A cost analysis comparing erythropoietin and red cell transfusions in the treatment of anemia of prematurity

BACKGROUND: Anemia of prematurity is invariably observed in very low birth weight infants and may become symptomatic enough to be treated with packed red cell transfusions. Recently, treatment of this condition with recombinant human erythropoietin has been advocated. STUDY DESIGN AND METHODS: To compare the costs of training symptomatic anemia in hospitalized premature infants with transfusions alone or with erythropoietin plus red cell transfusions as needed, cost estimates were derived from local hospital and published cost data. Decision analysis and sensitivity analysis were applied to a "base case." The base case was derived from results of a multicenter erythropoietin trial in the United States in which premature infants received 500 U of erythropoietin per kg of body weight each week. Because erythropoietin treatment began on average at 3 weeks of life, when infants were clinically stable, they had already received 3.5 red cell transfusions. During the 6-week treatment period, erythropoietin- treated infants received significantly fewer additional transfusions: a mean of 1.6 versus 1.1. RESULTS: The base-case cost in 1993 dollars for treating anemia in hospitalized premature infants with erythropoietin and transfusions was $1,326. This was nearly twice the cost of conventional treatment with transfusions alone ($721). If the 6-week treatment period alone is considered, erythropoietin is 3.6 times more costly: $840 versus $235. CONCLUSION: The largest available US study using erythropoietin to treat anemia in premature infants has demonstrated a small, but significant, reduction in transfusion needs. However, this study's cost data alone do not justify the widespread use of erythropoietin in premature infants. When this issue is probed in great depth, sensitivity analyses demonstrate that major reductions in erythropoietin's cost and/or improvements in its effectiveness quite possibly will make its use economically more attractive.     

Factor XI antigen and activity in human platelets

Washed platelets, contaminated with less than 0.20% plasma factor XI, were examined for the presence of factor XI antigen and activity. These platelets contained a factor-XI-like coagulant activity (0.67 +/- 0.11 U/10(11) platelets) that remained constant after successive washes. By means of indirect immunofluorescence, a monospecific antibody to factor XI showed specific staining of both normal platelets and platelets from patients deficient in plasma factor XI. Radiolabeled Triton extracts of washed platelets and labeled purified factor XI solutions were analyzed for factor XI antigen by Staph A immunoprecipitation analysis using antibody to purified plasma factor XI followed by SDS gel electrophoresis. On unreduced gels, the platelet material ran as a single band having an apparent molecular weight of 220,000 daltons, whereas purified plasma factor XI gave a single band at 160,000 daltons. On reduced gels, the platelet material analyzed as a single band at 52,000 daltons, whereas purified factor XI gave a single band of 80,000 daltons. Analysis of a partially purified factor XI preparation from platelets by immunoelectrophoresis revealed that the platelet preparation displayed a slightly lower cathodal electrophoretic mobility at pH 8.6 than did plasma factor XI and yet appeared to possess complete antigenic identity with plasma factor XI. These results indicate that platelets possess a form of factor XI that exists as a disulfide-linked 52,000-dalton tetramer in contrast to the plasma form that circulates as a 80,000-dalton disulfide-linked dimer.     

Calcitonin gene-related peptide activated ATP-sensitive K+ currents in rabbit arterial smooth muscle via protein kinase A.

1. Whole-cell K+ currents activated by calcitonin gene-related peptide (CGRP) in smooth muscle cells enzymatically isolated from rabbit mesenteric arteries were measured in the conventional and perforated configurations of the patch clamp technique. The signal transduction pathway from CGRP receptors to activation of potassium currents was investigated. 2. CGRP (10 nM) activated a whole-cell current that was blocked by glibenclamide (10 microM), an inhibitor of ATP-sensitive K+ channels. Elevating intracellular ATP reduced glibenclamide-sensitive currents. CGRP increased the glibenclamide-sensitive currents by 3- to 6-fold in cells dialysed with 0.1 mM ATP, 3.0 mM ATP or in intact cells. The reversal potential of the glibenclamide-sensitive current in the presence of CGRP shifted with the potassium equilibrium potential, while its current-voltage relationship exhibited little voltage dependence. 3. Forskolin (10 microM), an adenylyl cyclase activator, Sp-cAMPS (500 microM) and the catalytic subunit of protein kinase A increased glibenclamide-sensitive K+ currents 2.1-, 3.3- and 8.2-fold, respectively. 4. Nitric oxide and nitroprusside did not activate glibenclamide-sensitive K+ currents. 5. Dialysis of the cell's interior with inhibitors of protein kinase A (synthetic peptide inhibitor, 4.6 microM or H-8, 100 microM) completely blocked activation of K+ currents by CGRP. 6. Our results suggest the following signal transduction scheme for activation of K+ currents by CGRP in arterial smooth muscle: (1) CGRP stimulates adenylyl cyclase, which leads to an elevation of cAMP; (2) cAMP activates protein kinase A, which opens ATP-sensitive K+ channels.     

A survey of oral implantology teaching in the university dental hospitals and schools of the United Kingdom and Eire

AIM: To provide an overview of the currently available academic teaching and clinical training in oral implantology at the university dental schools and hospitals of the United Kingdom and Eire. METHOD: A questionnaire was sent to the dean or director of dental studies and forwarded to the respective units involved in the academic teaching and clinical training of oral implantology. The setting was the university dental hospitals, and dental schools of the UK and Eire. Information was collected between July 1997 and March 1999. The main outcome measures were course availability, duration and emphasis for undergraduate and postgraduate study in the clinical discipline of oral implantology. The units or departments responsible for training and teaching were identified and formal degree courses were distinguished from non-degree courses. RESULTS: All institutions replied to the survey. All university dental schools provide undergraduate training in oral implantology in accordance with the guidelines provided by the General Dental Council. However, the courses vary with regard to the departments involved and the level of student participation. Thirteen centres provide informal postgraduate training with the duration ranging from one to eighteen days. Just eight centres provide formal academic graduate training based on oral implantology leading to recognised degrees. CONCLUSION: All university dental schools provide undergraduate teaching in oral implantology. Most centres also provide informal postgraduate training based on oral implantology. However, opportunities for academic graduate training, leading to recognised qualifications in this subject, appear limited at present.     

Human fibrinogen polymorphic site analysis by restriction endonuclease digestion and allele-specific polymerase chain reaction amplification: identification of polymorphisms at positions A alpha 312 and B beta 448

In the fibrinogen molecule, a total of seven sites have been tentatively identified as polymorphic; however, disagreements about these sites have been observed among the various protein and DNA sequence data published. To allow examination of the potential polymorphic sites at the DNA level, human genomic DNA samples were prepared from 110 unrelated, healthy individuals. Either allele- specific polymerase chain reaction (ASPCR) amplification or PCR amplification followed by restriction endonuclease digestion was used to detect the presence of possible polymorphisms. Two polymorphic sites were confirmed, one at A alpha 312 (Thr/Ala) by RsaI restriction analysis, and a second at B beta 448 (Arg/Lys) by MnlI restriction analysis. Mendelian inheritance of both polymorphisms was demonstrated and allele frequencies were estimated as 0.76/0.24 and 0.85/0.15 for the A alpha 312 and B beta 448 sites, respectively. The sites at A alpha 47, A alpha 296, B beta 162, B beta 296, and gamma 88 showed no evidence of variation in any of our samples. The amino acid polymorphisms at A alpha 312 and B beta 448 reflect conservative residue changes with unknown effects on fibrinogen structure or function. An additional, previously unrecognized DNA sequence variant was detected in a single individual in the second intron of the A alpha chain using HinfI restriction analysis.     

Peak expiratory flow rate in healthy children aged 6–17 years

Peak expiratory flow rate (PEFR) was measured in a cross-sectional study in 861 healthy Danish schoolchildren aged 6–17 years using a Mini Wright peak flowmeter. We found a strong correlation between PEFR and height, age and sex. The results were comparable with those from previous studies using a Wright peak flowmeter. The equation for prediction of PEFR in boys was calculated as (3.8 × height) + (10.6 × age) - 313.2 ( p < 0.0001, r = 0.8), and for girls, PEFR = (2.2 × height) + (14.2 × age) - 143.9 ( p < 0.0001, r = 0.64). Our results appear to be reliable, as evidenced by the high correlation coefficient in this large sample. Among healthy children without previous asthma, earlier episodes of recurrent wheezing were reported in 8.8% and a significantly lower PEFR was found in this group.     

Mycobacteria and human heat shock protein—specific cytotoxic t lymphocytes in rheumatoid synovial inflammation

Objective. To study the cytotoxic capacity of mycobacteria-specific T lymphocyte lines and clones from sites of inflammation in patients with rheumatoid arthritis (RA). We also studied antigen specificity, surface phenotype, expression of T cell receptors (TCR), and HLA restriction. Methods. Autologous macrophages (Mπ) from the synovial membrane (SM), synovial fluid (SF), or peripheral blood (PB) were used as target cells in cytotoxicity assays. Results. All SM and SF cell lines tested thus far have shown specific lysis of the autologous Mπ from SM or PB that had been pulsed with BCG (bacillus Calmette-Guerin), but no cytotoxicity when the targets were pulsed with irrelevant antigens such as tetanus toxoid and Chlamydia. Both CD4+ and CD8+ cells were shown to be involved in the specific cytolysis. The majority of the cytotoxic T lymphocyte (CTL) lines were TCRα/β+ cells. However, both TCRα/β+ and TCRγ/δ+ clones (TCR δ1+) from one RA patient showed antigen-specific lysis. Antigen-specific recognition by a number of CTL lines and clones generated from SF and SM was restricted by HLA—DR molecules. Two Mycobacterium bovis 65-kd heat shock protein (HSP)–specific TCRα/β+ SF T cell clones also lysed Mπ that had been pulsed with a recombinant human 65-kd HSP. Conclusion. Joint inflammation and destruction might be partly attributable to a cross-reaction of mycobacteria-induced cytotoxic T cells with self HSP.