Disappearance of Tophi in Familial Juvenile Hyperuricemic Nephropathy after Kidney Transplantation

A 40-year-old man who had been on hemodialysis for 25 months due to familial juvenile hyperuricemic nephropathy (FJHN) received a kidney transplant. Biopsy of his native kidney had shown tubulo-interstitial nephropathy. Genetic analysis confirmed abnormal uromodulin expression due to a mutation in the exon 4 of the UMOD gene. He had multiple tophi on the day of transplantation, including some on his fingers. He received immunosuppressive treatment including polyclonal antilymphocyte antibodies, mycophenolate mofetil, steroids and cyclosporine and achieved excellent renal function, with serum creatinine at 13 mg/L on day 10 posttransplantation and 9.4 mg/L at 6 months. His uric acid excretion rate increased from 4.4% at day 2 posttransplantation to 7.7% 6 months after transplantation. The number and sizes of the tophi were reduced 3 months posttransplantation, and nearly disappeared at month 6. Serum uric acid level decreased slowly from 650 mumol/L before transplantation to 300 mumol/L. Reduction of tophi was probably due to the absence of the mutated UMOD gene in the transplanted kidney.     

Epitopes of the G1 glycoprotein of La Crosse virus form overlapping clusters within a single antigenic site

Antigenic sites on the G1 glycoprotein of La Crosse bunyavirus were defined by constructing a panel of neutralizing and nonneutralizing monoclonal antibodies (F. Gonzalez-Scarano, R. E. Shope, C. H. Calisher, and N. Nathanson (1982), Virology 120, 42-53). To analyze the relationship between the individual epitopes delineated by monoclonal antibodies, 11 neutralizing antibodies were used to select variant viruses. These variant viruses were tested against the panel of anti-G1 protein monoclonal antibodies by neutralization and by ELISA. The neutralization tests assigned the 11 epitopes to five groups, consisting of 6, 2, 1, 1, and 1 epitopes. ELISA tests gave a similar pattern, but also demonstrated interrelationships between four of the five epitope groups, suggesting that there may be a single immunodominant antigenic site on the G1 protein. When eight nonneutralizing anti-G1 monoclonal antibodies were tested in ELISA, they fell into three of the five epitope groups defined by neutralization; there was no evidence of a separate noneutralizing antigenic site on the G1 protein.     

Effects of cobalt and chromium ions on glycolytic flux and the stabilization of hypoxia‐inducible factor‐1α in macrophages in vitro

Implant wear and corrosion have been associated with adverse tissue reactions that can lead to implant failure. Wear and corrosion products are therefore of great clinical concern. For example, Co²⁺ and Cr³⁺ originating from CoCrMo‐based implants have been shown to induce a proinflammatory response in macrophages in vitro. Previous studies have also shown that the polarization of macrophages by some proinflammatory stimuli is associated with a hypoxia‐inducible factor‐1α (HIF‐1α)‐dependent metabolic shift from oxidative phosphorylation (OXPHOS) towards glycolysis. However, the potential of Co²⁺ and Cr³⁺ to induce this metabolic shift, which plays a determining role in the proinflammatory response of macrophages, remains largely unexplored. We recently demonstrated that Co²⁺, but not Cr³⁺, increased oxidative stress and decreased OXPHOS in RAW 264.7 murine macrophages. In the present study, we analyzed the effects of Co²⁺ and Cr³⁺ on glycolytic flux and HIF‐1α stabilization in the same experimental model. Cells were exposed to 6 to 24 ppm Co²⁺ or 50 to 250 ppm Cr³⁺. Glycolytic flux was determined by analyzing extracellular flux and lactate production, while HIF‐1α stabilization was analyzed by immunoblotting. Results showed that Co²⁺, and to a lesser extent Cr³⁺, increased glycolytic flux; however, only Co²⁺ acted through HIF‐1α stabilization. Overall, these results, together with our previous results showing that Co²⁺ increases oxidative stress and decreases OXPHOS, suggest that Co²⁺ (but not Cr³⁺) can induce a HIF‐1α‐dependent metabolic shift from OXPHOS towards glycolysis in macrophages. This metabolic shift may play an early and pivotal role in the inflammatory response induced by Co²⁺ in the periprosthetic environment.     

Skin angiography assisted mastectomy in secondary breast angiosarcoma: Complete clinical response after neoadjuvant immunotherapy

Radiation-induced breast angiosarcoma, or secondary angiosarcoma (SAS), is a rare entity with a high risk of metastatic recurrence. Herein, we describe the use of intraoperative fluorescence-based skin angiography to guide surgical resection following a novel immunotherapy-based regimen for SAS resulting in a complete pathological response.     

Cancer Patterns in the Middle East Special Report from the Middle East Cancer Society

To update its cancer statistics, the newly established Middle East Cancer Society examined the cancer frequency patterns in Egypt and the Gaza Strip. The results revealed differing overall patterns. For men the highest frequencies were found for lymphoma, bladder cancer and cancers of the oral cavity and pharynx in Egypt, and for lung cancer, leukaemia and lymphoma in Gaza. For women, breast cancer had the highest frequency in both areas, followed by cancers of the oral cavity and pharynx in Egypt, and leukaemia and lymphoma in Gaza. The distribution of cancer occurrence by organ system also varied. In the light of the different ethnicities, lifestyles, socioeconomic levels and carcinogenic exposure among the countries of the Middle East, this kind of comparison can provide the background for more sophisticated approaches for discerning risk factors in cancer. We believe that further cooperation among participating countries will overcome the present limitations in data collection, registration and access.     

Establishment of a formal program for retinoblastoma: Feasibility of clinical coordination across borders and impact on outcome

Retinoblastoma is an ocular tumor that occurs in young children, in either heritable or sporadic manner. The relative rarity of retinoblastoma, and the need for expensive equipment, anesthesia, and pediatric ophthalmologic expertise, are barriers for effective treatment in developing countries. Also, with an average age‐adjusted incidence of two to five cases per million children, patient number limits development of local expertise in countries with small populations. Lebanon is a small country with a population of approximately 4.5 million. In 2012, a comprehensive retinoblastoma program was formalized at the Children's Cancer Institute (CCI) at the American University of Beirut Medical Center, and resources were allocated for efficient interdisciplinary coordination to attract patients from neighboring countries such as Syria and Iraq, where such specialized therapy is also lacking. Through this program, care was coordinated across hospitals and borders such that patients would receive scheduled chemotherapy at their institution, and monthly retinal examinations and focal laser therapy at the CCI in Lebanon. Our results show the feasibility of successful collaboration across borders, with excellent patient and physician adherence to treatment plans. This was accompanied by an increase in patient referrals, which enables continued expertise development. However, the majority of patients presented with advanced intraocular disease, necessitating enucleation in 90% of eyes in unilateral cases, and more than 50% of eyes in bilateral cases. Future efforts need to focus on expanding the program that reaches to additional hospitals in both countries, and promoting early diagnosis, for further improvement of globe salvage rates.