Bryophyllum pinnatum enhances the inhibitory effect of atosiban and nifedipine on human myometrial contractility: an in vitro study.

BACKGROUND: The herbal medicine Bryophyllum pinnatum has been used as a tocolytic agent in anthroposophic medicine and, recently, in conventional settings alone or as an add-on medication with tocolytic agents such as atosiban or nifedipine. We wanted to compare the inhibitory effect of atosiban and nifedipine on human myometrial contractility in vitro in the absence and in the presence of B. pinnatum press juice (BPJ). METHODS: Myometrium biopsies were collected during elective Caesarean sections. Myometrial strips were placed under tension into an organ bath and allowed to contract spontaneously. Test substances alone and at concentrations known to moderately affect contractility in this setup, or in combination, were added to the organ bath, and contractility was recorded throughout the experiments. Changes in the strength (measured as area under the curve (AUC) and amplitude) and frequency of contractions after the addition of all test substances were determined. Cell viability assays were performed with the human myometrium hTERT-C3 and PHM1-41 cell lines. RESULTS: BPJ (2.5 µg/mL), atosiban (0.27 µg/mL), and nifedipine (3 ng/mL), moderately reduced the strength of spontaneous myometrium contractions. When BPJ was added together with atosiban or nifedipine, inhibition of contraction strength was significantly higher than with the tocolytics alone (p = 0.03 and p < 0.001, respectively). In the case of AUC, BPJ plus atosiban promoted a decrease to 48.8 ± 6.3% of initial, whereas BPJ and atosiban alone lowered it to 70.9 ± 4.7% and to 80.9 ± 4.1% of initial, respectively. Also in the case of AUC, BPJ plus nifedipine promoted a decrease to 39.9 ± 4.6% of initial, at the same time that BPJ and nifedipine alone lowered it to 78.9 ± 3.8% and 71.0 ± 3.4% of initial. Amplitude data supported those AUC data. The inhibitory effects of BPJ plus atosiban and of BPJ plus nifedipine on contractions strength were concentration-dependent. None of the test substances, alone or in combination, decreased myometrial cell viability. CONCLUSIONS: BPJ enhances the inhibitory effect of atosiban and nifedipine on the strength of myometrial contractions, without affecting myometrium tissue or cell viability. The combination treatment of BPJ with atosiban or nifedipine has therapeutic potential.

Inhibition of porcine detrusor contractility by the flavonoid fraction of Bryophyllum pinnatum--a potential phytotherapeutic drug for the treatment of the overactive bladder syndrome.

AIMS: To determine if the phytotherapeutic agent, Bryophyllum pinnatum, could serve as an alternative drug for the overactive bladder syndrome, and to characterise the fraction responsible for the inhibition of detrusor contractility. METHODS: Fractions were prepared from the MeOH extract of B. pinnatum and further analysed by HPLC-PDA-MS. Detrusor muscle strips were prepared from porcine bladders and the electrically induced muscle contractility measured by organ bath. The effect of B. pinnatum leaf press juice (2.5-10%), a flavonoid fraction (0.1-1 mg/ml), and a bufadienolide fraction (0.1-40 µg/ml) on detrusor contractility was assessed and compared with controls (polar fraction (0.5-5 mg/ml) and oxybutynin (10(-8)-10(-6) M)). RESULTS: The press juice, at a concentration of 10% led to a reduction of detrusor contractility. Bladder strips treated with the flavonoid fraction showed a significant reduction of the contractility to 21.3 ± 5.2% (1 mg/ml) while the bufadienolide fraction had no inhibitory effect in the investigated concentrations. The polar fraction showed a reduction of the contractility in a pH-dependent fashion. At 10(-6) M concentration oxybutynin reduced the detrusor contractility to 21.9 ± 4.7%. CONCLUSIONS: The flavonoid fraction of Bryophyllum pinnatum reduces the porcine detrusor contractility in a dose- and time-dependent manner. Fractions from B. pinnatum may be a new pharmacological approach for the treatment of OAB.

Sleep quality in pregnancy during treatment with Bryophyllum pinnatum: an observational study.

INTRODUCTION: Poor sleep quality in pregnancy is frequent. A treatment with sedatives is problematic due to possible adverse effects for mother and embryo/foetus. In the present study, we investigated the sedative effect of Bryophyllum pinnatum, a phytotherapeutic medication used in anthroposophic medicine. In previous clinical studies on its tocolytic effect, B. pinnatum showed a good risk/benefit ratio for mother and child. A recent analysis of the prescribing pattern for B. pinnatum in a network of anthroposophic physicians revealed sleep disorders as one of the most frequent diagnoses for which these preparations are prescribed. MATERIALS AND METHODS: In this prospective, multi-centre, observational study, pregnant women suffering from sleep problems were treated with B. pinnatum (350mg tablets, 50% leaf press juice, Weleda AG, Arlesheim, dosage at physician's consideration). Sleep quality, daily sleepiness and fatigue were assessed with the aid of standardised questionnaires, at the beginning of the treatment and after 2 weeks. Possible adverse drug reactions perceived by the patients during the treatment were recorded. RESULTS: The number of wake-ups, as well as the subjective quality of sleep was significantly improved at the end of the treatment with B. pinnatum. The Epworth Sleeping Scale decreased, indicating a decrease of the tiredness during the day. There was, however, no evidence for prolongation of the sleep duration, reduction in the time to fall asleep, as well as change in the Fatigue Severity Scale after B. pinnatum. No serious adverse drug reactions were detected. CONCLUSION: B. pinnatum is a suitable treatment of sleep problems in pregnancy. The data of this study encourage further clinical investigations on the use of B. pinnatum in sleep disorders.

Bryophyllum pinnatum inhibits detrusor contractility in porcine bladder strips--a pharmacological study towards a new treatment option of overactive bladder.

AIMS: A broad spectrum of synthetic agents is available for the treatment of overactive bladder. Anti-cholinergic drugs show a poor compliance due to side effects. There is an increasing use of plant extracts in medicine. We have therefore investigated the inhibitory effects of leaf press juice from Bryophyllum pinnatum (Lam.) Oken (Kalanchoe pinnata L.) on bladder strips and compared the effects to that of oxybutynin. METHODS: Strips of porcine detrusor were prepared in Krebs solution and contractility was measured in a myograph system chamber aired with O2/CO2 at 37 °C. To induce contractions, electrical field stimulation (32 Hz, 40 V) was used for the inhibitory effect measurements, and carbachol (50 µM) for the relaxant effect measurements. Recordings were obtained in the absence and presence of increasing concentrations of Bryophyllum pinnatum leaf press juice (BPJ, 0.1-10%), and oxybutynin (10⁻7-10⁻³ M) as a reference substance. RESULTS: In inhibition experiments, BPJ as well as oxybutynin inhibited electrically induced contractions of porcine detrusor. BPJ at concentrations of 5% inhibited the contraction compared to a time matched control significantly by 74.6±10.2% (p<0.001). BPJ as well as oxybutynin relaxed carbachol pre-contracted porcine detrusor strips. The maximum relaxant effect of BPJ compared to a time matched control was 18.7±3.7 (p<0.05) at a concentration of 10% BPJ. CONCLUSIONS: Our investigations show that BPJ inhibits contractions induced by electrical field stimulation and relaxes carbachol-induced contractions. However, the effect was lower than that of the reference substance oxybutynin. It is important to continue in vitro experiments as well as clinical studies with BPJ that might offer a new treatment option for patients with OAB.

Leaf press juice from Bryophyllum pinnatum (Lamarck) Oken induces myometrial relaxation.

AIMS: The use of preparations from Bryophyllum pinnatum (Lamarck) Oken (Kalanchoe pinnata (Lamarck) Persoon) in tocolysis is supported by clinical evidence. We studied here the effect of B. pinnatum leaf press juice and its chemical fractions on the response of human myometrial strips. No data are available if the influence on myometrial strips of the juice differs from that of its components in the chemical fractions, in order to increase the pharmacological effect. METHODOLOGY: In vitro study to test the effect of repeated addition of B. pinnatum leaf press juice (BPJ) and its chemical components in several dilutions (undiluted, 1-10%) on myometrium strips hang up in a myograph chamber. Chemical analysis is including HPLC, MPLC with Sephadex LH-20 and TLC. RESULTS: All test solutions are inhibiting contractility by reducing the amplitude and the area under the curve (AUC) of the contractions. Undiluted BPJ and its undiluted chemical fraction 4 are reducing most effective these two parameters: the amplitude was at 78% of the baseline (95% CI (77-89); p<0.05) at the second addition of the BPJ and at 70% (95% CI (50-90); p<0.05) of the first addition of fraction 4; the AUC was at 82% (95% CI (69-95); p<0.05) of the baseline at the first addition of the press juice and at 51% (95% CI (27-74); p<0.05) at the first addition of fraction 4. The BPJ decreased amplitude and AUC significantly faster and increased frequency significantly faster than the control. Fractions could be tentatively assigned to bufadienolids, flavonoids and cinnamic acids. Fraction 4, accounted for flavonoids, increased the frequency of the contractions most effectively: 557% of the baseline (95% CI (316-797); p<0.05) at the first addition. CONCLUSION: Leaf juice of B. pinnatum and its flavonoid fraction are most effective in relaxing myometrial strips by inducing frequency.

Juice of Bryophyllum pinnatum (Lam.) inhibits oxytocin-induced increase of the intracellular calcium concentration in human myometrial cells.

The use of preparations from Bryophyllum pinnatum in tocolysis is supported by both clinical (retrospective comparative studies) and experimental (using uterus strips) evidence. We studied here the effect of B. pinnatum juice on the response of cultured human myometrial cells to stimulation by oxytocin, a hormone known to be involved in the control of uterine contractions by increasing the intracellular free calcium concentration ([Ca2+]i). In this work, [Ca2+]i was measured online during stimulation of human myometrial cells (hTERT-C3 and M11) with oxytocin, which had been pre-incubated in the absence or in the presence of B. pinnatum juice. Since no functional voltage-gated Ca2+ channels could be detected in these myometrial cells, the effect of B. pinnatum juice was as well studied in SH-SY5Y neuroblastoma cells, which are known to have such channels and can be depolarised with KCl. B. pinnatum juice prevented the oxytocin-induced increase in [Ca2+]i in hTERT-C3 human myometrial cells in a dose-dependent manner, achieving a ca. 80% inhibition at a 2% concentration. Comparable results were obtained with M11 human primary myometrial cells. In hTERT-C3 cells, prevention of the oxytocin-induced increase in [Ca2+]i was independent of the extracellular Ca2+ concentration and of voltage-dependent Ca2+-channels. B. pinnatum juice delayed, but did not prevent the depolarization-induced increase in [Ca2+]i in SH-SY5Y cells. Taken together, the data suggest a specific and concentration-dependent effect of B. pinnatum juice on the oxytocin signalling pathway, which seems to corroborate its use in tocolysis. Such a specific mechanism would explain the rare and minor side-effects in tocolysis with B. pinnatum as well as its high therapeutic index.

Nifedipine concentration in maternal and umbilical cord blood after nifedipine gastrointestinal therapeutic system for tocolysis.

OBJECTIVE: To determine nifedipine concentrations in maternal plasma at steady state, and maternal and umbilical cord plasma at delivery, after tocolysis with nifedipine gastrointestinal therapeutic system (GITS) tablets. DESIGN: Prospective clinical pharmacokinetic study. SETTING: Department of Obstetrics at the Zurich University Hospital. POPULATION: Pregnant women treated for threatened preterm labour. METHODS: GITS dosage titrated to clinical response (30-150 mg/day). Nifedipine concentrations by high-performance liquid chromatography and turbo ion spray tandem mass spectrometry. MAIN OUTCOME MEASURES: Steady-state nifedipine concentrations in maternal blood and nifedipine concentrations in maternal and corresponding umbilical cord blood at delivery. RESULTS: Steady-state nifedipine concentrations (micrograms/l, mean +/- SE) were 54 +/- 6 (all doses, n = 31), 38 +/- 8 (60 mg/day, n = 13), and 92 +/- 12 (150 mg/day, n = 7) (P < 0.002). Umbilical cord and maternal concentrations both declined in a ln-linear regression with elimination half-lives of 20.4 and 17.4 hours. Linear regression showed a correlation between umbilical and maternal concentrations of 0.77 +/- 0.1 (n = 21, mean +/- SE). CONCLUSIONS: Steady-state plasma nifedipine concentrations after repeated dosing with nifedipine GITS 30-150 mg/day in pregnant women with preterm labour do not exceed 100 micrograms/l; fetal levels are 77% of maternal levels.

[Drug use in pregnancy]. / Drogen in der Schwangerschaft.

Drug use in pregnancy is associated with a number of serious complications for mother and fetus. There are safe data on destructive effects of alcohol, cocain, marijuana and tobacco on pregnancy and neonatal outcome. Of importance is the fact that for many drugs similar effects on pregnancy could be observed: vasoconstriction of the placental vessels resulting in placental abruption, preterm labour (mother), spontaneous abortion, intrauterine growth retardation, low birth weight, preterm delivery and stillbirth (fetus). Symptoms of withdrawal and neurodevelopmental disorders are the most important problems of the neonate. However, only small data exist about the effects of recently popular party drugs like ecstasy or LSD. In addition, from most drugs, with exception of alcohol, safe information about the risk of congenital malformations doesn't exist. Nevertheless they may be a useful guide in the diagnostic of potential malformations by ultrasound. Most of pregnant women using drugs are poly-drug users and are often in reduced general condition. They need therefore the intensive care of the obstetrician in cooperation with other specialists (internal medicine, psychiatry).

[Natural remedies during pregnancy and lactation]. / Naturheilmittel während Schwangerschaft und Stillzeit.

Up to date there is a lack of systematically gathered data on the use of natural remedies (phytotherapeutic, homeopathic, anthroposophic, spagyric, Bach and Schussler remedies) during pregnancy and lactation. The aim of this non-representative pilot study on 139 women, who came for delivery to three institutions between mid-1997 and the beginning of 1998, was to receive data about how often and within which spectrum natural remedies are used during pregnancy and lactation. During pregnancy 96% and within the lactation period 84% of the women consumed at least 1 natural remedy. Phytotherapeutic drugs were used most frequently. In contrast to the widespread use of natural remedies by pregnant women and nursing mothers in this study, little information on the effectiveness and possible risks is available. Therefore it seems necessary to examine and evaluate natural remedies used during pregnancy and lactation.

Time-course of leptin levels in term and preterm human milk.

OBJECTIVE: To compare the time-course of breast milk leptin levels between term and preterm pregnancy. DESIGN: Open longitudinal prospective randomised study. METHODS: RIA of leptin levels in milk from 33 mothers (term pregnancy: n=24; preterm: n=9) at three postpartum intervals: 2-3 days, 4-5 days and 6 weeks (intervals A, B and C), combined with serum in 23 mothers (term: n=17; preterm: n=6) in interval A. Milk samples were sonicated before incubation. RESULTS: Interval A leptin levels were approximately tenfold higher in serum than in milk (term: 13.24+/-2.48 vs 1.34+/-0.14 ng/ml, P<0.0001; preterm: 4.46+/-1.05 vs 0.63+/-0.18 ng/ml, P<0.0005), and higher in term than in preterm serum (P=0.03). Milk levels were higher in the term vs preterm group in intervals A (P<0.01) and B (P<0.05). In the term group they declined significantly from interval A to interval B (P<0.05) but did not vary significantly in the preterm group. Serum levels correlated with maternal body mass index; milk levels showed only moderate correlation with maternal and infant weight or body mass index. CONCLUSION: The reasons for the presence and differential longitudinal expression of leptin in human milk after term and preterm pregnancy remain unknown. A hypothesis, requiring further study, is that persistently lower leptin levels in preterm milk act as a compensatory release of a brake on neonatal growth.

Maternal and fetal nitric oxide production in normal and abnormal pregnancy.

OBJECTIVES: To characterize maternal and fetal nitric oxide (NO) production in normal and abnormal pregnancy by measuring nitrate (NO3-) and nitrite (NO2-) metabolites in maternal venous blood, umbilical venous and arterial blood and amniotic fluid. METHODS: This was a prospective cross-sectional study in 160 singleton pregnancies: 60 with one complication (infection, n = 37; gestational diabetes, n = 12; pre-eclampsia, n = 11) and 103 normal controls. Nitrate plus nitrite levels were assayed by reduction with Griess reagent. Comparisons were: maternal vs. fetal compartments; normal vs. abnormal pregnancy; and early vs. late pregnancy. RESULTS: Amniotic nitrate and nitrite levels increased from early to late normal pregnancy (20.79 to 28.42 micromol/l, p < 0.02), decreasing slightly at term, and increased from early to late abnormal pregnancy (23.29 to 39.18 micromol/l, p < 0.0001). Late pregnancy levels were higher in abnormal vs. normal pregnancy in amniotic fluid (36.25 vs. 21.70 micromol/l, p = 0.003) and maternal blood (25.80 vs. 18.26 micromol/l, p = 0.002). Overall levels were higher in amniotic fluid than in maternal plasma, and in fetal compartments than in co-sampled maternal plasma (p < 0.005, vs. normal pregnancy). CONCLUSIONS: NO metabolite levels increased through normal and particularly abnormal pregnancy, predominantly in the fetal compartments, suggesting that NO production is an additional instrument in the fetal control of the intrauterine environment.

[LSD and cannabis abuse in early pregnancy with good perinatal outcome. Case report and review of the literature]. / LSD- und Cannabis-Konsum während der frühen Schwangerschaft mit gutem perinatalen Ausgang. Fallbericht und Literaturübersicht.

This is a case report of a 27-year-old patient who had smoked a joint (cannabis) and 20 cigarettes (tobacco) daily up to the time of a positive pregnancy test at 7 4/7 weeks (p.c.). On day 20 p.c. she had an LSD minitrip. There are reports of chromosome aberrations in in vitro animal studies with LSD. In humans the main consequences are malformations of the fetal extremities and dysplasias of the eye. In both animals and humans cannabis causes changes in dopaminergic activity. Our recommendation was to continue the pregnancy, but to monitor it closely. The patient had a spontaneous term delivery-a lively boy with weight between the 5th and the 50th percentile, length between the 50th and the 90th percentile, normal umbilical arterial and venous pH values, and Apgar scores 7/9/10. There were no visible abnormalities, and behaviour was normal. If it is suspected that a pregnant patient consumes LSD, dysplasias of the fetal skeleton and eye should be checked for. With respect to LSD and to cannabis, too, the intellectual development of the child should be closely followed.

Pharmacokinetics of fenoterol in pregnant women.

The beta 2-sympathomimetic drug fenoterol (fenoterol hydrobromide, CAS 1944-12-3, Partusisten) is routinely used to inhibit uterine contractions (tocolysis). Investigations of plasma concentrations of those receiving i.v. or oral tocolysis often show different results, both within particular groups of pregnant women and in comparison with non-pregnant persons. The aim of this study was to determine the pharmacokinetics of fenoterol in pregnant women, an important factor which so far had not been known. Four healthy pregnant women with similar weight and gestational age and all with premature labor were administered a continuous intravenous infusion of 4 micrograms fenoterol/min. During and up to 24 hours after the end of the infusion, venous blood samples were taken in order to determine the fenoterol plasma concentrations by radioimmunoassay. From a steady state concentration (css) of 2242 +/- 391 pg/ml (x +/- S.E.), a non-linear two-phased plasma elimination was seen with half-lives t1/2 of 11.40 min and 4.87 h. The area under the plasma concentration-time curve (AUC0-12h) was 6.27 ng/ml x h. The total clearance (Cltot) was 114.8 l/h. These data are nearly the same as the data already known for healthy non-pregnant (male) volunteers. The deviations which are seen in the plasma concentrations in pregnant women in comparison to non-pregnant persons during or after continuous i.v. infusion can therefore not be caused by differences in the pharmacokinetics. Other factors, however, such as body weight and/or gestational age, might influence the results.

[Adrenergic beta-2 receptors and cyclic AMP in lymphocytes and their relationship to uterine contractility]. / beta 2-Adrenozeptoren und zyklisches AMP in den Lymphozyten und ihre Beziehung zur Uteruskontraktilität.

It is especially in the long-term application where the pharmacodynamics of the betamimetics determine their effectiveness. According to the time and dosis, there is a decrease in the density and function of the beta 2-adrenoceptors (desensitization). Clinically, this means a loss of effectiveness. This study investigated whether in the course of a normal pregnancy (n = 22) there is a change in the effectiveness of the betamimetics, as expressed by a change in the number of beta 2-adrenoceptors or their function. The results show a 50% decrease in the number of beta 2-adrenoceptors to the 36th gestational week and an increase to initial values after delivery. A similar pattern is found for the function of the beta 2-adrenoceptors (cyclic AMP). The implications for the uterus might be that, with advancing pregnancy, it becomes less prone to relaxation and that the betaadrenergic system, as a mechanism supporting prepare the way for delivery at term, becomes less significant. For tocolysis with betamimetics, the decrease of the beta 2-adrenoceptor density means that, with increasing gestational age, the responsiveness of the uterus to betamimetics decreases.

Maternal and cord serum vitamin E levels in normal and abnormal pregnancy.

The purpose of this study was to ascertain whether there is an association between reduced vitamin E levels and an abnormal pregnancy. Levels were measured by HPLC in maternal and, where possible, in paired umbilical cord serum from normal and abnormal pregnancies at delivery and in serial serum samples from healthy women during gestation. Abnormal pregnancies were compared with normals. In normal pregnancies, mean vitamin E levels rose from 12.9 +/- 1.1 micrograms/ml in early pregnancy to 22.5 +/- 1.5 micrograms/ml at term (p < 0.05, n = 11). In pregnancies with fetal complications or maternal risks, levels were lower than in normals at corresponding gestational age (p < 0.005 in smokers, n = 20 at > or = 30 weeks & p < 0.01 in hypertensives, n = 4 at 16-23 weeks). Mean maternal and paired cord serum levels in normal pregnancies at delivery > or = 37 weeks were 21.3 +/- 0.6 and 3.8 +/- 0.1 micrograms/ml respectively (p < 0.001, n = 56). Maternal levels in women with a low birthweight infant and in smokers (> 10 cig/day) were significantly lower (p < 0.05, n = 13 & p < 0.0005, n = 12); levels in women with a malformed infant (n = 6) were also reduced, but just barely below the level of significance (p = 0.06). Cord serum levels in complicated pregnancies, however, were unchanged. The results show lower maternal levels of vitamin E in abnormal pregnancies, suggesting a changed vitamin E metabolism.

Magnesium sulphate increases lymphocyte adenosine 3':5'-cyclic monophosphate in humans.

We determined the effect of i.v. magnesium sulphate, which is often combined with beta 2-adrenoceptor agonists for tocolytic therapy, on lymphocyte cyclic AMP production, extracellular magnesium and blood calcium concentrations. Sixteen healthy volunteers received i.v. magnesium sulphate 1 g h-1 over 8 h; seven volunteers also had infusion of NaCl 18 mg h-1 as control. Venous blood was taken pre- and post-infusion to determine basal lymphocyte cyclic AMP and the increase evoked by 0.1 mM isoprenaline, as well as serum and plasma concentrations of total and non-protein-bound magnesium and calcium. Following magnesium sulphate there was a significant rise in the isoprenaline-evoked increase in cyclic AMP (P < 0.05) and in the magnesium concentrations (P < 0.01) and a decrease in the free calcium concentration (P < 0.01).

Lymphocyte beta 2-adrenoceptors and adenosine 3':5'-cyclic monophosphate during and after normal pregnancy.

1. The beta 2-sympathomimetics, used to inhibit preterm labour, bind predominantly to beta 2-adrenoceptors, activating adenylate cyclase to form adenosine 3':5'-cyclic monophosphate (cyclic AMP), a messenger substance which inhibits the enzyme cascade triggering smooth muscle contraction. beta 2-Adrenoceptor density and cyclic AMP formation can be used as markers of beta 2-adrenergic effect. 2. The present study addresses the influence of pregnancy on the beta-adrenoceptor system. beta 2-Adrenoceptor density and cyclic AMP concentrations (basal and evoked by isoprenaline) in circulating lymphocytes were determined at three points in gestation (16, 29 and 37 weeks) and 9 weeks post partum in 22 normal pregnancies. (-)-[125Iodo]-cyanopindolol was used as the ligand to identify a homogeneous population of beta 2-adrenoceptors on lymphocytes. B- and T-cell fractions were estimated from the same samples. 3. beta 2-Adrenoceptor density decreased significantly during gestation until week 37 (P < 0.01), then increased post partum (P < 0.005). Cyclic AMP concentrations (basal and evoked by isoprenaline) were significantly lower after 16 weeks of gestation than post partum (P < 0.05). 4. The results, which cannot be explained in terms of a shift in the lymphocyte (B- and T-cell) ratio, indicate that beta-adrenoceptor density and function are reduced in normal pregnancy and only return to normal post partum. These findings may be of significance in devising future tocolytic therapy with beta 2-adrenoceptor agonists.

Ceftriaxone (single dose) versus cefoxitin (multiple doses): success and failure of antibiotic prophylaxis in 1052 cesarean sections.

The efficacy of perioperative antibiotic prophylaxis in cesarean section with a single dose of ceftriaxone, a long-acting cephalosporin not widely used for prophylaxis, was tested. Ceftriaxone as a single dose of 1 g i.v. versus three doses of cefoxitin 1 g i.v. respectively were used in a prospective, randomized, controlled study consisting of 1052 patients undergoing cesarean section. Postoperative infection rate as measured by fever, endometritis and wound infection was 6.5% with ceftriaxone and 6.4% with cefoxitin. Urinary tract infections were significantly more frequent in the cefoxitin than in the ceftriaxone group (17.8% vs. 9.7%, p < 0.001). Enterococci and Escherichia coli accounted for urinary tract infections 1.86-, respectively, 4.3-fold more frequently with cefoxitin than with ceftriaxone. The time of hospitalization in patients with urinary tract infections was significantly lower with ceftriaxone than with cefoxitin (11 vs. 12 days, p < 0.05). The tolerance in both groups was equally satisfactory. A single dose of ceftriaxone, which is simple, reliable (compliance), well tolerated, inexpensive (fewer urinary tract infections and therefore fewer treatment costs than with cefoxitin) and safe (no overgrowth of pathogens) in our opinion is the antibiotic regimen of choice for prophylaxis in cesarean section in the described circumstances.

Pharmacokinetic studies on fenoterol in maternal and cord blood.

Fenoterol plasma concentrations were measured by radioimmunoassay in 38 pregnant women at different stages of preterm labor and in cord blood. Eight women were treated intravenously until delivery with 1.0 to 4 micrograms/min of fenoterol for periods ranging from 27 hours to 27 days; blood samples were taken at the same time as cord blood. In these women the fenoterol concentrations in cord blood ranged from 18 to 53% of the maternal concentrations. In eight women treated intravenously with 1.2 to 4.0 micrograms/min for 2 to 15 days, the infusion was stopped 1.3 to 38 hours before delivery. In these instances the concentrations in cord blood reached as much as 90% of the maternal, meaning that the rate of elimination from fetal plasma is lower than that from maternal plasma. Five women were treated daily with 20 to 30 mg per os for 3 to 17 days (three of these women had also had intravenous treatment before). The ratio of cord to maternal blood concentrations was higher than in women receiving the drug intravenously, the relative times of sampling being the same. The findings suggest that: (1) the placental transfer of fenoterol is higher than that found in previous studies in humans and animals with tritium-labeled substances; (2) the rate of fenoterol elimination from fetal plasma after intravenous and oral long-term therapy is lower than that from maternal plasma; (3) after oral administration, the ratios of fetal to maternal fenoterol concentrations are higher than after intravenous infusion.

Overnight salivary caffeine clearance: a liver function test suitable for routine use.

The feasibility of measuring caffeine clearance from saliva (SCl) was assessed in ambulatory patients with liver disease and in a control group, and the results were compared with quantitative liver function tests. For this purpose, the subjects were given 280 mg caffeine p.o. in decaffeinated coffee powder between noon and 4 p.m., and caffeine concentrations were measured in saliva (using an enzyme immunoassay) before bedtime and upon arising. In the cirrhotics (n = 29), SCl was 0.58 +/- S.D. 0.45 ml per min X kg, thus being reduced to approximately one-third of drug-free, nonsmoking controls (1.53 +/- 0.46, n = 18); although patients with noncirrhotic liver disease showed intermediate values (0.95 +/- 0.47), their reduction in SCl was significant (p less than 0.001). SCl was correlated with indocyanine green fractional clearance, galactose elimination capacity and aminopyrine breath test; however, the closest relationship (Rs = 0.80) was observed with the aminopyrine breath test. It is suggested that the measurement of SCl represents a noninvasive and innocuous procedure for quantifying hepatic microsomal function, and is suitable for routine use. Since a.m. saliva concentrations of caffeine are highly correlated (Rs = -0.94) with SCl, further simplification of the test to a single-point measurement appears possible.