As an RNA binding protein, CUG-BP Elav-like family (CELF) has been shown to be critical for heart biological functions. However, no reports have revealed the function of CELF1 in hypertrophic cardiomyopathy (HCM). Hinted by RNA immunoprecipitation-sequencing (RIP-seq) data, the influence of the CELF protein on heme oxygenase-1 (HO-1) expression was tested by modulating CELF1 levels. Cardiac hypertrophy is related to oxidative stress-induced damage. Hence, the cardiovascular system may be protected against further injury by upregulating the expression of antioxidant enzymes, such as HO-1. During the past two decades, research has demonstrated the central role of HO-1 in the protection against diseases. Thus, understanding the molecular mechanisms underlying the modulation of HO-1 expression is profoundly important for developing new strategies to prevent cardiac hypertrophy.To elucidate the molecular mechanisms underlying HO-1 regulation by the CELF protein, we performed RNA immunoprecipitation (RIP), biotin pull-down analysis, luciferase reporter and mRNA stability assays. We found that the expression of HO-1 was downregulated by CELF1 through the conserved GU-rich elements (GREs) in HO-1 3′UTR transcripts. Correspondingly, CELF1 expression was regulated by controlling the release of carbon monoxide (CO) in H9C2 cells. The CELF1-HO-1-CO regulation axis constituted a novel positive feedback circuit. In addition, we detected the potential involvement of CELF1 and HO-1 in samples from HCM patients. We found that CELF1 and CELF2, but not HO-1, were highly expressed in HCM heart samples. Thus, a manipulation targeting CELF1 could be developed as a potential therapeutic option for cardiac hypertrophy.

In the last decade, liquid chromatography-tandem mass spectrometry (LC-MS/MS) has seen enormous growth in routine toxicology laboratories. LC-MS/MS offers significant advantages over other traditional testing, such as immunoassay and gas chromatography-mass spectrometry methodologies. Major strengths of LC-MS/MS include improvement in specificity, flexibility, and sample throughput when compared with other technologies. Here, the basic principles of LC-MS/MS technology are reviewed, followed by advantages and disadvantages of this technology compared with other traditional techniques. In addition, toxicology applications of LC-MS/MS for simultaneous detection of large panels of analytes are presented.

Charcot neuropathy is a painless, progressive, degeneration most notably of the ankle or midfoot joints, seen in patients with diabetes and neuropathy. This article will describe the etiology, diagnosis, and treatment of this potentially debilitating joint disease and provide implications for home care clinicians.

Congenital brachymetatarsia is often treated with callus distraction. This technique is associated with a variety of complications. We investigated complications encountered in treatment of brachymetatarsia in four female patients and reviewed adjunctive procedures performed to treat these complications. We reviewed five distraction osteogenesis procedures performed in four female patients with congenital shortening of the fourth metatarsal over a 3-year period. Serial radiographs were obtained weekly until bone consolidation was achieved, at which time the external fixator was removed. Follow-up ranged from 5 to 10 months. Three patients (four metatarsals) were satisfied with the cosmetic and functional outcomes of their procedure. One patient was dissatisfied with the cosmetic result owing to a short digit from a short proximal phalanx but was completely functional and resumed all of her normal activities. Complications associated with callus distraction were decreased range of motion and stiffness at the metatarsophalangeal joint, flexion deformity of the digit, angulation of the metatarsal, prolonged distraction time due to pain, fracture of the bone callus, pin-site infection, and an undesirable cosmetic appearance due to a short proximal phalanx. Adjunctive procedures were needed in some of these cases and yielded good results. Callus distraction is an effective treatment for congenital shortening of the fourth metatarsal, but the procedure is associated with a number of complications. Because most patients proceed with surgery for cosmetic reasons, it is important to present the possible complications and the adjunctive surgical procedures that may be necessary for a desirable outcome.

Synovial chondromatosis is a rare, generally benign condition characterized by the formation of multiple cartilaginous nodules in the synovium of joints and occasionally on the tendon sheath or bursae. If the nodules are intra-articular, the condition is referred to as synovial chondromatosis; if extra-articular, tenosynovial chondromatosis. This space-occupying lesion can lead to chronic pain and limit the function of involved joints. We report a case of synovial chondromatosis involving the subtalar joint and tenosynovial chondromatosis involving the posterior ankle and review current definitions of this uncommon lower-extremity condition.

We describe the management of a patient who presented to a family-practice clinic with gangrenous digits. After a thorough evaluation, she was found to have protein C deficiency, which produced a hypercoagulable state. Differential diagnosis in the evaluation of the coagulopathic patient with appropriate hematologic tests is briefly discussed.

In this retrospective review, 19 diabetic patients with significant lower-extremity pathology were assessed to determine the success of limb salvage in cases of varying complexity. The patients were either scheduled or at risk for below-the-knee amputation before intervention. After the limb-salvage procedure, patients were followed for 4 months to 9 years. Eighteen patients went on to have successful procedures, avoiding below-the-knee amputation; one patient had an above-the-knee amputation. The results demonstrate the benefits of an aggressive team approach with limb salvage as a goal.

Latex allergy in recent years has become a more visible problem in the medical community. There are certain populations found to be at greater risk for this problem. Those with myelodysplasia, congenital urinary anomalies, and a history of a significant number of prior surgeries are particularly at risk, followed less commonly by health care workers and the general population. A detailed patient history is the most reliable predictor of latex sensitivity. There are various immunological and serological screening tests on the market, which are not always reliable predictors of allergy or readily available to the physician. This article reviews the current literature on latex allergy and provides insight into populations at risk, the type of allergic response seen, predictors of sensitivity, management of patients with latex allergy, and measures to prevent it.

The authors present a case report of acral lentiginous malignant melanoma in a 77-year-old male. Melanoma is a rare but increasingly present malignant lesion of the lower extremity. It is the most common malignant neoplasm in blacks and is often misdiagnosed. Early, accurate diagnosis and biopsy of suspicious lesions is the cornerstone of treatment in order to decrease possible future morbidity and mortality. The authors discuss the clinical features, differential, diagnosis, predisposing factors, diagnosis, classification, and treatment of malignant melanoma.