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Biomedical subjects

R Gherardi

Publications and source records attributed to R Gherardi.

At least 19 recordsLinked to original sources
PubMed2003

Long term course of the H reflex after selective tibial neurotomy.

OBJECTIVES: This study was conducted to evaluate the long term clinical and electrophysiological outcome by recording the H reflex in a consecutive series of six patients treated by selective tibial neurotomy for spastic equinus foot. METHOD: The amplitudes of Hmax reflexes, Mmax responses, and Hmax:Mmax ratio were recorded in six patients with chronic lower limb spasticity, before and after surgery, at day 1 and 8 months and 24 months after selective tibial neurotomy. The passive range of movement, the stretch reflex score according to the Tardieu scale, the osteoarticular and tendon repercussions, and the quality of motor control of dorsiflexion were evaluated preoperatively and postoperatively. RESULTS: At the end of the study, all patients presented a reduction of equines. Gait and Tardieu's score of spasticity had improved in all patients. Active dorsiflexion of the ankle was unchanged in four patients, but two improved by 5 degrees to 12 degrees. In five cases, fascicular resection of the superior nerve to soleus was, alone, sufficient to reduce spastic equinus foot, without recurrence, for a mean follow up of 28 months. Two patients were reoperated on, one for remaining spasticity related to an underestimated spasticity of the gastrocnemius muscles, and the other for painful claw toes. Hmax, Mmax, and Hmax:Mmax ratios were significantly lower the day after surgery. The reduction of Hmax and Hmax/Mmax ratio remained stable over time and was still statistically significant two years after the operation. However, the value of Mmax eight months postoperatively was no longer significantly different from the preoperative value. CONCLUSION: This study shows the long term efficacy of the selective tibial neurotomy as treatment of spastic equinus foot. Neurotomy confined to fibres supplying the soleus muscle is sufficient in most cases and acts by decreasing sensory afferents without significant long term motor denervation.

Adolescent↗
PubMed2003

[Camptocornia presenting with a proximal myotonic myopathy].

We report the case of a 74-year-old patient who presented with an anterior inflexion of the trunk which increased during the day. His past medical history included treatment for hypothyroidism, a cure of cataracts and an increase of gammaGT. This camptocormic attitude revealed a proximal myotonic myopathy (PROMM). Clinical and paraclinical arguments (hypothyroidism, cataracts, weakness, EMG, muscle biopsy, biology) led to diagnosis.

Aged↗
PubMed2002

[Cellular aspect of neuroinflammation in Guillain-Barré syndrome: a key to a new therapeutic option?].

Guillain-Barré syndrome (GBS) is an acute inflammatory demyelinating neuropathy associated with long-lasting morbidity and substantial risk of mortality. The two reference treatments (plasma exchange-PE and intravenous immunoglobulins-IVIGs) do not change the functional prognosis in patients with very severe disease. Pathogenesis of GBS associates recently characterized humoral and cellular immune dysfunctions. Antibodies against nerve antigens may participate in complement activation, antibody-dependent macrophage cytotoxicity, and reversible conduction failure. Cellular immune reaction is associated with an increase of proinflammatory cytokines (for exemple TNF-alpha), a decrease of anti-inflammatory cytokines (such as TGF-B1), an increase of matrix metalloproteinases (MMP-9-gelatinase B), all abnomalities favoring adhesion to and transmigration across endothelium of immune cells, a key phenomenon in GBS. Recovery of GBS is characterized by the normalization of these abnormalities. Experimental allergic neuritis (EAN), the experimental model of GBS has strikingly similar immunological abnormalities. The treatments of GBS, PE and IVIGs, mainly target the humoral component of the immune response. IFN-B is a cellular immunomodulator that inhibits antigen presentation, TNF-alpha production and binding, modulates macrophages properties. IFN-B increases anti-inflammatory T cell functions and cytokines, such as TGF-B1. IFN-B has important properties on leukodiapedesis by modulating expression of cell adhesion molecules and the MMP-9 proteinase. IFN-B has been used with success in EAN, in some patients with acute exacerbation of chronic inflammatory demyelinating polyneuropathy, and in one patient with GBS. Pathophysiology of GBS, IFN-B properties, and experimental studies support the initiation of a trial of IFN-B in GBS.

Guillain-Barre Syndrome↗
PubMed2001

Impaired redox status and cytochrome c oxidase deficiency in patients with polymyalgia rheumatica.

OBJECTIVE: To evaluate redox status and muscular mitochondrial abnormalities in patients with polymyalgia rheumatica (PMR). METHODS: Prospective evaluation of deltoid muscle biopsy in 15 patients with PMR. Fifteen subjects matched for age and sex, with histologically normal muscle and without clinical evidence of myopathy, were used as controls. Cryostat sections of muscle were processed for conventional dyes, cytochrome c oxidase (COX), usual histochemical reactions, and Sudan black. A total of 300-800 fibres was examined in each case. Blood lactate, pyruvate, and lactate/pyruvate ratio were determined in all patients. RESULTS: Ragged red fibres were found in eight patients with PMR and accounted for 0-0.5% of fibres. Focal COX deficiency was found in 14 (93%) of 15 patients and in nine (60%) of 15 controls. COX deficient fibres were more common in patients with PMR (range 0-2.5%; mean 0.9%) than in controls (range 0-1.2%; mean 0.3%) (paired t test, p=0.001). Seven (47%) of 15 patients had high blood lactate levels (1.50-2.60 mmol/l) or high blood lactate/pyruvate ratios (22-25). CONCLUSIONS: PMR is associated with mitochondrial abnormalities not solely related to the aging process.

Aged↗
PubMed2000

Cytochrome c oxidase deficiency in the muscle of patients with zidovudine myopathy is segmental and affects both mitochondrial DNA- and nuclear DNA-encoded subunits.

Zidovudine (AZT) can induce a mitochondrial disorder associated with mitochondrial (mt) DNA depletion affecting skeletal muscle, heart, and liver. Zidovudine myopathy is characterized by ragged-red fibers and partial cytochrome c oxidase (COX) deficiency. We evaluated at a single fiber level the expression of COX II (mtDNA-encoded) and COX IV (nuclear DNA-encoded) subunits in 12 HIV-infected patients with zidovudine myopathy. We also evaluated COX activity on longitudinal muscle sections in one patient. In all patients, evaluation of the expression of COX II and COX IV subunits showed focal deficiency. All fibers negative for COX II or COX IV were negative by COX histochemistry; 32-92% (median 61%) of COX-negative fibers were negative for COX II antigens, and 7-58% (median 28%) were negative for COX IV antigens. One hundred and thirty-nine of 317 COX-negative fibers 139 (43.8%) were selectively negative for COX II; 28 of 317 (8.8%) COX-negative fibers were selectively negative for COX IV. A study of longitudinal distribution of COX activity demonstrated that COX deficiency was segmental with blurred borders, as previously observed in patients with myoclonus epilepsy with ragged-red fibers. We conclude that proteins encoded by mtDNA are predominantly, but not exclusively, involved in zidovudine myopathy. Our results confirm the value of single muscle fiber evaluation in the assessment of mitochondrial abnormalities related to zidovudine.

Chromosomes↗
PubMed1998

Acute, relapsing brain oedema with diffuse blood-brain barrier alteration and axonal damage in the acquired immunodeficiency syndrome.

A 38-year-old homosexual male with AIDS suffered four neurological episodes including headaches, confusion, visual impairment, memory disturbances, and dysarthria which resolved spontaneously in a few days. He was admitted to hospital during a fifth episode. Neurological examination revealed a cerebellar syndrome. General examination was normal. CD4 count was 90. CSF contained two WBCs/mm(3) and 12.30 mg/dL protein. MRI revealed diffuse ill defined increased signal on T2-weighted images in the white matter. His condition worsened rapidly with vomiting and he died 1 month after admission. Neuropathological examination revealed diffuse brain oedema with ventricular compression, central diencephalic herniation and bilateral tonsilar herniation in the absence of a focal lesion. Microscopical examination revealed predominant involvement of the white matter with diffuse myelin pallor and massive perivascular dilatation containing an exudate expressing serum proteins and occasional macrophages. The same exudate was also diffuse in the leptomeninges. Parenchymal damage predominated around the perivascular spaces and included loosening of tissue, axonal damage with spheroids and reactive astrocytosis. There was no evidence of productive HIV encephalitis, no multinucleated giant cells; p24 immunostaining and RT-PCR for HIV genome were negative. There was neither significant inflammation nor microglial activation. In this illustrative case, the relapsing course of the neurological signs, the diffuse topography of the blood-brain barrier breakdown and the absence of local cause make it likely that the diffuse leak and axonal damage could be related to circulating factors.

Acquired Immunodeficiency Syndrome↗
PubMed1998

DNA breaks detected by in situ end-labelling in dorsal root ganglia of patients with AIDS.

Distal sensory axonal polyneuropathy (DSP) is the most frequent HIV-associated peripheral neuropathy. DSPs tend to occur in full-blown AIDS and worsen as CD4 cell counts decrease in blood. To assess a possible role for apoptosis in the pathogenesis of the neuropathy, we used in situ end-labelling (ISEL) detecting DNA strand breaks in DRG neurons of 19 HIV-infected patients, of whom nine had axonal polyneuropathy, and 11 controls. Sensory neurons with ISEL-assessed DNA breaks were observed in 9/19 patients with AIDS, 0/3 patients with pre-AIDS, and 1/11 controls. The prevalence of DNA breaks in neurons was higher in AIDS patients than in controls (P < 0.05). Among AIDS patients, DNA breaks in neurons were more abundant in patients with peripheral neuropathy (P < 0.04). It is possible that DNA breaks of DRG neurons induce the axonopathy and consequently play a role in the pathogenesis of DSP. It cannot be excluded, however, that DNA breaks could represent the result rather than the cause of axonopathy. We suggest that ISEL may detect neurons that were primed to apoptosis before death in relation with the HIV infection, and undergo DNA fragmentation at time of death, rather than neurons that underwent premortem both priming and triggering steps of the apoptotic process. This hypothesis could explain why most ISEL-positive neurons lack typical apoptotic morphology and why normal controls do not show ISEL positive cells.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Pulmonary hypertension in POEMS syndrome: a new feature mediated by cytokines.

POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome is a rare variant of plasma cell dyscrasia with multiple systemic manifestations. We followed the progress of 20 patients with POEMS syndrome in our institution over a 10-yr period. Pulmonary hypertension (PH) was observed in five patients. All patients suffered dyspnea on exertion, which always appeared during an exacerbation of POEMS syndrome. The typical echocardiographic signs of PH were observed in all of these patients, and the median pulmonary-artery systolic pressure was 57 mm Hg (range, 50 to 65 mm Hg). Mean pulmonary-artery pressure during right side heart catheterization in two patients was 32 mm Hg. No other explanation for the PH could be found. Overproduction of cytokines was found in all cases, with high serum concentrations of interleukin-1beta, interleukin-6, tumor necrosis factor-alpha, and vascular endothelial growth factor. We suggest that PH should be added to the list of symptoms of POEMS syndrome. Cytokines may mediate POEMS syndrome-associated PH, as proposed for the other systemic manifestations of this disorder.

Adult↗
PubMed1998

[Chronic pseudo-hypertrophic myopathy in sarcoidosis. Apropos of 3 cases].

We report three cases of pseudohypertrophic chronic myopathy in patients with sarcoidosis. The patients were aged 41-50 years and were of African or mixed ethnic origin. All three patients had multiorgan sarcoidosis recently diagnosed by the presence of hiliary and/or mediastinal node enlargement with or without reticulomicronodulation in the lung fields. Hypertrophy of the proximal portion of the limbs dominated the clinical presentation. In 2 cases, the myopathy was preceded by myalgia and in 2 cases associated with muscle nodules. The muscle enzymes were elevated in 2 cases. The importance of tuberculoid granulomas and the discretion of the myopathy characterised the histological findings in all 3 cases. Cortisone therapy was given early and long-term treatment led to favorable course in 2 cases, probably due to the importance of the granulomatous muscle mass. In the third case, peripheral neuropathy developed.

Adult↗
PubMed1997

Cellular and mitochondrial toxicity of zidovudine (AZT), didanosine (ddI) and zalcitabine (ddC) on cultured human muscle cells.

Zidovudine (AZT), didanosine (ddI) and zalcitabine (ddC) are the reference antiretroviral therapy in patients with AIDS. A toxic mitochondrial myopathy can be observed in patients treated with AZT, but not with ddI and ddC. All 3 compounds can inhibit mitochondrial (mt)DNA polymerase and cause termination of synthesis of growing mtDNA strands and mtDNA depletion. The propensity to injure particular target tissues is unexplained. In our work, cultured muscle cells prepared from human muscle biopsies, were exposed to various concentrations of AZT (4-5000 micromol/l), ddI (5-1000 micromol/l) and ddC (1-1000 micromol/l) for 10 days. We evaluated cell proliferation and differentiation and measured lipid droplet accumulation, lactate production and respiratory chain enzyme activities. All 3 compounds induced a dose-related decrease of cell proliferation and differentiation. AZT seemed to be the most potent inhibitor of cell proliferation. AZT, ddI and ddC induced cytoplasmic lipid droplet accumulations, increased lactate production and decreased activities of COX (complex IV) and SDH (part of complex II). NADHR (complex I) and citrate sinthase activities were unchanged. Zalcitabine (ddC) and, to a lesser extent, ddI, were the most potent inhibitors of mitochondrial function. In conclusion, AZT, ddI and ddC all exert cytotoxic effects on human muscle cells and induce functional alterations of mitochondria possibly due to mechanisms other than the sole mtDNA depletion. Our results provide only a partial explanation of the fact that AZT, but not ddI and ddC, can induce a myopathy in HIV-infected patients. AZT myopathy might not simply result from a direct mitochondrial toxic effect of crude AZT.

Anti-HIV Agents↗
PubMed1997

Evidence of a non-conventional role for the urokinase tripartite complex (uPAR/uPA/PAI-1) in myogenic cell fusion.

Urokinase can form a tripartite complex binding urokinase receptor (uPAR) and plasminogen activator inhibitor type-1 (PAI-1), a component of the extracellular matrix (ECM). The components of the tripartite complex are modulated throughout the in vitro myogenic differentiation process. A series of experiments aimed at elucidating the role of the urokinase tripartite complex in the fusion of human myogenic cells were performed in vitro. Myogenic cell fusion was associated with increased cell-associated urokinase-type plasminogen activator (uPA) activity, cell-associated uPAR, and uPAR occupancy. Incubation of cultures with either uPA anticatalytic antibodies, or the amino-terminal fragment of uPA (ATF), which inhibits competitively uPA binding to its receptor, or anti-PAI-1 antibodies, which inhibit uPA binding to PAI-1, resulted in a 30 to 47% decrease in fusion. Incubation of cultures with the plasmin inhibitor aprotinin did not affect fusion. Decreased fusion rates induced by interfering with uPAR/uPA/PAI-1 interactions were not associated with significant changes in mRNA levels of both the myogenic regulatory factor myogenin and its inhibitor of DNA binding, Id. Incubation of cultures with purified uPA resulted in a decrease in fusion, likely due to a competitive inhibition of PAI-1 binding of endogenous uPA. We conclude that muscle cell fusion largely depends on interactions between the members of the urokinase complex (uPAR/uPA/PAI-1), but does not require proteolytic activation of plasmin. Since the intrinsic muscle cell differentiation program appears poorly affected by the state of integrity of the urokinase complex, and since cell migration is a prerequisite for muscle cell fusion in vitro, it is likely that the urokinase system is instrumental in fusion through its connection with the cell migration process. Our results suggest that the urokinase tripartite complex may be involved in cell migration in a non conventional way, playing the role of an adhesion system bridging cell membrane to ECM.

Antibodies↗
PubMed1997

[Muscular complications in HIV infection].

Skeletal muscle involvement may occur at all stages of HIV-infection and represents the first manifestation of the disease into some patients. We usually classify muscle involvement in HIV-infected patients in one of the following categories: HIV-associated myopathy, a myopathy that meets the criteria for polymyositis in a majority of patients, and those for acquired nemaline myopathy in some cases (1); zidovudine myopathy, a reversible mitochondrial myopathy (2); HIV-wasting syndrome and other AIDS-associated cachexias (3); opportunistic infections and tumor infiltrations of the skeletal muscle (4); vasculitic processes and iron pigment deposits (5); HIV-associated myasthenia gravis (6) and rhabdomyolysis (7). Immunohistology for major histocompatibility complex class I antigen and histochemical reaction for cytochrome coxidase are helpful in the correct classification of a myopathy as HIV polymyositis or zidovudine myopathy.

AIDS-Related Opportunistic Infections↗