Using research feedback loops to implement a disability case study with Aboriginal and Torres Strait Islander communities and service providers in regional and remote Australia.

While there is a well-developed body of literature in the health field that describes processes to implement research, there is a dearth of similar literature in the disability field of research involving complex conditions. Moreover, the development of meaningful and sustainable knowledge translation is now a standard component of the research process. Knowledge users, including community members, service providers, and policy makers now call for evidence-led meaningful activities to occur rapidly. In response, this article presents a case study that explores the needs and priorities of Aboriginal and Torres Strait Islander women in Australia who have experienced a traumatic brain injury due to family violence. Drawing on the work of Indigenous disability scholars such as Gilroy, Avery and others, this article describes the practical and conceptual methods used to transform research to respond to the realities of community concerns and priorities, cultural considerations and complex safety factors. This article offers a unique perspective on how to increase research relevance to knowledge users and enhance the quality of data collection while also overcoming prolonged delays of knowledge translation that can result from the research-production process.

"Rhabdoid meningioma" lacking malignant features. Report of two cases.

We report 2 cases of meningiomas with rhabdoid morphology but lacking histological features of malignancy. Both occurred in adult women, one arising from the superior surface of the tentorium and the other in the Sylvian fissure. The tumors showed light microscopic, immunohistochemical and ultrastructural evidence of meningothelial differentiation together with diffuse or focal areas exhibiting rhabdoid morphology. The rhabdoid areas were characterized by cells with large cytoplasmic eosinophilic inclusions and large eccentric nuclei. Both cases showed areas with sheet-like growth and one had macronucleoli and brain invasion. The same case showed areas of necrosis that most likely related to pre-operative arterial embolization. Unlike most cases reported in the literature, these "rhabdoid meningiomas" lacked significant mitotic activity or other atypical features. The diagnostic and prognostic significance of this tumor entity is discussed along with a review of the literature.

In vitro and in vivo efficacies of the new triazole albaconazole against Cryptococcus neoformans.

The activity of albaconazole (UR-9825; J. Uriach & Cía. S.A., Barcelona, Spain) was compared to that of fluconazole against 12 isolates of Cryptococcus neoformans in vitro and against 1 isolate in vivo in a rabbit model of cryptococcal meningitis. Albaconazole was 100-fold more potent in vitro than fluconazole on a per-weight basis and was fungicidal at potentially relevant concentrations for two isolates. MICs ranged from

Tactile corpuscle-like bodies in colonic mucosa.

During the routine examination of a segment of colon resected for adenocarcinoma, a diffuse proliferation of mucosal tactile corpuscle-like bodies was identified. The bodies showed a lamellar structure by light microscopy and were S-100 positive. Electron microscopy demonstrated parallel slender processes with prominent surface caveolae, arising from peripheral cell bodies. Similar structures sometimes occur in neurofibromas but they have not previously been reported in the gastrointestinal tract.

Microvillous inclusion disease: report of a case with atypical features.

Microvillous inclusion disease is a rare lethal disorder characterized by intractable, severe, watery diarrhea beginning in early infancy. The underlying defect is thought to be an autosomal recessive genetic abnormality resulting in defective brush-border assembly and differentiation. Normally, this diagnosis is easily established through the electron microscopic demonstration of characteristic microvilli-lined inclusions lying within the apical cytoplasm of surface enterocytes. In a small number of patients appearing to have microvillous inclusion disease it has not proven possible to demonstrate the typical inclusions. The existence of another entity, termed intestinal microvillous dystrophy, has been proposed to account for such occurrences. This assertion was founded in large part upon the observation that the few subjects studied all displayed a slightly atypical clinical presentation. The case now being presented exhibited the morphologic features ascribed to intestinal microvillous dystrophy but had a clinical presentation that was entirely typical of microvillous inclusion disease. It serves thus to conceptually unite intestinal microvillous dystrophy with microvillous inclusion disease.

Phaeochromocytoma in two coatimundi (Nasua nasua).

Two unrelated coatimundi (Nasua nasua) had bilaterally enlarged adrenal glands at necropsy, and sections of the glands from both animals had histopathological features consistent with neoplasia. They were differentiated from an adrenal cortical tumour on the basis of their light microscopical morphology, immunoperoxidase staining and electron microscopic studies and a final diagnosis of phaeochromocytoma was made. To the authors' knowledge, these are the first reported cases of phaeochromocytoma in coatimundi.

Identification and characterization of the Cryptococcus neoformans phosphomannose isomerase-encoding gene, MAN1, and its impact on pathogenicity.

The polysaccharide capsule surrounding Cryptococcus neoformans comprises manose, xylose and glucuronic acid, of which mannose is the major constituent. The GDP-mannose biosynthesis pathway is highly conserved in fungi and consists of three key enzymes: phosphomannose isomerase (PMI), phosphomannomutase (PMM) and GDP-mannose pyrophosphorylase (GMP). The MAN1 gene, encoding for the PMI enzyme, was isolated and sequenced from C. neoformans, and a disruption of the MAN1 gene was generated. One MAN1 disruption mutant, man1, which showed poor capsule formation, reduced polysaccharide secretion and morphological abnormalities, was chosen for virulence studies. In both the rabbit and the mouse models of invasive cryptococcosis, man1 was shown to be severely impaired in its virulence, with complete elimination of the yeast from the host. A reconstituted strain of man1 was constructed using gene replacement at the native locus. The wild-type and reconstituted strains were significantly more virulent than the knock-out mutant in both animal models. Our findings reveal that PMI activity is essential for the survival of C. neoformans in the host. The fact that the man1 mutant was not pathogenic suggests that blocking mannose synthesis could be fungicidal in the mammalian host and thus an excellent target for antifungal drug development.

Hyalinising spindle cell tumour with giant rosettes: report of a case with unusual features including original histological and ultrastructural observations.

Hyalinising spindle cell tumour with giant rosettes (HSCTGR) is an uncommon, recently described low-grade sarcoma which shares many histological features with low-grade fibromyxoid sarcoma (LGFMS). We report a case of HSCTGR occurring in the deep soft tissues of the thigh of a 46-year-old woman, that presented as a slowly growing, painless mass. Microscopically the tumour was composed of spindled stromal cells amongst which were scattered so-called collagen rosettes. The distinctive feature of this case was the previously unreported finding of lymphoid cells of T-cell phenotype admixed with fibrohistioctyic cells in the cellular cuff surrounding the collagenous core of the rosettes. The case was further unusual in that it included focal areas of increased cellularity with a mitotic count of up to three per 10 high-power fields. While the latter feature has been associated with increased recurrences and metastases in LGFMS, it is not known whether the significance is similar in HSCTGR. The spindled stromal cells showed ultrastructural features of poorly differentiated fibroblasts, while those at the edges of the rosettes showed features of altered fibroblasts, some with a fibrohistiocytic appearance. These findings support the interpretation that HSCTGR forms part of the spectrum of sarcomas showing fibroblastic differentiation.

Roles for inositol-phosphoryl ceramide synthase 1 (IPC1) in pathogenesis of C. neoformans.

Cryptococcus neoformans is a leading cause of life-threatening fungal infection in immunocompromised patients. Inositol-phosphoryl ceramide synthase 1 (Ipc1) is a fungus-specific enzyme, encoded by the essential IPC1 gene, that catalyzes the formation of complex sphingolipids and may also regulate the levels of phytoceramide and diacylglycerol. Here, we investigated the functions of this essential gene by modulating its expression in C. neoformans using a galactose-inducible promoter. Down-regulation of IPC1 significantly lowers the expression of certain virulence traits such as melanin pigmentation and, remarkably, impairs pathogenicity of C. neoformans in an established rabbit model. Interestingly, we found that IPC1 down-regulation significantly decreases the intracellular growth of C. neoformans in the J774.16 murine macrophage-like cells. Finally, we studied the effect of IPC1 expression under different stress conditions and found that down-regulation of IPC1 confers a defect on in vitro growth at low pH. Because this environment is similar to that in the phagolysosome of J774.16 macrophage-like cells, our findings indicate that down-regulation of IPC1 confers a growth defect in vivo through a pH-dependent mechanism. In conclusion, our study is the first to define a novel and crucial function of Ipc1 in fungal pathogenesis.

Microvillous inclusion disease: report of a case with atypical features.

Microvillous inclusion disease is a rare lethal disorder characterized by intractable, severe, watery diarrhea beginning in early infancy. The underlying defect is thought to be an autosomal recessive genetic abnormality resulting in defective brush-border assembly and differentiation. Normally, this diagnosis is easily established through the electron microscopic demonstration of characteristic microvilli-lined inclusions lying within the apical cytoplasm of surface enterocytes. In a small number of patients appearing to have microvillous inclusion disease it has not proven possible to demonstrate the typical inclusions. The existence of another entity, termed intestinal microvillous dystrophy, has been proposed to account for such occurrences. This assertion was founded in large part upon the observation that the few subjects studied all displayed a slightly atypical clinical presentation. The case now being presented exhibited the morphologic features ascribed to intestinal microvillous dystrophy but had a clinical presentation that was entirely typical of microvillous inclusion disease. It serves thus to conceptually unite intestinal microvillous dystrophy with microvillous inclusion disease.

Role of the influenza virus M1 protein in nuclear export of viral ribonucleoproteins.

The protein kinase inhibitor H7 blocks influenza virus replication, inhibits production of the matrix protein (M1), and leads to a retention of the viral ribonucleoproteins (vRNPs) in the nucleus at late times of infection (K. Martin and A. Helenius, Cell 67:117-130, 1991). We show here that production of assembled vRNPs occurs normally in H7-treated cells, and we have used H7 as a biochemical tool to trap vRNPs in the nucleus. When H7 was removed from the cells, vRNP export was specifically induced in a CHO cell line stably expressing recombinant M1. Similarly, fusion of cells expressing recombinant M1 from a Semliki Forest virus vector allowed nuclear export of vRNPs. However, export was not rescued when H7 was present in the cells, implying an additional role for phosphorylation in this process. The viral NS2 protein was undetectable in these systems. We conclude that influenza virus M1 is required to induce vRNP nuclear export but that cellular phosphorylation is an additional factor.

The application of ultrastructural studies in the diagnosis of bladder dysfunction in a clinical setting.

PURPOSE: We examine the ultrastructural changes reported to be present in dysfunctional bladders and determine whether they can be used as a predictor of urodynamic diagnosis in a clinical setting. MATERIALS AND METHODS: Subjects who required urodynamic diagnosis and cystoscopy as part of clinical management were recruited for this study. After urodynamic diagnosis cases were classified into 1 of 5 dysfunction groups as normal bladder outflow obstruction, idiopathic sensory urgency, obstruction with detrusor instability and pure detrusor instability. A detrusor muscle biopsy was taken from the lateral wall of the bladder at cystoscopy for subsequent electron microscopy. RESULTS: Of the 27 cases 6 were normal, 9 had bladder outflow obstruction and detrusor instability, 8 had pure detrusor instability and 4 had idiopathic sensory urgency. The obstructed group showed the myohypertrophy pattern previously reported. In contrast to previous reports, abnormal junctions were found in all patients. For each patient the ratios of abnormal-to-normal junctions were calculated. Mean and standard error ratios were 1.1+/-0.1, 2.7+/-0.2, 6.1+/-1.2, 13.3+/-4.4 for normal, idiopathic sensory urgency, obstruction with detrusor instability and pure detrusor instability, respectively (p = 0.0003, 0.0042 and 0.04). CONCLUSIONS: There are distinct morphological changes in the detrusor associated with bladder dysfunction. The ratio of abnormal-to-normal junctions is a novel measurement and can be used to predict urodynamic dysfunction. Ultrastructural studies may be useful as an adjunct in the diagnosis of bladder dysfunction.

Serum albumin and survival in CAPD patients: the implications of concentration trends over time.

HYPOTHESIS: Trends in serum albumin concentration over time provide a better prediction of clinical outcome in CAPD patients than a single mean value. METHODS: This was a retrospective review of outcome at 36 months in 225 adult CAPD patients. Mean serum albumin was determined for the first (SA1) and second (SA2) 6 months of treatment and patients grouped according to SA1 (group I, > 37; group II, 34-37; group III, < 34 g/l) and according to the change in serum albumin (delta SA) between the first and second 6 months (increased/static or decreased). Patient (PS) and technique (TS) survival were determined by Kaplan-Meier survival analysis. The effect of SA1 and delta SA on survival were determined in a multivariate Cox regression analysis model that included age and presence or absence of a systemic disease. RESULTS: By SA1 group, PS and TS survival at 36 months were 94 and 76% (group I), 64 and 53% (group II) and 70 and 52% (group III). If delta SA increased/remained static, then SA1 did not predict PS (group I, 100%; group II, 96%; group III, 74%; P = n.s.) or TS (group I, 72%; group II, 63%; group III, 65%; P = n.s.). If delta SA decreased, PS was worse in groups II and III, both as compared to group I (PS group I, 88%; group II, 52%; group III, 34%; P = 0.02) and as compared to the groups II and III when delta SA increased (PS group II, 74 vs 52%, P = 0.05; group III, 82 vs 34%, P = 0.005) The same trend was seen for TS. In the multivariate Cox regression model, age, direction of change in serum albumin, and presence of a multisystem disease were significant predictors of survival, whereas SA1 was not. CONCLUSION: Early hypoalbuminaemia in CAPD only predicts a worse patient and technique survival if mean serum albumin decreases further from the first to second 6 months of dialysis therapy. Change in serum albumin between the first and second 6 months of CAPD and the mean serum albumin over the first 6 months together offer better discrimination of outcome than either alone.