James F Howard Jr | University of North Carolina at Chapel Hill (original) (raw)
Papers by James F Howard Jr
Annals of Clinical Oncology, 2018
Physical Disabilities: Education and Related Services, 2016
The objectives of this study were to investigate types of supportive school services received and... more The objectives of this study were to investigate types of supportive school services received and factors related to provision of these services. We conducted a cross-sectional study to describe the school experience of males with Duchenne and Becker muscular dystrophies. Study subjects were identified through the Muscular Dystrophy Surveillance, Tracking, and Research Network. Non-ambulatory males with Duchenne muscular dystrophy (DMD) were significantly more likely to use an instructional assistant and resource room support when compared to ambulant males with DMD at the time of the caregiver interview. Males with DMD who received occupational therapy were more likely to use an instructional assistant, while those who received speech therapy were more likely to repeat a grade, use an instructional assistant, and receive resource room support. Males with DMD whose primary caregivers had less than 12 years of education were more likely to use an instructional assistant and resource ...
Physical Disabilities: Education and Related Services, 2016
The objectives of this study were to investigate types of supportive school services received and... more The objectives of this study were to investigate types of supportive school services received and factors related to provision of these services. We conducted a cross-sectional study to describe the school experience of males with Duchenne and Becker muscular dystrophies. Study subjects were identified through the Muscular Dystrophy Surveillance, Tracking, and Research Network. Non-ambulatory males with Duchenne muscular dystrophy (DMD) were significantly more likely to use an instructional assistant and resource room support when compared to ambulant males with DMD at the time of the caregiver interview. Males with DMD who received occupational therapy were more likely to use an instructional assistant, while those who received speech therapy were more likely to repeat a grade, use an instructional assistant, and receive resource room support. Males with DMD whose primary caregivers had less than 12 years of education were more likely to use an instructional assistant and resource ...
The Journal of the Acoustical Society of America, 2021
Contemporary clinical trials, Jul 24, 2017
Despite corticosteroids being the only treatment documented to improve strength and function in b... more Despite corticosteroids being the only treatment documented to improve strength and function in boys with Duchenne muscular dystrophy (DMD) corticosteroid prescription is inconsistent and in some countries, corticosteroids are not prescribed. We are conducting a clinical trial that (1) compares the 3 most frequently prescribed corticosteroid regimes; (2) standardizes treatment of DMD complications; and (3) standardizes prevention of corticosteroid side effects. Investigators at 38 sites in 5 countries plan to recruit 300 boys aged 4-7 who are randomly assigned to one of three regimens: daily prednisone; daily deflazacort; or intermittent prednisone (10days on/10days off). Boys are followed for a minimum of 3years to assess the relative effectiveness and adverse event profiles of the different regimens. The primary outcome is a 3-dimensional variable consisting of log-transformed time to rise from the floor, forced vital capacity, and subject/parent satisfaction with treatment, each ...
Contemporary clinical trials, Jul 24, 2017
Despite corticosteroids being the only treatment documented to improve strength and function in b... more Despite corticosteroids being the only treatment documented to improve strength and function in boys with Duchenne muscular dystrophy (DMD) corticosteroid prescription is inconsistent and in some countries, corticosteroids are not prescribed. We are conducting a clinical trial that (1) compares the 3 most frequently prescribed corticosteroid regimes; (2) standardizes treatment of DMD complications; and (3) standardizes prevention of corticosteroid side effects. Investigators at 38 sites in 5 countries plan to recruit 300 boys aged 4-7 who are randomly assigned to one of three regimens: daily prednisone; daily deflazacort; or intermittent prednisone (10days on/10days off). Boys are followed for a minimum of 3years to assess the relative effectiveness and adverse event profiles of the different regimens. The primary outcome is a 3-dimensional variable consisting of log-transformed time to rise from the floor, forced vital capacity, and subject/parent satisfaction with treatment, each ...
Electroencephalography and Clinical Neurophysiology/Electromyography and Motor Control, 1995
Handbook of clinical neurology, 2008
Publisher Summary The neuromuscular junction (NMJ) is sensitive to the effects of neurotoxins. Th... more Publisher Summary The neuromuscular junction (NMJ) is sensitive to the effects of neurotoxins. The neurotoxins directed to the NMJ come from many sources. Many occur as natural substances of plants or animals, others are prescribed pharmaceutical compounds and still others are environmental hazards or weapons of terror. Drugs that produce worsening of neuromuscular function can be categorized as (1) drugs that have a direct effect on neuromuscular transmission (NMT) in otherwise normal individuals; (2) drugs that disturb the immune system and result in the development of myasthenia gravis (MG); (3) drugs that unmask subclinical MG or worsen muscle strength in patients with disorders of NMT; (4) drugs that delay recovery of strength, particularly respiratory function, following general anesthesia during which neuromuscular blocking agents have usually been used. The clostridial neurotoxins are gram-positive, anaerobic, spore-forming bacteria found ubiquitously in the environment. The neurotoxins of clostridial organisms produce botulism and tetanus by the inhibition of neurotransmitter release via their metalol-proteolytic activity directed against SNARE proteins, although the site of action and clinical picture of each is quite different. Heavy metal intoxication is a rare cause of clinical neuromuscular toxicity. The metals include barium, erbium, cadmium, cobalt, gadolinium, lanthium, manganese, nickel, praseodymium, triethyltin, and zinc. Nearly all of these have multiple effects on synaptic transmission but they block the release of acetylcholine (ACh) from the presynaptic nerve terminal. The inadvertent use of potentially NMJ toxic drugs is a matter of concern. Health care personnel must carefully assess each patient's potential complications and risk of adverse events before prescribing these agents to someone whose neuromuscular transmission is perturbed.
Electroencephalography and Clinical Neurophysiology/Electromyography and Motor Control, 1995
Special Care in Dentistry, 1997
Handbook of clinical neurology, 2008
Publisher Summary The neuromuscular junction (NMJ) is sensitive to the effects of neurotoxins. Th... more Publisher Summary The neuromuscular junction (NMJ) is sensitive to the effects of neurotoxins. The neurotoxins directed to the NMJ come from many sources. Many occur as natural substances of plants or animals, others are prescribed pharmaceutical compounds and still others are environmental hazards or weapons of terror. Drugs that produce worsening of neuromuscular function can be categorized as (1) drugs that have a direct effect on neuromuscular transmission (NMT) in otherwise normal individuals; (2) drugs that disturb the immune system and result in the development of myasthenia gravis (MG); (3) drugs that unmask subclinical MG or worsen muscle strength in patients with disorders of NMT; (4) drugs that delay recovery of strength, particularly respiratory function, following general anesthesia during which neuromuscular blocking agents have usually been used. The clostridial neurotoxins are gram-positive, anaerobic, spore-forming bacteria found ubiquitously in the environment. The neurotoxins of clostridial organisms produce botulism and tetanus by the inhibition of neurotransmitter release via their metalol-proteolytic activity directed against SNARE proteins, although the site of action and clinical picture of each is quite different. Heavy metal intoxication is a rare cause of clinical neuromuscular toxicity. The metals include barium, erbium, cadmium, cobalt, gadolinium, lanthium, manganese, nickel, praseodymium, triethyltin, and zinc. Nearly all of these have multiple effects on synaptic transmission but they block the release of acetylcholine (ACh) from the presynaptic nerve terminal. The inadvertent use of potentially NMJ toxic drugs is a matter of concern. Health care personnel must carefully assess each patient's potential complications and risk of adverse events before prescribing these agents to someone whose neuromuscular transmission is perturbed.
Neurology® neuroimmunology & neuroinflammation, 2015
To characterize B-cell subsets in patients with muscle-specific tyrosine kinase (MuSK) myasthenia... more To characterize B-cell subsets in patients with muscle-specific tyrosine kinase (MuSK) myasthenia gravis (MG). In accordance with Human Immunology Project Consortium guidelines, we performed polychromatic flow cytometry and ELISA assays in peripheral blood samples from 18 patients with MuSK MG and 9 healthy controls. To complement a B-cell phenotype assay that evaluated maturational subsets, we measured B10 cell percentages, plasma B cell-activating factor (BAFF) levels, and MuSK antibody titers. Immunologic variables were compared with healthy controls and clinical outcome measures. As expected, patients treated with rituximab had high percentages of transitional B cells and plasmablasts and thus were excluded from subsequent analysis. The remaining patients with MuSK MG and controls had similar percentages of total B cells and naïve, memory, isotype-switched, plasmablast, and transitional B-cell subsets. However, patients with MuSK MG had higher BAFF levels and lower percentages o...
Neurology, 1980
Adult female Lewis rats were rendered immunologically tolerant to human gamma globulin, and were ... more Adult female Lewis rats were rendered immunologically tolerant to human gamma globulin, and were given a single intravenous injection of human myasthenic or normal control serum containing 7.5 to 12 mg of immunoglobulin G. The mean amplitude of miniature endplate potentials (MEPPs) in the forelimb flexor digitorum longus muscles from treated animals did not differ from control values during the first 24 hours after serum injection. Subsequently, MEPP amplitude was reduced in muscles from animals that had received myasthenic serum; maximum reduction was reached by 6 days after transfer. Mean MEPP amplitude at maximum reduction was 30 to 40% below the amplitude of controls and returned to control values 14 weeks after transfer. Similar reductions in endplate potential amplitudes were found in immunologically tolerant animals receiving myasthenic serum. No significant reduction of MEPP amplitude was seen in recipients that were not immunologically tolerant or that had received cobra venom factor to reduce complement activity. The delayed development of reduced MEPP amplitude indicated that the defect of neuromuscular transmission produced by myasthenic serum was not due entirely to a simple curare-like block of the acetylcholine receptor site by an IgG antibody.
Journal of Neurology, Neurosurgery & Psychiatry, 1980
Annals of the New York Academy of Sciences, 1998
Annals of the New York Academy of Sciences, 1993
Annals of Clinical Oncology, 2018
Physical Disabilities: Education and Related Services, 2016
The objectives of this study were to investigate types of supportive school services received and... more The objectives of this study were to investigate types of supportive school services received and factors related to provision of these services. We conducted a cross-sectional study to describe the school experience of males with Duchenne and Becker muscular dystrophies. Study subjects were identified through the Muscular Dystrophy Surveillance, Tracking, and Research Network. Non-ambulatory males with Duchenne muscular dystrophy (DMD) were significantly more likely to use an instructional assistant and resource room support when compared to ambulant males with DMD at the time of the caregiver interview. Males with DMD who received occupational therapy were more likely to use an instructional assistant, while those who received speech therapy were more likely to repeat a grade, use an instructional assistant, and receive resource room support. Males with DMD whose primary caregivers had less than 12 years of education were more likely to use an instructional assistant and resource ...
Physical Disabilities: Education and Related Services, 2016
The objectives of this study were to investigate types of supportive school services received and... more The objectives of this study were to investigate types of supportive school services received and factors related to provision of these services. We conducted a cross-sectional study to describe the school experience of males with Duchenne and Becker muscular dystrophies. Study subjects were identified through the Muscular Dystrophy Surveillance, Tracking, and Research Network. Non-ambulatory males with Duchenne muscular dystrophy (DMD) were significantly more likely to use an instructional assistant and resource room support when compared to ambulant males with DMD at the time of the caregiver interview. Males with DMD who received occupational therapy were more likely to use an instructional assistant, while those who received speech therapy were more likely to repeat a grade, use an instructional assistant, and receive resource room support. Males with DMD whose primary caregivers had less than 12 years of education were more likely to use an instructional assistant and resource ...
The Journal of the Acoustical Society of America, 2021
Contemporary clinical trials, Jul 24, 2017
Despite corticosteroids being the only treatment documented to improve strength and function in b... more Despite corticosteroids being the only treatment documented to improve strength and function in boys with Duchenne muscular dystrophy (DMD) corticosteroid prescription is inconsistent and in some countries, corticosteroids are not prescribed. We are conducting a clinical trial that (1) compares the 3 most frequently prescribed corticosteroid regimes; (2) standardizes treatment of DMD complications; and (3) standardizes prevention of corticosteroid side effects. Investigators at 38 sites in 5 countries plan to recruit 300 boys aged 4-7 who are randomly assigned to one of three regimens: daily prednisone; daily deflazacort; or intermittent prednisone (10days on/10days off). Boys are followed for a minimum of 3years to assess the relative effectiveness and adverse event profiles of the different regimens. The primary outcome is a 3-dimensional variable consisting of log-transformed time to rise from the floor, forced vital capacity, and subject/parent satisfaction with treatment, each ...
Contemporary clinical trials, Jul 24, 2017
Despite corticosteroids being the only treatment documented to improve strength and function in b... more Despite corticosteroids being the only treatment documented to improve strength and function in boys with Duchenne muscular dystrophy (DMD) corticosteroid prescription is inconsistent and in some countries, corticosteroids are not prescribed. We are conducting a clinical trial that (1) compares the 3 most frequently prescribed corticosteroid regimes; (2) standardizes treatment of DMD complications; and (3) standardizes prevention of corticosteroid side effects. Investigators at 38 sites in 5 countries plan to recruit 300 boys aged 4-7 who are randomly assigned to one of three regimens: daily prednisone; daily deflazacort; or intermittent prednisone (10days on/10days off). Boys are followed for a minimum of 3years to assess the relative effectiveness and adverse event profiles of the different regimens. The primary outcome is a 3-dimensional variable consisting of log-transformed time to rise from the floor, forced vital capacity, and subject/parent satisfaction with treatment, each ...
Electroencephalography and Clinical Neurophysiology/Electromyography and Motor Control, 1995
Handbook of clinical neurology, 2008
Publisher Summary The neuromuscular junction (NMJ) is sensitive to the effects of neurotoxins. Th... more Publisher Summary The neuromuscular junction (NMJ) is sensitive to the effects of neurotoxins. The neurotoxins directed to the NMJ come from many sources. Many occur as natural substances of plants or animals, others are prescribed pharmaceutical compounds and still others are environmental hazards or weapons of terror. Drugs that produce worsening of neuromuscular function can be categorized as (1) drugs that have a direct effect on neuromuscular transmission (NMT) in otherwise normal individuals; (2) drugs that disturb the immune system and result in the development of myasthenia gravis (MG); (3) drugs that unmask subclinical MG or worsen muscle strength in patients with disorders of NMT; (4) drugs that delay recovery of strength, particularly respiratory function, following general anesthesia during which neuromuscular blocking agents have usually been used. The clostridial neurotoxins are gram-positive, anaerobic, spore-forming bacteria found ubiquitously in the environment. The neurotoxins of clostridial organisms produce botulism and tetanus by the inhibition of neurotransmitter release via their metalol-proteolytic activity directed against SNARE proteins, although the site of action and clinical picture of each is quite different. Heavy metal intoxication is a rare cause of clinical neuromuscular toxicity. The metals include barium, erbium, cadmium, cobalt, gadolinium, lanthium, manganese, nickel, praseodymium, triethyltin, and zinc. Nearly all of these have multiple effects on synaptic transmission but they block the release of acetylcholine (ACh) from the presynaptic nerve terminal. The inadvertent use of potentially NMJ toxic drugs is a matter of concern. Health care personnel must carefully assess each patient's potential complications and risk of adverse events before prescribing these agents to someone whose neuromuscular transmission is perturbed.
Electroencephalography and Clinical Neurophysiology/Electromyography and Motor Control, 1995
Special Care in Dentistry, 1997
Handbook of clinical neurology, 2008
Publisher Summary The neuromuscular junction (NMJ) is sensitive to the effects of neurotoxins. Th... more Publisher Summary The neuromuscular junction (NMJ) is sensitive to the effects of neurotoxins. The neurotoxins directed to the NMJ come from many sources. Many occur as natural substances of plants or animals, others are prescribed pharmaceutical compounds and still others are environmental hazards or weapons of terror. Drugs that produce worsening of neuromuscular function can be categorized as (1) drugs that have a direct effect on neuromuscular transmission (NMT) in otherwise normal individuals; (2) drugs that disturb the immune system and result in the development of myasthenia gravis (MG); (3) drugs that unmask subclinical MG or worsen muscle strength in patients with disorders of NMT; (4) drugs that delay recovery of strength, particularly respiratory function, following general anesthesia during which neuromuscular blocking agents have usually been used. The clostridial neurotoxins are gram-positive, anaerobic, spore-forming bacteria found ubiquitously in the environment. The neurotoxins of clostridial organisms produce botulism and tetanus by the inhibition of neurotransmitter release via their metalol-proteolytic activity directed against SNARE proteins, although the site of action and clinical picture of each is quite different. Heavy metal intoxication is a rare cause of clinical neuromuscular toxicity. The metals include barium, erbium, cadmium, cobalt, gadolinium, lanthium, manganese, nickel, praseodymium, triethyltin, and zinc. Nearly all of these have multiple effects on synaptic transmission but they block the release of acetylcholine (ACh) from the presynaptic nerve terminal. The inadvertent use of potentially NMJ toxic drugs is a matter of concern. Health care personnel must carefully assess each patient's potential complications and risk of adverse events before prescribing these agents to someone whose neuromuscular transmission is perturbed.
Neurology® neuroimmunology & neuroinflammation, 2015
To characterize B-cell subsets in patients with muscle-specific tyrosine kinase (MuSK) myasthenia... more To characterize B-cell subsets in patients with muscle-specific tyrosine kinase (MuSK) myasthenia gravis (MG). In accordance with Human Immunology Project Consortium guidelines, we performed polychromatic flow cytometry and ELISA assays in peripheral blood samples from 18 patients with MuSK MG and 9 healthy controls. To complement a B-cell phenotype assay that evaluated maturational subsets, we measured B10 cell percentages, plasma B cell-activating factor (BAFF) levels, and MuSK antibody titers. Immunologic variables were compared with healthy controls and clinical outcome measures. As expected, patients treated with rituximab had high percentages of transitional B cells and plasmablasts and thus were excluded from subsequent analysis. The remaining patients with MuSK MG and controls had similar percentages of total B cells and naïve, memory, isotype-switched, plasmablast, and transitional B-cell subsets. However, patients with MuSK MG had higher BAFF levels and lower percentages o...
Neurology, 1980
Adult female Lewis rats were rendered immunologically tolerant to human gamma globulin, and were ... more Adult female Lewis rats were rendered immunologically tolerant to human gamma globulin, and were given a single intravenous injection of human myasthenic or normal control serum containing 7.5 to 12 mg of immunoglobulin G. The mean amplitude of miniature endplate potentials (MEPPs) in the forelimb flexor digitorum longus muscles from treated animals did not differ from control values during the first 24 hours after serum injection. Subsequently, MEPP amplitude was reduced in muscles from animals that had received myasthenic serum; maximum reduction was reached by 6 days after transfer. Mean MEPP amplitude at maximum reduction was 30 to 40% below the amplitude of controls and returned to control values 14 weeks after transfer. Similar reductions in endplate potential amplitudes were found in immunologically tolerant animals receiving myasthenic serum. No significant reduction of MEPP amplitude was seen in recipients that were not immunologically tolerant or that had received cobra venom factor to reduce complement activity. The delayed development of reduced MEPP amplitude indicated that the defect of neuromuscular transmission produced by myasthenic serum was not due entirely to a simple curare-like block of the acetylcholine receptor site by an IgG antibody.
Journal of Neurology, Neurosurgery & Psychiatry, 1980
Annals of the New York Academy of Sciences, 1998
Annals of the New York Academy of Sciences, 1993
Muscle & Nerve, 2015
To characterize a unique distribution of muscle involvement in sporadic Becker muscle dystrophy (... more To characterize a unique distribution of muscle involvement in sporadic Becker muscle dystrophy (BMD). Retrospective chart review, clinical examination, electrophysiological studies, cardiac testing, and genetic testing were performed in 5 patients. Predominant weakness and atrophy of biceps brachii, hip adduction, and quadriceps muscles was noted along with calf and extensor forearm hypertrophy. Finger flexor muscles were severely weak in 3 of 5 patients, a feature that could be misdiagnosed for inclusion body myositis (IBM). Creatinine kinase (CK) was only mildly elevated in most patients. Electromyography (EMG) was abnormal in all patients. Muscle biopsy in 1 patient demonstrated normal immunostaining for dystrophin. We found a unique and uniform distribution of muscle involvement in 5 sporadic cases of BMD. Recognizing these features is important for differentiating it from other myopathies that may have similar features and avoids unnecessary invasive procedures such as muscle biopsy. This article is protected by copyright. All rights reserved.
Volume 3B: Biomedical and Biotechnology Engineering, 2013
ABSTRACT Viscoelastic Strain Response (ViSR) ultrasound is a novel acoustic radiation force (ARF)... more ABSTRACT Viscoelastic Strain Response (ViSR) ultrasound is a novel acoustic radiation force (ARF)-based imaging method that noninvasively interrogates the viscoelastic properties of tissue by measuring the relaxation time constant for constant stress in the Voigt biomechanical model. The time constant is defined as the ratio of coefficient of viscosity to elastic modulus, so ViSR differentiates tissue with disparate viscosities and elasticities. ViSR ultrasound is performed by delivering two successive ARF impulses to a single region of exciation (ROE) and tracking the micrometer-scale displacements induced by the propagating longitudinal waves. ViSR does not rely on transverse wave propagation, which can be disrupted and difficult to track in heterogeneous and/or geometrically complex media. Another advantage to ViSR ultrasound is a large axial range relative to conventional ARF Impulse (ARFI) ultrasound.In this overview, ViSR methods are discussed and demonstrated in calibrated viscoelastic tissue mimicking materials. ViSR ultrasound is then applied to differentiating fatty and fibrous deposition in muscle in a golden retriever muscular dystrophy (GRMD) dog model and in boys with Duchenne muscular dystrophy (DMD) with correlation to standard physical testing. ViSR is also applied to delineating the structure and composition of atherosclerotic plaques in a hypercholesterolemic pig model with histochemical validation. ViSR’s key advantages and disadvantages are discussed in regard to its general clinical utility.
2012 IEEE International Ultrasonics Symposium, 2012
ABSTRACT Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder that is caused by a ... more ABSTRACT Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder that is caused by a mutation in the gene for dystrophin leading to a loss of the dystrophin protein from the muscle cell (myofiber) membrane. Viscoelastic Strain Response (ViSR) ultrasound is a new, quantitative acoustic radiation force (ARF) based elastographic imaging method to calculate τ, the viscoelastic relaxation time constant for constant stress. We have investigated the use of ViSR imaging in human DMD. Imaging was performed in vivo on the right rectus femoris (RF), sartorius (SART), and gastrocnemius (GAST) muscles of two boys with DMD. The boys were 5- and 9-years-old at the time of imaging. ViSR results in the 5-year-old showed an average of 27.0%, 6.6%, and 18.2% fat/necrosis composition in the RF, SART, and GAST, respectively. In the 9-year old subject, ViSR showed an average fat/necrosis composition of 66.7% in the RF, 9.1% in the SART, and 37.2% in the GAST. These results are consistent with both the known phenotypic response of the three muscles and with functional testing results and point to ViSR's potential relevance as a novel outcome measure for diagnostics and clinical trials in DMD.
Human gene therapy, Jan 8, 2015
We evaluated safety and feasibility of high-pressure transvenous limb perfusion in an upper extre... more We evaluated safety and feasibility of high-pressure transvenous limb perfusion in an upper extremity of adult patients with muscular dystrophy, after completing a similar study in a lower extremity. A dose escalation study of single limb perfusion with 0.9% saline was carried out in nine adults with muscular dystrophies under intravenous analgesia. Our study demonstrates that it is safe and feasible to perform high-pressure transvenous perfusion with 0.9% saline up to 30% of limb volume in the upper extremities of young adults with muscular dystrophy. Perfusion at 30-40% limb volume is associated with short-lived physiological changes in peripheral nerves without clinical correlates. This study provides the basis for a phase 1/2 clinical trial using pressurized transvenous delivery into upper limbs of non-ambulatory patients with Duchenne muscular dystrophy. Furthermore, our results are applicable to other conditions such as limb-girdle muscular dystrophy as a method for delivering...