The Potential of Utilizing Mid-Energy X-Rays for In-Line Phase Sensitive Breast Cancer Imaging.

OBJECTIVE: The objective of this study is to demonstrate the potential of utilizing mid-energy x-rays for in-line phase-sensitive breast cancer imaging by phantom studies. METHODS: The midenergy (50-80kV) in-line phase sensitive imaging prototype was used to acquire images of the contrast-detail mammography (CDMAM) phantom, an ACR accreditation phantom, and an acrylic edge phantom. The low-dose mid-energy phase-sensitive images were acquired at 60 kV with a radiation dose of 0.9 mGy, while the high-energy phase-sensitive images were acquired at 90 kV with a radiation dose of 1.2 mGy. The Phase-Attenuation Duality (PAD) principle for soft tissue was used for the phase retrieval. A blind observer study was conducted and paired-sample T-test were performed to compare the mean differences in the two imaging systems. RESULTS: The correct detection ratio for the CDMAM phantom for phase-contrast images acquired by the low-dose mid-energy system was 56.91%, whereas images acquired by the high-energy system correctly revealed only 40.97% of discs. The correct detection ratios were 57.88% and 43.41% for phase-retrieved images acquired by the low-dose mid-energy and high-energy imaging systems, respectively. The reading scores for all three groups of objects in the ACR phantom were higher for the mid energy imaging system as compared to the high-energy system for both phase-contrast and phase- retrieved images. The calculated edge enhancement index (EEI) from the acrylic edge phantom image for the mid-energy system was higher than that calculated for the high-energy imaging system. The quantitative analyses showed a higher Contrast to Noise Ratio (CNR) as well as a higher Figure of Merit (FOM) in images acquired by the low-dose mid-energy imaging system. CONCLUSION: The PAD based retrieval method can be applied in mid-energy system without remarkably affecting the image quality, and in fact, it improves the lesion detectability with a patient dose saving of 25%.

Clarithromycin vs ciprofloxacin as adjuncts to rifampicin and ethambutol in treating opportunist mycobacterial lung diseases and an assessment of Mycobacterium vaccae immunotherapy.

BACKGROUND: The mainstays of treatment for pulmonary disease caused by opportunist mycobacteria are rifampicin (R) and ethambutol (E). The role of macrolides, quinolones and immunotherapy with Mycobacterium vaccae is not clear. A trial was undertaken to compare clarithromycin (Clari) and ciprofloxacin (Cipro) as third drugs added to [corrected] 2 years of treatment with R and E for pulmonary disease caused by M avium-intracellulare (MAC), M malmoense and M xenopi (REClari and RECipro). An optional comparison of immunotherapy with M vaccae vs no immunotherapy was also performed. METHODS: Progress was monitored annually during the 2 years of treatment and for 3 years thereafter. If the patient was not improving at 1 year the regimen was supplemented by the addition of the drug not received in the original allocation of treatment. RESULTS: 371 patients (186 REClari, 185 RECipro) entered the study (170 MAC, 167 M malmoense, 34 M xenopi). All-cause mortality was high for both groups (44% REClari, 43% RECipro); for MAC it was higher with REClari than with RECipro (48% vs 29%) but for M malmoense (42% vs 56%) and M xenopi (29% vs 47%) it was higher with RECipro (p = 0.006). 3% died from their mycobacterial disease (REClari = RECipro). At the end of treatment, 4% of REClari and 10% of RECipro patients still had positive cultures. Among those with negative cultures at the end of treatment, 6% of the REClari group and 4% of the RECipro group had relapsed. At 5 years 30% of the REClari group were known to have completed treatment as allocated and to be alive and cured compared with 21% of the RECipro group (p = 0.04), but this difference was principally due to those with M malmoense (REClari 38%, RECipro 20%). Patients with MAC or M xenopi were more likely to have a poor outcome than those with M malmoense (p = 0.004), with no difference between REClari and RECipro. Overall, 20% in each group were unable to tolerate the regimen allocated, Cipro being associated with more unwanted effects than Clari (16% vs 9%, p = 0.05). No significant differences in outcomes were found between M vaccae-treated patients and those not treated with M vaccae immunotherapy. CONCLUSION: Considering all three species together, there were no differences in outcome between the REClari and RECipro groups. Immunotherapy did not improve outcome. New therapies, optimised management of co-morbid conditions and a more holistic approach must be explored in the hope of improving outcome.

Pulmonary disease caused by Mycobacterium xenopi in HIV-negative patients: five year follow-up of patients receiving standardised treatment.

The literature concerning the management of pulmonary disease caused by Mycobacterium xenopi is scanty and consists of retrospective reports, mostly of small series of patients. Our aim was to document the clinical features and response to treatment of this rare but challenging disease. Patients were treated in a randomised, multi-centre trial with either rifampicin plus ethambutol or rifampicin, ethambutol and isoniazid. Clinical, bacteriological and radiological progress was monitored at set intervals for 5 years. As no differences emerged between the two groups, the results have been combined to provide this prospective survey. Forty-two patients were studied. Mean age was 65 years, three-quarters were male and two-thirds had other lung disease(s). Sputum was positive on direct smear in 62%. Cavitation was present in 81%, mostly large cavities, and disease was extensive in 38%. Despite good clinical response and little toxicity the death rate was high (69%), but less than 10% died primarily because of the M. xenopi disease. The failure of treatment/relapse rate was 12%. Only 11 (26%) were known to be alive at 5 years of whom seven (17%) were known to be cured. There was no correlation between failure of treatment/relapse and in vitro resistance. Better methods of susceptibility testing and more effective regimens are needed, but it is also evident that improved management of concomitant diseases and better general health will play a major part in increasing survival.

Environmental mycobacteria in northern Malawi: implications for the epidemiology of tuberculosis and leprosy.

More than 36000 individuals living in rural Malawi were skin tested with antigens derived from 12 different species of environmental mycobacteria. Most were simultaneously tested with RT23 tuberculin, and all were followed up for both tuberculosis and leprosy incidence. Skin test results indicated widespread sensitivity to the environmental antigens, in particular to Mycobacterium scrofulaceum, M. intracellulare and one strain of M. fortuitum. Individuals with evidence of exposure to 'fast growers' (i.e. with induration to antigens from fast growers which exceeded their sensitivity to tuberculin), but not those exposed to 'slow growers', were at reduced risk of contracting both tuberculosis and leprosy, compared to individuals whose indurations to the environmental antigen were less than that to tuberculin. This evidence for cross protection from natural exposure to certain environmental mycobacteria may explain geographic distributions of mycobacterial disease and has important implications for the mechanisms and measurement of protection by mycobacterial vaccines.

Trends in antituberculosis drug resistance in Karonga District, Malawi, 1986-1998.

SETTING: Karonga District, Malawi. OBJECTIVES: To examine long term trends in initial and acquired resistance to antituberculosis drugs in a rural area of Africa. DESIGN: Monitoring of all patients with culture-confirmed tuberculosis 1986-1998. RESULTS: Initial drug resistance results were available for 1121 patients. The proportion resistant to any of the first line drugs (streptomycin, isoniazid, rifampicin or ethambutol) was 9.6%, and to isoniazid 7.2%. Initial resistance to at least isoniazid and rifampicin (multidrug resistance) was seen in only six patients. No initial resistance to ethambutol was found. There was no significant change in initial drug resistance over time. Overall, 22/120 (18%) patients with previous treatment were resistant to at least one drug; only one had multidrug resistance. Acquired resistance decreased over the period of the study. There were no associations between age, sex or human immunodeficiency virus (HIV) status and initial or acquired drug resistance. CONCLUSIONS: Changes in acquired resistance may reflect the recent performance of a control programme more quickly than those in initial resistance. It is encouraging that acquired resistance decreased and levels of multidrug resistance were low despite more than a decade of use of rifampicin. The lack of association between HIV and drug resistance confirms findings elsewhere in Africa.

Opportunist mycobacteria in England and Wales: 1982 to 1994.

Three thousand and fifty-two infections with opportunist mycobacteria were reported to the PHLS Communicable Disease Surveillance Centre from 1982 to 1994. The commonest reported species was Mycobacterium avium-intracellulare (MAI), followed by M. kansasii and M. malmoense. The annual totals of opportunist mycobacteria increased steadily over this period, mostly, but not exclusively, due to an increase in reports of MAI associated with HIV infection. There were also increases in reports of MAI not associated with HIV infection, and in reports of M. malmoense. The increase in reports of opportunist mycobacteria was seen throughout England and Wales, but underreporting of MAI infection in the National Health Service Thames regions appears to have increased in recent years. Continued referral of isolates of opportunist mycobacteria to one of the PHLS regional centres for mycobacteriology or the Mycobacterium Reference Unit, and reporting to CDSC, is essential for the surveillance of these infections.

Utility of PCR in diagnosing pulmonary tuberculosis.

At present, the rapid diagnosis of pulmonary tuberculosis rests with microscopy. However, this technique is insensitive and many cases of pulmonary tuberculosis cannot be initially confirmed. Nucleic acid amplification techniques are extremely sensitive, but when they are applied to tuberculosis diagnosis, they have given variable results. Investigators at six centers in Europe compared a standardized PCR system (Amplicor; Roche) against conventional culture methods. Defined clinical information was collected. Discrepant samples were retested, and inhibition assays and backup amplification with a separate primer pair were performed. Mycobacterium tuberculosis complex organisms were recovered from 654 (9.1%) of 7,194 samples and 293 (7.8%) of 3,738 patients. Four hundred fifty-two of the M. tuberculosis isolates from 204 patients were smear positive and culture positive. Among the culture-positive specimens, PCR had a sensitivity of 91.4% for smear-positive specimens and 60.9% for smear-negative specimens, with a specificity of 96.1%. Analysis of 254 PCR-positive, culture-negative specimens with discrepant results revealed that 130 were from patients with recently diagnosed tuberculosis and 94 represented a presumed laboratory error. Similar analysis of 118 PCR-negative, culture-positive specimens demonstrated that 27 discrepancies were due to presumed uneven aliquot distribution and 11 were due to presumed laboratory error; PCR inhibitors were detected in 8 specimens. Amplicor enables laboratories with little previous experience with nucleic acid amplification to perform PCR. Disease in more than 60% of the patients with tuberculosis with smear-negative, culture-positive specimens can be diagnosed at the time of admission, and potentially all patients with smear-positive specimens can immediately be confirmed as being infected with M. tuberculosis, leading to improved clinical management.

Feline tuberculosis: a literature review and discussion of 19 cases caused by an unusual mycobacterial variant.

The literature relating to feline mycobacterial disease is reviewed and 19 cats with tuberculosis caused by a previously unknown strain of mycobacterium are discussed. The bacteria were found to have characteristics between those of Mycobacterium tuberculosis and M bovis. The paper considers the clinical signs, epidemiology and diagnosis of the cases, and discusses the possible origins of the organism, treatment regimens and zoonotic potential.

Potentiation of the effects of chlorhexidine diacetate and cetylpyridinium chloride on mycobacteria by ethambutol.

Ethambutol enhanced the effects of chlorhexidine diacetate and cetylpyridinium chloride against Mycobacterium avium, M. bovis BCG, M. fortuitum and M. phlei. The findings show that it is possible to increase the susceptibility of mycobacteria to agents that normally exhibit poor activity against these organisms because of their reduced cellular penetration.

Patterns of initial and acquired antituberculosis drug resistance in Karonga District, Malawi.

There is concern that drug-resistant tuberculosis is increasing and may be concentrated among HIV-positive patients. Little information is available from developing countries, where surveillance studies are often unable to distinguish resistance in previously untreated patients (initial resistance) from resistance acquired following drug therapy, and where information on the HIV status of the patients is rare. Initial resistance patterns reflect the strains being transmitted in the community. We have studied patterns of resistance in northern Malawi, where the Lepra Evaluation Project has been collecting data on drug resistance since 1986. Initial drug sensitivity results were available for 373 new cases of tuberculosis. Initial resistance to at least one drug was found in 44 of these patients (11.8%, 95% CI 8.5-15.1): 13 were resistant to streptomycin alone, 13 to isoniazid alone, and 17 to more than one drug. Only 3 patients showed initial rifampicin resistance-1 in isolation, 1 in combination with streptomycin, and 1 with triple resistance. Drug resistance was not related to age, sex, or HIV status of the patient and there was no evidence of any increase over the period studied. There was no evidence of geographic clustering of the resistant strains, or of any increased risk of resistant strains in households with previous tuberculosis cases. Acquired resistance during follow-up was found in 5 of 329 patients with documented initially fully sensitive strains. 5 patients with initial resistance seemed to show reversion to sensitivity. The absence of an increase in drug resistance, despite an increase in tuberculosis cases over the period, is encouraging for the control programme. It emphasises the need to collect information from many areas before assuming that increases in antituberculosis drug resistance are occurring worldwide.

Isolation of Mycobacterium malmoense from the environment in Zaire.

Two strains of mycobacteria isolated from water and soil in Zaire were identified as Mycobacterium malmoense by biochemical tests and lipid analysis. Apart from the previously reported fatty acids characteristic of this species, both strains, as well as 5 clinical isolates of M. malmoense, contained 2,4-dimethyl-docosanoic acid. One of the environmental strains, with a glycolipid pattern II, additionally contained 2-methyltetradecanoic acid. The results confirm that M. malmoense may be subdivided in 2 sub-groups according to its lipid patterns. They also show that M. malmoense can be isolated from the environment which may be the source of the infection.

PCR amplification of variable sequence upstream of katG gene to subdivide strains of Mycobacterium tuberculosis complex.

PCR amplification of a species-specific 2-kb KpnI fragment of variable size located 10 kb upstream of the katG gene was used to subdivide 130 clinical isolates of Mycobacterium tuberculosis. Seven subtypes were identified, and their frequencies were distributed normally with respect to the size of the amplified product.

False-positive Mycobacterium avium-intracellulare cultures with the Bactec 460 TB system.

Isolation of Mycobacterium avium-intracellulare from a number of specimens cultured with the Bactec 460 TB system was suspected to be due to carry-over contamination. The analysis of culture records and of the typing results confirmed this hypothesis. The problem seems to have been eliminated after replacement of the needle heater and increase of the needle temperature. We recommend that a number of precautions should be taken to reduce the risk of reporting false positive mycobacterial cultures.