Lack of lithium-like behavioral and molecular effects in IMPA2 knockout mice.

Lithium is a potent mood-stabilizing medication in bipolar disorder. Despite 50 years of clinical use, the mechanism of action is unknown. Multiple effects have been attributed to lithium including the uncompetitive inhibition of inositol monophosphatase (IMPase). IMPA2, one of the genes that encode IMPase, is located in a region with linkage to bipolar disorder. Owing to the role of IMPase in cell signaling and the possibility that this enzyme is a target for mood-stabilizing drugs, we generated IMPA2(-/-) mice. Possible involvement of IMPase in complex behaviors related to affective disorders was assessed by monitoring the behavior of the IMPA2(-/-) mice in the forced swim test, the tail suspension test (TST), the elevated zero-maze and open field test. It has been described that chronically lithium-treated mice exhibit reduced immobility time in the forced swim test and decreased exploratory behavior. We found increased rearing of IMPA2(-/-) mice in the open field, suggesting an increased exploratory behavior. Although immobility time of IMPA2(-/-) female but not male mice in the forced swim test was reduced, no difference was found between male and female IMPA2(-/-) and IMPA2(+/+) mice in the TST and overall there was no clear effect of the deletion of IMPA2 on depression-like behavior. Frontal cortex IMPase activity and inositol levels in the IMPA2(-/-) mice did not differ from IMPA2(+/+) mice, but kidney inositol levels were reduced. In conclusion, phenotypic characterization of the IMPA2(-/-) mouse indicates that deleting IMPA2 does not mimic the effects of lithium treatment.     

Diagnostic compatibility of structural and haemodynamic parameters in open‐angle glaucoma patients

Purpose: Current evidence indicates that alteration in ocular blood flow may be relevant in open‐angle glaucoma (OAG) patients independent of intraocular pressure (IOP). Presently, the lack of an adequate methodology capable of assessing all vascular beds limits the clinical role of blood flow parameters in glaucoma management. We aimed to compare differences in retinal nerve fibre layer (RNFL) thickness and retrobulbar haemodynamics between OAG patients and healthy age‐matched control subjects. Methods: Sixty eyes of 30 OAG patients and 30 healthy age‐matched controls were enrolled into the prospective, randomized study. Retinal nerve fibre layer thickness was analysed by scanning laser polarimetry (SLP). Standard SLP parameters were determined, including: average temporal, superior, nasal, inferior thickness (TSNIT); superior and inferior averages; TSNIT standard deviation (TSNIT‐SD), and nerve fibre indicator (NFI). Retrobulbar haemodynamics were assessed using colour Doppler imaging (CDI). Peak systolic velocity (PSV), end‐diastolic velocity (EDV), pulsatility index (PI) and resistivity index (RI) in the ophthalmic artery (OA), central retinal artery (CRA) and short posterior ciliary artery (SPCA) were evaluated. Results: The RNFL in OAG patients was statistically significantly thinner compared with that in age‐matched controls: the NFI was 24.9 ± 10.24 in OAG patients and 16.13 ± 7.95 in healthy controls (p < 0.05). Statistically significant differences were observed: CRA PSV was 20.54 ± 7.84 cm/second in OAG subjects and 16.5 ± 6.19 cm/second in healthy controls (p = 0.0038); OA EDV was 8.99 ± 4.71 cm/second in OAG subjects and 5.93 ± 3.23 cm/second in healthy controls (p = 0.0048). Correlation analysis of NFI was in positive association with CRA EDV (r = 0.395; p < 0.05) and CRA PI (r = 0.403; p < 0.05) in OAG subjects, but no statistically significant association was seen in healthy controls. Conclusions: Statistically significant thinning of the RNFL in association with reduced retrobulbar blood flow velocities was observed in OAG patients. Combining ocular structural alterations with ocular circulation assessment may increase our ability to elucidate potential IOP‐independent glaucomatous risk factors.     

Intravenous pyelography in children with urinary tract infection and vesicoureteral reflux

In a previous study of the radiologic evaluation of children with urinary tract infection it was recommended that IVP be performed in all patients with either abnormal ultrasonographic or voiding cystourethrographic findings. However, the benefit from IVP was believed to be questionable in children with normal ultrasonography findings and vesicoureteral reflux of only a low grade (I or II of V). To gain a better understanding of the need for IVP in the radiologic evaluation of such children, the database was expanded and the findings concerning ultrasonography and IVP were analyzed in 52 children with urinary tract infection and vesicoureteral reflux seen during the last 3 years. Of a total of 72 instances of reflux, 44 (61.1%) were of low grade (I or II), 14 of medium grade (III), and 14 of high grade (IV or V). Of the 44 urinary systems with low-grade reflux, results were as follows: renal ultrasonography appeared normal in 38 and in 34 of these, the IVP also appeared normal; in the other four, only minor and negligible changes were seen with IVP. Surgical intervention was not necessary in any of these 38 urinary systems. In six systems with low-grade vesicoureteral reflux but with abnormal ultrasonography findings, IVP results were also abnormal, and surgery was necessary in two instances. Of the 14 urinary systems with medium-grade reflux, ultrasonography appeared normal in ten but in six of these the IVP appeared abnormal.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of epidural anesthesia for cesarean delivery on maternal femoral arterial and venous, uteroplacental, and umbilical blood flow velocities and waveforms

The effect of epidural anesthesia on the maternal femoral arterial and venous, uteroplacental, and umbilical circulations was studied by the pulsed Doppler technique in 13 women undergoing elective cesarean delivery. Resistance and pulsatility indices of umbilical arterial velocity waveforms did not change with the use of epidural anesthesia. In the uteroplacental circulation, these indices increased in 11 patients, suggesting an increase in resistance. Reduction of sympathetic tone in resistance and capacitance vessels was reflected in the femoral artery by an increase in systolic and end-diastolic velocities, a reversal of the post-systolic backward flow, and an increase in mean velocity. The latter also occurred in the femoral vein. The diameters of these large maternal vessels did not change. This study suggests an impairment in uteroplacental circulation associated with a drop in peripheral vascular resistance and an increase in leg blood flow after epidural anesthesia.     

Polycystic kidneys as the presenting feature of tuberous sclerosis

Tuberous sclerosis is an inherited neurocutaneous disorder characterized by seizures, mental retardation, cutaneous lesions and visceral hamartomas. We describe a 17-year-old boy in whom polycystic kidneys of the adult type were fortuitously detected on routine check-up. The patient enjoyed good health and had no evidence of renal dysfunction. Closer scrutiny of his past history and his physical and laboratory findings disclosed that he had tuberous sclerosis. Our case adds to the scant reported experience with the association of tuberous sclerosis and adult-type polycystic kidneys, and suggests that a search of additional manifestations of tuberous sclerosis is warranted in children in whom adult-type polycystic renal disease is detected.     

Citrate clearance in children receiving continuous venovenous renal replacement therapy

Anticoagulation is usually indicated in patients receiving continuous renal replacement therapy (CRRT) to prevent clotting of the extra-corporeal circuit. While heparin is the most frequently used anticoagulant, regional citrate anticoagulation is becoming the preferred choice in those patients at high risk for bleeding. However, it has been widely claimed that to avoid citrate toxicity, CRRT with citrate anticoagulation should utilize diffusive clearance (e.g., continuous venovenous hemodialysis). We studied citrate clearance in five children who received citrate anticoagulation during CRRT with a COBE PRISMA machine and an M-60 (AN-69) filter. The blood flow rate ranged from 50 to 150 ml/min (2.1-8.0 ml/kg per min). Citrate was infused in the circuit circulation as an acid citrate dextrose (ACD) solution at a rate of 1.6-3.7% of the blood flow rate to maintain the circuit ionized calcium (iCa) <0.5 mmol/l. Calcium-free replacement fluid with reduced alkali (NaHCO3 20 mEq/l) was infused in pre-filter mode at a rate of 1,800-2,000 ml/h per 1.73 m(2). In a separate central line, CaCl2 (0.8%) was infused (rate 25-50% of ACD infusion) to maintain systemic iCa between 1.0 and 1.3 mmol/l. Citrate concentration was measured using an enzymatic assay. Total CRRT duration was 1,224 h. Twenty-four filters were changed due to clotting, with a mean filter life of 51 h. Mean (range) citrate levels (mmol/l) were (1) before initiating CRRT ( n=2): patient baseline 0.13 (0.1-0.15), (2) during CRRT ( n=7): circuit 4.54 (3.95-6.25), effluent 4.31 (3.95-5.46), and patient 0.69 (0.30-1.13). Sieving coefficients for urea and citrate were 0.88-0.97 and 0.88-1.0, respectively. Citrate clearance (31-38 ml/min per 1.73 m(2)) was similar to that of urea (31-38 ml/min per 1.73 m(2)), and when evaluated in two patients, remained unchanged after substituting half of the convective clearance [continuous venovenous hemofiltration (CVVH)] by diffusive clearance [continuous venovenous hemodiafiltration (CVVHDF)]. The post-filter citrate load (mean+/-SD) delivered to the five patients during CRRT was 1.06+/-0.62 mmol/kg per hour. With the exception of alkalosis in one patient, no other complications were observed. Renal function recovered in all patients. We conclude that citrate anticoagulation in children is feasible, effective, and safe. Sufficient citrate clearance to prevent its toxic accumulation is achieved by convective clearance (CVVH) alone and diffusive clearance (CVVHDF) does not appear to be mandatory when utilizing citrate anticoagulation during CRRT.     

Recognizing spatial patterns: a noisy exemplar approach

Models of categorization typically rely on the use of stimuli composed of well-defined dimensions (e.g., Ashby & Maddox (1998) in Choice, decision, and measurement: Essays in honor of R. Duncan Luce, p. 251-301, Mahwah, NJ: Erlbaum). We apply a similar approach to the analysis of recognition memory. Using a version of short-term recognition paradigm (Sternberg, Science 153 (1966) 652), we asked whether NEMO Sternberg's, a noisy exemplar summed-similarity model, could account for variation in mean performance on individual trials. NEMO provided a very good overall fit to recognition data from three experiments. However, its failure to fit data for certain lists of stimuli suggested a revision of the summed-similarity assumption. Our model-based analysis showed that subjects used interitem similarity, in addition to probe-item similarity, as the basis for their decisions. This represents a major departure from existing recognition models that assume subjects' judgments depend exclusively on the summed similarity of the probe to the study items.     

Ocular perfusion abnormalities in diabetes

PURPOSE: To review the role of ocular perfusion in the pathophysiology of diabetic retinopathy, one of the leading causes of irreversible blindness in the industrialized world. METHODS: We carried out a Medline search of the literature published in English or with English abstracts from 1966 to 2000 using various combinations of relevant key words. RESULTS: Hyperglycaemia leads to a wide variety of vascular abnormalities at the microvascular and macrovascular levels, including abnormal autoregulation. CONCLUSION: Three major aspects of ocular perfusion in diabetic retinopathy require additional investigation. Firstly, the precise mechanisms that link elevated glucose to dysfunction of retinal vascular cells need to be identified. Secondly, those factors that lead to both capillary dropout and to angiogenesis, twin processes that are linked to tissue hypoxia and lead to excess perfusion, increased risk of extravascular leakage and frank haemorrhage, must be carefully delineated. Finally, once specific knowledge of disease fundamentals has been amassed, tests of therapies to reverse or prevent these pathological processes can move forward.     

Routine postoperative imaging is important after ureteroscopic stone manipulation

PURPOSE: Improved fiber optics and advanced intracorporeal lithotripsy devices have significantly decreased the incidence of complications during ureteroscopic procedures. Despite recent reports suggesting that radiographic imaging may not be necessary in all individuals after routine ureteroscopy silent obstruction may develop in some, ultimately resulting in renal damage. We determined the incidence of postoperative silent obstruction at our institution and assessed the need for routine functional radiographic studies after ureteroscopy. MATERIALS AND METHODS: We retrospectively reviewed the charts of 320 patients who underwent a total of 459 ureteroscopic procedures for renal or ureteral calculi in a 3-year period. Complete followup with imaging was available for 241 patients (75%). Average patient age was 47.2 years. The variables of interest reviewed included preoperative pain, preoperative obstruction, targeted calculous site, stone-free rate, postoperative pain and postoperative obstruction. Mean followup was 5.4 months (range 2 to 43). RESULTS: A total of 241 patients with complete followup were identified in this analysis. Preoperative pain was present in 202 patients (84%) and 168 (70%) had preoperative obstruction. Overall targeted calculous clearance was successful in 73% of the patients and an additional 15.8% had residual fragments less than 4 mm. The renal, proximal or mid and distal ureteral stone-free rate was 32.1%, 81.9% and 90.5%, while in an additional 46.4%, 6.3% and 6.7% of cases, respectively, residual fragments were less than 4 mm. Of the 241 patients 30 (12.3%) had obstruction postoperatively due to residual stone in 25 (83.3%), stricture in 3 (10%), edema of the ureteral orifice in 1 (3.3%) and a retained encrusted stent in 1 (3.3%). Postoperatively obstruction correlated with postoperative pain in 23 of the 30 patients (76.7%). Pain was present postoperatively in 30 of the 211 patients (14%) without evidence of ureteral obstruction postoperatively. However, silent obstruction developed in 7 patients (23.3%) or 2.9% of the total cohort. All 7 patients underwent secondary ureteroscopy to alleviate obstruction. A single patient ultimately received chronic hemodialysis for renal failure, 1 was lost to followup and in 5 there was documented successful resolution of the cause of obstruction. CONCLUSIONS: Our analysis suggests that silent obstruction remains a potentially significant complication after stone management. Relying on postoperative pain to determine the necessity of postoperative imaging places patients at risk for progressive renal failure due to unrecognized obstruction. Therefore, we recommend that imaging of the collecting system should be performed by excretory urography, spiral computerized tomography or ultrasound within 3 months after routine ureteroscopic stone treatment to avoid the potential complications of unrecognized ureteral obstruction.