Bronchial hyperresponsiveness in asthmatic adults--a long-term correlation study

BACKGROUND: Bronchial hyper responsiveness (BHR), is a risk factor for asthma. It is a state in which excessive narrowing of the airways occurs in response to varying stimuli. BHR seems to be due to the interaction of multiple factors and its relation to asthma is complex. Asthma without BHR is unusual. Indeed, patients who show a higher degree of symptoms have higher levels of BHR. To date no study has investigated the correlation between BHR in mild persistent asthmatic adults and a long-term therapy of five years. The aim of this study is to evaluate (i) the role of BHR in the clinical evaluation of asthma, (ii) the correlation between BHR and therapy in asthma. METHODS: Seventy patients (were recruited 34 men, age 21-55 years) suffering from: (a) mild seasonal allergic asthma (17/70), (b) mild perennial allergic asthma (34/70) and (c) mild non-allergic [corrected] asthma (19/70). 14 patients from group (a) and 28 patients from group (b) were treated with inhaled beta2-agonists, beclomethasone, disodiumcromoglycate and immunotherapy. 14 patients from group (c) underwent the same treatment regimen without immunotherapy. All patients were evaluated with a metacholine challenge test. The BHR (PD20 FEV1) was calculated at baseline and after a two-year symptom free period. Fifteen pts were followed-up for five years with an evaluation every year. All other patients did not receive any treatment. The results (expressed as mean +/- SE) were evaluated. RESULTS: Fourteen pts and three pts from group (a) showed a mean BHR value of 984 +/- 3.66 and 674 +/- 2.06; 343 +/- 7.60 and 208 +/- 7.70 respectively. The results were not statistically significant Twenty-eight and six pts from group (b) showed mean values of 685 +/- 1.45 and 1405 +/- 5.65; 856 +/- 7.09 and 435 +/- 2.20 with apparent improvement for the former. Five pts and fourteen pts from group (c) showed mean value of 2682 +/- 7.85 and 2099 +/- 6.82; 816 +/- 2.53 and 877 +/- 4.78 respectively. As for the 5-yr follow up ten pts and five pts from group (b) showed mean values of 705 +/- 1.6 and 861 +/- 7.15; 911 +/- 7.3 and 457 +/- 2.3 respectively. CONCLUSIONS: Although the clinical picture improved with therapy, BHR was not significantly affected in any patient group, at two and five years of follow-up. Furthermore, no correlation was found between the clinical picture and PD20 FEV1 values. BHR seems to result from the interaction of multiple factors that are worth further investigating. BHR cannot be considered a marker of disease activity in asthma and therefore is not a useful tool for guiding asthma therapy.     

Oral solution of levodopa ethylester for treatment of response fluctuations in patients with advanced Parkinson's disease.

Levodopa ethylester (LDEE), a highly soluble prodrug of levodopa, may overcome the impaired absorption of regular levodopa, due mainly to a combination of levodopa's poor solubility and delayed gastric emptying. We conducted a double-blind, levodopa-controlled, multicenter study of oral LDEE solution compared with standard levodopa-carbidopa (LD-CD) tablets. Sixty-two patients with Parkinson's disease who had "delayed on" and "no-on" subtypes of response fluctuations were randomly assigned for treatment with LDEE-CD or LD-CD 250/25 mg for 4 weeks (phase A). Only the first morning and first post-lunch dose of LD were replaced. This was followed by a 2-week extension with a supplementation of carbidopa (25 mg) to each replaced dose (phase B). Patients filled home diaries 2 weeks before and during the trial period in which times of turning on and off for the two doses were reported. In phase A, mean latency to turning on was reduced by 21% (morning dose) and 17% (post-lunch dose) in the LDEE-CD group. Percentage of no-on episodes after the post-lunch dose was decreased by 21% in the LDEE-CD group but increased by 36% in the LD-CD group (P < 0.01). In phase B, LDEE-CD decreased latencies to on after the morning and post-lunch doses and no-on episodes after the post-lunch dose. The beneficial effects of LDEE were supported by the pharmacokinetic data. Results indicate that LDEE solution is beneficial in ameliorating delayed on and no-on response fluctuations. This effect of LDEE is due to more rapid levodopa absorption.     

The rare Lu:-6 phenotype in Israel and the clinical significance of anti-Lu6

BACKGROUND: Lu6 is a high-incidence antigen of the Lutheran blood group. Examples of anti-Lu6 are rare and are of uncertain clinical significance. CASE REPORT: Three patients were encountered in whom anti-Lu6 was detected on pretransfusion screening. The patients were all Iranian Jews and were not known to be related. In vitro studies to ascertain the potential clinical significance of the antibody using the monocyte monolayer assay (MMA) were negative in two patients. The third patient received a two-unit transfusion of incompatible Lu6 RBCs with no signs of hemolysis. However, after the transfusion, the MMA and a chemiluminescence test were positive, whereas a chromium survival study was normal. Thus, the antibody may have changed in its clinical significance. CONCLUSION: Although anti-Lu6 does not appear to be a clinically significant RBC antibody in all circumstances, transfusion of Lu6 RBCs in patients with anti-Lu6 should be performed cautiously.     

Unreliability of Disc Diffusion Test for Screening for Reduced Penicillin Susceptibility in Neisseria meningitidis

The 2-U penicillin and 1-μg oxacillin discs proposed for screening meningococci for susceptibility to penicillin were evaluated by using MICs measured by the E test. The discs yielded unacceptably high frequencies of misclassification of susceptibility category and should be abandoned in favor of MIC estimations. An agreed breakpoint for reduced penicillin susceptibility in meningococci is needed for the E test.Penicillin susceptibility testing of meningococci has long been a difficult area, and authorities recommend MIC determination as the method of first choice (10). Nevertheless, the traditional disc diffusion test has remained in use as a practical and relatively inexpensive method. Campos and coworkers have argued that problems of interpretation encountered with regular 10-U penicillin discs may be reduced by using 2-U penicillin or 1-μg oxacillin discs (2, 3). These discs were introduced in Israel in 1992 and 1995, respectively, and since introduction of regular MIC measurements obtained by using the E test in 1995, sufficient strains have been examined to permit an adequate analysis of their value.The E test has been shown in several studies to be an acceptably accurate method for determining MICs for Neisseria meningitidis (1, 4–6). Despite the E test’s high cost, the relatively small number of cases of meningococcal disease encountered in Israel each year makes it an attractively practical option for MIC estimations.The present study was conducted from January 1995 through July 1997 with 133 consecutive clinical isolates of N. meningitidis submitted to the Israel National Center for Meningococci at Tel Hashomer. Laboratories isolating N. meningitidis from patients are required by law to submit the isolates to the Center for characterization. Internal audit has revealed that 95% of these N. meningitidis isolates are received at the Center, where they are serogrouped and serotyped, their antibiotic susceptibilities are tested, and they are stored at −70°C.Disc diffusion testing was performed by using 2-U penicillin and 1-μg oxacillin discs (Sanofi Diagnostics Pasteur, Marnes La Coquette, France) according to National Committee for Clinical Laboratory Standards recommendations (7). Blood (5%) was added to the Mueller-Hinton agar. Data on record at the Israel National Center for Meningococci from previous years, obtained with 10-U penicillin discs, showed that Mueller-Hinton agar without blood (MH) gave significantly larger zone diameters than Mueller-Hinton agar with 5% blood (MHB). A total of 278 strains examined with MH gave an average inhibition zone of 42.4 mm (median, 40 mm; standard deviation, 7.4), while 315 strains tested on MHB gave a mean of 35.6 mm (median, 35 mm; standard deviation, 4.7) (P < 0.0001 by the t test). Others have also found unsupplemented Mueller-Hinton media wanting, so various additions have been used, including blood (4, 8, 9). The definitions of reduced susceptibility used for the analyses were those proposed by Campos et al. (3): inhibition zone diameters of ≤26 mm around the 2-U penicillin disc and ≤10 mm around the 1-μg oxacillin disc.The penicillin E test (AB Biodisk, Solna, Sweden) was performed according to the manufacturer’s instructions, on MHB. With few exceptions, tests were performed by the same individual. The conventional penicillin MIC of ≥0.1 μg/ml was used to denote strains with reduced susceptibility. This has limitations in respect to the E test, which are elaborated below.Figures ​Figures11 and ​and22 indicate the relationships between disc diffusion zone diameters and MICs. The data show clearly that the 1-μg oxacillin disc was a poor predictor of penicillin susceptibility in this in-use evaluation. Four of 16 strains (25.0%) for which penicillin MICs were ≥0.125 μg/ml were misclassified as susceptible by the disc, whereas 59 of 112 sensitive strains (52.7%) were misclassified as having reduced susceptibility. The 2-U penicillin disc showed less “false susceptibility”: 1 of 18 (5.6%) strains with reduced susceptibility were misclassified as susceptible, but 34 of 115 (29.6%) susceptible isolates were judged resistant. Open in a separate windowFIG. 1Zone diameter measurements obtained by using 1-μg oxacillin discs versus MICs of 128 strains of N. meningitidis.Open in a separate windowFIG. 2Zone diameter measurements obtained by using 2-U penicillin discs versus MICs of 133 strains of N. meningitidis.These data were based on the conventional breakpoint, as mentioned above. The scale of MICs provided by the E test includes a value of 0.094 μg/ml. It would appear reasonable to take MICs at this value as representing organisms with reduced penicillin susceptibility, since it is very close to the 0.1-μg/ml cutoff. Citing pharmacokinetic considerations, Hughes et al. (4) defined reduced penicillin susceptibility as a MIC of >0.06 to 1 μg/ml. With 0.094 μg/ml as the breakpoint, the oxacillin disc method would have resulted in the misclassification of 8 of 27 of the less susceptible strains as susceptible (29.6%). Similarly, the rate of misclassification would also have been appreciably higher for the 2-U penicillin disc (4 of 29 isolates [13.8%]).Other investigators have also found the oxacillin disc to be grossly unreliable, with the 2-U penicillin disc being more useful (9), although for the organisms examined, different zone diameter cutoff points were suggested. Our data showed clearly that, in our hands, recommended methods for disc diffusion determination of penicillin susceptibility resulted in unacceptably high frequencies of misclassification of the susceptibility category and should therefore be abandoned in favor of MIC estimations. For some laboratories, the E test will be a practical method. As shown in our data, an appreciable number of strains straddle the 0.094- to 0.125-μg/ml MIC range, suggesting that the question of an agreed E-test breakpoint for reduced penicillin susceptibility also needs to be further addressed if data from different centers are to be compared.(This study was presented in part at the 37th Interscience Conference on Antimicrobial Agents and Chemotherapy, Toronto, Canada, 28 September to 1 October 1997.)     

Cryohemolysis for the detection of hereditary spherocytosis: Correlation studies with osmotic fragility and autohemolysis

Laboratory methods aimed to assess the presence of spheroidal cells such as osmotic fragility, autohemolysis, and glycerol lysis time are very elaborate, time consuming, and often give inconclusive results. We have developed a diagnostic test based on a unique sensitivity of HS cells to hypertonic cryohemolysis and analyzed blood samples of 55 HS patients. The patients were divided into two subgroups, clinically affected probands and their relatives. To get quantitative comparisons with the classic methods, the cryohemolysis results were compared to two parameters of the osmotic fragility test: the salt concentration that causes 50% hemolysis, and the percent lysis at a constant salt concentration. Autohemolysis results were also compared. To evaluate which of these tests has the best analytical power, we calculated the mean results and 2 SDs of each parameter in a control group, and then looked to see which of them was best in identifying the patients. The cryohemolysis test was the single parameter that identified all cases including asymptomatic carriers of the disease. The ability of this test to identify the less severe cases probably reflects the dependency of the cryohemolysis on factors that are more related to the primary membrane molecular defects and less by the surface area to volume ratio. Am. J. Hematol. 58:206–212, 1998. © 1998 Wiley-Liss, Inc.     

A comparison of trends in incidence and mortality rates of breast cancer, incidence to mortality ratio and stage at diagnosis between Arab and Jewish women in Israel, 1979-2002.

In Israel, breast cancer is the most common malignancy in women, but there are large intra-population differences. The aim of this study was to compare the incidence and mortality, incidence to mortality rate ratio and stage at diagnosis of breast cancer between Arab and Jewish women in Israel. Data on all cases of breast cancer, stage at diagnosis and mortality were obtained from the National Cancer Registry and the Central Bureau of Statistics. Trends in age-specific and age-adjusted incidence and mortality rates, rate ratios and stage at diagnosis were examined for Arab and Jewish women during 1979-2002. Five-year survival rates for 1995-1999 were compared by stage. Among Arab women, age-adjusted incidence rates increased by 202.1%, from 14.1 per 100,000 in 1979-1981 to 42.6 in 2000-2002. Among Jewish women, the rates increased by 45.7%, from 71.1 per 100,000 women in 1979-1981 to 103.6 in 2000-2002. Incidence to mortality rate ratio increased for both population groups, but it is still lower among Arab women. In every age group, Arab women were more likely to be diagnosed at a more advanced stage of the disease. The rise in breast cancer incidence and mortality rates and the later stage of diagnosis among Arab women emphasize the urgent need for increasing early detection of breast cancer in the Arab population by improving rates of compliance with screening mammography.     

The hypereosinophilic syndrome associated with CD4+CD3- helper type 2 (Th2) lymphocytes.

We describe herein the clinical and laboratory manifestations of a unique group of patients (pts) presenting with hypereosinophilic syndrome (HES) who were treated in our medical centers for 4-13 years. Skin biopsies, flow cytometry of peripheral blood mononuclear cells (PBMC), assays for cytokines and immunoglobulin (Ig) production in vitro, and Southern blots of T-cell receptor (TCR) genes were performed. All four pts had a persistent hypereosinophilia (> 1.9 x 10(9)/L) and chronic skin rash. Three of four had elevated IgE, thrombotic manifestations and lung involvement (asthma and/or infiltrates), and one had deforming sero-negative arthritis of the hands. 66-95% of their peripheral T-cells expressed CD4 but not CD3 or TCR molecules on the cell surface membrane. Activated CD4+CD3- cells secreted interleukin (IL)-4 and/or 5, and were required for maximal IgE secretion by autologous B-cells. Two pts had evidence of rearrangement of TCR genes of the CD4+CD3- cells, one of whom died of anaplastic lymphoma. In conclusion, HES with CD4+CD3- lymphocytosis may be associated with high serum IgE, dermatological, pulmonary, thrombotic and rheumatic manifestations which may be due to Th2 effects of CD4+CD3- cells migrating to end organs. Fatal systemic lymphoid malignancy may also develop in some pts with monoclonal expansion of the CD4+CD3- T-cells.