Opportunities and challenges in antiparasitic drug discovery

New antiparasitic drugs are urgently needed to treat and control diseases such as malaria, leishmaniasis, sleeping sickness and filariasis, which affect millions of people each year. However, because the majority of those infected live in countries in which the prospects of any financial return on investment are too low to support market-driven drug discovery and development, alternative approaches are needed. In this article, challenges and opportunities for antiparasitic drug discovery are considered, highlighting some of the progress that has been made in recent years, partly through scientific advances, but also by more effective partnership between the public and private sectors.     

Pyridoxamine lowers oxalate excretion and kidney crystals in experimental hyperoxaluria: a potential therapy for primary hyperoxaluria

In order to prevent kidney stones and nephrolithiasis in hyperoxaluria, a new treatment that specifically reduces oxalate production and therefore urinary oxalate excretion would be extremely valuable. Pyridoxamine(PM) could react with the carbonyl intermediates of oxalate biosynthesis, glycolaldehyde and glyoxylate, and prevent their metabolism to oxalate. In PM treated rats, endogenous urinary oxalate levels were consistently lower and became statistically different from controls after 12 days of experiment. In ethylene glycol-induced hyperoxaluria, PM treatment resulted in significantly lower (by ~50%) levels of urinary glycolate and oxalate excretion compared to untreated hyperoxaluric animals, as well as in a significant reduction in calcium oxalate crystal formation in papillary and medullary areas of the kidney. These results, coupled with favorable toxicity profiles of PM in humans, show promise for the therapeutic use of PM in primary hyperoxaluria and other kidney stone diseases.     

Preoperative versus postoperative radiation therapy for soft-tissue sarcomas

In this article, we report results from a retrospective consecutive series of 117 patients with soft-tissue sarcomas treated with adjuvant radiation and surgical resection at 2 associated institutions. Fifty-nine patients received preoperative radiation; 58 patients received postoperative radiation. Mean clinical follow-ups were 6.1 years and 8.4 years, respectively. Nineteen (32.2%) of 59 patients in the preoperative group and 17 (29.3%) of 58 patients in the postoperative group had wound complications (P = .89). Three (5.1%) of 59 sarcomas in the preoperative group and 7 (12.1%) of 58 sarcomas in the postoperative group recurred locally (P = .19). Improved local disease control and other potential advantages of using preoperative radiation make this a preferred adjuvant treatment.     

Qualitative assessment of breast reconstruction in a specialist breast unit

BACKGROUND: Breast reconstruction is an integral part of the surgical management of women with breast cancer. It is often performed by plastic surgeons but, in some centres, it is performed by breast surgeons trained in breast reconstruction and oncoplastic surgery. We evaluated the objective and subjective outcomes of reconstruction for breast cancer at the Royal Adelaide Hospital Breast Unit (Adelaide, Australia) between 1990 and June 2002. METHODS: A chart analysis was conducted of all patients who underwent breast cancer reconstruction at the Royal Adelaide Hospital Breast Unit with analysis of type of reconstruction and complications. Patients were interviewed and self-assessment quality of life questionnaires (FACT-B, body image), and overall satisfaction with reconstruction using an analogue scale were performed. Three observers carried out photographic analysis of the reconstructions. A comparison was then made between the different forms of reconstruction used. RESULTS: One hundred and ninety-two patients underwent a total of 219 breast reconstructions during this period. The reconstructions included 18 latissimus dorsi mini flaps, 83 tissue expander/implants, 43 latissimus dorsi flaps and 75 TRAM flaps. There were no perioperative deaths. Significant systemic complications occurred in four patients (2%). Significant implant related complications occurred in four patients (3.2% of patients with implants). Total flap loss occurred in four patients (2.9% of flaps). One hundred and twenty-three patients were able to be contacted and completed the questionnaires. Overall 77% of patients were highly satisfied with breast reconstruction and 82% scored a satisfactory result on photographic analysis. All four forms of reconstruction rated highly with respect to quality of life, body image, patient satisfaction and photographic assessment. CONCLUSIONS: Breast reconstruction undertaken by breast surgeons trained in breast reconstruction and oncoplastic techniques has been performed with an acceptable rate of complications and a high level of patient satisfaction. Satisfaction with breast reconstruction was similar across the four methods of reconstruction used.