Real-world effectiveness of long acting aripiprazole: Treatment persistence and its correlates in the Italian clinical practice.

OBJECTIVES: To identify the variables that are associated with persistence to Aripiprazole-Long Acting (A-LAI), in adult patients with schizophrenia. METHODS: Observational, retrospective, non-interventional study involving 261 patients with schizophrenia. RESULTS: Eighty-six percent of study subjects were persistent for at least 6 months. All subjects with baseline CGI-S of 1 or 2, 95% of subjects with CGI-S of 3, 86% with CGI-S of 4, 82% of subjects with CGI-S of 5, 73% of subjects with CGI of 6 and 90% of subjects with CGI of 7 were persistent. A-LAI treatment continuation rate was higher in patients with: 1) baseline CGI score ≤ 4; 2) schizophrenia dimension (LDPS) mania score ≤ 5; 3) psychotic spectrum schizoid score ≤ 11. CONCLUSIONS: A relatively high number of patients (n = 225, 86%) were persistent to A-LAI for at least 6 months. Not surprisingly, very severe patients were more unlikely to be persistent. However, it is noteworthy that a large number of subjects with high CGI score at the time when A-LAI was started (82% of subjects with CGI-S of 5, 73% of subjects with CGI of 6 and 90% of subjects with CGI of 7) were persistent. Larger, controlled, prospective and longer studies are warranted.

Accumulation of giant heterogeneous RNA molecules in acute myeloid leukemia blast cells.

Time course and "chase" experiments showed that, after incubation of acute myeloid leukemia blast cells with a labeled RNA precursor, a large proportion of radioactivity remained associated with RNA molecules larger than 45 S even after several hr. Double-labeling experiments with [5-3H]uridine and [methyl-14C]methionine indicated that unmethylated giant heterogeneous RNA larger than 45 S is processed much more slowly than the 45 S ribosomal precursor, so that relatively large amounts of fairly stable RNA of the former class accumulate in the cell. The measurement of labeled giant heterogeneous RNA molecules bound to polyuridylate-fiberglass filters showed that molecules carrying polyadenylate segments seemingly turn over faster than those lacking polyadenylate.

Immunological assay of double-helical segments in RNA fractions of different molecular size extracted from acute myeloid leukemia blast cells.

Whole-cell RNA, extracted from acute myeloid leukemia blast cells, was fractionated by sedimentation through sucrose gradients. The proportion of double-helical segments present in each fraction was then determined by a quantitative microcomplement fixation assay that specifically measures double-helical RNA. Sizable amounts of double-helical segments were detected in all fractions of cellular RNA corresponding to S values higher than approximately 20. In all cell populations examined the highest proportion of double-helical segments was found in RNA fractions sedimenting faster then the 45 S ribosomal precursors RNA, i.e., in fractions including only heterogeneous nuclear RNA.

Reassociation kinetics of the DNA of human acute leukemia cells.

Human DNA isolated from normal phytohaemagglutinin-stimulated human lymphocytes and from acute leukemia blast cells have been studied by renaturation techniques using hydroxyapatite binding and DNA hyperchromism. In the leukemic genome, the unique sequences account for 62% of the genome of leukemic DNA. Repetitive sequences may be subdivided into at least three fractions: (a) foldback sequences, which represent 5% of the genome; (b) sequences with high repetition frequency (3. 10(4) times on the average), which represent 12% of the genome; (c) sequences with low repetition frequency (10 times on the average), which represent 16% of the genome. The average length of the repetitive sequences is evaluated to be between 200 and 500 nucleotides. There are at least two patterns of interspersion of repetitive sequences with unique sequences of different length: short (about 2000 nucleotides on average) and long (not defined). The results of our experiments on DNA from normal phytohaemagglutinin-stimulated human lymphocytes are in close agreement with those reported by other authors studying different types of human cells. The human leukemic DNA, as far as the parameters that have been studied, does not significantly differ from normal human DNA.

Magnetic resonance of the temporomandibular joint: experience at an Italian university center.

AIM: The aim of this investigation was to suggest criteria in order to evaluate magnetic resonance imaging (MRI) of the temporomandibular joint (TMJ). Such criteria have been discussed on the basis of our experience at the Section of Prosthetic Dentistry, Department of Neurosciences, University of Pisa. METHODS: The study sample was constituted by 135 patients. All subjects underwent bilateral MRI of the TMJs to evaluate disc structure and position, bony structure abnormalities, joint effusion localization and entity. RESULTS: MRI allowed depiction of the articular disc in 98.9% of the TMJs, showing a normal disc structure in 91.1% of the cases and abnormal in 7.7%. The disc-condyle relationship was normal in 46.6% TMJs, while a disc displacement with reduction was revealed in 35.5% cases, a disc displacement without reduction in 16.7% and a posterior disc displacement in 1.5% joints. In the coronal images, the disc was positioned lateral to the condyle in 8.9% of the TMJs and medial in 6.7%. Osseous abnormalities have been found in 177 joints (65.5%), with cases of bony flattening (condyle and/or tuberculum), erosions, subchondral cysts, osteophytosis and sclerosis. T2 sequences showed effusion in 26.7% of the TMJs. CONCLUSIONS: These findings suggest that standardized methodology application and well-defined criteria can facilitate MR imaging observations and interpretation as well as the diagnosis of intra-articular pathologies.

Extremely low frequency pulsed electromagnetic fields increase interleukin-2 (IL-2) utilization and IL-2 receptor expression in mitogen-stimulated human lymphocytes from old subjects.

The effects of the exposure of mitogen-stimulated human lymphocytes from aged subjects to low-frequency pulsed electromagnetic fields (PEMFs) were studied by measuring the production of interleukin-2 (IL-2) and the expression of IL-2 receptor. PEMF-exposed cultures that presented increased [3H]thymidine incorporation showed lower amounts of IL-2 in their supernatants, but higher percentages of IL-2 receptor-positive cells and of T-activated lymphocytes. Taken together, these data suggest that PEMFs were able to modulate mitogen-induced lymphocyte proliferation by provoking an increase in utilization of IL-2, most likely acting on the expression of its receptor on the plasma membrane.

LAK activity is inducible in blood mononuclear cells from human fetus.

Lymphocyte subpopulations, NK and LAK activities have been studied in blood mononuclear cells from two human fetuses, the first affected by Down's syndrome, the other showing a normal karyotype. Fetuses presented similar subsets, with a scarcity of CD57+ lymphocytes but an appropriate amount of CD16+ and CD56+ cells, while negligible NK activity was detectable. After 18 h of incubation with human recombinant interleukin-2 (rIL-2), significant enhancement of the cytotoxic capability was observed. This stresses the role of IL-2 as a regulatory molecule during the development of the immune system in the human fetus.

Nimesulide as a downregulator of the activity of the neutrophil myeloperoxidase pathway. Focus on the histoprotective potential of the drug during inflammatory processes.

Neutrophils, recruited to tissue sites of inflammation, release a variety of oxidants and enzymes, which are responsible for tissue damage. Among the oxidants released are potent chlorinated compounds, such as hypochlorous acid and chloramines, which induce tissue cell damage and inactivate protease inhibitors, particularly alpha 1-antitrypsin, the specific inhibitor of neutrophil elastase. In studying a rational approach to the pharmacological control of neutrophil-mediated tissue injury, we investigated the activity of the anti-inflammatory drug nimesulide. This agent reduced the function of the myeloperoxidase pathway (which generates hypochlorous acid), by exerting a cell-directed inhibitory activity, as shown by measurement of superoxide anion and hydrogen peroxide production. Nimesulide also inactivated hypochlorous acid directly and protected alpha 1-antitrypsin from the neutrophil-mediated oxidation. Thus, neutrophil elastolytic activity may be attenuated by nimesulide-spared alpha 1-antitrypsin. The prevention of oxidative inactivation of alpha 1-antitrypsin by nimesulide strictly correlates with the drug's ability to suppress the extracellular availability of hypochlorous acid. Taken together, these data suggest that nimesulide may prevent tissue injury at sites of inflammation by maintaining natural host protective systems.

Kappa light chain gene rearrangement in a T-cell lymphoma.

Forty-three patients were studied to determine whether light chain gene rearrangements may occur in hematopoietic cells not pertaining to the B-lineage. In only one patient, affected by T-cell lymphoblastic lymphoma, one kappa light chain allele was rearranged. Neither at the protein level nor at the RNA level the rearranged gene was expressed. These data confirm that, although rarely, kappa light chain gene rearrangements may occur in neoplastic T-cells. Furthermore, as in our patient Ig heavy chain genes retained a germline configuration, the present data demonstrate that kappa light chain gene rearrangements may occur regardless of Ig heavy chain gene arrangement.

Presence of ACTH and beta-endorphin immunoreactive molecules in the freshwater snail Planorbarius corneus (L.) (Gastropoda, Pulmonata) and their possible role in phagocytosis.

The presence of ACTH and beta-endorphin immunoreactive molecules in the cell-free hemolymph and in the hemocytes of the freshwater snail Planorbarius corneus were demonstrated by immunocytochemistry and RIA tests. Only spreading phagocytic hemocytes were positive, in contrast with other hemocytes devoid of phagocytic activity, i.e., round hemocytes. These data were confirmed by flow cytometry. Another cell type with marked phagocytic activity, i.e., digestive cells of digestive gland, were also positive to anti-ACTH. Corticotropin-releasing factor immunoreactive molecules were found in the cell-free hemolymph and hemocytes, by RIA. Our data suggest that cells with phagocytic activity, the oldest immune response, may represent a suitable model to unravel the tangled web of the common ancestor of the immune and the neuroendocrine systems.

Absence of antibodies to HTLV-I and HIV in serum and cerebrospinal fluid of Italian patients with multiple sclerosis.

Because of the undecided question whether HTLV-related virus antibodies are present in multiple sclerosis (MS), we tested cerebrospinal fluid (CSF) and serum from 52 MS patients and 32 patients affected with other neurological diseases. ELISA procedure was used to detect antibodies against HTLV-I and HIV. Negative results were obtained in all samples examined.

Magnetic resonance imaging for the study of cervical myelopathy in rheumatoid arthritis.

Cervical myelopathy is found fairly often with rheumatoid arthritis. It is one of the worst complications of the disease and can lead to tetraplegia or even to sudden death. However, when we consider the high incidence of involvement of the cervical spine in rheumatoid arthritis, the number of cases of cervical myelopathy, even of slight degree, is not very high. We have used magnetic resonance to identify the condition of the cervical structures, especially the nerve structures, in 15 patients with rheumatoid arthritis, with involvement of the cervical articulations but without neurological symptoms. We found anterior compression of the spinal cord caused by the odontoid process of the epistropheus in 13 cases. One case had lateral deviation of the spinal cord and another had compression of a vertebral artery. In another the lumen of the nasopharynx was decreased and one had posterior compression of the spinal cord by the posterior arch of the atlas. Magnetic resonance also makes it possible to detect a rheumatoid pannus on the affected articulations. We conclude that magnetic resonance is at present a useful instrument for evaluation of the presence of cervical myelopathy in rheumatoid arthritis patients, to prevent more serious complications.

Post-marketing survey of nimesulide in the short-term treatment of osteoarthritis.

A multicentric trial was carried out to assess the therapeutic efficacy and tolerability of nimesulide in the treatment of patients with osteoarthritis. The trial involved 1600 general practitioners, 80 orthopedists and 88 specialists in internal medicine. A total of 22,938 ambulatory patients was admitted to the trial. Patients were given nimesulide tablets (40%) or granules (60%) from 100 to 400 mg/day for a length of time ranging from 1 to 3 weeks. The treatment was effective in relieving spontaneous pain and morning stiffness. The level of patients with adverse reactions, presumably related to nimesulide and mostly involving the gastro-intestinal tract, was 8%. The results of this study suggest that nimesulide is effective and well tolerated in the short-term treatment of a large number of patients with osteoarthritis.

Efficacy and tolerability of nimesulide in elderly patients with osteoarthritis: double-blind trial versus naproxen.

A double-blind trial was carried out to assess the therapeutic efficacy and tolerability of nimesulide versus naproxen in the treatment of elderly patients with osteoarthritis. A total of 40 elderly female patients with osteoarthritis of the hip and/or knee were entered into the study and treated with either 200 mg/day nimesulide or 500 mg/day naproxen for 28 days. Both treatments were very effective in alleviating spontaneous pain, pain on movement, morning stiffness and joint mobility. Nimesulide was better tolerated than naproxen with fewer and less serious side-effects being reported. The results of this study show nimesulide to be effective and well tolerated in the treatment of elderly patients with osteoarthritis.

Is clinical assessment valid for the diagnosis of temporomandibular joint disk displacement?

AIM: The aim of this work was to evaluate the predictive value of clinical examination for magnetic resonance imaging (MRI) findings of temporomandibular joint (TMJ) disk position abnormalities. METHODS: Participants in this study were 51 consecutive patients with signs and symptoms of temporomandibular disorders (TMD). All 102 temporomandibular joints (TMJ) were evaluated to detect disk position abnormalities by means of a standardized clinical assessement according to Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) and MRI performed by a blinded radiologist at the Section of Prosthetic Dentistry, University of Pisa, Italy. The accuracy of clinical assessment was evaluated with respect to MRI. RESULTS: Clinical assessment showed a good predictive value (PV) for the diagnosis of normal disk position (86.2%) and an acceptable PV for the diagnosis of disk displacement with reduction (70.3%), while it seems less accurate in predicting MRI diagnosis of disk displacement without reduction. The overall agreement between clinical RDC/TMD examination and MRI for the evaluation of disk position was 77.3%. CONCLUSION: Clinical RDC/TMD examination proved to be accurate in detecting normal disk position and disk displacement with reduction but not reliable in predicting MRI diagnosis of disk displacement without reduction in the temporomandibular joint.

Occlusal features are not a reliable predictor of bruxism.

AIM: The aim of this investigation was to estimate the contribution of occlusion to differentiate bruxers from non-bruxers. METHODS: Participants in the study were 160 patients consecutively selected among 20-30 year old patients attending the Section of Prosthetic Dentistry for conservative care. The presence of bruxism was clinically and anamnestically investigated. In each patient the following occlusal features were recorded: retruded contact position-intercuspal position slide length, vertical overlap, horizontal overlap, unilateral posterior crossbite, incisor dental midline discrepancy, mediotrusive interferences, laterotrusive interferences. A stepwise logistic regression model was used to identify the significant associations between occlusal features and bruxism. RESULTS: Diagnosis of bruxism was made in 67/160 subjects (41.8%). Differences between sex were not significant (p=0.814). Among the 8 occlusal variables included in the logistic regression analysis, those remaining in the final model were laterotrusive interferences (OR 2.47) and anterior open-bite (OR 0.88). This model showed good specificity (87%) but an unacceptable sensitivity (26.9%) to predict bruxism (accuracy=61.6%). Therefore, multivariate analysis did not lead to an improvement in bruxism predictability with respect to univariate analysis, which revealed that the presence of bruxism was significantly associated with laterotrusive interferences alone (p=0.040), and not with unilateral cross-bite (p=0.208), anterior open-bite (p=0.202), deep-bite (p=0.572), large horizontal overlap (p=0.261), dental midline discrepancy (p=0.519), mediotrusive interferences (p=0.119), slide >or=2 mm (p=0.857). CONCLUSION: According to our findings the contribution of occlusion to differentiate bruxers from non-bruxers is very poor. Infact, only laterotrusive interferences seem to be significantly associated with bruxism.

Comparison of masticatory dysfunction in temporomandibular disorders and fibromyalgia.

AIM: Many theories have been proposed as to the relationship between fibromyalgia (FM) and temporomandibular disorders (TMD). The aim of this study was to investigate the clinical features of the involvement of the stomatognathic system in patients with fibromyalgia, and to compare signs and symptoms of masticatory dysfunction between TMD and FM patients. METHODS: The study sample consisted of 30 subjects with fibromyalgia recruited at the Rheumatology Disease Department, University of Pisa, Italy, and of 30 with temporomandibular disorders at the Section of Prosthetic Dentistry, Department of Neurosciences, University of Pisa, Italy. Masticatory dysfunction has been compared between the 2 groups by means of a clinical assessment conducted according to the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). Patients of the TMD group underwent a rheumatologic examination to investigate for the presence of previously undiagnosed fibromyalgia. RESULTS: As regards specific clinical variables and RDC/TMD diagnoses, differences between the 2 groups appear to be not relevant, with the exception of the values of mouth opening, both voluntary and passive, and the presence of trigger points. FM patients showed a decrease in both maximum voluntary and passive mouth opening which was about 2 mm worse than that recorded in TMD patients. FM patients also showed a significantly higher number of trigger points, even though muscle palpation evoked tenderness in the same number of sites in the 2 groups. CONCLUSIONS: This study showed that most patients with fibromyalgia (86.7%) report signs and symptoms localized at the stomatognathic system; by contrast, only a minority of patients with temporomandibular disorders (10%) are actually affected by fibromyalgia.

Immunodetection of haemocyte subpopulations by N-acetylmuramic acid antibody in Planorbarius corneus (L.) (Gastropoda, Pulmonata).

The cell subpopulations in the haemolymph of Planorbarius corneus were distinguished by means of flow cytometry. An antibody against N-acetylmuramic acid was prepared and used as a cellular marker to recognize the cell types forming the subpopulations. The spreading haemocytes showed a positive reaction for anti-N-acetylmuramic acid; round haemocytes gave a negative reaction.

Is myelopathy of unknown origin related with tropical spastic paraparesis and myelopathy associated with human T cell lymphotropic virus type I?

Paired cerebrospinal fluid (CSF) and serum samples from 52 Italian patients affected by myelopathy of unknown origin (MUO) were tested for the presence of antibodies to human T cell lymphotrophic virus type I (HTLV-I) by an enzyme-linked immunosorbent assay, in an attempt to demonstrate a common retroviral origin of MUO, tropical spastic paraparesis (TSP) and HTLV-I-associated myelopathy (HAM). All the patients complained of weakness to the legs, while weakness to the arms, mild sensory disturbances, impaired bladder and bowel functions, and impotence were present in different percentages. All CSF and serum samples were devoid of HTLV-I antibodies. The possible relations between MUO, TSP and HAM are discussed.

Peripheral neuropathy in IgD myeloma. Cerebrospinal fluid paraprotein analysis in three cases.

High resolution polyacrylamide gel isoelectric focusing (IEF), followed by direct immunofixation with anti-delta chains monospecific antibodies, were used to detect and identify IgD paraprotein in the cerebrospinal fluid (CSF) of 3 patients affected by IgD myeloma. Two of these patients presented a paraproteinemic neuropathy. Blood-brain barrier damage was investigated by means of CSF/serum albumin ratio. IgG index and CSF and serum IgD/albumin ratio were also evaluated. An intrathecal origin of the IgD paraprotein was excluded. The correlation between the presence of the paraprotein in the CSF and the possible neurological involvement was also examined.