Evaluation of capsule endoscopy in active, mild-to-moderate, overt, obscure GI bleeding

BACKGROUND: The role of capsule endoscopy (CE) in the diagnosis of active mild-to-moderate GI bleeding (GIB) immediately after a negative EGD and ileocolonoscopy has not been prospectively evaluated. OBJECTIVE: To estimate the diagnostic yield and clinical significance of CE in patients with acute, obscure, overt, mild-to-moderate GIB. DESIGN: A single-center prospective study. PATIENTS: During a 3-year period, 573 patients admitted to the hospital with acute mild-to-moderate GIB were included in this study. Among them, 37 patients (6.5%) with negative endoscopic findings, after urgent upper- and lower-GI endoscopies, underwent CE within the first 48 hours to identify the source of bleeding. RESULTS: CE revealed active bleeding in 34 patients and a diagnostic yield of 91.9%, including angiodysplasias in 18 patients, ulcers in 3 patients, and tumors in 2 patients. In the remaining 11 patients (32%), CE revealed the site of bleeding: distal duodenum in 1 case (9%), jejunum in 6 cases (54%), ileum in 2 cases (18%), and cecum in 2 cases (18%). From the 37 bleeders, 16 were managed conservatively, 14 endoscopically, and 7 surgically. During a 12-month follow-up period, bleeding recurrence was observed in 5 of 32 (15.6%). LIMITATIONS: This study had a limited number of patients. CONCLUSIONS: CE appeared to have a high diagnostic yield in patients with acute, mild-to-moderate, active hemorrhage of obscure origin when performed in the hospital after a negative standard endoscopic evaluation and has important clinical value in guiding medical management.     

Assessment of obstruction in adult ureterocele by means of color Doppler duplex sonography

AIM: The purpose of this study is to present a method for identifying a ureteral obstruction in unilateral orthotopic ureterocele by means of conventional sonography and color Doppler duplex sonography. We focus on the measurement of the ureterocele dimensions, the degree of dilation it causes to the ipsilateral upper urinary tract, the registration of urine out-flow from the ureteral orifice into the bladder and its spectral analysis. MATERIAL AND METHOD: Over 2 years at our institutions, 8 adult patients (7 women, 1 man) were diagnosed as having a single system orthotopic ureterocele. Four of them presented with lumbar pain, dysuria and recurrent urinary tract infections, while the remainder were asymptomatic and diagnosed accidentally. The diagnosis was based on serial sonography of the upper and lower urinary tract confirmed by intravenous pyelography and cystoscopy. We also performed color Doppler duplex sonographic evaluation of the urine jets ejected from both ureteral orifices into the bladder. Using the flow spectral study we analyzed the waveforms and measured their duration and flow rate. The study was completed with a comparative analysis of the data obtained from both ureteral orifices. RESULTS: Cystic dilation of the lower ureteric extremity into the bladder was presented in all cases. Upper urinary tract dilation, of various grades, was present in 4 of 8 patients. Differences in urine jets between those derived from the ureterocele and those from the healthy contralateral ureteral orifice were significant in those patients with dilation of the upper urinary tract. The differences concerned mainly the frequency and symmetry of the jets as well as the pattern, duration and velocity of their waves. The 4 above-mentioned patients, with dilated upper urinary tracts and waveforms differentiated from the contralateral ones, were characterized as obstructive. On the other hand, the remaining 4 patients with subclinical ureterocele showed insignificant differences in urine jets and waveforms, and were found to be non-obstructive. CONCLUSION: Conventional sonography of the urinary tract in combination with color Doppler duplex sonography of the ureteral jets can be used in an attempt to diagnose and evaluate a unilateral orthotopic (single system) ureterocele and assess the necessity of intervention to identify the obstruction.     

Nephrogenic adenoma of the urinary bladder

Introduction: The nephrogenic adenoma (NA) is a benign metaplastic lesion of the urothelium and is attributed to chronic irritation of the mucosa, by injury, infection, stone disease or intravesical instrumentations. We present our experience on this morbid entity, its clinical appearance in the urinary bladder, its frequency and relapses. Furthermore we reviewed the related recent literature and focused on its potential to neoplastic degeneration and the value of the new diagnostic modalities. Patients and methods: Four patients with NA of the urinary bladder are presented. The papilloid or polypoid formations observed by the cystoscopy were identified after the TUR, as NA of the urinary bladder. Their mean follow-up was 3.5 years. Results: Remission of the symptoms was observed after TUR in all patients. Three out of four patients presented 1–7 relapses, while in one case, after seven NA relapses, a urothelial carcinoma of the bladder was diagnosed. Conclusions: Unlike histological features, the clinical – endoscopic characteristics of NA are non-specific. Even if it is not definitely considered like a premalignant condition, NA has to be followed up frequently and long lasting, because of its high recurrence rate. The combination of Cytology, Flow cytometry, DNA image analysis and Fluorescence in situ hybridisation of bladder washings or voided urine, are of high value in monitoring NA of the urothelium.     

Abnormal propeptide processing resulting in the presence of two abnormal species of protein C in plasma: characterization of the dysfunctional protein C Padua3 (protein C(R-1L/propeptide)).

A heterozygous G-->T transversion at position 1388 of the protein C (PC) gene which predicted the substitution of Arg(-1) to a Leu (PC(R-1L)) was identified in a thrombophilic patient. The PC(R-1L) was purified from the patient's plasma by immunoaffinity chromatography using Ca++-independent and Ca++-dependent monoclonal antibodies. NH2-terminal sequencing of the light chain of PC(R-1L) revealed two amino acid sequences: one was identical to the complete propeptide sequence of PC, while the other matched the normal PC light chain sequence elongated by one amino acid (Leucine at position 1). Activated PC(R-1L/propeptide) exhibited normal amidolytic and impaired anticoagulant activity. Thus, the substitution of a Leu for an Arg at position -1 of PC shifts the propeptidase cleavage site by one amino acid. In addition, in PC(R-1L/propeptide) the propeptide cleavage at Lys(-2) is less efficient since approximately 60% of PC variant molecules present in patient's plasma retained the entire propeptide. Our findings suggest that depending on the specific amino acid substitution at position-1, PC can be secreted in plasma containing the entire propeptide attached to the light chain. Impaired interaction of elongated APC molecules with a membrane-surface and/or factor Va which is the physiological substrate for APC, is manifested in vivo by thrombophilia.     

Abnormality of the N-terminal portion of von Willebrand factor in type IIA and IIC von Willebrand disease

We have established a new analytical method which allows the characterization of von Willebrand factor (vWF) degradation fragments in minute amounts (10 microliters) of plasma, without the need for immunopurification of vWF. Plasma vWF was hydrolysed by S aureus V-8 protease (V-8 protease) and the cleaved fragments separated by SDS-agarose gel electrophoresis followed by staining with 125I-labeled polyclonal or monoclonal antibodies against vWF and autoradiography. Quantification of the amount of each product was estimated by counting the incorporated radioactivity following excision. V-8 protease limitedly hydrolysed vWF in normal as well as type I von Willebrand disease (vWD) plasma and produced two distinct fragments with identical electrophoretic and antigenic characteristics to those produced from purified vWF, i.e. a C-terminal SpII and a series of N-terminal SpIII fragments (SpIIIa, b and c). The method was applied to further characterize the molecular abnormalities of vWF in eighteen patients with type II vWD. In seven individuals with type IIA and five patients with type IIC, SpIII appeared significantly modified as compared to normal. In type IIA, there was a marked decrease or absence of SpIIIa and an increase of SpIIIb and c. In type IIC, SpIIIb was lacking. In three patients with type IIB and in three patients with type IID, there was no significant modification of SpIII. In all cases, SpII was apparently not modified. In conclusion, the molecular abnormality of vWF in type IIA and IIC vWD appears to reside in SpIII, the N-terminal portion of the vWF-subunit (residues 1 to 1,365).     

Localization of a collagen-interactive domain of human von Willebrand factor between amino acid residues Gly 911 and Glu 1,365

A collagen-binding domain of von Willebrand factor (vWF) has been identified in the central part of the molecule by comparing the binding properties of vWF and Staphylococcus aureus V-8 protease-generated vWF fragments with collagen. The binding of purified human vWF to human type III collagen was found to be specific. At saturation, 38 to 50.2 micrograms of vWF bound per milligram of collagen. Scatchard plots derived from binding isotherms demonstrated the presence of at least two classes of binding sites. Purified vWF was digested with S aureus V-8 protease into two complementary fragments (SpIII and SpII). SpII, the C-terminal end of vWF (amino acid residues 1,366 to 2,050), was totally devoid of affinity for collagen. Contrarily, purified SpIII, the N-terminal part of vWF (residues 1 to 1,365), totally displaced vWF binding and specifically bound to collagen. At saturation, 25 to 45 micrograms of SpIII bound per milligram of collagen. Scatchard plots demonstrated the presence of a single class of binding sites. SpIII was further digested with the same enzyme to generate SpI, a 52-kilodalton fragment from the C-terminal part of SpIII (residues 911 to 1,365). Spl induced a dose-dependent inhibition of both vWF and SpIII binding to collagen. A series of six monoclonal antibodies against SpIII that completely abolished vWF and SpIII interaction with collagen also bound to SpI. In conclusion, SpI extending between amino acid residues 911 and 1,365 of vWF contains a specific site that interacts with human type III collagen.