytes marked by KP1 on paraffin-embedded fragments were present in every case and there were no T-lymphocytes. At ultrastructural examination macrophage-associated demyelination was observed in 17 cases, of which 6 had relapses separated by intervals of several months or years. Axonal lesions without associated primary demyelination were observed in 4 cases and 3 of these had relapses. Thirty-two patients had mixed lesions of demyelination and axonal involvement. This study confirms other recent data indicating that in all cases of CIDP, macrophages are present in the endoneurium. Macrophage-associated demyelination is the characteristic feature of demyelinating forms. On the other hand, isolated primary axonal forms, which have been known since 1989, are relatively frequent and prone to relapses.

Intracellular pH was measured with the pH-sensitive fluorescent probe BCECF in spinal cord neurones cultured from rat embryos. At an external pH of 7.3, the average steady-state pHi was 7.18 +/- 0.03 (SEM, n = 97) and 7.02 +/- 0.01 (n = 221) in HEPES-buffered and in bicarbonate-buffered medium, respectively. In both external media, pHi was strongly dependent on external pH (pHe). In HEPES-buffered medium, pHi recovery following an acid load induced by transient application of ammonium required external Na+ and was inhibited by amiloride, indicating the presence of a Na+/H+ exchange. Na(+)- and HCO3(-)-dependent, DIDS-sensitive alkalinizing mechanisms also contributed to pHi regulation in CO2/bicarbonate-buffered medium. The presence of an electrogenic Na(+)-HCO3- cotransporter was confirmed by the alkalinizing effect of KCl application. The fact that pHi is lower in CO2/bicarbonate- than in HEPES-buffered medium and the alkalinization observed upon suppression of external Cl- suggest that the acidifying Cl-/HCO3- transporter plays an important role in defining pHi.

Background: This study determined the histological features of the atrial myocardium connecting the coronary sinus and the left atrium in humans., Methods and Results: Ten necropsied hearts were studied by performing serial longitudinal sections parallel to the long axis of the coronary sinus that extended its full length using a large microtome. In all specimens, the venous wall of the coronary sinus was surrounded by a cuff of striated muscle extending 40+/-8 mm from the ostium. Striated myocardial connections of varying number and morphology left this coronary muscle cuff and connected to the left atrium; they ranged from 1 to 2 fascicles to a widely intermingled continuum (thickness, 2.79+/-2 mm; width, 2.91+/-3.5 mm). These connections originated 8.8+/-5.7 mm from the coronary sinus ostium and inserted 18+/-11 mm distally into the left atrium. The insulating compartment in which the connections traversed between the left atrium and the coronary sinus was mostly formed of adipose tissue. The valve of Vieussens was found in 6 hearts at a mean distance of 3.4+/-3.2 mm from the distal extremity of the coronary sinus muscle cuff., Conclusions: In the human heart, a consistent but morphologically variable left atrial coronary sinus myocardial connection was found. This emphasizes the need for surgical dissection or catheter ablation in or around the coronary sinus to eliminate these connections.

Unlabelled: This study evaluated the impact of the atrioventricular delay (AVD) on the pulmonary venous flow pattern (PVFP)., Methods: Transthoracic Doppler PVFP were obtained during atrial and ventricular pacing at a fixed rate of 70 beats/min in 20 patients equipped with a DDD pacemaker, diastolic dysfunction linked to an impaired relaxation, a mean ejection fraction of 49%, and AV block. Two subgroups were analyzed equally: group I: seven patients with a normal ejection fraction and group II: 13 patients with decreased ejection fraction. Three different AVDs were studied: short (50 ms), intermediate (150 ms), and long (250 ms)., Results: As the AVD increased, the diastolic filling time and the peak atrial reverse flow wave decreased (P < 0.001). There was a decreasing D wave and no significant change in the peak velocity of the S wave. The S wave became biphasic in all patients at the longest AVD of 250 ms. The systolic (S) velocity time integral (VTI) of the pulmonary wave and the systolic/total PVF-VTI ratio increased significantly (P < 0.001). A similar response was seen in both group of patients., Conclusions: These data correlated the AVD with PVFP, supplying critical systolic information completing the diastolic data obtained from mitral Doppler patterns. These systolic measurements were especially useful for patients with heart failure and a DDD pacemaker, in order to obtain the longest diastolic filling time at the lowest atrial pressure.

The study of heart rate variability allows analysis of modulations of heart rate by the sympathetic vagal system. The authors studied the course of sinus variability by 24-hour Holter monitoring preoperatively, and on the 6th and 42nd postoperative day, in 25 patients undergoing coronary bypass graft (group I) and 10 patients undergoing aortic valve replacement (group II). Surgery was performed under cardiopulmonary bypass with selective antegrade cold crystalloid cardioplegia. The preoperative ejection fraction of these patients was 62% with a mean age of 59.5 years in group I and 61.5 years in group II. All temporal or spectral parameters were significantly decreased in the two groups on the sixth day (p < 0.05). Parameters which remain altered on D42 compared to baseline values were temporal parameters: pNN50 and rMSSD for group I and ASDNN for group II, with a tendency to return to baseline values, but with a higher mean heart rate in group II on D6 and D42 (p < 0.05). In the spectral domain, TP (total power of the spectrum) and LF (Low frequencies) remained decreased in both groups. A reversible alteration of sinus variability parameters was therefore observed in the two groups of patients. Other studies are necessary to define the mechanisms of these alterations, which are most probably related to catecholaminergic flooding related to CPB or partial vagal denervation by ischaemic or surgical damage to nerve structures.

Supraventricular arrhythmias are frequently observed in pneumonectomy surgery. We retrospectively studied a series of 100 consecutive patients undergoing pneumonectomy for cancer between 1994 and 1996. We found 24% of significant supraventricular arrhythmias, corresponding to atrial fibrillation in 75% of cases, occurring in 80% of cases until the third postoperative day. The only risk factor significantly associated with these arrhythmias was the patient's age. These arrhythmias are easily reduced, spontaneously in 25% of cases, and usually by amiodarone, alone or associated with digitalis alkaloids. While the mortality of the overall group was 12%, 8% of patients with arrythmia died. These deaths concerned patients whose arrythmias occurred after the fourth postoperative day in a context of a pulmonary infection.

The neuropeptide substance P (SP) is known to play a key role in peripheral nociceptive processes. We investigated the in vitro pharmacological characteristics of functional tachykinin receptors expressed in dorsal root ganglia (DRG) sensory neurones by analysing intracellular free calcium concentration changes induced after stimulation by SP or specific tachykinin agonists. We observed that about 37% of the tested neurones were responsive to either SP or an NK1-, NK2- or NK3-specific agonist. Tachykinin-responsive neurones had a small soma diameter (<20 microm) and were sensitive to capsaicin. These results suggest the presence of NK1, NK2 and NK3 receptors in noxious sensory neurones.

Anatomopathological studies have considerably increased our understanding of the ablative technique by radiofrequency current. They have provided information on the nature, extent and time dependency of the lesions induced. Despite variable results according to whether the experiments were performed in vitro or in vivo, a correlation has been observed between the volumes of the lesions and the energies used. One factor is unquestionable: monitoring the temperature allows better control of the lesion size than monitoring current intensity. However, other technical points are essential for this control such as ensuring good contact between the catheter and the endocardium and the definition of the optimal surface area of the electrode. Now that the conditions of efficacy and security of ablation by high frequency currents are known, anatomopathological studies in man have become rare. These studies, which will take a long time to perform due to the very nature of the technique and pathologies treated, should provide interesting anatomo-electrical comparisons to increase our understanding of certain arrhythmias.

Several studies have shown that high amplification and averaging of the electrocardiographic P wave may soon enable better identification of people at high risk of paroxysmal atrial fibrillation. The results of this technique are closely dependent on the conditions of recording and analysis of the atrial signal but this factor has not been widely appreciated. The authors, therefore, undertook a study of the reliability of the manual method of measuring P wave duration, the influence of the filters used and the level of background noise on the 3 parameters of analysis: the duration of the P wave (DUR), the root mean square of the amplitude of the terminal 20 milliseconds (RMS20) and the integral under the P curve (IN). The recorder was a Predictor II 5.0 (Corazonix) with a special programme to identify and analyse the P wave in 3 bipolar non-orthogonal leads. DUR was determined manually after amplification and averaging; RMS20 and IN were calculated automatically. In order to assess the reliability of manual determination of the P wave, 48 consecutive patients were studied: two analyses were made with a least a 2 months' interval by entering the data through two filters (unidirectional and FIR). The role of the filters was then studied by passing the preceding 48 recordings to an analysis with three filters: unidirectional, bidirectional and FIR, and comparing the results.(ABSTRACT TRUNCATED AT 250 WORDS)

The thrombogenic risk of contrast agents in coronary angiography is still a topical issue, particularly in comparisons between ionic and nonionic contrast agents. As a complement to a preliminary study, the repercussions on sensitive markers of haemostasis were investigated in vivo in 38 patients undergoing a standard cardiac catheterisation. After randomization, an ionic low osmolality contrast agent (Ioxaglate 320) was used in 19 patients and a nonionic low osmolality contrast agent (Iopromide 370) was used in another 19 patients, according to an identical protocol. The following parameters were assayed in arterial blood samples obtained before and after the examination in each patient: platelet markers: beta-thromboglobulin (beta TG) and platelet factor IV (PF4); prethrombotic markers: thrombin-antithrombin 3 complex (TAT) and prothrombin fragments 1 and 2 (F1 + 2) as well as partial exploration of fibrinolysis: tissue plasminogen activator inhibitors (PAI). Comparison of the results demonstrated platelet activation and the presence of prethrombotic markers in both groups. No significant difference was detected between the two groups of patients. Consequently, there does not appear to be any difference in activation of coagulation between modern, low osmolality, ionic or nonionic contrast agents. This may suggest an equivalent thrombogenic risk.

We report a case of aneurysm of all three aortic sinuses. The patient suffered from both cardiac failure and angina pectoris. The diagnosis, suggested by echocardiography, was confirmed by magnetic resonance imaging (MRI) which showed marqued dilatation of all three aortic sinuses. At operation, we observed dilatation of all three aortic sinuses, measuring 2 to 6 cm and partially thrombosed. We performed a Bentall operation with reimplantation of the left coronary artery ostium. The right coronary ostium was thrombosed and was revascularized by a saphenous vein bypass. Despite prolonged circulatory assistance and an intra-aortic balloon counterpulsation, cardiopulmonary bypass could not be stopped and the patient died. This is a new case of multiple aneurysms of the aortic sinuses and also a case of aortic sinus aneurysm (ASA) complicated by coronary insufficiency. This last complication has a poor prognosis, as demonstrated by a review of the 28 cases described in the literature. MRI was found to be important for the diagnosis of the ASA, in combination with echocardiography and angiography which can underestimate the aneurysm because of the frequently associated mural thrombus.

Among the drugs recommended to prevent recurrences of atrial fibrillation after external electric shock, antiarrhythmic agents of classes Ia (quinidine, disopyramide), Ic (cibenzoline, flecainide, propafenone) and III (sotalol) seem to have the same effectiveness in maintaining the sinus rhythm in about 50 percent of the cases after 6 months and one year. Amiodarone, seldom used as first-line treatment, appears to be the most effective drug. The percentage of side-effects requiring discontinuation of treatment is the same for all drugs (about 10 percent). All these drugs have potential proarrhythmic effects. In case of recurrence electric shocks can be repeated in some special cases. The therapeutic strategy according to the clinical context (atrial fibrillation of vagal nerve or catecholergic origin, normal or altered left ventricular function) is discussed.

Signal averaging of the ECG P wave is a recent technique used for obtaining predictive and prognostic information in atrial arrhythmias. There have been few publications of its evaluation in this setting. The authors report their results of temporal analysis of the P wave of patients who had undergone electrical cardioversion of atrial fibrillation (group 3, n = 22 patients) and compared them with those of a control group without atrial arrhythmias (group 1, n = 25 patients). After recording signals in three bipolar leads (Predictor 5.0 II Corazonix recorder-analyser), the total duration of the P wave, the root mean square of the P wave amplitude (RMSt) and of the last 20 milliseconds (RMS 20) and the integral under the curve of the P waves (IN) were determined. The comparison was continued with data obtained from a population of patients with paroxysmal atrial fibrillation (group 2, n = 22). All patients had normal left atria on echocardiography, had no valvular heart disease, had no myocardial infarction or signs of cardiac failure. Results showed that the most discriminating parameter was the P wave duration (Group 3: 159.45 +/- 15.1 ms; group 1: 123 +/- 8.5 ms; group 2: 144.6 +/- 12.03 ms; group 1 versus group 2, p < 0.001, group 2 versus group 3, p < 0.01; group 1 versus group 3, p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Patients with dilated cardiomyopathy often have unsustained VT (15 to 60% of cases) but sustained VT is much less common (0 to 10% of cases). The predictive value of sudden death of VT in Holter monitoring is not unanimously accepted. Therefore, it appears that, in patients with non-symptomatic VT, it is the degree of left ventricular dysfunction which is the best predictive factor of mortality because Holter monitoring, signal averaged ECG and programmed stimulation have a low positive predictive value although their cumulated negative predictive value seems to be very good. Programmed ventricular stimulation should be proposed to patients considered to be at high risk of sudden death, presenting with symptomatic unsustained VT or sustained VT. Approximately 3 out of 4 of these arrhythmias will be inducible and benefit from this method for orientating the choice of treatment. In these high risk subjects about 1 in 3 will be satisfactorily protected by antiarrhythmic drug therapy: non-inducible patients from the outset and those remaining inducible despite antiarrhythmic therapy remain at high risk of sudden death. This group of patients probably represents the best indication of implantable cardioverter defibrillators.

Many anti-arrhythmic drugs modify the pharmacokinetics of digoxin and increase serum levels. This possibility is considered for the majority of main anti-arrhythmics on the basis of a review of the literature. Quinidine, propafenone, flecainide, amiodarone and verapamil increase blood digoxin levels, sometimes to twice their baseline values. Suggested mechanisms involve above all a decrease in clearance of digoxin and changes in its volume of distribution. Reported accidents considered to be a direct consequence of these interactions are nevertheless rare in the literature, and the need for modifying dose and increased cardiological surveillance in the case of such a combination is essentially a question of precaution. Disopyramide, procainamide and mexiletine do not appear to have any reported effects on the pharmacokinetics of digoxin, their combined prescription never having had any effect on blood digoxin levels.

Atrial fibrillation is a daily cardiological problem which poses three types of questions, which, though old, are only partially mastered: anticoagulation, reduction and prevention of recurrence. It is a potent source of embolism. The risk is the greatest in patients with rheumatic valvular disease when the fibrillation is recent and when underlying cardiac disease is uncompensated. Long term anticoagulation is mandatory when the cause is rheumatic heart disease. In other pathologies, though anticoagulation has not been shown to reduce mortality, it significantly reduces the number of cerebrovascular accidents, including in the elderly and with low-dose vitamin K antagonist drugs. The efficacy of anticoagulation in preventing arterial embolism has not been established. Reduction of atrial fibrillation is not essential if the arrhythmia is well tolerated, chronic, especially in elderly patients and when several recurrences have occurred despite preventive therapy. In other cases, medical reduction is to be preferred to cardioversion if the fibrillation is recent and well tolerated. Of the oral and injectable preparations, amiodarone seems to be the drug with best benefit/risk ratio. Prevention of recurrence of fibrillation is unnecessary for many after a first episode, especially when idiopathic. In other cases, there are many available drugs but results are uncertain except in those observed in atrial fibrillation related to the autonomic nervous system. Strictly controlled and statistically exploitable studies show comparable efficacy of quinine and other Class I drugs. Beta-blockers are not very useful and the excellent long term results with amiodarone require confirmation.(ABSTRACT TRUNCATED AT 250 WORDS)

The danger in utilizing electrocautery during a surgical procedure on a pacemaker patient depends, to a great extent, on the position of the electrodes. We have studied this influence in an experimental model consisting of a plexiglass tank filled with a saline solution. Seven pacemakers were successively attached to an immersed and fixed frame and connected to a lead whose tip remains in the same location throughout the experiments. An ERBOTOM T 400 C generator (450 kHz) was used in an unmodulated unipolar mode at a maximum output (400 W). The high frequency current was delivered between a patch located successively at six preset positions in the tank and another electrode applied to 176 surface locations. For each position, we measured the currents in the lead with a separate measurement circuit connected in parallel on the same lead. Results were displayed on a map. Regardless of the patch position, currents were: (1) at a maximum when high frequency was delivered close to the pacemakers and around the tip of the lead; (2) negligible when applied to the path followed by the lead; and (3) a function of the distance between electrodes. These results may help to formulate recommendations to prevent accidents when using electrocautery in pacemaker patients.

One of the hazards of high frequency electrical interference (electrocautery) with cardiac pacing is thought to be related to an increase in the threshold values leading to loss of pacing. This hypothesis was examined in an experimental study performed on 5 dogs. A pacing catheter was introduced via the right jugular vein and positioned at the apex of the right ventricle and connected successively to several stimulators implanted in a latero-cervical subcutaneous pocket. A Bovie 400 CT generator was used to deliver a high frequency 1.75 MHz current between a probe applied near to the pacemaker pocket and an electrode placed under the right leg. One or two 5 second bursts were applied for each make of pacemaker, making a total of 3 to 6 applications per animal. A detecting circuit enabled the measurement of the currents in the catheter during the application. The thresholds of pacing were measured before and after each manipulation for several pacing impulse durations. At the maximal output of the generator, the highest recorded current was 117 mA (modulated) and 141 mA (unmodulated). The thresholds of stimulation did not change significantly and the pacing catheter impedance was also stable. This study suggests that high frequency current does not modify the threshold of stimulation in cardiac pacemaker patients. The loss of pacing sometimes observed after the use of electrocautery is probably related to pacemaker dysfunction.

The aim in treating chronic atrial fibrillation, is not limited to simply achieving immediate regularization. What matters, is sustaining the sinus rhythm. The various methods of regularization, using either medical procedures or cardioversion, involve constraints and risks. Investigation of the relapse predicting factor is of great value in evaluating the benefit/risk ratio. For regularization, the absence ultrasound signs of heart disease, an undilated left atrium, recent atrial fibrillation and all forms of heart disease which are curable, albeit surgically, are indicative of success. With regard to prophylaxis, relapses occur more frequently in cases involving mitral valve disease, long-standing atrial fibrillation or a dilated left atrium.

Systemic embolism secondary to chronic atrial fibrillation usually affect the cerebral circulation. The risk of a cerebrovascular accident in patients with chronic atrial fibrillation, irrespective of the aetiology, is 1.8 to 7.5 times that of the general population. The embolic risk is 18 times greater in patients with atrial fibrillation related to the rheumatic heart disease. The risk of patients under 60 years of age with idiopathic atrial fibrillation does not seem to be different to that of the general population. The risk of early recurrence of embolism in the first 30 days ranges from 8 to 15%. The risk of late recurrence varies but seems to be higher than that of the general population. The prognosis of embolic cerebrovascular accidents is poor with a 20% mortality rate. The benefits of preventive therapy of embolism with oral anticoagulants have been clearly established in rheumatic atrial fibrillation and in other indications. In non-valvular atrial fibrillation the benefits have to be compared with the risks of treatment. The incidence of hemorrhage due to anticoagulant therapy is between 3 and 5% per year per patient (about 1% of severe haemorrhage). Three randomised studies of primary prevention have shown a significant reduction of the embolic risk in non-valvular atrial fibrillation treated by warfarin compared to patients on placebo. Only one study has shown a significant reduction of the embolic risk in patients under 75 years of age with non-valvular atrial fibrillation treated with 325 mg/day of aspirin. However, anticoagulant therapy does not seem necessary in carefully selected patients under 60 years of age with idiopathic atrial fibrillation (less than 5% of all patients).

All aortic aneurysms require a positive diagnosis, a differential diagnosis and an assessment of extension. Several exploratory methods can be contemplated. In patients with warning symptoms, conventional radiology may point to the diagnosis. The reference method remains retrograde aortography which may be either conventional and seriographic or, better, radiocinematic with orthogonal projections and, if possible, digital. The site and morphology of the aneurysm, and in particular its inner channel are thus demonstrated. Computerized tomography is less invasive and usually of great value, notably for the horizontal, thoracic and abdominal aorta, not only to confirm the diagnosis but also to determine the size of the inner channel, parietal thrombi and aortic walls, as well as relations with nearby structures. Other, totally non-invasive methods are widely utilized to explore aortic aneurysms. These are ultrasonography and its variants (notably Doppler-echocardiography and the transoesophageal route), and magnetic resonance imaging which provides three-dimensional and anatomical views of the vessel. These last two examinations alone usually confirm and outline the aortic aneurysms. They must therefore be utilized as first-line examination, arteriography it is various forms being reserved for emergencies or special cases.

A 63 year old man with ischemic heart disease underwent two sessions of catheter ablation in the inferior right atrium for poorly tolerated resistant and recurrent atrial flutter. After endocavitary mapping and comparison with surface recordings of the f waves, a shock of 50 joules was delivered to the zone situated anteriorly to the inferior vena cava, under the orifice of the coronary sinus and behind the tricuspid valve. Early recurrence of the arrhythmia led to a second attempt and another 50 joules shock was administered to the same area. Another short term recurrence led to definitive nodohisian interruption with a 270 joules shock. Thirty months later, the patient died suddenly during an episode of cardiac failure. Macroscopic examination of the right atrium showed a zone of parietal congestion measuring 4 x 3 cm with a very thin, translucid, central zone measuring 3 x 1.5 cm, just anterior to the inferior vena cava in the right atrial free wall. Histological examination of this zone showed an intense, mutilating fibrosis dissociating the muscular fibres, of the pectinate muscle and even replacing the myocardium in certain regions. In the Eustachian valve, there were muscular fibres, probably representing the posterior internodal pathway, which were also fibrosed. These observations suggest that: 1) in view of the extreme thinness of the atrial wall at the site of ablation there is a high risk of perforation even when right endoatrial catheter ablation is performed with low energy shocks; 2) the posterior internodal pathway does not seem to be an essential component for atrial flutter.

Complete atrioventricular block (AVB) following radiotherapy has been reported rarely, usually after high dose mediastinal irradiation for Hodgkin's disease or lung or breast carcinoma. We report six new cases of episodic complete infranodal AVB, requiring permanent pacemaker implantation. The mean age was 48-years old (ranging from 25-60) at the first Adams Stokes attack, mean delay was 12 years after irradiation (10-18), and mean radiation dose was 5,200 rads (4,000-6,500). All patients had abnormal interval electrocardiograms (right bundle branch block in two, left bundle branch block in three, alternating left and right bundle branch block in one). Electrocardiograms during the episode of AVB or Holter recordings were consistent with infranodal block in all patients; electrophysiological study performed in five patients confirmed infranodal AVB in four, and one was normal. Pericardial disease was constant, which included pericardial constriction in four patients. Two patients died after failure of pericardiectomy to improve congestive heart failure, due to epicardial, myocardial, and endocardial involvement. Noncardiac mediastinal lesions were present in four cases. Since this delayed complication may occur in patients of such age that the relation between the AVB and the chest irradiation is questionable, we propose the following etiologic criteria; high radiation dose (over 4,000 rads); delay of 10 years or more; abnormal interval tracings; pericardial involvement; and associated cardiac or mediastinal radiation-induced lesions.

Almost 50 percent of patients with chronic heart failure die of sudden death often due to arrhythmia. In these patients the prognosis is related to the severity of myocardial lesions and also, probably, to the presence of ventricular arrhythmias. The potential severity of which can be assessed by various methods, including ECG, Holter monitoring, late potentials study and programmed ventricular stimulation tests. The first therapeutic measure to improve the prognosis of heart failure is to improve the myocardial function by prescribing converting enzyme inhibitors. The second measure consists of acting on potentially dangerous ventricular arrhythmias with few or no symptoms. Among antiarrhythmic agents, only beta-blockers and amiodarone seem to be valuable.

Internal cardioversion is a new method of treating atrial fibrillation. It consists in delivering an electric shock between an electrode positioned in the right atrium and a dorsal electrode. A quadripolar electrophysiological catheter is used as the proximal electrode, the two distal poles of which are used to locate the His bundle deflection. Care is taken that the electrode used for cardioversion is not in contact with the atrial wall by using biplane fluoroscopy and unipolar endocavitary recordings. Twenty-eight patients (18 men and 10 women) average age 55 years, underwent this treatment for chronic atrial fibrillation resistant to one or two attempts at external cardioversion. Each patient was given one or two shocks (average 1.68) in the same session. There were 22 immediate reversions to sinus rhythm, giving a primary success rate of 78.57%. Four patients relapsed in the 3 days following the procedure, giving a short term success rate of 64.28%. The minimum effective energy would seem to be 200 joules. The only rhythm complications were sinus bradycardia and/or atrioventricular block lasting a few seconds, both countered by prophylactic ventricular pacing : no traumatic complications due to electric shock were observed. The long term results show sinus rhythm maintained in 66.66% of patients at 6 months and more. In conclusion, internal cardioversion is an effective method of treating cardiac arrhythmias resistant to external cardioversion. The procedure would seem to be reliable and relatively atraumatic. The long term results are promising, particularly the stability of sinus rhythm which seems to be longer than after external cardioversion, by they need further confirmation.

The authors report their experience involving 21 right endoatrial electroversions aimed at converting chronic atrial fibrillation resistant to external electroversion. All prior precautions were taken to ensure that the shocks were not in contact with an atrial wall nor over the node-His bundle (two dimensional radiological identification, endocavitary recordings). A total of 37 internal electric shocks were administered. Results were: 16 immediate successes out of 21 (72.2 per cent) and 12 short term successes out of 21 (57 per cent). The mean effective energy value was 200 Joules. There were no traumatic complications. The authors conclude that this technique is effective and reliable in the management of atrial fibrillation resistant to external electroversion.

We report a case of severe subacute autonomic and sensory neuropathy in a 52 year-old man. Cerebrospinal fluid protein was 275 mg/dl. Electrophysiological data were consistent with an axonal sensory neuropathy. Nerve biopsy showed a severe decrease in myelinated fibers, and a less severe loss of unmyelinated fibers. No cause was found and recovery was almost complete over 4 years, with minimal persistent dysautonomia. This case and 4 similar reported cases are compared with pure dysautonomia and with sensorimotor dysautonomic neuropathy. The site of damage is discussed and it is suggested that these cases are axonal forms of inflammatory polyneuropathy.

Peripheral nerve biopsies (PNB) from four children suffering from subacute or chronic inflammatory demyelinating polyneuropathy were studied by electron microscopy. Remyelinating features with onion bulb formations, inflammatory cell infiltrates and active demyelinating lesions were strongly suggestive of the disease. In the first case, a second PNB, performed after 7 months of severe subacute course, showed a striking evolution of the lesions. In the second case and in spite of severe neurological symptoms, the PNB was almost normal, suggesting that inflammatory lesions were mainly located in the proximal parts of the nerve. No signs of active demyelination could be seen in the third case but onion bulb formations and inflammatory cell infiltrates were present. In the fourth case, characteristic lesions of active demyelination were associated with a history of familial polyneuropathy; this association suggests an auto-immune process in certain kindreds with hereditary motor and sensory neuropathy.

The authors studied the possible consequences of the use of high frequency electrical currents of cardiac pacemaker function. Twenty-five unipolar pacemakers (22 single and 3 double chamber) were tested. They were connected to a pacing catheter, emerged in a saline bath and submitted to a modulated and then unmodulated current of 348 KHz in as many pacing modes as possible for each unit. Three dangerous deprogrammations were observed which could nevertheless be easily corrected. Five pacemakers immediately adopted the reversion mode specified by their manufacturer. The other changes observed only lasted as long as the electric current was applied. The commonest abnormality was a drop in the output voltage proportional to the energy delivered which sometimes led to true inhibition of the pacemaker. Two abnormal rate increases were observed reaching frequencies higher than 250/mn. No particular pacing mode seemed to protect the pacemakers from the effects of high frequency currents.

We report a new case of non-familial dysautonomia. The patient was a boy with no known Jewish ancestry in whom psychomotor retardation in early infancy failed to lead to specialized evaluation. Regressive episodes of ataxia developed at the age of three and infrequent generalized seizures occurred between four and seven. Diagnosis was first considered at the age of seven after neuroparalytic keratitis developed and rapidly became bilateral. This case has remained highly unusual throughout the course since none of the commonly reported complications (swallowing disorders, aspiration pneumonia, and dysautonomic "attacks") has occurred. No life-threatening manifestations have developed. Peripheral nerve biopsy specimens showed that myelinated fibers, especially of large diameters, were abnormally scarce, and that the histogram failed to exhibit the normal bimodal aspect. Ultrastructural studies also disclosed a marked reduction in the caliber of unmyelinated fibers, whose axons were flattened or occasionally missing. No evidence of regeneration was found. The atypical clinical features in our patient are discussed.

Cardiac involvement in Friedreich's disease is classically a hypertrophic myocardiopathy, concentric or assymmetrical with or without dilatation. It has nothing specific in comparison to other myocardiopathies. Nevertheless, forms with a dilated myocardiopathy are also possible, but much more unfrequent. A propos of three cases, we have studied the different aspects of myocardiopathies in Friedreich's ataxia. The problem raised by the case of an hypertrophic myocardiopathy evolving toward a dilated form, unusual element of this pathology, is presented. The therapeutic potential of hypertrophic myocardiopathies is classically represented either by beta-blockers or by the more recent slow calcium inhibitors.

Many in vitro and animal experimental studies seem to support the hypothesis of reentry as the physiopathological mechanism of atrial flutter. Clinically, these studies are much more difficult because of problems in determining the different sequences of atrial depolarisation. In this study, the authors attempted to improve the technique of endocavitary atrial mapping. Three or four multi-recording electrodes were positioned in the atria using biplane 30 degrees RAO and 60 degrees LAO incidences. Right atrial angiocardiography showed up the atrial borders and enabled the recording catheters to be more accurately positioned. Thirty to 47 recordings points were thereby determined within the atrial cavities, the left atrium being studied via the coronary sinus, right pulmonary artery, patent foramen ovale or by the endooesophageal approach. This method of spatial orientation of the catheters associated with recording of the endocavitary potentials allowed the construction of an isochronic map of atrial depolarisation, which was then analysed for each case of flutter. The study confirmed two hypotheses: the asynchronism of right and left atrial depolarisation, and the circus motion of depolarisation. Three types of flutter were observed: --The first two types were similar with cirus motion within the right atrium. The wave front ascended in part or all of the septum and descended in the external free wall of the right atrium. There was a transitional zone, possibly reentrant, in the groove located anterior to the inferior vena cava. --The third type of flutter was atypical and was associated with cirus motion in the left atrium. Two transitional zones, similar to those encountered in the right atrium, were detected in one patient between the orifices of the pulmonary veins, and, in another patient, on the anterior part of the roof of the left atrium. These transitional zones seem to be at the basis of the physiopathological mechanism of flutter. Unfortunately, their small size makes their analysis by endocavitary mapping difficult.

The superficial peroneal nerve was taken from 12 arteriosclerotic non-diabetic patients just after amputation of a leg. Preparations of teased fibers were performed in 8 cases. Specimens were studied by light and electron microscopy in all cases. Histograms of myelinated fibers in transverse semi-thin sections showed that depletion of myelinated fibers varied from case to case, with no selective vulnerability in either the large or the small diameter group. There was a dramatic loss of myelinated fibers in only one case. No real nerve infarct was observed. In most cases, regions of Wallerian-like degeneration were prevalent; however, myelino-axonal changes were severe only in a few cases. Axons with organelle aggregates were seen in some cases. Figures of segmental demyelination were not numerous in this series. Unmyelinated fibers were also damaged, and the degree of involvement differed from case to case. Pathological changes observed in this study confirm the relative resistance of peripheral nerve to ischemia.

Correlation between the endocardial electrocardiographic recording and the histological findings of the conduction pathways in one case of apparent atrial standstill makes it possible to state the following facts: 1. The presence of a supranodal block through an intraatrial conduction disturbance. 2. The presence of James' fibres by-passing the upper part of Tawara node. 3. The functional character of these James' fivres which constitute, in view of the presence of lesions of the upper part of the Tawara node, the only possible pathway from the atria to the ventricles in this case. 4. The possibility to record the action potentials of James' fibres in that exceptional case. The histological examination made it possible also to recognize the anatomical lesions responsible for the idiopathic dilatation of the right atrium and of the apparent atrial standstill which represented the end-stage of an atrial rhythm disease.

As has been shown during the course of experimental allergic neuritis, in the Guillain-Barré syndrome there is an invasion of the myelin sheath in certain fibres by a mononuclear cell, with an intact axon. In a series of 45 cases we have been able to show this feature in 31 cases. In certain cases the cytoplasm prolongation of the invading cell was seen in the myelin sheath, forcing apart two neighbouring layers. In five cases we have furthermore observed the presence of mononuclear cells located either between the myelin and the axon which is deformed, or on the inside of the axon. Such an anomaly was frequent in one recent case and was occasionally found in four other cases.

The peripheral nerve was taken from 25 diabetic patients with arteritis just before or after amputation of a leg. The ultrastructural study of myelinated fibers showed several alterations. Loss of fibers varied greatly from case to case. This was accompanied in some cases by hypertrophy of the Schwann cells around demyelinated fibers as has been observed in some ordinary diabetic neuropathies. Unusual abnormalities consisted of particular axonal degeneration and evidence of aberrant remyelination. This axonal injury was peculiar because of the accumulation of organelles which tended to transform some of the fibers into enlarged axons. Such a lesion might correspond to a hypoxic axonopathy.

A 25 year old patient presented with several types of paroxysmal tachycardia. Analysis of the recordings and the results of endocavitary electrophysiological investigation suggest the presence of nodoventricular and atrio-ventricular fibres. These two accessory pathways were latent in sinus rhythm but formed part of reentry loops. The reciprocating rhythms used the Kent bundle in the retrograde direction, and either the normal nodo-hisian or the Mahaim fibres in the anterograde direction. Simple echos ascending by the nodo-hisian pathway and descending by the nodo-ventricular pathway were also observed. The patient died of an unassociated cause and a pathological examination of the heart was performed. This confirmed the presence of a left posterior paraseptal Kent bundle and the presence of fibres relaying the inferior part of the atrioventricular node to the septal ventricular myocardium, this being made possible by a dehiscence of the central fibrous body.

Peripheral nerve biopsies from two patients with chronic sensorimotor neuropathy were studied. The first case was a non-Hodgkin malignant lymphoma and did not show any dysglobulinemia. The second case had a benign monoclonal gammopathy IgG, Lambda type. Direct immunofluorescence showed no deposits in the first case and slight deposits of anti IgG sera on a few myelinated fibers in the second case. There were numerous fibers showing uncompacted myelin lamellae, 7% in the first case and 4% in the second case. Some of these fibers had axons containing more tubules than filaments. The very few cases reported on neuropathies showing that uncompacted myelin lamellae were frequently associated with dysglobulinemic neuropathy. However, this ultrastructural abnormality of the myelin sheath can be observed without any dysglobulinemia.