Cytomegalovirus isolates can be grouped into 4 gB and 2 gH genotypes. gB genotypes were studied in patients infected with human immunodeficiency virus (HIV) and in allograft transplantation recipients. In allograft recipients, the distribution of gB 1, -2, -3, and -4 in leukocytes and urine, respectively, was 36%, 21%, 43%, and 0% and 39%, 30%, 17%, and 13%. However, in leukocytes of HIV-infected patients with <100/microL CD4 cells, gB1 was found significantly less often than in allograft recipients (11% vs. 36%) but gB2 was more frequent (56% vs. 21%; P < .05). The decreased incidence of gBl and increased incidence of gB2 compared with allograft recipients was also seen in urine of HIV-infected patients and reflected the distribution seen in leukocytes. gB4 was found significantly more often (P < .05) in semen than in leukocytes of HIV-infected patients with < 100/microL CD4 cells. gB1-4 genotypes were similar in patients with < 100/microL CD4 cells with or without retinitis.
A B S T R A C T PurposeEarly studies of patients with castration-resistant metastatic prostate cancer (CRMPC) suggest that chemotherapy administered with a dose of a bone-seeking radiopharmaceutical is superior to chemotherapy alone. To build on this strategy and fully integrate a repetitively dosed bone-seeking radiopharmaceutical into a contemporary chemotherapy regimen, we conducted a phase I study of docetaxel and samarium-153 ( 153 Sm) lexidronam.
Patients and MethodsMen with progressive CRMPC were eligible. Cohorts of three to six patients were defined by dose escalations as follows: docetaxel 65, 70, 75, 75, 75 mg/m 2 and 153 Sm ethylenediaminetetramethylenephosphonate (EDTMP) 0.5, 0.5, 0.5, 0.75, 1 mCi/kg. Each cycle lasted a minimum of 6 (cohorts 1 through 5) or 9 (cohort 6) weeks. Docetaxel was administered on days 1 and 22 (and day 43 for cohort 6), and 153 Sm-EDTMP was administered on day Ϫ1 to 1 of each cycle. Patients with acceptable hematologic toxicities were eligible to receive additional cycles until progression.
ResultsTwenty-eight men were treated in six cohorts. Maximum-tolerated dose was not reached, because full doses of both agents were well tolerated, even using an every-6-week dosing schedule of 153 Sm-EDTMP. Patients received an average of 5.6 docetaxel doses (range, one to 13 doses) and 2.9153 Sm-EDTMP doses (range, one to six doses). Fifteen patients demonstrated a more than 50% decline in prostate-specific antigen. Treatment significantly reduced indices of bone deposition and resorption.
Conclusion
Docetaxel and153 Sm-EDTMP can be combined safely at full doses over repeated cycles. Responses were seen in the small group of patients with taxane-resistant disease tested. The optimal phase II doses for patients with taxane-naïve disease may differ from those optimal for patients with taxane-resistant disease.
To test the hypothesis that human cytomegalovirus (CMV) gB genotype may differ with geographic origin or patient demographics, CMV DNA was amplified for gB typing from immunocompromised patients in Italy and Africa and compared with previously reported frequencies in California. Increased gB2 frequency occurred in Italian homosexual AIDS patients, as compared with both Italian heterosexual injection drug users with AIDS and heterosexual Zimbabwe AIDS patients. Occurrence of gB3 in Italy was higher in injection drug users than in homosexual AIDS patients. The incidence of gB4 was higher overall in the Italian as compared with the California patients. Therefore geographic and demographic differences in patients affect gB distribution and should be considered before associations of gB genotypes and virulence are made.
A quantitative DNA amplification assay for human cytomegalovirus (CMV) DNA has been used to evaluate the relationship between quantities of CMV DNA in plasma and those in infected leukocytes (WBC) from human immunodeficiency virus-infected patients. The target sequence for DNA amplification was a region of the immediate-early 1 gene of CMV. The quantitation assay uses an internal control that is coamplified with each patient sample DNA and contains a sequence for detection by colorimetric hybridization with the same bases, but in different order than in the CMV immediate-early 1 region used for hybridization of amplified patient sample DNA. Results showed that patients with CMV disease had more CMV DNA in both WBC and plasma than those without disease. However, in this study, copy numbers of CMV DNA in WBC were higher than those in plasma. The gB and gH variants were the same in plasma and WBC.
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