Hydrops fetalis due to ABO incompatibility

Hemolytic disease of the newborn due to ABO incompatibility was first observed by Halbrecht in 1944. This entity has a spectrum ranging from minimal hemolysis requiring no therapy, as is the case in most instances, to severe hemolytic disease requiring aggressive management including exchange transfusion in a small percentage of cases. An extreme degree of hemolytic disease of the newborn due to ABO incompatibility, i.e., hydrops fetalis, has not been well documented in the English literature. We present a case of hydrops fetalis due to ABO incompatibility. The severity of hemolytic disease due to ABO incompatibility can be forecast when indicated in selected cases.     

Endocrine cells in the ileum of patients with irritable bowel syndrome

AIM: To study the ileal endocrine cell types in irritable bowel syndrome (IBS) patients.METHODS: Ninety-eight patients with IBS (77 females and 21 males; mean age 35 years, range 18-66 years) were included, of which 35 patients had diarrhea (IBS-D), 31 patients had a mixture of both diarrhea and constipation (IBS-M), and 32 patients had constipation (IBS-C) as the predominant symptoms. The controls were 38 subjects (26 females and 12 males; mean age 40 years, range 18-65 years) who had submitted to colonoscopy for the following reasons: gastrointestinal bleeding, where the source of bleeding was identified as hemorrhoids (n = 24) or angiodysplasia (n = 3), and health worries resulting from a relative being diagnosed with colon carcinoma (n = 11). The patients were asked to complete the: Birmingham IBS symptom questionnaire. Ileal biopsy specimens from all subjects were immunostained using the avidin-biotin-complex method for serotonin, peptide YY (PYY), pancreatic polypeptide (PP), enteroglucagon, and somatostatin cells. The cell densities were quantified by computerized image analysis, using Olympus cellSens imaging software.RESULTS: The gender and age distributions did not differ significantly between the patients and the controls (P = 0.27 and P = 0.18, respectively). The total score of Birmingham IBS symptom questionnaire was 21 ± 0.8, and the three underlying dimensions: pain, diarrhea, and constipation were 7.2 ± 0.4, 6.6 ± 0.4, and 7.2 ± 0.4, respectively. The density of serotonin cells in the ileum was 40.6 ± 3.6 cells/mm² in the controls, and 11.5 ± 1.2, 10.7 ± 5.6, 10.0 ± 1.9, and 13.9 ± 1.4 cells/mm² in the all IBS patients (IBS-total), IBS-D, IBS-M, and IBS-C patients, respectively. The density in the controls differed significantly from those in the IBS-total, IBS-D, IBS-M, and IBS-C groups (P < 0.0001, P = 0.0001, P = 0.0001, and P < 0.0001, respectively). There was a significant inverse correlation between the serotonin cell density and the pain dimension of Birmingham IBS symptom questionnaire (r = -0.6, P = 0.0002). The density of PYY cells was 26.7 ± 1.6 cells/mm² in the controls, and 33.1 ± 1.4, 27.5 ± 1.4, 34.1 ± 2.5, and 41.7 ± 3.1 cells/mm² in the IBS-total, IBS-D, IBS-M, and IBS-C patients, respectively. This density differed significantly between patients with IBS-total and IBS-C and the controls (P = 0.03 and < 0.0001, respectively), but not between controls and, IBS-D, and IBS-M patients (P = 0.8, and P = 0.1, respectively). The density of PYY cells correlated significantly with the degree of constipation as recorded by the Birmingham IBS symptom questionnaire (r = 0.6, P = 0.0002). There were few PP-, enteroglucagon-, and somatostatin-immunoreactive cells in the biopsy material examined, which made it impossible to reliably quantify these cells.CONCLUSION: The decrease of ileal serotonin cells is associated with the visceral hypersensitivity seen in all IBS subtypes. The increased density of PYY cells in IBS-C might contribute to the constipation experienced by these patients.     

Morphology and motor function of the gastrointestinal tract examined with endosonography

Endosonography is a useful tool for studying the morphology and motor function of the gastrointestinal tract. Intraluminal ultrasonography is the common denomination of ultrasound examinations using intracorporal transducers which are inserted into the GI tract. Thus, the visceral wall and adjacent structures can be imaged in detail. This review describes the usefulness of endosonography in gastroenterology, in particular with respect to studies of the biomechanical and motor function of the gastrointestinal tract. New techniques such as 3-D EUS, elastography and strain rate imaging are discussed.     

Three-dimensional surface model analysis in the gastrointestinal tract

The biomechanical changes during functional loading and unloading of the human gastrointestinal (GI) tract are not fully understood. GI function is usually studied by introducing probes in the GI lumen. Computer modeling offers a promising alternative approach in this regard, with the additional ability to predict regional stresses and strains in inaccessible locations. The tension and stress distributions in the GI tract are related to distensibility (tension-strain relationship) and smooth muscle tone. More knowledge on the tension and stress on the GI tract are needed to improve diagnosis of patients with gastrointestinal disorders. A modeling framework that can be used to integrate the physiological, anatomical and medical knowledge of the GI system has recently been developed. The 3-D anatomical model was constructed from digital images using ultrasonography, computer tomography (CT) or magnetic resonance imaging (MRI). Different mathematical algorithms were developed for surface analysis based on thin-walled structure and the finite element method was applied for the mucosa-folded three layered esophageal model analysis. The tools may be useful for studying the geometry and biomechanical properties of these organs in health and disease. These studies will serve to test the structurefunction hypothesis of geometrically complex organs.     

Ultrasound-directed drug delivery

It has been proven, that the cellular uptake of drugs and genes is increased, when the region of interest is under ultrasound insonification, and even more when a contrast agent is present. This increased uptake has been attributed to the formation of transient porosities in the cell membrane, which are big enough for the transport of drugs into the cell (sonoporation). Owing to this technique, new ultrasound contrast agents that incorporate a therapeutic compound have become of interest. Combining ultrasound contrast agents with therapeutic substances, such a chemotherapeutics and virus vectors, may lead to a simple and economic method to instantly cure upon diagnosis, using conventional ultrasound scanners. There are two hypotheses for explaining the sonoporation phenomenon, the first being microbubble oscillations near a cell membrane, the second being microbubble jetting through the cell membrane. Based on modeling, high-speed photography, and recent cellular uptake measurements, it is concluded that microbubble jetting behavior is less likely to be the dominant sonoporation mechanism. Ultrasound-directed drug delivery using microbubbles is a promising method that has great potential in the treatment of malignant disorders.     

Sonoporation-Enhanced Chemotherapy Significantly Reduces Primary Tumour Burden in an Orthotopic Pancreatic Cancer Xenograft

Purpose

Adenocarcinoma of the pancreas remains one of the most lethal human cancers. The high mortality rates associated with this form of cancer are subsequent to late-stage clinical presentation and diagnosis, when surgery is rarely possible and of modest chemotherapeutic impact. Survival rates following diagnosis with advanced pancreatic cancer are very low; typical mortality rates of 50 % are expected within 3 months of diagnosis. However, adjuvant chemotherapy improves the prognosis of patients even after palliative surgery, and successful newer neoadjuvant chemotherapeutical modalities have recently been reported. For patients whose tumours appear unresectable, chemotherapy remains the only option. During the past two decades, the nucleoside analogue gemcitabine has become the first-line chemotherapy for pancreatic adenocarcinoma. In this study, we aim to increase the delivery of gemcitabine to pancreatic tumours by exploring the effect of sonoporation for localised drug delivery of gemcitabine in an orthotopic xenograft mouse model of pancreatic cancer.

Experimental Design

An orthotopic xenograft mouse model of luciferase expressing MIA PaCa-2 cells was developed, exhibiting disease development similar to human pancreatic adenocarcinoma. Subsequently, two groups of mice were treated with gemcitabine alone and gemcitabine combined with sonoporation; saline-treated mice were used as a control group. A custom-made focused ultrasound transducer using clinically safe acoustic conditions in combination with SonoVue® ultrasound contrast agent was used to induce sonoporation in the localised region of the primary tumour only. Whole-body disease development was measured using bioluminescence imaging, and primary tumour development was measured using 3D ultrasound.

Results

Following just two treatments combining sonoporation and gemcitabine, primary tumour volumes were significantly lower than control groups. Additional therapy dramatically inhibited primary tumour growth throughout the course of the disease, with median survival increases of up to 10 % demonstrated in comparison to the control groups.

Conclusion

Combined sonoporation and gemcitabine therapy significantly impedes primary tumour development in an orthotopic xenograft model of human pancreatic cancer, suggesting additional clinical benefits for patients treated with gemcitabine in combination with sonoporation.     

Common Pathogenetic Mechanisms in Symptomatic, Uncomplicated Gallstone Disease and Functional Dyspepsia (Volume Measurement of Gallbladder and Antrum Using Three-Dimensional Ultrasonography)

Following cholecystectomy for uncomplicatedgallstone disease (GS) some patients experiencepersistent symptoms suggesting an underlying functionaldisorder. To study this phenomenon, we have comparedsymptomatic GS with functional dyspepsia (FD) patients andhealthy individuals (C) with respect to putativepathogenetic mechanisms. Gallbladder and gastric antrumvolumes were estimated with three-dimensional (3D) ultrasonography before and 10 min afteringestion of 500 ml meat soup in 18 patients with GS.Volume estimation was performed digitally afterinteractive manual tracing and organ reconstruction inthree dimensions. Respiratory sinus arrhythmia (RSA)was calculated to index vagal tone. Abdominal symptomswere assessed by interview. The results were compared topreviously published data in patients with FD and C investigated with the exact samemethods. No significant differences were found betweengroups with respect to fasting gallbladder orgallbladder emptying. Antral volumes both fasting (P< 0.05) and postprandially (P < 0.01) were larger inGS and FD than in C. The soup meal induced dyspepticsymptoms in 2/18 (11% ) of C, 12/18 (67% ) of GS and15/17 (88%) of FD patients (P < 0.001). Compared with C, both GS and FD patients had significantlydecreased vagal tone (P < 0.001). There was nosignificant difference between GS and FD patients withrespect to antral volume, vagal tone, or symptoms. Weconcluded that both gallstone and functional dyspepsiapatients are characterized by dyspeptic symptoms inresponse to ingestion of 500 ml of meat soup, a widegastric antrum, low vagal tone, but normal gallbladder size and emptying. Thus, patients withsymptomatic, uncomplicated gallstone disease andfunctional dyspepsia seem to have common pathogeneticmechanisms.     

Hydrosonography of the small intestine: comparison with radiologic barium study

BACKGROUND: Transabdominal ultrasonography of the small intestine is hampered by luminal gas. We have developed a new sonographic method (hydrosonography) that largely eliminates the gas problem and have compared this method with radiologic barium study. METHODS: Fifty-six patients admitted for X-ray examination of the small bowel because of abdominal pain, diarrhoea, weight loss and/or known inflammatory bowel disease were examined. To remove luminal gas before performing transabdominal ultrasonography, 21 of polyethylene glycol solution was inserted through a nasojejunal tube by means of a peristaltic pump. Wall thickness, peristalsis, luminal narrowing, prestenotic dilatation, and extraintestinal complications were recorded. RESULTS: On ultrasonography we were able to visualize the terminal part of the ileum in 98% of the patients. Perfect agreement between hydrosonography and barium studies was seen in 50 of 55 patients. However, 44 patients had normal findings on both examinations. The sensitivity and specificity of hydrosonography were 64% and 100%, respectively. The positive predictive value was 100%. For X-ray examination sensitivity and specificity were 91% and 100%, respectively. Four patients with minor mucosal abnormalities or pathologic findings in the upper part of the small intestine accounted for the relatively low overall sensitivity found for hydrosonography compared with roentgenography. However, important extraintestinal complications were disclosed by ultrasound. CONCLUSIONS: Hydrosonography of the small bowel is a new, convenient, and reliable method for examining the lower part of the small intestine. However, it cannot replace barium studies in patients with mucosal abnormalities. especially in the upper part of the small bowel.