Discordant repeat size and phenotype in Kennedy syndrome

Previous reports in the literature have described correlation of increasing repeat length with severity of the phenotype, in Kennedy syndrome. We describe male siblings with different repeat lengths, with lack of expression of the phenotype in the sibling with the longer repeat length. The phenotype was identical to motor neurone disease. There is variability of expression in Kennedy syndrome and repeat length even in siblings cannot be taken as a conclusive indicator of severity. CAG repeat length cannot be used to predict the natural history of Kennedy disease. The diagnosis of Kennedy syndrome should be considered in male patients presenting with atypical motor neurone disease.     

The requirements of the brain for some amino acids.

1. A constant specific activity of radioactively labelled amino acids was maintained in the circulation by means of a new technique devised for this purpose. This has made it possible to measure accurately the entry rates of amino acids into the brain in vivo. 2. The rates of entry into the brain of seven nutritionally non-essential amino acids were measured. 3. Glycine and proline enter the brain relatively slowly, at rates comparable to those of amino acids which are not normally found in the blood. Thus their entry is due mainly if not entirely to passive diffusion. 4. Serine (which is used by the brain to make glycine) and alanine (which is used to make glutamate and aspartate) enter the brain as rapidly as the essential amino acids and thus, although not essential for the body as a whole, appear to be essential for the brain. 5. It is suggested that those amino acids that the brain is able to synthesize have low rates of entry, even though they are present at high concentrations in the plasma, but that the transport systems for those amino acids that are not synthesized in the brain ensure rapid entry at rates that are related to the rates of cerebral utilization.     

Imaging spectrum in disseminated histoplasmosis: Case report and brief review

The clinical manifestations of chronic disseminated histoplasmosis are non-specific and resemble those of other chronic infections and malignancies. We report the radiographic, sonographic and contrast-enhanced CT appearances of histoplasmosis in an adult male with non-insulin dependent diabetes mellitus, who was HIV negative and presented with weight loss and pyrexia. Imaging studies simulated tuberculosis with mediastinal lymphadenopathy, bilateral fibrotic lung lesions, hepatomegaly and bilateral hypoattenuating adrenal enlargement, without clinical or laboratory evidence of hypoadrenalism. Computed tomography-guided fine-needle aspiration biopsy of adrenal glands revealed Histoplasma capsulatum. We report our experience to increase awareness of the imaging spectrum of disseminated histoplasmosis and its similarity to tuberculosis as, with increasing incidence of AIDS, the chances of these infections are likely to increase. Moreover, awareness of this entity is important because it is known that untreated disseminated histoplasmosis is fatal.     

Acute Budd–Chiari syndrome due to a simple liver cyst

Simple liver cysts are common, rarely causing significant morbidity or mortality. Budd–Chiari syndrome (BCS) is caused by obstruction of hepatic venous outflow and is the leading cause of postsinusoidal liver failure. We present a rare case of BCS caused by a simple hepatic cyst.A 16cm × 16cm liver cyst was found on computed tomography of a 66-year-old woman presenting with abdominal pain. The cyst had become infected, thus enlarged, exerting mass effect with almost complete compression of the inferior vena cava. Shortly after admission, the patient developed acute liver failure, with deranged clotting and hepatic encephalopathy requiring full organ support on the intensive care unit. Cardiac output studies showed a low cardiac index of 1.4l/min/m².An emergency laparotomy with fenestration of the cyst and drainage of 2l of purulent material led to a full recovery. Intraoperative cystic fluid aspirates later confirmed no evidence of Echinococcus. Histology confirmed a simple cyst. Liver biopsies showed severe, confluent, bridging necrosis, without background parenchymal liver disease.Acute BCS due to rapid compression of all major hepatic veins leading to fulminant hepatic failure is rare. Our case highlights a clinically significant complication of a simple liver cyst of which clinicians should be aware when managing these ‘innocent’ lesions.     

ImmunoGlobulin galaxy (IGGalaxy) for simple determination and quantitation of immunoglobulin heavy chain rearrangements from NGS

Background

Toxic shock syndrome (TSS) is caused by an overwhelming host-mediated response to bacterial superantigens produced mainly by Staphylococcus aureus and Streptococcus pyogenes. TSS is characterized by aberrant activation of T cells and excessive release of pro-inflammatory cytokines ultimately resulting in capillary leak, septic shock, multiple organ dysfunction and high mortality rates. No therapeutic or vaccine has been approved by the U.S. Food and Drug Administration for TSS, and novel therapeutic strategies to improve clinical outcome are needed. Mesenchymal stromal (stem) cells (MSCs) are stromal cells capable of self-renewal and differentiation. Moreover, MSCs have immunomodulatory properties, including profound effects on activities of T cells and macrophages in specific contexts. Based on the critical role of host-derived immune mediators in TSS, we hypothesized that MSCs could modulate the host-derived proinflammatory response triggered by Staphylococcal enterotoxin B (SEB) and improve survival in experimental TSS.

Methods

Effects of MSCs on proinflammatory cytokines in peripheral blood were measured in wild-type C57BL/6 mice injected with 50 μg of SEB. Effects of MSCs on survival were monitored in fatal experimental TSS induced by consecutive doses of D-galactosamine (10 mg) and SEB (10 μg) in HLA-DR4 transgenic mice.

Results

Despite significantly decreasing serum levels of IL-2, IL-6 and TNF induced by SEB in wild-type mice, human MSCs failed to improve survival in experimental TSS in HLA-DR4 transgenic mice. Similarly, a previously described downstream mediator of human MSCs, TNF-stimulated gene 6 (TSG-6), did not significantly improve survival in experimental TSS. Furthermore, murine MSCs, whether unstimulated or pre-treated with IFNγ, failed to improve survival in experimental TSS.

Conclusions

Our results suggest that the immunomodulatory effects of MSCs are insufficient to rescue mice from experimental TSS, and that mediators other than IL-2, IL-6 and TNF are likely to play critical mechanistic roles in the pathogenesis of experimental TSS.     

Case report: solitary haemangioblastoma of the fourth ventricle in an adolescent male.

We report a solitary haemangioblastoma arising from a pedicle in the wall of the fourth ventricle of the brain, which we believe to be the first report of haemangioblastoma occurring in this location. Computed tomography (CT), angiography and magnetic resonance imaging (MRI) made possible accurate pre-operative tumour identification and localization which facilitated a minimally invasive surgical resection.     

Peripheral nerve lesions in HTLV-I associated myelopathy (HAM/TSP)

Peripheral nerve dysfunction (PND) was found in as many as 43% of our patients with human T-cell lymphotropic virus type I (HTLV-I)–associated myelopathy (HAM/TSP). To evaluate the PND further we biopsied the sural nerve in 6 patients. The histological features were varying degrees of demyelination, remyelination, axonal atrophy and degeneration, and perineurial fibrosis. “Globule” or “sausage” formation was prominent in two of the specimens. Inflammatory infiltrates were absent. No deposits of IgG, IgM, IgA, or complement were detected in the biopsies. No viral antigen or proviral DNA was detected. It is proposed that the PND and the histological findings noted are part of HTLV-I–associated disease and not an unrelated disorder. The pathogenesis of the PND remains unclear. There was no evidence of direct viral infection. The histological findings could represent primary changes induced by viral-triggered release of soluble factors, such as cytokines or secondary changes to more proximal disease, e.g., root involvement. © 1993 John Wiley & Sons, Inc.     

Behavioral treatments for post-prostatectomy incontinence

Despite improvements in surgical approaches to radical prostatectomy, many patients experience moderate to severe urinary incontinence during the first few postoperative weeks. For some patients, leakage continues for several months or years. Urinary incontinence has a significant impact on quality of life in these typically active patients. Surgical interventions are not recommended until after a 6 to 12 month trial of behavioral interventions. Behavioral interventions include supportive care, diet and medication management, pelvic floor rehabilitation, inhibition techniques, and patient education and support. This integrative review of the literature summarizes current knowledge of behavioral interventions for post-prostatectomy urinary incontinence for the primary care and home care clinician. Aspects of care specific to masculine culture are explored. Recommendations for further research include determination of optimal timing and protocols for pelvic floor rehabilitation, best practices for patient and family education, and development of a standard definition of urinary incontinence so the efficacy of treatments can be compared.