Urinary diversion following radical pelvic surgery

PURPOSE OF REVIEW: To describe the reconstructive techniques in urinary diversion utilized by the gynecologist after radical pelvic surgery. The radical resection of pelvic malignancies remains an important part of the armamentarium of the gynecological oncologist. Techniques in continent urinary diversion should be used to restore these women to an acceptable quality of life. Reconstruction is the surgical challenge of this and future generations of pelvic surgeons. It is imperative that pelvic surgeons begin to consider the quality of life and the functional reintegration into society of the patients we are able to salvage with these radical surgical efforts. RECENT FINDINGS: The advent of continent urostomies has significantly improved the quality of life of patients who undergo radical tumor resection involving the bladder. Such techniques prevent the need for urostomy bags, and thus all the physical and psychological ramifications associated with them. We will review recent literature associated with the complications and the management of these complications. SUMMARY: Familiarity with techniques in continent urinary diversion by the gynecologist is an important part of the management of patients with gynecological malignancies and permanent bladder atony.     

Stent-graft treatment of extracranial carotid and vertebral arterial lesions

Five patients with pseudoaneurysms of the carotid artery (n = 4) and an arteriovenous fistula of the vertebral artery (n = 1) were treated with stent-grafts. Commercially made devices were used in all but one of the patients. In four of the five patients, the pathology was successfully excluded. One patient had a small type-I endoleak. There were no immediate procedure-related complications or neurologic sequalae. All experienced immediate resolution of symptoms. One patient was lost to follow-up after discharge and another died 2 weeks after intervention. The remaining patients remained asymptomatic with patent stent-grafts after follow-up periods of 14, 16, and 46 months, respectively.     

Endoscope-assisted microsurgery for microvascular compression syndromes

OBJECTIVE: To discuss the results of endoscope-assisted surgery in microvascular decompression (MVD) of Cranial Nerves (CNs) V, VII, and VIII. METHODS: Neuroendoscopy was used as an adjunct to the surgical microscope in the MVD of the trigeminal (17 patients), facial (10 patients), and vestibulocochlear (1 patient) nerves in a series of 28 consecutive patients. After a standard microsurgical approach to CNs V, VII, and VIII, the endoscope was used to inspect all aspects of neural anatomy, to assess vascular compression, and to check the results of the decompression. Endoscope use was graded in four categories: Grade I, used but no definite role; Grade II, visualization assisted; Grade III, procedure assisted; and Grade IV, primary role. The usefulness of the endoscope was evaluated in each case. RESULTS: The endoscope was useful in visualizing the anatomy in all cases. It was especially useful in establishing trigeminal vein compression of CN V in Meckel's cave; observing multiple sources of vascular compression; ensuring adequate decompression after cauterization of vein, insertion of the Teflon felt, or a pexy procedure; and permitting observation of the compression of CN VII at the root exit zone by small arteries and veins. In six patients with trigeminal neuralgia, the trigeminal vein was cauterized and divided by using endoscopic vision only because the venous compression was not completely visualized with the microscope. During a follow-up period of 6 to 52 months (mean, 29 mo; median, 40 mo), all patients were asymptomatic and receiving no medication. CONCLUSION: The endoscope is a useful adjunct to MVD in the treatment of trigeminal neuralgia, hemifacial spasm, and disabling positional vertigo or tinnitus.     

TIPS reduction with use of stents or stent-grafts

This report describes new techniques to perform TIPS reduction in patients with post-TIPS complications. Methods included hourglass-shaped stents and stent-grafts, and parallel stents and stent-grafts. All procedures were technically successful, resulting in increased portosystemic gradients and decreased symptoms, although patient outcomes were mixed. None of the patients experienced recurrent variceal hemorrhage or ascites in short-term follow-up. Stent-grafts have the advantage of immediate exclusion of blood flow outside the reducing stent, resulting in an immediate reduction of the caliber of the shunt. Techniques that allow fine adjustment of shunt diameters may have further advantages.     

Regional brain responses to serotonin in major depressive disorder

BACKGROUND: Positron Emission Tomography (PET) studies have reported altered resting regional brain glucose metabolism in mood disorders. This study examines the relationship of such changes to serotonin system abnormalities associated with depression. METHODS: Thirteen male medication free subjects who were inpatients with a DSM-IIIR major depressive disorder and seven healthy male subjects underwent an [18F]-fluorodeoxyglucose (18FDG) PET scan on consecutive days. Three hours prior to 18FDG subjects received single blind placebo or fenfluramine. Comparisons of voxel level regional glucose metabolic rate responses (rCMRglu) between groups in the two states were performed with SPM99. RESULTS: Unlike healthy male subjects who have significant increases in rCMRglu in prefrontal and parietal cortical regions after receiving fenfluramine, depressed male subjects have no significant increases in rCMRglu. CONCLUSIONS: Blunted increases in rCMRglu in response to fenfluramine in prefrontal and parietal cortex are consistent with our previous pilot study and the indoleamine hypothesis of depression. Differences in specific brain regions affected between this study and previous studies may be attributable to gender differences.     

Are there racial differences in the way patients with psychotic disorders are treated at their first hospitalization?

BACKGROUND: It is now well documented that both black and white patients with severe mental illness are likely to use different types of treatment facilities, have different lengths of hospital stays, and receive different types and dosages of psychotropic medications. It is still uncertain, however, whether these differences exist at the early stages of treatment. METHOD: We examined treatment patterns for a countywide sample of patients with psychotic disorders recruited at their initial psychiatric hospitalization. Illness characteristics, prior treatment histories, admission conditions, and psychotropic medication use during this hospitalization were compared for both black and white patients. RESULTS: Black patients were less likely to have had out-patient treatment prior to their first hospitalization and were more likely to be hospitalized in public than in community psychiatric units than were white patients. Black patients were also more likely to be hospitalized primarily for a behavioral disturbance and escorted to the hospital by the emergency medical services or police, while white patients were more often hospitalized primarily for subjective suffering. These patterns were particularly significant for those with a non-schizophrenia diagnosis. However, there were few statistically significant differences between black and white patients on psychotropic medication use during the first hospitalization. CONCLUSIONS: Differences during the early stages of treatment between black and white patients with psychotic disorders appear to arise most prominently before, rather than during, their first hospitalization.     

Pharmacological and behavioral properties of A-349821, a selective and potent human histamine H3 receptor antagonist

Histamine H3 receptors regulate the release of a variety of central neurotransmitters involved in cognitive processes. A-349821 ((4'-(3-((R,R)2,5-dimethyl-pyrrolidin-1-yl)-propoxy)-biphenyl-4-yl)-morpholin-4-yl-methanone) is a novel, non-imidazole H3 receptor ligand, displaying high affinity for recombinant rat and human H3 receptors, with pKi values of 9.4 and 8.8, respectively, and high selectivity for the H3 receptor versus H1, H2, and H4 histamine receptors. A-349821 is a potent H3 receptor antagonist in a variety of models using recombinant human and rat receptors, reversing agonist induced changes in cyclic AMP formation (pKb= 8.2 and pKb= 8.1, respectively), [35S]-GTPgammaS binding (pKb= 9.3 and pKb= 8.6, respectively) and calcium levels (human pKb= 8.3). In native systems, A-349821 competitively reversed agonist induced inhibition of electric field stimulated guinea-pig ileum (pA2= 9.5) and histamine-mediated inhibition of [3H]-histamine release from rat brain cortical synaptosomes (pKb= 9.2). Additionally, A-349821 inhibited constitutive GTPgammaS binding at both rat and human H3 receptors with respective pEC50 values of 9.1 and 8.6, demonstrating potent inverse agonist properties. In behavioral studies, A-349821 (0.4 mg/kg-4 mg/kg) potently blocked (R)-alpha-methylhistamine-induced dipsogenia in mice. The compound also enhanced cognitive activity in a five-trial inhibitory avoidance model in spontaneously hypertensive rat (SHR) pups at doses of 1-10mg/kg, with the 1mg/kg dose showing comparable efficacy to a fully efficacious dose of ciproxifan (3mg/kg). These doses of A-349821 were without effect on spontaneous locomotor activity. Thus, A-349821 is a novel, selective non-imidazole H3 antagonist/inverse agonist with balanced high potency across species and favorable cognition enhancing effects in rats.     

Lipophilic 4-imidazoly-1,4-dihydropyridines: synthesis, calcium channel antagonist activity and protection against pentylenetetrazole-induced seizure

A group of alkyl, cycloalkyl and aryl ester analogs of nifedipine, in which the o-nitrophenyl group at position 4 is replaced by a 2-phenyl-4(5)-imidazolyl substituent, were synthesized and evaluated as calcium channel antagonist using the high K+ contraction of guinea-pig ileal longitudinal smooth muscle, and the activity of 5a-d, 8b and 8f against pentylenetetrazole (PTZ)-induced seizure was assessed. The results for symmetrical esters showed that lengthening of the methylene chain in C3 and C5 ester substituents increased activity. When increasing of the length is accompanied by increasing the hindrance, the activity decreased. In contrast to symmetrical derivatives, comparison of the activities of asymmetrical esters showed that increasing the length of the methylene chain was accompanied by a decrease in their activity. The results demonstrate that 8a was more active, and 5c and 8f were similar in effect to that of the reference drug nifedipine. The time-course of anticonvulsant effect on PTZ-induced seizure threshold of said compounds was assessed and showed that increasing the lipophilicity decreases the time needed for maximum effect. Mice treated with intraperitoneal injection of 25 mg/kg of these derivatives all exhibited increase seizure threshold as compared with control.     

Concentration dependency of modulatory effect of amlodipine on P-glycoprotein efflux activity of doxorubicin--a comparison with tamoxifen

Modulators of P-glycoprotein (P-gp) can enhance or limit the permeability of a number of therapeutic agents that are considered substrates of this efflux pump protein. The modulatory effect of amlodipine (4-dihydropyridine calcium antagonist) on P-gp efflux activity has not been fully elucidated. We have studied the concentration dependency of its modulatory effect and compared it qualitatively with tamoxifen (a non-esteroid anti-estrogen). The investigation was conducted on transmembrane efflux of doxorubicin at a fixed concentration of 5 microM across a Caco-2 monolayer in the presence of various concentrations of amlodipine or tamoxifen. The maximum flux of doxorubicin from basolateral to apical (ba) occurred at 4.5 microM amlodipine and at 0.02 microM tamoxifen. At higher concentrations, the apical to basolateral (ab) flux and the net flux of doxorubicin (ba - ab) declined steadily in a concentration-dependent manner. We analysed the observed net flux data by fitting different mathematical models to the data. A composite sigmoidal Emax/Imax (stimulatory/inhibitory) model was found to be the most appropriate to define the system. The observed and calculated parameters supported the modulatory role of both compounds and clearly indicated that the stimulation and inhibition of transmembrane efflux occurred simultaneously in the presence of amlodipine or tamoxifen. It was concluded that amlodipine, similar to tamoxifen, modulated the transporter-dependent transmembrane flux of the P-gp substrate in a concentration-dependent manner.