Biomedical subjects
Publications and source records attributed to J Duc.
The patient with nonsustained ventricular tachycardia represents a common management problem for the cardiologist. The challenges posed by this type of arrhythmia differs from those posed by other arrhythmias, because most instances of nonsustained ventricular tachycardia do not cause symptoms. This article reviews common situations in which nonsustained ventricular tachycardia occurs and their appropriate management.
BACKGROUND: Despite advances in medical therapy, congestive heart failure remains a major cause of death in the developed world. A disproportionate number of the deaths of patients with heart failure are sudden and presumed to be arrhythmic. Heart failure in humans and in animal models is associated with prolongation of the action potential duration (APD), the result of downregulation of K+ currents-prominently, the Ca2+-independent transient outward current (Ito). The mechanism for the reduction of Ito in heart failure is unknown. The K+ channel alpha-subunit Kv4.3, a homolog of the Drosophila Shal family, is most likely to encode all or part of the native cardiac Ito in humans. METHODS AND RESULTS: We used ribonuclease protection assays and whole-cell electrophysiological recording to study changes in the level of Kv4.3 mRNA and Ito in human tissues and isolated ventricular myocytes, respectively. We found that the level of Kv4.3 mRNA decreased by 30% in failing hearts compared with nonfailing controls. Furthermore, this reduction correlated with the reduction in peak Ito density measured in ventricular myocytes isolated from adjacent regions of the heart. There was no significant change in the steady-state level of any other mRNA studied (HERG, Kv1.4, Kir2.1, Kvss1.3, and the alpha1C subunit of the Ca2+ channel). mRNAs encoding Kv1.2, Kv1.5, and Kv2.1 were found in low abundance in human ventricle. CONCLUSIONS: These data provide further support for the hypothesis that Kv4.3 encodes all or part of the native cardiac Ito in humans and that part of the downregulation of this current in heart failure may be transcriptionally regulated.
Little is known about referral patterns to the allergist for hay fever. In a system with open access to the specialist, we investigated the reasons for consulting an allergist in 126 patients who completed a questionnaire on their first visit. Both sexes were equally represented, the median age was 29 years, the duration of the disease and the duration of seasonal symptoms were 9 years and 10 weeks (median), respectively, and 54% of patients reported a history suggestive of asthma. The symptoms were highly variable; on average, 5.6 on a 10-cm visual analog scale. Most of the patients (94%) had been treated for hay fever before. Only 30% were referred by another physician, the rest being self-referred. The reasons for referral were investigated. The overall motivation to consult was related to symptom severity in 63% of the patients; 37% consulted for other reasons, including an expectation of greater "know-how" on the part of the allergist concerning specific diagnosis, treatment, and advice or counseling. The stimulus triggering the consultation was clearly not related to symptoms or disease in 25% of the cases. We conclude from these data that many patients are clearly interested in benefiting from the professional skill of a fully trained allergist.
Studies are described that allow for the in vivo detection of helix-loop-helix (HLH) protein-protein interaction. The assay used requires HLH protein-protein interaction to reconstitute a functional GAL4 transcriptional activator, which in turn activates a reporter gene placed downstream of GAL4 DNA binding sequences. Using this assay, we are able to detect intracellular heterodimerization but not homodimerization of the MyoD, E12, and Id gene products. In addition, using this system we are unable to detect stable heterodimerization between MyoD and c-Jun. We also show that expression of activated rasH gene product does not inhibit and may stabilize HLH protein-protein interaction. This system may be of general utility in studying the modulation of transcription factor interactions.
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In giant cell arteritis, a common vasculitic disease of elderly patients, the biopsy of the temporal artery has been considered an important part of the diagnostic procedure. The necessity to perform this biopsy has recently been questioned. It has also been proposed to substantially reduce the high doses of steroids usually given.
A new assay for the determination of specific IgE in serum, using a monoclonal anti-IgE (Stallerzym), was evaluated. Compared with the results of skin prick tests, the Stallerzym was found to be 93% specific and 73% sensitive. In sera from patients selected to be either clearly allergic or not allergic (as defined by the concordant results of case history, skin prick test, and provocation test), Stallerzym proved to be as accurate and reliable as the Phadezym IgE RAST currently available.
Phadiatop (Pharmacia) is a new in vitro screening test for respiratory allergy which detects in serum the presence of specific IgE to a mixture of common inhalant allergens; results are either positive or negative. Among 100 patients suffering from rhinitis and/or asthma, investigated with 15 skin prick tests (SPT) and RAST for frequent allergens, the Phadiatop was positive in 63: all 63 had at least one positive SPT and RAST (specificity: 100%). Conversely, ther were 67 patients who had a positive RAST for at least one allergen: among these 67 the total IgE concentration in serum was high (greater than 100 kU/l) in 43 (64%) and the Phadiatop was positive in 63 (94%). Phadiatop was negative in serum obtained from 10 cord bloods and 10 non-allergic subjects (disease-free, 15 negative SPT and RAST). Results of the radio-immunoassay originally proposed by the manufacturer were similar to those obtained with a modified enzymo assay using a fluorometric substrate. In the prediction of respiratory allergy, Phadiatop was found to be specific and more accurate than the determination of total IgE in serum.
We study whether immunoelectrophoresis (IE) could be replaced by immunofixation (IF) for the routine diagnosis of monoclonal gammopathies and/or by a quantitative measurement of kappa-resp. lambda-Ig levels in serum. The values of these measurements, together with the level of each Ig class, were used to calculate two ratios. IF, IE and calculation of both ratios were simultaneously applied to 153 serum samples. A monoclonal gammopathy (MGP) was found with all three methods in 51 cases and by none of them in another 51 cases. The first two techniques were positive and the third one negative in 16 cases. In 15 cases, IF showed the presence of a MGP, which was not or incompletely identified with IE, these results being associated with normal (7x) or abnormal ratios (8x). Nineteen cases with normal IF and IE had one or two abnormal ratios. After comparison with clinical data and outcome, we conclude that IF revealed 15 cases of MGP, which were not or only partially shown by IE. IE did not show any case of MGP not detected by IF. One of the ratios appeared as an interesting adjunct to the diagnostic procedure, but insufficient to be used as a single test. The other appeared to be of no diagnostic help. We conclude that immunofixation is the test of choice in the routine diagnosis of monoclonal gammopathies.
Antinuclear antibodies (ANA) are found in the majority of patients with systemic lupus erythematosus (SLE). We report here the only documented case, out of a series of 38 patients, in which SLE was diagnosed in spite of the fact that we failed to demonstrate any type of autoantibodies. A 25-year-old black woman presented with 6 of the 11 criteria of the American Rheumatism Association for classification of SLE, between August 1984 and April 1985, i.e. malar rash, photosensitivity, arthritis, pleurisy and pericarditis, renal insufficiency and nephrotic syndrome, anemia and leukopenia. Renal biopsy revealed mesangial glomerulonephritis, tubulonephritis and many tubuloreticular inclusions in the capillary endothelium highly suggestive of SLE. Four ANA determinations were performed during the 8 months of observation which were all negative, as were all other antibodies (anti-nDNA, -Sm, -RPN, -Ro, -La). The outcome was very favourable under prednisone and cyclophosphamide. In the rare cases of ANA negative SLE (5-10%) photosensitive dermatitis is the prominent feature and renal or central nervous system involvement is less frequent. Those patients usually have other types of autoantibodies (especially anticytoplasmic) which was not the case in our patient. This indicates that the absence of autoantibodies does not rule out SLE.
In a prospective study of 100 adults, we determined the frequency of hypersensitivity to allergens most often diagnosed in patients suffering from rhinitis and bronchial asthma. Skin-prick tests and RAST for 15 allergens were performed in all patients. The most frequent allergen detected by skin-prick test was the extract "total house dust" (50%) but the corresponding RAST was rarely positive (16%); then came grass pollens (46%), house dust mites (D. pteronyssinus, 38%) and animal danders (cat 33%). On the other hand, a positive skin test with the two moulds chosen was rare (Alternaria tenuis 5%, Cladosporium herbarum 4%). For all the allergens investigated, the correlation between positive skin test and positive RAST was proportional to the intensity of the skin reaction (94% for the skin tests +, 40% for the skin tests ++). 35% of the patients with at least a positive skin test and a RAST for one of the allergens tested had in fact a total IgE concentration not suggestive of atopy (less than 100 kU/1). The results indicate that, with the exception of the 2 moulds chosen, the frequency of allergens diagnosed in Switzerland is very similar to what has been found in other countries with different climates.
To enable shorter and more convenient testing, the Phadezym RAST and Phadezym IgE PRIST procedures for the determination of specific and total IgE were modified in three ways: (i) allergen-coupled paper discs were tested in microtitre wells; (ii) the incubation times were reduced to 1 hr with serum and 2 hr with the anti-IgE by shaking the plates at room temperature; and (iii) the fluorogenic substrate used reduced the development time to 15 min. Determination of IgE antibody specific for fifteen inhalation allergens by the modified fluorescence test (FEIA) and by the conventional Phadezym RAST (EIA) was performed on the serum of thirty-two patients suffering from asthma/rhinitis: correlation studies for these sera showed that 96.1% of the results fell in the same class. In these patients, both FEIA and EIA detected the same proportion of skin-prick tests (SPT) positive results (67%). With the FEIA, 4/165 (2.4%) class 1 results were found in eleven non-atopic subjects (symptom free, fifteen negative SPT, total IgE lower than 80 kU/l), compared to 1/165 (0.6%) with the EIA. In twenty cord sera, both FEIA and EIA found 4/300 (1.3%) class 1 results. For the determination of total serum IgE, the microtitre FEIA showed a detection limit of 0.5 kU/l and an excellent correlation with Phadezym IgE PRIST (n = 66 serum, r = 0.99). These data indicate that the adaptation of Phadezym RAST and Phadezym IgE PRIST to microtitre plates and fluorescence technology has resulted in a time-saving and easy to perform within-day assay which provided results as reproducible, sensitive and specific as those of the conventional procedure.
We report here the case of a patient suffering from idiopathic cold urticaria who did not respond to H1 antihistamine but who responded dramatically to the combination of H1 and H2 antagonists. Under H1 treatment, the urticaria was florid and the ice cube test clearly positive. After the addition of an H2 antihistamine, all the symptoms disappeared and the ice cube test became negative. The different therapeutic schedules proposed thereafter, showed that only the combination therapy was effective H1 antihistamine alone or H2 antihistamine alone being unable to modify the course of the disease.
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We evaluated the efficacy of flecainide acetate (given intravenously to a maximal dose of 2 mg kg-1 and then orally in a dose of 100 mg b.d. or 100 mg t.d.s.) in the conversion to sinus rhythm of 50 patients exhibiting supraventricular arrhythmias (39 with atrial fibrillation, 6 with atrial flutter, 4 with supraventricular tachycardia and one with supraventricular tachycardia in association with the Wolff-Parkinson-White syndrome). Conversion was achieved in 36 patients (72%) (29 cases with atrial fibrillation, 4 cases with supraventricular tachycardia, 2 cases with atrial flutter and one case with Wolff-Parkinson-White syndrome), over a mean period of 7.4 +/- 9 h. The patients in which conversion was achieved had arrhythmias which had been in existence for a shorter time (5.3 +/- 9.8 days) than those in which conversion was not achieved (16.7 +/- 26.2 days) (P less than 0.01). The mean dosage of flecainide used to achieve conversion was 2.5 +/- 2.36 mg kg-1. Flecainide appears to be an effective agent for the conversion to sinus rhythm of atrial fibrillation and supraventricular tachycardias. Its efficacy in cases of atrial flutter has not yet been demonstrated.
The primary mesothelioma of the spermatic cord is a very rate tumor, histologically benign. Its evolution, because of the possibility of recurrence, is uncertain. We have found only six cases in the literature. Our observation relate the very quick apparition by a young Italian, 19 years old, of a left hydrocele under tension ascending into the inguinal fold. At operation, we discovered a mesothelioma in the spermatic cord and in the tunica vaginalis, covering both testicle and epididymis. Ten months after a left enlarged hemicastration, without scrotectomy, no recurrence has been reported.
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