Arylsulfonyl histamine derivatives as powerful and selective α-glucosidase inhibitors.

A series of simple N-arylbenzenesulfonyl histamine derivatives were prepared and screened against α-glucosidase. Inhibition was in the micromolar range for several N α,N τ-di-arylsulfonyl compounds, with N α,N τ-di-4-trifluorobenzenesulfonyl histamine (IId) being the best inhibitor. Compound IId is a reversible and competitive α-glucosidase inhibitor, and presented good selectivity with respect to other target enzymes, including ß-glucosidase and α-amylase, and interesting predicted physicochemical properties. Docking studies have been run to postulate ligand-enzyme interactions to account for the experimental results. In vivo, compound IId produced a similar hypoglycemic effect to acarbose with half of its dose.

Surgical treatment of large incisional hernias with intraperitoneal composite mesh: a cohort study.

PURPOSE: Patients with large incisional hernias have significant morbidity and their management is a challenge for the surgical team because of the large abdominal wall involvement. The choice of surgical technique is still controversial. The purpose of this study is to analyze the predictive factors for recurrence after intraperitoneal mesh repair in patients with large incisional hernias. METHODS: A retrospective cohort observational study with a prospectively collected database was performed in the Hospital Clinico San Carlos (Madrid, Spain). All consecutive patients operated on from January 2009 to December 2014 with incisional hernia of 10 or more centimeters in its transverse diameter were included. An intraperitoneal repair with a composite mesh fixed with discontinuous absorbable suture and fibrin sealant was performed. Demographic data, comorbidities, and early and long term outcomes were analyzed. The primary outcome was the presence of recurrence. RESULTS: One hundred and twenty patients were included. Mean age was 63.3 years (SD 12.9) and sex ratio was 1.4:1. Seventy-two patients (60%) were ASA III-IV. Forty-five patients (37.5%) had recurrent ventral hernias. Mean defect size was 14.7 cm (SD 3.21) of width. Overall postoperative morbidity rate was 25%. Median hospital stay was 6 days (IQR 4-8). Recurrence rate was 8.3%, after a median follow-up of 16 months (IQR 10-25). Multivariate analysis showed significant association between ASA III-IV, use of Composix Kugel™ mesh, superficial surgical site infection, and the presence of recurrence. CONCLUSIONS: The recurrence rate after intraperitoneal mesh repair in patients with large incisional hernias might be associated with ASA III-IV, use of Composix Kugel™ mesh, and superficial surgical site infection.

Reactivity of monoclonal antibody F36/22 with human ovarian adenocarcinomas.

Monoclonal antibody F36/22 recognizes high-molecular-weight glycoprotein components associated with neoplastic development of the ovary. Indirect immunoperoxidase staining techniques were performed on a panel of nonmalignant ovarian tissues, primary ovarian tumors, exfoliated ascitic tumor cells, and metastatic lesions. Normal ovarian tissue components (n = 20) failed to exhibit detectable levels of antigen, whereas benign ovarian tissues show a low incidence of immunostaining (three of 26) restricted to some ductal elements. One hundred % (19 of 19) of the immunopositive primary malignant tumors were histologically classified as adenocarcinomas. Each of the predominant adenocarcinoma histotypes consistently showed expression of the antigen with 30 to 100% of the tumor cells scored as immunopositive. Ascitic tumor cells obtained from all of the ovarian adenocarcinoma patients examined (47 of 47) displayed immunopositive reactions, whereas normal mesothelial cells in these specimens exhibited undetectable staining. In addition, ovarian adenocarcinoma metastases (12 of 12) exhibited very intense immunoreaction products. No detectable antigen was expressed by nonadenocarcinoma ovarian tumor cells.

Second-look laparoscopy prior to proposed second-look laparotomy.

A prospective study was carried out to evaluate the use of second-look laparoscopy in patients in complete clinical remission after prolonged chemotherapy for advanced ovarian adenocarcinoma. Twenty-two patients with FIGO stages IIB, III, and IV ovarian adenocarcinoma underwent second-look laparoscopy after a median of 23 months of therapy. Eight (36.3%) patients had documented evidence of persistent ovarian cancer and were thus spared second-look laparotomy. Moreover, in 4 patients (18.1%), malignant cells in cytologic washings were the only laparoscopic evidence of persistent ovarian cancer. The absence of visible tumor and malignant cells in cytologic washings allows for the use of second-look laparotomy while the patient is under 1 anesthesia; the presence of tumor or malignant cells in cytologic washings spares the patient second-look laparotomy at that time.

Limitations of drug sensitivity testing in soft agar for clinical management of patients with ovarian carcinoma.

Thirty specimens from 28 patients (15 previously treated, 13 previously untreated) with ovarian carcinoma were studied in a soft agar colony-forming assay to determine whether or not the assay could be useful for treatment planning. There were sufficient colonies for drug testing in 23 cases. An in vitro drug response was found in 12 of 106 drug tests. In vivo-in vitro correlations could be made for 28 drug trials in 16 patients. Eight patients were not evaluated for response because they were clinically disease free after debulking surgery. Single agents were evaluated in vitro, although most patients received combination chemotherapy. In 23 cases the tumor was resistant in vitro and in vivo. There were two false-negative and three false-positive results. Cell aggregates that may artificially increase growth rates and apparent in vitro drug resistance were a major problem technically. In view of the problems identified, the assay in its current form should not be used routinely to direct therapy.

Primary prostatic involvement in non-Hodgkin lymphoma.

We report 3 cases of primary extranodal lymphoma of the prostate, an unusual extranodal presentation rarely diagnosed antemortem. Symptoms of prostatism associated with an enlarged hard prostate with pyuria and hematuria in younger patients should suggest the diagnosis. Urine cytologic examination should aid in the diagnosis of this condition.

Fine-needle aspiration of metastatic lesions and regional lymph nodes in genitourinary cancer.

A percutaneous fine-needle aspiration biopsy of metastatic tumor and/or retroperitoneal, pelvic, or abdominal lymph nodes was accomplished in 101 patients. A diagnosis of metastatic disease was confirmed by this method in 49 patients. In 26 patients, surgical excisional biopsy or exploratory laparotomy was avoided. An unknown pelvic mass causation was diagnosed in 3 patients. In 15 of 57 patients with localized bladder, prostate, or testis cancer, involvement of regional lymph nodes was confirmed by transabdominal find-needle aspiration. All 57 transabdominal aspirations were performed without complications. The method is inexpensive, safe, and can have a high accuracy in diagnosing a local tumor spread or distant metastases.

Malignant peritoneal cytology in stage I endometrial adenocarcinoma: the effect of progesterone therapy (a preliminary report).

From February 1982-June 1986, 25 consecutive patients with surgical stage I endometrial adenocarcinoma (no evidence of metastasis at surgery or occult cervical or adnexal involvement on histopathologic review) and malignant peritoneal cytologic washings were treated with progesterone therapy. Twenty-two patients have undergone a second look laparoscopy and repeat cytologic washings, one of those also underwent a third look laparoscopy. Two patients refused second look laparoscopy, and in a third patient laparoscopy was medically contraindicated; all three have no evidence of disease (NED) at 15, 46, and 64 months respectively and are off therapy. Of the 22 patients who underwent second look laparoscopy, 21 (95%) had no macroscopic evidence of recurrent endometrial carcinoma and repeat negative peritoneal cytology; 1 patient (5%) had persistent malignant peritoneal cytology but was NED at third look laparoscopy one year later. All 25 patients are off progesterone therapy and remain clinically NED from 12-64 months. Although progesterone therapy for malignant peritoneal cytology resulted in a 100% reversal of malignant peritoneal cytology to normal in the 22 patients who underwent second or third look laparoscopy and all 25 patients remain clinically NED, the true value of progesterone therapy can only be ascertained by a randomized trial of progesterone versus no therapy.

[Mesiodistal inclination of permanent 2d molars Angles of bite]. / Les inclinaisons mésio-distales des secondes molaires permanentes. Angles de morsure

Measurement of the angles formed by the axes of the second permanent molars on the plane of bite in premolar sector was carried out by profile teleradiographies of 50 young adults. These patients showed no abnormality likely to affect the molar alveolar processes in the saggital plane. The results were as follows: Open angle in front of the second upper molar with plane of bite:80degres. Open angle in front of the second lowermolar with plane of bite: 110degrees. Angle of bite of the second molars: 170degrees, identical with the angle of bite of the first molars.

Sputum cytology for the detection of pulmonary metastases from colorectal carcinoma.

Twenty-two patients with pulmonary metastases from adenocarcinoma of the colon and rectum had sputum samples examined for cytology. All patients had lesions demonstrated on chest roentgenography and eight patients also underwent bronchoscopy. Three or more sputum samples were examined for eight patients, two samples for seven patients, and seven patients had one sample only examined. In five of 22 patients, the sputum samples were reported to be unsatisfactory for cytodiagnosis. Of the remaining 17, nine patients had at least one positive result for metastatic adenocarcinoma and in two additional cases the sample showed atypical cells. The result was therefore positive or atypical in 11 of 17 patients (65 percent). The positive cytology rate reported (79 percent for multiple pulmonary metastases) represents an improvement compared with previously published work. In this study 14 patients had either one or two samples collected for cytology and it is likely that the positivity rate would have been higher if three samples had been collected.

Scanning electron microscopic study of prostatic cancer.

Scanning electron microscopy is applied to the study of 3-dimensional surface and organization of a normal prostate gland and of samples of prostatic disease, including five cases of benign hyperplasia and 15 cases of prostatic adenocarcinoma of different degrees of differentiation. The study provided further evidence regarding the nature and origin of prostatic cancer at a cytologic level and indicated alternate pathways to the neoplastic spread within the prostate gland.

[Long-term results of glossectomies]. / Résultats à long terme des glossectomies.

Analysis of results of a series of marginal glossectomies, performed for orthodontic or orthopedic indications over the last 10 years, showed sustained improvement of alveolar process inclination with practically inexistant functional or psychologic sequelae.

Synthesis and release of glycoconjugates bearing N-linked oligosaccharides by ovarian carcinoma cells isolated from effusions.

Ovarian carcinoma cell clusters were isolated from patient effusions. The cell isolates were incubated in vitro with radioactive glycoconjugate precursors. Radiolabelled glycoconjugates released to culture media were analyzed for molecular mass heterogeneity and lectin binding activity. From 10 to 50% of the released glycoconjugates were present as a heterogeneous array of glycoconjugates of molecular mass greater than 250 kilodaltons. The remaining glycoconjugates were dispersed in a molecular mass range extending down to approximately 15 kilodaltons. Concanavalin A-Sepharose affinity chromatography revealed the presence of N-linked oligosaccharides. Interaction of glycoconjugates with lentil and pea lectins indicated the presence of L-fucose residues linked to asparagine-bound N-acetylglucosamine. Precipitation of glycoconjugates with ricinus communis agglutinin I showed the presence of nonreducing terminal N-acetyllactosamine residues. Collectively, the data indicate that ovarian carcinoma cells release to culture medium fucosylated glycoconjugates bearing complex-type oligosaccharides. The synthesis and release of these glycoconjugates showed no significant differences among different histologic types of ovarian carcinoma; however, modulation as a function of tumor progression may occur.

Characterization of glycoconjugates released in vitro by human ovarian carcinoma cells isolated from effusions.

Ovarian carcinoma cell clusters were isolated from patient effusions. The glycoconjugates released to culture medium in vitro were characterized by electrophoretic, immunoassay and gel filtration procedures. Metabolically radiolabelled glycoconjugates were heterodisperse with respect to molecular weight and this heterodispersity was independent of incubation time in vitro. This heterodispersity was also characteristic of mixed Mullerian tumor cells of endometrial origin whereas mesothelial cells released a discrete glycoconjugate of MW 65-70 kDa. Multiple Coomassie blue-stained polypeptides were released by the carcinoma cells. These polypeptides were not adsorbed serum components as assessed by immunodiffusion analyses. Periodic acid-Schiff-reactive macromolecules appeared only at the top of electrophoresis gels. The high molecular weight glycoconjugates synthesized by ovarian carcinoma cells precipitated with an effusion globulin fraction at low ionic strength, but the low molecular weight components (40-70 kDa) were soluble. Immunoprecipitation with anti-Ig failed to precipitate carcinoma glycoconjugates. Antisera raised against the released carcinoma macromolecules precipitated carcinoma glycoconjugates and normal ovarian polypeptides. Antisera raised against normal ovarian macromolecules precipitated ovarian polypeptides but reacted only slightly with carcinoma glycoconjugates. Immunodiffusion analyses showed the presence of alpha 1-acid glycoprotein and carcinoembryonic antigen (CEA)-like components in the carcinoma glycoconjugates. The presence of CEA-like glycoconjugates was confirmed by immunoprecipitation. The antigens and antisera for different histologic types of ovarian carcinoma were cross-reactive. The presence of beta 2-microglobulin suggested that some of the glycoconjugates were shed from the cell surface.