Prognostic MRI parameters in acute traumatic cervical spinal cord injury.

PURPOSE: The aim of this study is to estimate the prognostic value of some features documented on preoperative MRI study in patients with acute cervical spinal cord injury. METHODS: The study was conducted in patients operated for cervical spinal cord injury (cSCI) from April 2014 to October 2020. The quantitative analysis on preoperative MRI scans included: length of the spinal cord intramedullary lesion (IMLL the canal diameter at the level of maximal spinal cord compression (MSCC) and the presence of intramedullary hemorrhage. The canal diameter at the MSCC was measured on the middle sagittal FSE-T2W images at the maximum level of injury. The America Spinal Injury Association (ASIA) motor score was used for neurological assessment at hospital admission. At 12-month follow-up all patients were examined with the SCIM questionnaire. RESULTS: At linear regression analysis, the length of the spinal cord lesion [ß coefficient -10.35, 95% confidence interval (CI)-13.71 to-6.99; p < 0.001], the diameter of the canal at the level of the MSCC (ß coefficient 6.99, 95% CI 0.65 to 13.33; p = 0.032), and the intramedullary hemorrhage (ß coefficient - 20.76, 95% CI - 38.70 to - 2.82; p = 0.025), were significantly associated with the score at the SCIM questionnaire at one year follow-up: shorter spinal cord lesion, greater diameter of the canal at the level of the MSCC, and absence of intramedullary hemorrhage were predictors of better outcome. CONCLUSION: According to the findings of our study, the spinal length lesion, canal diameter at the level of spinal cord compression and intramedullary hematoma documented by the preoperative MRI study were associated with the prognosis of patients with cSCI.

Epidural plus general anesthesia vs general anesthesia alone for elective aortic surgery: effects on gastric electrical activity and serum gastrin secretion.

BACKGROUND: The aim of this study was to evaluate differences in electrogastrographic activity and serum gastrin secretion in patients subjected to general anesthesia (GA) vs blended anesthesia (BA = GA plus epidural analgesia) for abdominal aortic surgery. METHODS: Thirty-four patients (all males: 28 with abdominal aorta aneurysm, 6 with obstructive aorto-iliac disease; mean age: 68+/-7 years) were randomly assigned either to GA (N.=17) or to BA (N.=17) for abdominal aortic surgery. Each patient was evaluated for serum gastrin secretion at the time of electrogastrography (EGG) 24 h before and after surgery, using ambulatory equipment. Gastrin levels were tested under fasting conditions and after a standard meal. EGG shows gastric electrical activity that parallels gastric motor activity. RESULTS: Before surgery, no significant difference was found for any of the EGG parameters or the serum gastrin integrated value (area under the curve [AUC]) between the two groups of patients. After surgery, an increased frequency of electrical waves (tachygastria) was observed in 22% of those undergoing GA and in 5% of patients undergoing BA. The power ratio (postprandial/fasting total power) was exceedingly high (>4) in 53% of the GA patients and in 11% of the BA patients (P<0.05). The gastrin AUC was 263+/-58 pg/mL in the GA group and 179+/-92 pg/mL in the BA group (P<0.01). CONCLUSIONS: An excess of EGG activity and serum gastrin secretion was observed in patients undergoing GA vs those submitted to BA. Thus, the latter procedure seems to affect gastric function less than GA alone.

Wear debris and cytokine production in the interface membrane of loosened prostheses.

In this study, thirty-nine patients were examined. All of them suffered from hip joint prostheses loosening and underwent revision surgery. Bioptic samples were collected at the interface between bone and implant either at the stem or cotyle level. Immunohistochemistry was performed to detect IL-1alpha, IL-1beta, IL-6 and TNF, cytokines that directly cause bone resorption and indirectly induce synthesis of other bone resorbing cytokines. Quantitative analysis of the positive cells and correlation with clinical data was performed. It resulted that there is a great variability in positive cells for cytokines according to the harvest site; anyway, cytokines tend to be higher in patients carrying a joint prosthesis with polyethylene acetabular component and it is associated with plastic wear particles, even though there is no direct correlation between wear amount and cytokine levels. There is a statistically significant negative correlation between metal wear and a cytokine (IL-6); cytokines levels do not depend on the implant time to failure and do not correlate with pain score. As expected, cytokines levels tend to be lower in subjects being treated with non-steroidal antiinflammatory drugs. It can be concluded that plastic wear is the factor inducing the highest cytokine levels in the tissues around the prosthesis at the interface; cytokines that are an indicator of osteolysis risk.

Enhanced and coordinated in vivo expression of inflammatory cytokines and nitric oxide synthase by chondrocytes from patients with osteoarthritis.

OBJECTIVE: To evaluate the sites of expression of interleukin-1beta (IL-1beta), tumor necrosis factor alpha (TNFalpha), and inducible nitric oxide synthase (iNOS) in patients with inflammatory and degenerative joint diseases. METHODS: Cytokines and iNOS were detected by immunohistochemistry analysis of synovial and cartilage biopsy specimens obtained at knee arthroscopy in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), osteoarthritis (OA), and traumatic knee arthritis. Cytokine and iNOS expression was quantified using computerized image analysis. RESULTS: IL-1beta, TNFalpha, and iNOS were highly expressed by synovial cells (lining layer cells, infiltrating leukocytes, endothelial cells) from patients with inflammatory arthritides and significantly less by synovial cells from patients with OA and traumatic arthritis. In contrast, the latter patients showed high chondrocyte expression of cytokines and iNOS while RA and PsA patients had only minor chondrocyte positivity. In both joint compartments, IL-1beta expression, TNFalpha expression, and iNOS expression were strongly correlated. CONCLUSION: The enhanced and coordinated expression of IL-1beta, TNFalpha, and iNOS by chondrocytes strongly supports the hypothesis that chondrocytes are the major site of production of mediators of inflammation in human OA, thus playing a primary role in the pathogenesis of this disease.

Synovial expression of cell adhesion molecules in polymyalgia rheumatica.

Polymyalgia rheumatica (PMR) is a common disorder of the elderly: the pathogenesis of the syndrome is still debated, though active synovitis of the shoulder has recently been confirmed. To investigate the pathogenesis of this synovitis we evaluated cell adhesion molecule (CAM) expression in shoulder synovial tissue from patients with PMR, correlated synovial expression with the serum levels of soluble forms, and assessed the changes associated with corticosteroid treatment. Arthroscopic synovial biopsies were obtained from 12 untreated and seven corticosteroid (CS)-treated cases. CAM expression was evaluated by MoAb staining on frozen sections and computerized image analysis. Soluble CAM were quantified by ELISA. Endothelial cells expressed intercellular adhesion molecule-1 (ICAM-1), E- and P-selectins. Infiltrating cells were ICAM-1 and beta1-integrin-positive, while L-selectin expression was limited to intravascular leucocytes. Synovial lining cells strongly expressed vascular cell adhesion molecule-1 (VCAM-1), and less intensely ICAM-1. Only the soluble form of ICAM-1 (sICAM-1) was elevated in untreated patients. CS treatment was associated with a decrease in ICAM-1, VCAM-1 and E- and P-selectin expression. sICAM-1 levels were in the normal range in treated patients. VLA-5 and 6 expression was widely distributed among cell types, and was not CS-sensitive. Active shoulder synovitis is associated with different CAM expression in PMR. ICAM-1 expression is widely distributed and correlates with elevated levels of the soluble form; it is significantly lower in CS-treated asymptomatic cases.

Alteration of DNA ploidy and cell nuclearity in human hepatocellular carcinoma associated with HBV infection.

BACKGROUND/AIMS: Hepatocellular carcinoma usually arises in cirrhotic livers as a complication of chronic liver disease, and may show a variable trend towards increasing ploidy. The aim of this study was to investigate possible associations between different etiological factors, particularly hepatitis B virus and hepatitis C virus infection, and alteration of DNA-ploidy and nuclearity of neoplastic hepatocytes. METHODS: DNA-ploidy, the percentage of binucleated cells in the total cell population and the fraction of mononucleated hepatocytes in the polyploid compartment were assessed by image cytometry on cellular suspensions obtained by fine-needle biopsy from 60 hepatocellular carcinomas in patients whose viral status had previously been assessed. RESULTS: Significantly higher DNA-ploidy values (p = 0.005), with a reduction in the percentage of binucleated hepatocytes (p = 0.003) and an increase in the fraction of mononucleated hepatocytes in the polyploid compartment (p < 0.0001), were found in hepatocellular carcinoma with actual or previous hepatitis B virus infection (including also HCV+ve patients) in comparison to those not associated with hepatitis B virus infection, but not when HCV+ve hepatocellular carcinomas were compared to HCV-ve ones. Statistically significant differences for ploidy values (p < 0.05), percentage of binucleated hepatocytes (p < 0.05) and fraction of mononucleated hepatocytes in the polyploid compartment (p = 0.003) were also found between hepatocellular carcinoma associated only to hepatitis B virus infection ("pure" hepatitis B virus cases) and those associated only to hepatitis C virus infection ("pure" hepatitis C virus cases). CONCLUSIONS: Hepatocellular carcinoma associated with a previous or actual hepatitis B virus infection shows a peculiar phenotypical appearance, characterized by a trend towards increasing ploidy and reduction of binuclearity.

DNA ploidy analysis of squamous cell carcinomas of the oral and maxillofacial region: clinical and pathologic correlations.

DNA ploidy was investigated in 61 specimens obtained from 25 patients with squamous carcinoma of the oral and maxillofacial region. Biopsy specimens of normal tissue surrounding the tumor were also obtained in six patients. Single-cell suspensions for flow cytometric analysis were prepared. The DNA ploidy and histogram were calculated and compared with the histologic grade, presence of lymph node metastases, and course of the disease. The ploidy of the main stemline was peridiploid in 17 carcinomas, hyperdiploid in three, and aneuploid in five. Histologic grade but not nodal involvement was associated with the ploidy of the main stemline. Of 15 multisampled carcinomas 13 showed constant DNA ploidy and histogram classification. In the other two major changes in DNA ploidy (from peridiploid to hyperdiploid in the first and from peridiploid to aneuploid in the second) were found. Survival information was available for 24 patients. Ploidy values higher or lower than 2.5 c were strongly predictive of both overall (p < 0.001) and relapse-free survival (p < 0.001). The lymph node status proved a powerful prognostic indicator (p = 0.014) but was not related to the relapse-free time of survival. Multiparametric evaluation of survival revealed an independent role of both DNA ploidy and nodal involvement in the prognosis of squamous carcinoma of the oral and maxillofacial region.

Leukocyte infiltration in synovial tissue from the shoulder of patients with polymyalgia rheumatica. Quantitative analysis and influence of corticosteroid treatment.

OBJECTIVE: To investigate the immunologic features of synovitis in patients with polymyalgia rheumatica (PMR) and to assess the modifications induced by corticosteroids. METHODS: Arthroscopic biopsies of shoulder synovium were obtained from 12 patients with untreated PMR and from 7 patients with PMR that had been treated. Immunohistochemistry was performed on frozen sections utilizing a panel of monoclonal antibodies and computerized image analysis. RESULTS: Synovitis was present in 10 of 12 (83%) untreated patients and in only 2 of 7 (29%) treated patients. The synovitis was characterized by vascular proliferation and leukocyte infiltration. Infiltrating cells consisted predominantly of macrophages and T Lymphocytes. Almost all T lymphocytes were CD45RO positive. A few neutrophils, but no B cells, natural killer cells, or gamma/delta T cells were found. Intense expression of HLA class II antigens (DR moreso than DP moreso than DQ) was found in the lining layer cells as well as in macrophages and lymphocytes. DR, but not DP or DQ, was expressed by the endothelium of a few vessels. Class II antigen expression correlated with the number of macrophages and lymphocytes. Macrophage infiltration of arteriole walls was observed in 1 untreated patient without giant cell arteritis (GCA). In untreated patients, there was a positive correlation between the percentage of infiltrating T cells and the duration of disease. Steroid therapy was associated with a significant reduction in the number of blood vessels and of HLA class II expression. One treated patient who no longer had symptoms of PMR still had active synovitis: a relapse occurred 4 months after the biopsy. CONCLUSION: Our findings support the hypothesis that synovitis is a major cause of the musculoskeletal symptoms of PMR. There are immunologic similarities with the vascular inflammation observed in GCA. Corticosteroids act on both the vascular and cellular components of synovitis.

Enzymatic cytochemistry, DNA ploidy and AgNOR quantitation in hepatocellular nodules of uncertain malignant potential in liver cirrhosis.

Conventional histological examination of echo-guided biopsy specimens can be inconclusive in small nodular lesions in cirrhotic livers. We investigated the diagnostic potential of cytochemical analysis of dipeptidyl-peptidase IV (DPP IV), of image analysis of nuclear DNA content, and of interphase silver-stained nucleolar organizer regions (AgNORs) in 12 cases of small (13- to 29-mm in diameter) hepatic nodules visualized in cirrhotic patients by ultrasonography. All cases underwent an echo-guided liver biopsy at the time of detection and in none of them were histological signs of malignancy found. Characterization with the above-mentioned techniques was always done at the time of histological examination. These patients underwent a mean (+/- SD) follow-up of 27.0 (+/- 11.2) months after biopsy, with repeated ultrasound (US) examinations. In the seven patients with subsequent neoplastic growth, DPP IV score was altered in five of six; the fraction of mononucleated polyploid cells was altered in six of seven; and the AgNOR quantity exceeded the cutoff value of 4 microns2 in five of five cases. Among the five lesions whose US appearance remained unchanged during the follow-up, only one abnormality (AgNORs) was found in one case. The combined cytochemical analysis of DPP IV, nuclear DNA content, and quantitative evaluation of interphase AgNORs in biopsy samples may contribute to the differential diagnosis of hepatocellular nodules of uncertain type in the cirrhotic liver.

In hepatocellular carcinoma AgNOR protein expression correlates with tumour mass doubling time.

AIMS/METHODS: The relationship between AgNOR protein expression and doubling time was evaluated in 20 untreated nodules of hepatocellular carcinoma arising in cirrhotic liver. AgNOR protein quantity within the lesion was defined by image cytometry on histological sections from frozen biopsies obtained under ultrasound-guidance, selectively stained for AgNOR proteins. Tumour doubling time was calculated 6 months after diagnosis by measuring the volume variations of the nodules over a fixed period by "real time" ultrasonography. RESULTS: The doubling time of nodules characterized by high AgNOR protein area values (> 5.50 microns2, corresponding to the median AgNOR protein value) was shorter than that of nodules with low AgNOR protein area values (< 5.50 microns2). A highly significant difference in the mean doubling time values between the two groups (6.31 +/- 2.68 (E.S.) versus 15.92 +/- 3.03 (E.S.) months, respectively; p = 0.009) was found. Moreover, when the relationship between AgNOR protein and doubling time values was tested by linear regression analysis, a significant inverse correlation was observed (r = -0.68; p < 0.005). CONCLUSIONS: Our results indicate that AgNOR protein quantity represents a reliable parameter for predicting the tumour growth rate of untreated hepatocellular carcinoma nodules. Among the procedures commonly employed for the assessment of cell proliferation, the evaluation of the AgNOR parameter seems to be particularly suitable for kinetic analysis of ultrasound-guided fine-needle liver biopsies.

Differential expression of IL-1 and TNF receptors in inflammatory arthritis and osteoarthritis.

Pathological joint events in both inflammatory arthritis and degenerative arthritis are perpetuated by complex cytokine interactions. Two cytokines, IL-1 and TNF alpha, appear to be the major culprits in the pathogenesis of synovitis and in cartilage damage in these joint diseases. To analyze the expression of IL-1 and TNF alpha and their receptors on synovial and cartilage tissue, we performed an immunohistochemical study on knee biopsies from patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and osteoarthritis (OA). Results identified a prevalent positivity to cytokines and their receptors of synovial cells from RA and PsA with respect to OA patients. In cartilage specimens, most RA and PsA patients showed no expression of the studied receptors, whereas the majority of OA biopsies were positive for all types of examined receptors except IL-1R2. Our study suggests that the cartilage is the main target of these cytokines in OA, while in IA IL-1 and TNF alpha exert their action in synovial tissue. In all the studied pathologies (RA, PsA, OA) the synovial tissue and the cartilage were differentially involved, indicating the importance of investigating both structures in joint disease studies.

Cytochemical detection of a class 3 aldehyde dehydrogenase in human hepatocellular carcinoma.

The development of hepatocellular carcinoma in rodents treated with different chemical compounds is associated with the appearance in the cytosol of neoplastic liver cells of an unusual aldehyde dehydrogenase isozyme of class 3 (ALDH-3) which is very active with aromatic aldehydes. This tumor-associated isozyme is readily detected by enzyme cytochemistry using the substrate benzaldehyde with NADP as coenzyme. To determine whether human hepatocellular carcinomas express ALDH-3, the activity of this isozyme was examined in frozen sections from 68 echo-guided human liver biopsies. In 54 cases the guided biopsy was performed on one or more nodules suggestive for hepatocellular carcinoma found at ultrasonography within the liver parenchyma. The remaining 14 patients were affected by chronic active hepatitis or cirrhosis. An intense enzymatic activity was ascertained in 5 out of 36 hepatocellular carcinomas. In non-neoplastic liver, in macroregenerative nodules and in metastatic adenocarcinomas enzymatic activity was not detectable. ALDH-3-positive tumors were typical hepatocellular carcinomas (histological grade II and III). These results suggest that ALDH-3 is a phenotype associated with malignancy in human liver tumors.

Diagnostic and prognostic value of DNA ploidy and cell nuclearity in ultrasound-guided liver biopsies.

BACKGROUND: Focal nodule lesions in patients with cirrhotic livers may be visualized by using imaging techniques; however, the diagnostic and prognostic judgment of biopsies from borderline lesions may be difficult using conventional histologic criteria. METHODS: The diagnostic and prognostic value of DNA ploidy analysis determined by image cytometry of Feulgen-stained isolated hepatocytes was investigated in ultrasound-guided biopsies from 50 nodular lesions found in patients with cirrhotic livers (39 hepatocellular carcinomas [HCCs] and 11 macroregenerative nodules) and from 10 patients with livers affected by viral chronic hepatitis. Of the 11 macroregenerative nodules, 7 presented a subsequent neoplastic behavior. Specimens from the morphologically normal livers of five patients who underwent liver surgery served as control tissues. Image cytometry was performed on Feulgen-stained cytologic preparations, obtained by enzymatic digestion of formalin fixed biopsies. The DNA ploidy of the main stem line and the distribution of mononucleated and binucleated hepatocytes (nuclearity) were compared using histologic diagnosis, Edmondson's grade, tumor size, and patient follow-up. RESULTS: The main stem line was peridiploid in all benign specimens and in 31 clinically confirmed HCCs, peritetraploid in 11 HCCs, perioctaploid in 1 HCC, and aneuploid in 3 HCCs. The fraction of mononucleated polyploid hepatocytes was found to be the best diagnostic parameter in euploid HCCs and was significantly correlated with the Edmondson grade and the nodular size. Survival information was available for 43 patients, with a median observation period of 350 days. A DNA ploidy value of the main stem line greater than 3c was an important determinant of survival as a single parameter and in association with histologic grade and greatest dimension of tumor. CONCLUSIONS: This study suggests that the ploidy distribution analysis of mononucleated and binucleated hepatocytes can provide valuable information for making correct diagnoses and for predicting survival outcome for patients with HCCs.

Interphase AgNOR quantity and DNA content in endometrial adenocarcinoma.

The relationship between the amount of silver-stained nucleolar organizer regions (AgNORs) and the DNA content of interphase neoplastic cells in 63 cases of human endometrial adenocarcinoma was studied. Interphase AgNOR content was determined as the mean AgNOR area per nucleus by image cytometry in silver-stained samples from paraffin-embedded sections. DNA content was evaluated by cytofluorometry on single cells from the same specimen and expressed in c units as DNA ploidy. The mean AgNOR area ranged from 1.26 to 4.48 microns2 and the modal DNA ploidy from 1.90 to 4.00c. No significant associations were found between mean AgNOR area and modal DNA ploidy when analyzed either by linear regression (beta = 0.18; P = 0.15) or as dichotomized variables by chi 2 analysis (chi 2 = 0.82; P = 0.37). On a homogeneous subset of 45 cases of stage I adenocarcinomas we also evaluated the prognostic relevance of AgNOR content and DNA ploidy. In monovariate analysis both parameters were significantly related to patient survival. When the mean AgNOR area and the modal DNA ploidy were entered into regression analysis together with the depth of myometrial invasion and histological grading, they showed an independent, high prognostic value.

Interphase AgNOR quantity is not related to DNA content in 11 established human cancer cell lines.

The relationship between interphase AgNOR quantity and DNA ploidy was evaluated in 11 cell lines derived from human tumors of different origin. Interphase AgNOR quantity was measured by morphometric image analysis and DNA content by cytofluorometry. The mean interphase AgNOR area ranged from 5.56 to 21.12 microns 2 and DNA ploidy from 2.05 to 3.30c. The interphase AgNOR value and DNA content were not significantly related (r = 0.23, P = 0.52). No significant correlation was found between DNA content and cell doubling time, whereas a strict relationship was confirmed to exist between interphase AgNOR quantity and rapidity of cell proliferation.