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PubMed1996

[The impact of primary health care reform in the utilization of medical and nursing services. Working Group on the Utilization of of Health Services].

OBJECTIVES: To describe the use of medical and nursing services and changes attributable to the Primary Care reform. DESIGN: A crossover study based in the community. SETTING: The city of Mataró (Barcelona), divided into seven Health Districts, four of which are reformed. PATIENTS AND OTHER PARTICIPANTS: A representative sample of 1,880 beneficiaries of the public health service. INTERVENTIONS: A home survey (February to June 1994). MEASUREMENTS AND MAIN RESULTS: The annual rate of use of the doctor was 78.9% and the frequency of attendance was 7.74 visits per person per year. Both rates were higher among women and increased with age, the 0 to 14-year old group being exceptional. The rate of use was greater in the reformed Districts as against the non-reformed ones; with the difference in frequency of visits not reaching statistical significance. Reformed Health District users stated they made less administrative visits and more prevention or follow-up attendances. Nursing services were used in the 2 weeks before the interview by 6.3%. CONCLUSIONS: In both Primary Care models, factors meaning greater demand on both doctors and nurses are advanced age and being female.

Adult↗
PubMed2006

Diclofenac for treatment of nocturia caused by nocturnal polyuria: a prospective, randomised, double-blind, placebo-controlled crossover study.

OBJECTIVES: To investigate the efficacy of diclofenac 50 mg enteric-coated tablet (Non-Steroidal Anti-Inflammatory Drug) in the treatment of nocturnal polyuria. MATERIALS AND METHODS: 26 patients (20 male and 6 female) with a mean age of 72 years (range 52-90) diagnosed with nocturnal polyuria were recruited. The study period comprised 2 weeks of either placebo or active medication taken at 2100 h. Following one-week rest period, patients were crossed over to the other medication for a further 2 weeks. Frequency volume charts were completed during the second week of each of the two study periods along with feedback forms to assess any subjective improvement in symptoms during each of the study periods. RESULTS: A significant improvement in the symptoms was noted for diclofenac when compared with the placebo. The mean nocturnal frequency decreased from 2.7 to 2.3 (p<0.004) and the mean ratio of night-time to 24 h urine volume decreased from 44% to 39% (p<0.001). No significant side effects were reported. CONCLUSIONS: NSAIDs are effective in the treatment of nocturnal polyuria causing a decrease in nocturnal frequency with subjective symptom improvement. Our study suggests a novel treatment option for this common condition.

Aged↗
PubMed1981

Effect of crossover exposure on radiographic image quality of screen-film systems.

Modulation transfer functions (MTFs), Wiener spectra, and H & D curves of conventional and anticrossover screen-film systems were measured in an evaluation of the potential clinical use of anticrossover systems. The relative speed of anticrossover (3M) systems was reduced by 40%, compared with conventional (Kodak OG) systems. The anticrossover system improved both resolution and noise properties of screen-film systems (55% improvement of MTF at 2 cycles/mm and 40% reduction of radiographic mottle at low spatial frequencies) in a way that a combination of slow, sharp screens with conventional film may not accomplish, even when the speeds of different systems are matched. Detail visibility, in phantom images and radiographs of the hand, was considerably enhanced with anticrossover film compared with that of conventional film.

Humans↗
PubMed1988

Sleeping on a wedge diminishes exposure of the esophagus to refluxed acid.

In a randomized crossover study, we compared the effect on gastroesophageal reflux of three sleeping positions: elevation of the head of the bed on standard eight-inch bed blocks; elevation by a foam wedge; or a flat position. Fifteen subjects with moderate to severe reflux symptoms were studied in each position on consecutive nights using continuous intraesophageal pH monitoring. We found no difference in reflux frequency among the positions. The wedge caused a statistically significant decrease in the time that distal esophageal pH was less than 4 as compared to the flat position. The wedge also decreased the longest episode experienced by the subjects. Elevation on blocks caused a similar improvement in parameters but failed in this study to achieve statistical significance. Both elevation by a wedge and on blocks showed a trend towards a decrease in clearance time as compared to the flat position. The patients did not always prefer elevation on a wedge, but for some it is a valuable alternative to elevation by bed blocks.

Aged↗
PubMed1993

Comparative efficacy of nifedipine gastrointestinal therapeutic system versus diltiazem when added to beta blockers in stable angina pectoris.

To determine the relative efficacy of nifedipine gastrointestinal therapeutic system (GITS) and diltiazem, 20 patients with angina pectoris and coronary artery disease were studied in a double-blinded, placebo-controlled randomized crossover trial. All patients were taking concomitant beta blockers. Efficacy was assessed by symptoms, exercise treadmill testing, and ambulatory ST-segment monitoring at baseline and after 6 weeks on each medication. Mean daily dose was titrated to 119 +/- 7 mg (nifedipine GITS) and 342 +/- 59 mg (diltiazem). The addition of either nifedipine GITS or diltiazem resulted in a significant reduction in angina frequency, improvement in exercise treadmill duration (7 vs 7 and 8 minutes; baseline vs nifedipine GITS and diltiazem), time to angina onset (4 vs 7 and 7 minutes; baseline vs nifedipine GITS and diltiazem), and time to ST-segment depression (5 vs 6 and 7 minutes; baseline vs nifedipine GITS and diltiazem). There was no significant difference between nifedipine GITS and diltiazem with respect to the magnitude of improvement in anginal symptoms or exercise test parameters. Both nifedipine GITS and diltiazem reduced the overall frequency and duration of ischemic episodes on ambulatory monitoring, but this reduction was not statistically different. Thus, nifedipine GITS and diltiazem at maximally tolerated doses were equally effective at reducing angina and increasing exercise tolerance as beta blockers alone.

Adrenergic beta-Antagonists↗
PubMed1990

Introduction of specific point mutations into RNA polymerase II by gene targeting in mouse embryonic stem cells: evidence for a DNA mismatch repair mechanism.

We have introduced two specific point mutations, located 20 base pairs apart, into the endogenous murine gene that encodes the largest subunit of RNA polymerase II (RPII215). The first mutation conferred resistance to the mushroom toxin alpha-amanitin (amar), and the second mutation generated a restriction fragment length polymorphism without altering the protein sequence. Targeted amar clones were generated at a frequency of 1 in 30 totipotent embryonic stem cells that expressed stably integrated DNA vectors after electroporation. Thirty to 40% of these clones had acquired both mutations, whereas, surprisingly, the remaining clones had acquired the specific amar point mutation but lacked the restriction fragment length polymorphism. We suggest that the latter clones were generated by independent DNA mismatch repair rather than by double crossover or gene conversion. These results demonstrate that it is possible to introduce specific point mutations into an endogenous gene in embryonic stem cells. Thus it should be possible to introduce single base substitutions into other cellular genes, including nonselectable genes, by optimizing the efficiency of gene transfer and/or the sensitivity of screening for targeted clones.

Amino Acid Sequence↗
PubMed2006

A systematic review of the clinical effects of reducing dialysate fluid temperature.

BACKGROUND: Intradialytic hypotension (IDH) is a frequent complication of haemodialysis. Reducing the temperature of the dialysis fluid is a simple therapeutic strategy but is relatively underused. This may be due to concerns regarding its effects on symptoms and dialysis adequacy. We performed a systematic review of the literature to examine the effects of cool dialysis on intradialytic blood pressure, and to assess its safety in terms of thermal symptoms and small solute clearance. METHODS: We searched the Cochrane Central Register of Controlled Trials, Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, databases of ongoing trials, the contents of four major renal journals as well as hand-searching reference lists. We included all prospective randomized studies that compared any technique of reducing dialysate temperature with standard bicarbonate dialysis. These techniques included an empirical, fixed reduction of dialysate temperature or use of a biofeedback temperature-control device (BTM) to deliver isothermic dialysis or programmed patient cooling. RESULTS: A total of 22 studies comprising 408 patients were included (16 studies examined a fixed empirical temperature reduction and six examined BTM). All studies were of crossover design and relatively short duration. IDH occurred 7.1 (95% CI, 5.3-8.9) times less frequently with cool dialysis (both fixed reduction and BTM). Post-dialysis mean arterial pressure was higher with cool-temperature dialysis by 11.3 mmHg (95% CI, 7.7-15.0). No studies reported that cool dialysis led to a reduction in dialysis adequacy as assessed by urea clearance. The frequency and severity of thermal-related symptoms were generally reported inadequately. CONCLUSIONS: Reducing the temperature of the dialysate is an effective intervention to reduce the frequency of IDH and does not adversely affect dialysis adequacy. This applies to the fixed reduction of dialysate temperature and BTM. It remains unclear as to what extent cool-temperature dialysis causes intolerable cold symptoms during dialysis. There are no trials comparing fixed empirical temperature reduction with BTM, and no trials examining the long-term effects of cool dialysis on patient outcomes.

Blood↗
PubMed2006

A solid state paramagnetic maser device driven by electron spin injection.

In response to an external, microwave-frequency magnetic field, a paramagnetic medium will absorb energy from the field that drives the magnetization dynamics. Here we describe a new process by which an external spin-injection source, when combined with the microwave field spin pumping, can drive the paramagnetic medium from one that absorbs microwave energy to one that emits microwave energy. We derive a simple condition for the crossover from absorptive to emissive behavior. Based on this process, we propose a solid-state, paramagnetic device in which microwave amplification by stimulated emission of radiation is driven by spin injection.

Journal Article↗
PubMed2001

NMDA receptor- and metabotropic glutamate receptor-dependent synaptic plasticity induced by high frequency stimulation in the rat dentate gyrus in vitro.

1. The mechanisms of long-term potentiation (LTP) and long-term depression (LTD) induced by brief high frequency stimulation (HFS), paired with a particular pattern and amplitude of depolarisation has been investigated in the medial perforant pathway of the dentate gyrus of the 2- to 3-week-old rat hippocampus in vitro. 2. N-Methyl-D-aspartate (NMDA) receptor (NMDAR) activation was measured quantitatively during HFS-induced NMDAR-dependent LTP, LTD and at the LTD--LTP crossover point in order to test the hypothesis that the induction of the particular form of plasticity depends on the intensity of NMDAR activation. 3. The induction of LTD, the LTD--LTP crossover point and LTP was associated with an increasing NMDAR charge transfer. 4. In addition to the NMDAR-dependent LTD, a group I metabotropic glutamate receptor (mGluR)-dependent LTD could be induced by high intensity HFS paired with depolarisation under conditions of NMDAR inhibition. 5. The induction of mGluR-dependent LTD requires membrane depolarisation, Ca(2+) influx via L-type Ca(2+) channels and a rise in intracellular Ca(2+). 6. Quantal analysis involving minimal stimulation demonstrated that the mGluR-dependent LTD induction was associated with a decrease in potency and an increase in failure rate.

Animals↗
PubMed1983

Femoxetine - a new 5-HT uptake inhibitor - and propranolol in the prophylactic treatment of migraine.

The prophylactic effect of a 5-HT uptake inhibitor, femoxetine, was compared with that of propranolol in a double-blind crossover study of 6-months duration. 29 patients commenced the experiment. 3 subjects withdrew because of side effects and 2 because the program was inconvenient for them. In the 24 patients who continued the study to the end, the periods of propranolol (administered 160 mg daily) and of femoxetine (given 400 mg daily) differed significantly from each other with respect to the attack frequency and headache index. A significant reduction in the use of medication relieving attacks was observed during the propranolol treatment as compared with the pre-treatment period. The study showed that partial depletion of thrombocyte 5-HT uptake inhibitor did not lead to a marked improvement in headache, contrary to what might be expected on the grounds of the 5-HT hypothesis of migraine.

Adult↗
PubMed1975

The effect of wheat bran on intestinal transit.

In 18 students and two members of staff at a boys' boarding school, the time taken to pass 20 out of 25 radiopaque pellets varied from one to seven days while the subjects were eating a normal English diet. After the additon of bran, about 20 g daily, to this diet transit time fell from 2-75 plus or minus 1-6 to 2-0 plus or minus 0-9 days (P smaller than 0-025). Transit became faster in all nine subjects who had an initial time of three days or more, and in three of seven with an initial time of two days, but became slower in all four boys with an initial one-day transit. Frequency of defaecation correlated poorly with transit time (a once daily bowel action being found with transit times ranging from one to four days), and did not increase significantly with bran. In 10 additional adults with slow initial transit (three or four days) the effect of bran was compared with that of an equal volume of ground oatflakes in a double-blind crossover trial. Bran caused a significant acceleration of transit, wherease oatmeal had no effect. These studies confirm that bran accelerates slow intestinal transit and show that this is not simply a psychological effect. Bran may also slow down fast transit.

Adolescent↗
PubMed2000

Divergent outcomes of intrachromosomal recombination on the human Y chromosome: male infertility and recurrent polymorphism.

The Y chromosome provides a unique opportunity to study mutational processes within the human genome, decoupled from the confounding effects of interchromosomal recombination. It has been suggested that the increased density of certain dispersed repeats on the Y could account for the high frequency of causative microdeletions relative to single nucleotide mutations in infertile males. Previously we localised breakpoints of an AZFa microdeletion close to two highly homologous complete human endogenous retroviral sequences (HERV), separated by 700 kb. Here we show, by sequencing across the breakpoint, that the microdeletion occurs in register within a highly homologous segment between the HERVs. Furthermore, we show that recurrent double crossovers have occurred between the HERVs, resulting in the loss of a 1.5 kb insertion from one HERV, an event underlying the first ever Y chromosomal polymorphism described, the 12f2 deletion. This event produces a substantially longer segment of absolute homology and as such may result in increased predisposition to further intrachromosomal recombination. Intrachromosomal crosstalk between these two HERV sequences can thus result in either homogenizing sequence conversion or a microdeletion causing male infertility. This represents a major subclass of AZFa deletions.

Chromosome Breakage↗
PubMed2002

Comparison of polyethylene glycol 3350 and lactulose for treatment of chronic constipation in children.

Polyethylene glycol (PEG) 3350 and lactulose were compared in an unblinded, randomized, crossover design for treatment of constipation in 37 children aged 2 to 16 years. Subjects received lactulose (1.3 g/kg/d divided twice daily up to 20 g) or PEG 3350 (10 g/m2/day) for 2 weeks. PEG 3350 significantly decreased the total colonic transit time compared to lactulose (47.6+/-2.7 vs 55.3+/-2.4 hours, mean +/- SE, PEG 3350 vs lactulose, respectively, p = 0.038). The stool frequency, form, and the ease of passage were similar for each laxative. Polyethylene glycol 3350 is an effective laxative for the treatment of chronic constipation in children.

Adolescent↗
PubMed2001

The effects of an inhaled beta(2)-adrenergic agonist on lower esophageal function: a dose-response study.

STUDY OBJECTIVES: Albuterol, a beta(2)-adrenergic agonist that is commonly used to treat asthma, reduces bronchial smooth muscle tone. The pharmacodynamics of inhaled albuterol on esophageal function were studied in healthy volunteers. DESIGN: A prospective, randomized, placebo-controlled, double-blind crossover design. SETTING: An academic medical center. PATIENTS: Nine healthy volunteers (five men, four women; age, 22 to 30 years). INTERVENTIONS: Albuterol (2.5 to 10 mg) or placebo was given via nebulizer. Volunteers were studied at two sessions, 1 week apart, using a 6-cm manometry assembly and a low-compliance pneumohydraulic pump. The percentage of lower esophageal sphincter (LES) relaxation, the frequency of transient LES relaxations (TLESRs), and the amplitude, duration, and propagation velocity of esophageal contractions were measured at 5 and 10 cm above the LES. Dependent measures were evaluated using two-way, repeated-measures analysis of variance. MEASUREMENTS AND RESULTS: Albuterol therapy reduced LES basal tone in a dose-dependent manner (baseline, 17.0 +/- 2.6 mm Hg; at 10 mg, 8.9 +/- 2.1 mm Hg; p = 0.01). The frequency of TLESRs was not different from placebo (not significant). Albuterol reduced the amplitude of esophageal contractions at 5 cm above the LES (baseline, 72.5 +/- 18.6 mm Hg; at 10 mg, 48.8 +/- 10.0 mm Hg; p<0.05). A significant reduction in esophageal body contractile amplitudes was noted at 10 cm (F[1,6] = 7.05; p<0.05). CONCLUSIONS: Inhaled albuterol reduced LES basal tone and contractile amplitudes in the smooth muscle esophageal body in a dose-dependent manner. Inhaled beta(2)-agonists may increase the likelihood of acid reflux in a subset of patients who receive cumulative dosing.

Administration, Inhalation↗
PubMed1997

Improved oxygenation in a randomized trial of inhaled nitric oxide for persistent pulmonary hypertension of the newborn.

OBJECTIVE: To determine the effect of inhaled nitric oxide (NO) on clinical outcome in newborns with persistent pulmonary hypertension (PPHN). DESIGN: A prospective, randomized trial of patients referred to a level 3 nursery in a single large center. Clinicians were not masked to group assignment. Crossover of patients from control to NO treatment was not permitted. METHODS: We randomized 49 mechanically ventilated newborns, transferred to our center with clinical and echocardiographic evidence of severe PPHN (arterial oxygen tension [PaO2] <100; fractional inspired oxygen = 1) to treatment with or without NO. Patients with gestational age <34 weeks or with congenital heart disease or diaphragmatic hernia were excluded. High-frequency oscillatory ventilation was used but not allowed concomitantly with NO. Primary outcome variables were oxygenation, mortality, and use of extracorporeal membrane oxygenation (ECMO). RESULTS: Meconium aspiration syndrome and isolated PPHN were the most common diagnoses (32/49) and were distributed equally between groups. The median age at the time of entry into the study was similar between groups, 25 hours for control patients and 18 hours for NO patients. Median baseline oxygenation index (OI) was similar in 23 control (OI = 29) and 26 NO (OI = 30) patients. Mortality (8%), use of ECMO (33%), median days on mechanical ventilation (9 days), and duration of supplemental oxygen (13 days) were not different between treatment groups. PaO2, oxygen saturation, and OI improved in the NO group compared with baseline and to control patients at 15 minutes. The median percent change in OI (-31%) in the NO group was significantly different from baseline and from the control group. The difference in oxygenation between treatment groups was still apparent 12 hours after baseline. Before cannulation for ECMO, oxygenation was better in the NO group compared with control patients. Among patients who were placed on ECMO, the median time from baseline to ECMO cannulation was 2.4 hours (range, 1 to 12 hours) among control patients and 3.3 hours (range, 2 to 68 hours) for those randomized to receive NO. There was a tendency to observe fewer adverse neurologic events (seizure and intracranial hemorrhage) in the NO group (4/26 vs 8/23). One child with alveolar capillary dysplasia confirmed by postmortem examination could not be weaned from 80 parts per million of NO and transiently developed methemoglobinemia (peak methemoglobin level = 17%). No other side effects were observed. CONCLUSIONS: Although mortality and ECMO use were similar for both treatment groups using this study size and design, sustained improvement in oxygenation with NO and better oxygenation at initiation of ECMO may have important clinical benefits. We speculate that modification of treatment to include specific lung expansion strategies with NO treatment and recognition that early improvement of oxygenation may be sustained with NO may lead to reduced use of ECMO in NO treated patients compared with controls.

Administration, Inhalation↗
PubMed2000

Randomized trials of dichlorphenamide in the periodic paralyses. Working Group on Periodic Paralysis.

Although the carbonic anhydrase inhibitors have been used in the treatment of the primary periodic paralyses (PPs), their efficacy has not been demonstrated in double-blind, placebo-controlled trials. Therefore, we tested the efficacy of dichlorphenamide (DCP; Daranide), a potent carbonic anhydrase inhibitor, in the treatment of episodic weakness in the primary PPs. We performed two multicenter, randomized, double-blind, placebo-controlled crossover trials, one involving 42 subjects with hypokalemic periodic paralysis (HypoPP) and the other involving 31 subjects with potassium-sensitive periodic paralysis (PSPP). In each trial, two 8-week treatment periods were separated by an active washout period of at least 9 weeks. The primary outcome variable in the HypoPP trial was the occurrence of an intolerable increase in attack severity or frequency (end point). The primary outcome variable in the PSPP trial was the number of attacks per week. In the HypoPP trial, there were 13 subjects who exhibited a preference (in terms of the end point) for either DCP or placebo, and 11 of these preferred DCP. In the PSPP trial, DCP significantly reduced attack rates relative to placebo. DCP also significantly reduced attack rates relative to placebo in the HypoPP subjects. We conclude that DCP is effective in the prevention of episodic weakness in both HypoPP and PSPP.

Adolescent↗
PubMed1992

Comparative clinical profiles of triazolam versus other shorter-acting hypnotics.

The efficacy, safety, and performance of triazolam was compared with those of other shorter-acting hypnotics acting on the gamma-aminobutyric acid (GABA) receptor--zopiclone, zolpidem, midazolam, brotizolam, temazepam, lormetazepam, and loprazolam. In all, 5506 patients participated in 38 clinical and epidemiologic studies, of whom 2462 were treated with triazolam in parallel-design and crossover studies. To provide clinically relevant comparisons, only studies using comparator agents in doses equipotent to the triazolam doses were included. Two general findings emerged. First, "serious" central nervous system side effects, such as excitement and violence, were not demonstrated for any of the hypnotic agents, including triazolam. Other central nervous system side effects, such as depression and irritability, were reported with equal frequencies for all the hypnotics reviewed. Rebound insomnia, reported intermittently with most of these agents, was short-lived and not clinically significant. So-called early morning insomnia was noted only once and does not appear to be a valid clinical entity. Daytime anxiety was not observed in large numbers of triazolam-treated subjects studied, which is contrary to claims that the drug is anxiogenic. Second, a remarkable similarity was found among all of these shorter-acting agents in terms of efficacy, side effects, and performance-related effects. This was particularly of note for zopiclone and zolpidem. Although claims have been made suggesting differences, evaluation of the studies herein showed that these nonbenzodiazepine hypnotics were indistinguishable from triazolam and other benzodiazepine hypnotics in their clinical and pharmacologic activity. Thus, different chemical structures did not a priori predict different clinical profiles when drugs share a similar mechanism of action.

Azabicyclo Compounds↗
PubMed1988

A comparison of the long-term effects of sotalol and atenolol on QT interval and arrhythmias after myocardial infarction.

In order to dissociate the Class III effects of sotalol on QT interval and arrhythmias from those of chronic beta-receptor blockade, we compared the effects of sotalol 160 mg b.d. and atenolol 50 mg b.d. in a double-blind crossover study of 103 patients followed for one year after discharge following acute myocardial infarction. Sotalol caused a highly significant lengthening of the absolute and corrected QT (QTc) interval over atenolol which was apparent by day 6 and persisted unchanged throughout the follow-up period. The increase in QT interval averaged 43 ms (9%). Sotalol blunted the increase in ventricular premature beat frequency on ambulatory monitoring which occurred with atenolol, although direct comparison of arrhythmia frequency between the groups receiving atenolol and sotalol revealed no significant difference. Marked lengthening of QTc interval (greater than 500 ms) was observed on 29 occasions in patients receiving sotalol, most commonly at day 6, but no episodes of polymorphic ventricular tachycardia were recorded. The Class III action of sotalol persists over and above any response to beta-blockade during a one-year follow-up period. In a population with a low incidence of spontaneous arrhythmias, however, there was only a modest difference in antiarrhythmic efficacy between atenolol and sotalol. Episodes of marked lengthening of QT interval induced by sotalol in the absence of other adverse factors need not be arrhythmogenic.

Adult↗