Randomized study of didanosine monotherapy and combination therapy with zidovudine in hemophilic and nonhemophilic subjects with asymptomatic human immunodeficiency virus-1 infection. AIDS Clinical Trial Groups

To evaluate the safety and efficacy of didanosine (ddl) monotherapy and three different combinations of zidovudine (ZDV) and ddl in asymptomatic human immunodeficiency virus-1 (HIV-1) infection, we conducted an open-label, phase I/II study in 126 asymptomatic HIV-1- infected hemophilic and nonhemophilic subjects with a CD4 count of 200 to 500/mm3 stratified for prior zidovudine treatment and baseline CD4 count. Study arms included arm A, low-dose combination (ZDV 150 mg and ddl 134 mg, daily); arm B, moderate-dose combination (ZDV 300 mg and ddI 334 mg, daily); arm C, high-dose combination (ZDV 600 mg and ddl 500 mg, daily), and arm D, ddl monotherapy (ddl 500 mg, daily). Earlier, more frequent hepatotoxicity was experienced by hemophilic subjects (P = .008), but there were no differences in toxicity between treatment arms (P = .51), nor were there any differences in the rate of development of clinical endpoints by treatment (P = .41). Smaller median CD4 increases occurred over the first 12 weeks for arms A and D, 44/mm3 and 42/mm3, than arms B and C, 105/mm3 and 114/mm3, respectively, (P = .015). Hemophilia status (P = .0004) and prior ZDV experience (P = .044) independently predicted weaker CD4 responses during the first 12 weeks of treatment. Using a regression model and adjusting for hemophilia status, prior ZDV treatment, and baseline CD4, there was a significant reduction in quantitative viral load from baseline by week 12 for all treatment arms combined (P = .0001), with significantly lower median percent reduction for arm A (56.3%) than arms B, C, and D (94.6%, 98.5%, and 91.9%, respectively, P = .015). Although greater hepatoxicity and weaker CD4 responses occur in hemophilic subjects, didanosine monotherapy and combination therapy with zidovudine are safe and effective in asymptomatic HIV-1-infected patients.     

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.     

Lymphocyte-specific inducible expression of potassium channel beta subunits

Many studies have shown that voltage-gated potassium (Kv) channel activity is essential for T-lymphocyte proliferation. The IL-2-inducible neuroimmune gene, I2rf5 is the mouse homologue of the rat Kvβ2 subunit. In this study we show that in addition to constitutive expression in adult murine brain, expression of Kv channel subunits β1.1 and β2.1 is inducible in a cloned T-helper cell line stimulated with IL-2 and in normal murine splenocytes stimulated with Con A or LPS. This expression pattern appears to be lymphocyte specific, because stimulated fibroblasts and vascular smooth muscle cells do not express Kvβ channel subunit mRNA. These observations suggest that Kvβ subunit expression is tissue specific and inducible in stimulated lymphocytes. Because Kvβ subunits modulate K⁺ channel activity, the inducible and variable expression of these subunits in lymphocytes may represent an additional regulatory mechanism for lymphocyte proliferation.     

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.