Tumorigenicity assessment of cell therapy products: The need for global consensus and points to consider.

Pluripotent stem cells offer the potential for an unlimited source for cell therapy products. However, there is concern regarding the tumorigenicity of these products in humans, mainly due to the possible unintended contamination of undifferentiated cells or transformed cells. Because of the complex nature of these new therapies and the lack of a globally accepted consensus on the strategy for tumorigenicity evaluation, a case-by-case approach is recommended for the risk assessment of each cell therapy product. In general, therapeutic products need to be qualified using available technologies, which ideally should be fully validated. In such circumstances, the developers of cell therapy products may have conducted various tumorigenicity tests and consulted with regulators in respective countries. Here, we critically review currently available in vivo and in vitro testing methods for tumorigenicity evaluation against expectations in international regulatory guidelines. We discuss the value of those approaches, in particular the limitations of in vivo methods, and comment on challenges and future directions. In addition, we note the need for an internationally harmonized procedure for tumorigenicity assessment of cell therapy products from both regulatory and technological perspectives.

Short Duration Small Sided Football and to a Lesser Extent Whole Body Vibration Exercise Induce Acute Changes in Markers of Bone Turnover.

We aimed to study whether short-duration vibration exercise or football sessions of two different durations acutely changed plasma markers of bone turnover and muscle strain. Inactive premenopausal women (n = 56) were randomized to complete a single bout of short (FG15) or long duration (FG60) small sided football or low magnitude whole body vibration training (VIB). Procollagen type 1 amino-terminal propeptide (P1NP) was increased during exercise for FG15 (51.6 ± 23.0 to 56.5 ± 22.5 µg·L-1, mean ± SD, P < 0.05) and FG60 (42.6 ± 11.8 to 50.2 ± 12.8 µg·L-1, P < 0.05) but not for VIB (38.8 ± 15.1 to 36.6 ± 14.7 µg·L-1, P > 0.05). An increase in osteocalcin was observed 48 h after exercise (P < 0.05), which did not differ between exercise groups. C-terminal telopeptide of type 1 collagen was not affected by exercise. Blood lactate concentration increased during exercise for FG15 (0.6 ± 0.2 to 3.4 ± 1.2 mM) and FG60 (0.6 ± 0.2 to 3.3 ± 2.0 mM), but not for VIB (0.6 ± 0.2 to 0.8 ± 0.4 mM) (P < 0.05). Plasma creatine kinase increased by 55 ± 63% and 137 ± 119% 48 h after FG15 and FG60 (P < 0.05), but not after VIB (26 ± 54%, NS). In contrast to the minor elevation in osteocalcin in response to a single session of vibration exercise, both short and longer durations of small sided football acutely increased plasma P1NP, osteocalcin, and creatine kinase. This may contribute to favorable effects of chronic training on musculoskeletal health.

Visualisation of Kiss1 Neurone Distribution Using a Kiss1-CRE Transgenic Mouse.

Kisspeptin neuropeptides are encoded by the Kiss1 gene and play a critical role in the regulation of the mammalian reproductive axis. Kiss1 neurones are found in two locations in the rodent hypothalamus: one in the arcuate nucleus (ARC) and another in the RP3V region, which includes the anteroventral periventricular nucleus (AVPV). Detailed mapping of the fibre distribution of Kiss1 neurones will help with our understanding of the action of these neurones in other regions of the brain. We have generated a transgenic mouse in which the Kiss1 coding region is disrupted by a CRE-GFP transgene so that expression of the CRE recombinase protein is driven from the Kiss1 promoter. As expected, mutant mice of both sexes are sterile with hypogonadotrophic hypogonadism and do not show the normal rise in luteinising hormone after gonadectomy. Mutant female mice do not develop mature Graafian follicles or form corpora lutea consistent with ovulatory failure. Mutant male mice have low blood testosterone levels and impaired spermatogenesis beyond the meiosis stage. Breeding Kiss-CRE heterozygous mice with CRE-activated tdTomato reporter mice allows fluorescence visualisation of Kiss1 neurones in brain slices. Approximately 80-90% of tdTomato positive neurones in the ARC were co-labelled with kisspeptin and expression of tdTomato in the AVPV region was sexually dimorphic, with higher expression in females than males. A small number of tdTomato-labelled neurones was also found in other locations, including the lateral septum, the anterodorsal preoptic nucleus, the amygdala, the dorsomedial and ventromedial hypothalamic nuclei, the periaquaductal grey, and the mammillary nucleus. Three dimensional visualisation of Kiss1 neurones and fibres by CLARITY processing of whole brains showed an increase in ARC expression during puberty and higher numbers of Kiss1 neurones in the caudal region of the ARC compared to the rostral region. ARC Kiss1 neurones sent fibre projections to several hypothalamic regions, including rostrally to the periventricular and pre-optic areas and to the lateral hypothalamus.

Exercise intensity and the protection from postprandial vascular dysfunction in adolescents.

Acute exercise transiently improves endothelial function and protects the vasculature from the deleterious effects of a high-fat meal (HFM). We sought to identify whether this response is dependent on exercise intensity in adolescents. Twenty adolescents (10 male, 14.3 ± 0.3 yr) completed three 1-day trials: 1) rest (CON); 2) 8 × 1 min cycling at 90% peak power with 75 s recovery [high-intensity interval exercise (HIIE)]; and 3) cycling at 90% of the gas exchange threshold [moderate-intensity exercise (MIE)] 1 h before consuming a HFM (1.50 g/kg fat). Macrovascular and microvascular endothelial function was assessed before and immediately after exercise and 3 h after the HFM by flow-mediated dilation (FMD) and laser Doppler imaging [peak reactive hyperemia (PRH)]. FMD and PRH increased 1 h after HIIE [P < 0.001, effect size (ES) = 1.20 and P = 0.048, ES = 0.56] but were unchanged after MIE. FMD and PRH were attenuated 3 h after the HFM in CON (P < 0.001, ES = 1.78 and P = 0.02, ES = 0.59). FMD remained greater 3 h after the HFM in HIIE compared with MIE (P < 0.001, ES = 1.47) and CON (P < 0.001, ES = 2.54), and in MIE compared with CON (P < 0.001, ES = 1.40). Compared with CON, PRH was greater 3 h after the HFM in HIIE (P = 0.02, ES = 0.71) and MIE (P = 0.02, ES = 0.84), with no differences between HIIE and MIE (P = 0.72, ES = 0.16). Plasma triacylglycerol concentration and total antioxidant status concentration were not different between trials. We conclude that exercise intensity plays an important role in protecting the vasculature from the deleterious effects of a HFM. Performing HIIE may provide superior vascular benefits than MIE in adolescent groups.

Street football is a feasible health-enhancing activity for homeless men: biochemical bone marker profile and balance improved.

This case-control study investigated the feasibility of street football as a health-enhancing activity for homeless men, specifically the musculoskeletal effects of 12 weeks of training. Twenty-two homeless men participated in the football group (FG) and 10 served as controls (C). Plasma osteocalcin, TRACP5b, leptin, and postural balance were measured, and whole-body DXA scanning was performed. The attendance rate was 75% (2.2 ± 0.7 sessions per week). During 60 min of training, the total distance covered was 5534 ± 610 m, with 1040 ± 353, 2744 ± 671, and 864 ± 224 m covered by high-intensity, low-intensity, and backwards/sideways running, respectively. In FG, osteocalcin increased by 27% from 20.1 ± 11.1 to 25.6 ± 11.8 ng/mL (P = 0.007). Postural balance increased by 39% (P = 0.004) and 46% (P = 0.006) in right and left leg. Trunk bone mineral density increased by 1.0% from 0.959 ± 0.095 to 0.969 ± 0.090 g/cm(2) (P = 0.02). No effects were observed in C. In conclusion, street football appears to be a feasible training activity with musculoskeletal health benefits for homeless men. The attendance rate and the training intensity were high, and 12 weeks of training resulted in a substantial anabolic response in bone metabolism. Postural balance improved markedly, and the overall risk of falling, and hospitalization due to sudden trauma, could be reduced by street football for homeless men.

Do soccer and Zumba exercise improve fitness and indicators of health among female hospital employees? A 12-week RCT.

This randomized controlled study investigated the effectiveness of soccer and Zumba on fitness and health indicators in female participants recruited from a workplace. One hundred seven hospital employees were cluster-randomized to either a soccer group (SG), Zumba group (ZG), or control group (CG). Intervention effects for the two training groups were compared with CG. The training was conducted outside working hours as 2-3 1-h sessions per week for 12 weeks. Peak oxygen uptake (VO2peak ), fat percentage, fat mass, bone mineral content, and plasma osteocalcin were measured before and after the intervention period. Based on intention-to-treat-analyses, SG significantly improved the VO2peak relative to body mass (5%; P = 0.02) and decreased heart rate during 100-W cycle exercise (-7 bpm; P = 0.01), total body fat percentage (-1.1%; P = 0.002), and total body fat mass (-1.0 kg; P = 0.001) compared with CG. ZG significantly improved the VO2peak relative to body mass (5%; P = 0.03) and decreased total fat mass (-0.6 kg; P < 0.05) compared with CG. Plasma osteocalcin increased in SG (21%; P < 0.001) and ZG (10%; P = 0.01) compared with CG. The present study indicates that workplace initiated short-term soccer training as well as Zumba outside working hours may result in fitness and modest health benefits among female hospital employees.

Hirschsprung's disease in Barbados--a 16-year review.

OBJECTIVE: To assess the surgical outcome of patients with Hirschsprung's disease (HD) who were treated in Barbados, establish referral patterns and identify factors which can lead to better management. DESIGN AND METHODS: All patients with HD who had definitive surgery at the Queen Elizabeth Hospital, Barbados, over a 16-year period (between July 1991 and June 2007) were identified from the hospital records system. Data from patients' notes were collected to establish demographics, including age at referral and definitive surgery, gender presenting symptoms, surgical intervention(s) and definitive procedure. Long term outcome was assessed by the use of a simple questionnaire which was completed by the authors after personal or telephone contact with patients, their parents or guardians or the referring physician. RESULTS: Between July 1991 and June 2007, 27 children were identified with HD. There were 20 males and seven females. Fifteen of the 27 children (55%) were local Barbadians, who were referred earlier when compared to those from the surrounding Caribbean islands. The most common mode of presentation was chronic constipation (13/27; 48%). The majority (69%) of the children were fully continent in the long-term (mean follow-up of 64 months) and passed a bowel motion on an average of 2-3 times per day without the use of laxatives or enemas. CONCLUSION: Children who had definitive surgery for HD in Barbados (using Martin's modified Duhamel procedure) had an overall good long-term outcome comparable to international results. Children referred from the surrounding Caribbean islands were referred at an older age, but their overall outcome was not worse than local Barbadian patients.

Positive margins in laparoscopic partial nephrectomy in 855 cases: a multi-institutional survey from the United States and Europe.

PURPOSE: Open partial nephrectomy has emerged as the standard of care in the management of renal tumors smaller than 4 cm. While laparoscopic radical nephrectomy has been shown to be comparable to open radical nephrectomy with respect to long-term outcomes, important questions remain unanswered regarding the oncological efficacy of laparoscopic partial nephrectomy. We examined the practice patterns and pathological outcomes following laparoscopic partial nephrectomy. MATERIALS AND METHODS: A survey was sent to academic medical centers in the United States and in Europe performing laparoscopic partial nephrectomy. The total number of laparoscopic partial nephrectomies, positive margins, indications for intraoperative frozen biopsy as well as tumor size and position were queried. RESULTS: Surveys suitable for analysis were received from 17 centers with a total of 855 laparoscopic partial nephrectomy cases. Mean tumor size was 2.7 cm (+/-0.6). There were 21 cases with positive margins on final pathology, giving an overall positive margin rate of 2.4%. Intraoperative frozen sections were performed selectively at 10 centers based on clinical suspicion of positive margins on excised tumor. Random biopsies were routinely performed on the resection bed at 5 centers. Frozen sections were never performed at 2 centers. Of the 21 cases with positive margins 14 underwent immediate radical nephrectomy based on the frozen section and 7 were followed expectantly. CONCLUSIONS: Early experience with laparoscopic partial nephrectomy in this multicenter study demonstrates oncological efficacy comparable to that of open partial nephrectomy with respect to the incidence of positive margins. The practice of intraoperative frozen sections varied among centers and is not definitive in guiding the optimal surgical treatment.

Acute ureteric calculus obstruction: unenhanced spiral CT versus HASTE MR urography and abdominal radiograph.

The aim of this study is to compare the performance of unenhanced spiral CT to the combination of HASTE MR urography (MRU) and plain abdominal radiography (KUB) in patients suspected of having acute calculus ureteric obstruction. 64 patients with suspected acute calculus ureteric obstruction were evaluated. The presence of perirenal fluid, presence and level of ureteric obstruction and calculi were assessed on both techniques. 44 of 64 (69%) patients had acute calculus ureteric obstruction based on clinical, radiographic or surgical findings. MRU showed perirenal fluid in acute ureteric obstruction (77%) with a greater sensitivity than CT showed stranding (45%). The combination of fluid and ureteric dilation on MRU showed a sensitivity of 93% (CT 80%), specificity of 95% (CT 85%), and accuracy of 94% (CT 81%). There were 61 findings of either fluid or ureteric dilatation on MRU in 44 acutely obstructed kidneys compared with 37 similar findings on CT (p<0.005). Although there was excellent reproducibility (Kappa=/>0.75) in the finding of perirenal fluid on MRU, there was only fair interobserver agreement (Kappa<0.4) regarding perirenal stranding on CT. MRU/KUB showed ureteric calculi in 21/29 (72%) of patients with calculi seen by CT. Overall, MRU/KUB revealed 2.4 abnormalities per acutely obstructed ureter compared with 1.8 abnormalities detected by CT. MRU/KUB using HASTE sequences can diagnose the presence of acute calculus ureteric obstruction with similar accuracy to spiral CT. The technique has less observer variability and is more accurate than CT in detecting evidence of obstruction such as perirenal fluid.

Cocaine-induced anxiety: alleviation by diazepam, but not buspirone, dimenhydrinate or diphenhydramine.

Clinical reports and animal experiments indicate that both cocaine administration and cocaine withdrawal increase anxiety. We investigated the ability of a number of putative anxiolytic agents to alleviate these anxiety states using the elevated plus-maze. Rats in the cocaine condition received either saline or cocaine (20 mg/kg) 40 min prior to testing; those in the withdrawal condition were tested 48 h following a chronic treatment regime (saline or cocaine 20 mg/kg per day for 14 days). Prior to testing, animals received a benzodiazepine (1.0 or 2.0 mg/kg diazepam), a serotonergic agonist (0.5 or 1.0 mg/kg buspirone), an antihistamine (50 mg/kg dimenhydrinate or 27 mg/kg diphenhydramine) or a saline injection. All drugs were administered intraperitoneally. Cocaine administration and cocaine withdrawal reduced the percentage time spent on and the number of entries into the open arms. Diazepam dose-dependently alleviated cocaine withdrawal-induced anxiety and non-significantly attenuated cocaine-induced anxiety. Buspirone, dimenhydrinate and diphenhydramine did not consistently alleviate the anxiety caused by either cocaine pre-treatment regime; in the saline conditions, however, each of these treatments was anxiogenic. In summary, benzodiazepines alleviated cocaine-induced anxiety, while future research on the ability of serotonergic and antihistaminergic drugs to alleviate these anxiety states is warranted.

T and B cell repertoire in gastric lymph follicles in children with Helicobacter pylori infection.

Helicobacter pylori infection has been implicated in the development of gastrointestinal malignancy in adults and children. The histopathological processes that lead to such development are unknown. We compared the immune cell repertoire of mucosal lymph follicles in children with H. pylori infection to B cell type mucosal associated lymphoid tissue (MALT)-lymphoma of adults. The B and T cell populations residing within the lymph follicles and/or within B cell type MALT lymphoma were characteriZed by an immunohistochemical technique, utilizing B and T cell markers including: CD3, CD4, CD8 (T cells); CD20, CD40, GD74, BLA36, CD80, CD86 (B cells). Stain intensity was compared between the samples. T cell repertoire was observed within the lymph follicles, but not in the B cell MALT-lymphoma specimens. No significant difference was observed between the staining of CD40, CD74, CD8, and BLA36. The B cell markers, CD80 and CD86, were found within the centrocytic zone of the lymph follicle. In the B cell repertoire, no significant difference was observed between the lymph follicles of children with H. pylori infection and the adult MALT-lymphoma specimens except in CD20. B and T cells were in close anatomical proximity, enabling them to interact and exchange immunological information.

Differences in innate immunologic response to group B streptococcus between colonized and noncolonized women.

OBJECTIVE: To evaluate the functional capacity of granulocytes and monocytes from pregnant and nonpregnant women in relation to group B streptococcus (GBS) colonization status. METHODS: Engulfment of fluorescent GBS by peripheral blood phagocytes from GBS-colonized and noncolonized women was measured by flow cytometry. Intracellular superoxiode generated in response to GBS challenge to monocytes and granulocytes enriched from peripheral blood of these women was also measured by flow cytometry, and extracellular superoxide was determined by colorimetric assay. RESULTS: Monocytes and granulocytes from pregnant, GBS-colonized women engulfed significantly greater numbers of GBS than phagocytes from pregnant, noncolonized women. No difference in intracellular superoxide production was detected between any of the groups of women; however, monocytes from pregnant, colonized women released significantly more superoxide into the extracellular milieu than did granulocytes from the same women. No differences in extracellular release of superoxide were observed among noncolonized women whether they were pregnant or not. CONCLUSIONS: Monocytes from pregnant, colonized women engulf more GBS and release more of the superoxide into the extracellular environment, where it is unlikely to be an effective defense mechanism against intracellular bacteria. This suggests that components of the innate immune system that should serve in a protective role may function suboptimally, thereby contributing to the colonization process by GBS.

Electrokinetic movement and biodegradation of 2,4-dichlorophenoxyacetic acid in silt soil.

The coupling of electrokinetic movement of an organic contaminant, 2,4-dichlorophenoxyacetic acid (2,4-D), through soil and its biodegradation in situ has been demonstrated. In a first experiment, the direction and rate of movement of 2,4-D were determined using homogeneously contaminated soil (864 mg 2,4-D/kg dry weight soil) compacted into six individual compartments, 6 cm long, 3 cm wide, and 4 cm deep. Each compartment was bordered by a carbon felt anode and a stainless steel cathode. The application of a current density of 3.72 A/m(2) led to migration of 2,4-D towards the anode at a rate of approximately 4 cm/day. In a second experiment, electrokinetic movement and biodegradation were combined in situ. Sterilized silt soil contaminated with ring-labeled 14C-2,4-D (811 mg 2,4-D/kg dry weight soil) was compacted into a single soil compartment, 22 cm long, 7 cm wide, and 4 cm deep, in a 4.5 cm region adjacent to the cathode. The remainder of the compartment was filled with sterilized soil (to a total weight of 1,015 g). Burkholderia spp. RASC c2 (1.88 x 10(11) cells), a tetracycline-resistant bacterium with chromosomally encoded degradative genes for 2,4-D, was inoculated into the soil at a position 14-16 cm from the cathode. The reactor was placed within a sealed perspex box, with a constant air flow connected to sodium hydroxide traps. Under an applied current density of 0.89 A/m(2), the pollutant moved towards the bacteria. As it reached the inoculated region, its concentration decreased in the soil and 14CO2 was recovered in the traps. At the end of the experiment, 87.1% of radiolabel had been removed from the soil, 5.8% of which was recovered as 14CO2. A third, control, experiment showed a significant contrast in the absence of an electric current, where a slow rate of diffusion controlled the movement of both 2,4-D and bacteria in the soil and biodegradation occurred at the interface between the diffusing fronts.

Laparoscopic infrared imaging.

BACKGROUND: As an adjunct to direct visual imaging, an infrared endoscope was developed to assist in the identification of various anatomic structures and to assess tissue viability during laparoscopic procedures. A camera sensitive to emitted energy in the mid-infrared range (3 to 5 microm) was incorporated into a two-channel visible-light laparoscope. METHODS AND MATERIALS: Laparoscopic procedures were performed in a porcine model, inexperienced laparoscopists being asked to localize and differentiate structures before dissection using the visible-light system and then the infrared system. To determine clinical utility, nine laparoscopic urologic procedures were performed with the assistance of the infrared system. RESULTS: In the clinical evaluation, infrared imaging proved to be useful in differentiating between blood vessels and other anatomic structures. In contrast to the experience with the conventional endoscope, vessel identification, assessment of organ perfusion, and transperitoneal localization of the ureter was successful in all instances using the infrared system. In the porcine model, this system also permitted assessment of bowel perfusion during laparoscopic occlusion of mesenteric vessels and distinguished between the cystic duct and artery. CONCLUSION: Infrared imaging is a potentially powerful adjunct to laparoscopic surgery. It may improve the differentiation and localization of anatomic structures and allow assessment of physiologic features, such as perfusion, not previously attainable with laparoscopic techniques.

JP-8 jet fuel-induced DNA damage in H4IIE rat hepatoma cells.

We investigated the genotoxicity of middle distillate jet fuel, Jet Propulsion 8 (JP-8), on H4IIE rat hepatoma cells in vitro. DNA damage was evaluated using the comet (single cell gel electrophoresis) assay. Cells were exposed for 4h to JP-8 (solubilized in ethanol (EtOH) at 0.1% (v/v)) to concentrations ranging from 1 to 20microg/ml. Exposure to JP-8 resulted in an overall increase in mean comet tail moments ranging from 0.74+/-0.065 (0.1% EtOH control) to 3.13+/-0.018,4.36+/-0.32,5.40+/-0.29,7.70+/-0.52 and 11.23+/-0.77 for JP-8 concentrations 3, 5, 10, 15 and 20microg/ml, respectively. Addition of DNA repair inhibitors hydroxyurea (HU) and cytosine arabinoside (Ara-C) to cell culture with JP-8 resulted in accumulation of DNA damage strand breaks and increase in comet tail length. Inclusion of 4mM HU and 40microM Ara-C with 3, 5, 10 and 20microg/ml JP-8 concentrations resulted in increased mean tail moments to 5.94+/-0.43,10.12+/-0.72,17.03+/-0.96,and29.25+/-1.55. JP-8, in the concentrations used in this study, did not result in cytotoxicity or significant apoptosis, as measured using the terminal deoxynucleotidyl transferase (TDT)-mediated dUTP-X nick end labeling (TUNEL) assay. These results demonstrate that relevant exposures to JP-8 result in DNA damage to H4IIE cells, and suggest that DNA repair is involved in mitigating these effects.

Immunologic effects of gliotoxin in rats: mechanisms for prevention of autoimmune diabetes mellitus.

Various fungal products, such as gliotoxin (GT), have immunomodulating activity, a fact exploited previously by our group for prevention of autoimmune diabetes mellitus in BB/Wor rats. To understand better the immunologic effects in GT-treated rats, splenocytes from 65-day-old prediabetic diabetes-prone rats were phenotypically characterized after chronic treatment with GT. A parallel study examined the direct effects of GT on splenocyte preparations incubated with the mycotoxin. In vitro treatment of splenocytes with GT revealed relative decreases in CD4+ and increases in CD8+ T-cell subsets, whereas in vivo treatment with GT did not result in detectable alterations in relative CD4+ and CD8+ cell subsets. We were unable to show significant effects on NK cells or MHC class II cells. However, in vitro and in vivo GT treatments significantly enhanced the detectable RT6 surface marker, a key regulatory element in autoimmune diabetes pathogenesis. This study showed that GT selectively affects certain lymphocyte subsets, possibly through the mechanism of apoptosis, which was increased in vivo as well as in vitro.

Laparoscopic surgery in patients with ventriculoperitoneal shunts: safety and monitoring.

PURPOSE: It was suggested that patients with a ventriculoperitoneal shunt are at risk for increased intracranial pressure during pneumoperitoneum. Shunt pressure monitoring and ventricular drainage to maintain normal pressure were recommended. We evaluated a series of patients with a ventriculoperitoneal shunt who underwent laparoscopic surgery to determine the clinical indications of increased intracranial pressure. MATERIALS AND METHODS: We reviewed the anesthesia records of 12 females and 6 males with a mean age of 13.2 years who had a ventriculoperitoneal shunt and underwent a total of 19 consecutive laparoscopic operations. Data on operative time, carbon dioxide level, pulse, blood pressure and any untoward anesthetic events were obtained. Postoperative records were assessed for evidence of neurological change. RESULTS: Mean operative time was 7 hours 13 minutes and estimated mean laparoscopic time was 2 hours 52 minutes. Average insufflation pressure was 16 mm. Hg (range 12 to 20). There was no evidence of a trend to combined bradycardia and hypertension or surgically related neurological deterioration and no untoward anesthetic events. Ventriculoperitoneal shunt revision was done in 3 cases, a rate consistent with that in the literature. Mean followup was 23.4 months (range 1 to 58). CONCLUSIONS: There was no evidence of clinically significant increased intracranial pressure in our series or in the literature in patients with a ventriculoperitoneal shunt who undergo laparoscopy. Invasive methods for shunt monitoring are not without risk. Routine anesthetic monitoring should remain the standard of care in the absence of clear evidence to the contrary.

Plain abdominal x-ray versus computerized tomography screening: sensitivity for stone localization after nonenhanced spiral computerized tomography.

PURPOSE: Urolithiasis followup with plain abdominal x-ray requires adequate visualization of the calculus on the initial x-ray or computerized tomography (CT) study. We compared the sensitivity of plain abdominal x-ray versus CT for stone localization after positive nonenhanced spiral CT. MATERIALS AND METHODS: We evaluated 46 consecutive nonenhanced spiral CT studies positive for upper urinary tract lithiasis for which concurrent plain abdominal x-rays were available. X-ray and CT studies were compared for the ability to visualize retrospectively a stone given its location by CT. A consensus of 1 radiologist and 3 urologists was reached in each case. Cross-sectional stone size and maximum length were measured on plain abdominal x-ray. RESULTS: Plain abdominal x-ray and scout CT had 48% (22 of 46 cases) and 17% (8 of 46) sensitivity, respectively, for detecting the index stone (p <0.00004). Of the 39 stones overall visualized on plain abdominal x-ray only 19 (49%) were visualized on scout CT. Mean cross-sectional area and length of the stones on scout CT were 0.34 cm.2 (approximately 6 x 5.5 mm.) and 6. 5 mm., respectively, while the average size of those missed was 0.11 cm.2 (approximately 4 x 3 mm.) and 3.6 mm. The mean size differences in the groups were highly significant (p <0.0009). CONCLUSIONS: Plain abdominal x-ray is more sensitive than scout CT for detecting radiopaque nephrolithiasis. Of the stones visible on plain abdominal x-ray 51% were not seen on CT. To facilitate outpatient clinic followup of patients with calculi plain abdominal x-ray should be performed when a stone is not clearly visible on scout CT.

Cloacal outlet obstruction with an ectopic ureter.

Cloacal malformation occurs in approximately 1 in 50,000 live female births. Prenatal ultrasound may lead to the diagnosis in selected cases. We report an unusual case of prenatally detected single-system hydronephrosis with a nonvisible bladder and worsening oligohydramnios. Labor was induced at 35 weeks' estimated gestational age. On physical examination, a single perineal opening was noted consistent with cloaca. Endoscopy revealed an obstructed ectopic ureter at the level of the sphincter, an undeveloped bladder and vagina, and a fistula to the rectum. A low loop cutaneous ureterostomy and right upper quadrant loop colostomy were performed. The absence of a typical fluid-filled pelvic structure may confound the prenatal diagnosis of cloaca.