Assistive AI in Lung Cancer Screening: A Retrospective Multinational Study in the United States and Japan.

Purpose To evaluate the impact of an artificial intelligence (AI) assistant for lung cancer screening on multinational clinical workflows. Materials and Methods An AI assistant for lung cancer screening was evaluated on two retrospective randomized multireader multicase studies where 627 (141 cancer-positive cases) low-dose chest CT cases were each read twice (with and without AI assistance) by experienced thoracic radiologists (six U.S.-based or six Japan-based radiologists), resulting in a total of 7524 interpretations. Positive cases were defined as those within 2 years before a pathology-confirmed lung cancer diagnosis. Negative cases were defined as those without any subsequent cancer diagnosis for at least 2 years and were enriched for a spectrum of diverse nodules. The studies measured the readers' level of suspicion (on a 0-100 scale), country-specific screening system scoring categories, and management recommendations. Evaluation metrics included the area under the receiver operating characteristic curve (AUC) for level of suspicion and sensitivity and specificity of recall recommendations. Results With AI assistance, the radiologists' AUC increased by 0.023 (0.70 to 0.72; P = .02) for the U.S. study and by 0.023 (0.93 to 0.96; P = .18) for the Japan study. Scoring system specificity for actionable findings increased 5.5% (57% to 63%; P < .001) for the U.S. study and 6.7% (23% to 30%; P < .001) for the Japan study. There was no evidence of a difference in corresponding sensitivity between unassisted and AI-assisted reads for the U.S. (67.3% to 67.5%; P = .88) and Japan (98% to 100%; P > .99) studies. Corresponding stand-alone AI AUC system performance was 0.75 (95% CI: 0.70, 0.81) and 0.88 (95% CI: 0.78, 0.97) for the U.S.- and Japan-based datasets, respectively. Conclusion The concurrent AI interface improved lung cancer screening specificity in both U.S.- and Japan-based reader studies, meriting further study in additional international screening environments. Keywords: Assistive Artificial Intelligence, Lung Cancer Screening, CT Supplemental material is available for this article. Published under a CC BY 4.0 license.

An intentional approach to managing bias in general purpose embedding models.

Advances in machine learning for health care have brought concerns about bias from the research community; specifically, the introduction, perpetuation, or exacerbation of care disparities. Reinforcing these concerns is the finding that medical images often reveal signals about sensitive attributes in ways that are hard to pinpoint by both algorithms and people. This finding raises a question about how to best design general purpose pretrained embeddings (GPPEs, defined as embeddings meant to support a broad array of use cases) for building downstream models that are free from particular types of bias. The downstream model should be carefully evaluated for bias, and audited and improved as appropriate. However, in our view, well intentioned attempts to prevent the upstream components-GPPEs-from learning sensitive attributes can have unintended consequences on the downstream models. Despite producing a veneer of technical neutrality, the resultant end-to-end system might still be biased or poorly performing. We present reasons, by building on previously published data, to support the reasoning that GPPEs should ideally contain as much information as the original data contain, and highlight the perils of trying to remove sensitive attributes from a GPPE. We also emphasise that downstream prediction models trained for specific tasks and settings, whether developed using GPPEs or not, should be carefully designed and evaluated to avoid bias that makes models vulnerable to issues such as distributional shift. These evaluations should be done by a diverse team, including social scientists, on a diverse cohort representing the full breadth of the patient population for which the final model is intended.

Deep Learning Detection of Active Pulmonary Tuberculosis at Chest Radiography Matched the Clinical Performance of Radiologists.

Background The World Health Organization (WHO) recommends chest radiography to facilitate tuberculosis (TB) screening. However, chest radiograph interpretation expertise remains limited in many regions. Purpose To develop a deep learning system (DLS) to detect active pulmonary TB on chest radiographs and compare its performance to that of radiologists. Materials and Methods A DLS was trained and tested using retrospective chest radiographs (acquired between 1996 and 2020) from 10 countries. To improve generalization, large-scale chest radiograph pretraining, attention pooling, and semisupervised learning ("noisy-student") were incorporated. The DLS was evaluated in a four-country test set (China, India, the United States, and Zambia) and in a mining population in South Africa, with positive TB confirmed with microbiological tests or nucleic acid amplification testing (NAAT). The performance of the DLS was compared with that of 14 radiologists. The authors studied the efficacy of the DLS compared with that of nine radiologists using the Obuchowski-Rockette-Hillis procedure. Given WHO targets of 90% sensitivity and 70% specificity, the operating point of the DLS (0.45) was prespecified to favor sensitivity. Results A total of 165 754 images in 22 284 subjects (mean age, 45 years; 21% female) were used for model development and testing. In the four-country test set (1236 subjects, 17% with active TB), the receiver operating characteristic (ROC) curve of the DLS was higher than those for all nine India-based radiologists, with an area under the ROC curve of 0.89 (95% CI: 0.87, 0.91). Compared with these radiologists, at the prespecified operating point, the DLS sensitivity was higher (88% vs 75%, P < .001) and specificity was noninferior (79% vs 84%, P = .004). Trends were similar within other patient subgroups, in the South Africa data set, and across various TB-specific chest radiograph findings. In simulations, the use of the DLS to identify likely TB-positive chest radiographs for NAAT confirmation reduced the cost by 40%-80% per TB-positive patient detected. Conclusion A deep learning method was found to be noninferior to radiologists for the determination of active tuberculosis on digital chest radiographs. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by van Ginneken in this issue.

Deep learning for distinguishing normal versus abnormal chest radiographs and generalization to two unseen diseases tuberculosis and COVID-19.

Chest radiography (CXR) is the most widely-used thoracic clinical imaging modality and is crucial for guiding the management of cardiothoracic conditions. The detection of specific CXR findings has been the main focus of several artificial intelligence (AI) systems. However, the wide range of possible CXR abnormalities makes it impractical to detect every possible condition by building multiple separate systems, each of which detects one or more pre-specified conditions. In this work, we developed and evaluated an AI system to classify CXRs as normal or abnormal. For training and tuning the system, we used a de-identified dataset of 248,445 patients from a multi-city hospital network in India. To assess generalizability, we evaluated our system using 6 international datasets from India, China, and the United States. Of these datasets, 4 focused on diseases that the AI was not trained to detect: 2 datasets with tuberculosis and 2 datasets with coronavirus disease 2019. Our results suggest that the AI system trained using a large dataset containing a diverse array of CXR abnormalities generalizes to new patient populations and unseen diseases. In a simulated workflow where the AI system prioritized abnormal cases, the turnaround time for abnormal cases reduced by 7-28%. These results represent an important step towards evaluating whether AI can be safely used to flag cases in a general setting where previously unseen abnormalities exist. Lastly, to facilitate the continued development of AI models for CXR, we release our collected labels for the publicly available dataset.

Effects of ABO incompatibility in allogeneic hematopoietic stem cell transplantation.

INTRODUCTION: The impact of ABO mismatch on outcomes following allo-HSCT remains controversial. In this study, our aim is to define the effect of ABO mismatch on post-transplant outcomes, engraftment kinetics and complications in a large cohort. PATIENTS AND METHODS: We retrospectively identified 1000 patients who underwent allo-HSCT from either bone marrow or peripheral blood stem cells at our center between 1988 and 2016. P<0.05 was considered statistically significant. RESULTS: Five hundred and ninety (59%) patient-donor pairs were ABO matched, 164 (16.4%) were ABO major mismatched (MM), 191 (19.1%) were ABO minor MM, and 55 (5.5%) were ABO bi-directionally MM. ABO matched pairs were more common in transplants from related donors (P<0.001) and using bone marrow as a stem cell source (P<0.001). In minor ABO MM transplantations, mild delayed hemolytic reaction occurred more frequently compared to major and bidirectional ABO MM transplantations (47% vs 35% and 18%, P<0.001). Neutrophil engraftment was slightly delayed in ABO MM patient-donor pairs when compared ABO matched donor pairs according to median engraftment time in all group (167/410, 41% vs 204/590, 35%, P=0.046). Pure red cell aplasia was diagnosed in 6 patients (1%). Higher risk of death was shown in ABO MM transplants compared to ABO matched transplants in overall survival (OS) analysis (HR:1.201, 95% CI:1.004-1.437, P=0.045). The non-relapse mortality (P=0.546) and cumulative incidences of acute graft versus host disease (aGVHD) and chronic (c) GVHD were comparable between ABO MM and ABO matched patient-donor pairs (for aGVHD, P=0.235; for cGVHD, P=0.137). CONCLUSION: ABO MM transplants were associated with decreased OS and slightly delayed neutrophil engraftment. NRM and the risk of GVHD were not related to ABO incompatibility.

Author Correction: End-to-end lung cancer screening with three-dimensional deep learning on low-dose chest computed tomography.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

End-to-end lung cancer screening with three-dimensional deep learning on low-dose chest computed tomography.

With an estimated 160,000 deaths in 2018, lung cancer is the most common cause of cancer death in the United States1. Lung cancer screening using low-dose computed tomography has been shown to reduce mortality by 20-43% and is now included in US screening guidelines1-6. Existing challenges include inter-grader variability and high false-positive and false-negative rates7-10. We propose a deep learning algorithm that uses a patient's current and prior computed tomography volumes to predict the risk of lung cancer. Our model achieves a state-of-the-art performance (94.4% area under the curve) on 6,716 National Lung Cancer Screening Trial cases, and performs similarly on an independent clinical validation set of 1,139 cases. We conducted two reader studies. When prior computed tomography imaging was not available, our model outperformed all six radiologists with absolute reductions of 11% in false positives and 5% in false negatives. Where prior computed tomography imaging was available, the model performance was on-par with the same radiologists. This creates an opportunity to optimize the screening process via computer assistance and automation. While the vast majority of patients remain unscreened, we show the potential for deep learning models to increase the accuracy, consistency and adoption of lung cancer screening worldwide.

Early initiation of extracorporeal photochemotherapy increases response for chronic graft versus host disease following steroid failure.

OBJECTIVES: Chronic graft versus host disease (GVHD) is one of the major obstacles to achieve success in allogeneic hematopoietic stem cell transplantation (allo-HSCT). Extracorporeal photochemotherapy (ECP) has been demonstrated to be an effective modality for the treatment of GVHD in previous studies but they vary in terms of initiation and duration. Our aim is to demonstrate the characteristics of our patients who received ECP for chronic GVHD to clarify the best treatment scheme. MATERIAL AND METHODS: In this study, we retrospectively evaluated 34 patients with steroid refractory chronic GVHD (n=34) who were treated with ECP between 2001 and 2015. The initiation of ECP was determined according to patient status and the physician's preference. RESULTS: ECP was initiated early (≤3months) as the preferred second-line treatment after failure of methylprednisolone treatment in 12 patients (35%), 22 steroid refractory patients (65%) received ECP later. In all cohorts, 10 (29%) and 14 (41%) of 34 patients achieved complete response (CR) and partial response (PR), respectively, with an overall response rate (ORR) of 70. Early initiation of ECP after chronic GVHD diagnosis (≤3months vs more than 3months) was associated with increased rates of response (92% vs 59%, P=0.046) in which the severity of diseases were similar. Patients with skin involvement in early treatment group had statistically better response. Mild side effects were detected in only 6 patients (16%). CONCLUSION: ECP is a safe treatment modality and particularly effective when initiated soon after steroid failure in chronic GVHD.

Extracorporeal photochemotherapy in mycosis fungoides.

OBJECTIVES: Extracorporeal photo-chemotherapy (ECP, photopheresis) is an approved treatment modality for mycosis fungoides (MF). Our aim is to present our ECP data for MF. METHODS: We retrospectively evaluated 50 MF patients who received ECP for clinical activity, toxicity, and response and outcome rates, and we compared these with combination therapies. RESULTS: The overall response rate (ORR) was 42% (21/50), while the median time to response was 11months (range, 3-48months). Ten of the responders (48%) had 3 or more treatment lines prior to ECP. Eight patients (16%) had adverse events related to ECP. The overall survival (OS) of 50 patients was 72months (range, 3-211). There was no statistically significant difference in the OS in early-stage vs late-stage patients (77 vs 69months, P=0.077). The stage 3 and 4 patients received an average of 31 cycles compared to 55 cycles in stage 1 and 2 patients (P=0.006). The increased extent of ECP was not correlated with the response. Combined treatment with ECP significantly improved the OS (84months vs 62months, P=0.005). DISCUSSION: A low frequency of side effects and improved OS observed in combination therapy makes ECP a favorable option for treating MF.

Reproducibility of dynamic contrast-enhanced MR imaging. Part II. Comparison of intra- and interobserver variability with manual region of interest placement versus semiautomatic lesion segmentation and histogram analysis.

PURPOSE: To compare the inter- and intraobserver variability with manual region of interest (ROI) placement versus that with software-assisted semiautomatic lesion segmentation and histogram analysis with respect to quantitative dynamic contrast material-enhanced (DCE) MR imaging determinations of the volume transfer constant (K(trans)). MATERIALS AND METHODS: The study was approved by the institutional review board and compliant with HIPAA. The requirement to obtain informed consent was waived. Fifteen DCE MR imaging studies of the female pelvis defined the study group. Uterine fibroids were used as a perfusion model. Three varying types of lesion measurements were performed by five readers on each study by using DCE MR imaging perfusion analysis software with manual ROI placement and a semiautomatic lesion segmentation and histogram analysis solution. Intra- and interreader variability of measurements of K(trans) with the different measurement types was calculated. RESULTS: The overall interobserver variability of K(trans) with manual ROI placement (mean, 28.5% ± 9.3) was reduced by 42.5% when the semiautomatic, software-assisted lesion measurement method was used (16.4% ± 6.2). Whole-lesion measurement showed the lowest interobserver variability with both measurement methods (20.1% ± 4.3 with the manual method vs 10.8% ± 2.6 with the semiautomatic method). The overall intrareader variability with the manual ROI method (7.6% ± 10.6) was not significantly different from that with the semiautomatic method (7.3% ± 10.8), but the intraclass correlation coefficient for intrareader reproducibility improved from 0.86 overall with the manual method to 0.99 with the semiautomatic method. CONCLUSION: A semiautomatic lesion segmentation and histogram analysis approach can provide a significant reduction in interobserver variability for DCE MR imaging measurements of K(trans) when compared with manual ROI methods, whereas intraobserver reproducibility is improved to some extent.

Histogram analysis of whole-lesion enhancement in differentiating clear cell from papillary subtype of renal cell cancer.

PURPOSE: To compare histogram analysis of voxel-based whole-lesion (WL) enhancement to qualitative assessment and region-of-interest (ROI)-based enhancement analysis in discriminating the renal cell cancer (RCC) subtype clear cell RCC (ccRCC) from papillary RCC (pRCC). MATERIALS AND METHODS: In this institutional review board-approved, HIPAA-compliant retrospective study, 73 patients underwent magnetic resonance (MR) imaging prior to surgery for RCC between January 2007 and January 2010. Three-dimensional fat-suppressed T1-weighted gradient-echo corticomedullary phase acquisitions, obtained before and after contrast agent administration, were transferred to a workstation at which automated registration followed by semiautomated segmentation of the RCC was performed. Percent enhancement was computed on a per-voxel basis: (SI(post) - SI(pre))/SI(pre) .100, where SI(pre) and SI(post) indicate signal intensity before and after contrast enhancement, respectively. The WL quantitative parameters of mean, median, and third quartile enhancement and histogram distribution parameters kurtosis and skewness were computed for each lesion. WL enhancement parameters were compared with ROI-based analysis and qualitative assessment with regards to diagnostic accuracy and interreader agreement in differentiating ccRCC from pRCC. RESULTS: There were 19 pRCCs and 55 ccRCCs at pathologic examination. ccRCC had significantly higher WL mean, median, and third quartile enhancement compared with pRCC and hade significantly lower kurtosis and skewness (all P < .001). Third quartile enhancement had the highest accuracy (94.6%; area under the curve, 0.980) in discriminating ccRCC from pRCC, which was significantly higher than the accuracy of qualitative assessment (86.0%; P = .04) but not significantly higher than that of ROI enhancement (89.2%; P = .52). WL enhancement parameters had higher interreader agreement (κ = 0.91-1.0) compared with ROI enhancement or qualitative assessment (κ = 0.83 and 0.7, respectively) in discriminating ccRCC from pRCC. CONCLUSION: WL enhancement histogram analysis is feasible and can potentially be used to differentiate ccRCC from pRCC with high accuracy. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12111281/-/DC1.

Hepatocellular carcinoma: response to TACE assessed with semiautomated volumetric and functional analysis of diffusion-weighted and contrast-enhanced MR imaging data.

PURPOSE: To determine the association of early changes in posttreatment apparent diffusion coefficient (ADC) and venous enhancement (VE) with tumor size change after transarterial chemoembolization (TACE) by using an investigational semiautomated software. MATERIALS AND METHODS: This retrospective HIPAA-compliant study was approved by the institutional review board, with waiver of informed consent. Patients underwent magnetic resonance (MR) imaging at 1.5 T before TACE, as well as 1 and 6 months after TACE. Volumetric analysis of change in ADC and VE 1 month after TACE compared with pretreatment values was performed in 48 patients with 71 hepatocellular carcinoma (HCC) lesions. Diagnostic accuracy was evaluated with receiver operating characteristic (ROC) analysis, using tumor response at 6 months according to Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST as end points. RESULTS: According to RECIST criteria, 6 months after TACE, 30 HCC lesions showed partial response (PR), 35 showed stable disease (SD), and six showed progressive disease (PD). Increase in ADC and decrease in VE 1 month after TACE were significantly different between PR, SD, and PD. At area under the ROC curve (AUC) analysis of the ADC increase, there was an AUC of 0.78 for distinguishing PR from SD and PD and an AUC of 0.89 for distinguishing PR and SD from PD. The AUC for decrease in VE was 0.73 for discrimination of PR from SD and PD and 0.90 for discrimination of PR and SD from PD. CONCLUSION: Volumetric analysis of increase in ADC and decrease in VE 1 month after TACE can provide an early assessment of response to treatment. Volumetric analysis of multiparametric MR imaging data may have potential as a prognostic biomarker for patients undergoing local-regional treatment of liver cancer.

Automated CT scoring of airway diseases: preliminary results.

RATIONALE AND OBJECTIVES: The aim of this study was to retrospectively evaluate an automated global scoring system for evaluating the extent and severity of disease in a known cohort of patients with documented bronchiectasis. On the basis of a combination of validated three-dimensional automated algorithms for bronchial tree extraction and quantitative airway measurements, global scoring combines the evaluation of bronchial lumen-to-artery ratios and bronchial wall-to-artery ratios, as well as the detection of mucoid-impacted airways. The result is an automatically generated global computed tomographic (CT) score designed to simplify and standardize the interpretation of scans in patients with chronic airway infections. MATERIALS AND METHODS: Twenty high-resolution CT data sets were used to evaluate an automated CT scoring method that combines algorithms for airway quantitative analysis that have been individually tested and validated. Patients with clinically documented atypical mycobacterial infections with visually assessed CT evidence of bronchiectasis varying from mild to severe were retrospectively selected. These data sets were evaluated by two independent experienced radiologists and by computer scoring, with the results compared statistically, including Spearman's rank correlation. RESULTS: Computer evaluation required 3 to 5 minutes per data set, compared to 12 to 15 minutes for manual scoring. Initial Spearman's rank tests showed positive correlations between automated and readers' global scores (r = 0.609, P = .01), extent of bronchiectasis (r = 0.69, P = .0004), and severity of bronchiectasis (r = 0.61, P = .01), while mucus plug detection showed a lesser extent of positive correlation between the scoring methods (r = 0.42, P = .07) and wall thickness a negative weak correlation (r = -0.10, P = .40). Further retrospective review of 24 lobes in which wall thickness scores showed the highest discrepancy between manual and automated methods was then performed, using electronic calipers and perpendicular cross-sections to reassess airway measurements. This resulted in an improved Spearman's rank correlation to r = 0.62 (P = .009), for a global score of r = 0.67 (P = .001). CONCLUSION: Automated computerized scoring shows considerable promise for providing a standardized, quantitative method, demonstrating overall good correlation with the results of experienced readers' evaluation of the extent and severity of bronchiectasis. It is speculated that this technique may also be applicable to a wide range of other conditions associated with chronic bronchial inflammation, as well as of potential value for monitoring response to therapy in these same populations.

Computer-aided diagnosis of the airways: beyond nodule detection.

Although to date, the major impetus for the development of computer-assisted diagnosis (CAD) has been the detection of pulmonary nodules, CAD should properly be viewed as a potential tool for assisting radiologic interpretation of the entire gamut of chest diseases, including not just enhanced detection of disease but also characterization and quantification, ideally leading to improved patient management. The use of CAD to improve visualization of the airways using advanced computer techniques, including sophisticated methods for obtaining 3-dimensional segmentation of the central airways and, in particular, the development of virtual bronchoscopy has been recently studied. In this paper, the authors review the development of a specific series of CAD applications enabling automated identification and characterization of chronically inflamed airways. The advantages to the use of computer methodologies to quantify peripheral airway disease include reproducible visualization methods to display the location, severity, and extent of airway dilatation, bronchial wall thickening, and the presence of mucoid impacted airways. Currently, a number of semiquantitative global scoring systems have been proposed to assess disease extent and severity in patients with bronchiectasis. Unfortunately, with the exception of patients with cystic fibrosis, these are rarely if ever employed, largely owing to the considerable inconvenience of measuring individual airway dimensions and computing a global score. It is apparent that for this specific purpose, CAD may be ideally suited. Automated staging allows for more complete assessment of the entire bronchial tree while providing improved standardization and eliminating an otherwise tedious and time-consuming task.

The effect of taurine on mesenteric blood flow and organ injury in sepsis.

Endotoxin decreases mesenteric blood flow and inflicts organ injury via free radicals. We investigated whether taurine, an endogenous antioxidant and vasodilator, could attenuate the deleterious effects of endotoxin in a mouse model of sepsis. Swiss albino mice were allocated into four groups and treated either with taurine (150 mg/kg, i.p. at 0(th), 8(th), 16(th) h) or its solvent sterile saline (NaCl 0.9%, w/v) while E. coli endotoxin (20 mg/kg, i.p.) or its solvent saline were also given at 8(th) h. At 24(th) h the animals were anaesthetized and the mesenteric blood flow was measured by using perivascular ultrasonic Doppler-flowmeter. The animals were then exsanguinated, the spleen, liver, and kidneys were isolated for histopathological examination. Thiobarbituric acid-reacting substances (TBARS), glutathione, and myeloperoxidase activity were determined in the liver samples. Endotoxin significantly decreased the mesenteric blood flow and glutathione levels in liver while TBARS and myeloperoxidase activity were increased. However, taurine did not block the deleterious effects of endotoxin nor it did attenuate the histopathological injury. Therefore, we concluded that endotoxin-induced organ injury via free radicals is resistant to blockade by taurine.

Boundary-specific cost functions for quantitative airway analysis.

Computed tomography (CT) images of the lungs provide high resolution views of the airways. Quantitative measurements such as lumen diameter and wall thickness help diagnose and localize airway diseases, assist in surgical planning, and determine progress of treatment. Automated quantitative analysis of such images is needed due to the number of airways per patient. We present an approach involving dynamic programming coupled with boundary-specific cost functions that is capable of differentiating inner and outer borders. The method allows for precise delineation of the inner lumen and outer wall. The results are demonstrated on synthetic data, evaluated on human datasets compared to human operators, and verified on phantom CT scans to sub-voxel accuracy.

In vitro and in vivo studies of ibuprofen-loaded biodegradable alginate beads.

The irritation effects of ibuprofen, a widely used non-steroidal anti-inflammatory drug (NSAID), were evaluated on mouse gastric and duodenal mucosa when suspended in 0.5% (w/v) sodiumcarboxymethylcellulose (NaCMC) solution and loaded in alginate beads. The ionotropic gelation method was used to prepare controlled release alginate beads of ibuprofen. The influence of various formulation factors on the encapsulation efficiency, as in vitro drug release and micromeritic properties, was investigated. Other variables included the alginate concentration, percentage drug loading and stirring speed during the microencapsulation process. Scanning electron micrographs of alginate beads loaded with ibuprofen showed rough surface morphology and particle sizes in the range of 1.15 +/- 0.4 - 3.15 +/- 0.6 mm. The yield of microspheres, as collected after drying, was generally 80-90%. Formulation code H showing t50% value of 3.5 h was chosen for in vivo trials because of the appropriate drug release properties. For in vivo trials, free ibuprofen (100 mg kg(-1)), blank and ibuprofen (100 mg kg(-1)) loaded alginate beads (formulation code H) were suspended in 0.5% (w/v) NaCMC solution and each group was given to six mice orally by gavage. NaCMC solution was used as a control in experimental studies. In vivo data showed that the administration of ibuprofen in alginate beads prevented the gastric lesions.

Myogenesis within the human gubernaculum: histological and immunohistochemical evaluation.

BACKGROUND: The presence of varying amounts of smooth muscle (SM) in the patent processus vaginalis suggests that SM plays a role in the descent of the testis. Myogenesis within the gubernaculum (representing primitive mesenchymal tissue) has been evaluated. MATERIALS AND METHODS: Bilateral gubernacula of ten male and five female fetuses were obtained. Sections were stained with hematoxylin-eosin, van Gieson and Gomori trichrome. Expressions of human muscle actin, desmin, vimentin, alpha-smooth muscle actin, human myosin, fast myosin, slow myosin, and Myo-D were determined through immunohistochemistry. The structural alterations and expressions according to the fetal ages were determined within the gubernacula of both sexes. RESULTS: Gubernacula revealed striated muscle at twelve weeks of age. Despite expression of actin and desmin, those muscles did not express Myo-D. Actin and desmin expressing striated muscles ceased to exist until 22 weeks of age. Both vascular SM and cremaster muscle (CM) expressed Myo-D during the 22nd and 23rd weeks. CM additionally expressed alpha-smooth muscle actin. Detection of myofibroblasts in the 22nd week was followed by appearance of the SM in the 27th week in the gubernacula of male fetuses. The same alterations were encountered among the female fetuses at later time points. CONCLUSION: Both smooth muscle and CM develop within the gubernaculum. CM may have transdifferentiated from the vascular SM. If the gubernaculum represents primitive mesenchymal tissue, it ceases to exist after the development of muscles.

Early cirrhosis in a patient with type I citrullinaemia (CTLN1).

A 17-month-old girl with type I classical citrullinaemia (CTLN1) presenting with early cirrhosis and unusual ultrastructural features of the liver is reported. The patient is homozygous for a splicing mutation in intron 15 of the argininosuccinate synthase gene.