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Improved delivery through biological membranes. XLV. Synthesis, physical-chemical evaluation, and brain uptake studies of 2-chloroethyl nitrosourea delivery systems.

The dihydropyridine in equilibrium with pyridinium redox chemical delivery system (CDS) was supplied to two 2-chloroethylnitrosoureas, i.e., HECNU and CCNUOH, and the physicochemical properties of the delivery systems were studied to assess their potential as improved delivery forms to the CNS. Detailed physicochemical evaluation and brain uptake studies were performed on one of the delivery systems (CCNUOH-CDS) derived from trans-4-hydroxy-CCNU, an active metabolite of CCNU. Two aqueous-based formulations derived from hydroxypropyl-beta-cyclodextrin (HP beta CD) and Tween 80:ethanol:water system were developed for CCNUOH-CDS to overcome the poor aqueous solubility conferred upon it by its high lipophilicity. The formulations enabled a 200- to 400-fold improvement in the water solubility of CCNUOH-CDS. Dose- and vehicle-dependent comparative tissue distribution studies in rats indicated improved brain-to-organ ratios of the delivery system at lower doses.

Animals

[Critical notes on delivery and perinatal mortality in single breech presentation deliveries].

This report deals with 432 single breech presentation deliveries. Caesarean section frequency was 12,3%. As to the vaginal route of delivery, the simple Bracht manoeuvre had been prefered; in recent times, however, the assisted spontaneous delivery with oxytocin-infusion has been introduced. The corrected perinatal mortality was 4,9%. The rate of prematurely born infants amounted to 14,6%. The corrected perinatal mortality of infants up to 2500 g was 3,3%; of full term infants it was 1,4%. The importance of breech presentation delivery as a high risk delivery is being emphasized. Fetal monitoring and blood gas analysis were required. Indications of caesarean section and suggestions for the management of breech presentations were established. Generally caesarean section of primiparae is not recommended. The diminished rate of prematurely born infants is considered to be of great importance for the decrease of perinatal mortality of breech presentation infants. Intensive pregnancy care, widely used uterotocolysis, and cervix-cerclage in cases of breech presentation are recommended.

Birth Weight

Fetal risk in delivery with the Shute parallel forceps: analysis of 1,503 forceps deliveries.

A total of 1,503 vaginal deliveries with the Shute parallel forceps during a 10 year period are analyzed as to the risk of instrumental damage. In this series, 35 infants died intrapartum or neonatally. Eliminating all deaths from unrelated causes, three remain in which the forceps could possibly have been implicated. Investigation of these, however, revealed in each case the presence of other concomitant and potentially lethal factors, none of which could be completely ruled out as the primary cause of fetal death. Each of the three cases is discussed in detail. We conclude from our series that the Shute forceps is useful in the delivery of premature infants, but should be employed for this maneuver only by very experienced operators. In these cases, midforceps should be performed only for critical indications. The risk of damage with parallel forceps deliveries from the pelvic floor is minimal if decision for operation is based on cardiotocographic criteria, and under favorable degrees of oxygenation. In the delivery of the immature infants, the parallel forceps can, in fact, hardly be superseded by any other instrument because of its unique controlled protection of the fragile fetal head from even the pressures of the birth canal. Delivery with the Shute forceps can be performed effectively under pudendal block or local infiltration anesthesia.

Adult

A needleless liquid jet injection delivery method for cardiac gene therapy: a comparative evaluation versus standard routes of delivery reveals enhanced therapeutic retention and cardiac specific gene expression.

This study evaluates needleless liquid jet method and compares it with three common experimental methods: (1) intramuscular injection (IM), (2) left ventricular intracavitary infusion (LVIC), and (3) LV intracavitary infusion with aortic and pulmonary occlusion (LVIC-OCCL). Two protocols were executed. First (n&#x2009;=&#x2009;24 rats), retention of dye was evaluated 10&#xa0;min after delivery in an acute model. The acute study revealed the following: significantly higher dye retention (expressed as % myocardial cross-section area) in the left ventricle in both the liquid jet [52&#x2009;&#xb1;&#x2009;4] % and LVIC-OCCL [58&#x2009;&#xb1;&#x2009;3] % groups p&#x2009;<&#x2009;0.05 compared with IM [31&#x2009;&#xb1;&#x2009;8] % and LVIC [35&#x2009;&#xb1;&#x2009;4] %. In the second (n&#x2009;=&#x2009;16 rats), each animal received adeno-associated virus encoding green fluorescent protein (AAV.EGFP) at a single dose with terminal 6-week endpoint. In the second phase with AAV.EGFP at 6&#xa0;weeks post-delivery, a similar trend was found with liquid jet [54&#x2009;&#xb1;&#x2009;5] % and LVIC-OCCL [60&#x2009;&#xb1;&#x2009;8] % featuring more LV expression as compared with IM [30&#x2009;&#xb1;&#x2009;9] % and LVIC [23&#x2009;&#xb1;&#x2009;9] %. The IM and LVIC-OCCL cross sections revealed myocardial fibrosis. With more detailed development in future model studies, needleless liquid jet delivery offers a promising strategy to improve direct myocardial delivery.

Animals

Risk of pre-term delivery in patients with previous pre-term delivery and/or abortion.

Patients with a history of two or more pregnancies which ended spontaneously before 37 weeks gestation had an increased risk of spontaneous pre-term labour and delivery in future pregnancies. This increased risk related mainly to previous second trimester abortions and not to previous first trimester abortions. Patients with one previous spontaneous pre-term labour and delivery had a 37 per cent risk, and those with two or more pre-term deliveries a 70 per cent risk of again delivering pre-term. There appeared to be no beneficial effect of cervical suture on the incidence of pre-term delivery in these patients.

Abortion, Habitual

Incidence of preterm delivery in patients with previous preterm delivery and/or abortion.

Patients with a history of two or more pregnancies which ended spontaneously before 37 weeks' gestation had an increased risk of spontaneous labour and delivery in subsequent pregnancies. This risk was correlated with previous second trimester abortion and spontaneous preterm delivery but not with previous first trimester abortions. Patients with one or more pregnancies ending in spontaneous second trimester abortion or with preterm labour and delivery had a 38--43% risk of again delivering before term.

Abortion, Spontaneous

[Concerning the administration of pethidine (Dolantin during delivery: discussion to "Analgesia during delivery--delayed effects for the child? by Riegel, Messow and Pielsticker (author's transl)].

The obstetrical problematic of intrapartal infant death following administration of Dolantin were discussed with the help of both of the cases described in the article by Riegel et al. At the same time, the question of analgesia during delivery with pethidine in combination with a respiratory depressant antidote was examined. Lorfalgyl, according to current opinion, cannot compensate the antidepressive effect of pethidine. Instead, the application of pure pethidine is recommended for obstetric analgesia in the first stage of labor. Today, naloxone used as antidote is particularly suitable before delivery or can be injected into the umbilical vein of the child after delivery. A plan of treatment for pathidine therapy during the first stage of labor in combination with the antidepressant was suggested.

Anesthesia, Obstetrical

Breech delivery: evaluation of the method of delivery on perinatal results and maternal morbidity.

A retrospective study of 460 single-gestation infants in breech position was conducted at the University of Colorado Medical Center to assess the impact of a policy for the selection of cases for vaginal delivery. Among infants weighing more than 2,500 grams, there was an increase in the cesarean section rate from 13% to 54%, with an associated increase in maternal morbidity from 7% to 15%. This occurred with no significant reduction in adverse perinatal outcome. However, a case-by-case review suggests that more frequent and timely cesarean sections would have further reduced perinatal morbidity and deaths among term infants. Among the infants weighing 2,500 grams or less there was an increase in cesarean births from 5% to 55% following the introduction of the strict criteria for vaginal delivery. Among the infants weighing 1,501 to 2,500 grams there was no significant difference in survival between the cesarean and vaginally delivered patients. Although infants weighing 501 to 1,500 grams delivered by cesarean section survived more frequently than did those delivered vaginally, the differences in perinatal deaths may have been due to a higher birth weight in the cesarean-delivered infants or an over-all improvement in neonatal intensive care for infants of very low birth weight.

Apgar Score

The single-unit delivery system--a safe alternative to home deliveries.

The need has arisen for the development of a health care/delivery system that can allow for a natural and personalized childbirth experience, within the safe confines of a modern obstetric unit. The single-unit delivery system (SUDS) is designed to achieve this objective by: strict prenatal screening of patients into low- and high-risk categories, utilization of a single room for the entire labor process, and close personalized supervision of women in "normal" labor by trained midwives/monitrixes. Physicians supervise the entire unit and are directly responsible for the management of all high-risk and complicated labors. The SUDS concept has been tried in clinical practice and has been proved to be an effective method of providing safe and satisfying obstetric care without compromising modern obstetric standards.

Delivery, Obstetric

[Induction of lung maturation in pending premature delivery and scheduled premature delivery].

At the Women's Hospital of the Medical Academy of Erfurt we have examined the efficiency of dexamethasone on fetal lungs maturation at imminent premature birth and planned untimely delivery. Dexamethasone was given in a randomized series at a dosage of 12-mg per day orally on three successive days. The effectiveness of induction was measured at the percentage of the total phospholipid fraction in the amniotic fluid and at the mortality of RDS in both groups. A successful induction with dexamethasone we can only reach after the 32nd week of pregnancy.--Because this effect is not always continuous, we recommend to make the induction of fetal lungs maturation with dexamethasone and--if it necessary--its repetition after one week conditional upon the content of total phospholipids in amniotic fluid.

Adult

[Injury hazards in deliveries using the Shute forceps (analysis of 1016 forceps deliveries)].

Report about 1016 deliveries by means of the parallel forceps (W. B. Shute). This group contains pathologic-anatomical results of 30 stillbirthes or died newborns. Accordingly to the classification in subarachnoidal, subependymal or subdural hämorrhage there are only in two cases signs of obstetrical brain damage. The hypoxia is the most important reason of intracraniale haemorrhage. In order to an objektive indication, without progredient signs of fetal hypoxia the extraction by means of parallel forceps is not dangerous. We have used the instrument for extraction as well term as preterm infants with good results.

Adult

Improved delivery through biological membranes. 3. Delivery of N-methylpyridinium-2-carbaldoxime chloride through the blood-brain barrier in its dihydropyridine pro-drug form.

Administration of N-methyl-1,6-dihydropyridine-2-carbaldoxime hydrochloride, the pro-drug form of 2-PAM, resulted in an average of 13-fold increase in the amount of 2-PAM delivered into the brain of mice as compared to the administration of 2-PAM. The pro-drug which crossed the BBB resulted in a dramatic increase in the reactivation of AChE blocked by DFP. In vivo studies of the "aging" of the phosphorylated AChE in the brain of mice could also be studied using pro-2-PAM.

Acetylcholinesterase