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Biomedical subjects

W S David

Publications and source records attributed to W S David.

17 recordsLinked to original sources
PubMed2003

A randomized, placebo-controlled trial of topiramate in amyotrophic lateral sclerosis.

OBJECTIVE: To determine if long-term topiramate therapy is safe and slows disease progression in patients with ALS. METHODS: A double-blind, placebo-controlled, multicenter randomized clinical trial was conducted. Participants with ALS (n = 296) were randomized (2:1) to receive topiramate (maximum tolerated dose up to 800 mg/day) or placebo for 12 months. The primary outcome measure was the rate of change in upper extremity motor function as measured by the maximum voluntary isometric contraction (MVIC) strength of eight arm muscle groups. Secondary endpoints included safety and the rate of decline of forced vital capacity (FVC), grip strength, ALS functional rating scale (ALSFRS), and survival. RESULTS: Patients treated with topiramate showed a faster decrease in arm strength (33.3%) during 12 months (0.0997 vs 0.0748 unit decline/month, p = 0.012). Topiramate did not significantly alter the decline in FVC and ALSFRS or affect survival. Topiramate was associated with an increased frequency of anorexia, depression, diarrhea, ecchymosis, nausea, kidney calculus, paresthesia, taste perversion, thinking abnormalities, weight loss, and abnormal blood clotting (pulmonary embolism and deep venous thrombosis). CONCLUSIONS: At the dose studied, topiramate did not have a beneficial effect for patients with ALS. High-dose topiramate treatment was associated with a faster rate of decline in muscle strength as measured by MVIC and with an increased risk for several adverse events in patients with ALS. Given the lack of efficacy and large number of adverse effects, further studies of topiramate at a dose of 800 mg or maximum tolerated dose up to 800 mg/day are not warranted.

Adult↗
PubMed2000

Myoglobinuria.

Myoglobinuria refers to an abnormal pathologic state in which an excessive amount of myoglobin is found in the urine, imparting a cola-like hue, usually in association with myonecrosis and a clinical picture of weakness, myalgias, and edema. Myoglobinuria is produced by multiple causes: any condition that accelerates the use or interferes with the availability of oxygen or energy substrates to muscle cells can result in myoglobinuria, as can events that produce direct muscle injury, either mechanical or chemical. Acute renal failure is the most serious complication, which can be prevented by prompt, aggressive treatment. In patients surviving acute attacks, recovery of muscle and renal function is usually complete.

Biopsy↗
PubMed1999

Confirmation of linkage of hereditary partial lipodystrophy to chromosome 1q21-22.

Familial lipodystrophy is a genetically heterogeneous set of disorders characterized by a total or partial absence of subcutaneous fat, diabetes mellitus or impaired glucose tolerance, hyperlipidemia, and hypermetabolism [Senior and Gellis, 1964]. One subtype, familial partial lipodystrophy Dunnigan (FPLD), is a rare autosomal dominant trait that results in an gradual loss of subcutaneous fat in the lower trunk and limbs, Type V hyperlipoproteinemia, hypertriglyceridemia, and insulin-resistant diabetes. Previous reports of this condition have been limited to case reports or very small families. Recently, Peters et al. reported on linkage of five families of Western European descent to a 5.3 cM region on chromosome 1q21-22 between the flanking markers D1S305 and D1S1600 [Peters et al., 1998: Nat Genet 18:292-295]. We performed linkage and haplotype analysis using highly polymorphic, microsatellite markers on a large, multigeneration Caucasian kindred of German ancestry. The maximum two-point lod score achieved was 4.96 at theta(max) = 0 for marker D1S2721. Multipoint analysis gave an overall maximum lod score of 6.27 near marker D1S2721. The results of the haplotype analysis support the minimal candidate region as reported by Peters et al.

Adult↗
PubMed1999

Hyperlipidemia and neuropathy.

Detailed histories/physical examinations (n = 47) and nerve conduction studies (n = 34) were performed in a large kindred with congenital partial lipodystrophy (CPL) in an effort to evaluate the association of hyperlipidemia and neuropathy. CPL, in the absence of diabetes, did not predispose to either focal mononeuropathy or generalized polyneuropathy, and the likelihood of either did not correlate with the degree of cholesterol or triglyceride elevation. This study does not provide support for an association between neuropathy and hyperlipidemia.

Adolescent↗
PubMed1998

EMG findings in acute myopathy with status asthmaticus, steroids and paralytics. Clinical and electrophysiologic correlation.

We have reviewed the clinical and electrophysiologic features of eleven mechanically ventilated patients with asthma who developed persistent weakness following treatment with neuromuscular blocking agents and corticosteroids. All patients had electrophysiologic findings consistent with a myopathic process and no evidence of a neuromuscular transmission disorder or generalized neuropathy. Electrophysiologic improvement paralleled clinical improvement. The severity of the initial electrophysiologic findings did not predict the subsequent rate of recovery. All patients showed substantial recovery (to functional independence) over the first month.

Adrenal Cortex Hormones↗
PubMed1997

Polysomnographic studies in amyotrophic lateral sclerosis.

We retrospectively reviewed 17 polysomnograms (PSG) in symptomatic amyotrophic lateral sclerosis (ALS) patients to assess the type and frequency of sleep disordered events and correlated these findings with pulmonary function tests (PFTs), presenting complaints, presence of bulbar dysfunction, and response to bi-level positive airway pressure (PAP) treatment. PSG revealed abnormalities in 16 patients. Complaints of orthopnea, daytime sleepiness (but not morning headaches) and a low negative inspiratory force (NIF) correlated with sleep disruption. However, neither the forced vital capacity (FVC) nor the NIF reliably predicted any specific PSG finding. Twelve of 13 patients treated with bi-level PAP responded favorably. Since the response to bi-level PAP is frequently gratifying, PSG should strongly be considered in ALS patients with suspected sleep disturbances.

Adolescent↗
PubMed1996

Nonsystemic vasculitic mononeuropathy multiplex, cryoglobulinemia, and hepatitis C.

A 39-year-old man developed sequential acute mononeuropathies involving both median, both ulnar, and the right radial and left peroneal nerves. Electrophysiology demonstrated an asymmetric sensorimotor axonal polyneuropathy; nerve biopsy confirmed a vasculitis. Laboratory evaluation revealed a mixed cryoglobulinemia and active hepatitis C infection. The patient stabilized with prednisone/cyclophosphamide/interferon-alpha. Hepatitis C should be considered in the differential diagnosis of mononeuropathy multiplex. Accurate diagnosis is important, as interferon-alpha may prevent transition to chronic hepatitis/cirrhosis.

Adult↗
PubMed1996

Spasmodic dysphonia symptoms as initial presentation of amyotrophic lateral sclerosis.

A patient initially diagnosed with adductor-type spasmodic dysphonia was referred for botulinum toxin (Botox) injections, but found on subsequent evaluation to have amyotrophic lateral sclerosis, and therefore Botox was not administered. This unique case underscores the need to delay botulinum toxin treatments in any patient with recent onset symptoms, and to obtain thorough motor speech and voice, otolaryngologic, and neurologic evaluation in all patients prior to consideration for injection.

Aged↗
PubMed1996

Muscle weakness in mechanically ventilated patients with severe asthma.

Patients who undergo mechanical ventilation for severe asthma are at risk of developing diffuse muscle weakness because of acute myopathy. The relative importance of corticosteroids and neuromuscular paralysis in causing the myopathy is controversial, and it is uncertain whether the chemical structure of the drug used to induce paralysis influences the risk of myopathy. Using a retrospective cohort study design, we evaluated 107 consecutive episodes of mechanical ventilation for severe asthma to assess (1) the incidence of clinically significant weakness in patients treated with corticosteroids alone versus corticosteroids with neuromuscular paralysis, (2) the influence of the duration of paralysis on the incidence of muscle weakness, and (3) the relative risk of weakness in patients paralyzed with the nonsteroidal drug atracurium versus an aminosteroid paralytic agent (pancuronium, vecuronium). The use of corticosteroids and a neuromuscular blocking agent was associated with a much higher incidence of muscle weakness as compared with the use of corticosteroids alone (20 of 69 versus O of 38, p < 0.001). The 20 weak patients were paralyzed significantly longer than the 49 patients who received a neuromuscular blocking agent without subsequent weakness (3.4 +/- 2.4 versus 0.6 +/- 0.7 d, p < 0.001). Eighteen of the 20 weak patients had been paralyzed for more than 24 h. The incidence of weakness was not reduced when paralysis was achieved with atracurium as opposed to an aminosteroid neuromuscular blocking agent. In conclusion, corticosteroid-treated patients with severe asthma who undergo prolonged neuromuscular paralysis are at significant risk for the development of muscle weakness, and the risk of weakness is not reduced by use of atracurium.

Acute Disease↗
PubMed1994

Electromyography and biopsy correlation with suggested protocol for evaluation of the floppy infant.

Eighty infants with nonarthrogrypotic floppy infant syndrome (FIS) were evaluated between 1979 and 1990. Electromyographic data were correlated with results of muscle and nerve biopsies in 41 of 80 who had concomitant biopsies (38) or other diagnostic analyses (3). A diagnosis was made of Werdnig-Hoffmann disease (WHD) in 15, a congenital infantile polyneuropathy (IPN) in 3, neuromuscular transmission defect (NMTD) in 2, myopathy in 12, and presumed "central" hypotonia in 9. A very positive correlation rate between nerve conduction studies with electromyography and biopsy results was found in 93% (14 of 15) with WHD and 100% in IPN (3 of 3). However, only 4 of 10 infants (40%) with biopsy-proven myopathy had an abnormal EMG. Only once did the results of electromyography and biopsy conflict.

Biopsy↗
PubMedDate not supplied

Clinical heterogeneity of familial spastic paraplegia linked to chromosome 2p21.

The clinical features of four families with autosomal dominant spastic paraparesis (FSP) are described, along with the results of linkage analysis to markers from the regions of chromosomes 2, 14, and 15 which are known to contain spastic paraplegia genes. All families had 'pure' spastic paraparesis (FSP), but the severity of symptoms varied widely among families, and other mild neurologic signs were observed in some subjects. Although no family individually yielded a lod score >3.0, all families yielded positive lod scores with chromosome 2 markers, and a maximal lod score of 5.7 was obtained for the families combined using marker D2S352. There was no evidence of linkage to chromosome 14 or 15 in any of the families.

Adolescent↗
PubMedDate not supplied

Segmental near nerve sensory conduction studies of the medical and lateral plantar nerve.

Tarsal Tunnel Syndrome (TTS) can be difficult to diagnose: electrophysiologic corroboration is important and has therapeutic implications. Conventional electrodiagnostic techniques are insensitive: motor latency abnormalities exist in only 52%; sensory responses are frequently absent (a nonlocalizing finding). Additionally, previously described near nerve techniques do not isolate conduction velocity (CV) measurement to the short segment across the flexor retinaculum (FR), which would theoretically improve sensitivity. We describe a technique which allows for the determination of segmental sensory CVs of the medial (MP) and lateral (LP) plantar nerves, both below (BFR) and across (AFR) the FR. Seventeen normal patients (age 22-45) were studied. Near nerve recording electrodes were positioned close to the specified nerve below and above the FR. Ring electrode stimulation (RES) of digits I (MP) or V (LP) and direct near nerve stimulation (NNS) BFR were performed. With RES digit I (n = 17), mean CV (toe to BFR) was 39.0 +/- 7.1 m/s; CV (AFR) 47.9 +/- 6.2 m/s. CV (AFR) following NNS (MP) (n = 16) was 49.4 +/- 5.1 m/s. With RES digit V (n = 10), mean CV (toe to BFR) was 36.4 +/- 3.4 m/s; CV (AFR) 57.5 +/- 6.9 m/s. CV (AFR) with NNS (LP) (n = 14) was 59.8 +/- 6.2 m/s. In conclusion, segmental MP and LP sensory CVs can be reliably obtained with near nerve technique. This approach may improve the diagnostic sensitivity of EMG in TTS.

Adult↗