I.V. LIGNOCAINE IN REFLEX AND ALLERGIC BRONCHOCONSTRICTION

The protection against bronchospasm afforded by infusions oflignocaine was tested in dogs anaesthetized with thiamylal bychallenge with aerosols of citric acid (CAA) or ascaris antigen(AAA). During the infusion of lignocaine, the response to CAAwas blocked or markedly attenuated, but AAA still elicited alarge increase in pulmonary resistance (R_L). In untreated dogs,CAA increased R_L from 0.14±0.05 (mean±SEM) kPalitre^–1 s to 1.09±0.18, whereas in dogs treatedwith lignocaine, R_L was 0.19±0.09 before challenge withCAA and 0.44±0.13 after challenge. AAA increased R_L.from 0.14±0.06 kPa litre¹ s to 3.01±0.65 in untreateddogs, and from 0.34±0.10 kPa litre^–1 to 1.85±0.69in dogs treated with lignocaine. Blood concentrations of lignocainewere 1.5±0.3 and 2.5±0.6µg ml^–1 duringchallenge with CAA and AAA, respectively. We conclude that lignocaine,at blood concentrations which will reduce the risk of cardiacarrhythmia, markedly reduces reflex bronchoconstriction, buthas relatively little effect on that initiated by allergic mediators.     

Antigenic variants of influenza A virus (PR8 strain). V. Virulence,antigenic potency,and cross-protection tests in mice of the original and second series

Two series of variants of influenza PR8-S virus have been described. While all retain the same degree of pathogenicity for mice and fertile eggs, there was a progressive loss in the ability of the variants to provoke antibody following vaccination or infection of mice and ferrets. The immunogenicity of the variants was, therefore, less than that of the original strain. Although little or no serological relationship could be demonstrated between some of the variants and the PR8-S virus a considerable degree of cross-immunity could be demonstrated in the cross-protection tests with these viruses if observations were based solely on death or survival of the mice. By employing the occurrence of lesions in the lung and the titer of virus in the lung 48 hours after challenge, the amount of cross-protection in mice could be related to the amount of serological cross-reaction. In general mice vaccinated with PR8-S virus were less resistant to infection with the variant viruses than mice vaccinated with variants and challenged with the PR8-S parent virus. The role of the immune environment of the host in the production of the variant influenza viruses with their serological differences, decreasing antigenicity, and persisting pathogenicity as well as the epidemiological implications of these findings with respect to epidemic influenza in man are discussed.     

Percutaneous Balloon Aortic Valvuloplasty: The State of the Art. A Review of Two Years Experience in Rouen

Since the first case performed by us in September 1985, percutaneous transluminal aortic valvuloplasty (PTAV) has been applied in Rouen in a broad clinical spectrum of patients with aortic stenosis. After our encouraging initial experience, there have been changes in our objectives and technique which have allowed us to proceed more quickly, with less discomfort to the patient, lower risk, and improved results. The development of a new device, a triple lumen-double size balloon catheter has been a major advance as well as the use of extra-stiff guidewires and arterial sheaths. Our series has grown to more than 300 patients, mostly elderly (mean age 73 ± 11, 25% at or above 80) and very ill (71% in NYHA functional class HI or IV). Indication for PTA V was either absolute contraindication to valve replacement (30%), increased surgical risk (31%), refusal of surgery (10%), or attempt to postpone surgery (29%). The largest balloon size used has been 20 mm or above (23 mm or even 25 mm) in 70% of the cases. The double-balloon technique has been used in only 5% of the cases. In our series, PTAV resulted in a decrease in transvalvular peak gradient from 71 ± 26 mm Hg to 28 ± 13 mm Hg and an increase in aortic valve area from 0.54 ± 0.18 cm² to 0.96 ± 0.33 cm². With gained experience and the use of larger balloon sizes, the results have clearly improved: in the last 100 patients a valve area to or above 1 an² has been obtained in 55% compared to 30% of the cases in our early experience. Patients less than 70 years old had the best results but the aortic stenosis was less severe before PTAV. The total procedural and post-PTA V mortality was 4% and involved primarily very old patients. The nonfatal complication rate remained low. Clinical information for 204 patients followed for 12 ± 5 months has been obtained and repeat catheterization has been done in 56 patients at an average of 4.5 months after PTA V. The data confirms that PTA V is feasible and can be accomplished with a relatively low risk in an elderly and ill population and in patients with contraindication to valve replacement or very high surgical risk. The procedure alters the natural history of the disease in these patients, improving both symptoms and survival. Indications in other categories of patients deserve further studies.     

Trisomy 3 in marginal zone B-cell lymphoma: a study based on cytogenetic analysis and fluorescence in situ hybridization

Trisomy 3 represents the most frequent and consistent chromosomal abnormality characterizing the recently defined entity marginal zone B-cell lymphoma (MZBCL). By cytogenetic analysis and/or fluorescence in situ hybridization (FISH) on interphase nuclei we found an increased copy number of chromosome 3 in 22/36 (61%) successfully analysed cases, including 8/12 cases with extranodal MZBCL, 8/13 cases with nodal MZBCL, and 6/11 patients with splenic MZBCL. Sensitivity of interphase cytogenetics was somewhat higher than that of conventional cytogenetic investigation. Structural chromosomal changes involving at least one chromosome 3 were seen in 11/20 cases with an increased copy number of chromosome 3: +del(3)(p13) was demonstrated in three cases, and was the sole chromosomal abnormality in one of them; +i(3)(q10) was seen in two other patients; and rearrangements involving various breakpoints on the long arm of chromosome 3 were found in the remaining cases. FISH on metaphase spreads confirmed these structural abnormalities and additionally showed two unexpected translocations involving chromosome 3. We conclude that: (1) trisomy 3 occurs in a high proportion of extranodal, nodal and splenic MZBCL; (2) FISH on interphase nuclei is an additional and sensitive tool in detecting an increased copy number of chromosome 3 in MZBCL; (3) additional structural abnormalities involving the long arm of chromosome 3 are frequent but non-recurrent and are perhaps secondary changes; and (4) abnormalities such as +del(3)(p13) and +i(3)(q10) suggest that genes located on the long arm of chromosome 3 are of particular importance in the pathogenesis of MZBCL.     

DIFFUSE IDIOPATHIC SKELETAL HYPEROSTOSIS (DISH) OF THE SPINE: A CAUSE OF BACK PAIN? A CONTROLLED STUDY

This is the first controlled study of the frequency of backpain in a European caucasian population with diffuse idiopathicskeletal hyperostosis (DISH). Elderly patients admitted to hospital for reasons other thanback pain were assessed for the presence of spinal DISH usingthe routine lateral chest radiograph films. A total of 106 probands(82 males, 24 females) with a mean age of 70 years fulfilledthe criteria for DISH as defined previously. One hundred andseventyeight patients (117 males, 61 females) not meeting thesecriteria were used as controls. The prevalence of back painwas assessed by a blinded interviewer using a structured questionnaire.Our primary hymthesis was that spinal DISH positive probandshad not had back pain more often than controls. The controlledstudy showed no statistically significant difference in painfrequency between spinal DISH positive probands and controlsat any spinal level. We conclude that back pain does not occur more often in radiographicallydefined DISH positive probands than in controls. The radiologicalfinding of spinal DISH, as far as it does not lead to stenosisof the spinal canal or dysphagia, thus seems to be a findingwithout clinical relevance. KEY WORDS: Spine, Radiographs, Pain, Osteoarthritis, Forestier's disease, Ankylosing vertebral hyperostosis     

Ablation of Atrial Flutter in a Patient with a Tricuspid Valve Replacement after Endocarditis

Myocardial scars from heart surgery are a source of tachycardia, eventually causing late morbidity and sudden death. In general, catheter ablation has been shown to be an effective therapy for various rhythm disorders, but it has been rarely described after atrioventricular valve replacement. We report on a 45-year-old man who developed atrial flutter after implantation of a tricuspid valve bioprosthesis. An electrophysiological investigation revealed typical type-I counterclockwise atrial flutter that was successfully terminated by catheter ablation. A sinus rhythm was restored and remained stable during the course of treatment; the valvular function was not diminished. It is demonstrated that safe mapping and ablation of typical atrial flutter is possible after a tricuspid valve replacement.     

Chemical modification of ribonuclease A with 4-arsono-2-nitrofluorobenzene

4-Arsono-2-nitrofluorobenzene reacts selectively at the anion binding site of bovine pancreatic ribonuclease A. The major derivative is the inactive 41-(4-arsono-2-nitrophenyl) ribonuclease A (45% yield). Additional products are 1-α-(4-arsono-2-nitrophenyl) ribonuclease A (11% yield) which is enzymatically active and the disubstituted, inactive 1,41-bis-(4-arsono-2-nitrophenyl) ribonuclease A (25% yield). 2′ (3′)-O-Bromoacetyluridine reacts with 41-(4-arsono-2-nitrophenyl) ribonuclease A exclusively at the histidine-12 residue at a rate which is approximately one-fourth the rate observed with the unmodified enzyme. Saturation kinetics are observed and the dissociation constant for the protein-inhibitor complex is 0.096 ± 0.023 M. The first-order unimolecular decomposition constant for complex breakdown is 8.9 ± 2.9 times 10^-4s^-1. 2′-Bromoacetamido-2′-deoxyuridine reacts with 41-(4-arsono-2-nitrophenyl) ribonuclease A 25 times more slowly than 2′(3′)-O-bromoacetyluridine. Bromo-acetate reacts with 41-(4-arsono-2-nitrophenyl) ribonuclease A predominantly at the histidine-119 residue at a rate 45 times less than that found for the unmodified enzyme. The results of the alkylation studies imply that the dianionic arsonate does not occupy the phosphate binding site in the enzyme but is sufficiently proximate to account for a decrease in bromoacetate binding as well as a reduction in the nucleophilic reactivity of histidine-12 and -119. All these effects may be accounted for in terms of a local electrostatic perturbation of the active site region by the arsononitrophenyl group.