An anatomical way of treating ankle syndesmotic injuries

Treatment of tibiofibular syndesmotic ankle injury remains controversial in regard to the best method, although surgeons agree that the goal of treatment is reduction and operative stabilization. Ideally, the implant should stabilize the syndesmosis and allow physiologic micromotion and early mobilization, and conventional screws are limited in this regard. We reviewed use of the Ankle TightRope(?) fixation device for repair of syndesmotic injuries. From April to September 2006, 16 patients with evidence of syndesmotic injury were treated by means of ankle fracture open reduction with internal fixation, combined with use of the Ankle TightRope(?) device for repair of the syndesmosis. The mean age of the 16 patients was 36.6 ± 16.71 (range 15 to 69) years; they were followed up for at least 2 years. Mean follow-up duration was 26 ± 3.94 (range 24 to 38) months. The mean American Orthopaedic Foot and Ankle Society score at 2-year follow-up was 86.88 ± 11.49 (range 48 to 100). The mean time to full weight-bearing was 4.5 ± 0.87 weeks. Two (12.5%) patients had postoperative superficial wound infections, each of which was treated with oral antibiotics. One (6.25%) patient had the TightRope(?) removed because of irritation from the knot. There was no failure of syndesmotic fixation, despite early weight-bearing in the postoperative phase. The results of this case series indicate that tibiofibular syndesmosis repair with the Ankle TightRope(?) yields satisfactory results.     

Asymptomatic Papulo-nodules Localized to One Finger

Subcutaneous or deep granuloma annulare is a benign asymptomatic condition characterized by firm asymptomatic nodules in deep subcutaneous tissues that may be associated with intradermal lesions. A 53-year-old female presented with asymptomatic skin-colored, firm nodules over the right ring finger. Histopathology revealed a palisading granuloma with central degenerated collagen and mucin deposition in the dermis suggestive of granuloma annulare. Isolated and unilateral involvement of a single digit with clusters of nodules of subcutaneous granuloma annulare (GA) in an adult is rare and differentiation from its simulator rheumatoid nodule is essential.     

Serelaxin in acute heart failure: Most recent update on clinical and preclinical evidence

Heart failure continues to be a widely prevalent disease across the world, affecting millions of Americans annually. Acute heart failure (AHF) has a substantial effect on rising healthcare costs and is one of the major causes of morbidity and mortality. The search for new drugs for symptom relief and to improve long‐term outcomes in heart failure has led to development of serelaxin, a recombinant human relaxin‐2 hormone. Relaxin was discovered in pregnancy, but eventually found to have a number of other physiological actions, not only in pregnancy, but also in nonpregnant women and men. The actions of serelaxin are primarily via nitric oxide, leading to the observed vasodilatory effects, and increase in renal plasma flow. It has also been found to increase expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)‐2 and MMP‐9. The antifibrotic and antiinflammatory effects of the drug also play a role in heart failure. In Phase II studies, serelaxin has shown reduction in pulmonary arterial pressure, pulmonary capillary wedge pressure, and NT‐proBNP. The recently published results of the RELAX‐AHF, a phase III clinical trial on serelaxin, has opened new avenues into our understanding of its effects in heart failure. The trial showed improvement in short‐term dyspnea scores and 180‐day mortality, but, interestingly, failed to show any improvement of the secondary endpoints of death or readmission at 60 days. Ongoing Phase III trials like RELAX‐AHF‐2 and RELAX‐AHF‐ASIA would explain these data better and improve understanding of the use of serelaxin in clinical practice. This article summarizes the most updated published preclinical and clinical study data on serelaxin, including pharmacokinetic, pharmacodynamic, safety studies in hepatic, renal impaired patients, Phase II and Phase III trials.     

Is an Alternative Drug Delivery System Needed for Docetaxel? The Role of Controlling Epimerization in Formulations and Beyond

Purpose

The presence of 7-epidocetaxel in docetaxel injection and in vivo epimerisation has been reported to be the cause for development of tumor resistance to chemotherapy including docetaxel by inducing tumor cell protein cytochrome P450 1B1. The objective of this study was to determine systemic toxicity of Taxotere® containing 10% 7-epidocetaxel and to develop PEGylated liposomal injection that could resist epimerization in vivo. Another need for PEGylated liposomal delivery of docetaxel is to avoid reported hypersensitivity reactions of marketed products like Taxotere® and Duopafei® containing high concentration of tween-80.

Methods

The PEGylated liposomes loaded with docetaxel were prepared using thin film hydration method. The in vivo toxicity of Taxotere® containing 10% 7-epimer was studied in B16F10 experimental metastasis model.

Results

B16F10 experimental metastasis model using C57BL/6 mice injected with Taxotere® containing 10% 7-epimer showed higher weight loss as compared to Taxotere® containing no epimer at single dose of 40 mg/kg indicating higher systemic toxicity. Incubation of PEGylated liposomes with phosphate buffer saline (pH 7.4) containing 0.1% w/v Tween-80 for 48 h showed better resistance to docetaxel degradation when compared with Taxotere® injection indicating better in vivo stability of liposomal docetaxel. In addition, PEGylated liposomes showed enhanced in vitro cytotoxicity, against A549 and B16F10 cells, than Taxotere®.

Conclusion

We can therefore expect less in vivo conversion of liposomal loaded docetaxel into 7-epimer, more passive targeting to tumor tissues, decreased 7-epimer induced systemic toxicity and tumor resistance to chemotherapy compared to Taxotere®. Further in vivo studies are needed to ascertain these facts.     

Tortilla Corn Chip-Associated Esophageal Perforation: An Unusual Presentation of Achalasia

Laceration of the esophagus related to ingestion of tortilla corn chips has been described in the past. However, no cases of perforation of the esophagus are known to be associated with tortilla corn chip ingestion. We describe a case of previously undiagnosed achalasia in a patient who presented with an esophageal perforation after ingestion of tortilla corn chips.     

Gilbert's syndrome co-existing with and masking hereditary spherocytosis

 An unusual case of co-existing Gilbert's syndrome and hereditary spherocytosis is reported. Diagnostic strategies are presented, and the literature is reviewed for simultaneous presence of these disorders. Received: 6 January 1997 / Accepted: 14 March 1997     

Phase II evaluation of S-adenosyl-L-methionine (SAMe) for the treatment of hot flashes

Purpose

Hot flashes are a significant source of symptom burden that negatively impacts quality of life (QOL). For women who have contraindications to, or are unwilling to consider, estrogens or antidepressants for bothersome hot flashes, there are limited effective pharmacologic or complementary and alternative medicines.

Methods

This single-arm phase II trial studied the efficacy of S-adenosyl-L-methionine (SAMe) for the treatment of hot flashes. Eligible women were required to have reported ≥14 hot flashes per week for ≥1 month. The patients were treated with SAMe at a dose of 400 mg twice daily to evaluate whether a reduction in hot flash score appeared to be better than the historical placebo response of approximately 25 %. The women kept a daily hot flash diary during a baseline week and then daily during weeks 2–7. The primary endpoint was the change from baseline to week 7 in hot flash score and hot flash frequency. Secondary endpoints included toxicity analyses and the effect of SAMe on QOL.

Results

From October 28, 2010 to January 30, 2012, 43 women were treated with SAMe. The decrease in mean percent of baseline hot flash score and frequency was 35.4 and 32.6 %, respectively. When compared to the historical placebo response of 25 %, the effect of SAMe on hot flash score was not statistically significant (p?=?0.09). Treatment was well tolerated with expected grade 1/2 gastrointestinal toxicity and no negative effect on QOL.

Conclusions

The use of SAMe does not appear to significantly reduce hot flashes more than would be expected with a placebo.