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M Zanetti

Publications and source records attributed to M Zanetti.

At least 73 records · Page 4Linked to original sources
PubMed1999

SMAP-29: a potent antibacterial and antifungal peptide from sheep leukocytes.

SMAP-29 is a cathelicidin-derived peptide deduced from sheep myeloid mRNA. The C-terminally amidated form of this peptide was chemically synthesized and shown to exert a potent antimicrobial activity. Antibiotic-resistant clinical isolates highly susceptible to this peptide include MRSA and VREF isolates, that are a major worldwide problem, and mucoid Pseudomonas aeruginosa associated with chronic respiratory inflammation in CF patients. In addition, SMAP-29 is also active against fungi, including Cryptococcus neoformans isolated from immunocompromised patients. SMAP-29 causes significant morphological alterations of the bacterial surfaces, as shown by scanning electron microscopy, and is also hemolytic against human, but not sheep erythrocytes. Its potent antimicrobial activity suggests that this peptide is an excellent candidate as a lead compound for the development of novel antiinfective agents.

Animals↗
PubMed1999

Novel cathelicidins in horse leukocytes(1).

Cathelicidins are precursors of defense peptides of the innate immunity and are widespread in mammals. Their structure comprises a conserved prepropiece and an antimicrobial domain that is structurally varied both intra- and inter-species. We investigated the complexity of the cathelicidin family in horse by a reverse transcription-PCR-based cloning strategy of myeloid mRNA and by Southern and Western analyses. Three novel cathelicidin sequences were deduced from bone marrow mRNA and designated equine cathelicidins eCATH-1, eCATH-2 and eCATH-3. Putative antimicrobial domains of 26, 27 and 40 residues with no significant sequence homology to other peptides were inferred at the C-terminus of the sequences. Southern analysis of genomic DNA using a probe based on the cathelicidin-conserved propiece revealed a polymorphic DNA region with several hybridization-positive fragments and suggested the presence of additional genes. A null eCATH-1 allele was also demonstrated with a frequency of 0.71 in the horse population analyzed and low amounts of eCATH-1-specific mRNA were found in myeloid cells of gene-positive animals. A Western analysis using antibodies to synthetic eCATH peptides revealed the presence of eCATH-2 and eCATH-3 propeptides, but not of eCATH-1-related polypeptides, in horse neutrophil granules and in the secretions of phorbol myristate acetate-stimulated neutrophils. These results thus suggest that eCATH-2 and eCATH-3 are functional genes, whereas eCATH-1 is unable to encode a polypeptide.

Amino Acid Sequence↗
PubMed1999

Activation of CD4 T cells by somatic transgenesis induces generalized immunity of uncommitted T cells and immunologic memory.

Cellular immune responses were analyzed in vivo after a single intraspleen inoculation of DNA coding for a 12-residue Th cell determinant associated with a 12-residue B cell epitope, a process termed somatic transgene immunization. We show that CD4 T cells are readily activated and produce IL-2, IFN-gamma and IL-4, characteristics of an uncommitted phenotype. Linked recognition of the two epitopes coded in the same transgene promoted IgM-IgG1 switch and enhanced the total Ab response but had no effect on IgG2a Abs. Although originating in the spleen, T cell responsiveness was found to spread immediately and with similar characteristics to all lymph nodes in the body. A single inoculation was also effective in establishing long term immunologic memory as determined by limiting dilution analysis, with memory T cells displaying a cytokine profile different from that of primary effector T cells. These studies provide evidence that by initiating immunity directly in secondary lymphoid organs, an immune response is generated with characteristics that differ from those using vaccines of conventional DNA or protein in adjuvant administered in peripheral sites. Somatic transgene immunization can therefore be used to probe T cell responsiveness in vivo and represents a tool to further understanding of the nature of the adaptive immune response.

Animals↗
PubMed1999

Protein metabolism in glucagonoma.

Although protein wasting and reduced amino acid concentrations are common findings in glucagonoma patients, the mechanisms underlying these alterations are unclear. Therefore, we studied basal postabsorptive leucine, phenylalanine and tyrosine turnover following L-[D3]-Leucine, L-[D5]-Phenylalanine and L-[D2]-Tyrosine i.v. infusions in one male and one female patient with glucagonoma, compared with healthy control volunteers. Plasma amino acid concentrations were reduced (-40 to 80%, delta >2 SD vs. control subjects) in both patients. Plasma leucine, phenylalanine and tyrosine rates of appearance in patients with glucagonoma were similar to values in the control subjects, except leucine rate of appearence in the female patient with glucagonoma (+ approximately 30%, delta >2 SD). In contrast, the intracellular leucine rate of appearence, reflecting protein degradation, was considerably increased in both patients (+60-80%, delta >2 SD). Phenylalanine hydroxylation was moderately higher only in the male patient with glucagonoma (+ approximately 30%, delta >2 SD). Leucine, phenylalanine and tyrosine clearances (+100-300%), as well as phenylalanine hydroxylative clearance (+75-100%) were also increased in the patients. In conclusion, whole-body protein breakdown is enhanced in patients with glucagonoma compared with healthy control subjects. Phenylalanine hydroxylative clearance is also higher. Reduced plasma amino acid concentrations are probably due, at least in part, to their increased clearance. These alterations could contribute to the determination of the catabolic state of the glucagonoma syndrome.

Adult↗
PubMed1999

MR imaging and CT in osteoarthritis of the lumbar facet joints.

OBJECTIVE: To test the agreement between MR imaging and CT in the assessment of osteoarthritis of the lumbar facet joints, and thus to provide data about the need for an additional CT scan in the presence of an MR examination. DESIGN AND PATIENTS: Using a four-point scale, two musculoskeletal radiologists independently graded the severity of osteoarthritis of 308 lumbar facet joints on axial T2-weighted and on sagittal T1- and T2-weighted turbo-spin-echo images and separately on the corresponding axial CT scans. Kappa statistics and percentage agreement were calculated. RESULTS: The weighted kappa coefficients for MR imaging versus CT were 0.61 and 0.49 for readers 1 and 2, respectively. The weighted kappa coefficients for interobserver agreement were 0.41 for MR imaging and 0.60 for CT, respectively. There was agreement within one grade between MR and CT images in 95% of cases for reader 1, and in 97% of cases for reader 2. CONCLUSION: With regard to osteoarthritis of the lumbar facet joints there is moderate to good agreement between MR imaging and CT. When differences of one grade are disregarded agreement is even excellent. Therefore, in the presence of an MR examination CT is not required for the assessment of facet joint degeneration.

Adult↗
PubMed1999

Chondromyxoid fibroma of two thoracic vertebrae.

We report on a case of chondromyxoid fibroma involving two adjacent thoracic vertebrae with features of aggressive behaviour on radiographs, CT and MRI. Histology revealed typical chondromyxoid fibroma with unusually coarse calcifications. Chondromyxoid fibroma of the spine is rare, and only 30 of these tumours have been reported so far. Involvement of two contiguous vertebral bodies by chondromyxoid fibroma, as reported here, appears exceptional.

Adult↗
PubMed1999

Patient throughput times for orthopedic outpatients in a department of radiology: results of an interdisciplinary quality management program.

The purpose of this project was to employ quality management methods in order to decrease throughput times for orthopedic outpatients sent to the department of radiology. The following intervals were measured at the onset of the study and after 6 and 12 months: (a) between arrivals at outpatient clinic and radiology counter; (b) between arrival at radiology counter and time of last radiograph; and (c) between time of last radiograph and radiology report printing time. After the initial measurement, numerous changes were initiated both in radiology and in orthopedic surgery. The mean interval between arrival at the outpatient clinic and in radiology decreased by one third from 60 min during the first measurement to 40 (p < 0.001) and 41 min during the second and third measurement. The proportion of patients with total radiology times of more than 30 min decreased from 41 to 29 % between the first and third measurements (p < 0.001). The corresponding results for radiology times of more than 45 min were 17 and 11 % (p = 0.03). A standard type of quality management program can be employed successfully in order to reduce radiology throughput times for orthopedic outpatients.

Ambulatory Care↗
PubMed1999

Differences in estimates of forearm protein synthesis between leucine and phenylalanine tracers following unbalanced amino acid infusion.

We compared the leucine (Leu) and phenylalanine (Phe) tracer-determined response of forearm protein synthesis (PS) before and after stimulation of protein anabolism by intravenous infusion of Leu-enriched, Phe-deficient amino acids and insulin (increased to approximately 100 microU/mL) with the euglycemic clamp. Six healthy subjects received primed-constant infusions of L-[ring-2H5]-Phe and L-[1-(14)C]-Leu, and steady-state forearm Phe and Leu kinetics were determined. Following the combined infusion, the arterial Leu concentration increased approximately 70% (P < .001), whereas Phe decreased about 15% (P < .01). Forearm PS and net balance (NB) increased (P < .05 or less v basal) using both amino acid tracers. However, the relative increments observed with the Leu tracer were more than 75% larger (P < .05 or less) than those observed with the Phe tracer, even when the data were corrected for the standard relative abundance of these two amino acids in forearm protein(s). Thus, the calculated changes of forearm PS and NB in response to an unbalanced amino acid infusion with hyperinsulinemia were affected by the plasma level of leucine and phenylalanine, whose tracers were used to estimate forearm protein turnover. Since these two essential amino acids share the same transport system, a competition at this level cannot be excluded.

Adult↗
PubMed1999

Is there a role for NK cells in the pathogenesis of multiple sclerosis? A case study.

We report on a patient with multiple sclerosis (MS) in which we documented an elevated percentage of activated CD56+ natural killer (NK) cells in peripheral blood lymphocytes. NK cells from the patient lysed preferentially glioblastoma but not neuroblastoma cells. Killing of glial cells was not inhibited by a monoclonal antibody against a monomorphic determinant of MHC class I gene products. Lymphokine activated killer (LAK) cell function in the MS patient was comparable to that of controls. Analysis of cytokine production during resting or activated states demonstrated that this patient had a deficit in the ability to secrete T cell derived cytokines associated with increased production of TNFalpha, a product of NK cells. Taken together, these data indicate a possible involvement of NK cells in the pathogenesis of MS.

CD56 Antigen↗
PubMed1999

[Treatment of femoral neck fractures with duo cup prosthesis].

Between April 1992 and March 1994 Duo-cup endoprosthesis was inserted in 90 patients (mean age 80 years, 49-99 years) with fractures of the femoral neck, admitted to the Division of Trauma Surgery. University Hospital of Zürich, Switzerland. The purpose of this study was the clinical and radiological evaluation during a follow-up period of 3 to 24 months. The mechanism of trauma, pre-existing morbidity of the patients, operative stress and postoperative complications were analyzed retrospectively. The functional outcome of 75% of the patients was assessed according to a standardized protocol. In the follow-up, 85% of the patients showed good to excellent results. Radiolucent zones around the cement-bone interface were detected by x-ray scan in 7 patients without loosening of the prosthesis. In half of the patient group heterotopic ossifications appeared, but without clinical relevance. Complications appeared as followed: 3.3% superficial infections, 3.3% deep wound infections followed by replacement of the prostheses, 8.8% hematomas, 2.2% extraprothetic luxations. The perioperative lethality was 0%, whereas the lethality during hospitalisation was 2.2% and the average lethality of the first postoperative year 13%. Overall, 93% of the patients returned to their pre-existing housing environment. These results show that good to excellent clinical and functional results can be achieved in the treatment of femoral neck fractures with duo-cup prosthesis in elderly patients which enables the patients to return in their known social environment.

Aged↗
PubMed1999

Lesions of the reflection pulley of the long biceps tendon. MR arthrographic findings.

RATIONALE AND OBJECTIVES: The purpose of this study was to assess the diagnostic value of MR arthrography in detecting a lesion of the common insertion of the coracohumeral and the superior glenohumeral ligaments and the superior border of the subscapularis tendon (pulley lesion), which predisposes to biceps tendon subluxation and subsequent degeneration. METHODS: Parasagittal T1-weighted turbo spin-echo and axial gradient-echo (three-dimensional fast imaging with steady state-precession [FISP]) MR arthrographic images were obtained in 14 patients with surgically confirmed pulley lesions and in 10 patients with an intact pulley. Various MR arthrographic signs potentially associated with a pulley lesion were evaluated separately and independently in a blinded fashion by two radiologists. RESULTS: Abnormalities of the superior border of the subscapularis tendon on axial and parasagittal images, extra-articular contrast collection, and biceps tendon subluxation were the MR findings of a pulley lesion. The coracohumeral and superior glenohumeral ligaments were not readily visible in all patients and were not helpful in diagnosing pulley lesions in this study. The overall sensitivity for detecting a pulley lesion by MR arthrography was 86% and 93% for readers 1 and 2, with a specificity of 100% and 80% and an accuracy of 92% and 87% (kappa = 0.75). CONCLUSIONS: Based on the authors' experience, MR arthrography is valuable in detecting lesions of the reflection pulley of the long biceps tendon, although differentiation from an isolated lesion of the superior border of the subscapularis tendon may not be possible.

Adult↗
PubMed1999

Morton neuroma: effect of MR imaging findings on diagnostic thinking and therapeutic decisions.

PURPOSE: To determine the effect of magnetic resonance (MR) imaging results on diagnostic thinking and therapeutic decisions by orthopedic surgeons in cases of a possible Morton neuroma. MATERIAL AND METHODS: Orthopedic surgeons completed a questionnaire before and after MR imaging for 54 feet in 49 patients thought to have Morton neuroma. Clinical diagnosis (Morton neuroma, differential diagnosis), location, diagnostic confidence, and therapeutic decisions were noted before and after MR imaging. The influence of the size of the neuroma on therapeutic decisions was analyzed. MR imaging diagnoses were compared with surgical results for 23 revised intermetatarsal spaces. RESULTS: After MR imaging, the clinical diagnosis of Morton neuroma was withdrawn in 15 of 54 (28%) feet. In 14 of 39 maintained diagnoses, the location or number of neuromas was changed after MR imaging. Confidence levels for Morton neuroma increased substantially after MR imaging. In 31 (57%) feet, a change in treatment plan resulted after MR imaging. Diameters of neuromas on MR images were significantly larger (P = .003) in surgically treated feet than in conservatively treated feet. MR imaging diagnoses were correct in all 23 revised intermetatarsal spaces. CONCLUSION: MR imaging has a major effect on diagnostic thinking and therapeutic decisions by orthopedic surgeons when Morton neuroma is suspected, especially because MR imaging helps in localization and size assessment of Morton neuromas.

Adult↗
PubMed1999

Subscapularis tendon tears: detection and grading at MR arthrography.

PURPOSE: To assess diagnostic accuracy in the detection and grading of subscapularis tendon lesions at magnetic resonance (MR) arthrography. MATERIALS AND METHODS: MR arthrograms in 50 consecutive patients (29 with normal subscapularis tendons, 11 with a lesion in the cranial quarter, seven with a major tear but not complete detachment, three with complete detachment) with arthroscopic or surgical confirmation were evaluated independently by two radiologists. Diagnosis was established on findings from transverse and/or parasagittal images. RESULTS: With transverse images alone, sensitivity was 95%/100% (reader 1/reader 2); specificity was 55%/62%. With parasagittal images alone, sensitivity was 91%/91%; specificity was 76%/90%. With combined images, sensitivity was 91%/91%; specificity was 86%/79%. Interobserver agreement was substantial (kappa = 0.67). Forty-one of 50 (82%) grades for subscapularis abnormalities matched at MR imaging and surgery; nine mismatches differed by only one degree. Several signs were specific (90%-100%) but insensitive (29%-62%); these included leakage of contrast material onto the lesser tuberosity, fatty degeneration of the subscapularis muscle, and abnormality in the course of the long biceps tendon (luxation, subluxation). CONCLUSION: MR arthrography is accurate in the detection and grading of subscapularis tendon lesions. Specificity of findings on transverse images for this diagnosis can be improved by including indirect signs and findings on parasagittal images.

Adult↗
PubMed1999

Outcomes after partial neurectomy of Morton's neuroma related to preoperative case histories, clinical findings, and findings on magnetic resonance imaging scans.

Our purpose was to evaluate the reliability of preoperative case histories, clinical findings, and magnetic resonance imaging (MRI) scans in substantiating the diagnosis of Morton's neuroma and in predicting clinical outcomes after surgical intermetatarsal neurectomy. We studied 19 consecutive patients with histologically proved Morton's neuroma. All had preoperative MRI of the forefoot. Partial neurectomy was performed when there was forefoot pain with transmetatarsal compression and positive findings on MRI scans. Case histories, clinical findings, and findings on MRI scans were correlated with clinical outcomes. Preoperative clinical findings including localization correlated with intraoperative findings in 11 of 19 patients (58%), and MRI scans correlated in 16 of 19 patients (84%). Of the 19 patients, 74% achieved satisfactory outcomes. Neither reliable clinical findings or findings on MRI scans nor confirmation of clinical findings by MRI correlated with a superior result, but 77% of patients with neuromas measuring more than 5 mm in transverse measurement on MRI scans had good outcomes; only 17% with neuromas measuring 5 mm or less had good outcomes. Preoperative localization and diagnosis of Morton's neuroma is better achieved with MRI than through clinical findings. A more favorable clinical outcome can be expected after surgical intermetatarsal neurectomy when a Morton's neuroma has a transverse measurement larger than 5 mm on MRI scans.

Adult↗
PubMed1999

MR imaging for traumatic tears of the rotator cuff: high prevalence of greater tuberosity fractures and subscapularis tendon tears.

OBJECTIVE: The purpose of this study was to determine whether occult bony injuries or other characteristic MR abnormalities are frequent in patients suspected of having traumatic tears of the rotator cuff. SUBJECTS AND METHODS: MR arthrography of the shoulder was performed in 24 consecutive patients with suspected traumatic tears of the rotator cuff. MR findings were analyzed with regard to abnormalities of the supraspinatus, infraspinatus, and subscapularis tendons; and the humeral head. A comparison group of 24 consecutive patients with symptoms of nontraumatic tears of the rotator cuff was included in the investigation. RESULTS: Radiographically occult fractures of the greater tuberosity were found in nine (38%) of 24 patients with clinically suspected traumatic tears of the rotator cuff (seven of which occurred in patients <40 years old). Nine partial-thickness and five full-thickness supraspinatus tears were found in the trauma group. In the comparison group, the corresponding numbers were 13 and 10, respectively. Seven partial lesions of the cranial border of the subscapularis and six complete subscapularis tears (all six in patients >40 years old) were found in the trauma group (nine and one in the comparison group). CONCLUSION: Occult greater tuberosity fractures and complete subscapularis tears are commonly seen on MR images in patients suspected of having traumatic tears of the rotator cuff. Greater tuberosity fractures should be looked for specifically in patients younger than 40 years, and subscapularis tears should be looked for specifically in patients older than 40 years.

Adult↗
PubMed1999

Clinical impact of MR arthrography of the shoulder.

PURPOSE: To evaluate the effect of MR arthrography of the shoulder on diagnostic thinking and therapeutic decisions by orthopedic shoulder surgeons. MATERIAL AND METHODS: Orthopedic surgeons completed a questionnaire before and after MR arthrography for 73 consecutive patients. The main indications were suspected rotator cuff abnormalities. The clinical diagnosis, the degree of confidence in this diagnosis, and the therapeutic decision were noted before and after MR imaging. Surgical reports were available for 34 patients. RESULTS: Thirty-four percent of the pre-MR imaging diagnoses were withdrawn after MR imaging, and new diagnoses were made after MR imaging in 13% of the cases. Confidence in the diagnosis increased significantly after MR imaging for supraspinatus and infraspinatus lesions (p<0.05). Changes of therapeutic decision after MR imaging were noted in 36 of the 73 patients (49%). In 23 patients, more invasive therapeutic procedures were initiated after MR imaging, and a more conservative treatment was implemented for 13 patients. Agreement of MR diagnoses with surgery was 94% for supraspinatus tears, 87% for infraspinatus tears, 77% for subscapularis tears, and 81% for biceps tendon lesions. Agreement of clinical diagnoses with surgery was 56%, 83%, 50%, and 64%, respectively. CONCLUSION: MR arthrography of the shoulder has a major effect on diagnostic thinking and therapeutic decisions by orthopedic shoulder surgeons.

Adult↗
PubMed1999

Effects of branched-chain-enriched amino acids and insulin on forearm leucine kinetics.

Although amino acid mixtures enriched in branched-chain amino acids (BCAA) and deficient in aromatic amino acids (AAA) are often used together with insulin and glucose in clinical nutrition, their physiological effects on muscle protein anabolism are not known. To this aim, we studied forearm leucine kinetics in post-absorptive volunteers, before and after the systemic infusion of BCAA-enriched, AAA-deficient amino acids along with insulin and the euglycaemic clamp. The results were compared with the effects of insulin infusion alone. A compartmental leucine forearm model was employed at steady state. Hyperaminoacidaemia with hyperinsulinaemia (to approximately 80-100 micro-units/ml) increased the leucine plasma concentration (+70%; P<0.001), inflow into the forearm cell (+150%; P<0.01), disposal into protein synthesis (+100%; P<0.01), net intracellular retention (P<0.01), net forearm balance (by approximately 6-fold; P<0.01) and net deamination to alpha-ketoisocaproate (4-methyl-2-oxopentanoate) (+9%; P<0.05). Leucine release from forearm proteolysis and outflow from the forearm cell were unchanged. In contrast, hyperinsulinaemia alone decreased plasma leucine concentrations (-35%; P<0.001) and leucine inflow (-20%; P<0.05) and outflow (-30%; P<0.01) into and out of forearm cell(s), it increased net intracellular leucine retention (P<0.03), and it did not change leucine release from forearm proteolysis (-20%; P=0.138), net leucine deamination to alpha-ketoisocaproate, leucine disposal into protein synthesis or net forearm protein balance. By considering all data together, leucine disposal into protein synthesis was directly correlated with leucine inflow into the cell (r=0.71; P<0.0001). These data indicate that the infusion of BCAA-enriched, AAA-deficient amino acids along with insulin is capable of stimulating forearm (i.e. muscle) protein anabolism in normal volunteers by enhancing intracellular leucine transport and protein synthesis. These effects are probably due to hyperaminoacidaemia and/or its interaction with hyperinsulinaemia, since they were not observed under conditions of hyperinsulinaemia alone.

Adult↗