Novel oral phosphate binder with nanocrystalline maghemite-phosphate binding capacity and pH effect.

Hyperphosphatemia is one of the main risk factors contributing to morbidity and mortality in patients with end stage renal disease. The demand for a new phosphate binder is continuously increasing since the number of patients suffering under hyperphosphatemia is growing. However, side effects and high pill burden of currently available phosphate binders are the main reasons for low compliance and uncontrolled serum phosphate levels. Therefore, the aim of this study was to develop a novel phosphate binder with a high phosphate binding capacity over the entire gastrointestinal (GI) pH range. This novel phosphate binder C-PAM-10 is based on d-mannose coated nanocrystalline maghemite and belongs to the new class of phosphate binders, called the "iron based agents". It was possible to obtain a phosphate binding product that showed very high phosphate binding capacities with the characteristic of being pH independent at relevant pH ranges. The simulation of a GI passage ranging from pH 1.2 to pH 7.5 showed a 2.5 times higher phosphate binding capacity compared to the commonly used phosphate binder sevelamer carbonate. The simulation of a pH sensitive coating that releases the iron based phosphate binder at pH values ≥4.5 still showed a very high phosphate binding capacity combined with very low iron release which might decrease iron related side effects in vivo. Therefore, C-PAM-10 and its variations may be very promising candidates as a superior phosphate binder.

MR-guided periarterial ethanol injection for renal sympathetic denervation: a feasibility study in pigs.

PURPOSE: To evaluate the feasibility and efficacy of image-guided periarterial ethanol injection as an alternative to transluminal radiofrequency ablation. METHODS: Unilateral renal periarterial ethanol injection was performed under general anesthesia in 6 pigs with the contralateral kidney serving as control. All interventions were performed in an open 1.0 T MRI system under real-time multiplanar guidance. The injected volume was 5 ml (95 % ethanol labelled marked MR contrast medium) in 2 pigs and 10 ml in 4 pigs. Four weeks after treatment, the pigs underwent MRI including MRA and were killed. Norepinephrine (NE) concentration in the renal parenchyma served as a surrogate parameter to analyze the efficacy of sympathetic denervation. In addition, the renal artery and sympathetic nerves were examined histologically to identify evidence of vascular and neural injury. RESULTS: In pigs treated with 10 ml ethanol, treatment resulted in neural degeneration. We found a significant reduction of NE concentration in the kidney parenchyma of 53 % (p < 0.02) compared with the untreated contralateral kidney. In pigs treated with 5 ml ethanol, no significant changes in histology or NE were observed. There was no evidence of renal arterial stenosis in MRI, macroscopy or histology in any pig. CONCLUSION: MR-guided periarterial ethanol injection was feasible and efficient for renal sympathetic denervation in a swine model. This technique may be a promising alternative to the catheter-based approach in the treatment of resistant arterial hypertension.

Cardiac magnetic resonance angiography using blood-pool contrast agents: comparison of citrate-coated very small superparamagnetic iron oxide particles with gadofosveset trisodium in pigs.

PURPOSE: To compare citrate-coated very small superparamagnetic iron oxide particles (VSOP) with gadofosveset trisodium as blood pool contrast agents for cardiac magnetic resonance angiography (CMRA) in pigs. MATERIALS AND METHODS: Animal experiments were approved by the responsible authority. 10 CMRA-like examinations were performed at 1.5 T after administration of VSOP (0.06  mmol Fe/kg; 5 examinations) and gadofosveset trisodium (0.03  mmol Gd/kg; 5 examinations). The CMRA protocol included ECG-gated inversion-recovery-prepared T1-weighted gradient echo imaging (IR-GRE; one slice) and ECG-gated inversion recovery prepared steady state free precession imaging (IR SSFP; one slice) before and 1, 3, 5, 10, 15, 20, 25, 30, 40, 50, and 60  min after injection. At each time point, three different inversion times (TI; 200  msec, 300  msec, and 400  msec) were applied. Contrast-to-noise ratios (CNR) between blood and myocardium were calculated and compared using mixed linear models. RESULTS: No significant differences of CNR were found between IR-GRE and IR SSFP. At 3 and 5  min after contrast agent administration, VSOP showed a significantly higher CNR than gadofosveset trisodium when TI of 200  msec and 300 msec were applied (TI of 200  msec at 3 min: 8.2 ±â€Š0.7 vs. 5.4 ±â€Š0.7; TI of 200  msec at 5 min: 7.9 ±â€Š0.7 vs. 3.5 ±â€Š0.8; TI of 300  msec at 3  min: 11.7 ±â€Š0.7 vs. 8.8 ±â€Š0.8; TI of 300  msec at 5  min: 11.4 ±â€Š0.7 vs. 8.0 ±â€Š0.8; p < 0.05). Moreover, significant differences in favor of VSOP were found for all time points from 10 to 40  min irrespective of TI (p < 0.05). CONCLUSION: VSOP has superior blood-pool properties compared to gadofosveset trisodium resulting in prolonged improvement of CNR on CMRA.

Peripheral washout phenomenon in an animal tumour model: comparison of dynamic magnetic resonance imaging using a small molecular contrast medium with histology.

The peripheral washout sign was first described in delayed dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using a small molecular contrast medium in solid lesions of the human breast and liver. It was found to be 100% specific for malignant lesions and could therefore potentially be used as an additional noninvasive diagnostic tool differentiating malignant from benign lesions. The origin of this phenomenon has not yet been explained. The objective of this study was to translate the peripheral washout sign as seen in solid tumours in delayed DCE-MRI in human onto an animal model for further assessment of DCE-MRI characteristics and histological analysis. Small molecular contrast medium DCE-MRI was performed over 42 min in experimental colon carcinoma grown subcutaneously in rats. Qualitative and quantitative analyses for evaluation of presence and characteristics of the peripheral washout sign were accomplished, defining four centripetally distributed tumour zones (central, intermediate, peripheral and marginal). One hundred per cent of the carcinomas demonstrated a peripheral washout sign in DCE-MRI starting at 20 min after bolus injection. Histomorphological analysis was performed for tissue classification and evaluation of microvasculature. Quantitative analysis revealed different enhancement profiles of the four tumour zones. Histology indicated centripetally asymmetric vascularization and vascular endothelial growth factor VEGF/VEGF receptor 2 expression within the tumour tissue. Thus, peripheral washout sign can be translated to an animal model. However, comparison of small molecular contrast medium DCE-MRI with histology revealed that histology alone does not explain the occurrence of the peripheral washout.

Assessment of left ventricular volumes and function: intraindividual comparison of multi-slice spiral CT and electron beam CT in an animal model.

PURPOSE: To evaluate multi-slice spiral computed tomography (MSCT) for measurements of left ventricular volumes, ejection fraction (EF), and myocardial mass in comparison with electron beam CT (EBCT) as a reference method. MATERIAL AND METHODS: Six minipigs underwent both standardized contrast-enhanced MSCT (effective acquisition time per cardiac cycle 125.7+/-30.1 ms, reconstructed slice thickness 8 mm) and EBCT (acquisition time 50 ms, collimated slice thickness 8 mm). The contrast-to-noise ratio of the left ventricle was measured in each animal, and the contour sharpness of the myocardium was analyzed. Volumes (EDV, ESV, SV) ejection fraction (EF), and muscle mass were calculated by MSCT and by EBCT using the slice summation method. RESULTS: MSCT had a higher contrast-to-noise ratio and delineated the myocardial contours more sharply than EBCT. There was a close linear correlation between both modalities for all parameters (EDV: rP=0.88, ESV: rP=0.91, SV: rP=0.85, EF: rP=0.93; mass: rP=0.90; P<0.05 each). MSCT slightly overestimated ESV and slightly underestimated SV and EF compared with EBCT (P<0.05 each). CONCLUSIONS: Image quality in MSCT is superior to that of EBCT. Functional parameters correlate well between both modalities, but the accuracy of MSCT is limited by its lower temporal resolution.

[MR angiography of the coronary arteries: comparison of the blood pool contrast medium Gadomer and Gd-DTPA in pigs]. / MR-Angiographie der Koronararterien: Vergleich des Blutpoolkontrastmittels Gadomer mit Gd-DTPA am Schwein.

AIM: To investigate the signal-enhancing effects of the macromolecular contrast medium Gadomer in MR angiography of the coronary arteries compared to Gd-DTPA. MATERIAL AND METHODS: A total of 15 MRI examinations of the heart were performed in pigs at 1.5 T using a pulse-triggered, segmented 3D FLASH sequence with data acquisition during breathhold before and up to 30 min after contrast medium injection. Gadomer was investigated at two doses (0.05 and 0.1 mmol Gd/kg), Gd-DTPA at one (0.3 mmol Gd/kg) (n = 5 examinations per dose). Standard sequences without magnetization preparation were supplemented by sequences with magnetization saturation applied before data acquisition before and immediately after contrast medium injection. Analysis comprised quantitative determination of blood and myocardium signal to noise (S/N) and contrast to noise (C/N) and qualitative assessment of several parameters of image quality and coronary artery visualization. RESULTS: Gadomer leads to a significant C/N increase between blood and myocardium compared to the unenhanced examination and the increase is longer-lasting than that produced by Gd-DTPA (Gd-DTPA: only directly after injection; Gadomer: up to 5 min post injection at 0.05 mmol Gd/kg, up to 10 min at 0.1 mmol Gd/kg). The qualitative evaluation shows that visualization of the coronary arteries and branch vessels is significantly better with Gadomer at both doses than with Gd-DTPA. Magnetization saturation increases the C/N in combination with Gd-DTPA and at the higher dose of Gadomer with the latter producing a higher increase in C/N values. CONCLUSION: Gadomer is a suitable contrast medium for MR angiography of the coronary arteries with the dose of 0.1 mmol Gd/kg being superior to 0.05 mmol Gd/kg due to a longer imaging window.

Comparative analysis of two coxsackievirus B3 strains: putative influence of virus-receptor interactions on pathogenesis.

Strain-specific differences in the interaction of coxsackievirus B3 (CVB3) with the coxsackievirus-adenovirus receptor (CAR) and the decay-accelerating factor (DAF) co-receptor proteins were investigated using a non-haemagglutinating (CVB3) and a haemagglutinating (CVB3-HA) strain of CVB3. A panel of receptor-transfected hamster CHO cells, expressing either CAR (CHOCAR cells), DAF (CHODAF cells), or both receptor proteins (CHODC cells) were used to study the interplay of CAR and DAF receptor molecules with regard to binding and infection with CVB3 and CVB3-HA. Despite clear differences in their binding phenotypes, both virus strains were found to primarily depend on the CAR receptor protein for initialization of productive infections. Cytopathic effects induced by CVB3-HA were influenced by co-expression of DAF receptor proteins. The cardiotropic potential of both virus strains was investigated in A.BY/SnJ mice. Despite comparable virus replication of both CVB3 strains in individual myocytes, the number of infected heart muscle cells was significantly lower in CVB3-HA infected mice. Infections of pancreata correlated with myocardial infections. Together these data suggest that even small differences in virus-receptor interactions, influencing virus binding and virus spread, may have an impact on the pathogenesis of CVB-induced diseases.

The active magnetic resonance imaging stent (AMRIS): initial experimental in vivo results with locally amplified MR angiography and flow measurements.

RATIONALE AND OBJECTIVES: Magnetic resonance (MR) is limited by artifacts in vessels after stenting. An active MR imaging stent (AMRIS) allows for artifact-free imaging with local improvement in signal-to-noise ratio (SNR). In a rabbit model, we evaluated the imaging properties by MR angiography (MRA) and flow measurements. METHODS: The AMRIS was placed in the abdominal aorta of five rabbits. At 1.5 T, MRA (three-dimensional fast low-angle shot) was performed before and after intravenous injection of an iron oxide-based, blood-pool contrast medium (dose, 50 micromol Fe/kg), and flow measurements were performed (electrocardiographically triggered phase-contrast cine gradient-echo sequence). Mean SNRs were calculated and flow volume curves were generated. RESULTS: The SNR was 6.0 +/- 0.6 (outside the stent) versus 12.3 +/- 1.1 (inside the stent, P < 0.05) for plain MRA, 21.2 +/- 0.6 versus 40.6 +/- 5.2 (P < 0.05) for contrast-enhanced MRA, and 5.4 +/- 0.4 versus 13.7 +/- 2.1 (P < 0.05) for the magnitude images of flow measurements. Flow volume curves within and distal to the stent were comparable. CONCLUSIONS: By using the AMRIS as a vascular stent, the stented vessel segment can be examined with enhanced signal intensity on MRI.

Coronary magnetic resonance angiography: experimental evaluation of the new rapid clearance blood pool contrast medium P792.

The signal-enhancing characteristics of a new monodisperse monogadolinated macromolecular MR contrast medium (P792) were evaluated for magnetic resonance angiography (MRA) of the coronary arteries. A total of 15 cardiac examinations were performed in pigs at 1.5 T using a 3D gradient-echo sequence. Images were acquired during breath-hold before and up to 35 min after IV injection of Gd-DTPA (0.3 mmol Gd/kg), Gd-BOPTA (0.2 mmol Gd/kg), and P792 (13 micromol Gd/kg). An increase in the signal-to-noise ratio (SNR) of 97% +/- 17%, 108% +/- 37%, and 109% +/- 31% in coronary arteries and of 82% +/- 19%, 82% +/- 24%, and 28% +/- 18% in myocardium, respectively, was measured during the first postcontrast acquisition. The blood-to-myocardium signal-difference-to-noise ratio (SDNR) was significantly higher for P792 than for the other Gd compounds (P <.05) for up to 15 min after injection. Qualitative assessment showed that visualization of the coronary arteries and their branches was significantly better for P792 compared to the low-molecular Gd compounds (P <.05). The blood pool contrast medium P792 is well suited for MRA of the coronary arteries.

Ras1 interacts with multiple new signaling and cytoskeletal loci in Drosophila eggshell patterning and morphogenesis.

Little is known about the genes that interact with Ras signaling pathways to regulate morphogenesis. The synthesis of dorsal eggshell structures in Drosophila melanogaster requires multiple rounds of Ras signaling followed by dramatic epithelial sheet movements. We took advantage of this process to identify genes that link patterning and morphogenesis; we screened lethal mutations on the second chromosome for those that could enhance a weak Ras1 eggshell phenotype. Of 1618 lethal P-element mutations tested, 13 showed significant enhancement, resulting in forked and fused dorsal appendages. Our genetic and molecular analyses together with information from the Berkeley Drosophila Genome Project reveal that 11 of these lines carry mutations in previously characterized genes. Three mutations disrupt the known Ras1 cell signaling components Star, Egfr, and Blistered, while one mutation disrupts Sec61beta, implicated in ligand secretion. Seven lines represent cell signaling and cytoskeletal components that are new to the Ras1 pathway; these are Chickadee (Profilin), Tec29, Dreadlocks, POSH, Peanut, Smt3, and MESK2, a suppressor of dominant-negative Ksr. A twelfth insertion disrupts two genes, Nrk, a "neurospecific" receptor tyrosine kinase, and Tpp, which encodes a neuropeptidase. These results suggest that Ras1 signaling during oogenesis involves novel components that may be intimately associated with additional signaling processes and with the reorganization of the cytoskeleton. To determine whether these Ras1 Enhancers function upstream or downstream of the Egf receptor, four mutations were tested for their ability to suppress an activated Egfr construct (lambdatop) expressed in oogenesis exclusively in the follicle cells. Mutations in Star and l(2)43Bb had no significant effect upon the lambdatop eggshell defect whereas smt3 and dock alleles significantly suppressed the lambdatop phenotype.

Aromatization mediates testosterone's short-term feedback restraint of 24-hour endogenously driven and acute exogenous gonadotropin-releasing hormone-stimulated luteinizing hormone and follicle-stimulating hormone secretion in young men.

The present clinical study examines the neuroregulatory hypothesis that feedback restraint of LH and FSH secretion by testosterone requires in vivo aromatization. To test this postulate, we prospectively and randomly assigned 47 healthy young men to 1 of 5 parallel short-term (5-day) double-blind interventions with: 1) placebo; 2) high-dose ketoconazole (KTCZ, 400 mg orally 4 times daily) to block both Leydig-cell and adrenal steroidogenesis; 3) KTCZ and transdermal testosterone delivery (7.5 mg daily); 4) KTCZ and transdermal estradiol (0.05 mg daily); or 5) KTCZ, testosterone, and the selective and potent aromatase inhibitor, anastrazole (5 mg orally twice daily). Blood was sampled every 10 min for 27 h on the last day of intervention to quantitate 24-h mean spontaneous and 3-h post-GnRH-stimulated (100 ng/kg iv bolus) LH and FSH release. KTCZ administration lowered the serum total testosterone concentration markedly from (mean +/- SEM) 423 +/- 57 ng/dL (15 +/- 2.0 nmo/L) during placebo ingestion to 58 +/- 8.6 ng/dL (2.0 +/- 0.3 nmol/L) (P < 10(-3)). Transdermal androgen addback along with KTCZ blockade increased testosterone levels to 607 +/- 57 ng/dL (21 +/- 2.0 nmol/L). KTCZ exposure alone drove a 3-fold increase in serum LH concentrations (P < 10(-3)) and a 2.5-fold rise in FSH secretion (P = 0.015), as assessed by high-specificity immunoradiometric assays. Concomitant transdermal testosterone (or estradiol) delivery repressed the elevated secretion of both LH and FSH to mid-normal baseline values. A 3-fold administration of anastrazole, KTCZ, and testosterone completely opposed exogenous testosterone's suppression of 24-h LH and FSH secretion. Anastrazole coadministration likewise abolished testosterone-dependent inhibition of 3-h GnRH-stimulated LH and FSH release. In summary, assuming the specificity of anastrazole's inhibition of aromatase activity, we conclude that circulating testosterone in healthy men curtails endogenously driven as well as exogenous GnRH-stimulated LH and FSH secretion conditional on its in vivo aromatization.

Immune modulation after measles vaccination of 6-9 months old Bangladeshi infants.

Measles still causes high mortality in children younger than 1 year of age. Administration of high titre measles vaccines before 7 months of age led to increased overall mortality, raising questions as to the immunological effects of measles vaccine in young infants. We investigated the immune response to standard titre vaccines given to children in Bangladesh in a single dose at age 9 months, or two doses at 6 and 9 months. Of the children vaccinated at age 9 months, 95% serocoverted, compared with 70% at age 6 months. Delayed-type-hypersensitivity reactions to candida antigen were significantly reduced in both vaccine groups at 6 weeks post-vaccination, but responses to other recall antigens studied were not significantly different from controls. In both vaccine groups, peripheral blood lymphocytes isolated at 6 and 24 weeks after vaccination showed significantly higher expression of activation markers upon in vitro stimulation, and a sustained increase in IL-2 production. These findings suggest prolonged immune activation after measles vaccination at the same time as some reduction in delayed hypersensitivity responses. Further study of the clinical effects of these changes is warranted.

Impact of a cryopreservation program on the multiple pregnancy rate associated with assisted reproductive technologies.

OBJECTIVE: To determine the impact of a cryopreservation program on pregnancy rates and multiple-pregnancy rates in ART cycles. DESIGN: Retrospective study. SETTING: University teaching hospital. PATIENT(S): Women who underwent stimulation for in vitro fertilization at the Jones Institute for Reproductive Medicine between October 1987 and June 1999. INTERVENTION(S): Analysis of pregnancy and multiple-pregnancy rates based on the number of embryos transferred. MAIN OUTCOME MEASURE(S): Implantation; pregnancy and multiple-pregnancy rates. RESULT(S): Pregnancy rates per transfer increased from 9% when one embryo was transferred to 20% with two embryos, 35% with three embryos, 40% with four embryos, and 41% with five embryos. The rate of twin pregnancies increased to 21% with two embryos, 23% with three embryos, 21% with four embryos, and 22% with five embryos. The triplet pregnancy rates were 8% with three embryos, 9% with four embryos, and 2% with five embryos. A theoretical model limiting the number of embryos transferred to two with cryopreservation and subsequent transfer yields a cumulative pregnancy rate of 77%, a twin rate of less than 20%, and no triplet or higher-order pregnancies. CONCLUSION(S): The use of a cryopreservation program can help maximize pregnancy rates while minimizing multiple-pregnancy rates. Cryopreservation should be considered in all assisted reproductive technology cycles.

Vaginal misoprostol enhances intrauterine insemination.

This study examined whether the prostaglandin E(1) analogue misoprostol (400 microgram), when placed vaginally at the time of intrauterine insemination (IUI) improves pregnancy rates. A prospective, placebo-controlled, randomized and double-blind study involving 274 women in 494 IUI cycles resulted in a total of 64 pregnancies (13% per cycle). Misoprostol cycles totalled 253, with 43 pregnancies (17% per cycle), whereas placebo cycles totalled 241, with 21 pregnancies (9% per cycle). The cumulative pregnancy rate with misoprostol treatment was significantly greater than with placebo (P = 0.004, Cox proportional hazards regression). The benefit of misoprostol was seen in clomiphene cycles (14 versus 4%, P = 0.006), and was indicated in FSH cycles (33 versus 15%, borderline significance) and natural cycles (15.6 versus 7.7%, not significant), but was not seen in clomiphene/FSH cycles (18.2 versus 23.5%, not significant). Misoprostol treatment did not increase pain score on the day of IUI (1.1 versus 1.4) and at 1 day post IUI (0.6 versus 0.8). Complications were rare in both groups [six (2%) subject cycles in the misoprostol cycles compared with two (1%) in the placebo group]. It is concluded that the use of vaginal misoprostol may improve the chance for pregnancy in women having IUI in a wide variety of cycle types.

New generation of monomer-stabilized very small superparamagnetic iron oxide particles (VSOP) as contrast medium for MR angiography: preclinical results in rats and rabbits.

The purpose of this study was to evaluate the signal enhancement characteristics of very small superparamagnetic iron oxide particles (VSOP)-C63, a new monomer-coated, iron oxide-based magnetic resonance (MR) blood pool contrast medium with a very small particle size and optimized physical properties. Equilibrium MR angiography (MRA) of rats (thoracic and abdominal vessels) was performed at 1.5 T with a three-dimensional gradient-recalled echo (3D GRE) technique (TR/TE 6.6/2.3 msec, flip angle 25 degrees ) before and after (every 3-5 minutes up to 50 minutes) i.v. injection of VSOP-C63 [dosages: 15, 30, 45, 60, 75, and 90 micromol Fe/kg; diameter: 8 nm; relaxivities at 0.47 T: R1 = 30 l/(mmol * s); R2 = 39 l/(mmol * s)]. First-pass MRA images (3D-GRE, TR/TE 4.5/1.7 msec, flip angle 25 degrees ) were obtained with 45 micromol Fe/kg VSOP-C63 in comparison with 0.2 mmol Gd/kg of gadolinium diethylene triamine pentaacetic acid (Gd DTPA; before and every 5 seconds p.i.). MRA (3D GRE, TR/TE 4.5/1.7 msec, flip angle 25 degrees) of coronary vessels in rabbits was performed after i.v. injection of 45 micromol Fe/kg of VSOP-C63. In rats maximal S/N ratio in thoracic and abdominal arteries directly after i.v. injection of VSOP-C63 was 25 +/- 1, 43 +/- 2, 49 +/- 4, 57 +/- 3, 64 +/- 3, and 63 +/- 3 for the different dosages. Blood half-life was dose dependent (15 +/- 2, 20 +/- 3, 29 +/- 6, 37 +/- 5, 61 +/- 16, and 86 +/- 21 minutes). At a dose of 30 micromol Fe/kg even small intrarenal arteries were sharply delineated. First-pass MRA showed no significant difference in the S/N ratio between Gd-DTPA (71.5 +/- 11.5) and VSOP-C63 (65.1 +/- 18. 3). The proximal segments of the coronary arteries in rabbits were clearly depicted at a dose of 45 micromol Fe/kg. The monomer-coated, iron oxide-based contrast medium VSOP-C63 exhibits favorable properties as a blood pool agent for both equilibrium and first-pass MRA. J. Magn. Reson. Imaging 2000;12:905-911.

Evaluation of outpatient hysteroscopy, saline infusion hysterosonography, and hysterosalpingography in infertile women: a prospective, randomized study.

OBJECTIVE: To compare the diagnostic accuracy, pain scores, and procedure length of outpatient hysteroscopy (OHS), hysterosalpingography (HSG), and saline infusion hysterosonography (SIS) for evaluation of the uterine cavity of infertile women. DESIGN: Prospective, randomized, investigator-blind study. SETTING: Tertiary infertility clinic. PATIENT(S): Forty-six consecutive infertile women. INTERVENTION(S): Outpatient HSG, OHS, and SIS, followed by operative hysteroscopy (HS). MAIN OUTCOME MEASURE(S): Uterine abnormalities, procedure length, and subjective pain. RESULT(S): Fifty-nine percent of infertile subjects were found to have an abnormality on at least one of three outpatient uterine evaluations. When compared with the case of definitive operative HS, 60% of abnormalities were correctly classified by HSG, 72% by OHS, and 52% by SIS (P: NS). When comparing all combinations of 2 outpatient screening tests to operative hysteroscopy, 68% were correctly classified by HSG/OHS, 58% by HSG/SIS, and 64% by OHS/SIS (P: NS). The average time length for the OHS was 9.1 min., which was significantly greater than for both HSG (average, 5.3 min) and SIS (average, 6.1 min.) (P<.0001 for both). HSG and SIS were not statistically different regarding procedure time length. The average pain score (0-10) for SIS was 2.7, compared with 5.8 and 5.3 for HSG and OHS, respectively. Both HSG and OHS mean pain scores were significantly greater than the SIS mean. CONCLUSION(S): OHS, SIS, and HSG were statistically equivalent regarding evaluation of uterine cavity pathology in infertile women.