Maternal viral genotypic zidovudine resistance and infrequent failure of zidovudine therapy to prevent perinatal transmission of human immunodeficiency virus type 1 in pediatric AIDS Clinical Trials Group Protocol 076

Maternal samples were assessed from 96 women enrolled in Pediatric AIDS Clinical Trials Group protocol 076 to determine the prevalence of human immunodeficiency virus type 1 (HIV-1) genotypic zidovudine resistance at entry, if zidovudine resistance developed on study, and the role of zidovudine resistance in vertical transmission of HIV-1 despite zidovudine therapy. Low and high levels of genotypic resistance were assessed by differential hybridization, oligoligation, or direct sequencing of plasma HIV-1 RNA for codons K70R and T215Y/F. None of the women had high-level genotypic resistance to zidovudine at study entry or delivery. For low-level zidovudine resistance, the 95% confidence intervals were 0.3%-6.8% for baseline prevalence and 0.3%-14% for delivery incidence. Low-level zidovudine resistance, adjusted for plasma viral RNA level at delivery, was not strongly associated with an increase in vertical transmission risk (odds ratio, 4.8; 95% confidence interval, 0.2-131; P = .35).     

The comparative metabolism of diisopropyl methylphosphonate in mink and rats

This study reports the metabolism of carbon-14labeled diisopropyl methylphosphonate (DIMP) in mink and rats, undertaken to better understand the dose-related mortality reported for mink in a previous study. In both male and female mink and rats, DIMP was rapidly absorbed after oral administration; it was metabolized by a saturable pathway to a single metabolite, isopropyl methylphosphonate (IMPA), which was rapidly excreted, primarily in the urine (90%). Fecal radioactivity, also identified as IMPA, was 1.7-3.1% of the administered dose. Female rats had a slower rate of conversion of DIMP to IMPA and less total excretion of IMPA than male rats. Metabolism of DIMP administered intravenously was not very different from that given orally in both species. These data indicate that mink absorb, metabolize, and excrete DIMP (as IMPA) in a manner very similar to mice, rats, and dogs.     

Treatment of severe hypertriglyceridemia lowers plasma viscosity

PURPOSE: To assess the rate and duration of response to palliative radiotherapy (RT) in patients with metastatic melanoma or renal cell carcinoma. PATIENTS AND METHODS: From 1992 to 1995, 90 patients were entered into a nonrandomized study. Goals of palliative RT were prospectively defined and subjective response was documented at the end of RT, after 2-6 weeks, and every 3 months thereafter. Most patients were treated with 5 x 4 Gy or 10 x 3 Gy. RESULTS: Relief of pain from bone lesions was observed in 26 of 40 cases, with a duration of response of 2.4 months, corresponding to 57% of the remaining lifetime. A total of 55% of patients with persistent neurologic dysfunction despite corticosteroids improved, for a duration of 2.5 months (86% of the further lifespan). Freedom from symptoms in patients treated for impending neurological complications from metastases to the brain, spine, or nerve plexus was documented for 86-100% of their lifetime. CONCLUSIONS: Despite the methodological flaws discussed, the efficacy of a short course of palliative RT for so-called radioresistant tumors is demonstrated.     

Bioassay of thyrotropin receptor antibodies with Chinese hamster ovary cells transfected with recombinant human thyrotropin receptor: clinical utility in children and adolescents with Graves disease

OBJECTIVE: The objective of this study was to compare the clinical utility of a new bioassay for thyrotropin (TSH) receptor antibodies (Abs) with the conventional radioreceptor assay and with measurement of thyroid peroxidase Abs in the diagnosis of Graves disease in childhood. STUDY DESIGN: Serum samples obtained from 22 children and adolescents with Graves disease (19 hyperthyroid, 3 in remission), 13 children and adolescents with chronic lymphocytic thyroiditis, and 17 normal children in a control group were evaluated. RESULTS: TSH receptor Abs were detected by bioassay in 10 (91%) of 11 patients with active Graves disease but in 0 of 2 patients in remission, 0 of 13 normal members of the control group, and 0 of 11 patients with chronic lymphocytic thyroiditis including 1 with thyrotoxicosis. The sensitivity and specificity of TSH receptor Abs detected by radioreceptor assay studied in the same 11 patients and in an additional 11 patients was similar to bioassay. In contrast, thyroid peroxidase Abs were detected in only 12 (71%) of 17 patients with Graves disease but in 11 of 11 patients with chronic lymphocytic thyroiditis and in 0 of 17 members of the control group. CONCLUSION: Bioassay of TSH receptor Abs is both sensitive and specific for the diagnosis of active Graves disease in the young. When cost and simplicity are considered, however, bioassay offers no advantage over radioreceptor assay for initial diagnostic screening. Rather, bioassay for TSH receptor Abs may be useful in thyrotoxic patients who are negative initially in the radioreceptor assay or in treated patients whose clinical picture is discordant with results in the radioreceptor assay.     

Genetics of methane and methanol oxidation in gram-negative methylotrophic bacteria

Within the past few years, considerable progress has been made in the understanding of the molecular genetics of methane and methanol oxidation. In order to summarize this progress and to illustrate the important genetic methods employed, this review will focus on several well-studied organisms. These organisms include the gram-negative faculative methylotrophs Methylobacterium extorquens, Methylobacterium organophilum and Paracoccus denitrificans. In addition, the obligate methanotrophs Methylococcus capsulatus and Methylosinus trichosporium are discussed. We have chosen not to discuss the genetics of methanol oxidation in the yeasts or in gram-positive bacteria. Likewise, the genetics of related topics (for example, methylamine oxidation and carbon assimilation pathways) are not reviewed here. Broad host range conjugatable plasmids have enabled researchers to complement mutations and clone genes from gram-negative methylotrophic bacteria. More recently, 'promoter probe' derivative plasmids have been used to elucidate aspects of gene regulation. Also, alternative gene-cloning techniques are proving useful in circumventing problems in the genetic studies of the obligate methanotrophs, the group of bacteria that is the most refractory to traditional methods.     

Ultrafast computed tomographic scanning to assess patency of coronary artery stents in bypass grafts

Anginal chest pain after implantation of coronary stents in bypass grafts is a concern because it suggests the possibility of occlusion. Coronary angiography is the definitive method for determining patency of a stent; however, this procedure is relatively contraindicated in a patient receiving warfarin sodium, who has a therapeutic international normalized ratio. An alternative method for determining patency of a stent is by ultrafast computed tomography. This new, minimally invasive technique shows promise for determining blood flow within the large vessels of the thorax. Herein we describe a case in which a metallic stent placed in a vein graft was noninvasively established to be patent, despite chest pain in the patient. This method may be clinically applicable for determining patency of stents in vein grafts in the setting of patients with chest pain who have undergone complete anticoagulation.