ATX-101 for reduction of submental fat

Introduction: Facial esthetics are important for self-esteem. Undesired submental fat (SMF) deposits lead to an unappealing submental profile associated with aging and overweight. Compound ATX-101 is a proprietary formulation of purified synthetic deoxycholic acid for pharmacological submental contouring.

Review areas covered: This reviews covers anatomy of SMF, biochemistry of deoxycholic acid related to adipose tissue and tissue response to injection of ATX-101. Data from clinical trials were analyzed for efficacy and safety.

Methodology: Published studies using PubMed^© database 2000 – 2014 have been analyzed. The terms ‘deoxycholate’, ‘deoxycholic acid’, ‘ATX-101’ and ‘injection lipolysis’ were used.

Results: Deoxycholic acid causes adipocyte breakdown and an inflammatory tissue reaction leading to fat cell reduction and limited fibrosis. Four large clinical Phase III trials demonstrated efficacy of ATX-101 in reduction of SMF measured by validated scales and objective measurements. Patients reported improved psychological features and feeling. Adverse effects were mild and temporary.

Expert opinion: Adipocytolysis of SMF by ATX-101 is an important step forward to the development of approved drugs for reduction of localized fat pads. This could become a growing market.     

Increased Ca 2+-sensitivity of myofibrillar tension in heart failure and its functional implication

In human failing myocardium, an increased Ca ²⁺-sensitivity of myofilament tension development has been described in Triton X skinned cardiac myocytes compared to cardiomyocytes obtained from non-failing human donor hearts. The present study aimed to investigate whether there are functional implications of the increased Ca ²⁺-sensitivity in heart failure and whether alterations of myofilament function are already obvious at earlier stages of heart failure, such as in cardiac hypertrophy or whether alterations of the intracellular Ca ²⁺-homeostasis are able to induce alterations in myofilament function. Ca ²⁺-activated tension development was measured in Triton X-skinned fibers from human failing and non-failing myocardium. Ca ²⁺-sensitivity of myofilament tension development was significantly shifted to the left in human failing myocardium. Plots of diastolic free Ca ²⁺ versus diastolic tension development showed that in a range of similar diastolic Ca ²⁺-concentrations, diastolic tension was significantly enhanced in the failing hearts. The Ca ²⁺/tension relationship was shifted to the right in Triton X-skinned fiber preparations from transgenic renin overexpressing rats (TG(mREN2)27), shown to have concentric hypertrophy. In addition, the Ca ²⁺/tension relationship was unchanged in phospholamban knock-out mice with an increased systolic Ca ²⁺ (and enhanced diastolic Ca ²⁺-load). It is concluded that the increased Ca ²⁺-sensitivity of myofilament tension observed in single cardiomyocytes from failing human myocardium may be a phenomenon also present in multicellular preparations and may contribute to the diastolic dysfunction observed in human heart failure. Alterations of myofilament function occur at very early stages of heart failure and may be species dependent, or dependent on intracellular free Ca ²⁺-levels.     

Chronic sacral spinal nerve stimulation for fecal incontinence: Long-term results with foramen and cuff electrodes

PURPOSE: Sacral spinal nerve stimulation is a new therapeutic approach for patients with severe fecal incontinence owing to functional deficits of the external anal sphincter. It aims to use the morphologically intact anatomy to recruit residual function. This study evaluates the long-term results of the first patients treated with this novel approach applying two techniques of sacral spinal nerve stimulator implantation. METHODS: Six patients underwent either of two techniques for electrode placement: one closed (electrodes placed through the sacral foramen) and one open (cuff electrodes placed after sacral laminectomy). Follow-up evaluation of their continence status ranged from 5 to 66 months. RESULTS: Incontinence improved in all patients. The percentage of incontinent bowel movements decreased during chronic stimulation from a mean of 40.2 percent to 2.8 percent, and the Wexner score decreased from a mean of 17 to 2. The function of the striated anal sphincter improved during chronic stimulation: maximum squeeze pressure increased from a mean of 48.5 mmHg to 92.7 mmHg, and median squeeze pressure increased from a mean of 37.3 mmHg to 72.5 mmHg. No complications were encountered perioperatively or postoperatively. Two devices had to be removed because of intractable pain, in one patient at the site of the electrode after five months and in the other at the site of the impulse generator after 45 months. CONCLUSION: Long-term sacral spinal nerve stimulation persistently improves continence and increases striated anal sphincter function in patients with fecal incontinence owing to functional deficits, but in whom the striated anal sphincter is morphologically intact. Two different operative approaches can be applied effectively.Supported by grants from Bayerischen Chirurgen e.V., Munich, Germany; Wilhelm Sander Stiftung, Neustadt, Germany; and Bakken Research Center, Medtronic, Maastricht, the Netherlands.A preliminary report of this study was presented as a poster at the meeting of The American Society of Colon and Rectal Surgeons, San Antonio, Texas, May 2 to 7, 1998.     

Long-term treatment with deferiprone in a L1 veteran

We studied a patient with mild beta-thalassaemia major under treatment with the oral chelator deferiprone (DFP or L1) for about 10 yr (L1 veteran). Due to poor compliance with desferrioxamine, the patient started compassionate use of DFP at an age of 23 yr with a serum ferritin of 5200 microg/L. Monitoring iron overload by SQUID biosusceptometry revealed a dramatic decrease of liver iron concentrations from 4500 to 950 microg/g(liver) within 9.5 yr. A good clinical response to chelation treatment with DFP was observed together with an improvement of liver and cardiac function and a reduction in the hepatitis virus load.