Benign versus secondary-progressive multiple sclerosis: the potential role of proton MR spectroscopy in defining the nature of disability.

PURPOSEWe determined the clinical utility of proton MR spectroscopy in defining the extent of disability in benign versus secondary-progressive multiple sclerosis (MS).METHODSThirty patients with clinically definite MS, including 16 patients with benign MS and 14 with secondary-progressive MS, and a group of 13 healthy volunteers were studied with combined stimulated-echo acquisition mode proton MR spectroscopy and MR imaging (all patients received contrast material).RESULTSAcute enhancing lesions of benign and secondary-progressive MS were characterized by a reduction in N-acetylaspartate (NAA)/choline and NAA/creatine and an increase in inositol compounds/creatine as compared with normal white matter. Such variations were also detected in chronic unenhancing lesions in patients with secondary-progressive MS, although they were not found in chronic unenhancing lesions in patients with benign MS. Chronic lesions of the two forms of the disease have significative differences in NAA and inositol signals.CONCLUSIONProton MR spectroscopy is able to show metabolic changes occurring in the white matter of patients with MS. Such changes differ according to the phase (acute versus chronic) and the clinical form (benign versus secondary-progressive) of the disease.     

Split-liver transplantation eliminates the need for living-donor liver transplantation in children with end-stage cholestatic liver disease

BACKGROUND: End-stage cholestatic liver disease (ESCLD) is the main indication for liver replacement in children. Pediatric cadaver-organ-donor shortage has prompted the most important evolutions in the technique of liver transplantation, in particular living-donor liver transplantation (LDLT) and split-liver transplantation (SLT). METHODS: Between November 1997 and June 2001, 127 children with ESCLD were evaluated for liver transplantation, and 124 underwent 138 liver transplantations after a median time of 40 days. Causes of liver disease were congenital biliary atresia (n=96), Alagille's syndrome (n=12), Byler's disease (n=8), and other cholestatic diseases (n=8). RESULTS: Ninety (73%) patients received a split-liver graft, 28 (23%) a whole liver, and 6 (4%) a reduced-size liver. Overall 2- and 4-year patient survival rates were 93% and 91%, respectively; the 2- and 4-year graft-survival rates were 84% and 80%, respectively. In split-liver recipients, 4-year patient and graft-survival rates were 91% and 83%, respectively; these were 93% and 78%, respectively, in whole-liver recipients and 67% and 63%, respectively, in reduced-size liver recipients. Retransplantation rate was 11%, whereas mortality rate was 8%. Overall incidence of vascular and biliary complication were 16% and 27%, respectively. CONCLUSIONS: SLT can provide liver grafts for children with ESCLD with an outcome similar to the one reported following LDLT, eliminating mortality while they are on a transplantation wait list. The need for pediatric LDLT should be reevaluated and programs of SLT strongly encouraged and supported at a national and international level.     

Natural history of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a slowly growing tumor, whose natural history is not completely known. Since the hepatocarcinogenetic process may evolve for years in a stepwise fashion from premalignant to overt HCC, detection of early, better treatable tumors is made possible by surveillance of patients at risk. A 6-month interval surveillance with ultrasound is considered cost-effective, generally leading to the identification of a single < 3 cm tumor in 50-70% of the patients at risk. For greater than 2 cm tumors, demonstration of arterial hypervascularization of the node by sonovue US, triphasic spiral CT or MRI is diagnostic for HCC. The diagnosis of a less than 2 cm in diameter tumor may be more difficult due to the risk of false negative diagnoses with contrast imaging technique (50% of the cases) caused by immature arterial vascularization of the small nodules. Prognosis largely depends on the evolutionary stage at which HCC is detected, i.e. a size and number of HCC nodes, vascular invasiveness and degree of liver impairment. The multinodular pattern of HCC, representing one third of all early cancers, heralds poor prognosis, especially for patients not fitting the Milan criteria for liver transplantation. The best prognosis is for a single, less than 5 cm node in compensated cirrhosis without vascular invasion, since this tumor is amenable to both liver transplantation and hepatic resection which may confer long-term survival Better survivals of cirrhotic patients with a recently identified tumors reflect the application of accurate criteria for tumor staging and stringent criteria for curative treatments. However, ageing of the patients, deterioration of liver function during surveillance, occurrence of multinodular tumors and limited access to liver transplantation may hamper surveillance programs effectiveness.     

Alteration of Elastin, Collagen and their Cross-links in Abdominal Aortic Aneurysms

OBJECTIVES: although the mechanism of arterial dilation and aneurysm development has not been clarified, the degradation of elastin and collagen plays undoubtedly a critical role. We evaluated the elastin and collagen content through the detection of their cross-links in aneurysmal and non-aneurysmal abdominal aortic walls. MATERIALS AND METHODS: in 26 human abdominal aortic aneurysm specimens obtained during surgery and in 24 autopsy control samples of non-aneurysmal abdominal aorta the tissue content of elastin and collagen cross-links were measured by HPLC. Collagen was also detected by evaluating two characteristic amino acids, 4-hydroxyproline (4-hypro) with a colorimetric method and 5-hydroxylysine (5-hylys) by gas chromatography. RESULTS: significantly fewer elastin cross-links were found in aneurysm samples compared to controls (desmosines and isodesmosines: 90% reduction; p<0.01). The opposite was true for pyridinoline collagen cross-links (350% increase) and deoxypyridinolines (100% increase, p=0.01). Tissue content of 5-hylys, 4-hypro and total amino acids were reduced significantly by 50% in aneurysmal samples. CONCLUSIONS: beside confirming decreased elastin content in aneurysmal walls, these results show a concurrent increase of collagen cross-links. Since total collagen markers were decreased (decreased 4-hypro and 5-hylys) it is reasonable to suggest that in aneurysmal aortic walls old collagen accumulates cross-links while new collagen biosynthesis is somehow defective.     

Hepatocyte growth factor-modulated rat Leydig cell functions

Hepatocyte growth factor (HGF) regulates many cellular functions acting through c-Met, its specific tyrosine kinase receptor. We previously reported that in prepuberal rats HGF is secreted by the peritubular myoid cells during the entire postnatal testicular development and by the Sertoli cells only at puberty. We have also demonstrated that germ cells at different stages of development express c-Met and that HGF modulates germ cell proliferation and apoptosis. In the present article, we extend our study to the interstitial compartment of the testis and demonstrate that the c-Met protein is present on Leydig cells. The receptor is functionally active as demonstrated by the detected effects of HGF. We report in this article that HGF significantly increases the amount of testosterone secreted by the Leydig cells and decreases the number of Leydig cells undergoing apoptosis. The antiapoptotic effect of HGF is mediated by caspase-3 activity because the amount of the active fragment of the enzyme is decreased in Leydig cells cultured in the presence of HGF. However, treatment with the growth factor does not modify the expression levels of caspase-3 mRNA. These data indicate that HGF regulates the functional activities of Leydig cells. Interestingly, the steroidogenetic activity of the cells is increased by HGF in cultured explants of testicular tissues as well as the antiapoptotic effect of HGF. Therefore, our data indicate that HGF has a crucial role in the regulation of male fertility.     

Urine analysis performed by flow cytometry: reference range determination and comparison to morphological findings, dipstick chemistry and bacterial culture results--a multicenter study

AIM: To validate whether quantitative flow-cytometric analysis of particulate matter in urine would allow for accurate and rapid enumeration of red blood cells (RBC), leukocytes (WBC), squamous epithelial cells (EC), casts, and bacteria, a Sysmex UF-100 analyzer was tested in a multicenter study. MATERIAL AND METHODS: At first, reference values were established and found to be < 14 for RBC, < 16 for WBC, < 9 for EC, < 2 for casts and < 173 for bacteria, respectively (counts per microl; 97.5 percentile). Due to the wide use of dipstick and microscopic sediment analysis in routine urine diagnostics, comparative studies on 950 random urine samples were performed. Bacterial counting combined with WBC enumeration was further compared in 266 routine urinary microbiologic cultures. RESULTS: Good correlations were found comparing UF-100 results of RBC (r = 0.89), WBC (r = 0.94), and EC (r = 0.74) with Fuchs-Rosenthal Chamber (FRC) counts. However, some misclassification of casts (r = 0.32) could be observed. Correlations of UF-100 with dipstick and sediment testing was significant (p < 0.001), but the scatter of the latter two methods is too wide to consider them as quantitative methods. Promising results further revealed that the analyzer has a good negative predictive value (NPV) for microbiologically negative cultures, especially for cultures with bacterial counts of 10(5)/l (NPV = 95%). CONCLUSION: The analyzer is capable of providing rapid and reliable urine analysis of cellular particles avoiding the known imprecision of dipstick and sediment methodology. Thus, when used in an algorithm, combined with dipstick or quantitative urine chemistry analysis (for hemoglobin, esterase, protein, glucose, etc.), this analyzer might serve as a rapid and accurate screening tool in routine urine analysis, thereby reducing manual reviewing rate as well as the number of missed samples, compared to screening with dipstick alone.     

Reconfiguration of the severely fibrotic penis with a penile implant

PURPOSE: Using evidence based methods we prospectively evaluated the impact of a new surgical procedure on penile deformity caused by severe cavernous fibrosis. MATERIALS AND METHODS: In 10 patients with severe penile curvature, shortening and impaired penile rigidity due to fibrosis of the corpora cavernosa we made multiple relaxing incisions of the tunica albuginea and subsequently placed a 3-piece inflatable penile implant. Patients were evaluated before and after the procedure by the International Index of Erectile Function and several general assessment questions. Preoperatively and postoperatively we measured flaccid and erect penile length. RESULTS: At the 6-month followup all International Index of Erectile Function domains were significantly improved compared with preoperative values. Average penile length was increased 2.3 and 3 cm. while flaccid and erect, respectively, compared with before surgery. Complete penile straightening was achieved in 9 of 10 cases (90%). Surgical reoperation was performed in 1 patient (10%) in whom the implant was removed due to scrotal infection and in another (10%) in whom a further single relaxing incision of the fibrotic plaque was needed to attain complete penile straightening. CONCLUSIONS: Patients with severe penile curvature, shortening and impaired penile rigidity due to penile fibrosis may be offered this surgical alternative, which proved to be effective and safe in our preliminary series.     

Adjunctive azithromycin in the treatment of aggressive periodontitis: microbiological findings of a 12-month randomized clinical trial

Objectives

To compare the subgingival microbiological outcomes of azithromycin or placebo as adjuncts to scaling and root planing (SRP) in the treatment of aggressive periodontitis (AgP), and to secondarily evaluate the microbiological effect of supragingival scaling in AgP patients.

Methods

Twenty-four AgP subjects 13–26 years of age received a 15-day programme of supragingival scaling (SC) and were then randomly assigned to SRP with systemic azithromycin or placebo. Subgingival samples were taken with sterile paper points at baseline, 15 days after SC, and at 3, 6 and 12 months following SRP. Microbiological analysis was performed by the checkerboard DNA–DNA hybridization.

Results

Changes in bacterial levels from baseline to 15 days after SC were similar in the 2 groups. When subjects were analysed as a single group, significant reductions after SC were observed for Actinomyces gerencseriae, Capnocytophaga ochracea, and Treponema denticola. During the 12-month follow-up, levels of most of the bacteria decreased in both groups in a similar pattern. For instance, Actinomyces israelli, Veillonella parvula, Streptococcus gordonii, C. ochracea, Eikenella corrodens, Eubacterium nodatum, Fusobacterium periodonticum and Fusobacterium nucleatum ssp. polymorphum decreased significantly within the groups.

Conclusions

Azithromycin was ineffective in lowering the subgingival levels of important putative periodontal pathogens in young AgP subjects compared to placebo.

Clinical significance

Scaling and root planing with adjunctive systemic azithromycin provides little additional benefit compared to placebo in reductions of major subgingival periodontal pathogens.     

Facial movement before and after masseteric-facial nerves anastomosis: A three-dimensional optoelectronic pilot study

To quantify the effects of facial palsy reanimation, 14 patients aged 17–66 years were analysed. All patients had unilateral facial paralysis, and were candidates for surgical masseteric to facial nerve anastomosis. Two patient groups were measured: seven patients were waiting for surgery, the other seven patients had already been submitted to surgery, and had regained facial mimicry. Each patient performed three facial animations: brow raise; free smile; lip purse. These were recorded using an optoelectronic motion analyser.The three-dimensional coordinates of facial landmarks were obtained, their movements were computed, and asymmetry indices calculated (differential movements between the two hemi-faces: healthy and paretic/rehabilitated). Before surgery, mobility was larger in the healthy than in the paretic side; after surgery, the differences were reduced (brow raise and lip purse), or even reversed (smile). Before surgery, lip purse was performed with significant labial asymmetry (p = 0.042; larger healthy side movement). After surgery, asymmetry indices reduced. Total labial asymmetry during smiling was significantly different from 0 before surgery (p = 0.018, larger healthy side movement). After surgery, all asymmetry indices became non-significant. Before surgery the lateral displacements of all labial landmarks were towards the healthy side, while they normalized after surgery.     

Analysis of natural killer cells isolated from human decidua: Evidence that 2B4 (CD244) functions as an inhibitory receptor and blocks NK-cell function

While during the first trimester of pregnancy natural killer (NK) cells represent the most abundant lymphocyte population in the decidua, their actual function at this site is still debated. In this study we analyzed NK cells isolated from decidual tissue for their surface phenotype and functional capability. We show that decidual NK (dNK) cells express normal surface levels of certain activating receptors, including NKp46, NKG2D, and 2B4, as well as of killer cell immunoglobulin-like receptors (KIRs) and CD94/NKG2A inhibitory receptor. In addition, they are characterized by high levels of cytoplasmic granules despite their CD56(bright) CD16- surface phenotype. Moreover, we provide evidence that in dNK cells, activating NK receptors display normal triggering capability whereas 2B4 functions as an inhibitory receptor. Thus, cross-linking of 2B4 resulted in inhibition of both cytolytic activity and interferon-gamma (IFN-gamma) production. Clonal analysis revealed that, in the majority of dNK cell clones, the 2B4 inhibitory function is related to the deficient expression of signaling lymphocyte activation molecule (SLAM)-associated protein (SAP) mRNA. Moreover, biochemical analysis revealed low levels of SAP in the dNK polyclonal population. This might suggest that dNK cells, although potentially capable of killing, are inhibited in their function when interacting with cells expressing CD48.