Vasoconstrictive effects of endothelin-1, endothelin-3, and urotensin II in isolated perfused human lungs and isolated human pulmonary arteries.

BACKGROUND: Urotensin II (UII) has been identified as a ligand for the orphan receptor GPR14 through which it elicits potent vasoconstriction in humans and non-human primates. The pulmonary vasculature is particularly sensitive; human UII (hUII) exhibits a potency 28 times that of endothelin (ET)-1 in isolated pulmonary arteries obtained from cynomolgus monkeys. However, hUII induced vasoconstriction in isolated human intralobar pulmonary arteries is variable, possibly as a result of location dependent differences in receptor density or because it is only uncovered by disease dependent endothelial dysfunction. METHODS: The vasoactivity of both hUII and gobi UII (gUII) in comparison with ET-1 and ET-3 was studied in isolated perfused lung preparations (n = 14) and isolated intralobar pulmonary arteries (n = 40, mean diameter 548 (27) microm) obtained from 17 men of mean (SE) age 67 (2) years and eight women of mean (SE) age 65 (3) years with a variety of vascular diseases. RESULTS: ET-1 (10 pM-100 nM) and ET-3 (10 pM-30 nM) elicited vasoconstriction in the lung preparations, inducing comparable increases in pulmonary arterial pressure of 24.8 (4.5) mm Hg and 14.5 (4.9) mm Hg, respectively, at 30 nM (p = 0.13). Similarly, ET-1 (10 pM-300 nM) and ET-3 (10 pM-100 nM) caused marked vasoconstriction in isolated pulmonary arteries, inducing maximal changes in tension of 4.36 (0.26) mN/mm and 1.54 (0.44) mN/mm, respectively, generating -logEC(50) values of 7.67 (0.04) M and 8.08 (0.07) M, respectively (both p<0.05). However, neither hUII nor gUII (both 10 pM-1 micro M) had any vasoactive effect in either preparation. CONCLUSION: UII does not induce vasoconstriction in isolated human pulmonary arterial or lung preparations and is therefore unlikely to be involved in the control of pulmonary vascular tone.

The incidence of nephrolithiasis in patients with spinal neural tube defects.

PURPOSE: Bladder stones are common in patients with spinal neural tube defects but there are little data on the incidence of renal calculi in this population. We examined the incidence, nature and risk factors of nephrolithiasis in our clinic population of patients with neural tube defects. MATERIALS AND METHODS: We retrospectively reviewed the charts and radiological studies of 327 patients followed at our neural tube defects clinic with routine radiological imaging of the urinary tract. Additional confirmatory studies were performed when stones were noted. RESULTS: Renal calculi were identified in 20 patients with neural tube defects (6.1%). The incidence of nephrolithiasis increased with age. Renal stones were noted in 19 patients (10.7%) 12 years old or older. Management of the stones in these patients resulted in overall 53% stone-free and 87% recurrence rates after intervention. Major risk factors for new and/or recurrent renal stone formation were bacteriuria in 95% of the cases, lower urinary tract reconstruction in 80%, pelvicalicectasis in 70%, vesicoureteral reflux in 65%, a thoracic level spinal defect in 60% and renal scarring in 55%. CONCLUSIONS: These data suggest that there is a higher incidence of nephrolithiasis in patients with neural tube defects than in the general population and the risk of stone recurrence is also elevated. Most patients with stones had undergone lower urinary tract reconstruction. Other risk factors were bacteriuria, pelvicalicectasis, vesicoureteral reflux and a thoracic level neural tube defect.

Suppression of renal inflammation with vitamins A and E in ascending pyelonephritis in rats.

PURPOSE: We evaluated the effects of vitamin A and E supplementation alone or in combination with non-steroidal anti-inflammatory drugs (NSAIDs) on the development of inflammation in an animal model of ascending pyelonephritis. MATERIALS AND METHODS: Ascending pyelonephritis was induced in adult rats by surgical bladder inoculation with P-pili-forming Escherichia coli. Treatment of pyelonephritic rats was initiated at 72 hours post-infection. Treatment groups included no treatment, or a five day regimen of antibiotic only, antibiotic plus vitamins A and E, or antibiotic, vitamins and either of two NSAIDs. Kidneys were harvested at six weeks post-infection and assessed for histopathologic inflammation. RESULTS: Antibiotic treatment of pyelonephritic rats with vitamins A and E alone or in combination with NSAIDs resulted in significantly less kidney inflammation, as compared with untreated rats or rats treated with antibiotic alone. There was no significant difference in inflammation between animals treated with vitamins alone or vitamins plus NSAIDs. CONCLUSIONS: Antibiotic therapy and diet supplementation with vitamins A and E can significantly reduce the inflammation associated with ascending pyelonephritis, suggesting a potential use in the medical management of reflux nephropathy in children.

Epididymitis in children: the circumcision factor?

PURPOSE: Recommendations for circumcision have significantly altered in the last several years. Studies have objectively established an increased risk of urinary tract infection in uncircumcised boys. We evaluated the relationship between epididymitis and circumcision status. MATERIALS AND METHODS: We studied the relationships among the circumcision status of 36 consecutive boys with epididymitis in a review of 128 with acute scrotal inflammation (group 1), circumcision status of 43 in whom the diagnosis of epididymitis at discharge home had been made elsewhere (group 2), New York State hospital discharge figures for circumcision in newborns (group 3) and the regional prevalence of circumcision in 200 consecutive pediatric emergency department patients at the same institution with nonurological diagnoses (group 4). RESULTS: New York State Department figures indicate that 70% of male newborns are discharged home with a hospital code for circumcision. Similarly an evaluation of 200 consecutive male patients without urological diagnoses younger than 18 years in the emergency department revealed that 131 (65%) were circumcised. Comparatively in groups 1 and 2 only 25 and 26% of patients, respectively, were circumcised. The statistical difference in circumcision status among the 4 groups was significant (p >0.0004). CONCLUSIONS: These data demonstrate with highly statistical significance that a relationship exists between epididymitis and the presence of a foreskin. We found that an intact foreskin is an important etiological factor in boys with epididymitis.

Dating violence: the association between methods of coping and women's psychological adjustment.

The present study examined the psychological impact of dating violence and the relationship between methods of coping with dating violence and psychological adjustment in a nonclinical female student population. Analyses revealed that women who experienced dating violence were at significantly greater risk than a comparison group for experiencing psychological distress. More symptoms of psychological distress were observed even after controlling for differences between the groups in histories of sexual aggression since age 16 and violence experiences in childhood including physical abuse, sexual abuse, and witnessing physical conflict between one's parents. The dating violence group was also more prone to use disengagement methods of coping to deal with nondating violence stressful life events than was the comparison group. In addition, disengagement methods of coping with the dating violence per se accounted for unique variance in psychological adjustment even after controlling characteristics of dating violence and methods of coping with other stressors.

The relation between methods of coping during adulthood with a history of childhood sexual abuse and current psychological adjustment.

With a community sample of 192 women who had been sexually abused during childhood, the investigators determined if methods of coping in adulthood with the aftermath of child sexual abuse were associated with current symptoms of psychological distress. Multiple regression analyses indicated that disengagement methods of coping with the sexual abuse accounted for unique variance in general psychological distress even after controlling for characteristics of the abuse and methods of coping with other stressors. Disengagement methods of coping were also used more often to deal with the stressful aspects of having been sexually abused than to deal with other stressful events. In contrast, engagement methods of coping were used more often to deal with the other stressors than with sexual abuse.

Can fetal renal artery Doppler studies predict postnatal renal function in morphologically abnormal kidneys? A preliminary report.

PURPOSE: The diagnosis of multicystic kidney in utero can be made with reasonable reliability with real-time sonography. However, a cystic hydronephrotic kidney may be difficult to distinguish from a multicystic kidney, necessitating postnatal renography. We report our preliminary observations of Doppler waveform variation in normal and cystic fetal kidneys. MATERIALS AND METHODS: Five consecutive fetuses with a unilateral cystic kidney, and one with a unilateral hydronephrotic duplex kidney and cystic upper moiety were evaluated in utero with color Doppler renal sonography. RESULTS: Doppler signal on serial ultrasound was consistently absent in the ipsilateral cystic kidney, while normal renal artery Doppler waveforms with a systolic and diastolic component were obtained from the contralateral and unaffected moieties. Postnatal renography confirmed nonfunction in all cystic moieties. The hydronephrotic noncystic moiety of the duplex kidney showed a normal Doppler waveform and good function. CONCLUSIONS: Absence of renal artery Doppler waveforms in fetal cystic kidneys correlates with renal nonfunction. If this observation can be further confirmed by additional cases, fetal Doppler sonography would become an additional tool to diagnose confidently a multicystic kidney in utero, which may allow us to dispense with postnatal renography.

Mediators of the long-term impact of child sexual abuse: perceived stigma, betrayal, powerlessness, and self-blame.

Using a community sample of 192 adult women who had been sexually abused during childhood, the present study tested the hypothesis that perceived stigma, betrayal, powerlessness, and self-blame mediate the long-term effects of child sexual abuse. A path analysis indicated that the level of psychological distress currently experienced by adult women who had been sexually abused in childhood was mediated by feelings of stigma and self-blame. This result provides partial support for Finkelhor and Browne's (1985) traumagenic dynamics model of child sexual abuse. The limitations of the study are discussed.

Cytoreductive surgery for stage IV renal cell carcinoma.

To facilitate the regression of extra renal disease in response to systemic therapy, cytoreductive surgery has been advocated as step 1 in the treatment of stage IV renal cell carcinoma. To determine the effect of surgery on subsequent clinical course, we reviewed the treatment records of 30 patients with known stage IV carcinoma of the kidney who underwent nephrectomy or additional procedures in preparation for systemic therapy. Of 30 patients only 7 (23%) underwent systemic therapy postoperatively. Progression of the disease, surgical morbidity and mortality were the factors preventing 77% of our patients from continuing with treatment. Since regression of extra renal lesions is the goal of systemic therapy, our data suggest that nephrectomy and most other cytoreductive operations in preparation for systemic therapy are not efficient treatment strategies.

Children's understanding of knowledge acquisition: the tendency for children to report that they have always known what they have just learned.

Children's attention to knowledge-acquisition events was examined in 4 experiments in which children were taught novel facts and subsequently asked how long they had known the new information. In Experiment 1, 4- and 5-year-olds tended to claim they had known novel animal facts for a long time and also reported that other children would know the novel facts. This finding was replicated in Experiment 2, using facts associated with chemistry demonstrations. In Experiments 3 and 4, children were taught new color words. 5-year-olds, but not 4-year-olds, distinguished between novel and familiar color words, reporting they had not known the novel words before the test session, but they had always known the familiar words. 4-year-olds in Experiment 4 were better able to distinguish novel and familiar color words when the teaching of the novel words was an explicit and salient part of the procedure.

Characterization of the inhibitory 5-HT receptor in the rat vas deferens.

The inhibitory effects of 5-HT on the response of the rat isolated rat vas deferens preparation to electrical stimulation (0.1 Hz) has been investigated. A number of compounds, previously shown to possess antagonist activity at the rat central nervous system 5-HT autoreceptor, including methiothepin and the beta-blockers propranolol, alprenolol and cyanopindolol, have been found to possess virtually identical activity in the rat vas deferens. Cyanopindolol (Ke versus 5-HT = 4.9 nM) was the most potent antagonist tested, but was even more effective as a beta 2-antagonist (Ke = 0.14 nM) in this preparation. Prizidilol (Ke versus 5-HT = 30.2 nM, Ke versus isoprenaline = 75 nM) and acebutolol (Ke versus 5-HT = 297 nM, Ke versus isoprenaline = 3300 nM) have been identified as beta-blocking compounds that possess higher activity at the 5-HT receptor than at the beta 2-receptor. Several compounds, previously shown to possess 5-HT agonist activity, have been tested in this preparation and their potencies relative to 5-HT were as follows: 5-carboxyamidotryptamine (x 7), TFMPP (x 0.1) and LSD (x 0.04). RU24969 was found to behave as a low intrinsic activity partial agonist. All the evidence is consistent with the inhibitory 5-HT receptor present in this preparation being identical to the 5-HT autoreceptor found in the rat central nervous system which has been identified as the receptor with which the 5-HT1B binding site is associated.

Cardiac Na+, K+-adenosine triphosphatase inhibition by ouabain and myocardial sodium: a computer simulation.

The major evidence against the hypothesis that Na+, K+-adenosine triphosphatase (Na+, K+-ATPase) inhibition is the mechanism of the positive inotropic action of digitalis is that the myocardial sodium content does not increase at the time of the inotropic response. In order to understand the relationship between sodium pump inhibition and myocardial sodium content, a computer simulation of the intracellular sodium concentration ([Na+]i) during a cycle of myocardial function was performed. The model for the computer simulation is a small compartment adjacent to the inner surface of the sarcolemma. The change in [Na+]i in this compartment is determined by the rate of sodium influx (published data utilized) and the rate of active sodium transport was estimated from the activities of partially purified dog heart Na+, K+-ATPase preparations assayed with various concentrations of sodium and ouabain. The initial rapid sodium influx results in maximal sodium pump activation, but the pump activity decreases with time as the [Na+]i decreases. Thus, the sodium pump functions at a rate close to its maximal velocity during the initial phase of each cycle but at reduced rates during the later phase. Inhibition of Na+, K+-ATPase by ouabain decreases the maximal velocity during the intiial phase of each cycle but at reduced rates during the later phase. Inhibition of Na+, K+-ATPase by ouabain decreases the maximal velocity of the sodium pump but increases the time in each cycle at which the sodium pump operates at its highest possible rate under these conditions, i.e., a rate close to the inhibited maximal velocity. A 40% inhibition of Na+, K+-ATPase activity, caused by inotropic concentrations of ouabain, increases the peak [Na+]i but fails to cause intracellular sodium accumulation since [Na+]i approaches control levels before the beginning of the next cardiac cycle. With greater enzyme inhibition, caused by arrhythmic concentrations of ouabain, [Na+]i fails to return to the precycle level and thus each subsequent cycle causes a progressive accumulation of myocardial sodium. Computer simulation predicts that a positive inotropic concentration of ouabain causes a myocardial sodium accumulation at a high heart rate but not at a lower heart rate. This was confirmed by experiments with Langendorff preparations of guinea-pig hearts. It is concluded that a moderate sodium pump inhibition by inotropic concentrations of ouabain enhances the intracellular sodium transient (a transient increase in intracellular sodium concentration associated with each membrane excitation) but does not cause a significant myocardial sodium accumulation at normal heart rates. A progressive myocardial sodium accumulation occurs only when the degree of Na+, K+-ATPase inhibition exceeds a critical magnitude.

Non-tumoral stenosis of the aqueduct in adults.

Nine cases of non-tumoral stenosis of the aqueduct in adults are described. The deformed aqueducts are displayed diagrammatically. Patients may be divided into three groups, according to their presentation; papilledema with raised intracranila pressure, epilepsy, or intellectual impairment. Those patients in the first category tended to be younger, and to respond more favorably to treatment. A review of the literature is made.