Alpha-interferon-induced arthritis: clinical presentation, treatment, and prevention

Objective:

The therapeutic applications of alpha-interferon (IFN) have expandedgreatly to include chronic viral hepatitis and malignant disorders. Autoimmune phenomena occur frequently with IFN therapy, but arthritis is uncommon. We describe the clinical features and treatment of IFN-induced arthritis.

Methods:

A patient with chronic myelogenous leukemia who developed arthritis secondary to IFN therapy is presented. The clinical features and treatment of this condition in 37 additional cases are reviewed.

Results:

The most common clinical presentation was symmetric polyarthritis.This was associated with antinuclear antibodies in 72% of patients and rheumatoid factor in 34%. Cessation of IFN, with or without the addition of antiinflammatory or remittive agents, resulted in remission of arthritis in 89% and 71% of the cases, respectively. Restarting IFN therapy resulted in recurrence of arthritis in 63%. In the patient described in this report, recurrence of arthritis was prevented by coadministration of hydroxychloroquine (HCQ) and prednisone.

Conclusion:

Arthritis is an uncommon complication of IFN therapy; but it may lead to cessation of this treatment modality. In such cases, coadministration of a remittive agent such as HCQ may enable reinstitution of IFN therapy without recurrence of arthritis.     

Hepatic stem cells and transforming growth factor β in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common and lethal cancers worldwide. It arises from modulation of multiple genes by mutations, epigenetic regulation, noncoding RNAs and translational modifications of encoded proteins. Although >40% of HCCs are clonal and thought to arise from cancer stem cells (CSCs), the precise identification and mechanisms of CSC formation remain poorly understood. A functional role of transforming growth factor (TGF)-β signalling in liver and intestinal stem cell niches has been demonstrated through mouse genetics. These studies demonstrate that loss of TGF-β signalling yields a phenotype similar to a human CSC disorder, Beckwith-Wiedemann syndrome. Insights into this powerful pathway will be vital for developing new therapeutics in cancer. Current clinical approaches are aimed at establishing novel cancer drugs that target activated pathways when the TGF-β tumour suppressor pathway is lost, and TGF-β itself could potentially be targeted in metastases. Studies delineating key functional pathways in HCC and CSC formation could be important in preventing this disease and could lead to simple treatment strategies; for example, use of vitamin D might be effective when the TGF-β pathway is lost or when wnt signalling is activated.     

Effect of a niobium-containing titanium alloy on osteoblast behavior in culture

Background: The chemistry of titanium is a key factor in determining implant–tissue interactions. Reports that a vanadium-based titanium alloy (Ti–6Al–4V) exhibits some cytotoxicity led to a search for an alternative.
Aim: The aim of the present study was to investigate the behavior of human osteoblast-like cells (Saos-2) cultured on Ti–6Al–4V or Ti–6Al–7Nb disks with a rough or a machined surface.
Results: In all four groups, the cells proliferated rapidly between days 1 and 3, and then plateaued. On day 1 of culture, the highest proliferation rate was of cells cultured on disks containing Nb with a machined surface. On day 7, there was no significant difference in cell density on all the tested surfaces. Alkaline phosphatase (ALP) activity was lower on the machined surfaces, regardless of the material used, suggesting that cells on rough surfaces exhibit a more mature phenotype. On day 3, cells cultured on rough disks made of Ti–6Al–7Nb showed the highest ALP activity; the lowest activity was observed on the machined Ti–6Al–4V surface. The highest level of osteocalcin (day 7) was found in the cells cultured on rough Ti–6Al–7Nb disks. Also, higher levels of transforming growth factor (TGFβ) were noted for cells cultured on the rough Ti–6Al–7Nb disks, suggesting that the Nb-containing alloy supports more rapid maturation of the osteoblast.
Conclusions: The results of the present study suggest that according to our cell culture preclinical model, Ti–6Al–7Nb may replace the Ti–6Al–4V alloy as an implant material.     

Prevalence and impact of nocturia in a urogynecologic population

To determine the prevalence of nocturia and associated bother among patients presenting to a tertiary urogynecology clinic and to describe patient characteristics related to nocturic frequency and associated bother. Chart review of sequential new patients presenting to our clinic between June 2004 and May 2005. We recorded patients’ response to a question about their frequency of nocturia, the level of associated bother, demographic data, history of chronic medical illness and clinical urogynecologic diagnosis. Seven hundred sixty patients were of mean age 56 (19–95) years. Eighty-seven percent of patients voided at least once nightly, and 60% usually voided at least twice nightly. Forty one percent of patients reported bother ≥5/10 from nocturia. High bother rating was associated with increasing number of nocturic episodes (p < 0.0005) and mixed incontinence (p = 0.012). Nocturia is common and bothersome to women presenting for urogynecologic care. Concomitant mixed incontinence significantly increases bother arising from nocturia.     

Salvage of locally recurrent breast cancer with repeat breast conservation using 45 Gy hyperfractionated partial breast re-irradiation

Breast Cancer Research and Treatment - Mastectomy has long been the preferred approach for local salvage of recurrent breast cancer following breast-conservation therapy (BCT). Growing interest in...     

PNist: interactive volumetric measurements of plexiform neurofibromas in MRI scans

Purpose

Volumetric measurements of plexiform neurofibromas (PNs) are time consuming and error prone, as they require the delineation of the PN boundaries, which is mostly impractical in the daily clinical setup. Accurate volumetric measurements are seldom performed for these tumors mainly due to their great dispersion, size and multiple locations. This paper presents a semiautomatic method for segmentation of PN from STIR MRI scans.

Methods

Plexiform neurofibroma interactive segmentation tool (PNist) is a new tool to segment PNs in STIR MRI scans. The method is based on histogram tumor models computed from a training set.

Results

Experimental results from 28 datasets show an average absolute volume difference of 6.8 % with an average user time of approximately 7 min versus more than 13 min with manual delineation. In complex cases, the PNist user time is less than half in compared to state-of-the-art tools.

Conclusions

PNist is a new method for the semiautomatic segmentation of PN lesions. Its simplicity and reliability make it unique among other state-of-the-art methods. It has the potential to become a clinical tool that allows the reliable evaluation of PN burden and progression.