Oxidized-LDL and paraoxonase-1 as biomarkers of coronary artery disease in patients with sleep-disordered breathing.

UNLABELLED: Coronary Artery Disease (CAD) and OBJECTIVES: Sleep Disordered Breathing (SDB) are both oxidative stress disorders. SDB intermittent hypoxia induces oxidative stress, and reduces NO(·) availability, causing endothelial dysfunction. Low-density lipoprotein (LDL) peroxidation is involved in atherosclerosis, and is reported in SDB. Oxidized LDL (ox-LDL) and malondialdehyde (MDA) are lipid peroxidation markers. High-density lipoprotein (HDL) presents antiatherosclerotic properties related to paraxonase-1 (PON-1) activity. PON-1 hydrolyseyses lipid peroxides as ox-LDL. This study compares the relationship of HDL and PON-1, the lipid peroxidation markers ox-LDL and MDA, and 8-OHdG DNA damage marker in the association of SDB and CAD. DESIGN AND METHODS: 29 controls and 27 cases with CAD (defined as > 30% coronary narrowing) patients were included. The apnea-hypopnea index (AHI), and several lipid and oxidative stress parameters were measured in these patients. RESULTS: AHI is increased in CAD patients, and PON-1 activity and HDL levels are decreased. Regression analyseyses showed that lower PON-1 activity and higher ox-LDL levels are important CAD predictors, compared to HDL or MDA levels and present an age-dependent increase. Nitrites and nitrates, indirect NO(·) markers, are positive vs correlated with PON-1 and are negatively correlated to ox-LDL. SDB is not correlated to PON-1 activity decrease or ox-LDL increase. AHI is inversely correlated to HDL levels. CONCLUSIONS: These results indicate that PON-1 and ox-LDL are important predictors of CAD, however they may not be directly related to SDB.

Role of endothelin-1 in the active constriction of human atherosclerotic coronary arteries.

BACKGROUND: Atherosclerotic coronary arteries are prone to constriction but the underlying causes are incompletely understood. We tested the hypothesis that endothelin-1 (ET-1), a potent vasoconstrictor, contributes to the heightened tone of atherosclerotic human coronary arteries. METHODS AND RESULTS: In 8 patients with coronary artery disease (CAD) and 8 patients with angiographically smooth coronary arteries (normal), we infused BQ-123, an antagonist of the ET(A) receptor, into a major coronary artery (infused artery) at 40 nmol/min for 60 minutes. The infused artery in the CAD patients contained a >50% stenosis. Using quantitative angiography, we compared the dilation of the infused artery with another, noninfused coronary artery. To estimate the magnitude of the contribution of ET-1 to coronary tone, we compared the dilation to BQ-123 with that elicited by intracoronary nitroglycerin (200 microgram). BQ-123 induced significant dilation in the normal arteries (7.3% at 60 minutes, P<0.001 versus noninfused arteries) and a greater dilation in the CAD arteries (16.3% at 60 minutes, P<0.001 versus infused normal arteries). The dilation at stenoses was particularly pronounced (21.6% at 60 minutes, P<0.001 versus infused CAD arteries). Compared with the dilation from nitroglycerin, ET-1 contributed to 39% of the coronary tone in normal arteries, 74% of tone in CAD arteries, and 106% of tone at stenoses (P<0.01). CONCLUSIONS: ET-1 accounts for nearly all the resting tone in atherosclerotic coronary arteries, especially at stenoses. Inhibitors of ET-1, by relieving constriction, may significantly lessen the hemodynamic significance of coronary stenoses and thereby reduce myocardial ischemia.

Current indications for open stone surgery in the treatment of renal and ureteral calculi.

PURPOSE: The development and advances in extracorporeal shock wave lithotripsy and endourological procedures have greatly diminished the need for open surgery in the treatment of renal and ureteral stones. We reviewed our experience with open stone surgery to determine the current indications and efficacy of this treatment modality. MATERIALS AND METHODS: Hospital and office charts, operative notes and records, and pertinent radiographic studies of all patients undergoing open stone surgery from January 1991 through December 1995 at 3 university affiliated hospitals were reviewed. Patient characteristics, stone burden, indications, surgical factors and outcomes were reviewed for each patient. RESULTS: Of 780 procedures performed for stone removal, 42 were open surgical procedures (5.4%) including pyelolithotomy in 15 (extended pyelolithotomy or pyelonephrolithotomy in 7), anatrophic nephrolithotomy in 14, ureterolithotomy in 7 and radial nephrolithotomy in 6. There were 24 men and 18 women ranging in age from 1 to 90 years (mean age 51.5). The most common indications for open surgery were complex stone burden (55%); failure of extracorporeal shock wave lithotripsy or endourological treatment (29%); anatomic abnormalities such as ureteropelvic junction obstruction, infundibular stenosis and/or renal caliceal diverticulum (24%); morbid obesity (10%) and co-morbid medical disease (7%). Mean estimated blood loss was 428 cc. Average hospital stay was 6.4 days. The stone-free rate after surgery was 93%. Five patients had minor postoperative complications that resolved with appropriate therapy. CONCLUSIONS: While most patients with renal and ureteral stones can be treated with less invasive techniques, open stone surgery continues to represent a reasonable alternative for a small segment of the urinary stone population.

Periurethral pseudocyst following cystoscopic collagen injection.

Periurethral injection of collagen is widely used for treatment of stress urinary incontinence. It has been shown to be an effective, low risk, minimally invasive surgical procedure to treat carefully selected patients with intrinsic sphincter deficiency. Adverse reactions and complications from this technique are rare. We report an unusual complication following cystoscopic injection of collagen.

Sonography of the female urethra.

OBJECTIVE: The purpose of this study was to explore the role of sonography for women with urethral symptoms and a suspected urethral diverticulum. SUBJECTS AND METHODS: Nineteen women with urethral symptoms underwent voiding cystourethrography (VCUG) and transvaginal, transperineal, and urethral sonography (using a catheter-based transducer). VCUGs and sonograms were evaluated for diverticula, defined on sonography by direct visualization of the neck connecting the periurethral sac with the urethral lumen. The diverticular neck, size, location, and shape were noted. Lesions revealed by sonography as not connected to the urethra were also noted. RESULTS: Of 19 women, 14 had urethral diverticula and one had two diverticula, for a total of 15 diverticula. On sonography the diverticula ranged in diameter from 2 mm to 5 cm. Both sonography and VCUG showed 13 of the 15 diverticula. In addition, sonography revealed two infected periurethral cysts, a periurethral leiomyoma, a diffuse urethritis, and scarring or deformity of one patient's urethra from a prior diverticulectomy. On sonography, eight of the 13 diverticula wrapped around more than 50% of the urethral circumference. The neck was precisely seen (by definition) in 13 of 15 diverticula on sonography and in two of 13 diverticula on VCUG. CONCLUSION: Sonography is useful in this group of women with urethral symptoms and suspected urethral diverticula. It provides information on the extent and location of the diverticular neck, both of which are important in surgical excision. Also, sonography provides information on lesions not connected to the urethra. Sonography may prove useful in a broader group of women with urethral symptomatology.

Use of polyglycolic acid mesh to support parenchymal closure following partial nephrectomy.

PURPOSE: We describe the use of absorbable mesh for closure of a large parenchymal defect created by partial nephrectomy. MATERIALS AND METHODS: A circular piece of polyglycolic acid mesh was measured to approximate the diameter of the parenchymal defect and the edges were sutured to the renal capsule in a running fashion. RESULTS: This technique has been used in 3 patients without complications. This approach has been particularly helpful for repairing large and irregular renal parenchymal defects. CONCLUSIONS: Use of polyglycolic acid mesh is effective for rapid, hemostatic closure of the kidney in association with partial nephrectomy.

Atherosclerosis and acute arterial thrombosis in rabbits: a model using balloon desendothelization without dietary intervention.

Acute thrombosis can be induced in rabbits by a triggering protocol using Russell's viper venom and histamine given after 8 months of a 1% cholesterol diet and balloon desendothelization. In the present study, we tested the hypothesis that aortic desendothelization performed 4 months before the triggering protocol without a high cholesterol diet is a highly effective and less expensive way of producing arterial atherosclerosis and thrombosis. Nineteen male New Zealand white rabbits on a normal diet were studied. The control group (N = 9) received no intervention during the 4-month observation period, while the other group (N = 10) was submitted to aortic balloon desendothelization using a 4F Fogarty catheter. At the end of this period, all animals were killed 48 h after receiving the first dose of the triggering treatment. Eight of 10 rabbits (80%) in the balloon-trauma group presented platelet-rich arterial thrombosis while none of the animals in the control group had thrombus formation (P < 0.01). Thus, this model, using balloon desendothelization without dietary manipulation, induces arterial atherosclerosis and thrombosis and may provide possibilities to test new therapeutic approaches.

Atherosclerosis and acute arterial thrombosis in rabbits: a model using ballon desendothelization without dietary intervention

Acute thrombosis can be induced in rabbits by a triggering protocol using Russell's viper venom and histamine given after 8 months of a 1 per cent cholesterol diet and balloon desendothelization. In the present study, we tested the hypothesis that aortic desendothelization performed 4 months before the triggering protocol without a high cholesterol diet is a highly effective and less expensive way of producing arterial atherosclerosis and thrombosis. Nineteen male New Zealand white rabbits on a normal diet were studied. The control group (N = 9) received no intervention during the 4-month observation period, while the other group (N = 10) was submitted to aortic balloon desendothelization using a 4F Fogarty catheter. At the end of this period, all animals were killed 48 h after receiving the first dose of the triggering treatment. Eight of 10 rabbits (80 per cent) in the balloon-trauma group presented platelet-rich arterial thrombosis while none of the animals in the control group had thrombus formation (P<0.01). Thus, this model, using balloon desendothelization without dietary manipulation, induces arterial atherosclerosis and thrombosis and may provide possibilities to test new therapeutic approaches.

Comparison of effects of suture materials on wound healing in a rabbit pyeloplasty model.

OBJECTIVES: To compare the effects of chromic catgut, polyglactic acid, polydioxanone (PDS), and polytrimethylene carbonate suture on urothelial healing in a rabbit model simulating pyeloplasty. METHODS: Pyeloureterotomies were performed on 8-week-old rabbits [12 rabbits (24 renal units) and 3 control rabbits] and closed with interrupted 7-0 sutures. At 10 days, 5 weeks, and 12 weeks postoperatively, we assessed the upper tracts by examining microscopic sections of the renal pelvis and upper ureter. Acute and chronic inflammation, foreign body reaction, and fibrosis/scar formation were assessed blindly and scored from 0 to 4. RESULTS: Histologic evidence of acute and chronic inflammation and foreign body reaction was most severe at 10 days and 5 weeks in pyeloureterotomies closed with chromic catgut. There was mild inflammation in those closed with polyglactic acid at 10 days, but it was minimal in those closed with polyglactic acid, PDS, and polytrimethylene carbonate at 5 and 12 weeks. Reabsorption of polyglactic acid was complete by 5 weeks, but was incomplete with the other three sutures at that time. By 12 weeks, there was persistent suture in 50% of the renal units closed with polydioxanone and in 100% of those closed with polytrimethylene carbonate. No animal developed a renal calculus. CONCLUSIONS: Because of the mild inflammatory response and rapid tissue reabsorption of polyglactic acid in this animal model, this suture appears to be the best suture for pyeloplasty.

Antegrade techniques of collagen injection for post-prostatectomy stress urinary incontinence: the Washington University experience.

Treatment of sphincteric incontinence after radical retropubic prostatectomy remains a clinical challenge. Antegrade techniques of collagen injection are a relatively new method for treatment of post-prostatectomy incontinence. Early experience with this approach has demonstrated improved outcomes compared to the traditional retrograde technique. Overall response rates of 70% cure or significant improvement compare favorably with previously reported series. The theoretical advantages of this method include improved visualization of vesicourethral anastomosis and improved access to the bladder neck. Furthermore, suprapubic catheter drainage avoids the risks of collagen molding around the catheter. The use of a flexible cystoscope for this approach is a recent modification. The smaller diameter of the flexible cystoscope has facilitated access and reduced anesthetic requirements. This system affords unimpeded delivery of collagen to regions of the bladder neck where the submucosa accommodates the injectable agent. In addition, this modality allows more precise needle positioning to provide correct angle and depth of penetration into the submucosal plane. Short-term success rates of this procedure are encouraging and suggest that it may become the primary approach. While these antegrade techniques are more aggressive than the traditional retrograde approach, they are relatively simple and draw upon principles familiar to all urologists. It is hoped that the new flexible antegrade approach will further improve our results. Longer-term follow-up studies with larger numbers of patients will be required to see whether we can accomplish this goal.

Predisposing factors of systemic fungal infections of the genitourinary tract.

We reviewed 50 patients with genitourinary fungal infections between 1982 and 1992. Infections were classified as simple--localized to the bladder and complex--demonstrated evidence of upper tract and/or systemic infection. Predisposing factors of fungal infections, including diabetes mellitus, prolonged Foley catheter drainage and corticosteroid use, were not significantly different. The incidence of obstructive uropathy (88% versus 20%), malnutrition (88% versus 48%), neoplasia (56% versus 16%), renal failure (24% versus 8%) and prolonged antibiotic use (60% versus 32%) were significantly greater in patients with complex infections. The incidence of fungemia in patients with complex infections was 81% with an associated mortality rate of 36%. Of the patients with complex infections 56% required urological intervention. Given the high incidence of obstructive uropathy with complex fungal infections, upper tract imaging is essential.

Study of the usefulness of optic fundi examination of patients with hypertension in a clinical setting.

The purpose of this study was to evaluate the usefulness of direct opthalmoscopy by non-opthalmologists in patients with hypertension. In a cross-sectional survey, we analysed the association between optic fundi abnormalities, individually and according to the criteria of Keith and Wagener (KW), with blood pressure and duration of known hypertension in 400 non-diabetic hypertensive patients. The optic fundi abnormalities were more frequent in patients with diastolic blood pressure (DBP) > 105 mm Hg (P = 0.002), SBP > 180 mm Hg (P < 0.0001) and with a duration of known hypertension > 3 years (P = 0.002). The severity of hypertension did not vary in parallel with the KW classes I and II: 34.5% of patients classified as KW I had a diastolic pressure of > 105 mm Hg compared with only 25.3% of those classified as KW II. Class III abnormalities were infrequent (2.5% of the whole cohort). In a logistic regression model, diffuse arteriolar narrowing was associated with DBP (P = 0.002) and age (P < 0.001). Abnormalities of the arteriovenous crossings were associated with SBP (P = 0.001) and duration of disease (P = 0.008). The positive predictive value of any fundoscopic abnormality to estimate the severity of hypertension was 59% and the negative value was 60%. The results of this study demonstrate that optic fundi examination by internists and cardiologists does not give an accurate assessment of the severity of hypertension in most patients, and that the Keith-Wagener classification of retinopathy has a limited applicability.(ABSTRACT TRUNCATED AT 250 WORDS)

CWR22: androgen-dependent xenograft model derived from a primary human prostatic carcinoma.

The long-term propagation of primary human prostate cancer (PCA) in vivo or in vitro has been rare. Most such PCAs are phenotypically different from most PCAs in humans; i.e., they make little prostate specific antigen and respond little, if at all, to androgen deprivation. A serially transplantable, primary human PCA, designated CWR22, exhibits a clonal cytogenetic aberration, causes high elevations of prostate specific antigen in the peripheral blood of nude mice, and is unusually responsive to androgen deprivation as compared with other xenografts. Studies of mRNA from CWR22 have demonstrated the expression of prostate specific antigen and the epidermal growth factor receptor family including erbB1/epidermal growth factor receptor, erbB2/neu, and erbB3, but not erbB4. A ligand for these receptors, the neu differentiation factor, is also expressed.

[The sensitivity and specificity of the clinical, serological and tomographic diagnosis of Toxoplasma gondii encephalitis in the acquired immunodeficiency syndrome (AIDS)]. / Sensibilidade e especificidade do diagnóstico clínico, sorológico e tomográfico da encefalite por Toxoplasma gondii na síndrome da imunodeficiência adquirida (SIDA).

Toxoplasmic encephalitis (TE) is among the most common neurologic affections and it is the most prevalent cause of intracerebral mass lesions in AIDS patients. All patients with AIDS hospitalized at the Hospital de Clínicas de Porto Alegre between May/85 and December/91 (516 cases) had their files revised to determinate TE prevalence, serology, sensitivity and specificity of the computed tomography (CT) brain scan, clinical findings and serology to make its diagnosis. The prevalence on CT was 13% (presumptive diagnosis). Blood serology and cerebrospinal (CSF) serology to toxoplasma were positive respectively in 65% and 49%. Autopsies of 125 patients were also revised with a prevalence of 22% (definite diagnosis). CT scan had 65% of sensitivity and 82% of specificity. Sensitivity and specificity of serology on blood was respectively 95% and 30%, while the cerebrospinal fluid (CSF) serology had 77% of sensitivity and 56% of specificity. The following clinical findings were considered: fever (sensitivity = 92%; specificity = 56%), neurological focal signs (sensitivity = 59%; specificity = 82%) and headache (sensitivity = 41%; specificity = 69%). We conclude that, based on the high serology sensitivity and high CT scan specificity, they constitute an useful approach to make TE diagnosis.

[The pattern of the clinical use of digitalis. The need for a reassessment]. / Padrão de utilização clínica dos digitálicos. Necessidade de reavaliação.

PURPOSE: To evaluate the pattern of utilization of digitalis in an academic hospital. METHODS: Clinical files of all patients admitted in medical wards at the Hospital de Clínicas de Porto Alegre were studied. Data were collected during five different days, three in the winter and two in the summer, keeping an interval of at least two weeks between each data collection. Heart failure diagnosis was evaluated objectively by means of a score proposed by Carlson et al. RESULTS: From a total number of 881 patients, 114 (13%) were receiving digoxin. Mean age was 66 +/- 13 years and 47% were males. Considering the patients who were taking digoxin, 32% presented scores compatible with definite or possible heart failure; 26% had atrial flutter or fibrillation; 18% had heart failure and supraventricular tachyarrhythmias; and in 24% no clear indications were found according to our criteria. Previous use of digoxin was found in 85% of the patients and 32% were withdrawn during the hospitalization. Considering just the patients who had no reason for using digoxin, only 44% had the drug withdrawn. CONCLUSION: According to current criteria, many hospitalized patients receive digoxin without a definite indication. These data suggest that reassessment of the use of digitalis should be incorporated into clinical practice.

[The neuropathological findings in the acquired immunodeficiency syndrome (AIDS): a review of 138 cases]. / Achados neuropatológicos na síndrome da imunodeficiência adquirida (SIDA): revisão de 138 casos.

This is an autopsy study performed in a retrospective fashion to determine the incidence of diseases that could affect the central nervous system in AIDS. For this purpose, 138 autopsies of patients with AIDS performed at the "Hospital de Clínicas de Porto Alegre", Brazil, between January/85 and December/90 were studied. All the brains were evaluated macroscopically and microscopically mainly through hematoxylin-eosin staining and if necessary special techniques like PAS, Grocott, Giemsa and Ziehl-Nielsen were done. Results have revealed 29 (21%) cases with cerebral toxoplasmosis; cryptococcosis in 17 (12%); tuberculosis in two (1%) and one case (0.7%) of candidiasis. Besides these inflammatory lesions, 15 (10%) presented vascular lesion; 8 (6%) had gliosis and 7 (5%) cases had suggestive findings of HIV encephalopathy. We can conclude that the CNS is a important target affected by AIDS and that cerebral toxoplasmosis is the principal disease in the CNS in AIDS patients.

Lack of tolerance to imipramine or mianserine in two animal models of depression.

Few clinical reports describe tolerance induced by antidepressants and this question is considered an unsolved problem for clinical use of this group of drugs. The present report deals with the effects of imipramine and mianserine on two animal models of depression, after acute or prolonged previous treatment with these antidepressants. Imipramine and mianserine potentiated amphetamine-induced anorexia both after acute administration or after prolonged previous treatment with each drug. Mianserine effects were not detected in the behavioral despair test and imipramine reduced rats immobility equally after acute and prolonged previous treatment. It was concluded that imipramine and mianserine do not induce detectable tolerance when previously administered to animals submitted to amphetamine anorexia or behavioral despair.