Maternal use of selective serotonin-reuptake inhibitors and risk of persistent pulmonary hypertension of the newborn.

Use of selective serotonin reuptake inhibitors (SSRIs) in late pregnancy has been associated with persistent pulmonary hypertension of the newborn (PPHN), a rare condition with substantial infant mortality and morbidity. Although the increase in absolute risk is small on a population level, it may be of concern to many patients. It remains unclear the extent to which the increased risks reported for PPHN are explained by the underlying maternal illness rather than the use of SSRIs.

Reproductive decision making after the diagnosis of multiple sclerosis (MS).

OBJECTIVE: This study aimed to determine reproductive practices and attitudes of North Americans diagnosed with multiple sclerosis (MS) and the reasons for their reproductive decision making. METHODS: A self-administered questionnaire on reproductive practices was mailed to 13,312 registrants of the North American Research Committee on Multiple Sclerosis (NARCOMS) database who met inclusion criteria for the study. Completed questionnaires were then returned to the authors in an anonymous format for analysis. RESULTS: Among 5949 participants, the majority of respondents (79.1%) did not become pregnant following diagnosis of MS. Of these, 34.5% cited MS-related reasons for this decision. The most common MS-related reasons were symptoms interfering with parenting (71.2%), followed by concerns of burdening partner (50.7%) and of children inheriting MS (34.7%). The most common reason unrelated to MS for not having children was that they already have a "completed family" (55.6%). Of the 20.9% of participants who decided to become pregnant (or father a pregnancy) following a diagnosis of MS, 49.5% had two or more pregnancies. CONCLUSION: This study indicates that an MS diagnosis does not completely deter the consideration of childbearing in MS patients of both genders.

Associations of osseous abnormalities in Neurofibromatosis 1.

The characteristic sites of Neurofibromatosis 1-associated osseous manifestations are the long bones (usually the tibia and fibula), vertebrae and sphenoid wing. Although these focal bony lesions may cause profound clinical consequences, a minority of people with NF1 are affected. However, most people with NF1 are shorter than expected for their age, gender and family. The pathogenesis of NF1 focal osteopathy and its relationship, if any, to short stature are unknown. We examined associations between the occurrence of various osseous lesions in 3377 NF1 probands from the Children's Tumor Foundation NF International Database. Using logistic regression analysis among 260 NF1 probands who had undergone radiological examination of both the spine and skull, we found associations between the occurrence of sphenoid wing and long bone osteopathy (conditional odds ratio [OR] = 6.1; 95% confidence interval [CI] = 1.7-22.3; P = 0.006) and between sphenoid wing and vertebral osteopathy (OR = 16.9; 95% CI = 5.3-53.3; P < 0.001) after adjusting for age and gender. Similar findings were observed from all 3377 NF1 probands using a multivariate probit regression model. In a separate analysis, we found lower age- and gender-standardized height in patients who had characteristic vertebral or sphenoid wing lesions than in people who did not (P < 0.05). We found no relationship between height and tibial osteopathy. We conclude that some people with NF1 are more likely to develop osseous manifestations than others and speculate that there may be a common pathogenetic mechanism responsible for the development of osseous abnormalities and that of the vertebrae and long bones.

Is osseous dysplasia a primary feature of neurofibromatosis 1 (NF1)?

Characteristic skeletal lesions are a cardinal feature of the autosomal dominant condition, neurofibromatosis 1 (NF1). The most frequently involved skeletal sites are the sphenoid wing, vertebrae, and tibia. Osseous lesions may range in severity in NF1 but are often progressive. They may lead to serious clinical consequences and be resistant to treatment. The skeletal lesions of NF1 are usually considered to be 'dysplasias', i.e. primary defects of bone, although there is no direct evidence supporting this interpretation. Moreover, it is difficult to understand why a generalized dysplasia of bone would produce focal lesions that show such a striking predisposition to only a few bones. We review the clinical and pathological features of NF1 skeletal lesions and propose that they result from an abnormal response of NF1 halpoinsufficient bone to abnormal mechanical forces rather than from a primary osseous dysplasia.

Angiotensin II receptor antagonist treatment during pregnancy.

Angiotensin II (A-II) is the main effector of the renin-angiotensin system. A-II functions by binding its type 1 (AT1) receptors to cause vasoconstriction and retention of sodium and fluid. Several AT1 receptor antagonists-a group of drugs collectively called "sartans"-have been marketed during the past few years for treatment of hypertension and heart failure. At least 15 case reports describe oligohydramnios, fetal growth retardation, pulmonary hypoplasia, limb contractures, and calvarial hypoplasia in various combinations in association with maternal losartan, candesartan, valsartan, or telmisartan treatment during the second or third trimester of pregnancy. Stillbirth or neonatal death is frequent in these reports, and surviving infants may exhibit renal damage. The fetal abnormalities, which are strikingly similar to those produced by maternal treatment with angiotensin-converting enzyme (ACE) inhibitors during the second and third trimesters of pregnancy, are probably related to extreme sensitivity of the fetus to the hypotensive action of these drugs. Very little information is available regarding the outcome of human pregnancies in which the mother was treated with an AT1 receptor antagonist during the first trimester, but animal studies have not demonstrated teratogenic effects after maternal treatment with large doses of AT1 receptor antagonists during organogenesis. We conclude that pharmacological suppression of the fetal renin-angiotensin system through ACE inhibition or AT1 receptor blockade seems to disrupt fetal vascular perfusion and renal function. We recommend that maternal treatment with AT1 receptor antagonists be avoided during the second and third trimesters of pregnancy and that women who become pregnant while taking one of these medications be changed to an antihypertensive drug of a different class as soon as the pregnancy is recognized.

Adsorption of ammonium dinitramide (ADN) from aqueous solutions. 1. Adsorption on powdered activated charcoal.

Investigations on the adsorption of ammonium dinitramide (NH(4)N(NO(2))(2)) (ADN) from aqueous solutions on powdered activated charcoal (PAC) were carried out in order to find out an effective and easier method of separating ADN from aqueous solutions. The effectiveness of PAC in the selective adsorption of ADN from aqueous solutions of ADN (ADN-F) and ADN in presence of sulfate (SO(4)(2-)) and nitrate (NO(3)(-)) ions (ADN-PS) was examined and compared using batch and column methods. The adsorption process follows both Langmuir and Freundlich adsorption isotherms and the isotherm parameters for the models were determined. The observed data favor the formation of monolayer adsorption. The adsorption capacities were found to be 63.3, 119, 105.3 and 82 mg of ADN per g of PAC for ADN-F (batch), ADN-PS (batch), ADN-F (column) and ADN-PS (column), respectively. Break-through curves for ADN-F and ADN-PS were obtained for the optimization of separation of ADN from aqueous solutions. Elution curves were generated for the desorption of ADN from PAC using hot water as eluent.

N-nitrosoephedrine and N-nitrosopseudoephedrine: their dissolution, absorption, blood clearance and elimination studies.

Dissolution and absorption rates (in vitro); clearance from blood and elimination rates of N-nitrosoephedrine (NEP) and N-nitrosopseudophedrine (NPEP) in mice were determined. The two isomers obeyed first-order kinetics and from the slope of the regression line, the rate constant for each study was obtained. These constants were 0.023, 0.038 min-1 (dissolution); 0.192, 0.225 h-1 (stomach absorption); 2.898, 1.980 h-1 (intestinal absorption); 0.33, 0.55 h-1 (blood clearance) and 0.373, 0.393 h-1 (elimination from whole animal) of NEP and NPEP, respectively, and were tested by Student's t-test. Significant differences in the dissolution, absorption and blood clearance rates of NPEP from those of NEP have been observed (P less than 0.05-0.01). These differences are expected to exert their influence on the metabolic rates and the carcinogenic and/or spectral properties of NEP and NPEP, in a related pattern.

Superovulation and oocyte recovery in the ewe.

Thirty-eight adult ewes were superovulated following a 12 d progestagen treatment in association with either 135 mg crude horse anterior pituitary extract (HAP) or 30 mg soluble HAP with or without 1000 IU human chorionic gonadotrophin (hCG). Soluble HAP in combination with hCG significantly (P < 0.01) increased the ovulation rate as compared to HAP alone (14.5 vs 5.3, respectively). The number of oocytes recovered per ewe showing estrus following soluble HAP and HCG (6.9) was higher than after HAP alone (3.3), but this difference was not significant. A significantly higher (P < 0.05) ovulation rate and ovarian response were obtained following crude HAP than soluble HAP (14.0 vs 6.3 and 15.3 vs 9.4, respectively). There was a tendency for the proportion of follicles which ovulated to be higher in the crude HAP group. The mean number of oocytes or the proportion of oocytes recovered was significantly higher (P < 0.05) in the crude HAP group than in the soluble HAP group.

Production of nitrosamines from ephedrine, pseudoephedrine and extracts of Ephedra foliata under physiological conditions.

N-Nitrosoephedrine (NEP) and N-nitrosopseudoephedrine (NPEP) were synthesised at 5 degrees C using different concentrations of various acids. The reaction with acetic acid gave the highest yield (85%) of N-nitrosamine. Ephedrine and pseudoephedrine were reacted with nitrite under physiological conditions (37 degrees C, pH 1-3) to form NEP and NPEP. The yield of NEP, which is a known carcinogen, and NPEP were the highest (18.5%) at pH 2. Aqueous and alcoholic extracts of Ephedra foliata (100 g dry wt), nitrosated under physiological conditions, produced 0.77 mg and 8.3 mg, respectively, as total nitrosamines. This indicated the potential of the nitrosamine formation from the plant extracts specified.

The potential of carboxypeptidase G2-antibody conjugates as anti-tumour agents. I. Preparation of antihuman chorionic gonadotrophin-carboxypeptidase G2 and cytotoxicity of the conjugate against JAR choriocarcinoma cells in vitro.

Carboxypeptidase G2, a zinc metalloenzyme isolated from Pseudomonas sp. strain RS-16, which catalyses the hydrolytic cleavage of reduced and non-reduced folates to pteroates and L-glutamate, has been linked to a monoclonal antibody (W14A) raised to human chorionic gonadotrophin. The coupling efficiency and retention of antibody and enzymatic activities are compared for three separate methods of preparing 1:1 conjugates. Preliminary in vitro studies on the cytotoxicity of the free enzyme and the conjugated enzyme towards JAR choriocarcinoma cells are reported. Despite the limitations of the in vitro model, it could be demonstrated that a significant proportion of 10(6) choriocarcinoma cells lost viability when exposed to either free or conjugated enzyme for 72 hours at concentrations of carboxypeptidase G2 of 1-3 units ml-1 of medium.

Purification and properties of carboxypeptidase G2 from Pseudomonas sp. strain RS-16. Use of a novel triazine dye affinity method.

A folate-degrading enzyme, carboxypeptidase G2, has been purified on a large scale from Pseudomonas sp. strain RS-16. Homogeneous enzyme was obtained by a three-step procedure involving ion-exchange chromatography and a novel triazine dye (affinity) chromatography step which utilizes Zn2+ to promote adsorption of the enzyme. Enzyme was selectively eluted by the use of a chelating agent (EDTA) and a step change in pH. The enzyme is a dimeric protein (Mr 83000) with two identical subunits of 41800 and contains four atoms of zinc per enzyme molecule, which are required for full activity. The enzyme follows Michaelis-Menten kinetics with Km values of 4.0 microM for folate, 8.0 microM for methotrexate and 34.0 microM for 5-methyltetrahydrofolate, the predominant form of reduced folate found in plasma.