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David Lacomis

Publications and source records attributed to David Lacomis.

16 recordsLinked to original sources
PubMed2005

Neuropathy and Fabry's disease.

Fabry's disease is a multisystem disorder that is commonly associated with a painful, debilitating neuropathy. The common coexistence of arthralgias and an elevated erythrocyte sedimentation rate may lead to the misdiagnosis of a rheumatic condition. We report a 38-year-old man who was evaluated for progressive neuropathy and limb pain in the setting of longstanding arthralgias, presumed juvenile rheumatoid arthritis, and past renal transplantation. Histopathologic assessment of nerve and muscle biopsy specimens led to the diagnosis of Fabry's disease, thus allowing the patient to receive enzyme replacement therapy that may slow progression and preserve the transplanted kidney.

Adult↗
PubMed2005

Clinical utility of peripheral nerve biopsy.

Histopathologic evaluation of nerve biopsy specimens provides important diagnostic information in some patients with peripheral neuropathy. The role of nerve biopsy is more restricted than that of muscle biopsy. Nerve biopsy is utilized mainly for diagnosis of vasculitis and infiltrative neuropathies. It is also utilized in diagnosis of atypical inflammatory demyelinating neuropathies in which the clinical, electrodiagnostic, and laboratory features are inconclusive. In addition, the study of nerve histopathology can also enhance our understanding of disease pathogenesis.

Biopsy↗
PubMed2005

Proteomic profiling of cerebrospinal fluid identifies biomarkers for amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of motor neurons. We tested the hypothesis that proteomic analysis will identify protein biomarkers that provide insight into disease pathogenesis and are diagnostically useful. To identify ALS specific biomarkers, we compared the proteomic profile of cerebrospinal fluid (CSF) from ALS and control subjects using surface-enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI-TOF-MS). We identified 30 mass ion peaks with statistically significant (p < 0.01) differences between control and ALS subjects. Initial analysis with a rule-learning algorithm yielded biomarker panels with diagnostic predictive value as subsequently assessed using an independent set of coded test subjects. Three biomarkers were identified that are either decreased (transthyretin, cystatin C) or increased (carboxy-terminal fragment of neuroendocrine protein 7B2) in ALS CSF. We validated the SELDI-TOF-MS results for transthyretin and cystatin C by immunoblot and immunohistochemistry using commercially available antibodies. These findings identify a panel of CSF protein biomarkers for ALS.

Adult↗
PubMed2005

Myasthenic crisis.

Myasthenic crisis is a serious occurrence, affecting up to 27% of patients with myasthenia gravis. In the approach to the patient with myasthenic crisis, (1) the diagnosis of myasthenia gravis is confirmed; (2) respiratory failure is evaluated and treated in the intensive care unit, while potential precipitating factors are identified and managed; (3) immunomodulatory treatment is initiated; and (4) complications are avoided or managed promptly. The mortality rate should be 5% or less, with the elderly being most vulnerable.

Acute Disease↗
PubMed2004

Anti-signal recognition particle autoantibody in patients with and patients without idiopathic inflammatory myopathy.

OBJECTIVE: To determine the long-term outcome and associated clinical, serologic, and pathologic features in a cohort of patients with connective tissue disease (CTD) and the anti-signal recognition particle (anti-SRP) autoantibody. METHODS: Sera and clinical data were collected prospectively from consecutive adult patients with polymyositis (PM; n = 134), dermatomyositis (n = 129), or other CTDs (predominantly systemic sclerosis [SSc; n = 790]). Patients were first evaluated during 1973-2001. RESULTS: Nineteen patients with the anti-SRP autoantibody were identified, 16 (84%) of whom had pure PM and 3 (2 with SSc and 1 with antisynthetase syndrome) had yet to develop features of myositis after a mean followup of 4.5 years (range 2.5-6 years). More SRP-positive PM patients had severe proximal muscle weakness (50%) and muscle atrophy (67%) at initial presentation compared with antisynthetase-positive PM controls. Cardiac involvement occurred in only 2 of 16 SRP-positive PM patients (13%), and interstitial lung disease was noted in 3 of 13 SRP-positive PM patients (23%) and in the 3 SRP-positive nonmyositis patients. There was a relative lack of inflammation in muscle biopsy specimens from the SRP-positive PM cohort. Other autoantibodies in the SRP-positive patients included Ro/SSA (4 patients), Th/To (1 patient), and anti-PL-12 (1 patient). Survival in the SRP-positive PM patients was comparable with that seen in the cohort of SRP-negative PM patients. CONCLUSION: The anti-SRP autoantibody is not specific for PM. Severe muscle weakness and atrophy were prominent features in PM patients with anti-SRP. Cardiac involvement was less common and survival was better in patients with anti-SRP than has previously been reported.

Adult↗
PubMed2004

The utility of muscle biopsy.

Despite major advances in molecular genetics, histopathologic evaluation of muscle biopsy specimens continues to provide important diagnostic information in patients with suspected muscle diseases and in patients with vasculitic neuropathies. Muscle biopsy specimens are used in diagnosing many inherited as well as inflammatory and toxic myopathies. Furthermore, the study of muscle histopathology can also enhance our understanding of disease pathogenesis.

Biopsy↗
PubMed2003

Protective effect of HSV-mediated gene transfer of nerve growth factor in pyridoxine neuropathy demonstrates functional activity of trkA receptors in large sensory neurons of adult animals.

The distinct distribution of trkA receptors on small neurons and trkC receptors on large neurons in the dorsal root ganglion correlates with the dependence of these two classes of neurons on nerve growth factor and neurotrophin-3, respectively, for survival during development. In adult animals, the distribution of high affinity neurotrophin (trk) is complex and overlapping; neurotrophins are not required for cell survival, but may influence cell phenotype and the response to injury. In order to test the functional activity of trkA receptors in the sensory ganglia of adult animals in vivo, we examined the ability of a nerve growth factor-expressing recombinant replication-defective herpes simplex virus-based vector to prevent the selective degeneration of large sensory fibres caused by intoxication with pyridoxine. Transduction of dorsal root ganglion neurons in vivo by subcutaneous inoculation of the nerve growth factor-expressing vector prevented the development of pyridoxine-induced neuropathy measured by electrophysiological, morphological and behavioural measures. These results demonstrate a functional activity of trkA receptors expressed on large neurons in the dorsal root ganglion in mature animals; this observation has important implications for the choice of neurotrophic factors for treatment of peripheral nerve disease.

Animals↗
PubMed2002

Chronic eosinophilic perimyositis with persistent myalgias.

A 43-year-old man with an 8-year history of hypereosinophilia was evaluated for persistent muscle pain. Methotrexate and corticosteroids were ineffective. Examination, limited by pain even with passive motion, showed only mild weakness. Electromyography and muscle enzymes were normal. A needle muscle biopsy specimen revealed eosinophilic perimyositis. This case illustrates that the diagnosis of eosinophilic perimyositis requires histopathological evaluation, which should be pursued in patients with eosinophilia and persistent myalgia despite normal electromyography and muscle enzymes.

Adult↗
PubMed2002

Small-fiber neuropathy.

Small-fiber neuropathy is a common disorder. It is often "idiopathic" and typically presents with painful feet in patients over the age of 60. Autoimmune mechanisms are often suspected, but rarely identified. Known causes of small-fiber neuropathy include diabetes mellitus, amyloidosis, toxins, and inherited sensory and autonomic neuropathies. Occasionally, small-fiber neuropathy is diffuse or multifocal. Depending on the type of small-fiber neuropathy, autonomic dysfunction can be significant or subclinical. Diagnosis is made on the basis of the clinical features, normal nerve conduction studies, and abnormal specialized tests of small-fiber function. These specialized studies include assessment of epidermal nerve fiber density as well as sudomotor, quantitative sensory, and cardiovagal testing. The sensitivities of these tests range from 59-88%. Each has certain advantages and disadvantages, and the tests may be complementary. Unless an underlying disease is identified, treatment is usually directed toward alleviation of neuropathic pain.

Humans↗
PubMed2002

Critical illness myopathy.

Acute myopathy is a common problem in intensive care units. Those at highest risk for developing critical illness myopathy are exposed to intravenous corticosteroids and paralytic agents during treatment of various illnesses. Diffuse weakness and failure to wean from mechanical ventilation are the most common clinical manifestations. Serum creatine kinase levels are variable. Electrodiagnostic studies reveal findings of a myopathic process, often with evidence of muscle membrane inexcitability. Based on animal model studies, the loss of muscle membrane excitability may be related to inactivation of sodium channels at the resting potential. In addition, human and animal pathologic studies reveal characteristic loss of myosin with relative preservation of other structural proteins. In some patients, there is also upregulation of proteolytic pathways, involving calpain and ubiquitin, in conjunction with increased apoptosis. Fortunately, the disorder is reversible, but there may be considerable morbidity.

Creatine Kinase↗
PubMed2002

Electrodiagnostic approach to the patient with suspected myopathy.

Uncovering the cause of a suspected myopathy may be challenging. However, a careful approach starts with utilizing the wealth of available information regarding the clinical and laboratory features of myopathy. Electrodiagnostic testing is then obtained (in most cases). Recognition of the pattern of EMG findings in light of the clinical and laboratory features should narrow the differential diagnosis and dictate the next steps in the evaluation. Histopathologic or molecular studies, or both may follow. Ultimately, this approach usually allows the clinician to make the correct diagnosis.

Action Potentials↗
PubMed2002

Herpes simplex-mediated gene transfer of nerve growth factor protects against peripheral neuropathy in streptozotocin-induced diabetes in the mouse.

Peripheral neuropathy is a common and debilitating complication of diabetes. In animal models, neurotrophic factors can prevent progression of the neuropathy, but adverse effects prevent systemic administration in adequate doses to treat human disease. We examined whether gene transfer with replication-defective genomic herpes simplex virus (HSV) vectors modified to express nerve growth factor (NGF) could be used to prevent progression of neuropathy in mice. Diabetes induced by streptozotocin (STZ) resulted in a sensory neuropathy manifest by a decrease in the foot sensory nerve amplitude (FSA; control = 20 +/- 0.1 microV, treated = 14 +/- 0.1 microV). Transduction of dorsal root ganglia in vivo with an HSV-based vector expressing NGF under the control of the human cytomegalovirus immediate early promoter (vector SHN) or the HSV latency active promoter 2 (vector SLN) by footpad inoculation 2 weeks after STZ administration protected against the decrease in FSA (22 +/- 1.4 microV and 21 +/- 1.7 microV, respectively) measured 4 weeks later. Injection of SHN into inguinal adipose tissue 2 weeks after onset of diabetes also prevented the decrease in FSA (20 +/- 3.3 microV). These results suggest that gene transfer with an NGF-producing herpes-based vector may prove useful in the treatment of diabetic neuropathy.

Animals↗