Malignant melanoma: analysis of dose fractionation in radiation therapy

Thirty-five patients with 67 measureable cutaneous or lymph node metastases from malignant melanoma were treated with radiation therapy in a variety of total doses and dose fractions. There was no correlation between total dose and response rate. However, there was a strong correlation between fraction size and response rate. There were four (9%) complete responses in 43 lesions treated with fractions less than or equal to 500 rad (5 Gy) compared with 12 (50%) complete responses in 24 lesions treated with fractions greater than 500 rad (5 Gy) (P = .0006). Initial response rate was found to correlate strongly with local control at 1 year. The results were then analyzed with respect to lesion size, cutaneous versus nodal lesions, and site of cutaneous lesion (trunk, head and neck, or extremity). Correlation between fraction size and response rate was independent of lesion size, although there were fewer complete responses with increasing lesion size. Correlation was not seen in nodal lesions but was particularly striking in cutaneous lesions. This correlation was statistically significant only for cutaneous lesions of the extremities.     

The effect of cataract extraction with implant in glaucomatous eyes

The effect of cataract surgery in patients with glaucoma controlled by either topical medication or surgery was assessed in 64 patients. At one year there was a small significant fall in intraocular pressure (IOP) for eyes without previous surgery (preoperative IOP 18.9 ±4.7, range 12 to 35 mmHg; postoperative IOP 16.3 ±3.4, range 10 to 26 mmHg; P<0.01) and also for those with previous surgery (preoperative IOP 15.0 ±4.3, range 3 to 22 mmHg; postoperative IOP 14.2 ±3.7, range 6 to 22 mmHg, P<0.05). There was a significantly greater incidence of high rise in IOP to 30 mmHg or more immediately after operation in patients without (32%) than those with previous surgery (13%) ( x 2 = 3.9; P<0.05). Complications were minimal in each group. lridotomy to deliver the nucleus was necessary in nine eyes without and 21 with previous surgery. Cataract extraction usually causes only a small fall in IOP in glaucomatous patients. If a separate corneal section is used there is no loss of function of the filtering bleb in patients with previous glaucoma surgery.     

Dystrobrevin deficiency at the sarcolemma of patients with muscular dystrophy

Mutations in the genes encoding dystrophin or dystrophin-associated proteins are responsible for Duchenne muscular dystrophy or various forms of limb-girdle muscular dystrophies respectively. We have recently cloned the gene for the murine 87 kDa postsynaptic protein dystrobrevin, a dystrophin-associated protein. Anti-dystrobrevin antibodies stain the sarcolemma in normal skeletal muscle indicating that dystrobrevin co-localises with dystrophin and the dystrophin- associated protein complex. By contrast, dystrobrevin membrane staining is severely reduced in muscles of Duchenne muscular dystrophy patients, consistent with dystrobrevin being a dystrophin-associated protein. Interestingly, dystrobrevin staining at the sarcolemma is dramatically reduced in patients with limb-girdle muscular dystrophy arising from the loss of one or all of the sarcoglycan components. Normal dystrobrevin staining is observed in patients with other forms of limb- girdle muscular dystrophy where dystrophin and the rest of the dystrophin-associated protein complex are normally expressed and in other neuromuscular disorders. Our results show that dystrobrevin- deficiency is a generic feature of dystrophies linked to dystrophin and the dystrophin-associated proteins. This is the first indication that a cytoplasmic component of the dystrophin-associated protein complex may be involved in the pathogenesis of limb-girdle muscular dystrophy.