Biomedical subjects

William A Falkler

Publications and source records attributed to William A Falkler.

4 recordsLinked to original sources

PubMed2006

Noma (cancrum oris).

Noma is an opportunistic infection promoted by extreme poverty. It evolves rapidly from a gingival inflammation to grotesque orofacial gangrene. It occurs worldwide, but is most common in sub-Saharan Africa. The peak incidence of acute noma is at ages 1-4 years, coinciding with the period of linear growth retardation in deprived children. Noma is a scourge in communities with poor environmental sanitation. It results from complex interactions between malnutrition, infections, and compromised immunity. Diseases that commonly precede noma include measles, malaria, severe diarrhoea, and necrotising ulcerative gingivitis. The acute stage responds readily to antibiotic treatment. The sequelae after healing include variable functional and aesthetic impairments, which require reconstructive surgery. Noma can be prevented through promotion of national awareness of the disease, poverty reduction, improved nutrition, promotion of exclusive breastfeeding in the first 3-6 months of life, optimum prenatal care, and timely immunisations against the common childhood diseases.

Africa South of the Sahara↗

PubMed2004

Fungal biofilms and drug resistance.

Candida species, including the novel opportunistic pathogen Candida dubliniensis, are now emerging as major agents of nosocomial infections. Many such manifestations of infections associated with the formation of Candida biofilms include those occurring on devices such as indwelling intravascular catheters. Fungal biofilm-associated infections are frequently refractory to conventional therapy because of resistance to antimicrobial agents. This resistance could be in part due to the surface-induced upregulation of drug efflux pumps. Biofilm-associated Candida show uniform resistance to a wide spectrum of the currently available conventional antifungal agents, which implies that antimicrobial drugs that specifically target biofilm-associated infections are needed. The novel classes of antifungal agents, the lipid formulation of amphotericins, and the echinocandins have demonstrated unique antifungal activity against the resistant Candida biofilms, providing a breakthrough in the treatment of life-threatening invasive systemic mycoses. The use of drugs effective in combating biofilm-associated infections could lead to major developments in the treatment of fungal implant infections.

Antifungal Agents↗

PubMed2002

Nutrition and oral infectious diseases: state of the science.

Immunological competence and nutritional status are two of the most important determinants of morbidity and mortality. Oral diseases, particularly inflammatory periodontal lesions, are caused by viruses and specific periodontopathic bacteria. Paradoxically, the production of cytokines and oxidant molecules, which are supposed to be part of a highly effective mechanism for combating the periodontal pathogens, may damage the host. Malnutrition consistently impairs innate and adaptive defenses of the host, including phagocytic function, cell-mediated immunity, complement system, secretory antibody, and cytokine production and function. In protein-energy malnutrition, there are marked changes in the oral microbial ecology resulting in a preponderance of pathogenic anaerobic organisms, increased propensity of bacteria to bind to oral mucosal cells, attenuation of acute phase protein response, and dysfunction of the cytokine system. Cellular depletion of antioxidant nutrients promotes immunosuppression, accelerated replication rate of ribonucleic acid viruses, and increased disease progression. Therefore, malnutrition can intensify the severity of oral infections and may lead to their evolution into life-threatening diseases.

Acute-Phase Proteins↗

PubMedDate not supplied

Pro- versus anti-inflammatory cytokine profile in African children with acute oro-facial noma (cancrum oris, noma).

Fresh noma is a severe orofacial necrosis with an astonishingly rapid development. It is seen mainly in malnourished children less than 4 years old from developing countries. Cytokines play a central role in oral mucosal inflammation. We therefore studied the relevance of circulating cytokines to noma, and the key microorganisms associated with the lesion. Nigerian village children with acute noma (n=68) and their neighborhood village (n=63) as well as urban (n=45) counterparts of comparable age and free of overt infections were evaluated for serum cytokine levels by ELISA. Oral bacteria were studied by polymerase chain reaction. Evaluation of random cases of the village and noma children showed marked depletion (p<0.05 or 0.001) of the plasma antioxidant micronutrients (retinol, ascorbic acid, zinc) as well as albumin and blood hemoglobin in the latter, relative to the former group. Concentrations of the circulating, pro-inflammatory cytokines (IL-18, IL-6, IL-12, IL-8, IFN-gamma) and the soluble inhibitors (TNFR-p55, TNFR-p75 and IL-1ra) were significantly higher (p<0.01 or 0.001) in noma children than in the healthy urban children, but less so when compared to their neighborhood village counterparts. The increase in levels of the anti-inflammatory/regulatory cytokines (IL-4, IL-10 and TGF-beta) was less marked relative to the pro-inflammatory cytokines. Bacteria observed at the highest frequencies in noma lesions were P. intermedia (83%), T. forsythensis (83%), P. gingivalis (50%), C. rectus (50%) and T. denticola (50%). We conclude that noma is an immunopathological response to potent bacterial factors resulting in uncontrolled production of cytokines and possibly other, still unknown, inflammatory mediators.

Acute Disease↗