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M A Behr

Publications and source records attributed to M A Behr.

29 records · Page 2Linked to original sources

A historical and molecular phylogeny of BCG strains.

Bacillus Calmette-Guérin (BCG) is the name given to a family of vaccines derived in 1921 by the in-vitro attenuation of Mycobacterium bovis. Subsequently, BCG seed lots were distributed globally, and both phenotypic and genotypic differences between strains have been described. As a step to understanding BCG diversity, we have reviewed the English and French historical record on 13 strains and DNA was extracted from these strains for restriction-fragment-length-polymorphism study. The written record suggests "early strains" obtained from the Pasteur Institute between 1924 and 1926 and "later strains" obtained after 1931. Molecular typing resulted in 3 clades, based on variability in IS6110-typing and the presence of mpt64 gene. With two exceptions, these clades correspond with strains obtained in 1924-26 (IS6110-2/mpt64+), 1926-31 (IS6110-1/mpt64+), and 1931 or later (IS6110-1/mpt64-) This analysis demonstrates that BCG has undergone genetic changes since 1921, consistent with ongoing in-vitro evolution.

BCG Vaccine↗

Transmission of Mycobacterium tuberculosis from patients smear-negative for acid-fast bacilli.

BACKGROUND: The microscopic examination of sputum for acid-fast bacilli, is a simple and rapid test that is used to provide a presumptive diagnosis of infectious tuberculosis. While patients with tuberculosis with sputum smears negative for acid-fast bacilli are less infectious than those with positive smears, both theoretical and empirical evidence suggest that they can still transmit Mycobacterium tuberculosis. We aimed to estimate the risk of transmission from smear-negative individuals. METHODS: As part of an ongoing study of the molecular epidemiology of tuberculosis in San Francisco, patients with tuberculosis with mycobacterial isolates with the same DNA fingerprint were assigned to clusters that were assumed to have involved recent transmission. Secondary cases with tuberculosis, whose mycobacterial isolates had the same DNA, were linked to their presumed source case to estimate transmission from smear-negative patients. Sensitivity analyses were done to assess potential bias due to misclassification of source cases, unidentified source cases, and HIV-1 co-infection. FINDINGS: 1574 patients with culture-positive tuberculosis were reported and DNA fingerprints were available for 1359 (86%) of these patients. Of the 71 clusters of patients infected with strains that had matching fingerprints, 28 (39% [95% CI 28-52]) had a smear-negative putative source. There were 183 secondary cases in these 71 clusters, of whom a minimum of 32 were attributed to infection by smear-negative patients (17% [12-24]). The relative transmission rate of smear-negative compared with smear-positive patients was calculated as 0.22 (95% CI 0.16-0.32). Sensitivity analyses and stratification for HIV-1 status had no impact on these estimates. INTERPRETATION: In San Francisco, the acid-fast-bacilli smear identifies the most infectious patients, but patients with smear-negative culture-positive tuberculosis appear responsible for about 17% of tuberculosis transmission.

AIDS-Related Opportunistic Infections↗

Sauna-induced myocardial ischemia in patients with coronary artery disease.

PURPOSE: Sauna bathing is a popular recreational activity that is generally considered to be safe. However, there have been case reports of adverse cardiac events. We sought to determine whether sauna use caused myocardial ischemia in patients with coronary artery disease. METHODS: Sixteen patients with proven coronary artery disease were submitted to three conditions (rest, exercise, and sauna bathing) with continuous electrocardiographic (ECG) monitoring and regular blood pressure measurements. During each condition, patients were injected with Tc-99 sestamibi followed by nuclear scintigraphic imaging. Perfusion defect scores were calculated in 15 patients. RESULTS: Sauna bathing was well tolerated. There was a mean (+/- SD) increase in heart rate of 32% +/- 20% in the sauna (resting mean heart rate = 60 +/- 9 beats per minute vs sauna mean heart rate = 79 +/- 11 beats per minute, P <0.001) and a 13% +/- 6% drop in systolic blood pressure (resting mean systolic blood pressure = 142 +/- 14 mm Hg vs sauna mean systolic blood pressure = 123 +/- 15 mm Hg, P <0.001). There were no arrhythmias or ECG changes in the sauna. Compared with rest, there was significant ischemia during sauna bathing (average perfusion defect score at rest = -0.44 vs average sauna score = -0.93, P <0.001). The perfusion defect score in the sauna was worse than the resting score in 14 of the 15 patients. Sauna-associated perfusion defect scores were highly correlated with exercise-induced scores (R2 = 0.65, P <0.001). CONCLUSION: In patients with stable coronary artery disease, sauna use is clinically well tolerated but is associated with scintigraphically demonstrated myocardial ischemia.

Aged↗

Predictive value of contact investigation for identifying recent transmission of Mycobacterium tuberculosis.

Contact tracing, the evaluation of persons who have been in contact with patients having tuberculosis, is an important component of tuberculosis control. We used DNA fingerprinting to test the assumption that tuberculosis in contacts to active cases represents transmission from that person. Cases of tuberculosis in San Francisco between 1991 and 1996 with positive cultures who had been previously identified as contacts ("contact cases") to active cases ("index cases") were studied. Of 11,211 contacts evaluated, there were 66 pairs of culture-positive index and contact cases. DNA fingerprints were available for both members of these pairs in 54 instances (82%). The index and contact cases were infected with the same strain of Mycobacterium tuberculosis in 38 instances (70%; 95% CI: 56 to 82%); 16 pairs (30%) were infected with unrelated strains. Unrelated infections were more common among foreign-born (risk ratio [RR] = 5.22, p < 0.001), particularly Asian (RR = 3.89, p = 0.002) contacts. Contact investigation is an imperfect method for detecting transmission of M. tuberculosis, particularly in foreign-born persons. However, because such investigations target a group with a high prevalence of tuberculosis and tuberculous infection, these efforts remain an important activity in the control of tuberculosis.

Adult↗

Molecular fingerprinting of Mycobacterium tuberculosis: how can it help the clinician?

In just a few years, molecular fingerprinting of Mycobacterium tuberculosis has provided clinicians with significant insight into the epidemiology of tuberculosis. This methodology has allowed for a new understanding of the extent of new transmission of tuberculosis among residents of various communities and within institutions. It has also allowed for differentiation between episodes of reinfection and relapse, a task hitherto almost impossible to accomplish. In addition, molecular fingerprinting has allowed assessment of situations where laboratory cross-contamination is suspected. Thus, this technology has in many ways made clinicians reexamine many of their long-held beliefs regarding tuberculosis. In this report, Drs. Behr and Small provide a lucid description of molecular fingerprinting of M. tuberculosis, its current uses, and its future potential value.

DNA Fingerprinting↗

Fever duration in hospitalized acute pyelonephritis patients.

PURPOSE: To study persistence of fever in treated pyelonephritis with respect to guidelines recommending investigation and modification of therapy after 2 to 3 days of fever. PATIENTS AND METHODS: A retrospective chart review was made of 70 patients hospitalized for febrile pyelonephritis at a community hospital in Canada. RESULTS: Median duration of fever was 34 hours; persistence of fever at 48 and 72 hours was 26% and 13%, respectively. No patients had complications such as intrarenal or perirenal abscess. Prolonged fever was independently associated with increasing baseline creatinine (P = 0.0001), younger age (P = 0.027), and increasing total leukocyte count (P = 0.026). Results of ultrasonography and intravenous urograms were not predictors of fever duration. CONCLUSION: Fever in treated pyelonephritis can take 4 days to resolve, and routine urologic investigation after 2 to 3 days of fever may be unwarranted.

Acute Disease↗

A medium for the continuous cultivation of bloodstream forms of Trypanosoma lewisi at 37 C.

Trypanosoma lewisi has been maintained continuously at 37 C for more than 2 yr in Iscove's modified Dulbecco's medium with 10% fetal calf serum and a feeder layer of rat fibroblasts. In this medium the continuously reproducing hematozoic culture forms resemble bloodstream forms of T. lewisi in that they appear morphologically similar in Giemsa-stained preparations examined by light microscopy and have a surface coat that is absent in culture forms grown at ambient temperatures, when examined by electron microscopy. To determine whether these hematozoic culture forms also are similar functionally to bloodstream forms, comparative tests of the 2 forms were made of infectivity for the natural rat host, growth in vitro in the described culture medium, sensitivity to inhibition of reproduction by the rat antibody ablastin, and agglutinability by the 2 trypanocidal antibodies produced during a natural course of infection in the rat. Initially, differences between the 2 forms were minor, but after 16 mo in vitro greater differences began to emerge. Most marked was a reduction in infectivity by 22 mo, although sensitivity to ablastin, the single most important characteristic of bloodstream forms of T. lewisi, was still appreciable at this time. Nevertheless, despite this limitation, the culture system described supports hematozoic culture forms of T. lewisi for a considerably longer time than has been reported thus far.

Agglutination Tests↗

Comparative studies of antigens of erythrocytic and exoerythrocytic merozoites of Plasmodium lophurae: characterization of a surface glycoprotein from exoerythrocytic merozoites.

Rabbits were immunized with merozoite-enriched preparations of erythrocytic and exoerythrocytic Plasmodium lophurae. The antisera were used to compare antigens of the two types of merozoites. The indirect immunofluorescent antibody test showed the presence of common antigens. The growth of exoerythrocytic parasites was inhibited by the homologous antiserum and to a lesser extent by the antiserum prepared against erythrocytic forms. Cultures of exoerythrocytic parasites as well as their normal host cells were labeled metabolically with 35S-methionine, tritiated proline and glucosamine. Nonidet P-40 extracts of labeled merozoite-enriched preparations, infected cells, and normal cells were immunoprecipitated with the two types of antisera and the immunoprecipitates were analyzed on polyacrylamide gels. The results showed that erythrocytic and exoerythrocytic merozoites have several common proteins. A major difference was a glycoprotein with an approximate molecular weight of 110,000 daltons. This glycoprotein was associated with the surface of exoerythrocytic merozoites and was not recognized by antibodies prepared against erythrocytic forms.

Animals↗