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The mechanism of supraventricular tachycardia induced by a single premature beat in the isolated left atrium of the rabbit. I. Circus movement as a consequence of unidirectional block of the premature impulse.

In the isolated left atrium of the rabbit tachycardia could be elicited by a single stimulus shortly after the refractory period. The activation pattern of the preparation was mapped by means of multiple extracellular recordings. It could be demonstrated that a circus movement of the activation in a relatively small part of the atrial myocardium was responsible for the tachycardia. This phenomenon was studied on a cellular level with multiple microelectrode recordings. The impulse of the premature beat, when followed by a tachycardia, was one way only, while in the other directions the conduction failed completely or occurred with such decrement that the impulse died out. These differences in conductivity were connected with spatial differences in the refractory period. Therefore the excitability of the fibers surrounding the stimulating electrod was not restored to the same level at the moment the premature beat was elicited. Spatial dispersion in the refractory period was important for the occurrence of unidirectional block and thus for the initiation of circus movement and tachycardia.

Action Potentials↗

Sexual function of premature ejaculation patients assayed with Chinese Index of Premature Ejaculation.

AIM: To assess the psychometric properties of the Chinese Index of Premature Ejaculation (CIPE). METHODS: The sexual function of 167 patients with and 114 normal controls without premature ejaculation (PE) were evaluated with CIPE. All subjects were married and had regular sexual activity. The CIPE has 10 questions, focusing on libido, erectile function, ejaculatory latency, sexual satisfaction and difficulty in delaying ejaculation, self-confidence and depression. Each question was responded to on a 5 point Likert-type scale. The individual question score and the total scale score were analyzed between the two groups. RESULTS: There were no significant differences between the age, duration of marriage and educational level (P> 0.05) of patients with and without PE and normal controls. The mean latency of patients with PE and normal controls were 1.6 +/- 1.2 and 10.2 +/- 9.5 minutes, respectively. Significant differences between patients with (26.7 +/- 4.6) PE and normal controls (41.9 +/- 4.0) were observed on the total score of CIPE (P< 0.01). Using binary logistic regression analysis, PE was significantly related to five questions of the original measure. They are the so-called the CIPE-5 and include: ejaculatory latency, sexual satisfaction of patients and sexual partner, difficulty in delaying ejaculation, anxiety and depression. Receiver Operating Characteristic (ROC) curve analysis of CIPE-5 questionnaire indicated that the sensitivity and specificity of CIPE were 97.60 % and 94.74 %, respectively. Employing the total score of CIPE-5, patients with PE could be divided into three groups: mild (>15 point) 19.8 %, moderate (10-14 point) 62.8 % and severe (< 9 point) 16.7 %. CONCLUSION: The CIPE-5 is a useful method for the evaluation of sexual function of patients with PE and can be used as a clinical endpoint for clinical trials studying the efficacy of pharmacological intervention.

Adult↗

The natural ocular outcome of premature birth and retinopathy. Status at 1 year. Cryotherapy for Retinopathy of Prematurity Cooperative Group.

OBJECTIVE: To present the 1-year ocular outcome data from 2759 preterm infants. DESIGN: Data from all untreated eyes were tabulated. Retinopathy of prematurity (ROP) was listed by the lowest (most posterior) zone and highest (most severe) stage reached during the acute phase of ROP, based on examinations conducted at least biweekly. SETTING: Examinations were performed at 23 regional study centers. PATIENTS: The natural history cohort of the Multicenter Trial of Cryotherapy for ROP. MAIN OUTCOME MEASURES: Ocular structure and visual performance. RESULTS: The worst posterior fundus outcome rates were in eyes with zone I, stage 3 disease (59.3% unfavorable outcome) and zone II, stage 3+ ROP involving nine to 12 sectors of 30 degrees (43.9% unfavorable outcome). Eyes with zone II ROP without plus disease or with zone III ROP are at very low risk (< 1%) of unfavorable outcome. CONCLUSION: The more posterior the zone of ROP and the greater the extent of stage 3+ disease, the greater the unfavorable outcome rate.

Cohort Studies↗

The therapeutic efficacy and cost-effectiveness of aggressive tocolysis for premature labor associated with premature rupture of the membranes.

We conducted a randomized trial comparing bed rest with tocolysis to determine the therapeutic efficacy, safety, and cost-effectiveness of tocolysis for the treatment of preterm labor after membrane rupture. One hundred nine women participated over a 26-month interval. Treatment groups did not differ significantly in terms of gestational age at membrane rupture, gestational age at delivery, birth weight, maternal or fetal infectious morbidity, respiratory distress syndrome, necrotizing enterocolitis, or perinatal mortality. Prolongation of intrauterine time after the onset of uterine contractions was seen in women receiving tocolysis (105.2 +/- 157 hours versus 62.1 +/- 77 hours, p = 0.06). This prolongation was not associated with a significant reduction in the total cost per surviving infant (tocolysis, $38,593 +/- $40,887 versus bed rest, $43,158 +/- $37,116; p = 0.445). The cost difference was artifactual. The number of very premature infants born (less than 28 weeks' gestation) was unequal in the two groups (12 in the bed rest group and 5 in the tocolysis group) and skewed the results. Before 28 weeks' gestation tocolysis was associated with a significant increase in intrauterine time after the onset of regular contractions (p = 0.05). However, there was no identifiable perinatal benefit garnered from the additional 5 days. After 28 weeks there were no significant differences between treatment groups in terms of intrauterine time after the onset of regular contractions and total cost per surviving infant. Because tocolysis does not improve perinatal outcome and can itself be associated with major maternal morbidity, it should be avoided after 28 weeks' gestation. Before 28 weeks' gestation tocolysis may greatly increase intrauterine time, but the benefit of this prolongation is not clear.

Adult↗

Retinopathy of prematurity (ROP) and indomethacin therapy in premature infants with patent ductus arteriosus (PDA).

Recent studies suggested that prostaglandins (PGs) may play a role in the pathogenesis of retinopathy of prematurity (ROP). To evaluate if PGs inhibitor, indomethacin, would affect the incidence or severity of the ROP, an analysis was performed on 47 infants who participated in a double-blind controlled study of indomethacin for the closure of PDA. Twenty-three were in the control group and 24 in the indomethacin group. Indirect ophthalmoscopic examinations were performed from about 4 weeks of postnatal age and onward as needed. There was no significant difference between the groups with respect to birth weight, gestational age, postnatal age, Apgar score, and cardiopulmonary status shortly after birth and at the time of study. Six in the control and 2 in the indomethacin group (p = 0.58) developed active ROP; one in each group developed cicatricial ROP. It appears that with current doses of therapy, indomethacin does not increase the incidence or severity of ROP.

Clinical Trials as Topic↗

Prevalence of myopia between 3 months and 5 1/2 years in preterm infants with and without retinopathy of prematurity. Cryotherapy for Retinopathy of Prematurity Cooperative Group.

PURPOSE: The purpose of the study was to examine spherical equivalent refractive errors, especially myopia, at six ages between 3 months and 5 1/2 years post-term in preterm children with birth weights of less than 1251 g. DESIGN: A cohort study. PARTICIPANTS: There were a total of 827 participants in the multicenter study of cryotherapy for retinopathy of prematurity (ROP). Approximately one third of the eyes did not develop ROP, whereas two thirds developed mild-to-severe ROP. None of the eyes underwent cryotherapy. INTERVENTION: Refractive error was measured at 3 months, 1 year, and 5 1/2 years term due date at the five long-term follow-up centers. In most eyes, refractive error also was measured at 2, 3 1/2, and 4 1/2 years. MAIN OUTCOME MEASURE: Myopia was defined as 0.25 diopter (D) or greater with high myopia as 5 D or greater. RESULTS: The proportion of eyes with myopia in this preterm population was increased compared to published data on full-term children and was related to severity of both acute-phase and cicatricial-phase ROP. The percentage of eyes with myopia varied little across ages, ranging from 21.2% at 1 year to 15.7% at 4 1/2 years. The percentage of eyes with high myopia doubled from 1.8% to 3.9% between 3 months and 1 year and remained stable thereafter. The distribution of refractive errors in eyes with mild acute-phase ROP was similar to that of eyes with no ROP. In contrast, eyes with moderate or severe acute-phase ROP showed an increased prevalence of high myopia. The distribution of refractive errors changed between 3 months and 1 year with little change after 1 year. This pattern of refractive development differs from that of full-term infants. Birth weight, severity of ROP, and degree of myopia at 3 months predicted the presence of myopia and high myopia at 5 1/2 years of age. CONCLUSIONS: The distribution of refractive errors in preterm infants from age 3 months to 5 1/2 years varies with severity of acute-phase ROP and cicatricial disease. Changes in refractive error distribution occur primarily between 3 months and 1 year and involve a decrease in the proportion of eyes with hyperopia and an increase in the proportion with high degrees of myopia.

Acute Disease↗

Short-term neonatal morbidity associated with prematurity and the effect of a prematurity prevention program on expected incidence of morbidity.

With recent advances in neonatal medicine, the risk of mortality for premature newborns has been markedly reduced. Attention has shifted to the morbidity associated with preterm delivery. Consideration of anticipated neonatal morbidity at a particular gestational age plays an important part in the decision of whether or not to treat preterm labor. We have assessed eight indices of short-term morbidity in 170 liveborn infants delivered between 26 and 35 completed weeks of gestation and calculated the gestational age-specific rates of each measure of morbidity. Five measures of short-term morbidity were significantly reduced by extending the gestation from 34 to 35 weeks. To illustrate the effect of prolonged pregnancy on the incidence of short-term neonatal morbidity, the actual incidence of morbidity from a group of preterm labor patients who were part of a preterm birth prevention program was compared to the anticipated incidence of these same morbidity factors has birth occurred when preterm labor was first diagnosed. There was a significant decrease in the number of observed, as opposed to anticipated, neonatal deaths and in morbidity occurrences in four of the six factors tested. Implications for considering short-term neonatal morbidity in the decision to initiate treatment for preterm labor after 33 weeks gestation are discussed.

California↗

Postnatal changes in colloid osmotic pressure in premature infants: in healthy infants, in infants with respiratory distress syndrome, and in infants born to mothers with premature rupture of membranes.

Colloid osmotic pressure (COP) of blood plasma during the first 4 days of life was measured in 63 neonates: 16 healthy preterm infants, 36 infants with respiratory distress syndrome (RDS), and 11 infants born to mothers with premature rupture of membranes. The relation between COP and total protein content of blood was significant in all groups over times from 1-3 h to 96 h. COP rose significantly by the age of 3 h compared to COP of umbilical cord plasma in all groups investigated. Infants with RDS showed a significant increase in COP during the investigation period. In healthy preterm infants the increase was less significant. In infants with RDS there was a negative correlation between changes in COP and body weight not seen in the other groups investigated. COP in neonates seems to reflect the compartmentation between vascular and interstitial spaces. Measurement of COP could be clinically useful in assessing hemodynamic adaptation after birth and also in assessing edema formation and water balance in infants with RDS.

Birth Weight↗

Screening examination of premature infants for retinopathy of prematurity.

This statement revises a previous statement on screening of preterm infants for retinopathy of prematurity (ROP) that was published in 2001. ROP is a pathologic process that occurs only in immature retinal tissue and can progress to a tractional retinal detachment, which can result in functional or complete blindness. Recent development of peripheral retinal ablative therapy using laser photocoagulation has resulted in the possibility of markedly decreasing the incidence of this poor visual outcome, but the sequential nature of ROP creates a requirement that at-risk preterm infants be examined at proper times to detect the changes of ROP before they become permanently destructive. This statement presents the attributes on which an effective program for detecting and treating ROP could be based, including the timing of initial examination and subsequent reexamination intervals.

Humans↗

[Artificial amniotic fluid instillation in premature rupture of fetal membranes and extreme prematurity as alternative therapy].

We report two cases of premature rupture of membranes and oligohydramnios (gestational age: 23rd/24th week). In both pregnancies artificial instillation of amniotic fluid (AIF) was performed once a week. We hypothesize that fetal head compression with impaired cerebral perfusion due to oligohydramnios causes periventricular leukomalacia. Prolongation of gestation of 36/23 days without neurological lesion support this method. Surveillance of these pregnancies in a perinatal center has to include very early detection of chorioamnionitis. If not so, gained prolongation of pregnancy with a lower rate of cerebral damage becomes harmful due to infection. Clinical benefits and disadvantages of this technique have to be evaluated in a prospective randomized trial.

Amniotic Fluid↗

Risk factors for retrolental fibroplasia: experience with 3,025 premature infants. National Collaborative Study on Patent Ductus Arteriosus in Premature Infants.

The rate of retrolental fibroplasia in relation to prenatal and neonatal characteristics was explored on the basis of a cohort of 3,025 neonates with birth weight less than 1,750 g. The overall rate of retrolental fibroplasia of any degree at hospital discharge was 11%, varying from 43% for those with birth weight between 500 and 749 g to 3% for those in the 1,500- to 1,750-g category. Among the potential determinants, the main interest was in nonhyperoxic characteristics, conditional on measures of prematurity and oxygen supplementation. Maternal diabetes and antihistamine use during the last 2 weeks of pregnancy were associated with significantly higher rates of retrolental fibroplasia, whereas toxemia was associated with lower rates. Frequent apneic spells, bronchopulmonary dysplasia, and sepsis in the neonate were also associated with significantly higher rates. On the other hand, the data indicate no independent role of low Apgar score, intraventricular hemorrhage, exchange transfusion, patent ductus arteriosus, or certain other characteristics previously postulated as risk factors.

Anemia↗

[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↗

[Multicenter prospective study of retinopathy of prematurity--III. Timing of the coagulation therapy and the course of retinopathy of prematurity after coagulation].

We reviewed the records of 360 cases of retinopathy of prematurity (ROP) in 12 institutions in Japan, and investigated the timing of the coagulation therapy and the course of ROP after coagulation. The first coagulation therapy was performed at 9.6 weeks after birth and 35.9 weeks of postconceptional age on the average. The severity index in individual infants also showed that the disease became worse during the period from 32 to 36 weeks of postconceptional age. However, the fundus was clearly visible and there was no primary hazy media during this period. On the basis of the results of the timing of the first treatment, the visibility of the fundus, and the severity index in individual infants, we concluded that an ophthalmological examination with special care should be performed during the period from 32 to 36 weeks of postconceptional age.

Humans↗

Multicenter trial of cryotherapy for retinopathy of prematurity. Preliminary results. Cryotherapy for Retinopathy of Prematurity Cooperative Group.

We report the preliminary three-month outcome of a multicenter randomized trial of cryotherapy for treatment of retinopathy of prematurity (ROP). Transscleral cryotherapy to the avascular retina was applied in one randomly selected eye when there was threshold disease (defined as five or more contiguous or eight cumulative 30 degrees sectors [clock hours] of stage 3 ROP in zone 1 or 2 in the presence of "plus" disease). An unfavorable outcome was defined as posterior retinal detachment, retinal fold involving the macula, or retrolental tissue. At this writing, 172 infants had been examined three months after randomization. An unfavorable outcome was significantly less frequent in the eyes undergoing cryotherapy (21.8%) compared with the untreated eyes (43%). While the surgery was stressful, no unexpected complications occurred during or following treatment. These data support the efficacy of cryotherapy in reducing by approximately one half the risk of unfavorable retinal outcome from threshold ROP.

Clinical Trials as Topic↗

Statistical considerations in terminating randomization in the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity. Cryotherapy for Retinopathy of Prematurity Cooperative Group.

The Multicenter Trial of Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) was a randomized trial designed to test whether cryotherapy applied to the retina significantly decreased the incidence of retinal detachment, retinal fold, or retrolental "mass." Randomization into the trial was terminated on recommendation of the Data and Safety Monitoring Committee 9 months before the scheduled end of the intake period. At the time of the decision, a favorable outcome at 3 months posttreatment occurred more frequently in eyes treated with cryotherapy (78%) as compared to untreated eyes (57%) (chi 2 = 20.5). The basic statistical method used in monitoring the results was conditional power (or stochastic curtailment). Several other issues were considered in deciding to terminate the trial, including the examination of results across subgroups and clinical centers, the completeness of follow-up, clinical assessment of outcome, and long-term consequences of the treatment.

Bias↗

Incidence and early course of retinopathy of prematurity. The Cryotherapy for Retinopathy of Prematurity Cooperative Group.

In the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity (ROP), 4099 infants weighing less than 1251 g at birth underwent sequential ophthalmic examinations, beginning at age 4 to 6 weeks, to monitor the incidence and course of ROP. Overall, 65.8% of the infants developed ROP to some degree; 81.6% for infants of less than 1000 g birth weight. As expected, ROP incidence and severity were higher in lower birth weight and gestational age categories. Black infants appeared less susceptible to ROP, of all severity categories, than nonblack infants. The timing of retinal vascular events correlated more closely with postconceptional age than with postnatal age, implicating the level of maturity more than postnatal environmental influences in governing the timing of these vascular events. These results include the current incidence of various severity stages of ROP found in the United States and provide new insight into the development of ROP.

Cryosurgery↗

Psoralen plus UVA (PUVA) induced premature senescence as a model for stress-induced premature senescence.

Following psoralen photoactivation (PUVA treatment) human dermal fibroblasts undergo long-term growth arrest as well as morphological and functional changes reminiscent of replicative senescence. Although the molecular description of cellular senescence is still incomplete, replicative senescence of cultured human cells has been suggested to reflect cellular aging in vitro. Recently, the term stress-induced premature senescence (SIPS) was introduced to define in vitro models with longterm growth arrest upon exposure to sublethal stressors (i.e. hyperoxia, hydrogen peroxide, ethanol), which are characterized by morphological and functional changes common for replicative senescence. This mini review focuses on the morphological and functional changes in the fibroblast phenotype following exposure to psoralen plus UVA (PUVA) leading to SIPS and the role of reactive oxygen species in the switch from the proliferative to the post mitotic cell. Additionally, we will discuss the possible in vivo relevance of PUVA-SIPS fibroblasts in PUVA-treated patients.

Aging, Premature↗