Laparoscopic treatment of paraesophageal and mixed diaphragmatic hernias. Report of two cases.

Hiatal hernias are classified into 3 types: sliding hernia (type I), paraesophageal hernia (type II) and mixed hernia (type III), that is a combination of type I and II. The paraesophageal and mixed hernias represent about 5-10% of the surgically treated hiatal hernias. The surgical treatment of the paraesophageal and mixed hernias is unavoidable because of the high risk of severe complications and it has to be considered in a high percentage of cases. The most important technical difficulty in the video-laparoscopic treatment is represented by the hugeness of the hernial defect and by the challenging reduction of the stomach into the abdomen. A cautious dissection of hernial sac and diaphragmatic cruses as well as a careful crural repair make the video-laparoscopic procedure feasible. The operative times are not prolonged and the results are similar to the open technique ones. In literature, the incidence of both intra and postoperative complications doesn't exhibit statistically significant differences between laparoscopic and open techniques. Because of the complexity of the laparoscopic procedure, the minimally invasive access has to be reserved to surgeons who are well trained in those techniques. In this paper we describe 2 cases: one of paraesophageal hernia and the other of mixed hernia which were video-laparoscopically treated with the help, in the second case, of a Gore-Tex mesh. In both cases the technical results were positive. Intra and postoperative complications didn't occur and, one year after the surgical procedure, both patients were in good health and recurrence-free.

NIR Emitting Nanoprobes Based on Cyclic RGD Motif Conjugated PbS Quantum Dots for Integrin-Targeted Optical Bioimaging.

Here, silica-coated PbS quantum dots (QDs) with photoluminescence emission properties in the near-infrared (NIR) region are proposed as potential effective single particle optical nanoprobes for future in vivo imaging of tumors. The dispersibility in aqueous medium of hydrophobic PbS QDs was accomplished by growing a silica shell on their surface by exploiting a base assisted water-in-oil microemulsion method. The silica-coated PbS QDs were then conjugated with a specifically designed cyclic arginine-glycine-aspartic acid (cRGD) peptide that is able to specifically recognize αvß3 integrins, which are overexpressed in angiogenic tumor-induced vasculatures and on some solid tumors, to achieve tumor-specific targeting. The cRGD peptide PbS silica-coated QDs were systematically characterized, at each step of their preparation, by means of complementary optical and structural techniques, demonstrating appropriate colloidal stability and the maintenance of their optical futures in aqueous solutions. The cellular uptake of cRGD peptide functionalized luminescent nanostructures in human melanoma cells, where overexpression of αvß3 was observed, was assessed by means of confocal microscopy analysis and cytometric study. The selectivity of the cRGD peptide PbS silica-coated QDs for the αvß3 integrin was established, consequently highlighting the significant potential of the developed NIR emitting nanostructures as optically traceable nanoprobes for future αvß3 integrin receptor in vivo targeting in the NIR region.

Sutureless and stapleless laparoscopic splenectomy using radiofrequency: LigaSure device.

BACKGROUND: Bleeding is the main complication and cause of conversion during laparoscopic splenectomy (LS). We present the advantages of the LigaSure vessel sealing system added to the lateral approach for achieving safe vascular control. METHODS: We performed 63 consecutive LS in a 3-year period using LigaSure in two affiliated university hospitals. We employed a right semilateral position technique with dissection of the spleen and vessel sealing using LigaSure. Forty-two patients had benign hematological disease, 19 had malignant disease, and two had splenic cysts. RESULTS: A total of 58 LS were completed with five conversions due to hilar bleeding (three cases), difficult dissection (one), and massive splenomegaly (one). In all but five patients, blood loss was less than 100 ml. No transfusions were needed. There were five postoperative complications: portal thrombosis (one case), hemoperitoneum (two), surgical wound infection (one), and pleural effusion (one). CONCLUSIONS: The use of LigaSure, and the semilateral position, results in a gain of time and safety. Furthermore, average intraoperative bleeding is very low.

Maroteaux-lamy syndrome: five novel mutations and their structural localization.

Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI, MPS VI) is an autosomal recessive disorder due to the deficiency of the lysosomal enzyme N-acetylgalactosamine-4-sulfatase (arylsulfatase B, ASB). Mutation analysis in Maroteaux-Lamy syndrome resulted in the identification of approximately 40 molecular defects underlying a great genetic heterogeneity. Here we report five novel mutations in Italian subjects: S65F, P116H, R315Q, Q503X, P531R; each defect was confirmed by restriction enzyme or amplification refractory mutation system (ARMS) analysis. We also performed a three-dimensional (3-D) structure analysis of the alterations identified by us, and of an additional 22 point mutations reported by other groups, in an attempt to draw helpful information about their possible effects on protein conformation.

Peptide nucleic acids (PNA)-DNA chimeras targeting transcription factors as a tool to modify gene expression.

Peptide nucleic acids (PNAs)-DNA chimeras have been recently described as DNA mimics constituted of a part of PNA and of a part of DNA. We have demonstrated that double stranded molecules based on PNA-DNA chimeras bind to transcription factors in a sequence-dependent manner. Accordingly, these molecules can be used for transcription factor decoy (TFD) pharmacotherapy. Effects of double stranded PNA-DNA chimeras targeting NF-kappaB and Sp1 were determined on in vitro cultured human cells and were found to be comparable to those observed using double-stranded DNA decoys. The TFD molecules based on PNA-DNA chimeras can be further engineered by addition of short peptides facilitating cell penetration and nuclear localization. Therefore, these engineered molecules could be of great interest for in vivo experiments for non-viral gene therapy of a variety of diseases, including neoplastic and viral diseases, for which the TFD approach has been already demonstrated as a very useful strategy.

Specific interaction between bovine cyclophilin A and synthetic analogues of cyclolinopeptide A.

Like cyclosporin A, cyclolinopeptide A binds specifically bovine cyclophilin A, inhibiting its peptidyl-prolyl cis-trans isomerase activity. We describe here the protein interaction with several synthetic analogues of cyclolinopeptide A, which are either homodetic or disulphide bridged heterodetic cyclopeptides characterized by different ring dimensions, in terms of dissociation and inhibition constants evaluated by fluorescence and inhibition of the enzyme activity, respectively. Dissociation constants from fluorescence experiments are practically identical and about 20-fold lower than for cyclosporin A. On the other hand, inhibition constants differ from compound to compound and are higher than for cyclosporin A. This result is therefore difficult to rationalize, but we would suggest decoupling between binding and inhibitory ability of cyclopeptides. The Pro1 residue of cyclolinopeptide A seems to play a fundamental role in determining the inhibition of the rotamase activity of cyclophilin A, as the homodetic analogue lacking this residue does not show any inhibitory ability. Similarly, heterodetic analogues with a ring size smaller than 7 residues do not display inhibition. We presume that the sequence -Pro-Pro-Phe-Phe- and a ring size of 8 residues for homodetic cyclic peptides could be used as starting points in the targeted synthesis of cyclopeptides able to bind both cyclosporin A and calcineurin. The only peptide showing similar values of the dissociation and inhibition constant is cyclolinopeptide A. This compound can be considered a novel model for the molecular design of immunosuppressant drugs.

Double-blind, double-dummy, randomized, multi-centre clinical assessment of the efficacy, tolerability and dose-effect relationship of sulodexide in chronic venous insufficiency.

A multi-centre study was carried out in 476 patients with chronic venous insufficiency to compare the efficacy, tolerability and dose-effect relationship of sulodexide given orally as either capsules or as a new, enteric-coated tablet formulation. Three comparable groups of patients each with chronic venous insufficiency of thrombotic or varicose aetiology received during 60 consecutive days either sulodexide 250 LRU (= 25 mg) capsules twice daily, 50 mg sulodexide enteric-coated tablets twice daily or 100 mg sulodexide enteric-coated tablets once daily, according to a double-blind, double-dummy, randomized design. Doppler and echoduplex examinations, supine and standing peripheral venous pressure, specific symptoms and signs, peripheral haemodynamics and safety haematology and haematochemistry were monitored monthly. The results showed that peripheral venous pressure improved to a clinically relevant and statistically significant extent in all groups and symptoms and signs were rapidly and significantly relieved. These effects were dose-related, as in both cases the recovery was faster and greater with the 100 mg per day dose however administered. Both the thrombotic and varicose aetiologic sub-groups benefited from treatment to approximately the same extent. Mild to moderate gastro-intestinal adverse experiences occurred in 48 patients evenly split between groups but spontaneously disappeared within 72 hours, none leading to treatment withdrawal. No clinically relevant modifications of peripheral haemodynamics or of safety haematology and haematochemistry was observed. The haemocoagulation parameters failed to exhibit appreciable variations. While the known clinical usefulness of sulodexide 250 LRU (= 25 mg) capsules twice daily was confirmed in this trial, the enteric-coated tablets, 50 mg twice daily or 100 mg once daily, were shown to have greater efficacy and similar tolerability to the standard formulation and dose.

Molecular dynamics simulation in vacuo and in solution of [Aib5,6-D-Ala8] cyclolinopeptide A: a conformational and comparative study.

The conformation of a Cyclolinopeptide A analogue, c-(Pro-Pro-Phe-Phe-Aib-Aib-Ile-D-Ala-Val), has been investigated by means of molecular dynamics simulations, in various molecular environments. The molecular dynamics results are compared with that obtained for Cyclolinopeptide A and a detailed analysis of the different behaviour for the two compounds is reported. A complete analysis of hydrogen bonds is presented.

Computational analysis of the thermal stability in thioredoxins: a molecular dynamics approach.

The knowledge of the relationship between the three-dimensional structure of a protein and its biological and stability is one of the most challenging problem in protein chemistry, since offers the possibility of changing both the specific action of a protein and its stability. In this work, we have approached the problem with studies on a protein family, the thioredoxins, using homology procedures, molecular dynamics simulations in vacuo at 300 K and 500 K and in water solution at 300 K, to determine the relationship between the three-dimensional structure of these proteins and their thermal stability. A comparative analysis, using computational approach, was performed between two thioredoxins with different resistance to temperature. Results obtained using the molecular dynamics techniques and minimization procedures give explanations of the experimental data, underlining that these techniques are able to correlate the increase in protein stabilization with the conformational and structural changes caused by single amino acid replacement. In addition, we report the factors that can be used as a guide in protein engineering and in site-directed mutagenesis to increase or decrease thermal stabilization for this protein family.

Structure and dynamics of elastin building blocks. Boc-LG-OEt, Boc-VGG-OH.

Short di- and tripeptides such as Boc-LG-OEt, Boc-VG-OEt and Boc-VGG-OH, corresponding to abundant repetitive sequences in elastin, have been extensively studied both in solid state, by X-ray diffraction, and in solution by circular dicroism and nuclear magnetic resonance. Furthermore, theoretical procedures such as simulated annealing and molecular dynamics were also performed on these peptides. In general, the results indicate that no one single structure (be folded or extended) could be representative for these sequences in the protein, but rather that a multiplicity of interconverting conformers, ranging from folded to extended structures, should be considered. In any case, these structures, e.g. beta-turns, polyglycine II and beta-conformations, are those previously suggested to participate to conformational equilibria of elastin.

Computational procedures to explain the different biological activity of DNA/DNA, DNA/PNA and PNA/PNA hybrid molecules mimicking NF-kappaB binding sites.

Peptide nucleic acids (PNA) have recently been proposed as alternative reagents in experiments aimed to the control of gene expression. In PNAs, the pseudopeptide backbone is composed of N-(2-aminoethyl)glycine units and therefore is stable in human serum and cellular extracts. PNAs hybridize with high affinity to complementary sequences of single-stranded RNA and DNA, forming Watson-Crick double helices and giving rise to highly stable (PNA)2-RNA triplexes with RNA targets. Therefore, antisense and antigene PNAs have been synthetized and characterized. The major issue of the present paper is to describe some computational procedures useful to compare the behaviour of PNA double stranded molecules and PNA/DNA hybrids with the behaviour of regular DNA duplexes in generating complexes with DNA-binding proteins. The performed computational analyses clearly allow to predict that the lack of charged phosphate groups and the different shape of helix play a critical role in the binding efficiency of NF-kappaB transcription factors. These computational analyses are in agreement with competitive gel shift and UV-cross linking experiments. These experiments demonstrate that NF-kappaB PNA/PNA hybrids do not interact efficiently with proteins recognizing the NF-kappaB binding sites in genomic sequences. In addition, the data obtained indicate that the same NF-kappaB binding proteins recognize both the NF-kappaB DNA/PNA and DNA/DNA hybrids, but the molecular complexes generated with NF-kappaB DNA/PNA hybrids are less stable than those generated with NF-kappaB target DNA/DNA molecules.

Synthesis and structural characterization of 6I,6II-diamino-6I,6II-dideoxy-cyclomaltoheptaose, a difunctionalized beta-cyclodextrin.

6I,6II-Diamino-6I,6II-dideoxy-cyclomaltoheptaose was prepared using the regioselective procedure described by Tabushi. The difunctionalized beta-cyclodextrin crystallizes as hexadecahydrate in the orthorhombic space group P2(1)2(1)2(1), with a = 11.395(3), b = 32.989(9), c = 17.560(5) A, V = 6601 A3, Z = 4. The structure was solved by molecular replacement techniques using the program PATSEE and was refined to a conventional final R = 0.058 for the 5031 observed reflections with I > or = 3 sigma(I). The beta-CD macrocycle presents only slight differences with respect to uncomplexed hydrated or methylated beta-CD. The macrocycle structure maintains an approximate seven-fold symmetry. The round shape of the cyclodextrin ring is stabilized by intramolecular O-H ... O H-bonds between the secondary hydroxyl groups of neighbouring glucose residues. Along the a axis, the beta-CD molecules are arranged in columns; the macrocycles form a herring-bone pattern, so that the cavity of each beta-CD molecule is closed at each end by neighbouring molecules. The macrocycles are directly linked to each other by H-bonds involving either primary and secondary hydroxyl or amino groups of symmetry-related molecules. The resulting layers are connected to each other by a dense intermolecular hydrogen-bond network, in which solvent molecules participate.

[Costs and benefits in the follow-up of abdomino-perineal amputation of the rectum for cancer]. / Costi e benefici nel follow-up dopo amputazione addomino-perineale del retto per cancro.

A cost/benefit analysis has been carried out of the follow-up of abdomino-perineal amputation of the rectum for cancer in the light of the objectives pursuable with this practice and the diagnostic techniques available today. As regards early diagnosis of a return of the disease, it is necessary to distinguish between long-term recurrence, hepatic or pulmonary for example, in relation to their greater potential capacity for surgical exeresis and local pelviperineal recurrences which are more rarely susceptible to radical exeresis in spite of the introduction of computed tomography and nuclear magnetic resonance in the diagnostic/therapeutic routine. As for diagnosis and management of metachronous polyps as a prevention of metachronous cancer, the importance of periodic trans-stomal pancolonoscopic control of the residual colon in all patients emerges. Finally, in cost/benefit terms, the objective of a psychophysical rehabilitation of the colostomized patient is advantageous with a marked reduction in welfare expenditure for the community.

[Current principles in surgical therapy of rectal cancer]. / Principi attuali della terapia chirurgica del cancro del retto.

The Author critically analyzes the aims of curative surgery for rectal cancer, i.e. radical colonic resection, lymphoadenectomy, conservation of adequate post-surgical functionality of the remaining colon. Nowadays, therapy does not end with the exeresis of the primary cancer as an isolated stage but rather includes adequate follow-up to prevent metachronous cancer by detecting and removing recurrent adenomas. But it also includes early diagnosis of any recurrence of the primary cancer to facilitate adequate treatment.

[Sulfasalazine in rheumatology]. / La sulfasalazina in reumatologia.

Sulphasalazine (SLZ) has proved to be a drug effective in inducing clinical improvement or remission in chronic inflammatory rheumatic diseases (other than inflammatory bowel diseases) such as rheumatoid arthritis (RA) and some seronegative spondyloarthropathies, in a fashion similar to that of long-acting, second-line drugs in RA. Several clinical studies agree upon the efficacy of the compound employed at a dose of 2-3 g/day and upon the incidence of side effects, which appear to be equivalent to or lower than those related to traditional disease-modifying drugs employed in RA. The following points should be clarified and developed with regard to the use of SLZ in chronic rheumatic diseases: main mechanism(s) of action, improvement of therapeutic strategy (i.e.: combined treatments, maintenance therapy), prevention and control of main side effects, and its preferential use or limits in the management of a larger number of inflammatory rheumatic diseases.

[Surgical treatment of hemorrhoidal disease using circular mechanical stapler. Analysis of costs]. / Trattamento chirurgico della malattia emorroidaria mediante suturatrice meccanica circolare. Analisi dei costi.

BACKGROUND: An analysis of surgical treatment costs of haemorrhoid disease with the use of a new circular stapler, is made comparing this operation with Milligan Morgan's technique. The money and management saving due to the reduction of operation time and postoperative stay compensates present costs due to stapler. METHODS: 35 uniform patients (number, age, sex, grade of haemorrhoid disease and surgical equipe) are considered and divided into two groups of study to evaluate perspectively the surgical costs. RESULTS: The cost of treatment with stapler per patient is like Milligan Morgan's treatment (1.714.681 lire versus 1.681.893), with an important management saving of postoperative days (16 hours versus 42 hours). CONCLUSIONS: Moreover there are psychologic and social advantages, not quantifiable but considerable, due to the early physical recovery and to the absence of out-patient dressing cycles peculiar of this surgical technique, with a rapid social and working reinstatement of patients (4-5 days versus 4-5 weeks of conventional intervention).

[Inguinal hernia in childhood]. / L'ernia inguinale in età pediatrica.

The paper reviews the current methods of surgery for inguinal hernia in children. This is a relatively common pathology but there is still no consensus regarding the most important aspects, namely "who" should be operated, "why", "when", "what methods should be used", and "what results are achieved" The excellent outcome in addition to the rarity of relapse in cases of uncomplicated hernia, opposed to emergency operations due to strangulation which are accompanied by a significant rate of mortality, justify, with rare exceptions, early intervention once the diagnosis has been confirmed.

[Personal experience with vagotomy in the treatment of duodenal ulcer]. / La nostra esperienza in tema di vagotomia nel trattamento dell'ulcera duodenale.

Truncal vagotomy was employed in 120 cases of simple or complicated duodenal ulcer. Pyloroplasty was also performed in 98 cases, antroduodenostomy in 5, Billroth I or II in 12, and gastrojejunostomy in 5. No operative deaths were noted, even though the series included emergency situations and patients in poor condition. The incidence of complications and immediate sequelae was insignificant. Follow-up for 2-6 yr showed complete success in over 91%, with partial improvement in 3.8%. Poor results included 3 cases of recurrence, 1 of late scar stenosis on the pyloroplasty site, and 1 of intermittent gastroplegia.

[Personal experience with gastric resection in the treatment of gastroduodenal ulcer]. / La nostra esperienza in tema di gastroresezione nel trattamento dell'ulcera gastroduodenale.

Billroth I or II resection was adopted in the treatment of 85 subjects with simple or complicated gastroduodenal ulcer. Operative mortality was 1.4% in surgery of choice and 18.7% where emergency management was required to combat perforation of serious haemorrhage. Follow-up after 1-2 yr showed that marked benefit had been obtained from the operation in 83%, while partial success was achieved in 15,5%. Postoperative peptic ulcer was observed in one case only. Comparison with a series of 120 patients subjected of choice or in emergency to truncal vagotomy and gastric drainage during the same period for duodenal ulcer and followed for 2-6yr (no operative deaths and complete success in over 91%) made it clear trat, while resection was attended by a smaller number of recurrences (1.5% as opposed to 2.9%), this advantages was obtained at the price of a greater operative risk and by no means negligible long-term sequelae.

[Role of magnetic resonance in the diagnosis of cryptorchidism]. / Il ruolo della risonanza magnetica nella diagnostica del criptorchidismo.

The paper reports the authors' personal experience regarding the use of magnetic resonance imaging in the diagnosis of cryptorchidism. The result of the study of 13 patients with non-palpable gonads, who all underwent surgical confirmation (with positive outcome in 66% of cases), encourage the use of this non-invasive method with a high anatomic resolution, which can be used to diagnose both the site, dimensions and possible structural alterations of the gonad.