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Biomedical subjects

D Bernardini

Publications and source records attributed to D Bernardini.

At least 19 recordsLinked to original sources

Validation of an automated spectrophotometric assay for the determination of cholinesterase activity in canine serum.

The determination of enzymatic activity of cholinesterase is a useful diagnostic method to detect exposure to anticholinesterase compounds in human and in veterinary medicine. We validated a modification of the Ellman method in canine serum and applied it to the diagnosis of dogs poisoned with anticholinesterase substances. The method used butyrylthiocholine as substrate and potassium hexacyanoferrate as chromophore. The reference range calculated on 60 clinically healthy dogs was set between 3405 and 6561 U/L (chi-square test for normal distribution, p > 0.05). The overall mean intra-assay and inter-assay coefficients of variation were 0.53% and 3.83%, respectively. The assay was linear when using two sera with 12,538 U/L and 6604 U/L serum cholinesterase activity (r(2) = 0.997) and 0.999, respectively). The mean recovery values of pooled sera with a mean pseudocholinesterase (PChE) activity of 12,081 U/L and pooled sera with a mean PChE activity of 3415 U/L were 103.5% and 102.8%, respectively. Six dogs with a diagnosis of anticholinesterase compound intoxication showed a decrease in cholinesterase activity of at least 50% of normal activity with a mean +/- SD of 487 +/- 291 U/L ranging from 169 to 847 U/L. This technique conforms to the current standard for precision, linearity and accuracy and is a useful method for the complementary diagnosis of organophosphate or carbamate insecticide intoxication in dogs.

Animals↗

Dose-finding study of weekly 24-h continuous infusion of 5-fluorouracil associated with alternating oxaliplatin or irinotecan in advanced colorectal cancer patients.

PURPOSE: To determine maximum tolerated dose, safety and efficacy of weekly 24 h infusional 5-fluorouracil (5-FU) combined alternately with oxaliplatin and irinotecan. PATIENTS AND METHODS: Advanced colorectal carcinoma patients in first- or second-line chemotherapy received increasing doses of 5-FU (weekly 24 h continuous intravenous infusion without leucovorin) on days 1, 8, 15 and 22, irinotecan days 1 and 15; and oxaliplatin days 8 and 22, every 35 days. RESULTS: Thirty-four patients received 175 cycles. The median age was 64 years (range 47-78). Eighteen per cent of patients had the primary tumor in the rectum, with a median of one disease site (range one to three), and liver involvement in 88% and lung in 38%. Six (18%) patients had chemotherapy for prior advanced disease. The most frequent grade 3-4 toxicity was neutropenia (41% of patients), but the regimen was well tolerated clinically, with febrile neutropenia in two patients and grade 4 neutropenia lasting >7 days in one; grade 3-4 diarrhea, nausea and vomiting in 6% of patients; grade 3-4 peripheral neuropathy in 9% of patients. Seventeen patients had a partial response (50%; 95% confidence interval 33%-67%), 13 had stable disease and one had progressive disease. Five patients underwent metastatic surgical resection after tumor shrinkage. Median response duration was 14 months (range 4.7-29.2+) and median time to progression was 11.3 months (range 1.1+-30.7+). CONCLUSIONS: This combination three-drug regimen is feasible and well tolerated without toxicity overlap. Preliminary antitumor activity compares well with standard double combinations, with an unusually long median time to progression. The recommended dose is 5-FU 3000 mg/m(2), weekly for 4 weeks, irinotecan 100 mg/m(2) days 1 and 15, oxaliplatin 80 mg/m(2) days 8 and 22. Further assessment of antitumor activity and safety is warranted.

Aged↗

Vertebral mineral density measured by dual-energy X-ray absorptiometry (DEXA) in a group of healthy Italian boxer dogs.

We studied the feasibility of using dual-energy X-ray absorptiometry (DEXA) to obtain reference bone density values in relation to age, gender and body weight in growing and young adult Italian boxer dogs. The study was performed on eight animals (three males and five females) at 7, 12 and 18 months of age. Animals were carefully examined and blood samples were collected from each dog to detect any sign of metabolic and/or endocrine disease. Each subject underwent radiographs to evaluate growth of the spine and hip. One female was not considered in the statistical model because of the development of grade 4 spondylosis deformans during the study period. All animals were serially scanned using DEXA; the region of interest was the whole spine T12-L2, while the subregions of interest were the four vertebrae (T12-T13-L1-L2) within the scanned spine. Statistical analysis was performed separately for each region of interest. Age had the strongest relationship with bone density (P < 0.001). Gender effect on spinal mineral density was not significant while vertebral site effect was highly significant. Average bone mineral density (BMD) +/- SD for the whole spine trait was 0.862 +/- 0.108 g/cm2 while average BMD +/- SD for subregions of interest ranged from 0.836 +/- 0.141 g/cm2 for T12 to 0.928 +/- 0.119 g/cm2 for L2. Estimated reference BMD values at 7, 12 and 18 months of age for each vertebral site in males and females are provided.

Absorptiometry, Photon↗

Neurogenic inflammation in primary headaches.

The headache in migraine is thought to result from neuronal nociceptive activity in the trigeminovascular system, that is, the meninges. In addition, trigeminal axons projecting to the meninges contain vasoactive neuropeptides, such as substance P, calcitonin gene-related peptide and neurokinin A, that may promote, when released, plasma protein leakage and vasodilation within dura mater, characteristic of neurogenic inflammation. Thus, it has been hypothesized that a sterile neurogenic inflammation in the meninges may be involved in generating or sustaining, via occurrence of a vicious cycle, the pain accompanying the migraine attacks. We here review the evidence in support of this hypothesis as well as its potential significance in better tailoring therapies in migraine or other types of primary headaches.

Animals↗

A radiographic technique to assess the longitudinal balance in front hooves.

The aim of this study was to validate a radiographic technique to measure objectively the longitudinal hoof balance in the horse. Ten left third phalanges (P3) obtained from front hooves and 19 left front hooves were used in order to assess the reliability of the radiographic technique and to identify any effect of rotation or alignment of specimens or distance between the X-ray machine and the radiographic cassette, in measuring P3s structures and balance related parameters. A rotational support was made to hold specimens in order to standardise some of the conditions of X-raying. The main axis of the frog was used as a marker for the sagittal plane of P3. Results showed that single radiographic measurements could have wide limits of agreement with actual measurements of the hoof (gold standard values). In order to limit errors we suggest the use of a combination instead of single parameters to assess balance. Rotation of the hoof is also to be controlled when a measurement of angles is needed. The radiographic technique used in this study can be used to objecticely measure balance parameters considered important in order to assess hoof balance.

Animals↗

Distant lymph node metastases in esophageal cancer: impact of endoscopic ultrasound-guided biopsy.

BACKGROUND AND STUDY AIMS: The aim of this retrospective study was to evaluate the impact of endoscopic ultrasound (EUS)-guided biopsy in patients with esophageal carcinoma where distant lymph nodes which were possibly metastatic were visualized using EUS. PATIENTS AND METHODS: Out of 198 patients (150 men, mean age 66 years) examined over a 4-year period by EUS for local staging of esophageal cancer (121 squamous cell carcinomas and 77 adenocarcinomas), there was EUS visualization of distant lymph nodes in 40 (20%). EUS-guided biopsy was carried out in the latter patients, of cervical nodes with mediastinal tumors (n = 19), of celiac nodes with cervical tumors (n = 2) or superior mediastinal tumors (n = 9), and upper mediastinal lymph nodes in the case of distal adenocarcinomas (n = 10). RESULTS: On EUS-guided biopsy, results were positive in 31 patients, eight were correctly negative (as confirmed by surgery), and in one patient there was a technical failure, with positive findings on subsequent surgery. The sensitivity and specificity of the diagnosis of malignant lymph nodes were therefore 97% and 100% respectively. The positive results of EUS-guided biopsy modified the tumor staging in 31 of these cases (77.5%), proving distant lymph node metastasis which is classified as stage M1. With regard to actual clinical management, surgery was withheld from 24 patients (60% of 40 cases) who were then treated with concomitant radiotherapy and chemotherapy. CONCLUSION: EUS-guided biopsy of distant lymph nodes was indicated in 20% of patients with esophageal cancers, and the biopsy results led to upgrading of the tumor stage in about 80% of cases and influenced the treatment decision in about 60%.

Adenocarcinoma↗

Endoscopic mucosal resection (EMR): results and prognostic factors in 21 patients.

BACKGROUND AND STUDY AIMS: The aim of this study was to evaluate the efficacy of endoscopic mucosectomy (EM), and to present our experience with the endoscopic removal of superficial tumors of the gastrointestinal tract. PATIENTS AND METHODS: A total of 21 patients were included in the study (16 men, 5 women), between September 1995 and May 1997. In 16 cases the site of the lesions was an esophageal carcinoma, in two cases a gastric carcinoma, and in three cases a sessile polyp of the duodenum with severe dysplasia. Surgery was not recommended for the patients with esophageal or gastric tumors (on account of cardiac disease, cirrhosis or poor health). All patients underwent an endoscopic ultrasound (EUS) examination. The lesions were classified as usT1N0 in 20 cases, and usT0N0 in one case, according to the pretreatment EUS findings. We used the technique of polypectomy after submucosal injection of 10-15 ml of saline serum. RESULTS: Complications were encountered in 2/21 patients (9.5 %). Bleeding occurred in one case, but hemostasis was achieved endoscopically. In the other case, the patient presented with a thoracic pain and was treated by morphine injection. Endoscopic resection was considered to be complete in 19/21 patients (90.4%). In the other two cases, both involving esophageal tumors, histologic examination indicated only a partial tumor removal. However, these two patients had survived with negative EUS and endoscopic biopsy findings at 18 and 22 months later, respectively. None of the patients whose resections were considered complete presented with local recurrence, but three patients developed another superficial esophageal cancer, which was also treated by endoscopic mucosal resection (EMR). The mean follow-up was 20 months. CONCLUSIONS: EMR is a safe and efficient treatment of early gastrointestinal tumors. The development of high-frequency EUS probes may further improve the results of this technique in the future.

Adult↗

Relation between endoscopic ultrasound evaluation and survival of patients with inoperable thoracic squamous cell carcinoma of the oesophagus treated by combined radio- and chemotherapy.

AIM: Purpose of this study was to assess prognostic value of endoscopic ultrasound in patients with inoperable squamous cell carcinoma of oesophagus treated by radio-chemotherapy. PATIENTS AND METHODS: Between January 1993 and March 1996, 89 patients (77 males and 12 females, mean age 60.3 years) with squamous cell carcinoma of the oesophagus were treated exclusively by radio-chemotherapy consisting of 3 courses of chemotherapy using 5FU-Cis-platyl and 3 courses of radiation therapy (3 x 15 Gy). Endoscopy and endoscopic ultrasound (Pentax FG 32 UA) were performed before beginning treatment and two weeks after last cycle of radio-chemotherapy. Classical criteria for endoscopic ultrasound lymph node metastases were used after irradiation; response was considered as complete only if endoscopic ultrasound indicated that integrity of oesophageal wall was fully restored. RESULTS: Complete endoscopic ultrasound assessment was achieved in 73 cases (84.9%). Tumours were classified as T1N1 in 1 case, T2N1 in 7, T3N0 in 4, T3N1 in 24, T4N0 in 1 and T4N1 in 49. For patients with a non-invasive tumour (usT1 or T2), malignancy of lymph nodes was proved by endoscopic ultrasound guided biopsy. Eighty-two patients presented one or more suspicious lymph nodes. Metastatic lymph nodes were located in posterior mediastinum in 43 cases, at distant sites in 27 (laterotracheal in 16 and coeliac in 11) and in 16 lymph nodes were located simultaneously in mediastinum and at distant sites. Median overall survival in these 89 patients was 16 months. There was no significant difference in median survival between patients in stage T3 and T4. Conversely, there was a significant difference between patients with more or less than 4 metastatic lymph nodes (9 vs 36 months, respectively, p = 0.005). Site of lymph node metastasis was also a prognostic factor with better survival in patients presenting mediastinal nodes than those presenting coeliac nodes (30 vs 9 months, respectively, p < 0.0001). Median survival was also significantly better in patients considered as having achieved a complete response by both gastroduodenal fibrescopy and endoscopic ultrasound than in those considered to have a complete response by gastroduodenal fibrescopy but not by endoscopic ultrasound (49 vs 10 months). Conversely, there was no difference in survival in function of treatment response assessment by thoracic chemotherapy-scan. CONCLUSION: Endoscopic ultrasound findings regarding number and site of suspicious lymph nodes and degree of treatment response are significant prognostic factors in patients with squamous cell carcinoma of oesophagus treated exclusively by radio-chemotherapy.

Adult↗

Cystogastrotomy entirely performed under endosonography guidance for pancreatic pseudocyst: results in six patients.

BACKGROUND: There are increasing reports of endoscopic drainage of pancreatic pseudocysts. Endoscopic ultrasound (EUS) has been recommended for optimal localization of the puncture site and to reduce the risk of bleeding and perforation. We describe our experience with cystogastrostomy guided entirely by EUS. METHODS: EUS-guided cystogastrostomy was performed in six patients. No patient had an endoscopically visible bulge on the gastric wall; gastric varices were evident in one patient. Mean pseudocyst diameter was 4.5 cm (pancreatic body 2, tail 4). RESULTS: Pseudocyst puncture was successful on one pass in five patients; a nasocystic drain was placed in five, a stent in one. Mean follow-up was 8 months; the pseudocyst reoccurred in only one patient in whom the stent had clogged. There were no complications. CONCLUSION: EUS-guided drainage of pseudocysts is accurate and can be performed even if the cyst does not produce an endoscopically visible bulge. It may reduce the risk of complications.

Adult↗

Value of endoscopic ultrasonography for assessment of patients presenting elevated tumor marker levels after surgery for colorectal cancers.

BACKGROUND AND STUDY AIMS: This prospective study was undertaken to evaluate the role of endoscopic ultrasound (EUS) in patients presenting with elevated tumor marker levels (CEA, CA 19-9) after surgery for colorectal cancer. PATIENTS AND METHODS: During a 26-month period, colonic EUS was performed in 21 patients who had undergone surgical treatment for colorectal cancers. All patients presented with elevated tumor marker levels at the time of examination but all other diagnostic procedures (US, CT scan of the abdomen and thorax, bone scintigraphy and colonoscopy) did not demonstrate recurrence. Colonic EUS was performed using a linear convex probe (echoendoscopes Pentax: FG 32 UA, 36 U, 38 UX). In cases with normal findings on colonic EUS, upper gastrointestinal tract EUS was also performed. RESULTS: 21 colonic EUS and six upper gastrointestinal tract EUS examinations were performed. Of 21 colonic EUS examinations, 15 showed either local recurrence (n = 9) or peritoneal carcinomatosis (n = 6) and six EUS-guided biopsies were performed. Of these 15 patients, 13 were operated on and results were confirmed in 12 of 13 patients, namely in 8/9 cases with suspected anastomotic recurrence and in all four operated cases with presumed peritoneal carcinomatosis. EUS-guided biopsy had diagnosed three of the four cases before. Upper GI EUS was performed in the six cases with normal colonic EUS; two cases showed mediastinal lymph nodes and one showed celiac lymph nodes. EUS-guided biopsy confirmed the malignancy of these nodes. For the diagnosis of recurrence, sensitivity, specificity and accuracy of lower plus upper gastrointestinal EUS were 94.4%, 66.6% and 90.4% respectively. CONCLUSION: EUS of the colon and--in selected cases--also of the upper gastrointestinal tract is quite useful in this clinical setting. Further studies are needed to evaluate the impact of EUS on outcome in larger patient numbers.

Adult↗

5-Fluorouracil, high-dose folinic acid and mitomycin C combination chemotherapy in previously treated patients with advanced colorectal carcinoma.

The aim of this study was to evaluate the efficacy and tolerance of second-line continuous 5-fluorouracil (5FU) chemotherapy combined with folinic acid and mitomycin C in patients with advanced colorectal cancer who progressed on first-line chemotherapy. From June 1992 to April 1994, 24 consecutive patients, median age 59.7 years (range 41-73), performance status (PS) 0 to 2, were treated as second-line chemotherapy with mitomycin C, 7 mg/m2 every 4 weeks, folinic acid 200 mg/m2/day as a 2 h infusion followed by 400 mg/m2 of 5FU bolus and 600 mg/m2 continuous 5FU infusion for 22 h on days 1 and 2 and every 14 days; 19 patients did not respond to folinic acid and 5FU bolus regimen (in 2 patients, this was associated with pirarubicin in a continuous hepatic artery infusion) and 3 did not respond to irinotecan; 2 patients had disease progression during adjuvant chemotherapy with folinic acid and 5FU bolus. Tumor response was assessed every 12 weeks. One patient died before evaluation and 1 was lost to follow-up after 3 cycles; 7/24 patients had an objective response (29.2%, 95% confidence interval (CI): 11.0-47.4) including 2 complete responses; 7 additional patients had stable disease or minor response. Mean duration of response was 7.5 months. Median survival was 10 months and survival at 1 year was 39.4% (95% CI: 4-59.4). One patient who had a disease progression under irinotecan presented an objective response. No iatrogenic deaths occurred, nor was any grade 3 or 4 myelotoxicity seen. No hand-foot syndrome nor any cardiotoxicity arose but 2 grade II alopecia were seen. Digestive toxicities were the most frequent but with only 4 grade III toxicities (1 vomiting, 1 mucositis and 2 diarrhea) and no grade IV. With nearly 30% objective response and acceptable toxicity this treatment seems to offer a good alternative in the treatment of advanced colorectal cancers after the failure of first-line chemotherapy.

Adult↗

[Familial varices of the colon. Report of four cases].

We report four cases of ileo-colonic varices in one family. This congenital disease is uncommon with only 21 cases described in the literature. Recurrent digestive tract bleeding is the most common manifestation, but varices can be asymptomatic. Digestive endoscopy leads to the diagnosis. The diagnosis of familial colonic varices can be considered when colonic varices occur in several members of a family with no evident cause, particularly portal hypertension or venous thrombosis. No treatment is usually necessary except when major or recurrent bleeding indicates surgical resection. These malformations are classified as vascular ectasia in the subgroup of cavernous haemangiomas.

Adolescent↗

Time-related changes of cold-stored rat liver in University of Wisconsin solution. Effect of ursodeoxycholate.

Livers of Wistar rats were stored between 0 and 36 hrs. in the University of Wisconsin preservation liquid in order to determine time-related biochemical and morphological hepatic changes. Ursodeoxycholate (100 microM) was also added in the medium to test the hepatoprotective properties of the bile salt. Biochemical assays were performed on hepatic microsomes, plasma and biliary canalicular membranes. Protein and lipid composition of the microsomal and baso-lateral plasma membranes remained stable. Protein and cholesterol content of the biliary canalicular membranes decreased, phospholipid/cholesterol ratio increased between 0 and 36 hrs.; it resulted in a leak of 5'-nucleotidase and leucine amino peptidase activity of these biliary canalicular membranes, especially up to 12 hrs. Between 0 and 36 hrs., the lipid and protein content remained stable in the plasma membranes, as well as both tested enzymatic activities. Observations under electron microscopy showed alterations and underlined fragility of the bile canaliculi, particularly after 24 hrs. preservation. Ultrastructure of sinusoidal membranes showed damaged microvilli. Endoplasmic reticulum remained unchanged, in relation to the stability of the microsomal lipidic, proteic content and hydroxymethylglutaryl-coenzyme A reductase activity, except the decreased protein content after preservation for 36 hrs without ursodeoxycholate. Ursodeoxycholate by itself did not protect against the described disturbances.

Adenosine↗