Coronary flow reserve in the contralateral artery increases after successful coronary angioplasty in patients with spontaneously visible collateral vessels

Due to the large variability in the reported contribution of bladder dysfunction to postprostatectomy incontinence and the impact this dysfunction may have on the outcome of selected treatment, we retrospectively reviewed the videourodynamic findings of bladder and sphincteric function in patients with postprostatectomy incontinence. The contributions of bladder and sphincteric causes of incontinence are determined. Ninety-two patients had multichannel videourdynamic testing performed as part of a comprehensive evaluation for incontinence at least 1 year after prostatectomy. Using a 6-French double-lumen catheter in the bladder and a 10-French catheter in the rectum, all pressures were recorded continuously while in the upright position. Valsalva leak point pressures (VLPP) were measured in the absence of a bladder contraction at a 150-ml volume and at 50-ml increments thereafter until maximum functional capacity was reached. Bladder compliance and bladder capacity were determined and the presence of detrusor instability (DI) was documented. Sixty-five patients (71%) presented after radical prostatectomy (RP) and 27 patients (29%) after transurethral resection of the prostate (TURP). The predominant urodynamic finding was sphincteric incompetence as VLPP were obtained in 85 patients (92%) and ranged from 12 to 120 cm water. DI was a common finding, occurring in 34 patients (37%), and classified as follows: a) phasic instability in 22/34, b) tonic instability in 3/34, and c) mixed phasic and tonic instability in 9/34. However, we found DI to be the sole cause of incontinence in only 3/92 patients (3.3%). There was no statistically significant difference in the incidence of sphincteric incompetence after RP or TURP; however, TURP patients had a higher incidence of DI, which was statistically significant (P=0.019). There was no correlation of incontinence severity and VLPP when comparing preoperative pad usage to VLPP < or =70 or > or =71 cm water. Although bladder dysfunction may be contributing problem in patients with postprostatectomy incontinence, it is rarely the only mechanism for this disorder. VLPP does not correlate with incontinence severity. Although sphincteric incompetence is the most common mechanism contributing to incontinence after prostatectomy, bladder dysfunction may coexist or be an isolated cause of postprostatectomy incontinence. Therefore, urodynamic studies are important to illustrate the exact cause(s) of incontinence in each individual patient after prostatectomy.     

A genetic defect resulting in mild low-renin hypertension

Severe low-renin hypertension has few known causes. Apparent mineralocorticoid excess (AME) is a genetic disorder that results in severe juvenile low-renin hypertension, hyporeninemia, hypoaldosteronemia, hypokalemic alkalosis, low birth weight, failure to thrive, poor growth, and in many cases nephrocalcinosis. In 1995, it was shown that mutations in the gene (HSD11B2) encoding the 11beta-hydroxysteroid dehydrogenase type 2 enzyme (11beta-HSD2) cause AME. Typical patients with AME have defective 11beta-HSD2 activity, as evidenced by an abnormal ratio of cortisol to cortisone metabolites and by an exceedingly diminished ability to convert [11-3H]cortisol to cortisone. Recently, we have studied an unusual patient with mild low-renin hypertension and a homozygous mutation in the HSD11B2 gene. The patient came from an inbred Mennonite family, and though the mutation identified her as a patient with AME, she did not demonstrate the typical features of AME. Biochemical analysis in this patient revealed a moderately elevated cortisol to cortisone metabolite ratio. The conversion of cortisol to cortisone was 58% compared with 0-6% in typical patients with AME whereas the normal conversion is 90-95%. Molecular analysis of the HSD11B2 gene of this patient showed a homozygous C-->T transition in the second nucleotide of codon 227, resulting in a substitution of proline with leucine (P227L). The parents and sibs were heterozygous for this mutation. In vitro expression studies showed an increase in the Km (300 nM) over normal (54 nM). Because approximately 40% of patients with essential hypertension demonstrate low renin, we suggest that such patients should undergo genetic analysis of the HSD11B2 gene.     

Coronary collateral blood-flow velocity improves with repeated coronary occlusions during angioplasty in patients with coronary artery disease and systemic hypertension

The heterogeneity of schizophrenia has led to a multitude of diagnostic criteria systems. Thus, the best strategy for schizophrenia research might be the use of several diagnostic systems simultaneously. This polydiagnostic approach can be associated with isolating subtypes of symptoms or patients. In this way, the authors present several approaches such as, first, dimensional approaches, second, cluster analyses, and third the selection of a very homogeneous subtype with standardized criteria. One homogeneous subtype can be represented by deficit schizophrenia according to Carpenter as defined by the Schedule of Deficit Syndrome.     

The connection between absence-like seizures and hypothermia induced by penicillin: possible implication on other animal models of petit mal epilepsy

In this study we investigated the relationship between penicillin-induced hypothermia and petit mal epilepsy induced by this proconvulsant antibiotic. In order to find a possible dose-dependent relationship, we used two doses: 1500.000 and 1000.000 U/kg b.wt., both known as being sufficient to induce absence-like attacks with subsequent spike and wave discharges (SWD) in electrocorticogram (ECoG). Because of experimental data suggesting penicillin binding to benzodiazepine receptor recognition site, we also studied penicillin-induced changes in body temperature after diazepam pretreatment. Results of this study clearly show that penicillin in doses known to induce petit mal-like epilepsy concomitantly induces statistically significant dose-dependent decrease in body temperature. Pretreatment with diazepam completely prevents both penicillin-induced hypothermia and SWDs. On the other hand, both the diazepam and mixed diazepam + penicillin treatments did not significantly alter body temperature. These results suggest, however, that at least some of the penicillin effects described could be assigned to its binding to the benzodiazepine receptor recognition site at GABA(A) ionophore. This may have an important clinical implication because the inhibitory action of penicillin at the benzodiazepine receptor recognition site could account for the mechanism of penicillin-induced unspecific encephalopathies in humans. The relationship between petit mal epilepsy and hypothermia sheds new light on the action mechanisms of penicillin-induced absence seizures.     

Expression and function of recombinant endothelial nitric oxide synthase gene in canine basilar artery after experimental subarachnoid hemorrhage

BACKGROUND AND PURPOSE: Gene transfer with recombinant viral vectors encoding vasodilator proteins may be useful in therapy of cerebral vasospasm after subarachnoid hemorrhage (SAH). Relaxations mediated by nitric oxide are impaired in cerebral arteries affected by SAH. The present study was designed to determine the effect of SAH on the efficiency of ex vivo adenovirus-mediated gene transfer to canine basilar arteries and to examine whether expression of recombinant endothelial nitric oxide synthase (eNOS) gene may have functional effects on vasomotor reactivity of spastic arteries affected by SAH. METHODS: Replication-deficient recombinant adenovirus vectors encoding bovine eNOS (AdCMVeNOS) and Escherichia coli beta-galactosidase (AdCMVbeta-Gal) genes were used for ex vivo gene transfer. Rings of basilar arteries obtained from control dogs and dogs exposed to SAH were incubated with the vectors in minimum essential medium. Twenty-four hours after gene transfer, expression and function of the recombinant genes were evaluated by (1) histochemical or immunohistochemical staining, (2) beta-galactosidase protein measurement, and (3) isometric tension recording. RESULTS: Transduction with AdCMVbeta-Gal and AdCMVeNOS resulted in the expression of recombinant beta-galactosidase and eNOS proteins mostly in the vascular adventitia. The expression of beta-galactosidase protein was approximately 2-fold higher in SAH arteries than in normal arteries. Endothelium-dependent relaxations caused by bradykinin and substance P were suppressed in SAH arteries. The relaxations to bradykinin were significantly augmented in both normal and SAH arteries after AdCMVeNOS transduction but not after AdCMVbeta-Gal transduction. The relaxations to substance P were augmented by AdCMVeNOS transduction only in normal arteries. Bradykinin and substance P caused relaxations even in endothelium-denuded arteries, when the vessels were transduced with AdCMVeNOS. These endothelium-independent (adventitia-dependent) relaxations to bradykinin observed after AdCMVeNOS transduction were similar between normal and SAH arteries, whereas those to substance P were significantly reduced in SAH arteries compared with normal arteries. CONCLUSIONS: These results suggest that expression of recombinant proteins after adenovirus-mediated gene transfer may be enhanced in cerebral arteries affected by SAH and that successful eNOS gene transfer to spastic arteries can at least partly restore the impaired nitric oxide-mediated relaxations through local (adventitial) production of nitric oxide.     

ATP-dependent glutathione conjugate export pump

KCP4 cells are resistant to cisplatin and have a GS-X pump different from MRP. The GS-X pump was suggested to be involved in reducing the accumulation of cisplatin in KCP-4 cells. The expression of cMOAT was 4-to 6-fold higher in KCP-4 cells and two other cisplatin-resistant human cell lines. It is still not clear whether the cisplatin resistance in KCP-4 cells are attributed to cMOAT. Other members of the MRP/GS-X pump family have been reported. Amino acid sequence of EBCR of rabbit is 91% identical to that of human cMOAT. On the view of cancer chemotherapy, it is very important to understand the structure and function of GS-X pumps since they may be involved in not only drug resistance but also drug metabolism and side effects.     

Cloning and expression of a novel tissue specific 17beta-hydroxysteroid dehydrogenase

The 11beta-hydroxysteroid dehydrogenases (11betaHSD) modulate intracellular glucocorticoid levels, with 11betaHSD1 converting cortisone to cortisol mainly in the liver, and 11betaHSD2 performing the reverse reaction in sodium transporting epithelia and placenta. We have attempted to expand the 11betaHSD subfamily by isolating homologous cDNA's. Expressed Sequence Tag databases were screen with segments of the 11betaHSD1 enzyme amino acid sequence and Pan1b identified as a new member of the short chain alcohol dehydrogenase superfamily. Northern blot analysis of total RNA from human tissues showed a single band at 1.9 kb and a tissue specific pattern of expression with high levels in the liver, adrenal carcinoma, lung and small intestine, and much lower levels in the kidney, heart and placenta. Expression studies in a Chinese hamster ovary cell line (CHOP) showed that Pan1b did not metabolize glucocorticoids. However, preliminary studies on a range of substrates revealed that Pan1b acted as a dehydrogenase on 17beta-hydroxysteroids, although further kinetic analysis was confounded by large amounts of endogenous oxidoreductase activity in CHOP cells. These studies suggest the existence of a novel human 17betaHSD enzyme.     

Seasonal changes in the activity of antioxidative defense in the kidneys of the euthermic ground squirrel (Citellus citellus)

The aim of this work was to determine the activity of the antioxidant enzymes: superoxide dismutase (EC 1.15.1.1; SOD), catalase (EC 1.11.1.6; CAT), glutathione peroxidase (EC 1.11.1.9; GSH-Px), glutathione-S-transferase (EC 2.5.1.18; GST), glutathione reductase (EC 1.6.4.2; GR) and the low molecular mass antioxidants: ascorbic acid (ASA) and vitamin E (vit E) in the kidney of ground squirrels during circannual changes. Keeping the ground squirrel at the temperature of thermic neutrality (30 degrees C) provides a stable euthermic state during the whole year and thus any change is due to the circannual rhythm. The highest specific activity of all examined antioxidative defense enzymes in the kidney was found in the spring, when ground squirrels are seasonally the most active. In the summer, lower specific activity of GSH-Px as well as of SOD and CAT were noted and, when expressed per g wet mass, only a decrease in GSH-Px activity was recorded. In the kidney of ground squirrels kept at 30 degrees C, the lowest specific activity of all examined enzymes was found during the winter and, when expressed per g wet mass, only the SOD activity was lower than in the spring and summer. Higher amounts of vitamins C and E were found in the ground squirrel kidneys in the summer. The results obtained in this work demonstrate that circannual regulation of metabolic activity, which is inherent to seasonal hibernators, is also expressed at the level of antioxidative defense in the kidneys.     

Intake and digestion by Holstein steers consuming diets based on litter harvested after different numbers of broiler growing periods or with molasses addition before deep-stacking

We determined the effects on feed intake and digestibility by Holstein steers of 1) the number of broiler growing periods before litter harvest and dietary level of broiler litter and 2) level of molasses added to broiler litter before deep-stacking. In Exp. 1, eight steers (179+/-7.4 kg average BW) were used in two simultaneous 4 x 4 Latin squares (2 x 4 factorial) with 21-d periods. Broiler litter harvested after one, three, or six 6-wk growing periods (1P, 3P, and 6P, respectively) mixed with .5 or 1.5% BW of ground corn (.5C and 1.5C, respectively) was consumed ad libitum. Bermudagrass hay was fed to 1P, 3P, and 6P steers at .5% BW and was ingested ad libitum by Control steers, along with feeding of .5 or 1.5% BW of corn (DM basis). Broiler litter was 63, 43, and 35% NDF, 2.2, 3.5, and 4.1% N, and 18, 30, and 27% ash for 1P, 3P, and 6P, respectively. Total tract digestibility of NDF was 53.7, 29.4, 50.4, 58.1, 31.3, 30.8, 34.1, and 49.5% (SE 3.50), and digestible OM intake was 2.21, 1.70, 2.27, 2.39, 2.26, 3.18, 2.93, and 3.34 kg/d (SE .160) for .5C-Control, .5C-1P, .5C-3P, .5C-6P, 1.5C-Control, 1.5C-1P, 1.5C-3P, and 1.5C-6P, respectively. In Exp. 2, five steers (228+/-6.0 kg average BW) were used in a 5 x 5 Latin square with 21-d periods. Offered diets were 15% bermudagrass hay and 60% broiler litter (6P of Exp. 1; DM). Molasses was offered at 0, 3.2, or 6.7% of total DM, with the balance of the diet composed of corn. Molasses for two treatments was mixed with litter at meals, whereas for two other treatments molasses and litter were mixed before deep-stacking. Only a few minor treatment effects on intakes and digestibilities occurred. In conclusion, digestible OM intake by growing steers was less for litter harvested after one broiler growing period than after three or six when fed with only .5% BW of corn, although the effect of the number of periods was negligible with corn given at 1.5% BW. Molasses addition before deep-stacking or at meals did not enhance feeding value of litter harvested after six broiler growing periods.