High serum interleukin-2 receptor levels are related to advanced disease and a poor outcome in childhood non-Hodgkin's lymphoma

The clinical usefulness of serum interleukin-2 receptor (IL2R) measurements was determined in 59 children with non-Hodgkin's lymphoma (NHL) and six with B cell acute lymphoblastic leukemia (B-ALL). Levels of the receptor showed a clear relationship to disease stage, as follows: B-ALL greater than stage III or IV diffuse small noncleaved- cell NHL greater than stage III or IV lymphoblastic NHL greater than stage I or II NHL. Soluble IL2R levels were also closely correlated with serum lactic dehydrogenase levels (r = 0.7, P = .0001), a recognized indicator of tumor cell burden. Children with higher soluble IL2R levels (greater than 1,000 U/mL) were significantly more likely to fail treatment (P = .001), even when the analysis was limited to those with more advanced disease: stages III and IV NHL and B-ALL (P = .02). In a multivariate analysis, soluble IL2R level was found to have greater predictive strength than either serum lactic dehydrogenase level or disease stage. Thus, the measurement of soluble IL2R in children with NHL could be expected to improve existing methods of risk assignment in this disease.     

Identification of the probable site of choleragen-catalyzed ADP-ribosylation in a Go alpha-like protein based on cDNA sequence.

Go alpha, a 39-kDa guanyl nucleotide-binding protein, is functionally and structurally similar to the alpha subunits of the stimulatory and inhibitory guanyl nucleotide-binding proteins (Gs alpha, Gi alpha) of adenylate cyclase and to the alpha subunit of transducin (T alpha), the guanyl nucleotide-binding protein of the retinal photon reception system. A cDNA clone was isolated from a bovine retinal lambda gt10 library by using oligonucleotide probes complementary to sequences in two putative T alpha clones. Partial sequence analysis revealed a deduced amino acid sequence identical to sequences of four tryptic peptides from bovine brain Go alpha. Gs alpha and T alpha are known to serve as substrates for ADP-ribosylation by choleragen. Other workers have established the sequence of the tetrapeptide in T alpha containing the arginine that is ADP-ribosylated and its location in the amino acid sequence deduced from T alpha cDNA. The Go alpha cDNA described here includes a region encoding an amino acid sequence very similar to that surrounding the ADP-ribosylation site in T alpha, consistent with observations that Go alpha can also be a substrate for choleragen. A corresponding sequence in the recently identified Gs alpha cDNA is less homologous to that in T alpha or Go alpha. The reported differences in conditions that promote choleragen-catalyzed ADP-ribosylation of Gs alpha vs. Go alpha could be related to differences in amino acid sequence in the region of the acceptor arginine.     

One-week ranitidine bismuth citrate versus colloidal bismuth subcitrate-based anti-Helicobacter triple therapy: a prospective randomized controlled trial

OBJECTIVE: The efficacy of 1 wk bismuth triple therapy is adversely influenced by the presence of metronidazole resistance. In vitro studies suggest that ranitidine bismuth citrate (RBC) plus metronidazole exhibit synergistic activity against metronidazole resistant strains of Helicobacter pylori (H. pylori). Whether this confers a superior clinical efficacy remains unproven. This study compared the efficacy of RBC-based triple therapy with bismuth triple therapy in eradication of H. pylori. METHODS: Patients with H. pylori-related ulcer disease or gastritis were randomized to receive either 400/mg of RBC twice daily plus 400/mg of metronidazole and 500/mg of tetracycline four times daily for 1 wk (RMT) or 120/mg of colloidal bismuth subcitrate, 400/mg of metronidazole, and 500/mg of tetracycline, all given four times daily for 1 wk (BMT). Metronidazole susceptibility was determined by the E-test and pretreatment resistance was defined as minimum inhibitory concentration > or = 32/mg/L. RESULTS: Of 100 consecutive patients randomized, two patients were lost to follow-up in each group. Forty-three of 85 (51%) H. pylori isolates were metronidazole resistant. Per-protocol cure rate for RMT and BMT was 40 of 41 (98%) and 37 of 44 (84%), respectively (p = 0.058). Intent-to-treat cure rate for RMT and BMT was 46 of 50 and 41 of 50, respectively (92% vs 82%, p = 0.23). A significantly higher eradication of metronidazole resistant H. pylori was observed in the RMT group (25 of 25, 100%) than in the BMT group (12 of 16, 75%), (p = 0.018). Side effects observed in the two treatment groups were comparable. CONCLUSIONS: One week of RBC triple therapy with metronidazole and tetracycline is an effective anti-Helicobacter therapy. This regimen is more appropriate in areas of high prevalence of metronidazole resistance.     

The Relationship Between Multimorbidity and Patients’ Ratings of Communication

BACKGROUND  The growing interest in pay-for-performance and other quality improvement programs has generated concerns about potential performance measurement penalties for providers who care for more complex patients, such as patients with more chronic conditions. Few data are available on how multimorbidity affects common performance metrics. OBJECTIVE  To examine the relationship between multimorbidity and patients’ ratings of communication, a common performance metric. DESIGN  Cross-sectional study SETTING  Nationally representative sample of U.S. residents PARTICIPANTS  A total of 15,709 noninstitutionalized adults living in the United States participated in a telephone interview. MEASUREMENTS  We used 2 different measures of multimorbidity: 1) “individual conditions” approach disregards similarities/concordance among chronic conditions and 2) “condition-groups” approach considers similarities/concordance among conditions. We used a composite measure of patients’ ratings of patient–physician communication. RESULTS  A higher number of individual conditions is associated with lower ratings of communication, although the magnitude of the relationship is small (adjusted average communication scores: 0 conditions, 12.20; 1–2 conditions, 12.06; 3+ conditions, 11.90; scale range 5 = worst, 15 = best). This relationship remains statistically significant when concordant relationships among conditions are considered (0 condition groups 12.19; 1–2 condition groups 12.03; 3+ condition groups 11.94). CONCLUSIONS  In our nationally representative sample, patients with more chronic conditions gave their doctors modestly lower patient–doctor communication scores than their healthier counterparts. Accounting for concordance among conditions does not widen the difference in communication scores. Concerns about performance measurement penalty related to patient complexity cannot be entirely addressed by adjusting for multimorbidity. Future studies should focus on other aspects of clinical complexity (e.g., severity, specific combinations of conditions).     

A short version of the ADAM Questionnaire for androgen deficiency in Chinese men

BACKGROUND: A 10-question screening questionnaire for androgen deficiency in aging men (ADAM) was reported in previous white but not Chinese populations. We therefore investigated the validity of a Chinese version of the Saint Louis University ADAM questionnaire to screen for androgen deficiency in Chinese men. METHODS: This was a cross-sectional study. Seven hundred ninety-six ambulatory community-based Chinese men, 18-89 years old, were recruited from October 2003 through June 2006. Self-administered Chinese ADAM questionnaire and morning blood samples for serum total testosterone (TT) and bioavailable testosterone (BT) levels were collected from all participants. Low serum BT levels (androgen deficiency) were defined as <5th percentile of serum BT levels in young healthy Chinese men (18-29 years). RESULTS: The Chinese ADAM questionnaire had good internal consistency (Cronbach alpha = 0.74) and test-retest reliability (Pearson correlation coefficient, r = 0.86; p <.001, two-tailed). As a screening test for low serum BT levels, the Chinese ADAM questionnaire has a high sensitivity of 88% but low specificity of 32%. In 6 of the 10 questions, the mean serum BT levels were significantly lower in those who answered positively than in those who answered negatively. Using a cut-off score of > or =2, a six-question short Chinese ADAM questionnaire demonstrated sensitivity, specificity, and positive and negative predictive values of 86%, 40%, 46%, and 82%, respectively. CONCLUSION: We have validated a full Chinese version and developed a shortened version of the ADAM questionnaire, and demonstrated that they are sensitive but not specific screening tests for androgen deficiency in Chinese men.     

A randomized comparison of ketamine versus methohexital anesthesia in electroconvulsive therapy

To assess the clinical utility of ketamine as an anesthetic agent for electroconvulsive therapy (ECT), based upon recent findings that ketamine may have antidepressant properties. Depressed ECT patients were randomly assigned to receive anesthesia with either ketamine or methohexital. Outcome measures included assessments of depressive severity, cognition, post-anesthesia side effects, and hemodynamics. Twenty one patients were treated with ketamine and 17 with methohexital. There were no significant differences in depression or cognitive outcomes between the two drugs. Additionally, there were no measures of post-anesthesia tolerability or hemodynamics which favored ketamine. Ketamine anesthesia does not accelerate the antidepressant effect of ECT or diminish the cognitive side effects, at least as measured in this study. Furthermore, there is no apparent benefit of ketamine for speed or quality of post-ECT recovery, and it is associated with higher systolic blood pressures after the treatments. Ketamine is associated with longer motor seizure duration than methohexital.     

Initial experience in synthesis of (2S,4R)‐4‐[18F]fluoroglutamine for clinical application

We report initial experience in synthesis of (2S,4R)‐4‐[¹⁸F]fluoroglutamine, [¹⁸F]FGln, which has been used as a tool for monitoring glutamine metabolism in cancer patients. [¹⁸F]FGln was prepared by a fully automated PET‐MF‐2V‐IT‐I synthesizer under GMP‐compliant conditions for routine clinical studies. The total radiosynthesis time was about 65 minutes, the decay‐corrected radiochemical yield was 18.0 ± 4.2% (n = 59; failure n = 15), and the radiochemical purity was greater than 90%. In some situations, the yields were low (less than 5%), and the most likely cause of this problem is the initial fluorination step; the fluoride ion might not have been fully activated. In other occasions, low final radiochemical purity was often associated with the failure of the second step—removal of protection groups by anhydrous trifluoroacetic acid. A trace amount of water led to production of undesired 4‐[¹⁸F]fluoroglutamic acid. Knowledge learned from the successes and failures of synthesis may be helpful to identify critical steps and pitfalls for preparation of this clinically useful metabolic probe, [¹⁸F]FGln, for imaging glutamine utilization in tumor of cancer patients.