Impaired Compliance Research Articles

Effect of Electrical Stimulation and Biofeedback Therapy for Constipated Patients with Impaired Rectal Sensation

Purpose: Biofeedback therapy is widely used for the management of constipation associated with pelvic outlet obstruction. Some patients have shown poor outcome after biofeedback alone. A subgroup of patients complains of absence of desire to defecate. The main pathophysiology of constipation may be impaired rectal sensation or compliance. This study evaluated the effect of electrical stimulation and biofeedback therapy (EST-BF) for this subgroup of constipated patients with impaired rectal sensation. Methods: Of the 37 patients diagnosed with pelvic outlet obstruction by using cinedefecography, 9 patients (M：F=2：7, age=22～77 years, median=57 years) who had impaired rectal sensation (rectal desire threshold ≥100 ml) on anorectal manometry were selected. These patients were treated with EST-BF therapy 2～6 (median: 5) sessions, Kontinece, Multichannel system, HMT, Inc, Seoul, Korea). Treatment consisted of 20 minutes of variant-mode electrical stimulation and 20 minutes of EMG biofeedback therapy per week administered by a specialized colorectal surgeon. All patients were evaluated by using a standardized questionnaire and a threshold for rectal sensation based on balloon distention before and after treatment. Results: At post EST-BF, six (67%) patients had experienced an improvement in symptoms, including five (56%) patients with complete symptom relief. Significant improvement in rectal sensation, especially the rectal defecation desire threshold (pre-EST-BF vs. post- EST-BF: 181.0±38.7 vs. 88.3±29.1) was achieved. Conclusions: EST- BF may be an effective option for use in the treatment of functional constipation with impaired rectal sensation.

Impaired Arterial Compliance and Aerobic Endurance in Kidney Transplant Recipients

Cardiovascular disease is the leading cause of morbidity and mortality in kidney transplant recipients (KTR). Two risk factors for cardiovascular disease that have not been examined in this population are arterial compliance and aerobic capacity. The primary objective was to determine small and large artery compliance and aerobic endurance in KTR. A secondary objective was to explore the relationship between aging and arterial compliance and aerobic endurance in KTR. Sixty-two clinically stable KTR were recruited from the University of Alberta Renal Transplant Clinic. Small and large artery compliance was assessed using computerized arterial pulse waveform analysis. Aerobic endurance was determined using the six-minute walk test. Age-matched normative data from healthy individuals was used for comparison. Small arterial compliance was lower in KTR (5.5+/-3 ml/mm Hg x 100) compared to age-matched healthy individuals' predicted values (7.9+/-0.9 ml/mm Hg x 100, P<0.0001). No difference was found for large artery compliance between KTR (16.0+/-6.6 ml/mm Hg x 10) and age-matched healthy predicted values (15.2+/-1.3 ml/mm Hg x 10, P=0.5). Small and large artery compliance were 35% (P=0.026) and 36% (P=0.005) higher in younger (<51 years) versus older (>51 years) KTR, respectively. The six-minute walk distance was 28% lower in KTR (495+/-92 m) compared to healthy age-predicted values (692+/-56 m P<0.0001). Compromised arterial compliance and poor aerobic endurance may partially explain the high incidence of cardiovascular disease in KTR. Interventions demonstrated to improve these parameters may afford substantial clinical benefit in this population.

Airway Smooth Muscle Dysfunction Precedes Teratogenic Congenital Diaphragmatic Hernia and May Contribute to Hypoplastic Lung Morphogenesis

Fetal intervention aims to improve lung growth and survival in congenital diaphragmatic hernia (CDH). Airway smooth muscle (ASM) is important in lung development: ASM progenitors produce a key growth factor for lung morphogenesis (fibroblast growth factor 10); ASM contractility is also coupled to growth. ASM hyperreactivity occurs in postnatal CDH and may exacerbate barotrauma via impaired lung compliance. We hypothesize that ASM hyperreactivity and its sequelae are based on an early developmental lesion of ASM activity in hypoplastic lung. Sprague-Dawley rats were fed 100 mg nitrofen on Day 9.5 of pregnancy to induce lung hypoplasia in offspring (controls had vehicle alone). Normal and hypoplastic lung primordia were cultured from Day 13.5 of gestation at 37 degrees C in 5% CO(2) and loaded at 54 or 78 h with Ca(2+)-sensitive indicators: Fluo-4 for confocal imaging and Indo-1 or Fura-2 for photometric measurements of [Ca(2+)](i). Hypoplastic lung features spontaneous propagating ASM Ca(2+) transients with reduced frequency, increased amplitude, and significantly prolonged plateau duration, relative to control lung. Nonetheless, hypoplastic lung exhibits normal requirement for extracellular calcium entry and intracellular calcium release in initiation and regulation of ASM Ca(2+) waves. Early ASM dysfunction in lung hypoplasia is apparent as specific anomalies of Ca(2+) transients that indicate a problem with plasmalemmal ion channels/action potential generation. Elucidation of such an ASM lesion may allow pharmacologic amelioration not only of ASM hyperreactivity and its sequelae, but also of hypoplastic lung growth itself.

Abnormal cardiovascular response to exercise in patients with peripheral arterial disease: Implications for management

Exercise is beneficial in improving claudication and functional capacity in patients with peripheral arterial disease (PAD). However, the physiologic response during and after exercise testing in this patient population has not been fully described. This study examined the cardiovascular response to exercise and explored the potential contribution of vascular noncompliance to exercise-induced hypertension in 124 patients with PAD and claudication and 31 comparison (C) patients with PAD with no walking limitations. Maximal walking distance was determined by an exercise treadmill test. Heart rate and blood pressure were monitored before, during, and immediately after an exercise test. Vascular compliance of the small and large vessels was measured using pulse waveform analysis. Individuals with low supine resting heart rate had longer pain-free walking distance (r = -0.195, P = .019) and maximal walking versus the C group (62 beats/min, standard deviation [SD] = 10, P = .02). Systolic blood pressure during supine rest was significantly lower for the PAD group (mean = 141 mm Hg, +/- SD = 22) versus the C group (mean = 153 mm Hg, +/- SD = 20, P = .003). Vascular compliance of large vessels was higher in the C group (mean = 4.13 +/- 4.13 mL/mm Hg x 100) compared with the PAD group (mean = 2.95 +/- 1.6 mL/mm Hg x 100). This study describes the exaggerated exercise cardiovascular response and impaired vascular compliance in patients with PAD. These results provide further evidence supporting the importance of a monitored treadmill exercise test before initiation of an exercise program to ensure safe and accurate exercise recommendations, and to identify individuals that require more intensive pharmacotherapy to prevent exercise-induced hypertension and tachycardia.

Oxygen Attenuates Atelectasis-induced Injury in the In Vivo Rat Lung

Atelectasis results in impaired compliance and gas exchange and, in extreme cases, increased microvascular permeability, pulmonary hypertension, and right ventricular dysfunction. It is not known whether such atelectasis-induced lung injury is due to the direct mechanical effects of lung volume reduction and alveolar collapse or due to the associated regional lung hypoxia. The authors hypothesized that addition of supplemental oxygen to an atelectasis-prone ventilation strategy would attenuate the pulmonary vascular effects and reduce the local levels of vasoconstrictor eicosanoids. In series 1, anesthetized, atelectasis-prone mechanically ventilated rats were randomly assigned to one of six groups based on the inspired oxygen concentration and ventilated without recruitment. Series 2 was performed to determine the cardiac and pulmonary vascular effects of 21% versus 100% inspired oxygen. In series 3, computed tomography scans were performed after ventilation with a recruitment strategy (21% O2) or no recruitment strategy (21% O2 or 100% O2). In series 4, functional residual capacity was measured in animals where the gas was 21% or 100% O2. The partial pressure of arterial oxygen increased with increasing inspired oxygen, but the alveolar-arterial oxygenation gradient was also greater with higher inspired oxygen. Ventilation with 21% O2 (but not with 100% O2) was associated with progressive pulmonary vascular impedance and increased pulmonary vascular permeability. Prostaglandin F2alpha was increased by mechanical ventilation, especially without supplemental oxygen. Computed tomography scans demonstrated no atelectasis in recruited lungs, and atelectasis in nonrecruited lungs that was greater with supplemental oxygen. Increased atelectasis with 100% O2 (vs. 21% O2) was demonstrated by measurement of functional residual capacity. Although supplemental oxygen worsened atelectasis in this model, it prevented the pathologic effects of atelectasis, including microvascular leak and pulmonary hypertension. Atelectasis-induced lung injury seems to be mediated by hypoxia rather than by the direct mechanical effects of atelectasis.

Cutaneous Vesicostomy Revisited - the Second 15 Years

The aim of this paper was to review the authors' experience with cutaneous vesicostomy (CV) over the last 15 years including indications, results, and complications of CV. The records of 31 patients treated by CV between 1987 and 2002 were reviewed. There were 20 boys and 11 girls. The two main primary pathologies were neuropathic bladder (19 patients) and posterior urethral valve (PUV) (7 patients). All patients underwent a Blocksom-type operation at a mean age of 23 months (range 14 days-9 years). Pre- and postoperative conventional uromanometry was performed in 18 patients (58%) and bladder function was assessed. In 23 patients (74%) the CV provided a successful diversion with improvement of the upper urinary tract and/or stabilization of the renal function. In 5 patients (16%) with PUV, the improvement was temporary. In 3 patients (10%) the CV did not result in an improvement. Twenty-four patients underwent CV closure after a mean duration of 23 months (range, 1 month-7 years) of diversion. In 2 patients with myelomeningocele (MMC) and severe somato-mental developmental delay, CV was not closed and is being considered as a permanent treatment option. Urodynamic studies in 5 PUV patients showed impaired compliance and high intravesical pressure following a successful valve ablation and closure of CV. In the neuropathic bladder group the bladder function improved following closure of CV and commencement of anticholinergic medication and clean intermittent catheterization (CIC). Our augmentation ratio in the neuropathic bladder group was 22%. Complications of CV included: stenosis in 7 patients (22%), prolapse in 2 (6%), and cellulitis in 2 (6%). The revision rate was 16%. In young infants CV had a less favourable result in the PUV patients than in cases with high-pressure neuropathic bladder with upper tract dilatation and severe urinary tract infection (UTI), where CV provided decompression and prevented deterioration of the renal function. Cutaneous vesicostomy has stood the test of time in our changing paediatric urological practice and it remains a valuable weapon in the armoury of paediatric urologists in selected patients.

Continuous positive airway pressure causes lung injury in a model of sepsis

Continuous positive airway pressure, aimed at preventing pulmonary atelectasis, has been used for decades to reduce lung injury in critically ill patients. In neonatal practice, it is increasingly used worldwide as a primary form of respiratory support due to its low cost and because it reduces the need for endotracheal intubation and conventional mechanical ventilation. We studied the anesthetized in vivo rat and determined the optimal circuit design for delivery of continuous positive airway pressure. We investigated the effects of continuous positive airway pressure following lipopolysaccharide administration in the anesthetized rat. Whereas neither continuous positive airway pressure nor lipopolysaccharide alone caused lung injury, continuous positive airway pressure applied following intravenous lipopolysaccharide resulted in increased microvascular permeability, elevated cytokine protein and mRNA production, and impaired static compliance. A dose-response relationship was demonstrated whereby higher levels of continuous positive airway pressure (up to 6 cmH(2)O) caused greater lung injury. Lung injury was attenuated by pretreatment with dexamethasone. These data demonstrate that despite optimal circuit design, continuous positive airway pressure causes significant lung injury (proportional to the airway pressure) in the setting of circulating lipopolysaccharide. Although we would currently avoid direct extrapolation of these findings to clinical practice, we believe that in the context of increasing clinical use, these data are grounds for concern and warrant further investigation.

Distribution and Correlates of Arterial Compliance Measures in Asymptomatic Young Adults: The Bogalusa Heart Study

Impaired arterial compliance is an independent predictor of early vascular damage and related adverse cardiovascular (CV) outcome. Information is scant on the distributions and correlates of measures of arterial pulsatile function in a community-based, biracial cohort of young adults. In 800 African American and white subjects aged 18 to 44 years, pulsatile arterial function was assessed in terms of large artery (capacitive) compliance, small artery (oscillatory) compliance, systemic vascular resistance, and vascular impedance by noninvasive radial artery pressure pulse contour analysis. African Americans versus whites and women versus men had lower large and small artery compliances and higher systemic vascular resistance and vascular impedance (P < .001). In multiple regression analysis, mean arterial pressure, body mass index (BMI), insulin levels, and age were correlated inversely and body surface area positively with large artery compliance and accounted for 39.2% of the variance; mean arterial pressure, female gender, age, and triglyceride levels inversely and cardiac output positively with small artery compliance and explained 56.4% of the variance; mean arterial pressure and age positively and cardiac output inversely with systemic vascular resistance and accounted for 91.4% of variance; and mean arterial pressure and BMI positively and cardiac output and body surface area inversely with vascular impedance and contributed to 37.6% of the variance. The observed deleterious impact of traditional CV risk factors on the arterial wall dynamics in asymptomatic young adults has important implications for preventive cardiology. Noninvasive pulsatile arterial function assessment may be helpful for evaluation of early vascular damage in a high-risk young population group.

Cardiovascular complications in diabetes mellitus

Diabetes is strongly associated with coronary, cerebral and peripheral arterial disease, as well as with microangiopathy. In those with diabetes, the extent of macrovascular disease increases and atherosclerotic plaques are more prone to rupture. Both hormonal abnormalities (insulin resistance that is typically present for many years before the onset of type 2 diabetes) and metabolic abnormalities contribute. Multi-targeted intensive therapy is imperative; however, unfortunately it is underutilized. Functional and structural derangements contribute to impaired arterial and ventricular compliance predisposing to congestive heart failure that is increasingly recognized to be a cause of morbidity and mortality in patients with diabetes.

A urodynamics protocol to optimally assess men with post‐prostatectomy incontinence

To propose a urodynamic protocol to comprehensively assess all parameters of post prostatectomy incontinence (PPI). Sixty men with a history of PPI after radical prostatectomy prospectively underwent a standardized video urodynamics protocol. A 7F urethral catheter was used for standard cystometry, abdominal leak point pressure (ALPP), and pressure flow measurements. The International Continence Society nomogram classified obstruction and further classification of obstruction was based on fluoro voiding cystourethrography and non-invasive flow rates (free Qmax). Twenty-four (40%) men had detrusor overactivity with 8 (13%) also having detrusor overactivity incontinence. Only one patient had impaired compliance. All men had urodynamic stress incontinence, but 21 (35%) men demonstrated it only after removal of the urethral catheter. For men leaking with and without the urethral catheter, the respective ALPP was significantly different, 86.3 and 67 cmH2O, respectively (P = 0.002). The men who leaked only in the absence of the urethral catheter had significantly higher ALPP measurements, P < 0.001. After reclassification using the fluoroscopic images of the bladder outlet and free Qmax, only 13.3% patients were obstructed. The proposed urodynamic protocol allows for an optimal assessment of bladder and sphincter dysfunction and outlet obstruction in men with PPI.

Highly Purified 1000-cSt Silicone Oil for Treatment of Human Immunodeficiency Virus-Associated Facial Lipoatrophy

BACKGROUND Among human immunodeficiency virus-infected individuals, facial lipoatrophy has become epidemic. Those affected are stigmatized, leading to psychological distress, social and career impediments, and impaired compliance to human immunodeficiency virus medications. Temporary treatment options are limited by excessive cost, necessity of frequent treatments, and lack of a natural look or feel beneath the skin. Affected patients require more persistent, affordable, safe, and effective treatment options. OBJECTIVE The objective was to evaluate the safety and efficacy of highly purified 1000-cSt silicone oil injected by microdroplet serial puncture technique for the treatment of human immunodeficiency virus-associated lipoatrophy. METHODS Data on 77 patients with a complete correction were analyzed to determine the number of treatments, amount of silicone, and time required to reach complete correction, relative to initial severity. RESULTS The volume of silicone, number of treatments, and time required to reach a complete correction were directly related to initial severity of lipoatrophy (p < 0.0001). Supple, even facial contours were routinely restored, with all patients tolerating treatments well. No adverse events were noted. CONCLUSION In this pilot trial, we have demonstrated that highly purified 1000-cSt silicone oil is a safe and effective treatment option for human immunodeficiency virus facial lipoatrophy. Longer-term safety and efficacy in human immunodeficiency virus patients remain to be proven.

Relationship between albumin excretion rate and aortic stiffness in untreated essential hypertensive patients.

To evaluate, in a group of nondiabetic essential hypertensive patients with normal renal function, the relationship between albumin excretion rate (AER) and carotid-femoral pulse wave velocity (PWV), as an index of aortic stiffness. Cross-sectional study. Outpatient hypertension clinic. Seventy patients with mild-to-moderate essential hypertension, aged 42 +/- 8 years, never pharmacologically treated. All subjects underwent routine laboratory tests, 24-h ambulatory blood pressure (BP) monitoring, measurement of carotid-femoral PWV, by means of a computerized method, and AER. Microalbuminuric patients (AER > or = 20 microg min(-1); n = 19), when compared with normoalbuminuric subjects, showed more elevated 24-h BP (136/88 +/- 10/10 vs. 128/83 +/- 7/6 mmHg; P < 0.001 and P = 0.013, for systolic and diastolic BP respectively) and higher values of carotid-femoral PWV (10.4 +/- 2 m s(-1) vs. 9.2 +/- 1.3; P = 0.006). This latter difference remained statistically significant, even after correction by ancova for 24-h systolic and diastolic BP, and body mass index (BMI, P = 0.016). Univariate regression analysis disclosed a tight correlation between AER and carotid-femoral PWV (r = 0.42; P = 0.0003). This association was confirmed in a multiple regression model (beta = 0.35; P = 0.009) in which, as independent variables, besides PWV, 24-h BP, age, serum glucose values, smoking status, gender and BMI, were added. Our results seem to confirm that microalbuminuria may represent the early renal manifestation of a widespread vascular dysfunction, and therefore it is an integrated marker of cardiovascular risk.

Mechanical ventilation effect on surfactant content, function, and lung compliance in the newborn rat.

Studies of ventilator-associated lung injury in adult experimental animal models have documented that high tidal volume (TV) results in lung injury characterized by impaired compliance and dysfunctional surfactant. Yet, there is evidence that, in neonates, ventilation with a higher than physiologic TV leads to improved lung compliance. The purpose of our study was to evaluate how lung compliance and surfactant was altered by high TV ventilation in the neonate. We utilized a new model (mechanically air-ventilated newborn rats, 4-8 d old), and used 40 or 10 mL/kg TV strategies. Age-matched nonventilated animals served as controls. In all animals, dynamic compliance progressively increased after initiation of mechanical ventilation and was significantly greater than basal values after 60 min (p < 0.01). Lung lavage total surfactant with both TV strategies (p < 0.05) and the large aggregate fraction (only in TV = 40 mL/kg; p < 0.01) were significantly increased by 60 min of mechanical ventilation, compared with control animals. Ventilation with 40 mL/kg TV for 60 min adversely affected the lung surfactant surface-tension lowering properties (p < 0.01). After 180 min of ventilation with 40 mL/kg TV, the lung total surfactant content and dynamic compliance values were no longer distinct from the nonventilated animals' values. We conclude that, in the newborn rat, mechanical ventilation with a higher than physiologic TV increases alveolar surfactant content and, over time, alters its biophysical properties, thus promoting an initial but transient improvement in lung compliance.

Effect of Aerobic Exercise on Left Ventricular Diastolic Filling and Arterial Compliance in Older Hypertensives

0583 Left ventricular diastolic dysfunction (LVDD) and impaired arterial compliance (IAC) may be subtle, early indices of vascular dysfunction with aging, sedentary lifestyle and hypertension. LVDD and IAC may impair exercise performance in those at risk who engage in therapeutic exercise training; while exercise testing may “unmask” LVDD and IAC among those starting such training programs and be used as a marker of risk improvement in addition to blood pressure lowering. PURPOSE: To evaluate the effect of aerobic exercise on LVDD and IAC in older hypertensive patients prior to starting and following an 8 week exercise training program. METHODS: Eight subjects participated in the study. Measures of LVDD (early filling flow velocity (E), late filling flow velocity (A), E/A ratio, isovolumic relaxation time (IVRT) and deceleration time (DT)) and IAC (compliance (C) and distensibility (D) in carotid and brachial arteries) were assessed using VingMed-5 cardiac imaging system at rest before and following an 8 week exercise training program. RESULTS: LVDD indices (E, A, E/A, IVRT and DT) remained unaltered throughout the study (0.68 ± .13 vs 0.68 ± .15m/s, 0.82 ± .19 vs 0.89 ± .16m/s, 0.81 ± .24 vs 0.76 ± .05, 92.6 ± 1.0 vs 86.9 ± 7.6msec and 288.9 ± 59.6 vs 279.7 ± 75.1msec, respectively). None of IAC indices (C and D) in carotid artery changed during the exercise program (0.70 ± .12 vs 0.77 ± .08 cm2/mmHgx10−3, 0.18 ± .02 vs 0.24 ± .03 1/mmHgx10−2, respectively); however, IAC indices (C and D) in brachial artery changed significantly following the exercise program (0.20 ± .02 vs 0.29 ± .05 cm2/mmHgx10−3, 0.18 ± .02 vs 0.22 ± .02 1/mmHgx10−2, p<.05, respectively). CONCLUSION: These data suggest that in older hypertensives 8 week exercise training significantly improves the peripheral (brachial artery) artery compliance whereas no improvement in more “central” (left ventricle and carotid artery) artery compliance. Supported by A.M Anderson Award, Lawson Health Research Institute.

A Case of HIV-Associated Facial Lipoatrophy Treated With 1000-cs Liquid Injectable Silicone

BACKGROUND Patients infected with the HIV may experience HIV-associated lipodystrophy, a symptom of which is facial lipoatrophy, a dramatic loss of subcutaneous facial tissue. This visible manifestation of HIV infection causes significant psychosocial pain for patients and has been associated with impaired compliance with medical regimens. OBJECTIVE To improve the appearance of facial lipoatrophy in a safe, long-lasting, expeditious, and relatively economical manner. METHODS An HIV-associated lipodystrophy patient with facial lipoatrophy underwent multiple sessions of soft-tissue augmentation therapy with liquid injectable silicone (LIS) using the microdroplet serial puncture technique. RESULTS Administration of LIS by the microdroplet serial puncture technique produced satisfactory improvement of areas of facial atrophy. The treatment time is limited, the patient discomfort and morbidity are minimal, and results are long lasting. Patients report significant satisfaction with treatment. CONCLUSION LIS administered by the microdroplet serial puncture technique is a safe and effective method for treating HIV-associated facial lipoatrophy and compares favorably with other methods of tissue augmentation.

ASSESSMENT OF BLADDER AND URETHRAL SPHINCTER FUNCTION BEFORE AND AFTER RADICAL RETROPUBIC PROSTATECTOMY

In a prospective study we analyzed the effects of radical retropubic prostatectomy (RRP) on detrusor and urethral sphincter function by comparing urodynamic status preoperatively with that during longitudinal followup. A total of 49 consecutive patients underwent urodynamics with pressure flow studies and Valsalva leak point pressure measurements 3 to 7 days before RRP (baseline), and then 1 and 8 months after surgery. We assessed bladder compliance, detrusor overactivity, detrusor contractility and intrinsic sphincter deficiency (ISD). There was no significant change in detrusor overactivity at 1 and 8 months of followup. Decreased bladder compliance was observed in 20.4% of patients at baseline, and in 38.7% and 30.6% at 1 and 8 months, respectively. De novo decreased compliance was detected in 18.4% and 10.2% of patients at the same points. Impaired bladder compliance was comparable to that before surgery in 20% of cases. Impaired detrusor contractility was detected in 42.8% of patients at baseline, and in 61.2% (p <0.05) and 42.8% at 1 and 8 months, respectively. De novo hypocontractility was observed in 28.6% and 10.2% of patients at 1 and 8 months, respectively. A strong association between detrusor overactivity and ISD was observed at 1 and 8 months (p <0.01). Following RRP detrusor hypocontractility and decreased bladder compliance represent de novo transient dysfunction probably due to bladder denervation and an established condition not influenced by the operation. The strong association between overactivity and ISD suggests that stress urinary incontinence increases urethral afferent nerve activity and induces involuntary detrusor contractions.

Routine bladder biopsies in men with bladder outlet obstruction?

Objectives To establish whether routine evaluation of light microscopic changes in bladder biopsies in men with graded bladder outlet obstruction correlates with urodynamic parameters and to evaluate the performance of two pathologists in bladder biopsy interpretation. Methods In 63 consecutive patients presenting with lower urinary tract symptoms suggestive of bladder outlet obstruction, the workup included bladder biopsies, which were semiquantitatively and independently evaluated by two pathologists for fibrosis, elastosis, muscle cell degeneration, inflammation, and additional remarkable findings. Furthermore, as determined by their general impression, the pathologists gave a diagnosis of normal or graded abnormality. The pathologists' performance was compared and the clinical and urodynamic data were correlated to the consensus histologic diagnoses. Results Fifty-four of 63 cases could be evaluated. The intraobserver and interobserver reproducibility were reasonable, with a kappa of 0.35 and 0.50, respectively. The consensus diagnosis of abnormal bladder biopsy correlated with impaired bladder compliance and capacity. However, no correlation was found between the presence and severity of histologic abnormalities and Schäfer class, urethral resistance factor, instability, postvoid residual urine volume, symptom score, and prostate volume. Conclusions Although abnormal bladder biopsies correlated significantly with impaired bladder capacity and compliance, routine evaluation of bladder biopsies is not indicated in the evaluation of bladder outlet obstruction.

Carbon dioxide attenuates pulmonary impairment resulting from hyperventilation*

Deliberate elevation of PaCO2 (therapeutic hypercapnia) protects against lung injury induced by lung reperfusion and severe lung stretch. Conversely, hypocapnic alkalosis causes lung injury and worsens lung reperfusion injury. Alterations in lung surfactant may contribute to ventilator-associated lung injury. The potential for CO2 to contribute to the pathogenesis of ventilator-associated lung injury at clinically relevant tidal volumes is unknown. We hypothesized that: 1) hypocapnia would worsen ventilator-associated lung injury, 2) therapeutic hypercapnia would attenuate ventilator-associated lung injury; and 3) the mechanisms of impaired compliance would be via alteration of surfactant biochemistry. Randomized, prospective animal study. Research laboratory of university-affiliated hospital. Anesthetized, male New Zealand Rabbits. All animals received the same ventilation strategy (tidal volume, 12 mL/kg; positive end-expiratory pressure, 0 cm H2O; rate, 42 breaths/min) and were randomized to receive FiCO2 of 0.00, 0.05, or 0.12 to produce hypocapnia, normocapnia, and hypercapnia, respectively. Alveolar-arterial oxygen gradient was significantly lower with therapeutic hypercapnia, and peak airway pressure was significantly higher with hypocapnic alkalosis. However, neither static lung compliance nor surfactant chemistry (total surfactant, aggregates, or composition) differed among the groups. At clinically relevant tidal volume, CO2 modulates key physiologic indices of lung injury, including alveolar-arterial oxygen gradient and airway pressure, indicating a potential role in the pathogenesis of ventilator-associated lung injury. These effects are surfactant independent.

Therapeutic hypercapnia is not protective in the in vivo surfactant-depleted rabbit lung.

Permissive hypercapnia because of reduced tidal volume is associated with improved survival in lung injury, whereas therapeutic hypercapnia-deliberate elevation of arterial Pco2-protects against in vivo reperfusion injury and injury produced by severe lung stretch. No published studies to date have examined the effects of CO2 on in vivo models of neonatal lung injury. We used an established in vivo rabbit model of surfactant depletion to investigate whether therapeutic hypercapnia would improve oxygenation and protect against ventilator-induced lung injury. Animals were randomized to injurious (tidal volume, 12 mL/kg; positive end-expiratory pressure, 0 cm H2O) or protective ventilatory strategy (tidal volume, 5 mL/kg; positive end-expiratory pressure, 12.5 cm H2O), and to receive either control conditions or therapeutic hypercapnia (fraction of inspired CO2, 0.12). Oxygenation (alveolar-arterial O2 difference, arterial Po2), lung injury (alveolar-capillary protein leak, impairment of static compliance), and selected bronchoalveolar lavage and plasma cytokines (IL-8, growth-related oncogene, monocyte chemoattractant protein-1, and tumor necrosis factor-alpha) were measured. Injurious ventilation resulted in a large alveolar-arterial O2 gradient, elevated peak airway pressure, increased protein leak, and impaired lung compliance. Therapeutic hypercapnia did not affect any of these outcomes. Tumor necrosis factor-alpha was not increased by mechanical stretch in any of the groups. Therapeutic hypercapnia abolished the stretch-induced increase in bronchoalveolar lavage monocyte chemoattractant protein-1, but did not affect any of the other mediators studied. Therapeutic hypercapnia may attenuate the impairment in oxygenation and inhibit certain cytokines. Because hypercapnia inhibits certain cytokines but does not alter lung injury, the pathogenic role of these cytokines in lung injury is questionable.

Prolaktinplasmaspiegel und Häufigkeit der endokrinologischen Begleitwirkungen unter Therapie mit den atypischen Neuroleptika

Elevations in prolactin plasma concentration occur with antipsychotics due to their dopamine D2 receptor antagonism. Hyperprolactinemia may be associated with both acute (galactorrhea, amenorrhea, decreased libido etc.) and chronic (predisposition to osteoporosis and cardiovascular disease) treatment emergent effects in both men and women associated with apparently impaired compliance. The aim of our study was to investigate these supposed effects regarding clinically relevant endocrinologic symptoms under routine treatment conditions with newer, atypical antipsychotics. Our findings confirm that amisulpride frequently leads to a remarkable elevation of prolactin plasma concentration, same - in minor degree - for risperidone. Under treatment with quetiapine and olanzapine just temporary elevated prolactin levels were registered. However, no correlation between prolactin levels and dosage could be found. In females treated with amisulpride acute hormonal side effects were seen in a clinically relevant manner. Features of illness itself, stress factors, concomitant medication or other patient's conditions are supposed to be relevant factors for acute endocrine symptomatology.