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The NH2‐terminal blocking group of the Ca 2+‐binding B‐subunit of calcineurin (protein phosphatase‐2B) has been identified as myristic acid by fast atom bombardment mass spectrometry and gas chromatography. The sequence, myristyl‐Gly‐Asn‐Glu‐Ala‐, is very similar to that of the catalytic subunit of cyclic AMP‐dependent protein kinase, the only other protein known to contain this fatty acid. This finding, and the elution of all myristyl peptides at 57% acetonitrile on reverse phase HPLC, may facilitate the identification of other proteins with this blocking group.

SummaryBackgroundOvarian tissue cryopreservation with later reimplantation has been shown to preserve fertility in adult women, but this approach remains unproven and experimental in children and adolescents. We aimed to assess the use of the Edinburgh selection criteria for ovarian tissue cryopreservation in girls and young women with cancer to determine whether we are offering this invasive procedure to the patients who are most at risk of premature ovarian insufficiency.MethodsCryopreservation of ovarian tissue has been selectively offered to girls and young women with cancer who met the Edinburgh selection criteria since 1996. Between Jan 1, 1996, and June 30, 2012, 410 female patients younger than 18 years at diagnosis were treated for cancer (including leukaemia and brain tumours) at the Edinburgh Children's Cancer Centre, which serves the whole South East of Scotland region. We determined the ovarian status of these patients from review of clinical records and classified them as having premature ovarian insufficiency or not, or as unable to be determined. Patients younger than 12 years at time of data cutoff (Jan 31, 2013) were excluded from the analysis.Findings34 (8%) of the 410 patients met the Edinburgh selection criteria and were offered ovarian tissue cryopreservation before starting cancer treatment. 13 patients declined the procedure and 21 consented, and the procedure was completed successfully in 20 patients. Of the 20 patients who had ovarian tissue successfully cryopreserved, 14 were available for assessment of ovarian function. Of the 13 patients who had declined the procedure, six were available for assessment of ovarian function. Median age at the time of follow-up for the 20 assessable patients was 16·9 years (IQR 15·5–21·8). Of the 14 assessable patients who had successfully undergone ovarian cryopreservation, six had developed premature ovarian insufficiency at a median age of 13·4 years (IQR 12·5–14·6), one of whom also had a natural pregnancy. Of the six assessable patients who had declined the procedure, one had developed premature ovarian insufficiency. Assessment of ovarian function was possible for 141 of the 376 patients who were not offered cryopreservation; one of these patients had developed premature ovarian insufficiency. The cumulative probability of developing premature ovarian insufficiency after treatment was completed was significantly higher for patients who met the criteria for ovarian tissue cryopreservation than for those who did not (15-year probability 35% [95% CI 10–53] vs 1% [0–2]; p<0·0001; hazard ratio 56·8 [95% CI 6·2–521·6] at 10 years).InterpretationThe results of this analysis show that the Edinburgh selection criteria accurately identify the few girls and young women who will develop premature ovarian insufficiency, and validate their use for selection of patients for ovarian tissue cryopreservation. Further follow-up of this cohort of patients is likely to allow refinement of the criteria for this experimental procedure in girls and young women with cancer...

controlled for in the multivariate analvsis. Furthermore, the suggested risk factors occurring later in life, such as psychological mechanisms and drug availability and exposition, cannot explain the demonstrated associations between administration of drugs during the perinatal period and subsequent addiction in offspring. Also, genetic and socioeconomic factors were largely controlled for by matching addicts with their own siblings.In conclusion, effective pain relief is sometimes an important factor for a successful outcome of delivery, as well as for the ability of the mother to accept and care for the child in the future. At present, when considering the choice of analgesic method immediate risks and benefits are mainly taken into account. When depressant or sedative drugs are used their possible long term effects due to imprinting also seem to be important. From this point of view, analgesic methods not associated with passage of substantial amounts of drugs across the placenta are preferable. Our Abstract Objective-To see whether a prepregnancy clinic for diabetic women can achieve tight glycaemic control in early pregnancy and so reduce the high incidence of major congenital malformation that occurs in the infants of these women. Design-An analysis of diabetic control in early pregnancy including a record of severe hypoglycaemic episodes in relation to the occurrence of major congenital malformation among the infants.Setting-A diabetic clinic and a combined diabetic and antenatal clinic of a teaching hospital.Patients -143 Insulin dependent women attending a prepregnancy clinic and 96 insulin dependent women managed over the same period who had not received specific prepregnancy care.Main outcome measure-The incidence of major congenital malformation.Results-Compared with the women who were not given specific prepregnancy care the group who attended the prepregnancy clinic had a lower haemoglobin Al concentration in the first trimester (8.4% v 10-5%), a higher incidence of hypoglycaemia in early pregnancy (38/143 women v 8/96), and fewer infants with congenital abnormalities (2/143 v 10/96; relative risk among women not given specific prepregnancy care 7-4 (95% confidence interval 1-7 to 33.2)).Conclusion-Tight control of the maternal blood glucose concentration in the early weeks of pregnancy can be achieved by the prepregnancy clinic approach and is associated with a highly significant reduction in the risk of serious congenital abnormalities in the offspring. Hypoglycaemic episodes do not seem to lead to fetal malformation even when they occur during the period of organogenesis.

Summary. The progression of subclinical polyneuropathy over 2.5 years has been studied in a representative group of 75 young patients with Type I (insulin-dependent) diabetes (initial age 16-19years). The relationships between changes in nerve function, glycaemic control and concurrently developing microvascular complications (retinopathy, microproteinuria) were investigated. Deterioration of motor, sensory and autonomic nerve function, retinopathy and microproteinuria was related to poor glycaemic control. In addition, there was an association between developing neural and microvascular complications which was not diminished when their common relationship to hyperglycaemia was taken into account. These findings suggest that, although poor glycaemic control is an essential permissive factor in the early development of diabetic polyneuropathy, other influences, shared with microvascular complications, must also be important.