Effects of mirodenafil, a phosphodiesterase-5 inhibitor, on female rat bladder in a partial bladder outlet obstruction model: physiological and immunohistochemical aspects.

PURPOSE: We investigated the effects of mirodenafil, a phosphodiesterase-5 inhibitor developed in South Korea, on the female rat bladder in a partial bladder outlet obstruction (BOO) model. MATERIALS AND METHODS: Thirty-six female Sprague-Dawley rats were divided into four groups: the control group, BOO without medication group, BOO with mirodenafil 1 mg/kg group, and BOO with mirodenafil 4 mg/kg group. Mirodenafil was administered orally for 2 weeks after the induction of BOO. Two weeks after BOO, the rats in each group underwent cystometry under urethane anesthesia. After cystometry, the bladder was excised to perform immunohistochemical staining for connexin 43. RESULTS: The three BOO groups showed significant increases in mean bladder weight compared with the control group. Baseline pressure, threshold pressure, and maximum contraction pressure were not significantly different between the four groups. Although the contraction interval was decreased in all BOO groups compared with the control group, it was prolonged in the two groups treated with mirodenafil compared with the untreated BOO group. In the immunohistochemical examination, connexin 43 staining intensity in the lamina propria increased in the three BOO groups compared with the control group. The two groups treated with mirodenafil, however, showed decreased connexin 43 staining compared with the untreated BOO group. CONCLUSIONS: Mirodenafil may increase the contraction intervals of female rat bladders in a partial BOO model. Decreasing bladder overactivity by mirodenafil may be related to intracellular communication mechanisms involving connexin 43.

Treatment outcomes according to neuropathic bladder sphincter dysfunction type after treatment of oxybutynin chloride in children with myelodysplasia.

PURPOSE: We investigated the treatment outcomes according to neuropathic bladder sphincter dysfunction (NBSD) type after oral oxybutynin (OBT) treatment in children with NBSD caused by myelodysplasia. METHODS: Among 334 pediatric patients who were diagnosed with NBSD caused by myelodysplasia, only children treated with oral OBT for more than 1 year with pre- and post-treatment urodynamic studies and dimercaptosuccinic acid (DMSA) were retrospectively reviewed. We compared pre- and post-treatment urodynamic parameters including maximum cystometric capacity (MCC), MCC/estimated bladder capacity (EBC), and compliance by NBSD type in children. We also compared renal scarring on pre- and post-treatment DMSA by NBSD type in children. RESULTS: Our study population was comprised of 81 children (45 boys and 36 girls), with a mean age of 4.2 ± 3.4 years. The mean follow-up duration was 4.5 (range 1.0-15.1) years. After OBT treatment, MCC was increased significantly in all types of NBSD from 110.3 ± 62.2 to 202.3 ± 103.9 ml (p < 0.05), compliance was significantly improved from 6.4 ± 6.1 to 11.1 ± 9.6 ml/cmH2O (p < 0.05), but MCC/EBC was slightly decreased from 75.2 ± 46.9 to 69.8 ± 33.3 % (p = 0.40). Sub-analyzed by NBSD type, the pre-treatment compliance of children with acontractile detrusor with spastic sphincter (n = 16) was markedly decreased compared with other types of NBSD. Acontractile detrusor with spastic sphincter demonstrated the worst renal deterioration on DMSA. CONCLUSIONS: Although increases in MCC/EBC were limited, oral OBT treatment markedly improved MCC and compliance in all NBSD types. Children who had acontractile detrusor with spastic sphincter had a relatively high probability of renal deterioration and required specific attention.

Impact of cardio-pulmonary and intraoperative factors on occurrence of cerebral infarction after early surgical repair of the ruptured cerebral aneurysms.

OBJECTIVE: Delayed ischemic deficit or cerebral infarction is the leading cause of morbidity and mortality after aneurysmal subarachnoid hemorrhage (SAH). The purpose of this study is to reassess the prognostic impact of intraoperative elements, including factors related to surgery and anesthesia, on the development of cerebral infarction in patients with ruptured cerebral aneurysms. METHODS: Variables related to surgery and anesthesia as well as predetermined factors were all evaluated via a retrospective study on 398 consecutive patients who underwent early microsurgery for ruptured cerebral aneurysms in the last 7 years. Patients were dichotomized as following; good clinical grade (Hunt-Hess grade I to III) and poor clinical grade (IV and V). The end-point events were cerebral infarctions and the clinical outcomes were measured at postoperative 6 months. RESULTS: The occurrence of cerebral infarction was eminent when there was an intraoperative rupture, prolonged temporary clipping and retraction time, intraoperative hypotension, or decreased O(2) saturation, but there was no statistical significance between the two different clinical groups. Besides the Fisher Grade, multiple logistic regression analyses showed that temporary clipping time, hypotension, and low O(2) saturation had odds ratios of 1.574, 3.016, and 1.528, respectively. Cerebral infarction and outcome had a meaningful correlation (gamma=0.147, p=0.038). CONCLUSION: This study results indicate that early surgery for poor grade SAH patients carries a significant risk of ongoing ischemic complication due to the brain's vulnerability or accompanying cardio-pulmonary dysfunction. Thus, these patients should be approached very cautiously to overcome any anticipated intraoperative threat by concerted efforts with neuro-anesthesiologist in point to point manner.

Hemodynamic investigation of the left renal vein in pediatric varicocele: Doppler US, venography, and pressure measurements.

PURPOSE: To evaluate prospectively the hemodynamic state of the left renal vein with Doppler ultrasonography (US) and venography in pediatric patients with varicocele to assess the "nutcracker phenomenon." MATERIALS AND METHODS: The institutional review board considered this study ethically sound, and parental informed consent was obtained for all subjects. Doppler US of the left renal vein was performed in 27 consecutive boys with varicocele (age range, 7-15 years; mean, 11.9 years) and in 20 boys without varicocele as control subjects (age range, 7-17 years; mean, 11.4 years). Doppler US was used to evaluate left renal vein diameters and peak velocities in the proximal left renal vein near the renal hilum and in the left renal vein between the aorta and superior mesenteric artery (aortomesenteric portion). The diameter ratios and peak velocity ratios between two sites were obtained. For statistical comparison of results, the t test was used. Left renal venography and renocaval pressure measurement were performed in 13 patients with varicocele. The Fisher exact test was used to evaluate the associations between the nutcracker phenomenon (renocaval pressure gradient >/=3 mm Hg) and the development of collateral veins. RESULTS: The diameters of the proximal left renal vein and the peak velocities in the aortomesenteric portion of the left renal vein were significantly different between the varicocele group and the control group (P < .001). The diameter ratios (5.7 +/- 1.8 [standard deviation]) and peak velocity ratios (5.2 +/- 2.6) in patients with varicocele were significantly higher than those in control subjects (3.5 +/- 1.0 and 3.1 +/- 0.8, respectively) (P < .005). According to findings at left renal venography (n = 13), 10 patients (77%) met the criteria for the nutcracker phenomenon. The nutcracker phenomenon was significantly associated with the development of collateral veins (P = .035). CONCLUSION: Doppler US and venography of the left renal vein can show hemodynamic changes of the left renal vein and depict the presence of the nutcracker phenomenon in pediatric varicocele.

Factors associated with survival and neurological outcome after cardiopulmonary resuscitation of neurosurgical intensive care unit patients.

OBJECTIVE: We investigated predictors of survival and the neurological outcomes of neurosurgical patients who experienced cardiac arrest and received cardiopulmonary resuscitation after being admitted to the neurosurgical intensive care unit. METHODS: A retrospective study was conducted of adult patients in the neurosurgical intensive care unit who had experienced cardiac arrest and received cardiopulmonary resuscitation. Factors relevant to the cardiac arrest (before and after arrest) were used to study association with survival (immediate or short-term) and neurological outcome (unconscious or conscious) via statistical methods. RESULTS: Immediate survival was seen in 105 patients (49%), 19 survived until hospital discharge, and 11 were still alive at the conclusion of this study. Of the immediate survivors, 41 patients were conscious and 64 were unconscious. Multivariate analysis showed increased mortality in patients with infection, asystole, or resuscitation time exceeding 30 minutes (P < 0.05). Additional factors associated with high in-hospital mortality included lack of spontaneous respiration, no caloric-vestibular reflex, and unconsciousness after resuscitation (P < 0.05). In addition, neurological recovery was poor in patients with infection, asystole, no caloric-vestibular reflex, conscious recovery, or resuscitation lasting more than 30 minutes (P < 0.05). CONCLUSION: Even after initially successful resuscitation, survival and neurological recovery is quite dismal in patients with cerebral lesions. Prognostic factors for neurosurgical patients should be assessed on an individual basis to determine medical futility in the early post-resuscitation period.

Prognostic factors affecting urologic outcome after untethering surgery for lumbosacral lipoma.

OBJECTS: The authors report results of preoperative and postoperative urodynamic studies (UDS) and prognostic factors of urologic outcome in cases of lumbosacral lipomas for which prolonged follow-up data were available. MATERIALS AND METHODS: The present series includes 42 consecutive cases of lumbosacral lipoma in patients aged 2 months to 15 years who underwent untethering operation during the period from 1986 to 1997. All of them underwent preoperative and postoperative UDS. At the last follow-up (mean duration of follow-up 108 months, range 44 to 176 months), 26 cases maintained social continence with or without intermittent catheterization. Young age (< or =12 months) at operation, preoperative absence of urologic symptoms, and absence of neurologic abnormalities were significantly correlated with favorable urologic outcome. CONCLUSION: UDS in cases with lumbosacral lipomas is a valuable tool for detecting neurourologic abnormalities as well as for monitoring the postoperative course and guiding management. History taking and neurologic examination are also proved to be important aspects in the evaluation of children with lumbosacral lipomas, predictive of urologic outcome. Better urologic results are anticipated if surgery is performed when the child is 12 months old or younger.

A spontaneous giant pseudoaneurysm presenting with chronic headache in adolescent.

BACKGROUND: Intracranial pseudoaneurysms are rare vascular lesions, particularly in children and adolescents, and are characterized by the presence of organizing hematoma and fibrosis outside the true lumen, instead of true vascular elements. Most pseudoaneurysms result from an eminent insult, such as major trauma or grave infectious illness. Development of pseudoaneurysm without antecedent incident is rare. Furthermore, clinical manifestation with only a headache is also unusual in this age group. CASE HISTORY: We now describe one patient who had a giant pseudoaneurysm arising at the distal middle cerebral artery. A 17-year-old boy complained of headache that had become apparent 3 years ago and intractable to medicine 3 months ago. Brain computed tomographic scan and lumbar cerebrospinal spinal fluid study revealed no trace of recent hemorrhage. However, digital subtraction angiography revealed a huge aneurysmal dilatation along the right M2 segment with the features of delayed filling and emptying of contrast agent. Surgical obliteration of the corresponding aneurysm with tandem clipping and aneurysmectomy rendered him free of headache thereafter. CONCLUSIONS: The actual cause and mechanisms of this case are not certain; nonetheless, we suggest that traumatic cause produced such a lesion, and minor repeated bleeding also elicited headache, albeit no evidence of recent major injury.

Influence of lamina terminalis fenestration on the occurrence of the shunt-dependent hydrocephalus in anterior communicating artery aneurysmal subarachnoid hemorrhage.

Recently, it was reported that fenestration of the lamina terminalis (LT) may reduce the incidence of shunt-dependent hydrocephalus in aneurysmal subarachnoid hemorrhage (SAH). The authors investigated the efficacy of the LT opening on the incidence of shunt-dependent hydrocephalus in the ruptured anterior communicating artery (ACoA) aneurysms. The data of 71-ruptured ACoA aneurysm patients who underwent aneurysmal clipping in acute stage were reviewed retrospectively. Group I (n=36) included the patients with microsurgical fenestration of LT during surgery, Group II (n=35) consisted of patients in whom fenestration of LT was not feasible. The rate of shunt-dependent hydrocephalus was compared between two groups by logistic regression to control for confounding factors. Ventriculo-peritoneal shunts were performed after aneurysmal obliteration in 18 patients (25.4%). The conversion rates from acute hydrocephalus on admission to chronic hydrocephalus in each group were 29.6% (Group I) and 58.8% (Group II), respectively. However, there was no significant correlation between the microsurgical fenestration and the rate of occurrence of shunt-dependent hydrocephalus (p>0.05). Surgeons should carefully decide the concomitant use of LT fenestration during surgery for the ruptured ACoA aneurysms because of the microsurgical fenestration of LT can play a negative role in reducing the incidence of chronic hydrocephalus.

Giant pseudoaneurysm in adolescent.

BACKGROUND: Intracranial pseudoaneurysms, infrequent vascular lesion in children and adolescents, are characterized by the presence of organizing hematoma and fibrosis outside the true lumen instead of normal vascular elements. Because most pseudoaneurysms result from eminent insults such as major trauma or grave infection, development without preceding incident is extremely rare. Giant pseudoaneurysms in younger population, albeit unexceptionally unusual, are symptomatic in most instances and exhibit very high risk of rupture. Clinical manifestation as chronic headache without hemorrhage or neural compression is very unlikely. Once identified, only prompt surgical treatment guarantees favorable prognosis. CASE HISTORY: We report a case of a 17-year-old boy with a giant pseudoaneurysm arising at distal middle cerebral artery. He complained of headache that had become apparent 3 years ago and medically intractable 3 months ago. Brain computed tomographic scan and lumbar cerebrospinal spinal fluid study revealed no trace of recent hemorrhage. However, digital subtraction angiography revealed a huge aneurysmal dilatation along the right distal middle cerebral artery with the features of delayed filling and emptying of contrast agent. Surgical obliteration of the corresponding aneurysm with tandem clipping and aneurysmectomy made him free of headache postoperatively. CONCLUSIONS: We could not uncover the actual cause of formation and precise mechanism of clinical presentation for this unique aneurysm; nevertheless, we suggest that blunt head injury of fairly long history caused such a lesion, and repeated minute bleeding elicited headache. This assumption was possible only after full consideration of the histopathology.

Voltage-dependent ion channel currents in putative neuroendocrine cells dissociated from the ventral prostate of rat.

Prostate neuroendocrine (NE) cells play important roles in the growth and differentiation of the prostate. Following enzymatic digestion of rat ventral prostate, the whole-cell patch-clamp technique was applied to dark, round cells that exhibited chromogranin-A immunoreactivity, a representative marker of NE cells. Under zero current-clamp conditions, putative NE cells showed hyperpolarized resting membrane potentials of some -70 mV, and spontaneous action potentials were induced by an increase in external [K+] or by the injection of current. Using a CsCl pipette solution, step-like depolarization activated high-voltage-activated Ca2+ current (HVA I(Ca)) and tetrodotoxin-resistant voltage-activated Na+ current. The HVA I(Ca) was blocked by nifedipine and omega-conotoxin GVIA, L-type and N-type Ca2+ channel blockers, respectively. Using a KCl pipette solution, the transient outward K+ current (I(to)), Ca2+ -activated K+ currents (I(K,Ca)), the non-inactivating outward current and an inwardly rectifying K+ current (I(Kir)) were identified. I(K,Ca) was suppressed by charybdotoxin (50 nM), iberiotoxin (10 nM) or clotrimazol (1 microM), but not by apamine (100 nM). I(to) was inhibited by 4-aminopyridine (5 mM). I(Kir) was identified as a Ba2+ -sensitive inwardly rectifying current in the presence of a high-K+ bath solution. The voltage- and Ca2+ -activated ion channels could play significant roles in the regulation of neurohormonal secretion in the prostate.

Morphometric analysis of the collagen changes induced by subcutaneous injection of interferon-gamma after bladder outlet obstruction in the rat.

AIMS: The objective of this study was to examine the effects of interferon-gamma injection on changes in collagen content, after the creation of partial bladder outlet obstruction in the rats. METHODS: A total of 50 Sprague-Dawley female rats were subjected to partial bladder outlet obstruction by using metal rods. The rats were divided into five groups (n = 10 in each group): normal control (N), sham operation (S), bladder outlet obstruction for 4 weeks (BOO), interferon-gamma injection after sham operation (S + IFN), and interferon-gamma injection after bladder outlet obstruction (BOO + IFN). Interferon-gamma was subcutaneously injected (100,000 units per injection, LG chemical Co., Seoul, Korea) daily for 4 weeks in the injection groups, after which all rats were sacrificed. RESULTS: The collagen area percentage (collagen/collagen + muscle) in each bladder, calculated through image analysis, was 40.7 +/- 1.6% in the N, 38.2 +/- 2.0% in the S, 26.6 +/- 3.8% in the S + IFN, 19.9 +/- 2.5% in the BOO, and 12.4 +/- 2.0% in the BOO + IFN group (mean +/- standard error). The difference in the collagen area percentage between the N and S groups (P > 0.05) was not significant, but there were significant differences between the N and S + IFN groups (P < 0.05), between the S and S + IFN groups (P < 0.05), and between the BOO and BOO + IFN groups (P < 0.05). CONCLUSIONS: It appears that interferon-gamma decreases the collagen content in the obstructed rat bladder.

K+ channel currents in rat ventral prostate epithelial cells.

BACKGROUND: Electrophysiological function of the normal prostate has not been extensively studied. In particular, ion channel currents and their regulation have not been studied in freshly-isolated prostate cells. METHODS: Rat prostate secretory epithelial (RPSE) cells were isolated by collagenase treatment. Columnar epithelial cells were used for nystatin-perforated, whole-cell voltage clamp, and the intracellular Ca(2+) concentration ([Ca(2+)](i)) was measured using fura-2. RESULTS: Step-like depolarizing pulses (900 msec) starting from - 90 mV induced outwardly rectifying K(+) currents without inactivation. ACh (10 microM) or ATP (100 microM) increased the outward current and hyperpolarized the cell membrane potential. Ionomycin (0.1 microM), a Ca(2+) ionophore, induced a similar increase in the outward current. TEA (5 mM), charybdotoxin (50 nM), and iberiotoxin (30 nM) inhibited the effect of ACh (or ATP) on the outward current, whereas apamin (100 nM) had no effect. The [Ca(2+)](i) of RPSE cells was increased by ACh, ATP, and UTP. CONCLUSIONS: RPSE cells have iberiotoxin-sensitive Ca(2+)-activated K(+) channels that may play an important role in the exocrine secretions of the prostate.