Rapid, transient fluconazole resistance in Candida albicans is associated with increased mRNA levels of CDR

Fluconazole-resistant Candida albicans, a cause of recurrent oropharyngeal candidiasis in patients with human immunodeficiency virus infection, has recently emerged as a cause of candidiasis in patients receiving cancer chemotherapy and marrow transplantation (MT). In this study, we performed detailed molecular analyses of a series of C. albicans isolates from an MT patient who developed disseminated candidiasis caused by an azole-resistant strain 2 weeks after initiation of fluconazole prophylaxis (K. A. Marr, T. C. White, J. A. H. vanBurik, and R. A. Bowden, Clin. Infect. Dis. 25:908-910, 1997). DNA sequence analysis of the gene (ERG11) for the azole target enzyme, lanosterol demethylase, revealed no difference between sensitive and resistant isolates. A sterol biosynthesis assay revealed no difference in sterol intermediates between the sensitive and resistant isolates. Northern blotting, performed to quantify mRNA levels of genes encoding enzymes in the ergosterol biosynthesis pathway (ERG7, ERG9, and ERG11) and genes encoding efflux pumps (MDR1, ABC1, YCF, and CDR), revealed that azole resistance in this series is associated with increased mRNA levels for members of the ATP binding cassette (ABC) transporter superfamily, CDR genes. Serial growth of resistant isolates in azole-free media resulted in an increased susceptibility to azole drugs and corresponding decreased mRNA levels for the CDR genes. These results suggest that C. albicans can become transiently resistant to azole drugs rapidly after exposure to fluconazole, in association with increased expression of ABC transporter efflux pumps.     

Treating gastro-oesophageal reflux disease during pregnancy and lactation: what are the safest therapy options?

About 30% of patients who underwent percutaneous transluminal coronary angioplasty show evidence of restenosis, which appears to be independent of the angioplasty method used. The restenosis is due of two factors, firstly migration of smooth vascular muscle cells of the vascular media to the intima and multiplication which lead to the formation of a neo-intima. Irradiation limits the proliferation by acting of the cells in the mitotic stage. The vascular target volume is not very thick and is difficult to define it, that why brachytherapy seems to be the best procedure to prevent restenosis. However, the development of this treatment present many difficulties. Different irradiation techniques have been studied. Such techniques include catheter containing radioactive sealed source, radioactive stent, or balloon containing radioactive liquid inside. Each of these methods have their own advantages, inconveniences, problems and risks. Radioisotope may be either beta or gamma emitters. Gamma emitter presents problems for radioprotection but the satisfactory dose distribution may be difficult to obtain using beta emitter. Choice of dose, dose rate and delay between the end of angioplasty and the beginning of brachytherapy is subject to some discuss. Animal experiments using radioisotope have shown reduction in cell proliferation. Human trials showed feasibility, safety of the method and real impact on restenosis prevention. However, long-term efficacy has not been proved because the follow-up of the patients is too short. A randomized trial of 192Ir brachytherapy for prevention of restenosis has recently shown the efficacy in short and median term. However, long term efficiency and secondary effects have not yet been established as the follow up time of this study is still too short. That is why, collaboration between cardiologists and radiotherapists and physicists is indispensable to enable the development of an optimal technique.     

Six-year clinical evaluation of HTR synthetic bone grafts in human grade II molar furcations

A biocompatible microporous composite of PMMA (poly-methyl-methacrylate), PHEMA (poly-hydroxy-ethyl-methacrylate) and calcium hydroxide bone replacement graft material (Bioplant HTR Synthetic Bone) was evaluated in 16 maxillary molar and 10 mandibular molar Grade II furcations in 13 patients. Following initial preparation, full thickness flaps were raised to gain access to the furcations; mechanical hand and ultrasonic root and defect debridement and chemical tetracycline root preparation were performed; furcation and adjacent osseous defects in each patient were grafted with HTR Synthetic Bone; and the host flaps replaced or slightly coronally positioned. Weekly, then monthly deplaquing was performed until surgical re-entry at 6-12 months. Patients were then followed on approximate 3-month recalls for > or = 6 yr. Evaluation of the primary clinical outcome of furcation grade change showed that in the maxilla 5/16 furcations were clinically closed, 9/16 were Grade I, and 2/16 remained Grade II; while in the mandible 3/10 were clinically closed, 5/10 were Grade I, and 2/10 remained Grade II. Other significant clinical changes included decrease in mean horizontal furcation probing attachment level from 4.4 mm at surgery to 2.2 mm at re-entry to 2.0 mm at 6 yr, decrease in probing pocket depth from 5.4 mm at surgery to 3.0 mm at re-entry to 3.2 mm at 6 yr, and improvement in vertical clinical probing attachment level from 5.4 mm at surgery to 4.2 mm at re-entry to 4.1 mm at 6 yr (all p < 0.05 from surgery to re-entry and surgery to 6 yr, n.s. from re-entry to 6 yr via ANOVA). These favorable results with HTR polymer are similar to several reports with other graft materials and with GTR barriers, and suggest that HTR polymer may have a beneficial effect in the clinical management of Grade II molar furcations.     

A comparison of the critical thickness for MBE grown Lt-GaAs determined by In-Situ ellipsometry and transmission electron microscopy

The growth of low temperature (LT) GaAs by molecular beam epitaxy has been studied using ellipsometry. Different regimes of growth were observed in the data, depending on film thickness. Epitaxial growth of pseudomorphic LT-GaAs occurred immediately above the substrate, followed by a layer with changing dielectric properties. This upper layer can be modeled as a two-phase region consisting of epitaxial LT-GaAs and small grained, polycrystalline GaAs, which increases in volume fraction with increasing layer thickness. For sufficiently thick LT layers, cross-sectional transmission electron microscopy analysis showed pyramidal defects that were composed primarily of highly twinned regions. The ellipsometry data showed a deviation from the homogeneous growth model at a thickness less than the thickness at which the pyramidal defects nucleated in all samples.     

T-lymphocytopaenia, opportunistic infections and pathological findings in Ghanaian AIDS patients and their sexual partners

Ninety-nine patients at Center for Disease Control (CDC) clinical stage IV were studied. Twelve (12.12%) of these patients turned out to be HIV seronegative. Ten out of the 12 HIV negative patients were immunocompetent whereas the other two had proportional decreases in both CD4+ and CD8+ T-lymphocytes. HIV-1, HIV-2, and dual infection, were detected in 51.5%, 2%, and 22.2% respectively of clinical AIDS patients. The other 12.12% of clinical AIDS patients were indeterminate for HIV antibodies. All HIV positive patients with the exception of two, were immunocompromised with respect to CD4+ and CD8+ T-lymphocyte counts. Two healthy spouses and three children of patients who died from the disease were seronegative for HIV antibodies. Herpes simplex virus type 2 (HSV-2) and cytomegalovirus (CMV) antibody titres were higher in HIV infected than uninfected blood. Patients with chronic diarrhoea, lymphadenopathy, pneumonia, and tuberculosis, either alone or in combination of two or more of such symptoms, were found to be more likely to be confirmed by serology and immunology as definitive AIDS patients in Ghana. In postmortem studies on 20 patients, pneumonia due to tuberculosis constituted the major cause of death. Toxoplasmosis, cytomegaloviral eosophagitis and enteritis, and cryptococcosis were the major opportunistic infections detected. Programmed cell death (apoptosis) was found by the DNA gel electrophoresis method to be an unlikely major mechanism of accelerated culture induced death of PBMCs from CDC stage IV AIDS patients.     

A case of interatrial communication in a dog

A 4 month old female German Shepherd was presented for the work-up of a heart murmur that has been detected by the referring veterinarian. Clinical examination and thoracic radiography showed an enlargement of the right ventricle, and an increased pulmonary perfusion. Echocardiography showed an interatrial communication (atrial septum defect), and colour Doppler allowed the confirmation of a left to right shunt. The article discusses the diagnostic possibilities of this rare congenital cardiac malformation in the dog.