Intramolecular oxidative deselenization of acylselenoureas: a facile synthesis of benzoxazole amides and carbonic anhydrase inhibitors.

A mild, efficient and one pot procedure to access benzoxazoles using easily accessible acylselenoureas as starting materials has been discovered. Mechanistic studies revealed a pH dependent intramolecular oxidative deselenization, with ring closure due to an intramolecular nucleophilic attack of a phenoxide ion. All the benzoxazoles herein reported possessed a primary sulfonamide zinc binding group and showed effective inhibitory action on the enzymes, carbonic anhydrases.

Carbonic anhydrases and their functional differences in human and mouse sperm physiology.

Fertilization is a key reproductive event in which sperm and egg fuse to generate a new individual. Proper regulation of certain parameters (such as intracellular pH) is crucial for this process. Carbonic anhydrases (CAs) are among the molecular entities that control intracellular pH dynamics in most cells. Unfortunately, little is known about the function of CAs in mammalian sperm physiology. For this reason, we re-explored the expression of CAI, II, IV and XIII in human and mouse sperm. We also measured the level of CA activity, determined by mass spectrometry, and found that it is similar in non-capacitated and capacitated mouse sperm. Importantly, we found that CAII activity accounts for half of the total CA activity in capacitated mouse sperm. Using the general CA inhibitor ethoxyzolamide, we studied how CAs participate in fundamental sperm physiological processes such as motility and acrosome reaction in both species. We found that capacitated human sperm depend strongly on CA activity to support normal motility, while capacitated mouse sperm do not. Finally, we found that CA inhibition increases the acrosome reaction in capacitated human sperm, but not in capacitated mouse sperm.

Exploring QSARs of some benzenesulfonamides incorporating cyanoacrylamide moieties as a carbonic anhydrase inhibitors (specifically against tumor-associated isoforms IX and XII).

Benzenesulfonamides incorporating cyanoacrylamide moieties with activity against tumour-associated human (h) isoforms hCA IX and XII (which are validated antitumor targets) were investigated for their quantitative structural activity relationships (QSAR). Multiple linear regression analysis was used to develop model relationships between molecular descriptors and inhibition constants (Ki). The molecular geometry optimization were performed on all molecules at DFT-B3LYP/6-311++G(d,p) level. Over 1250 molecular descriptors were calculated using Gaussian 09, Hyperchem and EDRAGON programs. Multiple linear regression equations have been developed and validated using leave-one-out cross-validated technique. The derived QSAR models are found to be statistically significant and show good predictive ability.

How reliable is assessment of true vocal cord-arytenoid unit mobility in patients affected by laryngeal cancer? a multi-institutional study on 366 patients from the ARYFIX collaborative group.

PURPOSE: In clinical practice the assessment of the "vocal cord-arytenoid unit" (VCAU) mobility is crucial in the staging, prognosis, and choice of treatment of laryngeal squamous cell carcinoma (LSCC). The aim of the present study was to measure repeatability and reliability of clinical assessment of VCAU mobility and radiologic analysis of posterior laryngeal extension. METHODS: In this multi-institutional retrospective study, patients with LSCC-induced impairment of VCAU mobility who received curative treatment were included; pre-treatment endoscopy and contrast-enhanced imaging were collected and evaluated by raters. According to their evaluations, concordance, number of assigned categories, and inter- and intra-rater agreement were calculated. RESULTS: Twenty-two otorhinolaryngologists evaluated 366 videolaryngoscopies (total evaluations: 2170) and 6 radiologists evaluated 237 imaging studies (total evaluations: 477). The concordance of clinical rating was excellent in only 22.7% of cases. Overall, inter- and intra-rater agreement was weak. Supraglottic cancers and transoral endoscopy were associated with the lowest inter-observer reliability values. Radiologic inter-rater agreement was low and did not vary with imaging technique. Intra-rater reliability of radiologic evaluation was optimal. CONCLUSIONS: The current methods to assess VCAU mobility and posterior extension of LSCC are flawed by weak inter-observer agreement and reliability. Radiologic evaluation was characterized by very high intra-rater agreement, but weak inter-observer reliability. The relevance of VCAU mobility assessment in laryngeal oncology should be re-weighted. Patients affected by LSCC requiring imaging should be referred to dedicated radiologists with experience in head and neck oncology.

Three-dimensional, high-definition exoscopic parotidectomy: a valid alternative to magnified-assisted surgery.

The authors report their experience regarding parotidectomy performed under a three-dimensional-high-definition (3D-HD) exoscope, with the aim of evaluating its effectiveness in parotid surgery. This is a prospective study on nine patients treated by the same surgeon. All patients underwent parotidectomy for extrafacial primary tumours without preoperative involvement of the skin or of the facial nerve from March 2019 to June 2019 with the use of a 3D-HD exoscope. Magnification was variable from 8x to 30x with direct vision supplied by a 3D monitor. Six men and three women, mean (range) age 47.8 (19-74) years underwent parotidectomy. No patient experienced postoperative complications or definitive facial palsy. The mean (range) time of surgery was 149.4 (115 - 210) minutes. The 3D exoscope represents a valid alternative to the operative microscope or surgical loupe for parotid surgery. It is a light instrument allowing for precise surgical dissection of the parotid region by reducing the risks for iatrogenic lesions of the facial nerve using a real 3D magnification of the anatomical structures in HD. Furthermore, its use does not prolong the operative time and shows high potential for training and educational purposes since the operating room staff can better perceive the procedure and the surgeon's fine gestures. Although the preliminary applications show promising results, there is still a need for wider scientific validation.

[Identification of Legionella spp. by means of cultural and molecular methods in a public hospital]. / Isolamento di Legionella spp. mediante metodi colturali e tecniche molecolari in matrici ambientali prelevate in una struttura ospedaliera pubblica.

An epidemiologic study on the isolation of Legionella spp from the sanitary water of a public Hospital in Cagliari (Italy) has been performed. The aim of the study was the comparison between the isolation of various Legionella spp from different hospital sources and the real hazard of Legionella infection of the inpatients. Two test methods were used for Legionella detection: a) the culture on selective media, that has the disadvantage of being quite time-consuming and of isolating also other bacterial species. Furthermore, the culture method often fails the isolation of vital but not culturable bacteria (VBNC); b) the PCR molecular method, which is rapid and precise and recognizes also VBNC cells. The most relevant result of this work was that, in spite of the isolation of a considerable number of Legionella spp (even Legionella pneumophila), no case of infection was detected in the Hospital during the period of the study.

Parotid tumours: clinical and oncologic outcomes after microscope-assisted parotidectomy with intraoperative nerve monitoring.

Temporary and permanent facial nerve dysfunctions can be observed after parotidectomy for benign and malignant lesions. Intraoperative nerve monitoring is a recognised tool for the preservation of the nerve, while the efficacy of the operative microscope has been rarely stated. The authors report their experience on 198 consecutive parotidectomies performed on 196 patients with the aid of the operative microscope and intraoperative nerve monitoring. 145 parotidectomies were performed for benign lesions and 53 for malignancies. Thirteen patients treated for benign tumours experienced temporary (11 cases) or permanent facial palsy (2 cases, both of House-Brackmann grade II). Ten patients with malignant tumour presented with preoperative facial nerve weakness that did not improve after treatment. Five and 6 patients with malignant lesion without preoperative facial nerve deficit experienced postoperative temporary and permanent weakness respectively (the sacrifice of a branch of the nerve was decided intraoperatively in 2 cases). Long-term facial nerve weakness after parotidectomy for lesions not directly involving or originating from the facial nerve (n = 185) was 2.7%. Patients treated for benign tumours of the extra facial portion of the gland without inflammatory behaviour (n = 91) had 4.4% facial nerve temporary weakness rate and no permanent palsy. The combined use of the operative microscope and intraoperative nerve monitoring seems to guarantee facial nerve preservation during parotidectomy.

Sialendoscopy for salivary stones: principles, technical skills and therapeutic experience.

Obstructive sialadenitis is the most common non-neoplastic disease of the salivary glands, and sialendoscopy is increasingly used in both diagnosis and treatment, associated in selected cases with endoscopic laser lithotripsy. Sialendoscopy is also used for combined minimally invasive external and endoscopic approaches in patients with larger and proximal stones that would require excessively long laser procedures. The present paper reports on the technical experience from the Ear, Nose and Throat Unit of the Sant'Orsola-Malpighi Hospital of Bologna, and from the Department of Otorhinolaryngology of the University Hospital of Cagliari, Italy, including the retrospective analysis of the endoscopic and endoscopic assisted procedures performed on 48 patients (26 females and 22 males; median age 45.3; range 8-83 years) treated for chronic obstructive sialadenitis at the University Hospital of Cagliari from November 2010 to April 2016. The results from the Sant'Orsola-Malpighi Hospital of Bologna have been previously published. The technical aspects of sialendoscopy are carefully described. The retrospective analysis of the University Hospital of Cagliari shows that the disease was unilateral in 40 patients and bilateral in 8; a total of 56 major salivary glands were treated (22 submandibular glands and 34 parotids). Five patients underwent bilateral sialendoscopy for juvenile recurrent parotitis. 10 patients were treated for non-lithiasic obstructive disease. In 33 patients (68.75%) the obstruction was caused by salivary stones (bilateral parotid lithiasis in 1 case). Only 8 patients needed a sialectomy (5 submandibular glands and 3 parotids). The conservative approach to obstructive sialadenitis is feasible and can be performed either purely endoscopically or in a combined modality, with a high percentage of success. The procedure must be performed with dedicated instrumentation by a skilled surgeon after proper training since minor to major complications can be encountered. Sialectomy should be the "extrema ratio" after failure of a conservative approach.

Ocular Munchausen syndrome resulting in bilateral blindness.

PURPOSE: Münchausen syndrome is a factitious disorder in which patients knowingly harm themselves for subconscious psychological reasons in order to be hospitalized. Recognition of this psychopathology is important, to prevent potentially severe eye damage. Ocular Münchausen syndrome is uncommon. The authors describe an elderly woman with recurrent, probably self-induced, ocular trauma leading to bilateral blindness. The authors are unaware of any previously reported cases of Münchausen syndrome resulting in bilateral blindness and occurring in old age. CASE REPORT: A 73-year-old woman was first seen in 1991 with a closed-globe injury to the right eye, apparently following a household fall. Physical examination showed no sign of extraocular trauma. Right visual acuity was 20/30 after 2 months. She was readmitted in May 2003 with left globe rupture, allegedly following a domestic fall. No extraocular trauma was found. She developed ocular phthisis 6 months postoperatively. The patient was admitted again in February 2004 with right globe rupture, following another alleged domestic fall. Physical examination showed no sign of extraocular trauma. Right visual acuity was 20/400 2 months postoperatively. Psychiatric evaluation revealed Münchausen syndrome. Psychotherapy was prescribed, but refused by her family. CONCLUSIONS: Diagnosis of Münchausen syndrome is difficult to make in the ophthalmic department. Münchausen patients have little or no ability to control their self-destructive behavior. A sympathetic and supportive approach is therefore required and these patients should be urgently referred to a psychiatrist with experience in factitious disorders. Even with psychotherapy, which is often refused, the prognosis remains poor.

Corneal graft rejection after penetrating keratoplasty for keratoconus in Turner's syndrome.

PURPOSE: To report a patient with Turner's syndrome who developed graft rejection after penetrating keratoplasty (PK) for keratoconus and to review the ophthalmic literature on the association between keratoconus and Turner's syndrome. METHODS: A woman with bilateral keratoconus and Turner's syndrome (45,XO) was referred for progressive visual loss in the right eye. Best-corrected visual acuity was 20/400 in the right eye. Slit-lamp examination revealed corneal thinning with ectatic protrusion of the central cornea and Vogt's striae in the right eye. The patient underwent PK in the right eye in January 2001. She developed graft rejection in April 2003 and visual acuity dropped to hand motion. After treatment with topical and systemic steroids and systemic cyclosporine A, visual acuity recovered to 20/80 in July 2003. RESULTS: The authors know of only three other reported patients (six eyes) with keratoconus in Turner's syndrome. Five eyes underwent PK with good visual rehabilitation, but one developed immunologic graft rejection 7 years after surgery. On the whole, considering the current report and the other cases described in the literature, graft rejection occurred in 2 out of 6 eyes (33.3%). The graft survival rate was 80% after 2 years and 40% after 7 years. CONCLUSIONS: The results suggest that grafts for keratoconus in patients with Turner's syndrome might have an increased risk of immunologic rejection. Corneal grafts in Turner's syndrome need to be monitored closely. Early detection of graft rejection and aggressive treatment with topical and systemic steroids and systemic cyclosporine A can save the graft and restore useful vision.

Glucose 6-phosphate dehydrogenase deficiency and cataract of patients in northern Sardinia.

We determined the activity level of glucose 6-phosphate dehydrogenase in 467 patients with cataract from northern Sardinia. Of 226 men, 18 (8%) had glucose 6-phosphate dehydrogenase deficiency. Of 241 women, 30 (12%) were heterozygous and two (1%) were homozygous for glucose 6-phosphate dehydrogenase deficiency. These prevalences were not significantly different from those expected in the general population. We concluded that patients with glucose 6-phosphate dehydrogenase deficiency do not have a higher risk of developing cataract.

The treatment and follow up of adult chlamydial ophthalmia.

Sixty two patients diagnosed as having adult chlamydial ophthalmia were treated with oral doxycycline and roxithromycin in association and tetracycline eye wash for 2 weeks. Chlamydial ophthalmia was diagnosed by laboratory detection of the micro-organism in ocular specimens using direct immunofluorescent monoclonal antibody staining for Chlamydia trachomatis, chlamydial culture in cycloheximide treated McCoy cells, and Giemsa staining. An immunoenzymatic method for detection of specific IgG and IgA in patients' serum was used as an additional test to confirm the diagnosis. All patients were reexamined 3 weeks after completing their course of antibiotics and in the case of persistent infection a further course of treatment was given. With this treatment regimen 48 out of 62 patients (77.4%) were cured after three courses. Because of the risks of an inadequate response to therapy, we recommend a proper post-treatment follow up in all patients with chlamydial eye infections.

Identification and antibiotic susceptibility of coagulase negative staphylococci isolated in corneal/external infections.

AIMS: To identify and determine antibiotic susceptibility of coagulase negative staphylococci (CoNS) isolated from patients with chronic blepharitis, purulent conjunctivitis, and suppurative keratitis. METHODS: A retrospective review of all culture positive cases of chronic blepharitis, purulent conjunctivitis, and suppurative keratitis between July 1995 and December 1996 was performed. Cases in which CoNS were the sole isolates were analysed. Species identification was performed by using a commercially available standardised biochemical test system. Antibiotic susceptibility to penicillin, gentamicin, tetracycline, erythromycin, ciprofloxacin, and teicoplanin was determined by agar disc diffusion (Kirby-Bauer method). Teicoplanin resistance was confirmed by agar dilution. RESULTS: 42 Staphylococcus epidermidis, four S warneri, three S capitis, two S hominis, one each of S xylosus, S simulans, S equorum, and S lugdunensis were identified. 37 CoNS were penicillin resistant, 12 gentamicin resistant, 28 tetracycline resistant, 18 erythromycin resistant, four ciprofloxacin resistant, and one teicoplanin resistant (MIC, 32 microg/ml). In total, 16 strains were resistant to three or more antibiotics. CONCLUSION: Species of CoNS apart from S epidermidis may be isolated from patients with corneal and external infection. Antibiotic susceptibility of CoNS is unpredictable and multiresistant strains are common. As a result, antibiotic susceptibility testing should be performed in all cases of clinically significant ocular infections caused by CoNS.

Traumatic intracerebral hematomas. 72 cases surgically treated.

This report concerns 72 patients who underwent surgery for postraumatic intracerebral hematoma. The clinical findings of this pathology have been delineated as well as the diagnostic and therapeutic characteristics.

Removal of tumours of the orbital apex via a postero-lateral orbitotomy.

BACKGROUND: The surgical management of pure apical tumours of the orbit may be problematic with traditional approaches. A postero-lateral approach, specifically designed for apical growths, provides a more favourable angle of vision through a relatively small bone opening. METHODS: A series of 103 consecutive cases of intraorbital tumours, operated on in a community-based institution, was retrospectively reviewed. Out of this series, 8 patients, harbouring lesions located in the posterior intraconal space, underwent a postero-lateral orbitotomy. This approach, through a small opening on the orbital and temporal portions of the greater wing of the sphenoid, with the lesser sphenoidal wing, the orbital plate of the frontal bone, the lateral rim of the orbit being maintained intact, allowed adequate exposure of the orbital apex and successful extirpation of the tumours. In four patients the histological examination disclosed a cavernoma; the other patients had, respectively, a dermoid cyst, a lymphoma, a hemangiopericytoma and a metastatic melanoma. RESULTS: No recurrences were observed in a follow-up period ranging from 1 to 7 years postoperatively (the patient with melanoma died 16 months after operation for systemic complications of her illness). One patient showed transient weakness of lateral rectus muscle due to surgical manipulation, which subsided in few months. CONCLUSIONS: The postero-lateral orbitotomy represents a reliable alternative to other traditional surgical approaches when dealing with tumours of the orbital apex, providing excellent exposure of this region with a low rate of operative morbidity.

Simultaneous storage and degradation of PHB and glycogen in activated sludge cultures.

Bacteria in activated sludge are subjected to periods of substrate availability and absence of external substrates. The response of bacteria to such dynamic conditions was studied in a 2 L sequencing batch reactor (SBR) by subjecting a mixed microbial population to successive periods of external substrate availability (feast period) and no external substrate availability (famine period). In previous studies, acetate or glucose was used as single substrate leading to the storage of polyhydroxybutyrate or glycogen, respectively. In this study, a mixture of acetate and glucose was used. It appeared that both substrates were consumed simultaneously. The relative contribution of growth and storage processes was in these experiments similar as in the systems fed with a single substrate only. The ratio of substrate uptake over substrate storage was 0.6 Cmol/Cmol for both substrates. The uptake rate of acetate was not influenced by the simultaneous uptake of glucose. The degradation kinetics and rates of the storage compounds were the same as for the systems in which only one compound was stored in the activated sludge. The global performance of the culture grown on mixed substrates could therefore be described as the sum of the conversions observed in cultures fed with the individual substrates.

Role of the intraoperative real-time sonography in the tumours of the pineal region and third ventricle.

Real-time ultrasound was used to assist localization and surgical removal of ten cases of tumours of pineal region and third ventricle. Two illustrative cases are reported in which intraoperative ultrasound greatly facilitates the surgical procedure.

Hematomyelia during anticoagulant therapy.

An unusual case of hematomyelia during anticoagulant therapy is reported in a patient after cardiac surgery. A review of the pertinent literature is presented. After medical and surgical treatment, the transverse symptoms largely subsided with rehabilitation of the patient.

Transpedicular decompression and stabilization of burst fractures of the lumbar spine.

Twenty-seven consecutive patients with neurological impairment due to burst fractures of the lumbar spine were operated upon, via the postero-lateral route, over a 38-month-period. Transpedicular fixation devices [posterior segmental fixator (PSF) or variable screw placement system (VSP)] were applied in all cases, in order to achieve short-segment fusion of the fractured spinal segment. Return to useful motor power or neurological normality (median follow-up: 18.7 months) occurred in 22 cases (81% of the whole series), with this outcome resulting in all but one of the cases with preoperative incomplete neurological deficit. Postoperative encroachment of the spinal canal, degree of kyphotic deformity, and reduction of the vertebral height showed statistically significant differences compared with the corresponding preoperative values.