Search PubMed⌕ Search

Biomedical subjects

R Gherardi

Publications and source records attributed to R Gherardi.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1997

[Neuronal apoptosis in the central and peripheral nervous system in HIV infection].

Apart from the unique changes characteristic of "HIV encephalitis", the productive infection of central nervous system by HIV, which predominantly involves the white matter and basal ganglia, evidence is accumulating that the cerebral cortex may also be affected in AIDS patients. Neuronal loss, suspected at microscopic examination, has been demonstrated by a number of morphometric studies. However, the cause and mechanism of neuronal damage in HIV infection, are still unclear. In an attempt to look for an apoptotic process at the origin of neuronal loss in AIDS, we examined samples of frontal cortex, temporal cortex and basal ganglia from 12 patients who died from AIDS and 4 asymptomatic HIV-positive cases using in situ end labelling to demonstrate characteristic DNA fragmentation. These were compared with 5 asymptomatic seronegative controls, and 2 seronegative patients with Alzheimer's disease. We demonstrated neuronal apoptosis in all AIDS cases and in the Alzheimer's cases. Positive in situ end labelling was usually associated with morphological changes suggestive of neuronal apoptosis. Semiquantitative assessment of the density of apoptotic neurons showed that neuronal apoptosis was more severe in atrophic brains. In contrast, no correlation was found between the density of apoptotic neurons and the presence of HIV-encephalitis or a history of cognitive disorder. Only occasional apoptotic neurons were found in one asymptomatic, HIV-positive case. Apoptosis was never observed in asymptomatic seronegative cases. We also looked for apoptotic neurons in spinal ganglia of 20 AIDS cases, 5 of whom had a terminal sensory distal neuropathy, and 10 seronegative controls devoid of neuropathy. Apoptotic neurons were found in 6 of the AIDS patients and in none of the seronegative controls. However, no correlation was found between the severity of neuronal apoptosis in the spinal root ganglia and the presence of absence of a terminal distal sensory neuropathy. Experimental studies tend to support our in vivo findings. HIV-infection of primary cultures of human embryonic central nervous system induced frequent apoptosis of neurons. No apoptotic cell was identified in non infected control cultures.

AIDS Dementia Complex↗
PubMed1996

Cytochrome c oxidase deficiencies in the muscle of patients with inflammatory myopathies.

We studied mitochondrial function in inflammatory myopathies, using cytochrome c oxidase (COX) reaction on muscle biopsy samples from 30 patients (15 with dermatomyositis, 12 with polymyositis, and 3 with inclusion body myositis) and 30 age-matched controls. We also performed immunocytochemistry for COX II and COX IV subunits in 7 of these patients who had COX deficiency. COX-deficient fibers were a constant finding in patients or controls older than 65 years and the percentage of COX-deficient fibers correlated with age in both patients and controls. Focal COX deficiency was found in 24 patients (13 of 15 with dermatomyositis, 8 of 12 with polymyositis, and 3 of 3 with inclusion body myositis) and 18 controls. The percentages of COX-deficient fibers were higher in patients with inflammatory myopathies (range: 0-4.7%; mean: 1.2%) than in age-matched controls (range: 0-1.9%; mean: 0.4%) (P < 0.01). In the subgroup of patients under age 65, COX-deficient fibers were more frequent in dermatomyositis than in polymyositis (mean: 0.8% vs 0.2%, P = 0.02). In patients with dermatomyositis, capillary loss correlated positively with COX deficiency (P < 0.02). Immunocytochemistry for COX II and IV showed that 82% of COX-negative fibers were COX II-negative and 26% were COX IV-negative, suggesting that proteins encoded by mitochondrial DNA are predominantly, but not exclusively, involved in COX deficiency. We conclude that mitochondrial dysfunction and COX deficiency can occur in inflammatory myopathies. Such a mitochondrial dysfunction is not solely related to the aging process. We suggest that muscle ischemia contributes to mitochondrial dysfunction in dermatomyositis.

Adult↗
PubMed1996

Lipid-lowering drugs and mitochondrial function: effects of HMG-CoA reductase inhibitors on serum ubiquinone and blood lactate/pyruvate ratio.

1. Statins inhibit synthesis of mevalonate, a precursor of ubiquinone that is a central compound of the mitochondrial respiratory chain. The main adverse effect of statins is a toxic myopathy possibly related to mitochondrial dysfunction. 2. This study was designed to evaluate the effect of lipid-lowering drugs on ubiquinone (coenzyme Q10) serum level and on mitochondrial function assessed by blood lactate/pyruvate ratio. 3. Eighty hypercholesterolaemic patients (40 treated by statins, 20 treated by fibrates, and 20 untreated patients, all 80 having total cholesterol levels > 6.0 mmol l-1) and 20 healthy controls were included. Ubiquinone serum level and blood lactate/pyruvate ratio used as a test for mitochondrial dysfunction were evaluated in all subjects. 4. Lactate/pyruvate ratios were significantly higher in patients treated by statins than in untreated hypercholesterolaemic patients or in healthy controls (P < 0.05 and P < 0.001). The difference was not significant between fibratetreated patients and untreated patients. 5. Ubiquinone serum levels were lower in statin-treated patients (0.75 mg l-1 +/- 0.04) than in untreated hypercholesterolaemic patients (0.95 mg l-1 +/- 0.09; P < 0.05). 6. We conclude that statin therapy can be associated with high blood lactate/ pyruvate ratio suggestive of mitochondrial dysfunction. It is uncertain to what extent low serum levels of ubiquinone could explain the mitochondrial dysfunction.

Adult↗
PubMed1996

Antineutrophil cytoplasmic antibodies, abnormal angiograms and pathological findings in polyarteritis nodosa and Churg-Strauss syndrome: indications for the classification of vasculitides of the polyarteritis Nodosa Group.

The present study attempted to define the clinical, radiological, immunological and pathological characteristics of microscopic polyangiitis (MPA), and to separate them from classic PAN (c-PAN) and Churg-Strauss syndrome (CSS). In most cases, patients presenting microaneurysms and/or multiple vessel stenoses, which reflect medium-sized vessel involvement, did not have antineutrophil cytoplasmic antibodies (ANCA) (6.6%). Conversely, patients with glomerulonephritis almost never had abnormal angiograms. Furthermore, the clinical characteristics of ANCA-positive patients also indicate small-sized vessel involvement. Skin involvement (73.1 vs 26.7%, P < or = 0.05), glomerulonephritis (38.5 vs 0%, P < or = 0.001) and the presence of ANCA (34.6 vs 6.7%, P < or = 0.05) were significantly more frequent in patients with normal than abnormal angiograms, respectively. Conversely, hypertension (66.7 vs 23.1%, P < or = 0.02), renal vasculitis (46.7 vs 0%, P < or = 0.001) and hepatitis B antigenaemia (60 vs 11.5%, P < or = 0.01) were significantly more common in patients with abnormal angiograms. Stratification of patients according to vessel size showed that, except for skin involvement (P < or = 0.05) and glomerulonephritis (P < or = 0.01), which are direct manifestations of small-sized vessel diseases, clinical symptoms of PAN or CSS, angiographic findings and ANCA were not correlated to arteriole size. Although at present it is not possible to separate definitively MPA from c-PAN, our results show that ANCA should be considered diagnostic for MPA and, in most cases, should be an exclusion criterion for c-PAN. Conversely, small-sized vessel involvement can be observed in patients presenting characteristics of c-PAN, MPA or CSS and, therefore, is not a sufficient criterion for assigning diagnosis.

Adult↗
PubMed1996

Acute arterial obliteration: a new feature of the POEMS syndrome?

The POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammapathy, and skin changes) syndrome is a rare variant of plasma cell dyscrasia with multisystemic manifestations. We present 4 cases with arterial symptoms typical of acute arterial obliteration (AAO) and review 9 similar cases in the literature. The clinical course of AAO was unusual and particularly severe when affecting the lower limbs; recurrent events required amputations. As demonstrated by angiographic and histologic studies, thrombotic and atheromatous lesions were the main pathologic features of AAO. Atherosclerotic risk factors were absent or moderate in 3 of our cases, and no cause of thrombosis other than the POEMS syndrome was found. A high production of cytokines was found in all cases, with elevated serum levels of interleukin-1 beta (9/9 samples), interleukin-6 (7/9 samples), and tumor necrosis factor-alpha (6/9 samples). We suggest that arterial manifestations should be added to the spectrum of manifestations of the POEMS syndrome. Cytokines may mediate the POEMS syndrome-associated AAO, as previously proposed for the other systemic manifestations of this disorder.

Acute Disease↗
PubMed1995

Dermatomyositis without muscle weakness. Long-term follow-up of 12 patients without systemic corticosteroids.

BACKGROUND AND DESIGN: We retrospectively studied 12 patients with dermatomyositis (DM) with at least one laboratory criterion of muscle involvement but without muscle weakness. We reported their outcome without systemic corticosteroid treatment and searched for distinctive baseline data and associated neoplasia among a group of 29 patients with classic DM. RESULTS: After a mean follow-up of 5.3 years, complete or partial skin improvement occurred in nine patients with DM without muscle weakness, and muscle enzyme levels were normalized in all. When compared with the classic DM group, no statistical differences were found for associated neoplasia or for any baseline data studied except, as expected, for muscle parameters. CONCLUSIONS: The lack of distinctive baseline data between DM without muscle weakness and classic DM suggests that there is a continuum from amyopathic to classic DM. However, DM without muscle weakness is a clinical entity with respect to favorable long-term prognosis. Unless frank muscle weakness develops, treatment with systemic corticosteroids can be avoided.

Adolescent↗
PubMed1995

Proinflammatory cytokine expression in cervicovaginal secretions of normal and HIV-infected women.

Proinflammatory cytokines may stimulate replication and spread of HIV. To evaluate to what extent the female genital tract represents a source of these cytokines, we determined TNF-alpha, IL-1 beta and IL-6 concentrations in paired serum and cervicovaginal washings from 45 HIV-negative and 50 HIV-positive women, and then we looked for the relevant mRNAs in cervicovaginal secretions by RT-PCR. Cytokines were detected by ELISA in cervicovaginal fluid from most healthy women. Cervicovaginal washing levels of TNF-alpha were increased above the control value +2 SD in 11/50 HIV-positive women, those of IL-1 beta in 13/50, and those of IL-6 in 14/50. The prevalences of TNF-alpha, IL-1 beta and IL-6 increase and their levels in cervicovaginal washings were significantly higher in the 20 patients at stage IV than in the 30 patients at earlier stages of the disease. In HIV-infected patients, serum and cervicovaginal washing levels correlated positively for TNF-alpha and IL-6, but not for IL-1 beta. Nine of 15 cytokine mRNAs determinations were positive in HIV-infected women versus 1 of 15 in controls (P < 0.01). These findings could be relevant to bidirectional heterosexual transmission of HIV.

Case-Control Studies↗
PubMed1995

Myopathy and HIV infection.

Skeletal muscle involvement may occur at all stages of HIV infection. The most simple classification of muscular disorders in HIV-infected patients is 1) HIV-associated myopathies, 2) zidovudine myopathy, 3) HIV wasting syndrome, and 4) opportunistic infections and tumoral infiltrations of muscle. Immunohistology for major histocompatibility complex class I antigen and histochemical reaction for cytochrome c oxidase are helpful in correctly classifying a myopathy as HIV polymyositis or zidovudine myopathy. Studies of cytokine expression in HIV-infected patients and of supplementation with compounds such as carnitine or micronutrients such as selenium might yield new insights into the pathogenesis and treatment of the various AIDS-associated muscular disorders.

AIDS-Related Opportunistic Infections↗
PubMed1995

Cytochrome c oxidase deficiency in zidovudine myopathy affects perifascicular muscle fibres and arterial smooth muscle cells.

In order to assess the pathogenesis of myopathological alterations induced by zidovudine, we studied muscle samples from 21 patients infected by human immunodeficiency virus with zidovudine myopathy. Cytochrome c oxidase histoenzymatic reaction was evaluated in skeletal muscle fibres and arterial smooth muscle cells. Other investigations included immunocytochemistry for membrane attack complex and endomysial capillary counts. All patients had partial cytochrome c oxidase deficiency. A perifascicular distribution of cytochrome c oxidase-deficient fibres was found in 14 of 21 patients. Cytochrome c oxidase-deficient fibres were significantly more frequent in perifascicular areas than in the complete muscle sections (28% vs 12%, P < 0.001). Cytochrome c oxidase-deficient arteries were found in 11 patients, of whom 10 also had a perifascicular deficiency. Mononuclear microvascular inflammation was observed in four patients and membrane attack complex deposition in capillary walls in two patients. The capillary counts were not significantly different in the patients and in the controls. These results suggest that, in addition to a direct action of zidovudine on mitochondrial DNA, chronic muscle ischaemia related to zidovudine-induced vascular dysfunction might be implicated at the inception of muscle damage in zidovudine myopathy.

Adult↗
PubMed1995

Fenoverine-induced rhabdomyolysis.

Fenoverine is a spasmolytic drug that inhibits calcium channel currents. We describe the clinicopathologic findings in two patients with fenoverine-induced rhabdomyolysis, of whom one died. A transient left-bundle-branch block was observed in both patients. In one case, pre-existing hepatic dysfunction may have induced accumulation of the drug. Concurrent treatment by fibrates, as observed in the second patient, may have been a predisposing factor for fenoverine-induced rhabdomyolysis. The incidence of muscular complications of fenoverine therapy could be reduced by avoidance of prescription of the drug in patients with hepatopathy or those being treated with cholesterol-lowering agents. Physicians should be aware of life-threatening adverse effects of apparently innocuous drugs.

Aged↗
PubMed1995

[Muscular involvement in HIV infection].

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

HIV Infections↗
PubMed1994

Determination of the blood lactate:pyruvate ratio as a noninvasive test for the diagnosis of zidovudine myopathy.

OBJECTIVE: To evaluate the use of the lactate: pyruvate ratio as a test for the detection of zidovudine myopathy. METHODS: Twenty consecutive human immunodeficiency virus-infected patients with muscle involvement and 20 without muscle involvement were studied prospectively. Blood lactate and pyruvate levels and serum creatine kinase levels were tested, muscle involvement was assessed both clinically and electrophysiologically, and muscle biopsy was performed in patients with myopathy. RESULTS: Nine patients had biopsy-proven zidovudine myopathy. All 9 had a high lactate:pyruvate ratio, with elevations on 2 of 2 determinations in 6 patients and on 1 of 2 in 3 patients. Two of 11 patients with other myopathies and 2 of 20 patients without myopathy had a high lactate:pyruvate ratio on 1 of 2 determinations. CONCLUSION: The lactate:pyruvate ratio, when determined repeatedly, is a sensitive test for detecting mitochondrial muscular toxicity of zidovudine.

Adult↗
PubMed1994

Uncompacted myelin lamellae in polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes syndrome. Ultrastructural study of peripheral nerve biopsy from 22 patients.

Mechanisms of peripheral neuropathies in polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes (POEMS) syndrome are poorly understood. A peripheral nerve biopsy was performed in 22 patients. Of these 9 had histological features of Castleman's disease on lymph node biopsies, and 19 had a monoclonal lambda light chain in their serum. Certain nerve fragments were paraffin embedded, others were frozen and studied by direct immunofluorescence, and others were fixed for ultrastructural examination. Paraffin-embedded fragments did not show any amyloid deposits, and at direct immunofluorescence there was no immunoglobulin fixation. At ultrastructural examination, features of uncompacted myelin lamellae (UML) were present in 19 patients, and their frequency varied from 1% to 16% of myelinated fibres. Up to now UML have been reported only in 7 patients with POEMS syndrome in the literature. UML have also been noticed in a few cases of inflammatory demyelinating polyradiculoneuritis and inherited tendency to pressure palsy.

Aged↗
PubMed1994

Expression of cytochrome c oxidase subunits encoded by mitochondrial or nuclear DNA in the muscle of patients with zidovudine myopathy.

The present study was carried out to determine whether a selective decrease of mitochondrial (mt) DNA-encoded cytochrome c oxidase (CCO) subunits occurs in zidovudine myopathy, as expected with a compound known to induce selective mtDNA depletion. Fourteen HIV-infected patients with zidovudine myopathy were studied. Thirteen had partial CCO deficiency assessed by histochemistry. Western blot analysis of CCO subunits (II/III, IV, Va, Vb, VIa, VIb, VIc, VIIa, VIIb, and VIIc) was performed on muscle biopsy samples. We evaluated the mtDNA-encoded subunits to nuclear DNA-encoded subunits ratio with the II/III to IV ratio. Patients had either a selective decrease of mtDNA-encoded CCO subunits (3 patients), or an overall decrease affecting both mtDNA-and nuclear DNA-encoded subunits (5 patients), or a normal expression of CCO subunits (6 patients). Positive correlations could not be established between the pattern of expression of CCO subunits and total zidovudine intake, degree of inflammation, and percentages of ragged-red fibers or CCO-deficient fibers. The finding of a decrease of both mtDNA- and nuclear DNA-encoded CCO subunits suggests that a factor additional to zidovudine could be implicated in the pathogenesis of the myopathy, at least in some patients. New insights into the pathogenesis of zidovudine myopathy might come from the use of more sensitive methods, including evaluation of CCO subunits in single fibers.

Adult↗