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Chronic mucocutaneous candidiasis (CMC) is a primary immunodeficiency disorder characterised by susceptibility to chronic Candida and fungal dermatophyte infections of the skin, nails and mucous membranes. Molecular epidemiology studies of CMC infection are limited in number and scope and it is not clear whether single or multiple strains inducing CMC persist stably or are exchanged and replaced. We subjected 42 C. albicans individual single colony isolates from 6 unrelated CMC patients to multilocus sequence typing (MLST). Multiple colonies were typed from swabs taken from multiple body sites across multiple time points over a 17-month period. Among isolates from each individual patient, our data show clonal and persistent diploid sequence types (DSTs) that were stable over time, identical between multiple infection sites and exhibit azole resistant phenotypes. No shared origin or common source of infection was identified among isolates from these patients. Additionally, we performed C. albicans MLST SNP genotype frequency analysis to identify signatures of past loss of heterozygosity (LOH) events among persistent and azole resistant isolates retrieved from patients with autoimmune disorders including CMC.

We recently reported the genetic cause of autosomal dominant chronic mucocutaneous candidiasis (AD-CMC) as a mutation in the STAT1 gene. In the present study we show that STAT1 Arg274Trp mutations in the coiled-coil (CC) domain is the genetic cause of AD-CMC in three families of patients. Cloning and transfection experiments demonstrate that mutated STAT1 inhibits IL12R/IL-23R signaling, with hyperphosphorylation of STAT1 as the likely underlying molecular mechanism. Inhibition of signaling through the receptors for IL-12 and IL-23 leads to strongly diminished Th1/Th17 responses and hence to increased susceptibility to fungal infections. The challenge for the future is to translate this knowledge into novel strategies for the treatment of this severe immunodeficiency.

Cytologic investigations of 16 proven cases of gallbladder carcinomas were analyzed in order to establish the usefulness of cytological methods, including exfoliative bile cytology, fine needle aspiration and endoscopic brushing, in the preoperative and intraoperative diagnosis and management of gallbladder carcinoma. Fine needle aspiration cytology had a sensitivity of 88% and exfoliative cytology of bile a sensitivity of 50%, but both brushings performed yielded false negatives. A preoperative diagnosis was made in 69% (9/13) of cases, and cytologic diagnosis was helpful in planning surgical management. We recommend its wider application in the preoperative diagnosis of gallbladder carcinoma.

A total of 51 technetium-99m (99mTc)-labelled autologous red cell (LRC) scans performed on 49 patients for the localization of obscure gastrointestinal bleeding over a 5-year period was reviewed. The sensitivity for LRC scanning was 72.7% with a positive predictive value of 84.2%. Forty patients underwent both LRC scanning and visceral angiography during the same admission; angiography had a sensitivity of 38.9% compared with 66.7% for LRC scanning and the positive predictive values were 77.8% and 85.7%, respectively. Overall, the site of bleeding was located in 22 (45%) of 49 patients, but LRC scanning alone was successful in identifying the lesion in 16 (33%) cases. In patients who continue to bleed to the point of requiring operation, a combination of scintigraphy and angiography will localize a source in 70% of patients.

A case of metastatic angiosarcoma of the ovary, complicated by disseminated intravascular coagulation, is described. The tumour was diagnosed by histopathologic examination and immunohistochemical studies. Angiosarcoma of the ovary, although extremely rare, appears to be a highly malignant neoplasm with an aggressive course and effective therapy is unknown.

Duodenocaval fistula is exceedingly rare. Penetrating trauma, gunshot wounds and toothpick perforation of the duodenum are known aetiological factors. Two recent case reports have implicated radiation-induced ulceration of the duodenum. We describe the first case of duodenocaval fistula resulting from a giant peptic ulcer of the descending duodenum.

This review describes our use of the Dor operation in the management of 22 patients with achalasia of the cardia over the period 1970 to 1989. There was a male to female ratio of 1.8:1. All presented with dysphagia of varying degree, with regurgitation (86%), weight loss (73%), pain (59%) and chest infections (14%) being associated symptoms. Two patients had undergone previous balloon dilatation, with temporary benefit. The morbidity was low and follow-up results were good in 94% of cases. None of the patients had symptoms of gastro-oesophageal reflux in the postoperative period. In our experience, the Dor modification of the Heller operation has yielded gratifying results.