The modern endoscopic approach to ureterocele

PURPOSE: During the last 20 years the surgical approach to ureterocele has evolved from major open surgery to minimally invasive endoscopic puncture. We believe that the endoscopic approach decreases the need for open surgical procedures. We identified specific factors that predict the need for repeat surgery. MATERIALS AND METHODS: We reviewed the charts of 60 new patients with ureterocele treated with primary endoscopic incision between 1991 and 1995. Followup ranged from 4 to 62 months (mean 20). Mode of presentation, ureterocele location, associated vesicoureteral reflux and association of the ureterocele with a duplex system were evaluated. Ureterocele wall thickness was assessed subjectively via radiographic and cystoscopic methods, and categorized as thin, intermediate and thick. RESULTS: All 9 patients with a single system ureterocele had an intravesical ureterocele. No patient had associated reflux nor did any require a secondary open procedure. In 3 cases new onset ipsilateral reflux into the ureterocele spontaneously resolved. Of the 51 patients with a duplex system and associated ureterocele 19 (37%) required a secondary open procedure. The ureterocele was intravesical and ectopic in 22 (43%) and 29 (57%) cases, respectively. Reflux was associated with the ureterocele in 27 patients (53%), and 12 (44%) required a secondary open procedure. A total of 11 patients underwent ureteral reimplantation of 15 refluxing renal units and only 2 renal units required ureteral tapering. Reflux is no longer present in 14 of the 15 renal units (93%). Patients with a thick walled ureterocele required repeat puncture more frequently than those with a nonthick ureterocele. CONCLUSIONS: With the use of modern endoscopic techniques children with intravesical and single system ureteroceles require secondary open surgery less frequently than those with ectopic and duplex system ureteroceles. The mode of presentation does not predict the need for a repeat open procedure. Thick walled ureteroceles require repeat endoscopic puncture more frequently than thin and intermediate walled ureteroceles.     

Coping with dementia: evaluation of four nonpharmacologic interventions

To evaluate nonpharmacologic interventions, caregivers (65 women, 38 men) and their dementia-diagnosed spouses (patients) were randomized to one of four treatment programs (cognitive stimulation, dyadic counseling, dual supportive seminar, and early-stage day care) or to a wait-list control group. Assessments occurred initially and at postintervention (3 months). Patients were evaluated on memory, verbal fluency, and problem-solving ability, and caregivers were assessed on marital interaction, emotional status, and physical health, along with stress, coping, and social support. Caregivers also completed a program evaluation. Repeated measures procedures showed that patients in the cognitive stimulation group demonstrated more improvement over time in cognitive outcomes, and caregivers decreased in depressive symptoms. Early-stage day-care and dual supportive seminar group caregivers reported a decrease in hostility and a decrease in use of negative coping strategies, respectively. Although qualitatively derived benefits differed across groups, similarities in program content reduced the potential for quantitative differentiation among the groups.     

General anesthetics selectively modulate glutamatergic and dopaminergic signaling via site-specific phosphorylation in vivo

Isoflurane, propofol and ketamine are representative general anesthetics with distinct molecular mechanisms of action that have neuroprotective properties in models of excitotoxic ischemic damage. We characterized the effects of these agents on neuronal glutamate and dopamine signaling by profiling drug-induced changes in brain intracellular protein phosphorylation in vivo to test the hypothesis that they affect common downstream effectors. Anesthetic-treated and control mice were killed instantly by focused microwave irradiation, frontal cortex and striatum were removed, and the phosphorylation profile of specific neuronal signaling proteins was analyzed by immunoblotting with a panel of phospho-specific antibodies. At anesthetic doses that produced loss of righting reflex, isoflurane, propofol, and ketamine all reduced phosphorylation of the activating residue T183 of ERK2 (but not of ERK1); S897 of the NR1 NMDA receptor subunit; and S831 (but not S845) of the GluR1 AMPA receptor subunit in cerebral cortex. At sub-anesthetic doses, these drugs only reduced phosphorylation of ERK2. Isoflurane and ketamine also reduced phosphorylation of spinophilin at S94, but oppositely regulated phosphorylation of presynaptic (tyrosine hydroxylase) and postsynaptic (DARPP-32) markers of dopaminergic neurotransmission in striatum. These data reveal both shared and agent-specific actions of CNS depressant drugs on critical intracellular protein phosphorylation signaling pathways that integrate multiple second messenger systems. Reduced phosphorylation of ionotropic glutamate receptors by all three anesthetics indicates depression of normal glutamatergic synaptic transmission and reduced potential excitotoxicity. This novel approach indicates a role for phosphorylation-mediated down-regulation of glutamatergic synaptic transmission by general anesthetics and identifies specific in vivo targets for focused evaluation of anesthetic mechanisms.     

Pharmacologic profile of chemically stable analogs of peptide leukotrienes

Peptide leukotrienes are potent constrictors of airway smooth muscle but lack chemical stability. Replacement of the natural triene backbone of leukotrienes with 9-(x-heptylphenyl)-7-nonenoic acid (x = 2, 3, or 4) renders these analogs chemically stable and pharmacologically active. The para, meta and ortho substitutions of the heptyl (C7H15) moiety were combined with the different leukotriene peptide substitutions of glutathionyl, C-peptide of leukotriene C4, cysteinylglycinyl, D-peptide of leukotriene D4, and cysteinyl, E-peptide of leukotriene E4 rendering nine active analogs. The pharmacology of these analogs was evaluated in isolated guinea-pig tracheal strips. The para-substituted C-peptide analog was the most potent; however, it was 100-fold less potent than leukotriene C4. The contractile activities of the para- and meta-substituted C-peptide analogs were enhanced by L-serine borate (45 mM), indicating they were substrates for gamma-glutamyl transpeptidase. FPL55712 (10 microM) failed to antagonize the substituted C-peptide analogs independent of the presence of L-serine borate. The contractile activities of the three substituted D-peptide analogs were enhanced by L-cysteine, indicating they are all substrates for aminopeptidase. The para-substituted D-peptide analog was the most potent D-peptide analog, but it was 10- and 1,000-fold less active than the para-substituted C-peptide analog and leukotriene D4, respectively. The para- and meta-substituted E-peptide analogs were approximately 1,000-fold less potent than leukotriene E4, and like the substituted D-peptide analogs, they were antagonized by FPL55712. In contrast, the ortho-substituted E-peptide analog was devoid of intrinsic activity but antagonized leukotriene E4-induced contractions.(ABSTRACT TRUNCATED AT 250 WORDS)