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Caffeine, in the dose usualiy recommended (12-5 mg/kg loading dose and 3 mg/kg daily maintenance), and a higher dose regimen (25 mg/kg loading and 6 mg/kg daily maintenance), was compared with theophylline (7.5 mg/kg loading and 3 mg/kg thrice daily maintenance). The study was a randomised controiled trial in the treatment of a group of 44 infants of less than 31 weeks' gestation (mean gestational age 28.3 weeks) who were suffering from frequent apnoeic attacks. AU three regimens produced a significant reduction in apnoeic attacks within 24 hours, but only the higher dose caffeine and theophyfline groups showed a significant improvement in apnoea within eight hours.The use of caffeine for the treatment of neonatal apnoea is recommended, because a once daily dose is more easily administered, and because it was found that plasma concentrations were more predictable than those of theophylline. If used in very preterm infants, however, its is suggested that a higher dose regimen than that previously recommended be used to achieve a faster response. The methylxanthines-theophylline (and aminophylline) and caffeine-are widely used for the treatment of this condition.3 Theophylline has been the drug most commonly used to treat neonatal apnoea in the UK.4 5 Caffeine, however, has many potential advantages: it has a higher therapeutic ratio, it is absorbed more reliably when administered enterally and has a longer half life, thus enabling the drug to be administered only once daily.6 Caffeine has also been shown to be effective in apnoeic infants who are unresponsive to theophylline. Infants were included in our study if they were less than 31 weeks' gestation at birth and if they had either 10 (or more) apnoeic attacks in eight hours or four apnoeas in one hour. Apnoea was defined as a drop in heart rate of more than 40 beats/minute (bpm) below the resting heart rate in an infant who was not breathing, and who required stimulation to correct the problem. Infants prospectively entering the trial were randomly allocated (by random numbers in sealed envelopes) to one of three treatment groups. Group A ('standard dose caffeine')-a loading dose of 25 mg/kg caffeine citrate (12-5 mg/kg caffeine) and a maintenance dose of 6 mg/kg caffeine citrate (3 mg/kg caffeine) once daily were given to produce a desired plasma concentration of 15 mg/l caffeine (range [13][14][15][16][17][18][19][20] mg/l). Group B ('higher dose caffeine')-a loading dose of 50 mg/kg caffeine citrate (25 mg/kg caffeine) and maintenance dose of 12 mg/kg (6 mg/kg caffeine) once daily were given to produce a desired plasma concentration of 30 mg/l (range 26-40 mg/l). Group C ('theophylline')-a loading dose of 7.5 mg/kg theophylline and a maintenance dose of 3 mg/kg theophylline three times daily were given to produce a desired plasma concentration of 15 mg/l (range 13-20 mg/l). RegionalIn all three treatment groups the maintenance dose of the drug was adjusted if the plasma concentrations were out of the desired range, but in none of these patients were...

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The efficiency of embryo banking for rat and mouse models of human disease and normal biological processes depends on the ease of obtaining embryos. Authors report on the effect of genotype on embryo production and rederivation. In an effort to establish banks of cryopreserved embryos, they provide two databases for comparing banking efficiency: one that contains the embryo collection results from approximately 11,000 rat embryo donors (111 models) and another that contains the embryo collection results from 4,023 mouse embryo donors (57 induced mutant models). The genotype of donor females affected the efficiency of embryo collection in two ways. First, the proportion of females yielding embryos varied markedly among genotypes (rats: 16-100 %, mean =71 %; mice: 24-95 %, mean =65 %). Second, the mean number of embryos recovered from females yielding embryos varied considerably (rats: 4-10.6, mean =7.8; mice 5.3-32.2, mean =13.7). Genotype also affected the efficiency of rederivation of banked rat and mouse embryos models by embryo transfer. For rats, thawed embryos (n =684) from 33 genotypes were transferred into 66 recipient females (pregnancy rate, 78 %). The average rate of developing live newborns for individual rat genotypes was 30 % with a range of 10 to 58 %. For mice, thawed embryos (n =2,064) from 59 genotypes were transferred into 119 pseudopregnant females (pregnancy rate: 76 %). The average rate of development of individual mouse genotypes was 33 % with a range of 11 to 53 %. This analysis demonstrates that genotype is an important consideration when planning embryo banking programs.

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