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Biomedical subjects

S Monaco

Publications and source records attributed to S Monaco.

At least 37 records · Page 2Linked to original sources
PubMed1998

HIV-associated PML presenting as epilepsia partialis continua.

Two patients with human immunodeficiency virus (HIV) type 1 infection presented new-onset epilepsia partialis continua (EPC) as an early manifestation of progressive multifocal leukoencephalopathy (PML). EPC occurred with no other seizures and was associated with negative radiographic and electrophysiological findings for several weeks. PML represents an increasingly recognized cause of new-onset seizures in both seropositive and seronegative patients, with no report of EPC as a presenting complaint.

AIDS Dementia Complex↗
PubMed1998

Antisulfatide polyneuropathy: antibody-mediated complement attack on peripheral myelin.

Increased titers of circulating antisulfatide antibodies are consistently associated with a variety of chronic axonal and demyelinating polyneuropathy syndromes. Previous studies have shown that the pattern of antisulfatide binding to neural tissues correlates with the type of neuropathy. This suggests a possible role for antisulfatide antibodies in inducing peripheral nerve dysfunction, although their exact contribution to the pathogenesis of neuropathy is still unknown. We examined sural nerve biopsy specimens from two patients with sensorimotor and small fiber sensory neuropathy associated with high titers of IgM monoclonal antibodies to sulfatide. Electrophysiological and pathological findings were consistent with predominant demyelination in the patient with sensorimotor involvement, whereas evidence of demyelination was obtained only by teased fiber examination in the other patient. The ultrastructural study disclosed in both cases the presence of myelinated fibers with widely spaced myelin, due to a separation of leaflets of the intraperiod lines. Immunocytochemistry, performed on frozen sections, demonstrated the presence of IgM and complement product C3d bound to myelin sheaths of almost all fibers. Few fibers were immunoreactive for complement components C1q and C5. In addition, the terminal complement complex neoantigen C5b-C9, not associated with S protein, was detected on some myelinated fibers. The results suggest that, at the least in some forms of demyelinating neuropathy associated with antisulfatide antibodies, pathological changes are complement mediated. Our data further confirm previous clinical and experimental observations that complement activation initiates separation of myelin intraperiod lines.

Aged↗
PubMed1998

Transient tonic pupils in botulism type B.

We report a 29-year-old woman who developed unilateral unreactive mydriasis and cycloplegia after 5 days of persistent constipation. During the next hours the patient complained of dry mouth and difficulties in swallowing food; iris and ciliary muscle palsies spread over the second eye. Ocular motility was normal and there were no clinical signs of neuromuscular involvement. Conventional electromyography and evoked muscle action potentials following repetitive nerve stimulation were normal; single-fiber electromyography showed normal jitter and absence of blocking. The diagnosis of botulism was considered as most likely, and the patient was given botulinum antitoxin. The post-treatment course was characterized by bilateral tonic pupillary reaction to near, sectoral iris contractions to light and pupillary constriction to 2 mm in 40 min following topical instillation of 0.1% pilocarpine. Ocular manifestations completely disappeared within 5 weeks. Botulism type B toxin was demonstrated in the pretreatment stool of the patient but not the serum.

Adult↗
PubMed1998

Omeprazole 20 or 40 mg daily for healing gastroduodenal ulcers in patients receiving non-steroidal anti-inflammatory drugs.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are strongly associated with gastroduodenal ulcers, and the management of patients with NSAID-associated ulcers represents a common clinical dilemma. AIM: To assess NSAID-associated ulcer healing during treatment with either standard (20 mg) or high dosage (40 mg) omeprazole. METHODS: One hundred and sixty-nine patients chronically ingesting diclofenac, ketoprofen, indomethacin or naproxen for osteoarthritis or rheumatoid arthritis, who had abdominal pain and an endoscopically proven gastroduodenal ulcer, were evaluated in a randomized, double-blind, dose regimen trial with omeprazole 20 mg o.m. (n = 81) or omeprazole 40 mg o.m. (n = 88). Ulcer healing was assessed endoscopically at 4 and 8 weeks in the case of unhealed ulcers. Patients continued their usual daily dose of anti-inflammatory medication throughout the study period. RESULTS: One hundred and fifty-six patients completed the study (77 patients taking 20 mg omeprazole and 79 patients taking 40 mg omeprazole); 12 patients were lost during follow-up and one patient reported an adverse event. Cumulative ulcer intention-to-treat healing rates at 8 weeks were 88% (95% confidence interval (CI) = 79-95%) for the 20 mg omeprazole group and 96.2% (95% CI = 89-99%) for the 40 mg group, and 97.1% (95% CI = 90-100%) for the 20 mg omeprazole group and 98.6% (95% CI = 93-100%) for the 40 mg group by per protocol analysis. There were no statistically significant differences between the two groups. Symptom relief did not differ significantly between the two treatment groups. CONCLUSION: Both standard and high doses of omeprazole are equally safe and effective regimens for the treatment of NSAID-induced gastroduodenal ulcers when anti-inflammatory treatment is not discontinued.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1997

T-cell-mediated epineurial vasculitis and humoral-mediated microangiopathy in cryoglobulinemic neuropathy.

We used immunohistochemistry to assess the role of humoral and cellular factors in endoneurial microangiopathy and epineurial vasculitis in 15 nerve biopsies of patients with axonal neuropathy and monoclonal or mixed cryoglobulinemia (CG). Deposition of immunoglobulins and cytolytic complement was detected in endoneurial capillaries of patients with mixed CG. Epineurial inflammatory infiltrates containing beta2-integrin-positive lymphocytes and monocytes surrounded arterioles expressing cell adhesion molecules, thus suggesting a cell-mediated pathogenesis of the epineurial vasculitis. On the other hand, the absence of immune complex deposition and polymorphonuclear elements suggests a minor role for the humoral mechanisms in the formation of the vasculitic lesions. This study indicates that both cell-mediated mechanisms and immune complexes/cryoglobulins are involved, although at different levels, in the pathogenesis of CG neuropathy.

Aged↗
PubMed1996

Cytoskeletal changes in cultured human fibroblasts following exposure to 2,5-hexanedione.

In the present study, the effects of the 2,5-hexanedione (HD) on the various cytoskeletal components of human eukaryotic cells were investigated. Primary cultures of human fibroblasts from three healthy donors were exposed to 2.8 mM HD for 14 days; unexposed cultures were used as controls. At different time intervals, cells were counted and the growth curves compared. After 14 days of treatment, the cultures were processed for immunoblotting, immunocytochemistry and ultrastructural studies. As compared to controls, morphological abnormalities induced by HD consisted of modification of the cell shape, formation of tangles composed by 10 nm filaments and cytoplasmic segregation of microtubules and membrane-bound organelles. By immunocytochemistry, the tangles of cytoplasmic filaments were stained by an antibody specific for vimentin. By immunoblotting, the anti-vimentin antibody recognized only bands of 50-60 kDa. Comparison of growth curves between treated and control fibroblasts clearly revealed an interference of HD with the cell cycle. The present results demonstrate that the cytotoxicity of HD is not restricted to intermediate filaments, but affects other cytoskeletal components, such as microtubules, as suggested by the impairment of cell division cycle.

Cell Count↗
PubMed1995

Role of HIV in the pathogenesis of distal symmetrical peripheral neuropathy.

We report the results of a clinical, electrophysiological and pathological study conducted in 18 AIDS patients presenting a distal symmetrical predominantly sensory polyneuropathy (DSPN) characterized by painful dysesthesias as main complaint. Onset of the neuropathy was at CDC (Center for Disease Control) stage II in 2 patients, at CDC stage III in 5 patients and at CDC stage IV in the remainder. Electrophysiological investigation confirmed the presence of an axonal alteration in the sensory nerves, but also revealed motor involvement in all cases. The neuropathological features of sensory nerves were fiber loss and axonal degeneration with macrophagic activation. The expression of monocyte-macrophage markers and of major histocompatibility complex class II antigens appeared up-regulated in endoneurial ramified cells, while expression of CR3, a complement receptor involved in the process of phagocytosis, was down-regulated. In six nerve biopsy samples and in two out of five DSPN dorsal root ganglia we found HIV-related mRNA and protein located in scattered cells of the endoneurium which we presume to be macrophages. These data suggest that: (a) DSPN may occur early in the course of the disease and is not limited to later stages; (b) DSPN is not a ganglionitis but is actually a sensory-motor neuropathy; (c) the virus enters the peripheral nervous system and induces changes in the immunocompetent cell population with activation of macrophages. Storage of the virus inside macrophages may act both as a reservoir for the virus and as a putative cause of nerve damage, probably through release of cytotoxins and/or interaction with trophic factors.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Experimental induction of myelin changes by anti-MAG antibodies and terminal complement complex.

We investigated the role of anti-myelin-associated glycoprotein (MAG) IgM and complement (C) in the pathogenesis of myelin alterations occurring in patients with anti-MAG-associated polyneuropathy. For this purpose, we separately studied the effects of anti-MAG antibodies and terminal C complex (TCC) after injection into the rabbit sciatic nerve. The two different local treatments produced identical ultrastructural abnormalities such as intramyelinic edema, myelin vesiculation and, in particular, separation of the major dense lines with the formation of widely spaced myelin, a peculiar feature encountered in human peripheral nerve disorders with circulating anti-myelin monoclonal IgM. In nerves treated with anti-MAG IgM ultrastructural myelin alterations were concurrent with activation of the rabbit's own C to the formation of TCC. Contrary to the immunological and ultrastructural findings obtained in C-sufficient animals, in C6-deficient rabbits injected with anti-MAG IgM no myelin alterations nor C completion were observed. This study identifies anti-MAG IgM as the mediator and the C as the effector of myelin changes observed in the present model and, for extension, in human neuropathies associated with anti-MAG IgM.

Animals↗
PubMed1995

Expression and distribution of GAP-43 in human astrocytes in culture.

By combining mRNA analysis and immunocytochemistry, we investigated the expression of the growth associated protein 43 (GAP-43) in enriched populations of astrocytes, obtained from mixed cultures of human fetal brains. Total cellular RNA was extracted from cell pellets and reverse transcribed into cDNA; cDNA was subjected to PCR amplification using primers specific for GAP-43 and PCR products were separated through polyacrylamide gels. Double immunofluorescence staining was performed on dissociated cell cultures using antibodies to glial fibrillary acidic protein (GFAP) and to GAP-43. Results showed that both transcription and translation for GAP-43 occur in cultured astrocytes. GAP-43 immunoreacting material was detected in the cell processes and diffusely in the cytoplasm of GFAP-positive astrocytes, during early stages of maintenance in vitro. In older cultures, GAP-43 immunoreactivity persisted in a large percentage of cells, with a tendency to accumulate in perinuclear areas. These observations provide evidence that GAP-43 is not restricted to neuronal cells. The close spatial association with cytoskeletal constituents, as observed in astrocytes, suggests a role for this protein in the control of cell shape, motility and adhesion processes.

Astrocytes↗
PubMed1994

Frequency and clinical correlates of anti-neural IgM antibodies in neuropathy associated with IgM monoclonal gammopathy.

We studied the frequency and clinical correlates of different IgM specificities in 75 patients with neuropathy associated with IgM monoclonal gammopathy. Patients were tested for IgM reactivity with the myelin-associated glycoprotein, P0, neurofilaments, and tubulin by immunoblot; with GM1, asialo-GM1, GM2, GD1a, GD1b, sulfatide, and chondroitin sulfate C by enzyme-linked immunosorbent assay; and with brain and nerve glycolipids by overlay high-performance thin-layer chromatography. Forty-two patients (56%) had high titers of IgM antibodies to MAG; 4 (5%), to sulfatide (1 also to myelin-associated glycoprotein); 4 (5%), to the 200-kd neurofilament (2 also to myelin-associated protein); and 1 each, to GD1b and chondroitin sulfate C. No reactivity was found in 26 patients (35%). More patients with anti-myelin-associated glycoprotein IgM (62%) than with unknown IgM reactivity (31%) had a predominantly sensory neuropathy (p < 0.025). Nerve conduction findings were consistent with a demyelinating neuropathy in 77% of patients reactive to myelin-associated glycoprotein and 24% with unknown reactivity (p < 0.0001) and the mean conduction velocity of peroneal nerve was lower in the former group (22.9 m/sec) than in the latter group (39.6 m/sec) (p < 0.000001). Patients with anti-sulfatide IgM had a sensorimotor neuropathy with morphological evidence of demyelination while anti-neurofilament IgM was not associated with homogeneous findings. Patients with anti-GD1b or anti-chondroitin sulfate C IgM had a predominantly motor impairment. The frequent occurrence of anti-neural IgM antibodies in neuropathy associated with IgM gammopathy, and their frequent, though not constant association with similar neuropathy features, support their possible pathogenetic role in the neuropathy.

Adult↗
PubMed1994

Increased serum levels of ICAM-1, ELAM-1 and TNF-alpha in inflammatory disorders of the peripheral nervous system.

Endothelial intercellular adhesion molecule-1 (ICAM-1) and glycoprotein E-selectin (ELAM-1) allow the homing of leukocytes to inflammation sites. A circulating form of ICAM-1 markedly increases in inflammatory CNS disorders. In the present study, the serum levels of ICAM-1, ELAM-1 and tumor necrosis factor-alpha (TNF-alpha) were measured in patients with acute (AIDP) and chronic (CIDP) inflammatory demyelinating polyneuropathies and cryoglobulinemic neuropathy (CGN). Immunoenzymometric assays revealed increased sICAM-1 levels in some of these patients; furthermore, high titres of ELAM-1 and TNF-alpha were detected in two patients with AIDP and one patient with CGN. Our data extend previous observations on inflammatory PNS disorders by showing that, in addition to ICAM-1, ELAM-1 also represents a useful marker of endothelial activation and that, taken together, the two molecules may serve as an indicator of specific pathogenetic mechanisms.

Adult↗
PubMed1993

Human peripheral nerve macrophages in normal and pathological conditions.

We investigated, by immunocytochemistry and immune electron microscopy, the immunophenotype, morphology and functional properties of human peripheral nervous system (PNS) macrophages (M phi) under normal and pathological conditions. Endoneurial M phi disclosed an elongated, ramified morphology, with the main processes oriented along the major axis of nerve fibers; they shared several lineage-related and functional markers with monocyte/macrophages and central nervous system (CNS) microglia, including CD4, CR3, CR4 and FcRIII. In addition, basal expression of HLA-DR antigens was exclusively confined to M phi in normal PNS. In the course of unrelated pathological conditions, resident M phi underwent activation with transformation to hypertrophic cells or foamy phagocytes and up-regulation of the markers expressed in normal conditions; new expression of a macrophagic antigen was detected on activated M phi. In different neuropathies, HLA-DR expression was also detected on non-myelin forming Schwann cells with ultrastructural features indicative of denervation. The present results demonstrate that the human PNS is provided with an intrinsic population of immunocompetent and potentially phagocytic M phi, which represent the peripheral counterpart of CNS microglia.

Adolescent↗
PubMed1993

IDPN impairs post-traumatic regeneration of rat sciatic nerve.

The role played by cytoskeletal proteins in nerve regeneration was investigated in a model in which the axonal transport of neurofilaments (NF) is almost selectively impaired. The administration of beta, beta'-iminodipropionitrile (IDPN), a synthetic lathyrogenic compound, induces an axonopathy characterized by proximal axonal enlargements, due to NF accumulation, and by diffuse atrophic changes associated with spatial segregation of NF from microtubules (MT). We investigated post-axotomy regeneration of rat sciatic nerve following IDPN administration. Changes induced by IDPN, as examined in the proximal and distal nerve stump at 15 and 30 days after lesion, consisted of a statistically significant reduction of the mean axonal diameter (P < 0.0001) as compared to control rats. In addition, the number of regenerating myelinated fibres was smaller in dosed rats (P < 0.001) 15 days after crush, whereas at the later stage the number of axons approached that of control animals. Electrophysiological investigation revealed a delay in target reinnervation in dosed rats. Regenerating IDPN axons, both 15 and 30 days after crush contained fewer NF (P < 0.001), while the number of MT was slightly increased as compared to controls. Taken together, our results suggest that severe alteration of NF transport, coupled with mild alteration of other components of cytoskeletal proteins, impairs the longitudinal and radial growth of regenerating myelinated axons and confirm that the number of NF is the major determinant of the cross-sectional area of each segment of the axon.

Animals↗
PubMed1993

Three-month therapy with calcium-heparin in comparison with ticlopidine in patients with peripheral arterial occlusive disease at Leriche-Fontaine IIb class.

Forty patients with a mean age of 62.6 +/- 6 years, 36 men and 4 women, with peripheral arterial occlusive disease (PAOD) at Leriche-Fontaine IIb class, were randomly allocated to one of two treatment groups, receiving either 12,500 IU/day of subcutaneous (sc) calcium-heparin (CAE) or 250 mg/day of oral ticlopidine, each given for ninety days. The following parameters were evaluated before the start of the active treatment period and after thirty and ninety days of treatment: pain-free walking distance (PWD), maximum walking distance (WDmax), systolic and diastolic blood pressure (BP), posterior tibial arterial pressure and Winsor index at rest and after exercise (treadmill), transcutaneous oxygen and carbon dioxide pressures at rest (TcPO2 and TcPCO2 respectively), and time to 50% TcPO2 recovery after three-minute ischemia. Both treatments induced an improvement in PWD/WDmax, which, at the end of the study, were increased by 50.7/58.7% and 31.7/36.2%, respectively, for CAE and ticlopidine treatments, respectively.

Arterial Occlusive Diseases↗
PubMed1992

MHC-positive, ramified macrophages in the normal and injured rat peripheral nervous system.

Resident endoneurial macrophages form a prominent, but little recognized component of the PNS. We have studied immunocytochemically the distribution, morphology and immunophenotype of endoneurial macrophages in several normal peripheral nerves of the rat. In addition, we investigated the macrophage response following crush injury of the sciatic nerve. Resident endoneurial macrophages had a ramified morphology with processes oriented parallel to the long axis of nerve fibres. They were positive for several monocyte/macrophage markers such as ED1, ED2 and the recently-described MUC 101 and MUC 102 antibodies. They furthermore expressed the complement type three receptor, the CD4 antigen and MHC class I and II molecules. These results were consistent in all the peripheral nerves studied. In addition, 1000 rad of gamma-irradiation led to a strong reduction in the number of MHC class II-positive ramified cells in the peripheral nerves similar to that observed in other peripheral organs such as the heart. A considerable percentage of resident macrophages in the PNS and/or their precursor cells are therefore radiosensitive and could be related to the lineage of dendritic cells. Following crush injury, ED1-3-, OX-42-, MUC 101- and MUC 102-positive round macrophages were observed from 24 h postlesion onward at the site of trauma. In the distal part, they were observed to form strings of round, foamy macrophages probably involved in myelin phagocytosis. In contrast, the number of MHC class II-positive resident macrophages was only slightly increased at the site of trauma and in the distal part. These cells transformed from a ramified to a round morphology, but did not appear as typical strings of foamy macrophages. These results demonstrate that the PNS is provided with a resident macrophage population analogous in many respects to microglial cells in the CNS. These constitutively MHC class II-positive PNS microglial-like cells could act as the major antigen-presenting cells in the peripheral nerve. They may thus constitute a local immune defense system of the PNS with a function similar to that of microglial cells in the CNS.

Animals↗