Electronic basis of the comparable hydrogen bond properties of small H2CO/(H2O)n and H2NO/(H2O)n systems (n = 1, 2).

The electronic and structural properties of dihydronitroxide/water clusters are investigated and compared to the properties of formaldehyde/water clusters. Exploring the stationary points of their potential energy surfaces (structurally, vibrationally, and energetically) and characterizing their hydrogen bonds (by both atoms in molecules and natural bond orbitals methods) clearly reveal the strong similarity between these two kind of molecular systems. The main difference involves the nature of the hydrogen bond taking place between the X-H bond and the oxygen atom of a water molecule. All the properties of the hydrogen bonds occurring in both kind of clusters can be easily interpreted in terms of competition between intermolecular and intramolecular hyperconjugative interactions.

Structure-based secondary structure-independent approach to design protein ligands: Application to the design of Kv1.2 potassium channel blockers.

We have developed a structure-based approach to the design of protein ligands. This approach is based on the transfer of a functional binding motif of amino acids, often referred as to the "hot spot", on a host protein able to reproduce the functional topology of these residues. The scaffolds were identified by a systematic in silico search in the Protein Data Bank for proteins possessing a group of residues in a topology similar to that adopted by the functional motif in a reference ligand of known 3D structure. In contrast to previously reported studies, this search is independent of the particular secondary structure supporting the functional motif. To take into account the global properties of the host protein, two additional criteria were taken into account in the selection process: (1) Only those scaffolds sterically compatible with the positioning of the functional motif as observed in a reference complex model were retained. (2) Host proteins displaying electrostatic potentials, in the region of the transferred functional motif, similar to that of the reference ligand were selected. This approach was applied to the development of protein ligands of the Kv1.2 channel using BgK, a small protein isolated from the sea anemone Bunodosoma granulifera, as the reference ligand. Four proteins obtained by this approach were produced for experimental evaluation. The X-ray structure of one of these proteins was determined to check for similarity of the transferred functional motif with the structure it adopts in the reference ligand. Three of these protein ligands bind the Kv1.2 channel with inhibition constants of 0.5, 1.5, and 1.6 microM. Several mutants of these designed protein ligands gave binding results consistent with the presumed binding mode. These results show that protein ligands can be designed by transferring a binding motif on a protein host selected to reproduce the functional topology of this motif, irrespective to the secondary structure supporting the functional motif, if the host protein possesses steric and electrostatic properties compatible with the binding to the target. This result opens the way to the design of protein ligands by taking advantage of the considerable structural repertoire of the Protein Data Bank.

The Trabucco technique in the treatment of inguinal hernias; A six-year experience.

BACKGROUND: The introduction of both polypropylene prosthesis and the new tension-free methods for the treatment of inguinal hernias, induced us to choose the Trabucco technique since August 1994. METHODS: Up to April 2001 983 inguinal hernia repairs were carried out in 825 patients, 948 with the Trabucco technique. RESULTS: Minor complications (hematoma, seroma, inguino-crural pain) were 42 (5.1%) with no wound infections. There were 3 relapses (0.36%), one treated in an other hospital and the other two were surgically treated because of the small dimension of the hernia and they were not troublesome for the patients, although they were strictly controlled. CONCLUSIONS: In spite of the limited follow-up period, there is satisfaction for the short-term period outcomes which showed the superiority of the Trabucco method compared with the traditional techniques both as to hospitalization and good recovery and to the early relapse.

[Carcinoid of the appendix. Clinical report of 3 cases and diagnostic and therapeutic considerations]. / Il carcinoide dell'appendice. Osservazione clinica di 3 casi e considerazioni diagnostiche e terapeutiche.

The Authors report three cases of carcinoid of the appendix and discuss the difficult preoperative diagnosis and the different therapeutic options available. Over the period from January 1994 to December 1999, in the Surgery Unit of Penne Hospital, 424 appendicectomies were performed in 182 males and 242 females (age: 12-86 years; mean age: 39.9 years). In three cases the histological response was positive for carcinoid of the appendix. No postoperative mortality or morbility were reported. The authors analyze the biological peculiarities and the prognostic factors associated with appendiceal carcinoid tumours, such as tumour size and the lymphatic or vascular infiltration of the mesoappendix (and the corresponding more aggressive surgical treatments) and recommend an appropriate postoperative follow-up since synchronous or metachronous bowel carcinomas are likely to occur. Pharmacological therapy has also made important progress, with the possibility of administering compounds capable of interfering with tumour development and neoplastic growth.

[Mesogastrectomy in the surgical treatment of gastric carcinoma. Experience with 61 cases]. / La mesogastrectomia nella chirurgia del carcinoma gastrico. Esperienza di 61 casi.

BACKGROUND: In gastric cancer surgery, to search for a technique to remove the entire posterior mesogastric region using a standardised operation using well defined methods and anatomic-embryological planes. METHODS: A concise description of the embryological evolution of the posterior mesogastrium allow the formation of the mesogastric fascia (and the supramesocolic fascia of the omentum--which is a continuation) to be documented. It is also clear that the mesogastric fascia is the embryological--anatomical equivalent of Treitz's fascia, pancreatic retro-head, and Toldt's retrocolic fascia, of which it is a structural continuation. Like Treitz's and Toldt's fascias, the mesogastric fascia also represents the surgical plane for the detachment of the region in question and allows maximum safety and radicality. By carrying out primary ligature of the arteries at the origin and the veins at the outlet, the entire posterior mesogastric region, with the relative lymph node stations, can be removed en bloc with maximum radicality and safety, and also in line with the principle of "no touch isolation". We used this technique to operate 61 cases, 17% of all cases of gastric carcinomas between 1973 and 1994. RESULTS: Mesogastrectomy was required in 87% of cases with carcinoma in a high localisation or widespread nature of the linitis plastica type. Only 23 cases (37%) were at pTNM II and III A stages. Thirty-eight cases (63%) were at stages III B and IV. In non-selected cases and those with severe associated pathologies and undergoing emergency surgery, and those cases that were extended beyond mesogastrectomy, morbidity was above all linked to pleural effusion. There were only 2 cases (3%) of operating mortality owing to two technical errors: an esophago-jejunal anastomotic dehiscence (the only case in the series, 1.6%) caused by esophageal cancer nests in the suture and a case of necrosis in the left hepatic region following the section of the left gastric artery at the origin despite the existence of a large hepatic collateral vessel. The results for stages II and III A were excellent: stage II, 100% survival at 5, 10 and 15 years; stage III A 88% survival at 5 years, 70% at 10 years, 55% at 15 years, but only two deaths from neoplasia at 2.7 and 4.6 years. The results for stages III B and IV are comparable to large series undergoing traditional forms of surgery. Postoperative conditions of nutrition and quality of life were good and patients resumed activities with the aid of constant chlorhydric-peptic replacement treatment and the total extraction of gastric mucosa. CONCLUSIONS: We believe that mesogastrectomy represents a real advance in both technical terms and results for stages II and III A; it is debatable for stages III B and IV, although individual cases who survived for more than 10 years were also reported. The case of a stage pT3N0M1 = IV pathology, with a single hepatic metastasis that increased until one year and then spontaneously resolved leaving the patient alive and in good health 20 years and 6 months after the operation is truly amazing.

[The single-stage surgery of perforated colon carcinoma. Our experience of 46 cases]. / La chirurgia in un tempo del carcinoma colico perforato. Esperienza di 46 casi.

BACKGROUND: 46 cases of perforated colonic neoplasm (4.6% of the entire series): 11 (24%) of the right colon, 35 (76%) of the left colon; 19 males (41%) and 27 females (59%); mean age 67 years old, range 32-92 years. pTNM: stage II, 1 case (2%); stage III: 27 cases (59%); stage IV, 18 cases (39%). The aim of this study was to resolve the perforation and to treat the neoplasm in a single operation. METHODS: The various types of perforation included: 35/46 = 76% perforations in situ; 6/47 = 13% recent perforations upstream; and 5/46 = 11% at a distance from the neoplasia. The following types of peritonitis were observed: purulent localised 10/46 = 22%, purulent generalised 12/46 = 26%, fecaloid 18/46 = 39%, fecal 6/46 = 13%. In 24 cases/46 = 52% the perforation had occurred in an occluded colon. The preoperative finding of pneumoperitoneum in 12/46 = 26% indicated generalised fecaloid-fecal peritonitis. Surgery commenced by suturing the perforation followed wherever possible by standard colectomy: on the right in all 11 cases = 100%, on the left in 15/35 = 43%; only in the event of prohibitive local or in particular general conditions was Hartmann's segmentary colectomy used in 10 cases/35 = 29%, or a definitive preternatural anus in 10/35 = 29%. The following aspects are essential in this single-stage surgery: the emergency nature of the operation; massive dose antibiotic treatment limited to the pre- and perioperative stages and above all peritoneal cleansing using accurate, methodical, repeated and abundant lavage with 8-10-20 or more litres of polysaline isotonic solution at 37 degrees C, but only used 500 ml at a time. This lavage is essential to reduce bacterial load contributes to the rapid hydroelectrolytic re-equilibrium in severe conditions of peritonitis. When necessary, colonic preparation was carried out using direct colostomic perioperative lavage. The peritonisation of the retroperitoneum with the omentum is important, as is the protection of the anastomosis using omental wrapping and active lavage and aspiration of the colorectal anastomosis, even using the 3-way tube, in a transanal trans- or subanastomotic position. Total parenteral feeding is useful and almost indispensable for 6-8 days. RESULTS: Postoperative morbidity was negligible and mortality occurred in 14/46 cases = 30%, of whom 13/32 = 41% were over 60 and 1/14 = 7% under 60; if the cases are divided into two periods, pre-Gullino tube (1974-84) mortality was 8/22 = 36% and with Gullino's tube (1985-95) it was 6/24 = 25%; postoperative stay was 18 days in the first period and only 11 days in the second. The 11 cases at stage IV who survived the operation all died following the spread of neoplasms within 2-30 months, mean 10 months; the over-5-year survival rate for the only case at stage II and the 19 at stage III was 38% (Kaplan-Meier). CONCLUSIONS: By using this courageous single-stage surgery and operating patients at such a severe stage, both the immediate and long-term results appear to be more than satisfactory. It is important to underline, however, that not all neoplastic perforations appeared to be caused by endoluminal hypertension-ischemia; in those cases with non-occluded colon, about half might have been the consequence of biological problems of immune hyperreactivity of a rejection reaction type (Arthus, Snarelli-Shwartzman phenomenon and similar).

[The single-stage surgery of colorectal neoplastic occlusion. The experience of 133 cases]. / La chirurgia in un tempo dell'occlusione neoplastica colon-rettale. Esperienza di 133 case.

BACKGROUND AND AIM: 133 cases of occluded colorectal neoplasms (14% of the entire series): 30 (23%) of the right colon, 103 (77%) of the left colon-rectum; 69 males (52%) and 64 females (48%); mean age 67.5 years old, range 33-91 years. pTNM: stage II, 28 cases (21%); stage III: 43 cases (32%); stage IV, 62 cases (47%). The aim of this study was to resolve the occlusive symptoms and to treat the neoplasm in a single operation. METHODS: In the 62 cases at stage IV, surgery was solely palliative: 49 (79%) derivations, 13 (21%) entero-enterostomies and 36 (58%) preternatural anus; 11 (18%) standard hemicolectomies, extended in two cases to hepatic resection, and 2 (3%) Hartmann's operations. In the 71 cases at stages II and III, surgery took the form of standard colic exeresis with primary ligature of the colonic vessels at source and at the outlet; 15 (21%) right colectomies, 50 (70%) left colectomies, extended in 6 cases (8%) to abdomino-perineal amputation; 6 segmentary colectomies, 3 (4%) of the transverse colon and 3 (4%) Hartmann's operations. The following aspects are essential in this single-stage surgery: urgency; massive dose antibiotic treatment limited to the pre- and perioperative stages; peritoneal cleansing using accurate, methodical, repeated and abundant lavage; perioperative colonic preparation using direct colotomic perioperative lavage or using a trans-buccoenteric access (using Grosz-Dennis tube); the peritonisation of the retroperitoneum with the omentum and the protection of the anastomosis using omental wrapping and active lavage and, for colorectal anastomosis, even using the 3-way tube, lavage and active aspiration, in a transanal trans- or sub-anastomotic position. Total parenteral feeding is useful for 6-7 days. RESULTS: In the 62 cases at stage IV, postoperative morbidity was 3 cases (6%): 3 suppurations of laparotomy, and mortality occurred in 10 cases (16%): one case of anastomotic disunion (pre-Gullino's tube), 3 cases of septic shock and 6 cardiorespiratory failures. Mean postoperative hospitalisation was 14 days. All these patients died owing to the spread of neoplasms within 1-40 months, mean 13 months. The worst results were obtained in entero-enterostomies: 1-9 months, mean 5 months. In the 71 cases at stages II and III, postoperative morbidity was 3 cases (4%): a small anastomotic filtration after right colectomy and 2 suppurations of the laparotomic incision; mortality amounted to 10 cases (14%): one case of septic shock, one of acute hepatitis, one intestinal infarction and one cardiac infarction, 3 pulmonary embolisms and 3 cardiorespiratory failures. Mean postoperative hospitalisation was 13 days, only 10 in cases of left colectomy with anastomosis protected by Gullino's tube. The long-term results were very good in these 71 patients: over 5-year survival of 50% (Kaplan-Meier). CONCLUSIONS: Using this courageous single-stage surgery, the results are optimal even at a distance, together with reduced surgical trauma and a shorter hospital stay.

Sex-related influence of body size and sexual maturation on blood pressure in adolescents.

OBJECTIVE: This study is aimed at investigating the influence of body size, body fat and sexual maturation on blood pressure (BP) in adolescents. DESIGN: A cross-sectional study. SETTING: A suburban student population of Southern Italy. SUBJECTS: One hundred ninety students attending the first and second year of a secondary school. Five were excluded because they were affected by major diseases. The remaining were 98 M and 87 F (mean age for either group = 12.0+/-0.8 y). METHODS: Blood pressure was measured by a mercury sphygmomanometer, body weight by a platform beamscale, other measurements included height, biceps, triceps, subscapular and suprailiac skinfolds by a caliper; sexual maturation was evaluated according to Tanner. RESULTS: Body size was greater than in Tanner's population: in particular body weight (but not height) in our sample markedly exceeded that of the children of the same age in Tanner's population. Boys had higher systolic blood pressure (SBP) than girls (BP = 109/64+/-12/10 vs. 103/63+/-11/8 mm Hg, P<0.02 for SBP), while heart rate and waist/hip ratio were lower. During puberty evaluated on the basis of pubic hair growth BP in girls was higher than in the prepubertal phase (107/66+/-9/7 vs. 99/61+/-10/7, P<0.01). Pubertal boys showed a reduced percent of body fat (calculated from four skinfold measurements) in comparison to prepubertal ones (21.0%+/-4.5 vs. 24.5%+/-7.1, P<0.01). In linear correlation analysis, height, BW, BMI and lean body mass were found to be significantly associated with SBP in both sexes and to diastolic blood pressure (DBP) in girls. Percent body fat was correlated with SBP in boys, while sexual maturation was associated to SBP and DBP in girls only. Multiple regression analysis indicated a significant contribution of body size to BP variability, particularly in the girls. Sexual maturation was excluded from the final regression equations when height, BW or lean body mass were present. CONCLUSIONS: These data indicate that body weight in these adolescents is greater that in Tanner's population of the same age and sex. Body size appears to be a major determinant of BP, whereas sexual maturation seems to influence BP levels mainly through body growth. The influence of percent body fat on BP setting seems to be of limited importance.

[Perforated diverticular disease of the left colon. Proposed single-stage left colectomy protected by a three-way lavage and active aspiration tube (di Gullino) positioned inside or below the anastomosis. Experience in 65 cases]. / Malattia diverticolare perforata del colon sinistro. Proposta di colectomia sinistra in un tempo, protetta dal tubo a tre vie (di Gullino) di lavaggio ed aspirazione attiva, trans- o sottoanastomotico. Esperienza di 65 casi.

BACKGROUND: The incidence of perforative diverticulitis of the left colon is steadily increasing. Today the decision is generally taken to perform two-stage surgery: segmentary resection without (Hartmann's operation) or with anastomosis, but protected by a colostomy ("limited intervention"). This study aimed to examine standard colectomy performed in a single operation ("ideal intervention"). METHODS: Left colectomy with primary ligature of the lower mesenteric artery and vein at the source and outlet, en bloc removal of the colon-mesocolon and immediate transverse colorectal anastomosis. Anastomosis protected by the omentum which is also used to peritonise the retroperitoneum and to wrap around the anastomosis, and anastomosis also protected by the author's three-way lavage and active aspiration tube in either a trans- or subanastomosis and transanal position. Urgency is essential for this single-stage operation, together with massive dose antibiotic treatment limited to the pre- and postoperative stages, but above all peritoneal cleansing using accurate, methodical, repeated and abundant lavage with 8-10-20 or more litres, but only used 500 ml at a time. Of these 65 cases, 40 (62%) were purulent localised peritonitis and 25 (38%) were generalised (14 purulent, 4 fecaloid and 7 fecal). 8 cases (12.3%) underwent surgery in three stages and 16 (24.6%) underwent sigmoidectomy in one or two stages ("limited intervention"), 41 cases (63%) (1985-95, when Gullino's three-way tube became available) underwent standard colectomy in a single stage. RESULTS: Morbidity in 10 cases/65 (15%) and septic mortality in 5 cases/65 (7.7%) (limited to generalised peritonitis alone) only affected patients undergoing "limited interventions", but none of the 41 patients undergoing "ideal intervention". Mortality was significantly influenced by age: 50% of over 80 year-olds, none below 60. Postoperative hospitalisation was 17.1 days (in the first stage) of "limited interventions" and 9.7 days for "ideal interventions". CONCLUSIONS: The results argue clearly in favour of the "courageous" ideal colectomy with peritoneal lavage and protection of the colorectal anastomosis using Gullino's three-way tube.