Residual fragments following ureteroscopic lithotripsy: incidence and predictors on postoperative computerized tomography.

PURPOSE: Residual fragments following ureteroscopy for calculi may contribute to stone growth, symptoms or additional interventions. We reviewed our experience with ureteroscopy for calculus disease to define the incidence and establish factors predictive of residual fragments. MATERIALS AND METHODS: Records associated with 667 consecutive ureteroscopic lithotripsy procedures for upper urinary calculi were reviewed. In 265 procedures (40%) computerized tomography was done between 30 and 90 days postoperatively. They comprised the study group. Residual fragments were defined as any residual ipsilateral stone greater than 2 mm. RESULTS: Included in the study were 121 men and 127 women with a mean age of 47 years. Mean target stone diameter was 7.6 mm. The stone location was the kidney in 30% of cases, ureter in 50%, and kidney and ureter in 20%. Residual fragments were detected on computerized tomography after 101 of 265 procedures (38%). Pretreatment stone size was associated with residual fragments at a rate of 24%, 40% and 58% for stones 5 or less, 6 to 10 and greater than 10 mm, respectively (p <0.001). Additionally, stone location in the kidney (p <0.001) or the kidney and ureter (p = 0.044), multiple calculi (p = 0.003), longer operative time (p = 0.008) and exclusive use of flexible ureteroscopy (p = 0.029) were associated with residual fragments. In a multivariate model only pretreatment stone diameter greater than 5 mm was independently associated with residual fragments after ureteroscopy (diameter 6 to 10 and greater than 10 mm OR 2.03, p = 0.03 and OR 3.74, p = 0.003, respectively). CONCLUSIONS: Of patients who underwent ureteroscopic lithotripsy for calculi 38% had residual fragments by computerized tomography criteria, including more than 50% with stones 1 cm or greater. Such data may guide expectations regarding the success of ureteroscopy in attaining stone-free status.

Activated macrophages inhibit enterocyte gap junctions via the release of nitric oxide.

Enterocytes exist in close association with tissue macrophages, whose activation during inflammatory processes leads to the release of nitric oxide (NO). Repair from mucosal injury requires the migration of enterocytes into the mucosal defect, a process that requires connexin43 (Cx43)-mediated gap junction communication between adjacent enterocytes. Enterocyte migration is inhibited during inflammatory conditions including necrotizing enterocolitis, in part, through impaired gap junction communication. We now hypothesize that activated macrophages inhibit gap junctions of adjacent enterocytes and seek to determine whether NO release from macrophages was involved. Using a coculture system of enterocytes and macrophages, we now demonstrate that "activation" of macrophages with lipopolysaccharide and interferon reduces the phosphorylation of Cx43 in adjacent enterocytes, an event known to inhibit gap junction communication. The effects of macrophages on enterocyte gap junctions could be reversed by treatment of macrophages with the inducible nitric oxide synthase (iNOS) inhibitor l-Lysine omega-acetamidine hydrochloride (l-NIL) and by incubation with macrophages from iNOS(-/-) mice, implicating NO in the process. Activated macrophages also caused a NO-dependent redistribution of connexin43 in adjacent enterocytes from the cell surface to an intracellular location, further suggesting NO release may inhibit gap junction function. Treatment of enterocytes with the NO donor S-nitroso-N-acetylpenicillamine (SNAP) markedly inhibited gap junction communication as determined using single cell microinjection of the gap junction tracer Lucifer yellow. Strikingly, activated macrophages inhibited enterocyte migration into a scraped wound, which was reversed by l-NIL pretreatment. These results implicate enterocyte gap junctions as a target of the NO-mediated effects of macrophages during intestinal inflammation, particularly where enterocyte migration is impaired.

Dopaminergic polymorphisms in Tourette syndrome: association with the DAT gene (SLC6A3).

Tourette syndrome (TS) is a chronic neuropsychiatric disorder characterized by involuntary motor and phonic tics. The pattern of inheritance and associated genetic abnormality has yet to be fully characterized. A dopaminergic abnormality in this disorder is supported by response to specific therapies, nuclear imaging, and postmortem studies. In this protocol, dopaminergic polymorphisms were examined for associations with TS and attention-deficit hyperactivity disorder (ADHD). Polymorphisms investigated included the dopamine transporter (DAT1 DdeI and DAT1 VNTR), dopamine receptor (D4 Upstream Repeat and D4 VNTR), dopamine converting enzyme (dopamine beta-hydroxylase), and the acid phosphatase locus 1 (ACP1) gene. DNA was obtained from 266 TS individuals +/- ADHD and 236 controls that were ethnicity-matched. A significant association, using a genotype-based association analysis, was identified for the TS-total and TS-only versus control groups for the DAT1 DdeI polymorphism (AG vs. AA, P = 0.004 and P = 0.01, respectively). Population structure, estimated by the genotyping of 27 informative SNP markers, identified 3 subgroups. A statistical re-evaluation of the DAT1 DdeI polymorphism following population stratification confirmed the association for the TS-total and TS-only groups, but the degree of significance was reduced (P = 0.017 and P = 0.016, respectively). This study has identified a significant association between the presence of TS and a DAT polymorphism. Since abnormalities of the dopamine transporter have been hypothesized in the pathophysiology of TS, it is possible that this could be a functional allele associated with clinical expression.

Norepinephrine transporter polymorphisms in Tourette syndrome with and without attention deficit hyperactivity disorder: no evidence for significant association.

Noradrenergic abnormalities have been proposed in the pathophysiology of Tourette syndrome and attention-deficit hyperactivity disorder. Patients with Tourette syndrome with (n=115) and without (n=110) attention-deficit hyperactivity disorder were evaluated for association with two single nucleotide polymorphisms of the norepinephrine transporter gene (SLC6A2); a T-182C single nucleotide polymorphism located in the 5' flanking promoter region and a silent mutation (G1287A) occurring in exon 9. A polymerase chain reaction restriction enzyme assay was developed for the T-182C single nucleotide polymorphism based on a prior sequencing methodology. In this case-control study, no association was identified between either polymorphism and Tourette syndrome or attention-deficit hyperactivity disorder. In a small subset, these NET polymorphisms did not predict therapeutic response to the noradrenergic transporter inhibitor atomoxetine. Further research with additional NET polymorphisms and larger sample sizes are indicated in the pursuit of biomarkers for therapeutic responders.

Methodologic factors affect the measurement of anti-basal ganglia antibodies.

An autoimmune etiology has been proposed for a variety of movement disorders, making the detection of autoantibodies a high investigative priority. Recognizing the existence of different methodologic approaches to identify these antibodies, we sought to investigate the effects of tissue preparation, antibody selection, and Western immunoblot detection methods on outcome. ELISA and immunoblotting studies were performed in healthy controls evaluating non-pathogenic autoantibodies. Our results indicate that enhanced data can be obtained by using fresh, rather than frozen, postmortem tissue homogenates for Western immunoblots and enzyme-linked immunosorbent assays and support the use of electrochemiluminescent detection for Western immunoblots. Molecular localization is significantly affected by the selected standard. Removal of lipids from homogenates does not affect anti-basal ganglia antibody (ABGA) results. Methodological variables should be taken into consideration when performing and interpreting neuroimmunological assays using sera or isolated IgG.