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Biomedical subjects

G T Carter

Publications and source records attributed to G T Carter.

At least 19 recordsLinked to original sources

A4V superoxide dismutase mutation in apparently sporadic ALS resembling neuralgic amyotrophy.

We report a case of apparently sporadic amyotrophic lateral sclerosis (ALS) in a young pregnant woman presenting subacutely with severe left shoulder pain followed by progressive weakness and wasting of the left arm, mimicking neuralgic amyotrophy. She was later found electrophysiologically to have widespread denervation involving more than just the arm and an alanine for valine substitution in codon 4 (A4V) in the gene for Cu/Zn superoxide dismutase 1 (SOD1). Her case illustrates that pain on initial presentation, though uncommon, does not exclude a diagnosis of ALS.

Adult↗

Distal symmetric polyneuropathy: a definition for clinical research: report of the American Academy of Neurology, the American Association of Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation.

The objective of this report was to develop a case definition of distal symmetric polyneuropathy to standardize and facilitate clinical research and epidemiologic studies. A formalized consensus process was employed to reach agreement after a systematic review and classification of evidence from the literature. The literature indicates that symptoms alone have relatively poor diagnostic accuracy in predicting the presence of polyneuropathy; signs are better predictors of polyneuropathy than symptoms; and single abnormalities on examination are less sensitive than multiple abnormalities in predicting the presence of polyneuropathy. The combination of neuropathic symptoms, signs, and electrodiagnostic findings provides the most accurate diagnosis of distal symmetric polyneuropathy. A set of case definitions was rank ordered by likelihood of disease. The highest likelihood of polyneuropathy (useful for clinical trials) occurs with a combination of multiple symptoms, multiple signs, and abnormal electrodiagnostic studies. A modest likelihood of polyneuropathy (useful for field or epidemiologic studies) occurs with a combination of multiple symptoms and multiple signs when the results of electrodiagnostic studies are not available. A lower likelihood of polyneuropathy occurs when electrodiagnostic studies and signs are discordant. For research purposes, the best approach to defining distal symmetric polyneuropathy is a set of case definitions rank ordered by estimated likelihood of disease. The inclusion of this formalized case definition in clinical and epidemiologic research studies will ensure greater consistency of case selection.

Clinical Protocols↗

Distal symmetrical polyneuropathy: definition for clinical research.

The objective of this report was to develop a case definition of "distal symmetrical polyneuropathy" to standardize and facilitate clinical research and epidemiological studies. A formalized consensus process was employed to reach agreement after a systematic review and classification of evidence from the literature. The literature indicates that symptoms alone have relatively poor diagnostic accuracy in predicting the presence of polyneuropathy; signs are better predictors of polyneuropathy than symptoms; and single abnormalities on examination are less sensitive than multiple abnormalities in predicting the presence of polyneuropathy. The combination of neuropathic symptoms, signs, and electrodiagnostic findings provides the most accurate diagnosis of distal symmetrical polyneuropathy. A set of case definitions was rank ordered by likelihood of disease. The highest likelihood of polyneuropathy (useful for clinical trials) occurs with a combination of multiple symptoms, multiple signs, and abnormal electrodiagnostic studies. A modest likelihood of polyneuropathy (useful for field or epidemiological studies) occurs with a combination of multiple symptoms and multiple signs when the results of electrodiagnostic studies are not available. A lower likelihood of polyneuropathy occurs when electrodiagnostic studies and signs are discordant. For research purposes, the best approach for defining distal symmetrical polyneuropathy is a set of case definitions rank ordered by estimated likelihood of disease. The inclusion of this formalized case definition in clinical and epidemiological research studies will ensure greater consistency of case selection.

Electrodiagnosis↗

Charcot-Marie-Tooth neuropathy: clinical phenotypes of four novel mutations in the MPZ and Cx 32 genes.

Charcot-Marie-Tooth Hereditary Neuropathy is a heterogeneous syndrome associated with mutations in several different genes including peripheral myelin protein 22, myelin P0, connexin 32, and early growth response 2. There is considerable variability in the phenotypic expression of this syndrome and the relationship of this variability to mutation genotypes requires extensive analysis. Here we describe the phenotypes and genotypes of four new mutations underlying the Charcot-Marie-Tooth syndrome and document segregation with disease. Four families with Charcot-Marie-Tooth were ascertained, examined, and evaluated electrophysiologically. Each family had peripheral blood DNA screened for mutations in myelin protein 22, myelin P0, and connexin 32. Two families were found with new mutations in the myelin P0 gene: S140T in the extracellular domain and K236del in the cytoplasmic domain. All families showed segregation of the mutations with the Charcot-Marie-Tooth phenotype as did a new family with the rare G163R mutation in the membrane domain. A 49-year-old man with the S140T mutation demonstrated conduction block on electrophysiological testing. A family with a novel S49P mutation in the connexin 32 gene had a neuropathy with very slow nerve conduction. These new mutations in the myelin P0 and connexin 32 genes help to clarify the pathophysiology of the clinical Charcot-Marie-Tooth syndrome. The S140T mutation in myelin P0 can be associated with conduction block and Charcot-Marie-Tooth should be part of the differential diagnosis of that phenomenon. Mutations in the cytoplasmic domain of myelin P0 can cause clinical neuropathy. The S49P mutation in the connexin 32 gene can produce aspects of a demyelinating type of X-linked hereditary neuropathy.

Adult↗

Immobilized artificial membrane chromatography with mass spectrometric detection: a rapid method for screening drug-membrane interactions.

A high-performance liquid chromatography (HPLC)/electrospray ionization mass spectrometry method for measuring drug-membrane interactions was developed using immobilized artificial membrane (IAM) fast-screening mini-columns. The HPLC mobile phase consisted of phosphate-buffered saline (i.e., 5.0 mM phosphate buffer at pH 7.4, 1.35 mM KCl, and 68.5 mM NaCl) and acetonitrile. This method facilitated the measurement of IAM retention time of over ten compounds in one experiment, significantly reducing analysis time compared with the earlier IAM-HPLC method. The particular electrospray source used demonstrated the ability to tolerate the high salt-containing nonvolatile buffer used for retention time measurement.

Chromatography, High Pressure Liquid↗

New biotransformation products of nemadectins.

Selected nemadectins (formerly LL-F28249 series) have been fed to a panel of microorganisms with the aim of generating new derivatives. In addition to products resulting from the oxidation of the terminal methyl group (C-29), a unique phosphorylated nemadectin was isolated. The phosphate group was determined to be at C-23 by HMBC between phosphorus and H-23. Milbemycin or nemadectin derivatives with natural substituents involving the 23-hydroxyl group were hitherto unknown.

Animals↗

Advances in the management of neuropathic pain.

Much progress has been made in the assessment and management of neuropathic pain over the past 5 years. Assessment has improved with the Neuropathic Pain Scale, a new, easily administered, diagnostic tool. Mechanistically, recent studies indicate that peripheral neuropathic pain is generated through a focal inflammatory process rather than axonal destruction. This process also appears to involve mRNA regulation of fast sodium channels, which produce ectopic discharges and are presumably responsible for pain generation. In addition the entire neuraxis undergoes neuroplastic changes as a result of peripheral nerve injury. The available clinical trial data indicate that newer antiepileptic drugs (AEDs), most notably gabapentin, are better alternatives to older medications such as carbamazepine or phenytoin in the treatment of neuropathic pain. Gabapentin is at least as good with respect to actual pain relief as the antidepressants, including amitriptyline, but has a much better safety profile with minimal drug-drug interactions and side effects. Mexiletine is a reasonable alternative agent in patients who have not had a satisfactory response to, or cannot tolerate, the AEDs or antidepressants. Long-acting opioids should be considered in patients refractory to these adjunctive agents. With the advent of the topical lidocaine patch, the first drug with an FDA-approved indication for postherpetic neuralgia, a revolutionary new agent is now available for the treatment of neuropathic pain that does not have any systemic side effects.

Anesthetics↗

Health-related quality of life in peripheral neuropathy.

It is now possible for the clinician to use multidimensional measures to assess the quality of life of their patients. Some of the more widely used instruments to measure HRQOL are the Medical Outcomes Study Short Form 36, the Nottingham Health Profile, the Sickness Impact Profile, and the World Health Organization Quality of Life instrument. Potential uses of quality of life assessment tools include: (1) monitoring the health and social status of a given population, (2) evaluating health care policy, (3) conducting clinical trials, (4) assessing the effectiveness of rehabilitation services, (5) justifying the allocation of limited social and health care resources, and (6) tailoring management to the needs of the patient.

Humans↗

Relative and absolute configurations of ganefromycin alpha.

The full structure of ganefromycin alpha has been determined. The relative configurations were determined from 3JH,H coupling constants and NOE data, while the absolute configurations in moleties A and B were determined separately by difference CD of their acylate derivatives, which showed typical exciton couplets. The configurations of the stereogenic centers in ganefromycin alpha are 8S, 9S, 11R, 12S, 13S, 21S, 22R, 23R, 24R, and 26S.

Aminoglycosides↗

Absolute stereochemistry of the strevertenes.

The CD exciton chirality method was applied to determine the absolute stereochemistry of the strevertenes, antifungal pentaene macrolides produced by Streptoverticillium sp. LL-30F848. The CD difference spectrum of strevertene A methyl ester 15-dimethylaminobenzoate showed a positive couplet between the dimethylaminobenzoate and the pentaene chromophores, and therefore established the 15R configuration. Thus, by considering the relative configurations of the remaining stereogenic centers as derived from X-ray crystallography and ROESY experiments, the absolute stereochemistry of the strevertenes is established as 2R, 3S, 5S, 7S, 11R, 13R, 14R, 15R, 26S and 27R.

Anti-Bacterial Agents↗

Magnetic resonance imaging of denervated muscle: comparison to electromyography.

The purpose of the study is to further assess the usefulness of short TI (time to inversion) recovery (STIR) magnetic resonance imaging (MRI) in detecting denervation of skeletal muscle compared to needle electromyography (EMG). Ninety subjects with clinical evidence of peripheral nerve injury or radiculopathy underwent STIR MRI and EMG of the affected limb. In 74 (82%) of these subjects, a positive correlation was found between STIR MRI and EMG (P < 0.009). STIR MRI has a relative sensitivity of 84% and specificity of 100% for detecting denervation. A subset of 28 subjects underwent quantitative assessments of signal intensity ratio (SIR) from the STIR MRI. The rank order correlation coefficient between the SIR and abnormal spontaneous activity on EMG was 0.70 (P < 0.001). Increased signal intensity on STIR MRI corresponds closely with spontaneous activity on EMG in denervated muscle. Although less sensitive than EMG in detecting muscle denervation, STIR MRI may be a useful adjunctive diagnostic tool in this setting.

Adult↗

Pursed lips breathing improves ventilation in myotonic muscular dystrophy.

OBJECTIVE: To determine the effects of pursed lips breathing on ventilation, chest wall mechanics, and abdominal muscle recruitment in myotonic muscular dystrophy (MMD). DESIGN: Before-after trial. SETTING: University hospital pulmonary function laboratory. PARTICIPANTS: Eleven subjects with MMD and 13 normal controls. INTERVENTION: Pursed lips breathing. OUTCOME MEASURES: Electromyographic (EMG) activity of the transversus abdominis, external oblique, internal oblique, and rectus abdominis was recorded with simultaneous measures of gastric pressure, abdominal plethysmography, and oxygen saturation. Self-reported sensations of dyspnea, respiratory effort, and fatigue were recorded at the end of each trial. RESULTS: Pursed lips breathing and deep breathing led to increased tidal volume, increased minute ventilation, increased oxygen saturation, reduced respiratory rate, and reduced endexpiratory lung volume. Dyspnea, respiratory effort, and fatigue increased slightly with pursed lips breathing. EMG activity of the transversus abdominis and internal oblique muscles increased in MMD only and was associated with an increase in gastric pressure. CONCLUSIONS: Pursed lips breathing and deep breathing are effective and easily employed strategies that significantly improve tidal volume and oxygen saturation in subjects with MMD. Abdominal muscle recruitment does not explain the ventilatory improvements, but reduced end-expiratory lung volume may increase the elastic recoil of the chest wall. Further clinical studies are needed to ascertain if the ventilatory improvements with pursed lips breathing and deep breathing improve pulmonary outcomes in MMD.

Abdominal Muscles↗

Electrodiagnostic evaluation of traumatic nerve injuries.

This article reviews the techniques of motor and sensory nerve conduction studies and needle electromyography methods, which are particularly useful for localizing nerve injuries in upper extremity and hand trauma. Included are details of methods for detecting and quantifying the degree of axon loss and for using this information to make treatment decisions and predict outcomes. The epidemiology and classification of traumatic peripheral nerve injuries, the effects of these injuries on nerve and muscle, and the means by which electrodiagnosis is used to help classify the injury are described. An overview of recovery mechanisms also is presented.

Action Potentials↗

Isolated superior gluteal nerve injury: two case reports.

Isolated superior gluteal nerve injury has been infrequently described in the literature, mainly from injections or hip surgery. Its course through the greater sciatic foramen renders it at risk in pelvic or hip trauma. We report 2 cases of electromyographically documented isolated superior gluteal nerve injury following pelvic trauma. These cases illustrate that weakness in hip abduction following pelvic trauma may indicate the presence of a superior gluteal nerve injury, warranting further clinical and electrodiagnostic evaluation.

Accidental Falls↗

Neuropathic pain in Charcot-Marie-Tooth disease.

OBJECTIVES: To determine the frequency and extent to which subjects with Charcot-Marie-Tooth (CMT) disease report pain and to compare qualities of pain in CMT to other painful neuropathic conditions. STUDY DESIGN: Descriptive, nonexperimental survey, using a previously validated measurement tool, the Neuropathic Pain Scale (NPS). PARTICIPANTS: Participants were recruited from the membership roster of a worldwide CMT support organization. MAIN OUTCOME MEASURES: NPS pain descriptors reported in CMT were compared with those reported by subjects with postherpetic neuralgia (PHN), complex regional pain syndrome, type 1 (CRPS-1), also known as reflex sympathetic dystrophy, diabetic neuropathy (DN), and peripheral nerve injury (PNI). RESULTS: Of 617 CMT subjects (40% response rate), 440 (71%) reported pain. with the most severe pain sites noted as low back (70%), knees (53%), ankles (50%), toes (46%), and feet (44%). Of this group, 171 (39%) reported interruption of activities of daily living by pain; 168 (38%) used non-narcotic pain medication and 113 (23%) used narcotics and/or benzodiazepines for pain. The use of pain description was similar for CMT, PHN, CRPS-1, DN, and PNI in terms of intensity and the descriptors hot, dull, and deep. CONCLUSIONS: Neuropathic pain is a significant problem for many people with CMT. The frequency and intensity of pain reported in CMT is comparable in many ways to PHN, CRPS-1, DN. and PNI. Further studies are needed to examine possible pain generators and pharmacologic and rehabilitative modalities to treat pain in CMT.

Charcot-Marie-Tooth Disease↗

Biosynthesis of ganefromycin: results from blocked mutants and bioconversion experiments.

The biosynthetic pathway of ganefromycin alpha (8) was investigated using blocked mutants of Streptomyces lydicus spp. tanzanius, the ganefromycin alpha producer, in conjunction with bioconversion experiments with the products of these mutants. Compounds 1-7 and 9-15, which are structurally related to ganefromycin alpha, were produced by cultures of secretor mutants showing blockage or diminished production of 8. These compounds were isolated, characterized, and subjected to bioconversion experiments using converter and other secretor mutants. Some of the compounds were shown to be products resulting from blocks at various stages in the biosynthetics pathway beyond construction of the polyketide skeleton (e.g., furan ring closure, hydroxylation, glycosylation, etc.). Other compounds were not bioconverted by biosynthetically capable mutants and were deemed shunt products. A mutant's metabolites and bioconverting ability were used to surmise the location of the block. A picture of the later sequence of events leading to the synthesis of ganefromycin alpha emerged, including C23-hydroxylation, C13a-O-methylation, C21a-hydroxylation, and C21a-O-glycosylation. Some of the later steps in the biosynthetic pathway for ganefromycin alpha are proposed.

Anti-Bacterial Agents↗