[Deafness, diabetes and cancer: chance association or etiological link?].
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Colonic Pseudo-Obstruction↗
Biomedical subjects
J M Mussini
Publications and source records attributed to J M Mussini.
Peripheral neuropathy during stavudine-didanosine antiretroviral therapy.
Peripheral neuropathy (PN) is among the most frequent side effects described with nucleoside reverse transcriptase inhibitors (NRTIs). We investigated the incidence, evolution and predictive factors of PN during stavudine (d4T)-didanosine (ddI) combination therapy in 65 HIV infected patients, previously treated with zidovudine and/or zalcitabine (ddC) for at least 3 months. A subset of 16 patients was referred for systematic electromyographic examination at weeks 0 and 24: six among the 16 exhibited nerve conduction abnormalities at day 0, probably related to previous ddC treatment in four of those and to HIV infection in the other two, with worsening of abnormalities in one patient at week 24. In total, seven of the 59 assessable patients (11.8%) exhibited grade 2-3 neuropathy, with a median time of occurrence of 17 weeks. Distal, symmetrical paraesthesias of the extremities were the first symptoms in all the patients; none had motor symptoms. In all the patients, PN resolved rapidly after stopping d4T. There were no statistically different parameters between the seven cases and the other 52 patients according to CD4 T cells, HIV RNA, Centers for Disease Control and Prevention (CDC) stage C or d4T daily dose. In our study, the d4T-ddI combination did not seem to increase the incidence of PN; risk factors for PN could not be identified, probably in part because of the low number of patients with PN.
Adult↗
[Macrophagic myofasciitis. Study and Research Group on Acquired and Dysimmunity-related muscular diseases (GERMMAD)].
UNLABELLED: MACROPHAGIC MYOFASCIITIS: A most unusual inflammatory myopathy, first described by Germmad had been reported with increasing frequency since 1993 in the leading French myopathology centers. We present our experience with this new disease: macrophagic myofasciitis. CLINICAL FEATURES: By November 1999, 70 cases of macrophagic myofasciitis had been recorded since our first description. The first 22 patients (sex ratio M/F = 1:3) referred with the presumptive diagnosis of polymyositis (n = 11), polymyalgia rheumatica (n = 5), mitochondrial cytopathy (n = 4), and congenital myopathy or muscle dystrophy (n = 1 each). Symptoms included myalgia (91%), anthralgia (68%), marked asthenia (55%), muscle weakness (45%), and fever (32%). LABORATORY FINDINGS: Abnormal laboratory findings included elevated CK levels (50%), markedly increased erythrocyte sedimentation rate (37%), and myopathic EMG (35%). Muscle biopsy showed a unique myopathological pattern characterized by: i) centripetal infiltration of epimysium, perimysium and perifascicular endomysium by sheets of large cells of the monocyte/macrophage lineage (CD68+, CD1a-, S100-, with a PAS-positive content; ii) absence of necrosis, of both epithelioid and giant cells, and of mitotic figures; iii) presence of occasional CD8+ T-cells; iv) inconspicuous muscle fiber damage. The picture was easily distinguishable from sarcoid myopathy and fasciitis-panniculitis syndromes. The infectious diseases know to be associated with reactive histiocytes, including Whippleís disease, Mycobacterium avium intracellulare infection and malakoplakia, could not be documented. Patients improved under corticosteroid therapy and/or immunomodulatory therapeutic CONCLUSION: A new inflammatory muscle disorder, characterized by a distinctive pathological pattern of macrophagic myofasciitis is emerging in France.
Adult↗
Chester-Erdheim disease: a neoplastic disorder.
Chester-Erdheim disease is a rare non-langerhans cell histiocytosis characterized by a xanthomatous infiltration of foamy macrophages. The cause and pathogenesis remain unclear. The aim of the present study was to determine whether Chester-Erdheim disease is a polyclonal reactive disease or a clonal neoplastic disorder. The clonal status of samples obtained from five patients with Chester-Erdheim disease was studied. DNA was extracted from fixed and paraffin-embedded sections after microdissection and clonal status was studied using the Xchromosome inactivation pattern of the human androgen receptor gene (HUMARA assay). One patient was homozygous for the HUMARA gene and noninformative. Three other cases were monoclonal. One was polyclonal, and this case showed a dense reactive infiltrate in association with spumous macrophages. This study suggests strongly that Chester-Erdheim disease is a monoclonal lesion consistent with neoplastic disorder. Thus, Chester-Erdheim disease may be considered as the "macrophage" counterpart of Langerhan's cell histiocytosis in the histiocytosis spectrum. Further studies are needed to establish the origin of this clonal proliferation.
Adult↗
[Macrophagic myofasciitis: description and etiopathogenic hypotheses. Study and Research Group on Acquired and Dysimmunity-related Muscular Diseases (GERMMAD) of the French Association against Myopathies (AFM)].
PURPOSE: A new type of inflammatory myopathy of unknown etiology has recently been described in France. The myopathy, called macrophagic myofasciitis, had never been described in the literature. METHODS: In December 1998, 35 cases of macrophagic myofasciitis were reported, showing an increase in its incidence since the description of the first case in 1993. The first 22 cases are described. RESULTS: The 22 patients were each referred with a presumptive diagnosis of either polymyositis (11 patients), polymyalgia rheumatica (5 patients), mitochondrial cytopathy (4 patients), or congenital myopathy or muscle dystrophy (1 patient for each). Clinical symptoms included myalgias (91%), arthralgias (68%), marked asthenia (55%), muscle weakness (45%), and fever (32%). Laboratory findings included elevated CK levels (50%) and a marked increased in the erythrocyte sedimentation rate (37%). Electromyographic recordings showed the existence of myopathy (35%). Muscle biopsy showed a unique pattern characterized by: (i) centripetal infiltration of the epimysium, perimysium and perifascicular endomysium by non epitheloid, cells of the monocyte/macrophage lineage (CD68+, CD1a-, S100-) with both large cytoplasm and PAS-positive content; (ii) absence of necrosis, of both epithelioid and giant cells, and of mitotic figures; (iii) occasional CD8+ T-cells; and, (iiii) minimal myocyte suffering. The disease symptoms were easily distinguishable from those of sarcoid myopathy and fasciitis-panniculitis syndromes. Infectious diseases known to be associated with reactive histiocytosis, including Whipple's disease, Mycobacterium avium intracellulare infection and malakoplakia, could not be documented. Patients' condition improved under corticosteroid therapy, associated or not with non-specific antibiotic therapy. CONCLUSION: A new inflammatory muscle disorder of unknown etiology, characterized by a distinctive pathological pattern of macrophagic myofasciitis, is emerging in France. Diagnosis is based on muscular biopsy. Numerous clinical, epidemiological and etiopathologic studies initiated by the GERMMAD (Groupe d'études et de recherche sur les maladies musculaires acquises) are in progress.
Adult↗
Macrophagic myofasciitis: an emerging entity. Groupe d'Etudes et Recherche sur les Maladies Musculaires Acquises et Dysimmunitaires (GERMMAD) de l'Association Française contre les Myopathies (AFM).
BACKGROUND: An unusual inflammatory myopathy characterised by an infiltration of non-epithelioid histiocytic cells has been recorded with increasing frequency in the past 5 years in France. We reassessed some of these cases. METHODS: We did a retrospective analysis of 18 such cases seen in five myopathology centres between May, 1993, and December, 1997. The myopathological changes were reassessed at a clinopathology seminar. FINDINGS: Detailed clinical information was available for 14 patients. The main presumptive diagnoses were polymyositis and polymyalgia rheumatica. Symptoms included myalgias in 12 patients, arthralgias in nine, muscle weakness in six, pronounced asthenia in five, and fever in four. Abnormal laboratory findings were occasionally observed, and included raised creatine kinase concentrations, increased erythrocyte sedimentation rate, and myopathic electromyography. Muscle biopsy showed infiltration of the subcutaneous tissue, epimysium, perimysium, and perifascicular endomysium by sheets of large macrophages, with a finely granular PAS-positive content. Also present were occasional CD8 T cells, and inconspicuous muscle-fibre damage. Epithelioid and giant cells, necrosis, and mitotic figures were not seen. The images were easily distinguishable from sarcoid myopathy and fasciitis-panniculitis syndromes. Whipple's disease, Mycobacterium avium intracellulare infection, and malakoplakia could not be confirmed. Ten patients were treated with various combinations of steroids and antibiotics; symptoms improved in eight patients, and stabilised in two. INTERPRETATION: A new inflammatory muscle disorder of unknown cause, characterised by a distinctive pathological pattern of macrophagic myofasciitis, is emerging in France.
Adult↗
Treatment of graft-versus-host disease by extracorporeal photochemotherapy: a pilot study.
BACKGROUND: Graft-versus-host disease (GVHD) is a major complication after bone marrow transplantation, which may be refractory to immunosuppressive drugs. As preliminary case reports suggested that extracorporeal photochemotherapy (ECP) using a Therakos device might be beneficial, we conducted a pilot study to assess the efficacy and safety of a new ECP method that does not require administration of 8-methoxypsoralen (8-MOP) to the patient. METHODS: ECP was performed three times a week for 3 weeks and then tapered according to the patient's course. Soluble 8-MOP was added ex vivo to an enriched mononuclear cell suspension obtained by a cell separator. This cellular suspension was then ultraviolet A irradiated and reinfused into the patient. Evaluation was performed using specific objective tests depending on clinical conditions. RESULTS: The two patients in the study with acute GVHD and severe liver dysfunction resistant to steroid pulse showed no improvement with ECP treatment. The five patients with chronic GVHD (c-GVHD) had the following clinical features: three patients had myositis and two patients had severe cutaneous c-GVHD, including one patient with sclerodermoid lesions, one with bronchiolitis obliterans, one with bronchitis, and one with liver involvement. Immunosuppressive drugs were either prohibited or ineffective. The number of procedures for each patient ranged from 13 to 30. Cytapheresis required the use of a double-lumen catheter (4/5) or an arteriovenous fistula (1/5). No side effects were related to 8-MOP or ultraviolet A irradiation. Four of five patients improved after ECP; one patient with bronchiolitis obliterans, a fibrotic condition, remained stable. CONCLUSIONS: ECP treatment may be helpful for the treatment of severe c-GVHD and the avoidance of increased immunosuppression.
Acute Disease↗
Neurotoxicological assessment after intracisternal injection of liposomal bupivacaine in rabbits.
UNLABELLED: Experiments were performed on rabbits randomly assigned to intracisternally receive 0.3 mL of plain bupivacaine 5 mg/mL, liposomal bupivacaine 5 mg/mL, bupivacaine-free liposomes, or isotonic phosphate-buffered saline. Mechanical ventilation was initiated or intravenous dopamine was infused when respiratory depression or hypotension occurred. Seven days after the injection, the whole spinal cord was removed and histopathologic characteristics were studied on transverse sections. All preparations were devoid of phosphatidylcholine hydrolysis or oxidation compounds. Solutions without bupivacaine produced transient irritative signs that required sedation in most rabbits. Despite the similar duration of respiratory depression in groups receiving liposomal or plain bupivacaine, liposomes produced significantly prolonged motor blockade (126 vs 70 min). Correction of hypotension after plain bupivacaine required a longer dopamine infusion and larger doses than after liposomal bupivacaine (28 vs 18 min and 74 vs 47 mg). Necrosis was observed in the cervical area of two rabbits (one in the liposomal bupivacaine group and another in the phosphate buffer group). No demyelinated areas were noted in spinal cord examinations. We conclude that liposomal bupivacaine leads to a less severe sympathetic block and to a prolonged motor block, whereas histologic changes are not significantly different among groups. IMPLICATIONS: Multilamellar liposomes containing bupivacaine administered intracisternally to rabbits produce spinal cord histopathologic changes not significantly different from those observed with plain bupivacaine. Sustained release of bupivacaine from liposomes is suggested by the prolonged motor blockade and the reduced severity of arterial hypotension. Use of these liposomes could prolong the local anesthetic effects of bupivacaine.
Anesthetics, Local↗
A prospective study of criteria for the diagnosis of toxoplasmic encephalitis in 186 AIDS patients. The BIOTOXO Study Group.
OBJECTIVE: To define the factors associated with diagnosis of toxoplasmic encephalitis (TE) in AIDS patients; and to establish a rational procedure for the clinician faced with a decision concerning empiric antitoxoplasma therapy. DESIGN: A 15-month prospective multicentre cohort study in France. METHODS: One hundred and eighty-six consecutive HIV-positive inpatients undergoing empiric antitoxoplasma therapy for a first episode of presumed TE were monitored. The clinician's initial estimation of the probability of response to antitoxoplasma therapy was recorded. In addition, a validation committee classified cases as TE or non-TE. RESULTS: Among the 186 patients, the following variables were significantly more frequent in TE (n = 113) than non-TE (n = 73) patients: fever (59% versus 40%). headache (55% versus 33%), seizures (22% versus 11%), suggestive lesions on the brain scan (98% versus 76%), positive Toxoplasma serology (97% versus 71%). Median CD4+ lymphocyte count was significantly higher in TE than in non-TE (27 x 10(6)/l versus 11 x 10(6)/l). The rate of TE in patients on systemic antiprotozoal prophylaxis at entry was 43% as compared with 75% in patients without previous prophylaxis. Pre-therapy estimation of response to empiric therapy was highly correlated with final diagnosis. Multivariate logistic regression analysis showed that the following variables contributed independently to the diagnosis of TE: clinician's estimation of response to treatment at entry > 75%; absence of systemic antiprotozoal prophylaxis; seizures; headache; suggestive lesions on CT or MRI brain scan; and positive Toxoplasma serology. CONCLUSIONS: A linear logistic model is proposed which uses significant variables, which are readily available. This model gives good accuracy to classify suspected cases of TE.
AIDS-Related Opportunistic Infections↗
Pathology of the central nervous system in Chester-Erdheim disease: report of three cases.
Chester-Erdheim disease is a rare form of non-Langerhans cell histiocytosis consisting of disseminated xanthogranulomatous infiltration and fibrosis that primarily involves the bones, visceral organs and systemic fatty spaces. Involvement of the central nervous system is variable, and neuropathological features have seldom been documented. We report the neuropathological findings in 3 autopsy cases. One patient had radiological and pathological bone changes characteristic of Chester-Erdheim disease. Neuropathology revealed multiple characteristic xanthogranulomas disseminated in the cerebral hemispheres, hypothalamus, cerebellum, and brainstem. The second patient presented first with cutaneous lesions characteristic of Langerhans cell histiocytosis. She subsequently developed bone abnormalities suggestive of Chester-Erdheim disease, which was confirmed by autopsy, raising the possibility of a common spectrum of histiocytosis including both diseases. Gross examination of the brain was normal, however, microscopy showed infiltration of the brain by characteristic non-Langerhans cell xanthogranulomas. The third patient presented with systemic features characteristic of Chester-Erdheim disease. Neurological signs included gait disturbance, seizures and confusion. Examination of the brain did not show any histiocytic infiltration, but did show changes suggestive of Hallervorden-Spatz syndrome. Association of Chester-Erdheim disease and Hallervorden-Spatz syndrome has not been previously reported. The relationship between both conditions is unclear.
Adult↗
Enalapril-induced vasculitis resembling rheumatoid arthritis, lupus, sicca syndrome, and giant cell arteritis.
We report a case of vasculitis in a 67-year-old woman who successively developed over a four-month period clinical manifestations suggestive of rheumatoid arthritis, lupus, sicca, syndrome and finally giant cell arteritis. All her symptoms resolved promptly upon discontinuation of enalapril and none recurred over the five-year follow-up period. The only residual manifestation is Jaccoud's arthropathy of the hands.
Aged↗
[Cutaneous and neurologic vasculitis disclosing EBV-selective immunodeficiency].
INTRODUCTION: Purtilo's syndrome or X-linked lymphoproliferative syndrome (XLP) is a rare genetic disorder affecting boys who have a selective immunodeficit towards Epstein Barr Virus (EBV) and who develop extremely severe forms of EBV infection, of which there are four major types: severe or fatal infectious mononucleosis (60 p. 100), lymphoma (23 p. 100), acquired hypo- or agamaglobulinemia (25 p. 100) and anemia or pancytopenia. We report a case of vasculitis (cutaneous and neurologic) which led to the discovery of a selective immunodeficit towards EBV, similar to Purtilo's syndrome. CASE REPORT: A 17 year-old male with no significant past medical history presented with an eruption initially felt to be consistent with pityriasis lichenoid. Treatment with erythromycin was initiated, this did not prevent the subsequent eruptions of cutaneous vasculitis lesions which were severe, prolonged, debilitating, and associated with fever and general deterioration of the patient condition. All etiologic studies were negative. A course of systemic corticosteroids was begun, but the cutaneous eruptions persisted; and in addition the patient developed signs of polyneuropathy in the lower extremities secondary to neurologic vasculitic lesions. New studies revealed an abnormal EBV serology (absence of anti-EBNA antibodies) as well as hypogammaglobulinemia, suggestive of a selective immunodeficit towards EBV resembling Purtilo's syndrome. DISCUSSION: In our patient, the development of an extensive vasculitis, characterized histologically by an intense lymphocytic infiltrate, positive for EBV, associated with hypogammaglobulinemia, and with abnormal serology suggests an anomaly in the immune response to EBV. Although the age of the patient and absence of family history make the Purtilo's syndrome uncertain, the nature of the immunodeficit is very similar and the patient could well develop a lymphoma. This case is significant in that the disease initially manifested itself as a cutaneous vasculitis, which was not been described previously.
Adolescent↗
[Guillain-Barré syndrome in Horton disease].
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Aged↗
[Cerebral atrophy of vascular origin in the course of neurofibromatosis].
The authors report the case of a 39-year-old woman with type I neurofibromatosis who presented a right incomplete proportional hemiplegia which progressively worsened over a 6-month period. Left hemispheric atrophy with heterogeneous features, predominant in the temporoparietal region, was revealed by computerized tomography. Atrophy was associated with diffuse vascular lesions in the distal part of the left sylvian and anterior cerebral arteries, leading to major cortical hypoperfusion. Vascular examination showed no hypertension nor any sign of arterial involvement in another region. This case illustrates the nature of vasculopathy associated with neurofibromatosis. Its expression is polymorphous, with lesions inducing stenosis (the most common ones), aneurysmal lesions or veritable angiodysplasias (either hypo- or hyperplastic). The vascular expression of neurofibromatosis is often overlooked. However, in the presence of an inexplicable occlusive or aneurysmal vasculopathy, it is advisable to search for signs of neurofibromatosis since ill-defined forms exist.
Adult↗
Is ketamine or its preservative responsible for neurotoxicity in the rabbit?
BACKGROUND: Although ketamine has been administered spinally in humans, previous neurotoxicity studies have shown that it can induce spinal cord lesions in various animal models. The aim of this work was to evaluate by histologic and blood-brain barrier studies whether different components of the commercial ketamine solution might be responsible for the microscopic lesions observed. METHODS: Forty white New Zealand rabbits were randomly assigned to four groups of 10. One-percent preservative-free ketamine (0.3 ml), 1% d-ketamine, 0.05% chlorobutanol, and 1% lidocaine were intrathecally injected through the atlantooccipital membrane. Laminectomy was performed on day 8, and the dura was preserved using paraformaldehyde-glutaraldehyde fixative. Light and fluorescence microscopy were performed on transverse spinal cord sections by a neuropathologist unaware of injected agents used. Specimens were then graded as normal or abnormal as compared with a control group receiving lidocaine. RESULTS: Isomers of ketamine did not induce spinal cord lesions in either study, but chlorobutanol (the preservative used in the ketamine solution) induced significant severe spinal cord lesions in both studies. CONCLUSIONS: The appearance of spinal cord lesions after intrathecal chlorobutanol strongly suggests that this preservative is responsible for apparent toxicity of ketamine and therefore should not be used in any solution intrathecally injected into humans.
Animals↗
Acute lymphoblastic leukemia associated with dermatomyositis in a child.
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Adolescent↗
Degeneration and subsequent regeneration of mouse skeletal muscle after a single injection of chlorpromazine: changes in mitochondrial calmitine and calcium content.
We studied experimental models capable of showing muscle degeneration and subsequent regeneration and observed the changes in calmitine, calcium uptake and calcium concentration in mitochondria during these processes. The results presented here are based on the study of mitochondria of mouse skeletal muscle after a single intramuscular injection of chlorpromazine. This drug induces myotoxic effects followed by muscle regeneration. Our results show that the muscle degeneration process, as shown by histological studies, was associated with some changes in mitochondria: a decrease in calmitine, a calcium overload and a decrease in calcium uptake; the subsequent regeneration process was associated with an increase in calmitine, a decrease in calcium concentration and an increase in calcium uptake, these 3 parameters returning to normal values. It seems that there is a correlation between a decrease in calmitine and muscle degeneration, and an increase in calmitine and muscle regeneration, as shown by our biochemical and histological observations.
Animals↗
Ketamine and midazolam neurotoxicity in the rabbit.
Ketamine and midazolam can produce analgesia following intrathecal administration in rabbits. However, neurotoxicity studies are required before these agents can be considered safe for clinical use. The aim of this study was to evaluate by histologic and blood-brain barrier (BBB) studies whether ketamine or midazolam could be used as an alternative to local anesthetics or opioids to produce spinal analgesia. Forty white New Zealand rabbits were randomly assigned to four groups of 10. In the conscious animal, 0.3 ml 0.9% saline solution, 1% lidocaine, 1% ketamine, or 0.1% midazolam was intrathecally injected intracisternally using a modification of the technique of Yaksh et al. Light and fluorescence microscopy were performed on transverse spinal cord sections by a neuropathologist unaware of the administered agents. All spinal cord section slides were scored within four zones: upper cervical, lower cervical, median thoracic, and lumbar segments. Spinal cord homogeneous lesions with higher scores than those of lidocaine-treated animals were considered abnormal. The BBB study showed evidence of neurotoxicity for ketamine, whereas light microscopy indicated no significant differences in comparison with saline and lidocaine. Midazolam-treated rabbits showed significant changes in both BBB and light microscopy studies. In view of these results, the intrathecal use of midazolam should be avoided in humans. Lesions observed following ketamine suggest the need for further experimental studies of the solvent and different ketamine enantiomers to establish definitively the safety of intrathecal free ketamine in humans.
Animals↗