Use of antidepressants and association with elective termination of pregnancy: population based case-control study.

OBJECTIVE: To assess whether the use of selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, mirtazapine, venlafaxine or other antidepressants is associated with late elective termination of pregnancy. DESIGN: Case-control study using data from national registers. SETTING: Denmark, Finland, and Norway during the period 1996-2007. POPULATION: A total of 14,902 women were included as cases and 148,929 women were included as controls. METHODS: Cases were women with elective termination of pregnancy at 12-23 weeks of gestation. Controls continued their pregnancy and were matched with cases on key factors. MAIN OUTCOME MEASURES: Association between antidepressant use during pregnancy and elective termination of pregnancy at 12-23 weeks of gestation for fetal anomalies, or for maternal ill health or socio-economic disadvantage. RESULTS: At least one prescription of antidepressants was filled by 3.7% of the cases and 2.2% of the controls. Use of any type of antidepressant was associated with elective termination of pregnancy for maternal ill health or socio-economic disadvantage (odds ratio, OR 2.3; 95% confidence interval, 95% CI 2.0-2.5). Elective termination of pregnancy for fetal anomalies was associated with the use of mirtazapine (OR 2.2, 95% CI 1.1-4.5). There was no association between the use of any of the other antidepressants and elective termination of pregnancy for fetal anomalies. CONCLUSION: The use of any type of antidepressants was associated with elective termination of pregnancy at 12-23 weeks for maternal ill health or socio-economic disadvantage, but not with terminations for fetal anomalies. Further studies need to confirm the findings concerning mirtazapine and termination of pregnancy for fetal anomalies.

Combined costimulation blockade prevents rejection of allogeneic islets in mice.

There is a need for immunosuppressive protocols in islet transplantation that are neither nephrotoxic nor diabetogenic. We have examined blockade of the CD28-B7, CD40-CD40L and ICAM-LFA-1 pathways in a model of allogeneic islet transplantation in mice to determine the efficacy of this blockade in prolongation of graft survival. Histological evidences of inflammation and function were evaluated in grafts that had been functioning for 100 days. Treatment with a combination of all three drugs, or with CTLA4Ig and anti-CD40L, administered four times during the first six postoperative days, resulted in an excellent graft survival. All animals had a graft survival of >100 days (i.e. indefinitely). Mice treated with CTLA4Ig and anti-CD40L all showed well-preserved islets without signs of degeneration or destruction. There were no signs of rejection, as evidenced by the absence of infiltrating lymphocytes. This group had the least amount of rejection/inflammation changes according to ranking of all grafts. In conclusion, a short induction treatment with anti-CD40L and CTLA4Ig totally prevents rejection and preserves the allogeneic islets transplanted to mice. The addition of anti-LFA-1 did not confer any benefit.

The safety of proton pump inhibitors in pregnancy: a multicentre prospective controlled study.

BACKGROUND: Proton pump inhibitors are used to treat gastro-oesophageal reflux and peptic ulcers. Gastro-oesophageal reflux is a common condition in pregnancy. Human pregnancy experience with lansoprazole or pantoprazole is very limited. More data exist on the safety of omeprazole in pregnancy. AIM: To assess the safety of proton pump inhibitors in pregnancy. METHODS: The rate of major anomalies was compared between pregnant women exposed to omeprazole, lanzoprazole, or pantoprazole and a control group counselled for non-teratogens. The study design is a multicentre (n = 8), prospective, controlled study of the European Network of Teratology Information Services. RESULTS: We followed up 295 pregnancies exposed to omeprazole [233 in the first trimester (T1)], 62 to lansoprazole (55 in T1) and 53 to pantoprazole (47 in T1), and compared pregnancy outcome to that of 868 European Network of Teratology Information Services controls. The rate of major congenital anomalies did not differ between the exposed and control groups [omeprazole nine of 249 (3.6%), lansoprazole two of 51 (3.9%) and pantoprazole one of 48 (2.1%) vs. controls 30 of 792 = 3.8%]. No differences were found when exposure was limited to the first trimester after exclusion of genetic, cytogenetic or infectious anomalies. CONCLUSIONS: This study suggests that proton pump inhibitors do not represent a major teratogenic risk in humans.

Valproate embryopathy in three sets of siblings: further proof of hereditary susceptibility.

The fetal valproate syndrome (FVS) is characterized by distinctive facial appearance, major and minor malformations, and developmental delay. Generally, only a small proportion of prenatally exposed children are affected. The authors describe three families in whom the occurrence of FVS in all the siblings strongly suggests hereditary susceptibility to valproic acid-induced adverse outcome. The risk for recurrence in a subsequent pregnancy may be high and should be taken into account in the counseling of parents and in considering drug treatment.

Prospective, controlled, multicentre study of loperamide in pregnancy.

BACKGROUND: Loperamide is a synthetic piperidine derivative used for the treatment of both acute and chronic diarrhea. Little is known about its safety and risk in pregnancy. Human data are limited to one surveillance study of Michigan Medicaid patients, with 108 women exposed in the first trimester. In this study there were six major birth defects, three of which were cardiovascular anomalies. OBJECTIVES: To determine whether loperamide use in pregnancy is associated with an increased risk of major malformations. The secondary end points were rates of minor malformations, spontaneous and therapeutic abortions, and premature births, and mean birth weights. PATIENTS AND METHODS: Women counselled by five teratogen information centres on the safety and risk of loperamide in pregnancy were followed after delivery and compared with a similar group of women matched for age, smoking, alcohol and other exposures. RESULTS: One hundred and five follow-ups were completed; 89 of the women were exposed to loperamide in the first trimester of pregnancy. There were no statistically significant differences between the study group and the control group in any of the end points that were analyzed. However, of women who took loperamide throughout their pregnancy, 21 of 105 had babies who were 200 g smaller than babies in the control group. CONCLUSIONS: The results of this study suggest that the use of loperamide during pregnancy is not associated with an increased risk of major malformations.

Nonlinear diffusion filtering of images obtained by planar laser-induced fluorescence spectroscopy.

The application of nonlinear anisotropic diffusion filtering to reduce noise and enhance contours in images obtained by two-dimensional planar laser-induced fluorescence (PLIF) spectroscopy is presented. In this process the diffusion coefficient is locally adapted, becoming negligible as object boundaries are approached. Noise is efficiently removed, and object contours are strongly enhanced. The technique is demonstrated with PLIF images obtained from the OH radical recorded in turbulent flames. We show that nonlinear diffusion is suitable as a preprocessing step, before image segmentation becomes possible, and we demonstrate how the technique is applied for the quantitative extraction of flame reaction boundaries from PLIF data.

Marathon run stimulates more prostacyclin than thromboxane synthesis and differently in men and women.

To study the effect of strenuous physical exercise on the balance between vasodilatory and antiaggregatory prostacyclin (PGI2) and its endogenous antagonist thromboxane A2 (TxA2), we measured the urinary output of two metabolites of PGI2 (6-keto-prostaglandin F1 alfa, 6-keto, and 2,3-dinor-6-keto), as well as two metabolites of TxA2 (thromboxane B2, TxB2, and 2,3-dinor-TxB2) ten days before, during and one, three and five days after a marathon run by 15 women and ten men. The basal urinary outputs of women and men were similar. In women, 6-keto excretion increased 10-fold (p < 0.001) and in men 30-fold (p < 0.05) during the run, and 2,3-dinor-6-keto increased 2-fold in women (p < 0.05) and 7-fold in men (p < 0.05). During the run, TxB2 output increased only in women (3-fold, p < 0.05) and 2,3-dinor-TxB2 only in men (4-fold, p < 0.05). The marathon-induced changes lasted maximally one day. The greater PGI2-than TxA2-stimulation during marathon run may be involved with the favorable effects on the cardiovascular system of physical exercise.

Marathon running accompanied by transient decreases in urinary calcium and serum osteocalcin levels.

We evaluated the effects of marathon running on bone metabolism in 23 noncompetitive athletes (15 women, 8 men, age range 23-55 years). The volunteers were studied 10 days before, immediately after, and 1, 3, and 5 days after the run. Serum osteocalcin levels were decreased on average by 20% (from 4.9 to 3.9 micrograms/liter, P = 0.005) in men and by 10% (from 4.9 to 4.4 micrograms/liter, P < 0.05) in women at the end of the marathon, with lowest osteocalcin levels (67-55% of the prerun levels) encountered 1 day after the marathon. The activity of bone alkaline phosphatase was decreased in women (from 66.3 to 62.3 U/liter, P < 0.05) after the run, and this drop was detectable at each checkup after the run. Urinary excretion of calcium was lowered on average by 82% in men (from 2.8 to 0.5 mumol/minute, P < 0.05) and by 76% in women (from 2.5 to 0.6 mumol/minute, P < 0.005) after the run, but had already returned to prerun levels 1 day after the marathon. Urinary excretion of hydroxyproline tended to rise in both men and women, but the change did not reach statistical significance in either sex. These changes suggest a transient suppression in osteoblast function during the marathon.

Killing, letting die, and simple conflicts.

KIE: Proponents of the moral equivalence of killing and letting die argue that in cases of simple conflict, where one agent must either perform a positive act and kill one person, or not perform that act and allow another person to die, the agent's alternatives are clearly morally equivalent. Malm rejects this view in a three part essay. He argues that in cases of simple conflict, the acts of killing and letting die are morally different, and that killing is not in itself worse than letting die. Malm considers and rejects the suggestion that the agent should decide randomly between the two alternatives. He concludes that while simple conflict cases require us to recognize a morally significant difference between killing and letting die, they do not require us to recognize a morally significant difference between acting and refraining.^ieng

Operational dimensions of one multihospital system.

The pressing realities of health care delivery in the 1970s call for new solutions and fresh approaches to health care administration. The Lutheran Hospitals and Homes Society of America was founded to assist communities that were encountering difficulties in providing for the health care needs of their people. This article describes how the society meets these needs through a multihospital approach in which the "parent" organization totally operates its member facilities rather than fragmenting its services by allowing member units to utilize one or more of its services.