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Lack of interaction between diazepam and nimodipine during chronic oral administration to healthy elderly subjects.

1. Nimodipine (30 mg three times daily) and diazepam (10 mg once daily), were given orally to 24 elderly healthy subjects in a randomized, non-blinded, threefold-crossover study. Each of the three treatment periods lasted 5 days separated by 2 week washout phases. 2. Plasma concentrations of nimodipine and diazepam were not affected by the combined treatment. 3. No clinically relevant changes in haemodynamics, ECG recordings, clinical chemistry or haematology were observed after all of the three treatments. The overall frequency of side effects was lowest during monotherapy with nimodipine and highest during diazepam monotherapy. 4. In the test of subjective rating of tiredness (VAS) and the Pauli calculation test, diazepam, alone and with nimodipine co-medication, produced an increase in tiredness and a clear reduction in performance and endurance. After nimodipine monotherapy an improvement was observed only in the Pauli test. Using the critical flicker fusion frequency test (CFF) significant decrements in performance were found after diazepam monotherapy only. 5. In summary, there was no evidence that either nimodipine or diazepam affected the pharmacokinetics, safety and tolerance of each other. However, the CNS-effects of diazepam were compensated partially by nimodipine.

Administration, Oral↗

NBU1 integrase: evidence for an altered recombination mechanism.

NBU1 is a 10.3 kbp Bacteroides mobilizable transposon. A previous study had identified a 2.7 kbp segment of the excised circular intermediate that was sufficient to mediate integration of the element after transfer. This segment contained an integrase gene, intN1, and a region spanning the ends of the circular form within which integration occurred (attN1). The integrase protein, IntN1, appeared to be a member of the tyrosine recombinase family because it contains the canonical C-terminal RKHRHY [RK(H/K)R(H/W)Y] motif that characterizes members of that family. In this study, we describe an Escherichia coli-based integration assay system that has allowed us to characterize attN1 in detail. We first localized attN1 to a 250 bp region. We then used site-directed mutations to identify directly repeated sequences within attN1 that were required for site-specific integration. The locus of NBU1 site-specific integration in the Bacteroides thetaiotaomicron chromosome, attBT1-1, contains a 14 bp sequence that is identical to a 14 bp sequence that spans the joined ends of the NBU1 attN1 site (common core sequences). The effects of mutations in the common core were different from the expected results if NBU1 integration was similar to lambda integration. In particular single base changes near one end of the common core region, which introduced heterology, actually increased the frequency of integration. By contrast, compensating changes that restored homology in the common core region reduced the integration frequency. The recombination mechanism also differs from the one used by conjugative transposons that have coupling sequences between the sites of strand cleavage and exchange. These results indicate that although NBU1 integrase is considered to be a member of the tyrosine recombinase family, it catalyses an integrative recombination reaction that occurs by a different crossover mechanism.

Attachment Sites, Microbiological↗

Comparison of clinical effects of propranolol (Inderal) with once daily slow-release oxprenolol (Slow Trasicor) in angina pectoris.

In a double-blind, crossover, randomized study, the therapeutic effectiveness of a single daily dose of slow-release oxprenolol (160 mg/day) was compared with a conventional dosage schedule of propranolol (40 mg three times daily) in eighteen patients with uncomplicated, stable exercise-induced angina pectoris. Compared to control values both drugs produced equipotent reduction in the frequency and severity of anginal attacks accompanied by a significant increase in exercise tolerance, a significant suppression of exercising heart rate and an appreciable reduction in the electrocardiographic evidence of myocardial ischaemia when tested on a treadmill. The possible advantages offered by a single dose treatment with slow-release oxprenolol are discussed.

Adult↗

Effects of Various Modalities of Oral Furosemide Administration in Mild or Severe Congestive Heart Failure.

BACKGROUND: This study evaluated the optimal formulation (tablet vs solution) and frequency (once vs twice daily) of maintenance oral furosemide in compensated congestive heart failure (CHF). METHODS AND RESULTS: Eighteen patients with mild (group 1) and 18 with severe (group 2) CHF were studied. On 2 consecutive days each patient's individual fixed oral furosemide daily dosage was administered in tablet or solution in a crossover design. In an additional study, 14 patients with severe CHF received the daily dosage in tablet or solution form in two divided doses. Pharmacokinetic data were obtained in six randomly allocated patients of each group, during the once daily administration periods of either formulation. Twenty-four-hour urinary sodium and 12-hour volume were significantly greater in group 1 following furosemide solution versus tablets. In group 2, all parameters were comparable in response to single identical doses in tablets or solution, as well as to once versus twice daily administration of either formulation. These results coincided with a higher C(max) and a shorter t(max) following solution. CONCLUSIONS: A once-daily oral furosemide solution is more effective than the same dosage in tablet form in patients with mild, but not those with severe, CHF. In patients with severe CHF, the natriuretic and diuretic effects are similar whether oral furosemide in tablet or solution is administered in a once or twice daily schedule.

Journal Article↗

Intranasal corticosteroid therapy for obstructive sleep apnoea in patients with co-existing rhinitis.

BACKGROUND: Increased nasal airflow resistance (NAR) may contribute to the pathophysiology of obstructive sleep apnoea syndrome (OSAS) but studies investigating the effects of relieving nasal obstruction in OSAS have produced differing results. There are no reports of intranasal corticosteroid therapy in adult OSAS patients with reversible nasal obstruction. METHODS: We evaluated an intranasal corticosteroid, fluticasone propionate, in 24 consecutive snorers with associated rhinitis using a randomised, placebo controlled, crossover design. Patients underwent polysomnography, snoring noise, and NAR measurements at baseline and after each 4 week treatment period. RESULTS: Twenty three patients completed the protocol and were divided into an apnoeic group (group A; 13 patients) and a non-apnoeic snoring group (group S; 10 patients) based on an apnoea-hypopnoea frequency (AHI) of > or =10/h or <10/h. AHI was significantly lower following treatment with fluticasone than with placebo in the total population (median (quartile range) 11.9 (22.6) v 20 (26.3); p<0.05) and in group A (23.3 (21.3) v 30.3 (31.9); p<0.05). Median (95% confidence interval) within subject differences for AHI were -3.2 (-17.7 to -0.2) in the total population and -6.5 (-29.5 to 1.8) in group A. NAR was also lower on fluticasone (2.74 (1.21) v 3.27 (1.38), p<0.01), within subject difference being -0.45 (95% CI -0.87 to -0.21). The changes in AHI and NAR in group A were significantly correlated (r=0.56; p<0.05). Snoring noise and sleep quality were unchanged but daily diary records indicated subjective improvements in nasal congestion and daytime alertness with fluticasone (p<0.02). CONCLUSIONS: Intranasal fluticasone is of benefit to some patients with OSAS and rhinitis. The data suggest that this form of nasal obstruction may contribute to the pathophysiology of OSAS.

Administration, Intranasal↗

Domperidone, metoclopramide, and placebo. All give symptomatic improvement in gastroesophageal reflux.

A double-blind crossover study was conducted of two gastric prokinetic drugs in 23 patients with gastroesophageal reflux. Patients were divided into two groups on the basis of a dual-isotope mixed-meal study of their gastric emptying (GE). Group I had normal GE and group II delayed GE. Nine gastrointestinal symptoms were assessed for frequency and severity before treatment. The trial had three 1-month treatment periods using metoclopramide 10 mg q.i.d., domperidone 20 mg q.i.d., or placebo on a random basis. Symptoms were reassessed at the end of each month. Taken as a whole, the group showed a significant symptomatic response in all three treatment periods (p less than 0.0001), but patients with delayed or normal GE did not differ significantly in their symptomatic response. Eleven patients complained of side effects with metoclopramide and three stopped therapy before the 1-month course was completed. Two patients described side effects with domperidone, including one woman with galactorrhea after 36 h of treatment. Three patients on placebo also complained of important side effects. We conclude that a significant placebo effect is present in the treatment of gastroesophageal reflux. No significant difference was demonstrated in symptomatic improvement between placebo, domperidone, and metoclopramide in this study.

Adult↗

Reduction in obstructive breathing events during body rocking: a controlled polygraphic study in preterm and full-term infants.

OBJECTIVE: To investigate the effect of body rocking on infant respiratory behavior during sleep. METHODS: Eighteen infants with documented obstructive sleep apneas were studied. There were eight premature infants with persistent bradycardias and 10 infants born full-term, admitted after an idiopathic apparent life-threatening event. No cause for the obstructive apneas was found. The infants were recorded with polygraphic techniques during two successive nights. They were randomly assigned to a rocking or a nonrocking mattress. The conditions were reversed the following night, in a crossover design. RESULTS: In both groups of infants, no significant difference was seen between the two consecutive nights for most of the variables studied: total sleep time, the proportion of non-rapid-eye-movement and rapid-eye-movement sleep, the number of arousals, the number and maximal duration of central apneas, the frequency of periodic breathing, the level of oxygen saturation, and heart rate. During the nonrocking nights, all infants had repeated obstructive breathing events. In seven of the eight preterm infants and in nine of the 10 full-term subjects, body rocking was associated with a significant decrease in the frequency of obstructive events. During rocking, in the preterm infants the obstructions fell from a median of 2.5 to 1.8 episodes per hour (P = .034). In the full-term infants, rocking reduced the obstructive events from a median of 1.5 obstructions per hour to 0.7 (P = .005). No difference was seen for the duration of the obstructive episodes. CONCLUSION: In preterm and full-term infants prone to obstructive sleep apneas, gentle side-to-side body rocking is associated with a significant decrease in the frequency of upper-airway obstructions.

Beds↗

Reduction of postprandial hyperglycemia and frequency of hypoglycemia in IDDM patients on insulin-analog treatment. Multicenter Insulin Lispro Study Group.

Insulin lispro, an insulin analog recently developed particularly for mealtime therapy, has a fast absorption rate and a short duration of action. We compared insulin lispro and regular human insulin in the mealtime treatment of 1,008 patients with IDDM. The study was a 6-month randomized multinational (17 countries) and multicenter (102 investigators) clinical trial performed with an open-label crossover design. Insulin lispro was injected immediately before the meal, and regular human insulin was injected 30-45 min before the meal. Throughout the study, the postprandial rise in serum glucose was significantly lower during insulin lispro therapy. At the endpoint, the postprandial rise in serum glucose was reduced at 1 h by 1.3 mmol/l and at 2 h by 2.0 mmol/l in patients treated with insulin lispro (P < 0.001). The rate of hypoglycemia was 12% less with insulin lispro (6.4 +/- 0.2 vs. 7.2 +/- 0.3 episodes/30 days, P < 0.001), independent of basal insulin regimen or HbA1c level. The reduction was observed equally in episodes with and without symptoms. When the total number of episodes for each patient was analyzed according to the time of occurrence, the number of hypoglycemic episodes was less with insulin lispro than with regular human insulin therapy during three of four quarters of the day (P < 0.001). The largest relative improvement was observed at night. In conclusion, insulin lispro improves postprandial control, reduces hypoglycemic episodes, and improves patient convenience, compared with regular human insulin, in IDDM patients.

Adult↗

Reversal of inappropriate peripheral vascular responses in hypertrophic cardiomyopathy.

OBJECTIVES: We assessed the frequency of abnormal forearm vasodilator responses during lower body negative pressure (LBNP) in 21 non-obstructive hypertrophic cardiomyopathy (HCM) patients (31 +/- 8 [20 to 43] years) with abnormal blood pressure response (ABPR) to exercise and the effects of three drugs used to treat vasovagal syncope (propranolol, clonidine, and paroxetine) in a double-blind crossover study. BACKGROUND: Some HCM patients have an ABPR to exercise, which may be due to paradoxical peripheral vasodilatation. A similar proportion has paradoxical forearm vasodilatation during central volume unloading using LBNP. These abnormal reflexes may be caused by left ventricular mechanoreceptor activation. Similar mechanisms may also contribute to some cases of vasovagal syncope. METHODS: Blood pressure changes were assessed during exercise, and forearm vascular responses and baroreceptor sensitivity were assessed during LBNP using plethysmography. RESULTS: Nine (43%) patients (group A) had paradoxical vasodilator responses (forearm vascular resistance [FVR] fell by 7.5 +/- 4.6 U), and 12 (57%) patients (group B) had normal vasoconstrictor responses during LBNP (FVR increased by 7.7 +/- 4.9 U). Paroxetine augmented systolic blood pressure (SBP) during exercise in group A (21 +/- 6 mm Hg vs. 14 +/- 11 mm Hg at baseline, p = 0.02); no effect was detected in group B. Paroxetine reversed paradoxical vascular responses during LBNP in seven (78%) patients from group A. Propranolol and clonidine had no significant effect on SBP during exercise but reversed paradoxical vascular responses in some patients from group A (n = 5 and n = 3). CONCLUSIONS: Paradoxical vasodilatation during LBNP occurs in 40% of patients with ABPR during exercise and is reversed by propranolol, clonidine, and paroxetine. Paroxetine also improved SBP response to exercise.

Adrenergic beta-Antagonists↗

A baseline study of medication error rates at Baylor University Medical Center in preparation for implementation of a computerized physician order entry system.

OBJECTIVE: To determine baseline levels of medication errors and their root causes so as to highlight areas of potential process improvements and serve as a ruler against which to measure future improvements. DESIGN: A prospective pharmacist intervention study determining errors in 1014 medication orders at Baylor University Medical Center. Only errors in the process of medication ordering were documented; errors in drug administration were not considered. Root causes of errors were examined. RESULTS: The baseline medication error rate was 111.4 per 1000 orders (n = 1014). Most common were dosing errors (43.4 per 1000 orders), followed by frequency errors (19.7 per 1000 orders) and unavailable drug errors (12.8 per 1000 orders). Of the 113 total errors found, 52 (46%) had a transcription-based cause, i.e., an error in inputting the handwritten physician order into a computer system. System- or process-related root causes (such as duplicate orders or lack of crossover from one information system to another) accounted for 35.4% of the errors, and prescribing based causes (such as wrong dosage or nonformulary drugs) accounted for 18.6% of errors. CONCLUSIONS: Implementing a computerized physician order entry (CPOE) system would eliminate order-entry transcription-based errors. Its ability to resolve system/process-based and prescribing-based root causes of error is not as clear. Furthermore, the modification of processes due to implementation of CPOE could lead to new types of errors. Present processes must be redesigned according to evidence-based medicine, and future processes must be anticipated as technological changes occur. Such efforts-rather than outright reliance on technology--are more likely to lead to an error-free environment after CPOE is implemented.

Journal Article↗

In vivo physiologic comparison of two ventilators used for domiciliary ventilation in children with cystic fibrosis.

OBJECTIVE: Home noninvasive mechanical ventilation (NIMV) is used with increasing frequency for the treatment of patients with respiratory failure caused by cystic fibrosis, yet the optimal mode of ventilation in such children is unknown. We compared the physiologic short-term effects of two ventilators with different modes (one pressure support and the other assist control/volume-targeted [AC/VT]) commonly used for domiciliary ventilation. DESIGN: Prospective, randomized, crossover comparison of two ventilators with different modes. SETTING: Tertiary pediatric university hospital. PATIENTS: Eight children with cystic fibrosis (age, 11-17 yrs) and chronic respiratory failure (pH 7.4 +/- 0.0; PaO2, 57.5 +/- 7.5 torr; PaCO2, 46.1 +/- 2.5 torr), naive to NIMV. INTERVENTIONS: Two 20-min runs of pressure support and AC/VT ventilation were performed in random order, each run being preceded and followed by 20 mins of spontaneous breathing. MEASUREMENTS: Flow and airway pressure and esophageal and gastric pressures were measured to calculate esophageal (PTPes) and diaphragmatic pressure-time product (PTPdi) and the work of breathing. RESULTS: The two NIMV sessions significantly improved blood gas variables and increased tidal volume with no change in respiratory rate. Indexes of respiratory effort decreased significantly during the two modes of NIMV compared with spontaneous breathing, with PTPdi/min decreasing from 497.8 +/- 115.4 cm H2O x sec x min(-1) during spontaneous breathing to 127.8 +/- 98.3 cm H2O x sec x min(-1) and 184.3 +/- 79.8 cm H2O x sec x min(-1), during AC/VT and pressure support, respectively (p <.0001), and the work of breathing decreasing from 1.83 +/- 0.12 J.L-1 during spontaneous breathing to 0.48 +/- 0.32 J.L-1 and 0.75 +/- 0.30 J.L-1, during AC/VT and pressure support, respectively (p <.0001). In addition, the effect of AC/VT ventilation was significantly superior to pressure support judged by PTPes and the work of breathing, but this result was explained by three patients who adapted extremely well to the AC/VT ventilation, with the disappearance of ventilator triggering, in effect adopting a controlled mode. There was a correlation between the improvement in PTPdi/min or the work of breathing and patient's subjective impression of comfort during the AC/VT ventilation. CONCLUSIONS: In awake, stable children with cystic fibrosis, both AC/VT and pressure support unloaded the respiratory muscles. The disappearance of ventilator triggering occurred in a subgroup of patients during AC/VT ventilation, and this explained the good tolerance and the superiority of this mode in the present study.

Adolescent↗

Progabide: a controlled trial in partial epilepsy.

Progabide (SL 76002) was studied in a randomized double-blind crossover trial using 20 outpatients suffering from partial complex seizures. Progabide was added to the concomitant antiepileptic treatment in a fixed dosage schedule. The design included an open therapy control unit. No significant difference was established between the number of partial seizures during treatment with progabide and placebo. A trend was observed for lower seizure frequency of secondary generalized seizures during treatment with progabide. Only mild and transient side effects were observed. There was no difference between the side effects of progabide and placebo.

Anticonvulsants↗

[Laxative effect and tolerance of lactulose administrated in one or two intakes in the treatment of chronic idiopathic constipation. Groupe d'Investigateurs O'Ile-de-France (GIIF)].

OBJECTIVES: The aim of this study was to compare the tolerance and effects of lactulose taken at a daily dose of 20 mg in one or two intakes, in the treatment of idiopathic chronic constipation. METHODS: A total of 121 outpatients (30 men, 91 women, mean age 55) was included in a prospective double blind crossover multicentric study. Patients took lactulose according to two different ways of administration and for two successive 3-week periods. Each period consisted in 2 weeks of adaptation and one week of evaluation. At the end of each period, a global visual satisfactory scale was evaluated as a global index. Patients collected every day the frequency and the aspects of the stools, the quality of exoneration and the existence of digestive symptoms. RESULTS: Number of stools per week (7.29 +/- 3.20 vs 7.08 +/- 3.03), consistency, quality of exoneration, were equivalent whatever the number of intakes and the period of treatment. With one or two intakes, the satisfactory index was the same but significantly better at the end of the second period. With one or two intakes, frequency and intensity of side effects were low and identical. They mostly occurred during the first period. CONCLUSION: Effects and tolerance with one single intake of lactulose (20 g) in the evening and with two intakes, were found to be equivalent. Effect on exoneration persists during the six weeks of administration and then tolerance improves.

Adolescent↗

Multicenter controlled clinical trial of high-frequency jet ventilation in preterm infants with uncomplicated respiratory distress syndrome.

OBJECTIVE: To test the hypothesis that high-frequency jet ventilation (HFJV) will reduce the incidence and/or severity of bronchopulmonary dysplasia (BPD) and acute airleak in premature infants who, despite surfactant administration, require mechanical ventilation for respiratory distress syndrome. DESIGN: Multicenter, randomized, controlled clinical trial of HFJV and conventional ventilation (CV). Patients were to remain on assigned therapy for 14 days or until extubation, whichever came first. Crossover from CV to HFJV was allowed if bilateral pulmonary interstitial emphysema or bronchopleural fistula developed. Patients could cross over to the other ventilatory mode if failure criteria were met. The optimal lung volume strategy was mandated for HFJV by protocol to provide alveolar recruitment and optimize lung volume and ventilation/perfusion matching, while minimizing pressure amplitude and O2 requirements. CV management was not controlled by protocol. SETTING: Eight tertiary neonatal intensive care units. PATIENTS: Preterm infants with birth weights between 700 and 1500 g and gestational age <36 weeks who required mechanical ventilation with FIO2 >0.30 at 2 to 12 hours after surfactant administration, received surfactant by 8 hours of age, were <20 hours old, and had been ventilated for <12 hours. Outcome Measures. Primary outcome variables were BPD at 28 days and 36 weeks of postconceptional age. Secondary outcome variables were survival, gas exchange, airway pressures, airleak, intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), and other nonpulmonary complications. RESULTS: A total of 130 patients were included in the final analysis; 65 were randomized to HFJV and 65 to CV. The groups were of comparable birth weight, gestational age, severity of illness, postnatal age, and other demographics. The incidence of BPD at 36 weeks of postconceptional age was significantly lower in babies randomized to HFJV compared with CV (20.0% vs 40.4%). The need for home oxygen was also significantly lower in infants receiving HFJV compared with CV (5.5% vs 23.1%). Survival, incidence of BPD at 28 days, retinopathy of prematurity, airleak, pulmonary hemorrhage, grade I-II IVH, and other complications were similar. In retrospect, it was noted that the traditional HFJV strategy emphasizing low airway pressures (HF-LO) rather than the prescribed optimal volume strategy (HF-OPT) was used in 29/65 HFJV infants. This presented a unique opportunity to examine the effects of different HFJV strategies on gas exchange, airway pressures, and outcomes. HF-OPT was defined as increase in positive end-expiratory pressure (PEEP) by >/=1 cm H2O from pre-HFJV baseline and/or use of PEEP of >/=7 cm H2O. Severe neuroimaging abnormalities (PVL and/or grade III-IV IVH) were not different between the CV and HFJV infants. However, there was a significantly lower incidence of severe IVH/PVL in HFJV infants treated with HF-OPT compared with CV and HF-LO. Oxygenation was similar between CV and HFJV groups as a whole, but HF-OPT infants had better oxygenation compared with the other two groups. There were no differences in PaCO2 between CV and HFJV, but the PaCO2 was lower for HF-LO compared with the other two groups. The peak inspiratory pressure and DeltaP (peak inspiratory pressure-PEEP) were lower for HFJV infants compared with CV infants. CONCLUSIONS: HFJV reduces the incidence of BPD at 36 weeks and the need for home oxygen in premature infants with uncomplicated RDS, but does not reduce the risk of acute airleak. There is no increase in adverse outcomes compared with CV. HF-OPT improves oxygenation, decreases exposure to hypocarbia, and reduces the risk of grade III-IV IVH and/or PVL.

Bronchopulmonary Dysplasia↗

Treatment of insomnia with two benzodiazepines: a double-blind crossover study.

Twenty-eight patients (12 M, 16 F) with insomnia were treated with nitrazepam 5 mg/d and oxazepam 25 mg/d, each for 11 days, in a double-blind crossover comparison with placebo. Half the patients received nitrazepam in the first drug period, and oxazepam in the second and the other half followed the contrary sequence. Both nitrazepam and oxazepam were found to be effective in inducing sleep and increasing sleep quality. No effects on dreaming or adverse effects were found. Nitrazepam did influence the frequency of awakening, but only in the second drug period. In the first period it reduced self-waking. It is concluded that both nitrazepam and oxazepam were effective in inducing sleep and in improving sleep quality.

Adult↗

Genetic control of synapsis and recombination in Lolium amphidiploids.

Homologous bivalent formation in amphidiploids of Lolium is promoted during meiosis by diploidising genes carried by A-chromosomes, and by supernumerary B-chromosomes. The site and mode of action of these diploidising factors were investigated by comparing the relative frequencies of pairing configurations at meiotic prophase and metaphase I in several different hybrid genotypes. The results indicate that diploidising genes act predominantly by increasing the stringency of synapsis at early stages of meiotic prophase. By contrast, B-chromosomes appear to promote bivalent formation by ensuring that homoeologously paired chromosome segments within multivalents do not crossover. The results show that the additive effects of diploidising genes and B-chromosomes are to a certain extent separable in terms of their mode of action and timing during meiosis.

Chromosome Mapping↗

Antibody repertoire development in fetal and neonatal piglets. V. VDJ gene chimeras resembling gene conversion products are generated at high frequency by PCR in vitro.

The recovery of VDJ rearrangement is most often accomplished by PCR amplification of DNA extracted from mixtures of B-cells. Using this procedure in swine, VDJs containing chimeric V(H) genes that resemble gene-conversion products, are frequently encountered. To examine whether these chimeras could be the result of PCR artifacts, we used different combinations of swine VDJ templates, each having unique CDR1, CDR2 and D(H) segments, to generate >2600 clones. Using equal amounts of two templates and 30 cycles of PCR, up to 45% of the resultant clones were VDJ chimeras. The frequency of chimeras was independent of the specific VDJ template and the chimeras were generated regardless of whether Taq-, Pfu- or mixtures of Taq- and Pfu-polymerases were employed or whether PCR extension time was prolonged six-fold. The frequency of generating chimeras was dependent on the ratio of the two target DNAs although even ratios approximately 1:10 generated approximately 10% chimeric VDJs. Chimeras could be generated using only 10 cycles of PCR or using the initial template DNAs diluted as much as 1:10000. Of the 279 chimeric VDJs generated, 61% of the crossovers occurred in FR3, 21% in FR2 and 18% in both FR2 and FR3. We interpret these results to mean that in vivo gene conversion in this species can only be unambiguously proven when the VDJs from individual B-cells are bearing a single VDJ rearrangement amplified and sequenced or when VDJs are cloned without the use of PCR.

Animals↗

The effect of trimoprostil (trimethyldesoxy prostaglandin E2) on the intrauterine pressure in women.

Prostaglandin E2 is uterotonic. Trimoprostil, a prostaglandin E2 analog, is a gastric antisecretory and cytoprotective agent. The effects of single doses of 0, 0.125, 0.75, and 3.0 mg trimoprostil on intrauterine pressure were measured in a double-blind, crossover study in eight surgically sterile women. The 3 mg dose was not tolerated because of abdominal cramps. The other doses caused a dose-related increase in resting uterine tone and peak pressure with peak effect occurring between 30 and 60 minutes after administration with a duration of about 120 minutes. No effects on the frequency of uterine contractions occurred. Peak mean tone increased from 11.0 to 71.2 mm Hg (p less than 0.01) and peak pressure from 24.6 to 125.1 mm Hg (p less than 0.01) after placebo compared with the 1.5 mg dose. Adverse reactions included abdominal pain that correlated with an increase in intrauterine pressure and tone.

Adult↗