An ultra-miniinvasive treatment for stress urinary incontinence in complicated older patients

Objective

To evaluate use of bulking agents (polydimethylsiloxane) as an alternative treatment of female stress urinary incontinence (SUI) in older patients.

Study design

Prospective cohort study.

Main outcome measures

Women with age >75 years old, affected by stress urinary incontinence, presenting to our institution between January 2005 and January 2008 were considered for eligibility in this prospective study. All patients were submitted to transurethral implantation using Macroplastique Implantation System (MIS) (Uroplasty, Minneapolis, Minnesota). Cure of SUI was defined as the resolution of SUI symptoms. Objective cure rate was assessed by urogynecological physical examination and urodynamic assessment performed at 6 and 12 months after surgery respectively. Subjective cure rate was assessed during the interview of the 12th month with a visual analogue scale (VAS) for quantification of SUI severity and a standardized question about the repeatability of the procedure.

Results

A total of 27 consecutive patients were enrolled in this study. After 12 months of surgery the objective cure rate was 44% (12 of 27 patients), the improvement rate was 33% (9 of 27) and the failure rate was 22% (6 of 27). The overall success rate was 77% (12 patients cured and 9 improved). 23 (85%) patients would like to repeat this surgical procedure if necessary.

Conclusion

Transurethral implantation of bulking agents should be considered as alternative treatment of SUI in complicated older patients.     

Proteomic and postproteomic characterization of keratan sulfate-glycanated isoforms of thyroglobulin and transferrin uniquely elaborated by papillary thyroid carcinomas

Previous studies have suggested that surface components of papillary thyroid carcinoma (PTC) cells may be aberrantly glycanated, but the precise nature of these molecules has not been unveiled nor documented to be of clinical relevance. A monoclonal antibody was raised against a unique keratan sulfate (KS) determinant and used to differentially screen benign and malignant thyroid tissue for the expression of components carrying these moieties. In a total of 349 cases of benign and malignant thyroid lesions, 100% of the 115 PTC cases examined (including various histological subtypes) were found to contain KS-bearing molecules, whereas these were virtually absent from benign tissues and other thyroid tumors, with the exception of 21% of the follicular carcinoma cases analyzed. A composite immunoaffinity chromatography, immunochemistry, and mass spectrometric approach revealed that the PTC-specific KS-bearing macromolecules were unique glycoforms of thyroglobulin and transferrin. Combined, reciprocal immunoprecipitation and Western blotting further indicated that the former glycoform predominated and that most of the transferrin produced by PTC was glycanated with KS moieties. Fluorescent keratanase II-based fingerprinting of the KS moieties bound to these isoforms further demonstrated several PTC-specific peculiarities: 1) that a considerable portion of the moieties was covalently attached via a novel core protein linkage structure; 2) they had an unusual extended average length; 3) an unusual relative ratio of highly sulfated disaccharides terminating with alpha (2-3)-linked N-acetylneuraminic acid capping residues; and 4) a novel unidentified oligosaccharide moiety at the nonreducing terminus. Comparative analysis of the relative distribution of transferrin in benign versus PTC tissues highlighted a marked malignancy-associated abundance of the molecule, with a >75% frequency in expression in PTC. These findings demonstrate that PTC cells synthesize unique post-translationally modified thyroglobulin and transferrin variants in situ that may be directly exploitable for diagnosis, through histological and noninvasive cytological procedures; for devising novel strategies for antibody-guided imaging of this tumor in vivo; and for postsurgery follow-up of PTC patients.     

Morphological features in human cortical brain microvessels after head injury: a three-dimensional and immunocytochemical study

We studied the morphology of cortical microvessels in the brains of 10 patients who had died after receiving a traumatic head injury (THI). Scanning electron microscopy (SEM) of vascular corrosion casts, confocal microscopy of histological sections after immunocytochemistry, and detection of apoptosis by terminal dUTP nick end labeling (TUNEL) were used. Microvascular casts showed an angioarchitectonic distribution that was defined as normal according to results obtained in a previous, nontraumatic series of subjects. However, when we compared them with previous works, the cast surface of some of the microvessels showed three types of morphological alterations: longitudinal folds, sunken surfaces with craters, and a significant flattening with reduction of lumen. The vessels that were primarily affected were the arterioles and capillaries of the middle and deep cortical vascular zones. Immunostaining with the monoclonal antibody MAS-336 against endothelial cells also showed the presence of longitudinal folds with a thinning of the vascular lumen, cytoplasmic round bodies, and a thickening of the endothelial cell membrane. The TUNEL technique revealed a positive staining of some endothelial cells. The structural alterations we observed indicate that microvessels undergo endothelial cell damage after THI. We suggest that this kind of lesion and the secondary functional injury to the blood-brain barrier (BBB) could play an important role in the development of the secondary lesions that these patients show in the subacute phase.     

Endotics system vs colonoscopy for the detection of polyps

AIM: To compare the endotics system (ES), a set of new medical equipment for diagnostic colonoscopy, with video-colonoscopy in the detection of polyps. METHODS: Patients with clinical or familial risk of colonic polyps/carcinomas were eligible for this study. After a standard colonic cleaning, detection of polyps by the ES and by video-colonoscopy was performed in each patient on the same day. In each single patient, the assessment of the presence of polyps was performed by two independent endoscopists, who were randomly assigned to evaluate, in a blind fashion, the presence of polyps either by ES or by standard colonoscopy. The frequency of successful procedures (i.e. reaching to the cecum), the time for endoscopy, and the need for sedation were recorded. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the ES were also calculated. RESULTS: A total of 71 patients (40 men, mean age51.9 ± 12.0 years) were enrolled. The cecum was reached in 81.6% of ES examinations and in 94.3% of colonoscopies (P = 0.03). The average time of endoscopy was 45.1 ± 18.5 and 23.7 ± 7.2 min for the ES and traditional colonoscopy, respectively (P < 0.0001). No patient required sedation during ES examination, compared with 19.7% of patients undergoing colonoscopy (P < 0.0001). The sensitivity and specificity of ES for detecting polyps were 93.3% (95% CI: 68-98) and 100% (95% CI: 76.8-100), respectively. PPV was 100% (95% CI: 76.8-100) and NPV was 97.7% (95% CI: 88-99.9). CONCLUSION: The ES allows the visualization of the entire colonic mucosa in most patients, with good sensitivity/specificity for the detection of lesions and without requiring sedation.     

Major histocompatibility complex status in breast carcinogenesis and relationship to apoptosis

Major histocompatibility complex (MHC) molecules are of central importance in regulating the immune response against tumors. In this study we used immunohistochemistry to study human leukocyte antigen (HLA) class I and II antigen expression in normal breast tissues and benign, preneoplastic, primary, and metastatic breast lesions using antibodies against beta-2-microglobulin (beta2-m), heavy-chain, and HLA-DR antigens. Whereas all normal tissues and benign lesions were positive for beta2-m and HLA-A, -B, and -C antigens, total loss of HLA class I antigens was found in 37% (11 of 30) of in situ carcinomas, in 43% (56 of 131) of the primary tumors, and in 70% (31 of 45) of the lymph node metastases. HLA-DR was also underexpressed in breast cancer cells; thus 20% (6 of 30) of in situ carcinomas, 15% of invasive carcinomas (20 of 131), and only 1 metastatic case were positive for this antigen. Both HLA class I and II antigen expression were more frequently down-regulated in metastatic lesions than in primary breast lesions (P <0.05), and a tendency toward a simultaneous defective expression of HLA class I and II antigens was observed in primary carcinomas (P = 0.07). However, no correlation was found between the expression of any of the aforementioned molecules and pathological parameters or survival. Interestingly, HLA class I expression was expressed more frequently in tissues with high apoptotic activity and was significantly associated with the expression of the proapoptotic bax gene (P = 0.02), and was inversely associated with expression of the antiapoptotic bcl-2 gene (P = 0.03). We conclude that alterations in HLA class I and II antigen expression are early events in breast carcinogenesis and play significant roles in metastatic progression. In addition, their expression is correlated with apoptosis-regulating proteins, which may influence the cytotoxicity of T cells against HLA class I-specific tumor antigens.     

Migration of human blood dendritic cells across endothelial cell monolayers: adhesion molecules and chemokines involved in subset-specific transmigration

Distinct subsets of dendritic cells (DCs) are present in blood, probably "en route" to different tissues. We have investigated the chemokines and adhesion molecules involved in the migration of myeloid (CD11c(+)) and plasmacytoid (CD123(+)) human peripheral blood DCs across vascular endothelium. Among blood DCs, the CD11c(+) subset vigorously migrated across endothelium in the absence of any chemotactic stimuli, whereas spontaneous migration of CD123(+) DCs was limited. In bare cell migration assays, myeloid DCs responded with great potency to several inflammatory and homeostatic chemokines, whereas plasmacytoid DCs responded poorly to all chemokines tested. In contrast, the presence of endothelium greatly favored transmigration of plasmacytoid DCs in response to CXCL12 (stromal cell-derived factor-1) and CCL5 (regulated on activation, normal T expressed and secreted). Myeloid DCs exhibited a very potent transendothelial migration in response to CXCL12, CCL5, and CCL2 (monocyte chemoattractant protein-1). Furthermore, we explored whether blood DCs acutely switch their pattern of migration to the lymph node-derived chemokine CCL21 (secondary lymphoid-tissue chemokine) in response to microbial stimuli [viral double-stranded (ds)RNA or bacterial CpG-DNA]. A synthetic dsRNA rapidly enhanced the response of CD11c(+) DCs to CCL21, whereas a longer stimulation with CpG-DNA was needed to trigger CD123(+) DCs responsive to CCL21. Use of blocking monoclonal antibodies to adhesion molecules revealed that both DC subsets used platelet endothelial cell adhesion molecule-1 to move across activated endothelium. CD123(+) DCs required beta(2) and beta(1) integrins to transmigrate, whereas CD11c(+) DCs may use integrin-independent mechanisms to migrate across activated endothelium.     

Neural regions essential for writing verbs

Functional imaging data collected during cognitive tasks show which brain regions are active during those tasks, but do not necessarily indicate which regions are essential for those tasks. Here, in a study of two cases of selectively impaired written naming of verbs after focal brain ischemia, we combined imaging and behavioral testing to unambiguously identify brain regions that are crucial for a specific cognitive process. We used magnetic resonance perfusion imaging to show that the selective impairment in each case was due to hypoperfusion (low blood flow) in left posterior inferior frontal gyrus (PIFG) and precentral gyrus (PrG); the impairment was immediately reversed when blood flow was restored to these regions, indicating that parts of the left frontal lobe are crucial for representing and processing verbs.