Patisiran for the treatment of patients with familial amyloid polyneuropathy.

Onpattro, also commonly known as patisiran, is a small interfering RNA (siRNA) molecule packaged within a lipid nanoparticle and is transported into the cell to target transthyretin gene (TTR) messenger mRNA (mRNA) by attaching to its complementary sequence. The target mRNA is degraded and both mutant and wild-type amyloid transthyretin (ATTR) protein production becomes suppressed. This drug was developed by Alnylam Pharmaceuticals to treat a rare disease called hereditary ATTR (hATTR) amyloidosis. This disease develops as a result of the deposition of toxic aggregates of misfolded TTR protein, and is progressive causing the affected individual to be bed bound and to eventually die if left untreated. However, variable expressivity and incomplete penetrance cause carriers of TTR gene variants to be asymptomatic for a prolonged time. The heterogeneity of symptoms makes correct diagnosis of the disease difficult, therefore management of symptoms and proper treatment are delayed as a result. However, certain TTR variants are found in endemic or cluster regions, which facilitates their detection. In this review paper, different aspects of the drug are discussed in detail, including its preclinical and clinical studies, as well as its pharmacokinetic properties along with drug interactions leading to its approval by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).

Micro-CT evaluation of sonically and ultrasonically activated irrigation on the removal of hard-tissue debris from isthmus-containing mesial root canal systems of mandibular molars.

AIM: To evaluate the efficacy of sonically and ultrasonically activated irrigation on removal of accumulated hard-tissue debris (AHTD) in mesial root canal systems of mandibular molars using micro-computed tomographic (micro-CT) analysis. METHODOLOGY: Forty mesial roots of mandibular molars with two independent canals joined apically by an isthmus (Vertucci type II) were selected. The root canals were instrumented using Reciproc R25 instruments, and specimens were scanned at a resolution of 10.5 µm. Subsequently, n = 10 roots were assigned to each of the four final irrigation groups such that the group means and variances were almost identical: sonically activated irrigation with EndoActivator (EA) or EDDY (ED), ultrasonically activated irrigation (UAI) and manual irrigation without activation (MI). The final irrigation procedures were performed using a total of 5 mL 1% NaOCl and 5 mL 15% EDTA per canal over 5 min with activation time of 4 × 20 s. Reconstructed data sets were coregistered, and the mean percentage reduction of AHTD after final irrigation was compared statistically between groups using analysis of variance at a significance level set at 5%. RESULTS: A significant reduction of AHTD was achieved after final irrigation in all groups (P < 0.05), ranging from 44.1% to 66.8%. The vol% of debris after irrigation was 3.7 ± 1.9% for EA, 3.3 ± 2.3% for ED, 2.1 ± 1.6% for UAI and 4.4 ± 2.3% for MI, with no significant difference between groups (P > 0.05). CONCLUSIONS: None of the final irrigation protocols completely removed AHTD from mesial root canal systems in extracted human mandibular molars. Sonically and ultrasonically activated irrigation performed no better compared to manual irrigation.

Network geometry of evidence from randomised controlled trials addressing donor selection and source of haematopoietic progenitor cells used in allogeneic transplantation: a systematic scoping review.

BACKGROUND AND METHODS: A scoping review of randomised controlled trials (RCTs) addressing source of cells and choice of donor for allogeneic haematopoietic cell transplantation (HCT) was performed to create a network of best evidence that allows us to identify new potential indirect comparisons for the strategic development of future studies that connect to the existing evidence network. RESULTS: A total of 19 eligible RCTs (2589 total patients) were identified. Nine studies (1566 patients) compared clinical outcomes following the use of peripheral blood progenitor cells (PBPCs) with bone marrow (BM) from matched related donors (eight studies) or matched unrelated donors (one study). The remaining studies compared BM or PBPCs with various methods of BM stimulation or manipulation (six studies), compared different methods of surface molecule-based selection and/or depletion of grafts (two studies) or compared the optimal number of units for paediatric cord blood transplantation (two studies). No published RCTs compared different types of donors. The geometry of the evidence network was analysed to identify opportunities for potential novel indirect comparisons and to identify opportunities to expand the network. Few indirect comparisons are currently feasible due to small sample size and heterogeneity in patient diagnoses and demographics between treatment nodes in the network. CONCLUSION: More RCTs that enrol greater numbers of similar patients are needed to leverage the current evidence network concerning donor choice and source of cells used in allogeneic HCT.

Efficacy of the ProTaper retreatment system in removing Thermafil, GuttaCore or vertically compacted gutta-percha from curved root canals assessed by micro-CT.

AIM: To evaluate ex vivo the efficacy of ProTaper Universal Retreatment files (Dentsply Sirona, Ballaigues, Switzerland) in removing Thermafil, GuttaCore (both Dentsply Sirona) or vertically compacted gutta-percha from curved root canals using micro-CT. METHODOLOGY: Sixty curved molar roots with the same mean canal curvatures and radii in two directions were prepared using ProFile instruments (Dentsply Sirona) to size 30 with .04 taper and obturated with either Thermafil, GuttaCore or vertically compacted gutta-percha and AH Plus (n = 20). Specimens were retreated using the ProTaper Universal Retreatment files D1, D2 and D3 to working length, and root canal preparation was completed with ProTaper Next (Dentsply Sirona) to size ×4. Percentages of residual filling material and dentine removal were assessed using micro-CT imaging. Working time and procedural errors were recorded. Statistical analysis was performed using Kruskal-Wallis and Wilcoxon tests. RESULTS: No significant differences between carrier-based and warm vertical compaction regarding residual filling material (14.2-19.3%) and dentine removal (2.7-3.2 mm3 ) were detected (P > 0.05). Time to reach working length was significantly faster for canals filled with GuttaCore than that observed for Thermafil and warm vertical compaction (P < 0.05). Five lateral perforations with the D3 file occurred during retreatment, one in the Thermafil and four in the vertical compaction group. CONCLUSIONS: Remaining filling material and dentine removal were similar for all canal filling techniques. Regaining working length was significantly faster for GuttaCore compared with Thermafil and vertically compacted gutta-percha. Procedural errors occurred during retreatment of severely curved root canals with the ProTaper Universal Retreatment files in 5 of 60 canals (8%).

Effectiveness of nickel-titanium springs vs elastomeric chains in orthodontic space closure: A systematic review and meta-analysis.

The aim of this study is to explore the effectiveness of nickel titanium closing springs (NiTi-CS) and elastomeric power chains (EPC) in orthodontic space closure and to assess the adverse periodontal effects, cost efficiency and patient-centred outcomes between both of these methods. METHODS: An electronic search of online databases (Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Scopus, LILACS and Web of Science), reference lists and grey literature as well as hand search were conducted without language restriction up to November/2017. Two authors blindly and in duplicate were involved in study selection, quality assessment and the extraction of data. Only randomized clinical trials (RCTs) were included. The quality of the studies was assessed using the Cochrane Collaboration's risk of bias tool. 95% confidence intervals and mean difference for continuous data were calculated. A meta-analysis that generated a random-effect model for the comparable outcomes was conducted, and heterogeneity was measured using I2 statistic. RESULTS: Of 187 records, 4 RCTs met the criteria and were included in the quantitative synthesis featuring 290 test quadrants. Faster space closure with NiTi-CS was observed with a mean difference of (0.20 mm/month, 95% CI: 0.12 to 0.28). Loss of anchorage appears to be similar within both groups when synthesized qualitatively. With exception to anchorage loss, secondary outcomes could not be investigated in the included trials. CONCLUSIONS: There is a moderate quality of evidence suggesting a faster orthodontic space closure with the NiTi-CS when compared to EPC. A comparable amount of anchorage loss was observed regardless of the utilized method of space closure. Further high-quality RCTs with parallel-groups, reporting on the adverse effects and patient-centred values, are recommended.

Injection laryngoplasty through a transoral approach using the Guedel oral airway.

Injection laryngoplasty has gained popularity as a treatment modality for glottal insufficiency. Several approaches have been described, specifically transcutaneous, transoral and transnasal. The authors describe a novel technique performed successfully on three subjects, namely endoscopic injection laryngoplasty using the modified Guedel oral airway. There was marked improvement in dysphonia, maximum phonation time and closed quotient in all three subjects with a decrease in the Voice Handicap Index-10 score. This new approach is a viable approach for the treatment of glottal insufficiency.

Comparative in vivo antioxidant levels in Schistosoma mansoni infected mice treated with praziquantel or the essential oil of Melaleuca armillaris leaves.

Plant extracts are continuously investigated for their extensive inclusion of biologically active constituents that exert therapeutic activities against many diseases. The aim of this study was to assess the antioxidant/anti-schistosomal activities of the essential oil of the fresh leaves of Melaleuca armillaris (M. armillaris) compared to Praziquantel (PZQ) on normal and Schistosoma mansoni-infected mice. The oil was isolated by hydrodistillation and analyzed by gas chromatography/mass spectrometry (GC/MS). The oil was rich in 1,8-cineole (33.93%), terpinen-4-ol (18.79%), limonene (10.37%) and B-pinene (6.59%). M. armillaris oil (150 mg kg(-1), orally) was administered from the second week post infection twice per week for six weeks. PZQ (500 mg kg(-1), orally) was administered for two successive days 8 weeks post infection and mice sacrificed one week later. Total protein, Malondialdehyde (MDA), Glutathione (GSH), vitamins C and E, the antioxidant enzymes catalase and superoxide dismutase, as well as liver weights and liver/body weight were determined in the liver tissues. Results showed that, both treatments significantly ameliorated the disturbed levels ofGSH and MDA in infected mice. Both vitamins were significantly elevated after treatment with the oil while a significant increase in catalase accompanied by a pronounced decrease in SOD were obtained after treatment with PZQ. Both treatments markedly improved liver and body weights in infected mice compared to the infected-untreated ones. In conclusion, natural plant sources may be used as promising alternative agents to chemical drugs for schistosomiasis treatment, since the latter may result in drug-induced resistance arising from repeated use.

Effects of acute low doses of gamma-radiation on erythrocytes membrane.

It is believed that any dose of ionizing radiation may damage cells and that the mutated cells could develop into cancer cells. Additionally, results of research performed over the past century on the effects of low doses of ionizing radiation on biological organisms show beneficial health effects, called hormesis. Much less is known about the cellular response to low doses of ionizing radiation, such as those typical for medical diagnostic procedures, normal occupational exposures or cosmic-ray exposures at flight altitudes. Extrapolating from the effects observed at higher doses to predict changes in cells after low-dose exposure is problematic. We examined the biological effects of low doses (0.01-0.3 Gy) of γ-radiation on the membrane characteristics of erythrocytes of albino rats and carried out osmotic fragility tests and Fourier transform infrared spectroscopy (FTIR). Our results indicate that the lowest three doses in the investigated radiation range, i.e., 0.01, 0.025 and 0.05 Gy, resulted in positive effects on the erythrocyte membranes, while a dose of 0.1 Gy appeared to represent the limiting threshold dose of those positive effects. Doses higher than 0.1 Gy were associated with the denaturation of erythrocyte proteins.

Randomized study comparing endoscopic ultrasound-guided Trucut biopsy and fine needle aspiration with high suction.

OBJECTIVES: Endoscopic ultrasound (EUS)-guided Trucut biopsy (TCB) enables acquisition of tissue cores for histological assessment. Because of the rigid needle and the spring mechanism, tissue acquisition can be difficult from regions that require sharp angulation of the echoendoscope. Fine needle aspiration with high suction (FNAHS) has been proposed as a method to obtain histological tissue cores while affording the flexibility to obtain specimens even with extreme endoscope angulation. The objective was to compare prospectively these two methods in their ability to obtain specimens for histological assessment and in their diagnostic accuracy, including cytological diagnosis when achieved. METHODS: Eighty lesions in 77 patients were amenable to transoesophageal, transgastric or transrectal biopsy and were randomized to TCB (n = 44) or FNAHS (n = 36). Each specimen was assessed for adequacy (scoring system where a score of 0 was no material, 1-2 was considered cytological, and 3-5 was considered histological). Follow-up information was obtained to establish a gold standard final diagnosis. RESULTS: The median histological scores for FNAHS and TCB were 2 and 5, respectively. Histological cores were obtained in 95.3% of TCB, as opposed to 27.8% in the FNAHS group (P < 0.0001). Although the diagnostic accuracy for TCB was greater than that for FNAHS (88.3% and 77.8%, respectively), this was not statistically significant (P = 0.24). CONCLUSION: If histological information is required, TCB is superior to FNAHS. The difference in diagnostic accuracy did not reach statistical significance due to low numbers and the fact that FNAHS often enabled a cytological diagnosis.

Removal of some heavy metals ions from wastewater by copolymer of iron and aluminum impregnated with active silica derived from rice husk ash.

Recently because of increasing of the environmental awareness and demands, several attempts were carried out for the conversion of by-products of natural materials, especially agricultural wastes, to highly sorption capacity materials. In recent years, attention has been focused on the utilization of unmodified or modified agro-residues as sorbents for removal of pollutants. Various modifications have been reported to enhance sorption capacities for heavy metals. The present study deals with the adsorption equilibrium of iron, manganese, lead and arsenic ions from aqueous solutions on copolymer of Al(+3), Si(+4) and Fe(+3) using batch techniques. The influence of various parameters, such as agitation time, sorbent mass and pH of sorbate solution were investigated. Under this study the maximum adsorption capacity of iron and aluminum copolymer impregnated with silica (PAlFeClSi) for lead, iron, manganese and arsenic are found to be 416, 222, 158, 146 mg/g, respectively.

Serum interleukins and urinary microglobulin in children with idiopathic nephrotic syndrome.

We studied 60 children affected with idiopathic nephrotic syndrome (INS) plus 20 age and sex matched controls. The children with INS were divided into 3 groups of 20: first presentation, remission and relapse. A complete blood picture and complete urinalysis were done. Serum interleukin (IL)-1beta, IL-6, tumour necrosis factor (TNF) and quantitative urinary beta-2-microglobulin (beta-2-m) excretion were estimated. IL-1beta and IL-6 were significantly higher in the study groups, the first presentation and relapse groups having the highest concentrations. Serum TNF concentration and urinary beta-2-m excretion were significantly higher in the first presentation and relapse groups. Serum IL-1beta, IL-6 and TNF concentrations were able to select positively (100%) the first presentation and relapse groups, while these plus urinary beta-2-m excretion selected negatively (100%) the control group.

Evaluation of tumour markers in molar pregnancy.

METHODS: Circulating CA 125, CA 19-9, CA 15-3 and carcinoembryonic antigen (CEA) levels were studied in sixty patients with hydatidiform mole and in twenty normal pregnant women of a corresponding duration of pregnancy. DISCUSSION: Serum levels of CA 125, CA 15-3 and CEA are not affected by molar pregnancy. The mean level of CA 19-9 in maternal serum is significantly lower in cases of molar pregnancy when compared with cases of normal pregnancy. The amnion cell origin of CA 19-9 could explain the statistically significant difference between cases of therapeutic abortion and cases of HM (complete HM lacks amniotic membrane).

Voltammetric determination of praziquantel in tablets and biological fluids.

A simple method is described for the determination of praziquantel (CAS 55268-74-1) in its pure form, tablet formulations and biological fluids. The proposed method depends upon the polarographic activity of praziquantel at the dropping mercury electrode (DME) in Britton Robinson buffers, whereby a well-defined catholic wave is produced over the pH range 7-12. The wave was characterized as being irreversible diffusion-controlled with limited adsorption properties. The diffusion current constant (Id) was 0.56 +/- 0.004 (n = 11). The current-concentration relationship was found to be rectilinear over the range 8-48, 3.2-38.4 and 0.48-20 micrograms.ml-1 using direct current (DCt), differential pulse polarographic (DPP) and alternating current (ACt) odes, respectively, with minimum detection limit (S/N = 2) of 0.32 microgram.ml-1 (1.02 x 10(-6) mol/l and 0.02 microgram.ml-1 (6.4 x 10(-8) mol/l) for DPP and ACt modes respectively. The average percent recovery was favourably compared to a reference method with a satisfactory standard deviation. The proposed method was applied to spiked human urine and plasma. The percentage recoveries were 99.33 +/- 0.79 and 98.23 +/- 0.53, respectively.

Pycnodysostosis: clinical, radiologic, and endocrine evaluation and linear growth after growth hormone therapy.

Pycnodysostosis is a rare hereditary bone abnormality with an autosomal recessive mode of inheritance. We report the clinical, radiologic, and endocrine status of 8 children with this rare disease. All patients had the characteristic phenotype of the disorder including short stature (8 of 8), increased bone density (7 of 8), separated cranial sutures (8 of 8), large fontanel with delayed closure (8 of 8), obtuse mandibular angle (8 of 8), delayed teeth eruption (8 of 8), enamel hypoplasia (7 of 8), dysplastic acromial ends of the clavicles (6 of 8), frontal bossing (6 of 8), ocular proptosis (8 of 8), and dysplastic nails (8 of 8). Developmental evaluation according to the revised Denever developmental screening showed normal motor, fine motor-adaptive language, and personal social abilities in all the children. All had normal hepatic and renal functions. Serum calcium and phosphorus concentrations were normal. Two children had low serum alkaline phosphatase concentration. Short stature is a characteristic feature of pycnodysostosis. Seven of the 8 children were born short (length standard deviation score [SDS] = -3 to -1.5). Deceleration of linear growth was significant during the first 3 years of life. All the children had height SDS below -3 at the end of their third year of life. Although short stature is a feature of this genetic disorder, defective growth hormone (GH) secretion in response to provocation with clonidine and glucagon was found in 4 of the 8 patients. These 4 patients had pituitary hypoplasia on the magnetic resonance imaging (MRI) of their brain. In addition, 3 of these 4 patients had demyelination of the cerebrum. Patients with pycnodysostosis (n = 8) had low circulating concentrations of insulin-like growth factor-1 (IGF-1) compared with normal age-matched short children with constitutional short stature (CSS). IGF-I increased significantly after injecting GH for 3 days in these patients. Physiologic replacement with GH (18 U/m(2)/week) divided in daily evening doses subcutaneously increased IGF-1 concentration and improved linear growth velocity and height standard deviation scores (HtSDS) in the 4 children with GH deficiency. These data ruled out GH resistance and proved the usefulness of GH therapy in the management of short stature in these patients. In summary, some patients with pycnodysostosis have partial GH deficiency and low IGF-1 concentration. GH therapy markedly increases IGF-I secretion and improves their linear growth. MRI study of the brain including the hypothalamic-pituitary area is recommended in these children because of the high incidence of pituitary hypoplasia and cerebral demyelination.

In vitro studies of the efficacy of antimicrobials against fungi.

OBJECTIVE: The purpose of this study was to compare the efficacy of Listerine Antiseptic, Tartar Control Listerine Antiseptic, and Peridex mouthrinses and a 0.2% chlorhexidine digluconate solution against known pathogenic fungi. STUDY DESIGN: Standardized methods were used to compare the antimicrobial efficacy of the above agents versus representative fungal species. Minimum inhibitory concentration-minimum fungicidal concentrations in macrobroth dilutions, suspension kill-time, and effectiveness against an artificial biofilm-attached population were studied. RESULTS: All antimicrobials tested were effective against the fungal species under investigation at the concentration available commercially. Listerine Antiseptic showed a greater efficacy against attached artificial biofilm populations than the other antimicrobials tested. CONCLUSIONS: Listerine Antiseptic, Tartar Control Listerine Antiseptic, and Peridex mouthrinses show promise as a means to control the pathogenic fungal species under investigation and may have applications to reduce oral colonization.

In vitro effect of oral antiseptics on human immunodeficiency virus-1 and herpes simplex virus type 1.

AIM: The antiviral effectiveness of widely used commercial mouthrinses has not been well studied. A project was undertaken to evaluate and compare the in vitro antiviral effectiveness of essential oil-containing mouthrinses (LA & TLA) and chlorhexidine mouthrinses (PX & CHX) on 2 different enveloped viruses, human immunodeficiency virus (HIV-1) and Herpes simplex virus (HSV-1) McIntyre strain. METHOD: HIV-1(89.6) (1x10(5)/ml) and HSV-1 (1x10(6)/ml) in RPMI-1640 medium were treated with two commercially available forms of LA & TLA (tartar control LA), and 2 formulations of chlorhexidine [(PX), 0.12% chlorhexidine & (CHX), 0.2% chlorhexidine] for 30 sec. The antiviral effect was estimated by inhibition of the syncytia formation or the cytopathic effect (CPE) for HIV-1 on MT-2 cells and by inhibition of the plaque formation for HSV-1 on Vero cell monolayers. RESULTS: Undiluted LA, TLA, PX and CHX completely inhibited both HIV-189.6 and HSV-1 McIntyre strain. PX and CHX inhibited HIV-1 up to 1:4 dilution, whereas, LA and TLA inhibited HSV-1 up to 1:2 dilution. The antiviral effects of LA and TLA were found to be similar and also the antiviral effect of PX and CHX were also found to be comparable. CONCLUSIONS: The methods used in this investigation allow easy and reproducible evaluations of antiviral efficacy. The anti-HIV-1 and anti-HSV-1 effects of LA, TLA, PX and CHX as evidenced in our in vitro study suggest that we should investigate potential in vivo effects during the use of essential oil-containing or chlorhexidine containing products when used by patients as mouthrinses. If the clinical studies confirm the in vitro data, pre-procedural use by clinicians may be beneficial in reducing viral contamination of bio-aerosols during the delivery of dental care.

Use of cytokeratins 7 and 20 in determining the origin of metastatic carcinoma of unknown primary, with special emphasis on lung cancer.

Metastatic carcinoma of unknown primary is a common problem, accounting for up to 10-15% of all solid tumours at presentation. Proper identification of the site of origin has prognostic and therapeutic significance. Prior immunohistochemical methods to identify the site of origin have been useful in a limited number of cases. Differential cytokeratin staining may be useful in this setting, particularly in identifying metastases from lung cancer. We have identified 144 cases of metastatic carcinoma of unknown primary to bone, lung or liver at Brigham and Women's Hospital between 1 January 1997 and 1 July 1998. Cytokeratin (CK) 7 and CK20 were used in 75 of these cases to narrow down the possible sites of the primary tumours. All of these cases were ambiguous as to the site of the primary tumour. Forty-five cases were CK7+/CK20-, 15 cases were CK7-/CK20-, 9 cases were CK7-/CK20+ and 6 cases were CK7+/CK20+. Three of the cases were selected for detailed presentation and discussion as well as a discussion of the pertinent literature. Overall, the CK7+/CK20- phenotype favours a lung primary, the CK7+/CK20+ phenotype strongly favours transitional cells (urothelial) carcinoma, the CK7-/CK20+ phenotype favours colorectal carcinoma, while the CK7-/CK20- profile is not helpful.

Enhanced interleukin-1beta, interleukin-6 and tumor necrosis factor-alpha production by LPS stimulated human monocytes isolated from HIV+ patients.

Periodontal disease and tooth loss is a common finding among advanced HIV+ patients. In addition to local oral lipopolysaccharide (LPS) stimulation, systemic up-regulation of monocyte pro-inflammatory cytokine secretion may also be involved in the pathogenesis of HIV disease. A study was undertaken to investigate IL-1beta, IL-6 and TNF-alpha production by resting and LPS stimulated monocytes isolated from HIV+ patients and also to investigate the relationship of the patient's HIV viral load status to the cytokine production. Whole blood samples in EDTA were collected from 39 HIV-1 infected patients and 20 age and sex matched uninfected controls. Plasma was separated by centrifugation. Viral load was determined using a quantitative RT-PCR. Monocytes were isolated by Ficoll-hypaque gradient separation followed by overnight plastic adherence. Cultured monocytes (1x10(6)/ml) were stimulated with LPS (1 microg/ml) of either P. gingivalis or F. nucleatum for 2, 8, 24 and 48 h and supernatant fluids were collected. IL-1beta, IL-6, and TNF-alpha levels in supernatant fluids were estimated by ELISA. Increased overall production of IL-1beta, IL-6 and TNF-alpha by LPS stimulated monocytes isolated from HIV-1 infected patients was observed when compared to HIV-1 uninfected controls. LPS stimulated monocytes from HIV-1 infected patients with high viral load (HVL) produced significant (p<0.05) elevations in these pro-inflammatory cytokines when compared to HIV-1 uninfected controls. Both LPS of P. gingivalis and F. nucleatum produced a comparable cytokine production by monocytes after 8 h of stimulation. These data suggest that enhanced IL-1beta, IL-6 and TNF-alpha is produced by monocytes/macrophages isolated from HVL HIV+ patients and may be involved in the overall pathogenesis of HIV-1 infection.

Retrospective identification and characterization of Candida dubliniensis isolates among Candida albicans clinical laboratory isolates from human immunodeficiency virus (HIV)-infected and non-HIV-infected individuals.

Fungal opportunistic infections, and in particular those caused by the various Candida species, have gained considerable significance as a cause of morbidity and, often, mortality. The newly described species Candida dubliniensis phenotypically resembles Candida albicans so closely that it is easily misidentified as such. The present study was designed to determine the frequency at which this new species is not recognized in the clinical laboratory, to determine the patient populations with which C. dubliniensis is associated, to determine colonization versus infection frequency, and to assess fluconazole resistance. Over a 2-year period, 1,251 isolates that were initially identified as C. albicans by a hospital clinical laboratory were reevaluated for C. dubliniensis by inability to grow at 45 degrees C, colony color on CHROMagar Candida medium, coaggregation assay with Fusobacterium nucleatum, and sugar assimilation profiles (API 20C AUX yeast identification system). A total of 15 (1.2%) isolates from 12 patients were identified as C. dubliniensis. Ten of the patients were found to be immunocompromised (these included patients with human immunodeficiency virus infection or AIDS, cancer patients receiving chemotherapy, and patients awaiting transplantation). Thirteen isolates were highly susceptible to fluconazole (MIC, <0.5 microgram/ml). Three isolates from one patient, genotypically confirmed as the same strain, showed variable susceptibility to fluconazole. The first isolate was susceptible, whereas the other two isolates were dose-dependent susceptible (MIC, 16.0 microgram/ml). These data confirm the close association of C. dubliniensis with immunocompromised states and that increased fluconazole MICs may develop in vivo. This study emphasizes the importance of screening germ-tube-positive yeasts for the inability to grow at 45 degrees C followed by confirmatory tests in order to properly identify this species.