Fulminant Neisseria meningitidis septicaemia with purpura fulminans requiring limb amputation.

Despite the isolation of Neisseria meningitidis over 200 years ago, meningococcal disease remains a feared cause of bacterial sepsis, with significant morbidity and mortality, despite prompt antibiotic use and modern critical care support. Neisseria meningitides is a Gram-negative encapsulated diplococcus, which exists only in the human host (Kvalsvig and Unsworth, 2003). The bacterium can cause life-threatening septic shock and coagulopathy, which may rapidly manifest within a matter of hours from preceding mild symptoms (Kvalsvig and Unsworth, 2003). Whilst N. meningitidis is recognised as a common commensal organism in the nasopharynx, associated with asymptomatic carriage in up to 10 %, manifestation of life-threatening disease is rare (Rappuoli and Pizza, 2015). We report the case of 31-year-old male presenting with devastating meningococcal septicaemia with disseminated intravascular coagulopathy (DIC) and purpura fulminans, requiring surgical debridement and a right above-knee amputation for sepsis-driven skin necrosis. The patient suffered extensive tissue loss secondary to a type 3 immune hypersensitivity reaction involving immune-complex mediated inflammation and tissue necrosis. Due to a strong immune component driving the patient's failure to convalesce pulsed intravenous methylprednisolone was used alongside antimicrobial therapy. The use of steroids was associated with fever subsidence and significant clinical improvement, highlighting the benefit of corticosteroid use in immune-complex mediated pathology.

Restoration of maxillary anterior esthetics using lava all-ceramic fixed dental prostheses.

The success of all-ceramic crowns and increased patient demand for metal-free, tooth-colored restorations has led to the development of many different restorative systems for all-ceramic fixed dental prostheses (FDPs). The most recent core materials for all-ceramic FDPs are the yttrium-tetragonal zirconia polycrystal (Y-TZP)-based materials. Yttrium oxide is a stabilizing oxide added to pure zirconia to stabilize it at room temperature and to generate a multiphase material known as partially stabilized zirconia. This exhibits very high flexural strength and fracture toughness along with good biocompatibility and excellent esthetics. This clinical report describes the use of the Lava All-ceramic system, based on Y-TZP, for the fabrication of two fixed dental prostheses (FDPs) in the maxillary anterior region of the patient, restoring both esthetics and function.

Identification of HNF1A-MODY and HNF4A-MODY in Irish families: phenotypic characteristics and therapeutic implications.

AIM: The prevalence of hepatocyte nuclear factor (HNF)-1A and HNF4A mutations, and the clinical implications following the genetic diagnosis of maturity-onset diabetes of the young (MODY) in the Irish population, remain unknown. The aim of this study was to establish the occurrence of HNF1A and HNF4A mutations in subjects classified clinically as MODY to identify novel mutations, and to determine the phenotypic features and response to therapy. METHODS: A total of 36 unrelated index cases with a clinical diagnosis of MODY were analyzed for HNF1A/HNF4A mutations. OGTT was performed to determine the degree of glucose tolerance and insulin secretory response. Also, 38 relatives underwent OGTT and were tested for the relevant known mutations. HNF1A-/HNF4A-MODY subjects were compared with nine HNF1A mutation-negative relatives and 20 type 2 diabetic (T2DM) patients. RESULTS: Seven different HNF1A mutations were identified in 11/36 (30.5%) index cases, two of which were novel (S352fsdelG and F426X), as well as two novel HNF4A mutations (M1? and R290C; 6%). Family screening revealed 20 subjects with HNF1A and seven with HNF4A mutations. Only 51.6% of HNF1A mutation carriers were diagnosed with diabetes by age 25 years; 11 of the mutation carriers were overweight and four were obese. Insulin secretory response to glucose was significantly lower in HNF1A-MODY subjects than in T2DM patients and HNF1A mutation-negative relatives (P=0.01). Therapeutic changes occurred in 48% of mutation carriers following genetic diagnosis. CONCLUSION: There was an HNF1A-MODY pick-up rate of 30.5% and an HNF4A-MODY pick-up rate of 6% in Irish MODY families. Genetically confirmed MODY has significant therapeutic implications.

Ectodermal dysplasia with total anodontia: rehabilitation of a seven year old child.

Total anodontia in a paediatric patient is a difficult prosthetic problem. Upper and lower complete dentures were fabricated for a 7 year old patient with anodontia. The problems encountered on account of the age of the child, the absence of alveolar processes, the tooth size and acceptability of the dentures are discussed herein.

Performance evaluation of QuantiBRITE phycoerythrin beads.

BACKGROUND: The performance of QuantiBRITE phycoerythrin (PE) beads to standardize quantitation in terms of antibodies bound per cell (ABC) was evaluated by measuring precision, variation across multiple instruments, and variation across time. METHODS: For CD4 quantitation, whole blood was stained with a two-color CD4 reagent using a no-wash/no-lyse format. For CD69 quantitation, whole blood was activated with either phorbol myristate acetate (PMA) or CD3 beads and then stained with a three-color CD69 reagent using a lyse-no-wash format. RESULTS: Across 20 normal donors, the mean CD4 ABC was 51,000. Within-assay precision on quantitation of CD4 ABC on T cells had a coefficient of variance (CV) of <1.0%. Across multiple flow cytometers, quantitation of CD4 ABC had a CV of <5.0%. Within-donor CV on CD4 ABC on 20 donors across 2 months ranged from 1.3% to 3.2%. Within-assay precision on quantitation of CD69 on T cells activated with either PMA or CD3 beads had a CV of <3.0%. Within-donor CV of CD69 ABC across 1 month ranged from 2% to 18% on PMA-activated samples and from 7% to 24% on CD3 bead-activated samples. CONCLUSIONS: Our results indicate that the QuantiBRITE PE beads provide a useful tool for standardized analysis across labs. When used in conjunction with 1:1 conjugates of PE-to-monoclonal antibody, the QuantiBRITE PE beads provide a simple yet robust means of quantitating expression levels in terms of ABC.