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M J McCullough

Publications and source records attributed to M J McCullough.

At least 19 recordsLinked to original sources
PubMed2006

In vitro antifungal susceptibility to six antifungal agents of 229 Candida isolates from patients with diabetes mellitus.

The most common antifungal drugs in current clinical use for the treatment of oral candidosis are polyenes and azoles, mainly used topically. Poor glycaemic control in association with other local factors, such as the presence of oral dental prostheses, salivary pH, salivary flow rate and tobacco habits, may lead to the development of oral candidosis. Topical antifungal agents are frequently used to prevent the development of candidal infections in patients with poor metabolic control, particularly in the elderly wearing dentures. The aim of this study was to assess the antifungal susceptibility of Candida isolates to six antifungal agents using a commercially available kit, Fungitest. The isolated were collected from patients affected by diabetes mellitus from two different geographic localities (London, UK, and Parma, Italy) and from a group of healthy non-diabetic subjects. No differences in antifungal susceptibility to the six agents tested were observed between Candida isolates from diabetic and non-diabetic subjects. However, differences were observed between the two geographically different diabetes mellitus populations. Oral yeast isolates from diabetes mellitus patients in the UK more often displayed resistance or intermediate resistance to fluconazole (P=0.02), miconazole (P<0.0001), and ketoconazole (P=0.01) than did isolates from diabetes mellitus patients in Italy. In addition, more C. albicans isolates were found in diabetic and non-diabetic subjects that were susceptible to fluconazole (P=0.0008 and P=0.01, respectively) than non-albicans isolates. The difference in the antifungal resistance of isolates from the two populations of diabetes mellitus patients may be related to differences in the therapeutic management of candidal infections between the two centres.

Antifungal Agents↗
PubMed2006

In vitro evaluation of virulence attributes of Candida spp. isolated from patients affected by diabetes mellitus.

BACKGROUND: Diabetes mellitus is a common disease found worldwide and it has been previously suggested that oral candidal infections may be more frequent or severe in patients with this disease. Systemic and local factors may influence the balance between the host and yeasts, and favour the transformation of Candida isolates from commensal to pathogenic microorganisms. Candida species have developed specific virulence mechanisms that confer the ability to colonise host surfaces, to invade deeper host tissue, or to evade host defences. Few studies have investigated the expression of the virulence attributes of oral Candida isolates in patients with diabetes mellitus. MATERIAL AND METHODS: The in vitro extracellular proteinase production and the in vitro ability to adhere to fibronectin of 229 Candida isolates of two geographic different groups of patients with diabetes mellitus and of healthy subjects were assessed. RESULTS: Candida isolates of patients with diabetes mellitus expressed a higher ability to adhere than those of healthy subjects. Higher levels of adhesion were also recorded in patients with a lower oral Candida colonisation. No differences were observed in the in vitro expression of extracellular proteinase of Candida isolates of patients with diabetes mellitus and those of non-diabetic subjects. Isolates of patients with type 2 diabetes mellitus expressed greater levels of proteinase than isolates of type 1 diabetes mellitus. CONCLUSIONS: Diabetes mellitus could be considered as an additional variable that may influence not only oral Candida carriage but also the ability of isolates to enhance the expression of virulence attributes.

Candida↗
PubMed2006

Analysis of the strain relatedness of oral Candida albicans in patients with diabetes mellitus using polymerase chain reaction-fingerprinting.

To increase our understanding of Candida pathogenicity, the identification of those strains most frequently associated with infections is of paramount importance. Polymerase chain reaction (PCR)-based methods are extremely effective in differentiating and determining reproducibility, they require minimum starting material and are rapid and simple to perform. In this study, the genetic relatedness of Candida albicans was assessed for two geographically different patient groups (London, UK and Parma, Italy) affected by diabetes mellitus. C. albicans samples from the oral cavities of non-diabetic healthy subjects were also examined by PCR fingerprinting to evaluate the possible genetic differences among endogenous strains in individuals with and without diabetes mellitus. PCR fingerprinting, with subsequent phylogenetic analysis of C. albicans isolates from the diabetic patients from London and Italy and from the non-diabetic subjects, revealed that there were significant differences (P < 0.0001) between C. albicans isolates indicative of the distinct ecological niches that occur in the oral cavities of these patient cohorts. The most diverse group comprised the isolates from the diabetic patients in the UK, possibly reflecting the antifungal treatment that these patients had received. Further studies that include isolates from patient cohorts with systemic diseases other than diabetes mellitus, and from more diverse geographic localities are required to explain the relatedness of C. albicans isolates in the mouth.

Candida albicans↗
PubMed2005

In vitro activity of a monoclonal killer anti-idiotypic antibody and a synthetic killer peptide against oral isolates of Candida spp. differently susceptible to conventional antifungals.

BACKGROUND/AIMS: A monoclonal killer anti-idiotypic antibody (mAbK10) and a synthetic killer peptide, acting as internal images of a microbicidal, wide-spectrum yeast killer toxin (KT) have been recently shown to express candidacidal in vitro and an in vivo therapeutic activity against experimental mucosal and systemic candidosis models caused by a reference strain of Candida albicans (10S). MATERIAL AND METHODS: The in vitro candidacidal activity of mAbK10 and synthetic killer peptide was compared using a colony forming unit assay against a large number of isolates of different Candida spp., obtained from oral saliva of adult diabetic (type 1 and 2) and nondiabetic subjects from Parma (Italy) and London (UK). RESULTS: Both the KT-mimics exerted a strong dose-dependent candidacidal activity, probably mediated by the interaction with beta-glucan KT receptors on target yeast cells, against all the tested strains, regardless of their species and pattern of resistance to conventional antifungal agents. CONCLUSIONS: These observations open new perspectives in the design and production of candidacidal compounds whose mechanism reflects that exerted in nature by killer yeasts.

Adult↗
PubMed2005

Oral viral infections and the therapeutic use of antiviral agents in dentistry.

This paper reviews the current concepts of viral classification, infection and replication. The clinical presentation of common oral viral infections encountered in the dental practice are discussed, including: herpes simplex virus types 1 and 2; Epstein-Barr virus; varicella-zoster virus; Coxsackie virus; human papilloma virus; and human immunodeficiency virus. The diagnosis, principles of management and pharmacological agents available for the treatment of oral viral infections are also discussed.

Antiviral Agents↗
PubMed2005

Oral candidosis and the therapeutic use of antifungal agents in dentistry.

This paper reviews the current concepts of mycology and candidal infections as they relate to the oral cavity. Proposed classification for the presentation of oral candidosis is outlined as are examples of these topical infections, such as erythematous, pseudomembranous and hyperplastic candidosis, as well as angular chelitis and median rhomboid glossitis. The diagnosis and principles of management of oral candidosis are discussed, the therapeutic agents available for the management of these infections are presented and a treatment protocol for the management of patients with oral candidosis is given.

Antifungal Agents↗
PubMed2005

Topical corticosteroids in dental practice.

Topical corticosteroids represent an important therapeutic aid in the management of a range of oral mucosal disease conditions. Like all medications, their successful use depends upon an understanding of the disease process. This includes an appropriate diagnosis, a clear view of the desirable treatment outcomes and knowledge of whether treatment is aimed at management of a chronic disease or enhanced resolution of a short-term condition. This paper reviews the use of topical corticosteroids and their possible roles in the management of oral disease.

Administration, Topical↗
PubMed2004

Update on diabetes mellitus and related oral diseases.

Diabetes mellitus (DM) is a group of complex multisystem metabolic disorders characterized by a relative or absolute insufficiency of insulin secretion and/or concomitant resistance to the metabolic action of insulin on target tissues. The chronic hyperglycaemia of diabetes is associated with long-term systemic dysfunction. The present article summarizes current knowledge of DM and details the oral and dental implications of this common endocrine disorder.

Diabetes Complications↗
PubMed2002

The isolation, identification and molecular analysis of Candida spp. isolated from the oral cavities of patients with diabetes mellitus.

Previous studies have shown a high incidence (77%) of isolation of Candida spp. from the oral cavities of patients with type 1 diabetes mellitus. The aim of the present study was to assess the prevalence of yeast in the oral cavities of patients suffering from type 1 and type 2 diabetes mellitus. The patients were classified according to the level of diabetic control (HbA1c), and further stratified on the presence or absence of dental prosthesis. Oral rinse samples were assessed for the growth of yeast and the degree of colonization. Oral isolates were defined to the species level by both phenotypic and novel molecular methods. The overall proportion (60%) of diabetic patients who had Candida spp. isolated from the oral cavity was similar to that previously reported. Local oral factors, such as the presence of dentures, seemed to have a greater influence than diabetic status on the amount and species of Candida isolated from the oral cavities of diabetic patients. Diabetic patients with dentures had more non-albicans Candida isolated from their mouths than dentate diabetic patients. Candida dubliniensis was isolated from diabetic patients and may have a predilection for dentate patients.

Adult↗
PubMed2002

Clinical and microbiological studies of periodontal disease in Sjögren syndrome patients.

BACKGROUND: Little is known about the periodontal status of patients with Sjögren's Syndrome (SS), a chronic inflammatory autoimmune disease characterized by xerophthalmia and xerostomia. The aim of the present study was to evaluate whether the periodontal status of SS patients, in terms of clinical and microbiological parameters, differs from systemically healthy age- and gender-matched controls. METHODS: 8 primary SS and 10 secondary SS patients were examined in comparison with 11 control subjects. All patients were diagnosed by the European Community Criteria. Control subjects were systemically healthy and not undergoing periodontal treatment. The comparison of clinical status was made in terms of mean periodontal parameters (plaque index, gingival index, gingival recession, probing pocket depth, probing attachment level and bleeding on probing) as well as the frequency distribution of probing pocket depth and probing attachment level measurements. Microbiological assays of the subgingival dental plaque samples were carried out by both a chairside enzyme test (Periocheck) for the detection of peptidase activity (PA) and a polymerase chain reaction (PCR) analysis for 9 selected periodontal micro-organisms (Actinobacillus actinomycetemcomitans, Fusobacterium nucleatum, Prevotella intermedia, Treponema denticola, Porphyromonas gingivalis, Eikenella corrodens, Campylobacter rectus, Bacteroides forsythus, Streptococcus oralis). RESULTS: The occurrence, severity and extent of periodontal lesions were not significantly different between the 3 patient groups for all periodontal parameters examined. No significant differences in the sub-gingival plaque samples from control, primary or secondary SS patients for the PA test, frequency or type of periodontal micro-organisms observed. CONCLUSION: No significant differences could be detected in either clinical or microbiological parameters of primary or secondary SS patients compared with that of control subjects. The results of the present study thus support the notion that the periodontal status of patients with SS do not differ from systemically healthy age- and gender-matched controls.

Adult↗
PubMed2001

Initial isolation of Candida dubliniensis from the Middle East.

Two isolates of Candida dubliniensis were identified from a collection of 30 examined from Israel in a molecular epidemiology study. The 30 isolates were tentatively identified as Candida albicans. The new species, C. dubliniensis, is being reported from new geographic locales. These two isolates, from an Arab and a Druze patient, are the first to be reported from the Middle East.

Adult↗
PubMed2000

Molecular epidemiology of Blastomyces dermatitidis.

The inhalation of conidia of Blastomyces dermatitidis, a fungus found in soil, causes disease in humans and animals. We studied the genetic diversity of this pathogen by extracting DNA yeasts and analyzing them with a polymerase chain reaction (PCR)-based typing system we developed, which used restriction fragment analysis of amplicons from the regions between the rDNA repeats and allowed us to class isolates into 3 major groups. Strains were further differentiated by use of PCR fingerprinting with 3 different primers. Fifty-nine isolates collected over 35 years from 15 regions (United States, India, Africa, Canada) were analyzed. Genotypic groups A, B, and C contained 17, 23, and 19 isolates, which were divided into 5, 15, and 12 types, respectively. All 16 isolates from North America in group A were from the upper midwestern United States or Canada, whereas 0 of 20 isolates from the southeastern United States were in group A. Studies of the largest collection from 1 locale (Eagle River, WI), revealed that the soil isolates studied were not responsible for the majority of cases in this outbreak, as previously proposed, and that >1 strain was present in the environment and in patients. Overall, these results provide a tool for the epidemiological study of blastomycosis and illuminate the genetic and geographic diversity of this important pathogen.

Africa↗
PubMed1999

Molecular epidemiology of the global and temporal diversity of Candida albicans.

The epidemiology of Candida albicans has changed with the rise in immunocompromised patients and the pressures of antifungal treatment and prophylaxis. We assessed the genotype distribution of recently obtained, globally diverse isolates in comparison with isolates recovered in the United States and United Kingdom before 1985, in order to determine temporal and geographic differences. We used EcoRI digestion of cellular DNA to generate restriction fragment length polymorphisms, dividing the isolates into 4 groups. From 15 diverse geographic areas, 439 isolates obtained over 20 years were divided into 121 genotypes within groups A (289 isolates), B (85), C (56), and D (9). Differences in genotype distribution existed among the localities (P<.0001) and between isolates obtained before 1990 versus those recovered since then (P=.009). Comparison of pre-1985 United States/United Kingdom isolates with post-1994 United States isolates revealed a trend toward a changing genotype distribution (P=.057). Global post-1985 isolates were different in genotype distribution from United States/United Kingdom isolates (P<.0001). The distribution of isolates from Israel was unique (P<.0001). These differences could be due in part to the increasing prevalence of group C strains worldwide.

Candida albicans↗
PubMed1999

Molecular and phenotypic characterization of genotypic Candida albicans subgroups and comparison with Candida dubliniensis and Candida stellatoidea.

There have been increased reports of the isolation of unusual genotypic groups of Candida albicans (groups C and D) based on a well-defined genotypic method; this method uses cellular DNA digested with the EcoRI enzyme and the restriction fragment length polymorphisms (RFLPs) generated by agarose gel electrophoresis. The aim of the present study was to use additional molecular tools to characterize these unusual strains and to compare them with authentic strains of C. dubliniensis, a recently delineated species, and type I C. stellatoidea. The RFLPs of PCR products generated from the intergenic transcribed spacer (ITS) region did not differentiate among C. albicans genotypes A, B, and C and type I C. stellatoidea. However, this method did differentiate the C. albicans genotype D strains, which were identical to C. dubliniensis. The RFLPs generated by HaeIII digestion of the PCR products of the V3 region of the 25S rRNA gene (rDNA) could differentiate the same groups as RFLP analysis of the PCR amplicon of the ITS region. C. albicans genotype B isolates have been shown to have a transposable intron in the 25S rDNA, whereas genotype A isolates do not; C. dubliniensis strains also have an intron that is larger than that in genotype B C. albicans strains but that is in the same location. PCR designed to span this region resulted in a single product for C. albicans genotype A (450 bp), B (840 bp), type 1 C. stellatoidea (840 bp), and C. dubliniensis (1,080 bp), whereas the C. albicans genotype C isolates had two major products (450 and 840 bp). All C. albicans genotype D isolates gave a PCR product identical to that given by C. dubliniensis. These results indicate that those strains previously designated C. albicans genotype D are in fact C. dubliniensis, that no differences were found between type 1 C. stellatoidea and C. albicans genotype B strains, and that the C. albicans genotype C strains appear to have the transposable intron incompletely inserted throughout the ribosomal repeats in their genomes. The results of the antifungal susceptibility testing of 105 of these strains showed that, for fluconazole, strains of C. dubliniensis were significantly more susceptible than strains of each of the C. albicans genotypes (genotypes A, B, and C). The flucytosine susceptibility results indicated that strains of C. albicans genotype A were significantly less susceptible than either C. albicans genotype B or C. albicans genotype C strains. These results indicate that there is a correlation between the Candida groups and antifungal susceptibility.

Antifungal Agents↗
PubMed1998

Direct allelic variation scanning of the yeast genome.

As more genomes are sequenced, the identification and characterization of the causes of heritable variation within a species will be increasingly important. It is demonstrated that allelic variation in any two isolates of a species can be scanned, mapped, and scored directly and efficiently without allele-specific polymerase chain reaction, without creating new strains or constructs, and without knowing the specific nature of the variation. A total of 3714 biallelic markers, spaced about every 3.5 kilobases, were identified by analyzing the patterns obtained when total genomic DNA from two different strains of yeast was hybridized to high-density oligonucleotide arrays. The markers were then used to simultaneously map a multidrug-resistance locus and four other loci with high resolution (11 to 64 kilobases).

Alleles↗
PubMed1998

Epidemiological investigation of vaginal Saccharomyces cerevisiae isolates by a genotypic method.

Saccharomyces cerevisiae is a ubiquitous, ascomycetous yeast, and vaginitis caused by this organism has been reported only very rarely. The aim of the present investigation was to assess the epidemiological relatedness of a group of vaginal and commercial S. cerevisiae isolates by a previously reported genetic typing method, which divided the isolates into two broad groups with numerous subtypes. Nineteen S. cerevisiae isolates obtained from patients suffering from vaginitis and four isolates from commercial products in the same city were analyzed. The cellular DNA from each isolate was digested with the restriction endonuclease EcoRI, and restriction fragment length polymorphisms were generated by horizontal gel electrophoresis. The results showed that although vaginal isolates did not cluster in any particular genetic subtype, multiple patients were infected with indistinguishable strains (there were nine distinct strains among 23 isolates). For two of three patients, all three with two episodes of S. cerevisiae vaginitis, different strains were isolated during the recurrence of this disease. Three other patients with indistinguishable isolates were epidemiologically related in that two were practitioners in the same clinic and the third was a patient at this clinic. We also found that one commercial strain was indistinguishable from the strain isolated from three different women at the time that they were suffering from vaginitis. The findings of the present study suggest that some S. cerevisiae strains may possess properties permitting persistence in the human host. Furthermore, person-to-person contact and the proliferation of the use of S. cerevisiae as a health-food product, in home baking, and in home brewing may be a contributing factor in human colonization and infection with this organism.

Adult↗
PubMed1998

Intergenic transcribed spacer PCR ribotyping for differentiation of Saccharomyces species and interspecific hybrids.

The taxonomy of the genus Saccharomyces has undergone significant changes recently with the use of genotypic rather than phenotypic methods for the identification of strains to the species level. The sequence of rRNA genes has been utilized for the identification of a variety of fungi to the species level. This methodology, applied to species of Saccharomyces, allows unknown Saccharomyces isolates to be assigned to the type strains. It was the aim of the present study to assess whether typing of the intergenic spacer region by using restriction fragment length polymorphisms of PCR products (intergenic transcribed spacer PCR [ITS-PCR] ribotyping) could distinguish among type strains of the 10 accepted species of Saccharomyces and further to assess if this method could distinguish strains that were interspecific hybrids. Cellular DNA, isolated after the lysis of protoplasts, was amplified by PCR using ITS1 and ITS4 primers, purified by liquid chromatography, and digested with restriction endonucleases. Ribotyping patterns using the restriction enzymes MaeI and HaeIII could distinguish all species of Saccharomyces from each other, as well as from Candida glabrata, Candida albicans, and Blastomyces dermatitidis. The only exception to this was the inability to distinguish between Saccharomyces bayanus and S. pastorianus (S. carlsbergensis). Furthermore, interspecific hybrids resulting from the mating of sibling species of Saccharomyces were shown to share the ITS-PCR ribotyping patterns of both parental species. It should now be possible, by this simple PCR-based technique, to accurately identify these strains to the species level, thereby allowing an increase in our understanding of the characteristics required by these interspecific hybrids for their particular ecological niches.

DNA, Fungal↗