Tracer adenosine: a novel myocardial flow marker.

Local myocardial blood flow measurements are of great importance in experimental and clinical settings. However, a lack of ideal markers is evident. Adenosine is suggested to be a potential candidate because of its high uptake and rapid intracellular sequestration. We specifically tested the hypothesis that the local deposition density of labeled adenosine within the heart reflects local myocardial blood flow. METHODS: Tracer microspheres, the recognized standard for local blood flow measurements, were injected and compared with simultaneously injected labeled adenosine ((3)H/(14)C) in tracer concentration into the left atrium of anesthetized Beagle dogs (n = 7). Myocardial deposition densities were assessed through beta-scintillation and gamma-counting measurements in samples (100-128 per heart) of an average wet mass of 487 +/- 54 mg. To challenge local myocardial blood flow distribution, alprostadil was infused into the left circumflex artery in 3 experiments. In 2 other experiments, erythro-9-hydroxy-nonyl-adenine (EHNA) was infused to inhibit degradation of injected adenosine to inosine. RESULTS: Tracer adenosine and microspheres did not exert significant local or systemic hemodynamic effects. Both were almost completely extracted from blood within 2 min and locally retained in the tissue. Deposition densities of tracer microspheres and labeled adenosine correlated closely in each experiment, independently of the respective protocol (control, EHNA, or alprostadil), over a wide range of local myocardial blood flows (0.23-12.9 mL min(-1) g(-1)). The mean correlation coefficient (n = 293) was r = 0.93 (r(2) = 0.86; P < 0.0001), indicating that the deposition density of (3)H-adenosine could explain local blood flow as measured with the tracer microsphere technique with 86% probability. CONCLUSION: Adenosine appears to be a reliable marker of local blood flow in dog myocardium.     

Intermediate-dose intravenous methotrexate and mercaptopurine therapy for non-T, non-B acute lymphocytic leukemia of childhood: a Pediatric Oncology Group study

Methotrexate (MTX) and mercaptopurine (MP) are the mainstays of continuation therapy for acute lymphocytic leukemia (ALL). These drugs are stored in tissues as active metabolites. Relapse in ALL might reflect failure to achieve adequate intracellular drug levels. Assured (parenteral) delivery of higher doses of MTX and MP should maximize tissue levels of these drugs by overcoming individual variations in absorption, metabolism, clearance, and compliance. Fifty-nine children with ALL at lower risk of relapse received 12 intensive MTX/MP courses immediately after 4 weeks of standard vincristine, prednisone, and asparaginase induction. Each 2-week intensive course included: MTX, 200 mg/m2 intravenous (IV) push then 800 mg/m2 IV over 24 hours on day 1; MP, 200 mg/m2 IV push then 800 mg/m2 IV over 8 hours on day 2; MTX, 20 mg/m2 intramuscularly on day 8; and MP, 50 mg/m2 orally daily on days 8 to 14. After the 6 months of intensive therapy, continuation therapy was weekly MTX/MP (as on days 8 to 14) for 1 or 2 years. Age-based MTX was given intrathecally (IT) for CNS prophylaxis. All patients entered remission. Three patients relapsed: bone marrow (at 24 and 37 months), and bone marrow and CNS (at 34 months). There were no isolated CNS relapses or deaths in remission. Event-free survival at 4 years is 94% (SE, 7%) by Kaplan-Meier analysis. Toxicities (infection, mucositis) occurred in less than 10% of intensive MTX/MP courses. However, a child with Down's syndrome withdrew after three courses because of recurrent severe mucositis. Further studies of this regimen are in progress.     

Prognostic indicators in multiple sclerosis

The influence of sex, age at onset, course of the disease and initial symptomatology on the mortality of patients with multiple sclerosis is analysed. A sample of 1926 patients was followed up prospectively over 4.9 years. Both, the mortality ratio (number of observed to expected deaths) and the excess death rate are calculated. Whereas the mortality ratio as a parameter of overall mortality is influenced by a variety of factors, such as age and sex; the excess death rate represents the number of extra deaths per 1000 exposed to risk in an indicated year and is, therefore, a parameter of the mortality which is attributed to MS. The excess death rate was comparable for the sexes, it was slightly higher for patients with a higher age at onset and it was clearly higher for the progressive course. Patients with initial diplopia and sensory signs and symptoms had the lowest excess death rate, whereas patients with pareses, cerebral and sphincter disturbances at onset showed the highest excess death rate.     

Comparative evaluation of radiometric tryptic soy broth versus radiometric tryptic soy broth with 10% sucrose for detection of bacteremia and fungemia in pediatric patients.

We compared BACTEC radiometric blood culture media with (8B) and without (6B) 10% sucrose for the detection of bacteremia and fungemia in pediatric patients at four university teaching hospitals that used identical methods for obtaining and processing specimens. Overall, the yields of microorganisms from 5,714 blood culture sets were no different in the two media, although a trend was noted favoring 6B for the detection of pneumococci. Speed of detection of positive results was faster in the 6B than in the 8B medium (P less than 0.05), largely due to the faster detection of Staphylococcus aureus in the 6B medium. We conclude that, overall, with pediatric patients the hypertonic 8B radiometric medium has no advantage and that it possibly has a modest disadvantage, compared with isotonic 6B radiometric medium.     

Immunosuppression following 7,12-dimethylbenz[a]anthracene exposure in B6C3F1 mice. I. Effects on humoral immunity and host resistance

It has previously been demonstrated that the polycyclic aromatic hydrocarbon (PAH), benzo(a)pyrene (B[a]P), suppresses the terminal step in B-cell differentiation, resulting in a decrease in antibody production to T-dependent and B-2 T-independent antigens. The purpose of this study was to ascertain if this effect was common to carcinogenic PAHs or specific for B[a]P. The PAH 7,12-dimethylbenz[a]anthracene (DMBA) was administered to B6C3F1 female mice by ten sc injections of 0.5, 5, or 10 micrograms/g over a 2-week period (i.e., total dose of 5, 50, and 100 micrograms/g). Immune function and host resistance assays were performed 3 to 5 days following the last injection. The 10 micrograms/g dosage resulted in a marked decrease in spleen weights and spleen and bone marrow cellularity, while thymus and body weights were not significantly altered. The ability to generate B-lymphocyte colonies in vitro from spleen precursor cells was also suppressed at the 10 micrograms/g dose. Exposure to DMBA at 5 micrograms/g or greater resulted in a reduction of up to 97% in the number of IgM plaque-forming cells in response to the T-dependent antigen sheep red blood cells (SRBC). The IgG response to SRBC was similarly depressed. The IgM response to the hapten-conjugated T-independent antigens trinitrophenyl-lipopolysaccharide (TNP-LPS) (specific for B-1 cells) and trinitrophenyl (TNP)-Ficoll (specific for B-2 cells) was also depressed (88 and 97%, respectively) at 10 micrograms/g. DMBA exposure resulted in an increased susceptibility to challenge with the PYB6 transplantable sarcoma and the bacterium Listeria monocytogenes, in contrast to B[a]P exposure, which had no effect on host resistance assays. Thus, DMBA, a more potent carcinogen than B[a]P, produces a more extensive B-cell suppression than B[a]P as well as alters host resistance to tumor and bacterial challenge.     

Renal functional reserve in humans. Effect of protein intake on glomerular filtration rate

This study was designed to investigate the effect of protein intake on glomerular filtration rate, and to demonstrate and evaluate the functional reserve of the kidney. Normal subjects ingesting a protein diet had a significantly higher creatinine clearance than a comparable group of normal subjects ingesting a vegetarian diet. A progressive increment in protein intake in normal volunteers resulted in a significant increase in creatinine clearance. Diurnal variations in creatinine clearance were found. These daily variations correlated well with the periods of food intake. The capacity of the kidney to increase its level of function with protein intake suggests a renal function reserve. In short-term studies, the effect of a protein load on glomerular filtration rate was evaluated. Normal subjects showed an increase in glomerular filtration rate two and a half hours after protein load to a maximal glomerular filtration rate of 171.0 +/- 7.7 ml per minute. In patients with a reduced number of nephrons, renal functional reserve may be diminished or absent.     

Niedriger oder hoher positiver endexpiratorischer Druck bei Patienten mit „acute respiratory distress syndrome“?

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