Protective effect of carnosine during nitrosative stress in astroglial cell cultures.

Formation of nitric oxide by astrocytes has been suggested to contribute, via impairment of mitochondrial function, to the neurodegenerative process. Mitochondria under oxidative stress are thought to play a key role in various neurodegenerative disorders; therefore protection by antioxidants against oxidative stress to mitochondria may prove to be beneficial in delaying the onset or progression of these diseases. Carnosine has been recently proposed to act as antioxidant in vivo. In the present study, we demonstrate its neuroprotective effect in astrocytes exposed to LPS- and INFgamma-induced nitrosative stress. Carnosine protected against nitric oxide-induced impairment of mitochondrial function. This effect was associated with decreased formation of oxidatively modified proteins and with decreased up-regulation oxidative stress-responsive genes, such as Hsp32, Hsp70 and mt-SOD. Our results sustain the possibility that carnosine might have anti-ageing effects to brain cells under pathophysiological conditions leading to degenerative damage, such as aging and neurodegenerative disorders.

Weekly docetaxel and gemcitabine as first-line treatment for metastatic breast cancer: results of a multicenter phase II study.

OBJECTIVES: We conducted a multicenter phase II study to evaluate the clinical efficacy, toxicity, and dose intensity of a new weekly schedule of docetaxel and gemcitabine as first-line treatment of metastatic breast cancer patients. METHODS: We enrolled 58 patients, 52% of whom had received a previous anthracycline-containing chemotherapy. The treatment schedule was: docetaxel 35 mg/m2 and gemcitabine 800 mg/m2 i.v. on days 1, 8, 15 every 28 days. RESULTS: All patients were assessable for toxicity and 56 for efficacy. Overall response rate was 64.3% with 16.1% of complete responses and 48.2% of partial responses. Median survival was 22.10 months (95% CI: 15.53-28.67) and median time to tumor progression was 13.6 months (95% CI: 10.71-16.49). The most common hematological toxicity was neutropenia (no febrile neutropenia), which occurred in 28 patients (48.3%) but grade 3-4 in only 8 patients (14%). Alopecia, the most common nonhematological toxicity, occurred in 20 (34.5%) patients, but only 5 patients (8.6%) experienced grade 3 alopecia. CONCLUSION: The activity of docetaxel and gemcitabine in metastatic breast cancer is confirmed. The promising results of the employed schedule, in agreement with other published studies, need to be further confirmed within a phase III study.

Randomised, open-label, phase II trial of paclitaxel, gemcitabine and cisplatin versus gemcitabine and cisplatin as first-line chemotherapy in advanced transitional cell carcinoma of the urothelium.

The purpose of the study was to evaluate the antitumor activity and the safety of paclitaxel combined with gemcitabine and cisplatin in patients affected by advanced transitional cell carcinoma of the urothelium (TCC). Eighty-five patients affected by advanced TCC and measurable disease were randomized to receive either paclitaxel at dosage of 70 mg/m2, gemcitabine 1000 mg/m2 and cisplatin 35 mg/m2 on days 1 and 8 every 3 weeks (GCP) or gemcitabine 1000 mg/m2 on days 1, 8, 15 and cisplatin 70 mg/m2 on day 2 every 4 weeks (GC). All enrolled patients were considered evaluable for response and toxicity (intention to treat). The observed response rate was 43% for GCP and 44% for GC combination, respectively. Median time to treatment failure was 32 weeks for GCP and 26 weeks for GC and overall survival 61 vs 49 weeks, respectively (p-value not significant). Grade 3-4 neutropenia was observed in 49% of patients treated with GCP vs 35% of those treated with GC (P=0.05) and grade 3-4 thrombocytopenia was observed in 36% of GCP treated patients as compared to 21% of those treated with GC (P=0.01). Seven patients over 70 years old or with poor PS were removed from the study: 6 patients from GCP group (2 toxic deaths, 2 grade 4 myelotoxicity and 2 grade 3 asthenia) and 1 from GC group was lost to follow-up after the first cycle. The combination of paclitaxel, gemcitabine and cisplatin is effective in the treatment of TCC. However, the addition of paclitaxel to the combination of gemcitabine plus cisplatin seems to increase toxicity, therefore it seems not suitable for poor PS patients and those over 70 years old. Larger and more powered studies are needed to exactly define the role of paclitaxel in this combination.

[Erythropoietin and cisplatin-induced neuropathies in cancer patients]. / Eritropoietina e neuropatie da cisplatino nei pazienti oncologici.

Anaemia commonly occurs in cancer patients on chemotherapy, often necessitating blood transfusion, and, in most recent years, treatment with human recombinant cythropoietin (rHuEPO). However, several extra-hematological effects were reported for EPO, and multi-organ physiological effects on development and repair of tissues are described both on nerves and muscles. Moreover, EPO is presently used in oncological patients with the goal of preventing or limiting anemia secondary to chemotherapy. Ten patients with advanced lung cancer and without neurological impairment assessed by Siegal score and without severe anemia, were studied. Patients (age 56.2 +/- 8.3 years) were random assigned to two groups of 5 patients each: the control group and the EPO treated group. In both groups, at the end of the study, hemoglobin concentration was not different (above 9 mg/dl). In EPO treated group neurological score was 4.00 +/- 1.87, significantly lower (p < 0.004) in comparison with untreated group (score 9.20 +/- 4.32). From these preliminary data we suggest that EPO treatment in cancer patients can exert also a limiting effect on cisplatin peripheral neurotoxicity.

MR dacryocystography: comparison with dacryocystography and CT dacryocystography.

BACKGROUND AND PURPOSE: Several techniques have been used to image the nasolacrimal system, providing functional (dacryoscintigraphy) or morphologic (dacryocystography, CT dacryocystography [CTD]) information. Using gadopentetate dimeglumine-diluted solution injected into the lacrimal canaliculus or instilled into the conjunctival sac, we compared the sensitivity of MR dacryocystography (MRD) with that of CTD. METHODS: Eleven healthy volunteers and 25 patients affected by primary epiphora (21 patients) or postsurgical recurrent epiphora (four patients) underwent MRD after the topical administration of contrast media or cannulation of the lacrimal canaliculus. The MR imaging findings were compared with irrigation and CTD data. All patients underwent surgical treatment (dacryocystorhinostomy), which served as a standard of reference for confirming the MRD findings. RESULTS: The topical administration of contrast-enhanced saline solution and the injection of contrast-enhanced saline solution after cannulation were always well tolerated. In healthy volunteers, outflow of contrast media was always revealed by MRD. Eight (32%) of 25 patients with epiphora had stenosis proximal to the lacrimal sac revealed by MRD, whereas 17 (68%) of 25 showed a dilated lacrimal sac and nasolacrimal duct stenosis, as confirmed by surgical findings. The findings of MRD after the topical administration of contrast medium and MRD after cannulation of the lacrimal canaliculus were comparable with irrigation or CTD data for all patients except one. CONCLUSION: In patients with epiphora, MR imaging performed after the topical administration of diluted contrast material can reveal stenosis of the lacrimal apparatus and can be added to the standard orbital imaging protocol when lacrimal system involvement is suspected.

[Update on the treatment of choledocholithiasis]. / Attualità nel trattamento della calcolosi coledocica.

Primitive or residual common bile duct calculi following common bile duct surgery can now be treated with minimum surgery using an endoscopic or X-ray guided approach. Having examined the etiopathogenetic theories, the authors analyse the treatment, in particular the possibility of endoscopic papillosphincterotomy and X-ray guided dilatation of the papilla, affirming that the latter can be extremely valuable in cases where it is difficult to canalize the latter.

[Conservative surgical treatment in differentiated thyroid carcinoma]. / Trattamento chirurgico conservativo nel carcinoma differenziato della tiroide.

BACKGROUND: Purpose of the present study was to compare survival of patients affected by differentiated thyroid carcinoma after total and partial thyroidectomy. METHODS: The study has been carried in a retrospective way; mean follow-up has been 160 months. Surgical setting has been the Institute of Emergency Surgery at the University of Catania, where about 80 thyroid surgical procedures are performed every year. Patients have been divided into two groups: the first included 65 patients who underwent total thyroidectomy, while the second group included 67 patients who underwent partial thyroidectomy. Ten patients affected by a T3-T4, N0-N1 tumor were ruled out of the study to allow better uniformity of data. Besides early postoperative complications (recurrent nerve lesion, hypoparathyroidism), patients have been followed by periodic clinical and instrumental examinations. RESULTS: Follow-up has shown similar survival between patients treated by total thyroidectomy and those who underwent partial thyroidectomy (respectively 92.3% and 92.5%). Postoperative complications were instead significantly less in group 2. CONCLUSIONS: For patients affected by differentiated thyroid carcinoma at early stages it is suggested to perform a partial thyroidectomy since, compared to total thyroidectomy, a similar survival rate and a lower incidence of postoperative complications are obtained. According to personal opinion, total thyroidectomy should be performed in cases of thyroid carcinoma with vascular involvement and metastases.

[The use of Dacron prostheses in laparoceles]. / L'impiego di protesi in Dacron nei laparoceli.

BACKGROUND: Purpose of the study was to evaluate indications and efficacy of Dacron prostheses in the treatment of incisional hernias. METHODS: The study has been carried out in a retrospective way; mean follow-up has been 20 months. Surgical setting has been the Institute of Emergency Surgery at the University of Catania, where about 500 abdominal operations are performed every year. Thirty patients affected by incisional hernias have been considered (mean age 66.8 years). In 12 patients the Mayo technique was performed, whereas a Dacron prosthesis was placed in 18 patients. Other than early postoperative complications, patients have been followed by periodical clinical exams in order to find out possible recurrences as well as other late complications. RESULTS: Among 18 patients treated with insertion of Dacron prosthesis no infection, recurrence, bowel fistula, haematoma or dislocation have been observed. Only in one case an intestinal occlusion secondary to adhesions between prosthesis and bowel has occurred; in this patient a new operation has been necessary to remove the prosthesis. CONCLUSIONS: Considering that prostheses have been used in large incisional hernias or in patients with a weak abdominal wall, the high successful percentage (94%) obtained suggests the use of Dacron prostheses which guarantee long stability and minimum risk of recurrences.

[Ogilvie's syndrome]. / La sindrome di Ogilvie.

"Ogilvie's syndrome" or the idiopathic dilatation of the colon is an infrequent pathology whose underlying physiopathology is not yet well known. On the basis of their experience and having reviewed the literature, the authors affirm that this syndrome is caused by the inhibition of gastrointestinal hormones which, under the control of the neurohypophysis, contribute to colon motility. This supposition is backed up by the fact that medical treatment with somatostatin or octreotide leads to the resolution of the disorder.

Blood-ocular barrier damage: use of contrast-enhanced MRI.

The blood-ocular barrier (BOB) shares similar neuroepithelial origin, microanatomy and functions with the blood-brain barrier. There are many natural (e. g. diabetes, hypertension) or iatrogenic (chemotherapy, retinal photocoagulation) conditions which can cause a BOB breakdown, resulting in visual acuity impairment or loss. The authors examined 42 patients affected by BOB damage in different pathological conditions. All patients previously underwent a conventional fluoroangiographic (FA) study. Nine patients with normal FA exam were evaluated also. Despite normal MRI findings immediately after Gd-DTPA injection, contrast leakage into the vitreous body or into the aqueous fluid was demonstrated in delayed scans (40-50 min after contrast administration), proving the existence of a BOB damage (sensitively 94 %). Although FA exam remains the choice modality in BOB breakdown demonstration, we propose MRI as a useful diagnostic tool when optic media opacity (cataract, haemovitreous, intraocular silicon oil) occurs, preventing direct retinal fundus imaging and/or an early screening tool.

[Treatment of stage IV breast carcinoma]. / Il trattamento del carcinoma della mammella al IV stadio.

The authors report a study carried out in 4 patients with stage 4 breast cancer. The treatment protocol was selected according to age and the general conditions of patients. Two out of four patients were treated with adjuvant chemotherapy associated with cyclophosphamide, adriblastin, 5-fluorouracil and folic acid; one patient received neoadjuvant chemotherapy with the same treatment protocol, while the fourth patient was treated with hormone and immunotherapy. Results were satisfying given that survival was considerably increased in 3 patients together with an improvement in general conditions.

[Complications of ileal lymphoma]. / Le complicanze del linfoma dell'ileo.

Non-Hodgkin lymphoma of the ileum accounts for some 3% of all extranodal onset lymphoma and 20% of gastrointestinal lymphoma given that the ileum is more frequently affected than the jejunum and duodenum. The large majority of primary extranodal lymphomas present a diffuse histological structure and in particular involve the cervico-fascial and gastrointestinal regions. Moreover, it is not uncommon to find an association between gastroenteric involvement and Waldeyer's ring (cervico-fascial region). Primary intestinal involvement may not present specific symptoms and remain silent for some time. It is manifested by the onset of complications caused by occlusion and perforation. Two cases of ileal lymphoma were treated at the Institute of Emergency Surgery of Catania University between 1992 and 1993. They were complicated by intestinal perforation and occlusion respectively. Both patients underwent emergency intestinal resection. Surgery represents the elective treatment for primary forms, followed by polychemotherapy and radiotherapy. Prognosis depends on the spread of disease and the hystotype. The administration of NTP and somatopstatin resulted in a shorter postoperative period with fewer surgical complications.

N-ethyl-tauroursodeoxycholic acid, a novel deconjugation-resistant bile salt analogue: effects of acute feeding in the rat.

The purpose of this study was to investigate the physicochemical/biological properties and the effects of acute administration of N-ethyl-tauroursodeoxycholic acid in bile-fistula rats. In vitro determination of high-performance liquid chromatography mobility, octanol/ water partitioning, cholesterol solubilizing capacity, and sensitivity to enzyme deconjugation by bacteria and cholylglycine-hydroxylase were performed. In vivo determination of the following was also performed: (1) maximum secretory rate (SRmax) and choleretic/secretory properties during intravenous (IV) administration; (2) site/ extent of absorption, effects on bile flow, lipid secretion, and biotransformations after intraduodenal infusion. N-ethyl-tauroursodeoxycholate has a lipophilicity slightly higher than tauroursodeoxycholate, close to taurocholate, and similar cholesterol solubilizing capacity. Deconjugation of N-ethyl-tauroursodeoxycholate was 3.4 +/- 2.1% after 72 hours, that of tauroursodeoxycholate was 100% after 24 hours. During IV infusion of 300 nmol/min/ 100g, biliary secretion of N-ethyl-tauroursodeoxycholic and tauroursodeoxycholic acids averaged 185 +/- 76 (standard deviation) nmol/min/100 g and 221 +/- 77 nmol/min/ 100 g (not significant). Increasing infusion rates caused progressive enhancement of bile flow and bile salt secretion until the SRmax was reached (1,305 +/- 240 nmol/min/ 100 g for N-ethyl-tauroursodeoxycholic acid and 3,240 nmol/min/100 g for tauroursodeoxycholate). The two bile salts were similarly choleretic. IV feeding of N-ethyl-tauroursodeoxycholic promoted a greater lipid secretion than tauroursodeoxycholate. After intraduodenal feeding of 800 mumol, 38.8 +/- 14.0% and 43.4 +/- 12.4% of the two bile salts were recovered in bile. No unconjugated bile salts nor unusual metabolites were detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Idiopathic intracranial hypertension: orbital MRI.

The case is reported of a patient with idiopathic intracranial hypertension examined with magnetic resonance imaging. Marked enhancement of the optic nerve heads was found, which might be related to blood-retinal barrier breakdown related to a sudden rise in intracranial cerebrospinal fluid pressure.

[Laparoscopic appendectomy]. / L'appendicectomia per via laparoscopica.

The authors report their experience of 6 cases of appendicectomy using a laparoscopic route of which 5 were performed under local anesthesia and 1 under general anesthesia. The results indicate that this new technique is easy to perform and as rapid and safe as the traditional operation. The possibility of using local anesthesia, the lack of complications when operating on obese patients, the lower incidence of wound infections and rapid postoperative mobilisation all argue in favour of this alternative approach to conventional open surgery.

Long term treatment with omeprazole 20 mg three days a week or 10 mg daily in the prevention of duodenal ulcer relapse.

BACKGROUND: The aim of this study was to compare omeprazole 10 mg o.m. (daily) with omeprazole 20 mg o.m. on Friday to Sunday inclusive (weekend) in the prevention of duodenal ulcer relapse over a 6-month period. METHODS: After an open healing phase (4 to 8 weeks) with omeprazole 20 mg o.m., 81 patients entered the follow-up phase. Forty-two were randomized in a double-blind double-dummy technique, to omeprazole 10 mg o.m., and 39 to omeprazole 20 mg at weekends. At 3 and 6 months or on symptomatic relapse the patients underwent endoscopy with gastric biopsies (quantitative assessment of argyrophilic and gastrin cells), symptom evaluation, and laboratory screening with fasting serum gastrin. RESULTS: Five patients in the 10 mg group and four in the weekend group were lost to follow-up. The estimated relapse rates over six months in the two groups receiving 10 mg daily or 20 mg at weekends were 19% and 31%, respectively (95% CI of percentage difference: -33% to 8%: intention-to-treat analysis, P = N.S.). During the follow-up phase, symptoms tended to be milder in the omeprazole 10 mg daily group compared to the weekend group. Gastrin levels increased significantly during the healing phase but then stayed almost constant in the omeprazole 10 mg group, and significantly decreased with weekend treatment. The median number of argyrophilic cells showed a slight but statistically significant increase in the omeprazole 10 mg daily group, but did not change in the weekend group. Both the healing and long-term therapies were well tolerated. CONCLUSIONS: Our data do not show a clear difference between the two treatment regimens, but there was a tendency towards a lower recurrence rate with omeprazole 10 mg daily compared with 20 mg weekend therapy.

[Levosulpiride versus domperidone in the treatment of functional dyspepsia]. / Levosulpiride vs domperidone nel trattamento della dispepsia funzionale.

Levosulpiride, a dopaminergic antagonist was compared in a double-blind randomized study with domperidone for treatment of functional dyspepsia in 50 patients divided into two groups of 25 subjects each. Group I received 25 mg levosulpiride 3 times daily, group II received 10 mg domperidone 3 times daily, all for 30 days. Periodic clinical examination at days 0, 7, 15, 30 showed symptomatic changes. Gallbladder and gastric emptying was studied by ultrasonography at the start and end of treatment. Both drugs had a positive influence on dyspeptic symptoms and on gastric and gallbladder emptying, but the latter parameters were improved significantly more effectively by levosulpiride. As to tolerability, there have been 3 drop-outs and a further 6 patients complained of sides effects that did not require suspension of treatment.

[Spontaneous hematoma of the rectus muscle]. / L'ematoma spontaneo del muscolo retto.

The possibility of heart surgery and vascular surgery and the increased number of dialyzed patients receiving dicourmarin and heparin treatment raises the question of the probable rupture of the abdominal muscles, in particular the rectus muscles, following the onset of lancing abdominal pain. The authors report a clinical case referred to them in emergency conditions. They examine the possible etiopathogenetic causes and underline the symptoms of acute abdomen in patients being treated with anti-coagulating drugs.