ABSTRACT
Duchenne Muscular Dystrophy (DMD) is a genetic disorder involving progressive muscle deterioration leading to loss of mobility, cardiomyopathy, and respiratory complications leading to an early death by the fourth decade of life. Males are affected more often as DMD results from a mutation in the dystrophin gene residing on the X chromosome. The DMD genetic mutation results in a complete functional lack of dystrophin, which culminates as an inadequate connection between the intracellular actin filaments and the extracellular skeleton of muscle. Boys affected by DMD clinically present with muscle weakness before age five, are often wheelchair-bound by age 12, and rarely survive beyond the third decade of life. Traditional treatment strategies have focused primarily on quality-of-life improvement and have included the use of glucocorticoids and physical therapy. No cure currently exists, however many novel treatments for DMD are currently being explored. Some of these involve gene therapy, exon skipping, stop codon skipping, CRISPR technology interventions, and the use of a retinal dystrophin isoform. In this comprehensive review, we recapitulate the literature findings to summarize the history, epidemiology, genetics, clinical presentation, diagnosis, and current and future strategies for the treatment of Duchenne Muscular Dystrophy.
ABSTRACT
BACKGROUND: Hypofractionated radiotherapy in the radical treatment of localized prostate cancer has potential biological advantages relative to conventional fractionation. We report prospectively collected toxicity data from a cohort of patients treated with a 3D conformal technique (3DCRT). MATERIALS AND METHODS: 90 patients receiving curative intent hypofractionated radiotherapy with 57Gy in 19 daily fractions over 3.8 weeks were evaluated prospectively for the development of radiation related toxicity over a 3 year period. RESULTS: All patients completed treatment. Maximal acute toxicity experienced was 58.6, 10 and 1.1% for grade 1, 2 and 3 genitourinary (GU) toxicity respectively and 75.6, 9 and 0% for gastrointestinal (GI) toxicity. For late toxicity the three year actuarial rates of grade 1, 2 and 3 GU and GI toxicity respectively were 47.3, 2.4 and 0%; and 40, 9.3 and 4.7%. There were no grade 4 or worse acute or late toxicities. 97.6% of evaluable patients remained free of biochemical failure 36 months post radiotherapy. CONCLUSIONS: A 57Gy in 19 daily fraction radiotherapy schedule using 3D conformal radiotherapy for the definitive treatment of localized prostate cancer has acceptable early and late toxicity.
ABSTRACT
Data from studies in Mwanza Region in Tanzania suggest stabilising HIV prevalence. The objective was to determine the factors that may have contributed to the relatively stable pattern of the HIV prevalence observed in the comparison communities of the Mwanza STD treatment trial in rural Mwanza Region; Tanzania between 1991 and 2001. Socio-demographic; sexual behaviour and HIV prevalence data in two surveys conducted 10 years apart in the same communities using similar sampling schemes were compared. The age standardised HIV prevalence was 3.8(95CI: 3.2-4.6) in 1991 and 4.3(95CI: 2.8-6.4) in 2001 for males (Z= - 0.56; P= 0.58); and 4.5(95CI: 3.8-5.3) in 1991 and 3.9(95CI: 2.6-5.6) in 2001 for females (Z= 0.64; P= 0.52). Participants in the 2001 survey reported significantly fewer lifetime and recent sexual partners (12 months); Sexually Transmitted disease syndromes (12 months) and significantly more condom use at last sex with casual partners than those in the 1991 behaviour survey. We conclude that STD/ HIV infection prevention activities in rural Mwanza may be responsible for changes in risky sexual behaviour and have successfully impeded the spread of HIV infection. These activities should therefore be enhanced to reduce HIV incidence even further. In addition; modelling studies are needed to assess whether mobility of HIV infected people out of rural communities may stabilise the prevalence of the HIV infection in the general populations