Datasets:
vgainullin
/
xciting_data

Dataset card Data Studio Files
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3
INTRODUCTION
1
18
[ "B18", "B19" ]
16,941,739
pmid-12760428|pmid-9860068|pmid-1940125|pmid-10757471|pmid-8681895|pmid-10403219|pmid-10082337|pmid-9095401|pmid-10073425|pmid-12423385|pmid-11999624|pmid-10331710
Previous studies have suggested that TPM is effective for the treatment of infantile spasm when it is used as an add-on therapy.18 Although a pilot study attempted to evaluate TPM as a monotherapy for infantile spasm,19 there remains a need for a more effective first-line treatment with reduced adverse effects.
[ "18", "19" ]
312
41,819
0
false
Previous studies have suggested that TPM is effective for the treatment of infantile spasm when it is used as an add-on therapy.18 Although a pilot study attempted to evaluate TPM as a monotherapy for infantile spasm,19 there remains a need for a more effective first-line treatment with reduced adverse effects.
[]
Previous studies have suggested that TPM is effective for the treatment of infantile spasm when it is used as an add-on therapy.18 Although a pilot study attempted to evaluate TPM as a monotherapy for infantile spasm,19 there remains a need for a more effective first-line treatment with reduced adverse effects.
true
true
true
true
true
7,212
3
INTRODUCTION
1
18
[ "B18", "B19" ]
16,941,739
pmid-12760428|pmid-9860068|pmid-1940125|pmid-10757471|pmid-8681895|pmid-10403219|pmid-10082337|pmid-9095401|pmid-10073425|pmid-12423385|pmid-11999624|pmid-10331710
The aim of this study was to assess the effectiveness and tolerability of TPM when used as the initial treatment for patients with newly diagnosed infantile spasm.
[ "18", "19" ]
163
41,820
0
false
The aim of this study was to assess the effectiveness and tolerability of TPM when used as the initial treatment for patients with newly diagnosed infantile spasm.
[]
The aim of this study was to assess the effectiveness and tolerability of TPM when used as the initial treatment for patients with newly diagnosed infantile spasm.
true
true
true
true
true
7,212
0
DISCUSSION
1
1
[ "B1" ]
16,941,739
pmid-11918468|NA|pmid-2502382|pmid-11918468
Infantile spasm is a catastrophic childhood epilepsy syndrome1 that is characterized by flexor or extensor spasm, hypsarrhythmia and psychomotor regression.
[ "1" ]
156
41,821
0
false
Infantile spasm is a catastrophic childhood epilepsy syndrome1 that is characterized by flexor or extensor spasm, hypsarrhythmia and psychomotor regression.
[]
Infantile spasm is a catastrophic childhood epilepsy syndrome1 that is characterized by flexor or extensor spasm, hypsarrhythmia and psychomotor regression.
true
true
true
true
true
7,213
0
DISCUSSION
1
1
[ "B1" ]
16,941,739
pmid-11918468|NA|pmid-2502382|pmid-11918468
Despite the use of a variety of therapies for infantile spasm, complete seizure control is difficult to achieve and the optimal treatment remains uncertain at best.
[ "1" ]
164
41,822
0
false
Despite the use of a variety of therapies for infantile spasm, complete seizure control is difficult to achieve and the optimal treatment remains uncertain at best.
[]
Despite the use of a variety of therapies for infantile spasm, complete seizure control is difficult to achieve and the optimal treatment remains uncertain at best.
true
true
true
true
true
7,213
0
DISCUSSION
1
1
[ "B1" ]
16,941,739
pmid-11918468|NA|pmid-2502382|pmid-11918468
The efficacy of the various drugs used in the treatment of infantile spasm is often difficult to determine because of the short follow-up periods of the studies and the lack of data on the long-term effects.
[ "1" ]
207
41,823
0
false
The efficacy of the various drugs used in the treatment of infantile spasm is often difficult to determine because of the short follow-up periods of the studies and the lack of data on the long-term effects.
[]
The efficacy of the various drugs used in the treatment of infantile spasm is often difficult to determine because of the short follow-up periods of the studies and the lack of data on the long-term effects.
true
true
true
true
true
7,213
1
DISCUSSION
1
20
[ "B20", "B4", "B21", "B23", "B6", "B10", "B24" ]
16,941,739
pmid-11701267|pmid-10757471|pmid-2821097|pmid-11999624|NA|pmid-11701267|pmid-11781414|pmid-6312008|pmid-2821097|pmid-3017235|pmid-6244378
Adrenocorticotrophic hormone (ACTH) was first reported in the 1950s to have rapid effects on spasms.20 For approximately 50 years, ACTH has been widely used as the drug of choice for the treatment of infantile spasm.4 ACTH induces a reduction or cessation of spasms and the disappearance of hypsarrhythmia on the EEG in ...
[ "20", "4", "21", "23", "6", "10", "24" ]
606
41,824
0
false
Adrenocorticotrophic hormone (ACTH) was first reported in the 1950s to have rapid effects on spasms.20 For approximately 50 years, ACTH has been widely used as the drug of choice for the treatment of infantile spasm.4 ACTH induces a reduction or cessation of spasms and the disappearance of hypsarrhythmia on the EEG in ...
[]
Adrenocorticotrophic hormone (ACTH) was first reported in the 1950s to have rapid effects on spasms.20 For approximately 50 years, ACTH has been widely used as the drug of choice for the treatment of infantile spasm.4 ACTH induces a reduction or cessation of spasms and the disappearance of hypsarrhythmia on the EEG in ...
true
true
false
true
false
7,214
2
DISCUSSION
1
25
[ "B25", "B27", "B28", "B29" ]
16,941,739
pmid-2217531|pmid-8641230|pmid-10227614|pmid-10227615|pmid-10768308|pmid-6275826|pmid-7919570|pmid-3102998|pmid-11981230
Although valproate and the benzodiazepines have therapeutic effects, conventional antiepileptic drugs are usually ineffective in reducing seizure activity.25-27 Furthermore, adverse effects on the fetus, including irreversible hepatotoxicity, have been associated with the use of valproate.28 Benzodiazepines usually req...
[ "25", "27", "28", "29" ]
534
41,825
0
false
Although valproate and the benzodiazepines have therapeutic effects, conventional antiepileptic drugs are usually ineffective in reducing seizure activity.25-27 Furthermore, adverse effects on the fetus, including irreversible hepatotoxicity, have been associated with the use of valproate.28 Benzodiazepines usually req...
[]
Although valproate and the benzodiazepines have therapeutic effects, conventional antiepileptic drugs are usually ineffective in reducing seizure activity.25-27 Furthermore, adverse effects on the fetus, including irreversible hepatotoxicity, have been associated with the use of valproate.28 Benzodiazepines usually req...
true
true
true
true
true
7,215
2
DISCUSSION
1
25
[ "B25", "B27", "B28", "B29" ]
16,941,739
pmid-2217531|pmid-8641230|pmid-10227614|pmid-10227615|pmid-10768308|pmid-6275826|pmid-7919570|pmid-3102998|pmid-11981230
Because of recent advances in the understanding of the basic neuropathology, neuropharmacology, and neurophysiology of epilepsy, several new antiepileptic drugs have been developed and use in therapeutic trials.
[ "25", "27", "28", "29" ]
211
41,826
0
false
Because of recent advances in the understanding of the basic neuropathology, neuropharmacology, and neurophysiology of epilepsy, several new antiepileptic drugs have been developed and use in therapeutic trials.
[]
Because of recent advances in the understanding of the basic neuropathology, neuropharmacology, and neurophysiology of epilepsy, several new antiepileptic drugs have been developed and use in therapeutic trials.
true
true
true
true
true
7,215
3
DISCUSSION
1
30
[ "B30", "B5", "B31", "B32", "B33", "B34", "B35", "B11", "B12", "B36" ]
16,941,739
pmid-12760428|pmid-9860068|pmid-1940125|pmid-10757471|pmid-8681895|pmid-10403219|pmid-10082337|pmid-9095401|pmid-10073425|pmid-12423385|pmid-11999624|pmid-10331710
Since vigabatrin (VGB) was first reported as an add-on therapy for resistant infantile spasm in 1991,30 it has been considered as another drug to use as first-line therapy for infantile spasm in many countries outside the United States.5,31 In an open-label study of VGB as a first-line treatment for infantile spasm, 26...
[ "30", "5", "31", "32", "33", "34", "35", "11", "12", "36" ]
358
41,827
0
false
Since vigabatrin (VGB) was first reported as an add-on therapy for resistant infantile spasm in 1991,30 it has been considered as another drug to use as first-line therapy for infantile spasm in many countries outside the United States.5,31 In an open-label study of VGB as a first-line treatment for infantile spasm, 26...
[]
Since vigabatrin (VGB) was first reported as an add-on therapy for resistant infantile spasm in 1991,30 it has been considered as another drug to use as first-line therapy for infantile spasm in many countries outside the United States.5,31 In an open-label study of VGB as a first-line treatment for infantile spasm, 26...
true
true
false
true
false
7,216
3
DISCUSSION
1
30
[ "B30", "B5", "B31", "B32", "B33", "B34", "B35", "B11", "B12", "B36" ]
16,941,739
pmid-12760428|pmid-9860068|pmid-1940125|pmid-10757471|pmid-8681895|pmid-10403219|pmid-10082337|pmid-9095401|pmid-10073425|pmid-12423385|pmid-11999624|pmid-10331710
Another study showed that 64% of the subjects had a clinical response that included the complete cessation of spasms.33 In our study, as in the above earlier studies, TPM has shown a similar reduction of spasm response rates (30% of the subjects became spasm-free, and 40% of the subjects experienced more than a 50% red...
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358
41,828
0
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Another study showed that 64% of the subjects had a clinical response that included the complete cessation of spasms.33 In our study, as in the above earlier studies, TPM has shown a similar reduction of spasm response rates as compared with VGB.
[ "30% of the subjects became spasm-free, and 40% of the subjects experienced more than a 50% reduction of spasm" ]
Another study showed that 64% of the subjects had a clinical response that included the complete cessation of spasms.33 In our study, as in the above earlier studies, TPM has shown a similar reduction of spasm response rates as compared with VGB.
true
true
true
true
true
7,216
3
DISCUSSION
1
30
[ "B30", "B5", "B31", "B32", "B33", "B34", "B35", "B11", "B12", "B36" ]
16,941,739
pmid-12760428|pmid-9860068|pmid-1940125|pmid-10757471|pmid-8681895|pmid-10403219|pmid-10082337|pmid-9095401|pmid-10073425|pmid-12423385|pmid-11999624|pmid-10331710
Several reports have demonstrated that VGB has excellent efficacy, with complete control occurring in about 95% to 100% of the patients with infantile spasm due to tuberous sclerosis.34,35 However, recent reports of visual field defects associated with VGB treatment may limit its utility.11,12,36
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297
41,829
0
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Several reports have demonstrated that VGB has excellent efficacy, with complete control occurring in about 95% to 100% of the patients with infantile spasm due to tuberous sclerosis.34,35 However, recent reports of visual field defects associated with VGB treatment may limit its utility.11,12,36
[]
Several reports have demonstrated that VGB has excellent efficacy, with complete control occurring in about 95% to 100% of the patients with infantile spasm due to tuberous sclerosis.34,35 However, recent reports of visual field defects associated with VGB treatment may limit its utility.11,12,36
true
true
false
true
false
7,216
4
DISCUSSION
1
37
[ "B37", "B38", "B39", "B40", "B19", "B41", "B42", "B43", "B44", "B45", "B39", "B40", "B46", "B47" ]
16,941,739
pmid-7968065|pmid-11673015|pmid-15701562|pmid-10372900|pmid-9860068|pmid-12091848|pmid-10545555|pmid-12350395|pmid-9097361|pmid-8628501|pmid-15701562|pmid-10372900|pmid-9579944|pmid-11701273
Some open-label trials on instituting monotherapy or adjunctive therapy with the new antiepileptic drugs, including lamotrigine (LTG),37 felbamate,38 levetiracetam,39 zonisamide (ZNS),40 and topiramate,19 have reported preliminary evidence for the efficacy of these drugs in treating infantile spasm.
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300
41,830
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Some open-label trials on instituting monotherapy or adjunctive therapy with the new antiepileptic drugs, including lamotrigine (LTG),37 felbamate,38 levetiracetam,39 zonisamide (ZNS),40 and topiramate,19 have reported preliminary evidence for the efficacy of these drugs in treating infantile spasm.
[]
Some open-label trials on instituting monotherapy or adjunctive therapy with the new antiepileptic drugs, including lamotrigine (LTG),37 felbamate,38 levetiracetam,39 zonisamide (ZNS),40 and topiramate,19 have reported preliminary evidence for the efficacy of these drugs in treating infantile spasm.
true
true
true
true
true
7,217
4
DISCUSSION
1
37
[ "B37", "B38", "B39", "B40", "B19", "B41", "B42", "B43", "B44", "B45", "B39", "B40", "B46", "B47" ]
16,941,739
pmid-7968065|pmid-11673015|pmid-15701562|pmid-10372900|pmid-9860068|pmid-12091848|pmid-10545555|pmid-12350395|pmid-9097361|pmid-8628501|pmid-15701562|pmid-10372900|pmid-9579944|pmid-11701273
However, there are only limited reports on using LTG, felbamate and levetiracetam in patients with infantile spasm.
[ "37", "38", "39", "40", "19", "41", "42", "43", "44", "45", "39", "40", "46", "47" ]
115
41,831
0
false
However, there are only limited reports on using LTG, felbamate and levetiracetam in patients with infantile spasm.
[]
However, there are only limited reports on using LTG, felbamate and levetiracetam in patients with infantile spasm.
true
true
true
true
true
7,217
4
DISCUSSION
1
37
[ "B37", "B38", "B39", "B40", "B19", "B41", "B42", "B43", "B44", "B45", "B39", "B40", "B46", "B47" ]
16,941,739
pmid-7968065|pmid-11673015|pmid-15701562|pmid-10372900|pmid-9860068|pmid-12091848|pmid-10545555|pmid-12350395|pmid-9097361|pmid-8628501|pmid-15701562|pmid-10372900|pmid-9579944|pmid-11701273
LTG was reported to be effective as an add-on therapy for 30 patients with infantile spasm who were resistant to several other drugs.41
[ "37", "38", "39", "40", "19", "41", "42", "43", "44", "45", "39", "40", "46", "47" ]
135
41,832
0
false
LTG was reported to be effective as an add-on therapy for 30 patients with infantile spasm who were resistant to several other drugs.41
[]
LTG was reported to be effective as an add-on therapy for 30 patients with infantile spasm who were resistant to several other drugs.41
true
true
false
true
false
7,217
4
DISCUSSION
1
37
[ "B37", "B38", "B39", "B40", "B19", "B41", "B42", "B43", "B44", "B45", "B39", "B40", "B46", "B47" ]
16,941,739
pmid-7968065|pmid-11673015|pmid-15701562|pmid-10372900|pmid-9860068|pmid-12091848|pmid-10545555|pmid-12350395|pmid-9097361|pmid-8628501|pmid-15701562|pmid-10372900|pmid-9579944|pmid-11701273
However, this condition may progress to the potentially life-threatening Stevens-Johnson syndrome or toxic epidermal necrolysis.42 Because of this possibility, one recent report suggested the effectiveness of using low-dose LTG in 3 patients.43 Felbamate may be effective for infantile spasms, as a response was noted in...
[ "37", "38", "39", "40", "19", "41", "42", "43", "44", "45", "39", "40", "46", "47" ]
344
41,833
0
false
However, this condition may progress to the potentially life-threatening Stevens-Johnson syndrome or toxic epidermal necrolysis.42 Because of this possibility, one recent report suggested the effectiveness of using low-dose LTG in 3 patients.43 Felbamate may be effective for infantile spasms, as a response was noted in...
[]
However, this condition may progress to the potentially life-threatening Stevens-Johnson syndrome or toxic epidermal necrolysis.42 Because of this possibility, one recent report suggested the effectiveness of using low-dose LTG in 3 patients.43 Felbamate may be effective for infantile spasms, as a response was noted in...
true
true
true
true
true
7,217
4
DISCUSSION
1
37
[ "B37", "B38", "B39", "B40", "B19", "B41", "B42", "B43", "B44", "B45", "B39", "B40", "B46", "B47" ]
16,941,739
pmid-7968065|pmid-11673015|pmid-15701562|pmid-10372900|pmid-9860068|pmid-12091848|pmid-10545555|pmid-12350395|pmid-9097361|pmid-8628501|pmid-15701562|pmid-10372900|pmid-9579944|pmid-11701273
Yet after reports of aplastic anemia44 and hepatotoxicity,45 the use of felbamate as a treatment option for infantile spasm may be limited.
[ "37", "38", "39", "40", "19", "41", "42", "43", "44", "45", "39", "40", "46", "47" ]
139
41,834
0
false
Yet after reports of aplastic anemia44 and hepatotoxicity,45 the use of felbamate as a treatment option for infantile spasm may be limited.
[]
Yet after reports of aplastic anemia44 and hepatotoxicity,45 the use of felbamate as a treatment option for infantile spasm may be limited.
true
true
true
true
true
7,217
4
DISCUSSION
1
37
[ "B37", "B38", "B39", "B40", "B19", "B41", "B42", "B43", "B44", "B45", "B39", "B40", "B46", "B47" ]
16,941,739
pmid-7968065|pmid-11673015|pmid-15701562|pmid-10372900|pmid-9860068|pmid-12091848|pmid-10545555|pmid-12350395|pmid-9097361|pmid-8628501|pmid-15701562|pmid-10372900|pmid-9579944|pmid-11701273
One case report described the successful use of levetiracetam therapy in an 11-month-old infant with infantile spasms.
[ "37", "38", "39", "40", "19", "41", "42", "43", "44", "45", "39", "40", "46", "47" ]
118
41,835
0
false
One case report described the successful use of levetiracetam therapy in an 11-month-old infant with infantile spasms.
[]
One case report described the successful use of levetiracetam therapy in an 11-month-old infant with infantile spasms.
true
true
true
true
true
7,217
4
DISCUSSION
1
37
[ "B37", "B38", "B39", "B40", "B19", "B41", "B42", "B43", "B44", "B45", "B39", "B40", "B46", "B47" ]
16,941,739
pmid-7968065|pmid-11673015|pmid-15701562|pmid-10372900|pmid-9860068|pmid-12091848|pmid-10545555|pmid-12350395|pmid-9097361|pmid-8628501|pmid-15701562|pmid-10372900|pmid-9579944|pmid-11701273
The dose was gradually increased to 15 mg/kg/day up to a dosage of 60 mg/kg per day.39 ZNS has been used in Japan since 1989, and several reports have suggested that ZNS can be effective as the initial treatment for infantile spasm.40,46,47 However, there is only limited published data concerning the use of ZNS for inf...
[ "37", "38", "39", "40", "19", "41", "42", "43", "44", "45", "39", "40", "46", "47" ]
346
41,836
0
false
The dose was gradually increased to 15 mg/kg/day up to a dosage of 60 mg/kg per day.39 ZNS has been used in Japan since 1989, and several reports have suggested that ZNS can be effective as the initial treatment for infantile spasm.40,46,47 However, there is only limited published data concerning the use of ZNS for inf...
[]
The dose was gradually increased to 15 mg/kg/day up to a dosage of 60 mg/kg per day.39 ZNS has been used in Japan since 1989, and several reports have suggested that ZNS can be effective as the initial treatment for infantile spasm.40,46,47 However, there is only limited published data concerning the use of ZNS for inf...
true
true
true
true
true
7,217
5
DISCUSSION
1
19
[ "B19", "B16", "B48", "B49", "B50", "B51" ]
16,941,739
pmid-9860068|pmid-10227615|pmid-12694931|pmid-10768307|pmid-15519117|pmid-11248537
The data on using TPM as a potential first-line therapy for infantile spasm are relatively scarce.
[ "19", "16", "48", "49", "50", "51" ]
98
41,837
0
false
The data on using TPM as a potential first-line therapy for infantile spasm are relatively scarce.
[]
The data on using TPM as a potential first-line therapy for infantile spasm are relatively scarce.
true
true
true
true
true
7,218
5
DISCUSSION
1
19
[ "B19", "B16", "B48", "B49", "B50", "B51" ]
16,941,739
pmid-9860068|pmid-10227615|pmid-12694931|pmid-10768307|pmid-15519117|pmid-11248537
Glauser et al.
[ "19", "16", "48", "49", "50", "51" ]
14
41,838
0
false
Glauser et al.
[]
Glauser et al.
true
true
true
true
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7,218
5
DISCUSSION
1
19
[ "B19", "B16", "B48", "B49", "B50", "B51" ]
16,941,739
pmid-9860068|pmid-10227615|pmid-12694931|pmid-10768307|pmid-15519117|pmid-11248537
first reported that TPM might be effective as a first-line therapy for infantile spasm.19 The dose titration schedule of that study was 2-4 times faster, it was rapidly titrated over four weeks, and it was increased up to a dosage of 24 mg/kg per day, a greater dose increase than in previous pediatric TPM studies.16,48...
[ "19", "16", "48", "49", "50", "51" ]
323
41,839
0
false
first reported that TPM might be effective as a first-line therapy for infantile spasm.19 The dose titration schedule of that study was 2-4 times faster, it was rapidly titrated over four weeks, and it was increased up to a dosage of 24 mg/kg per day, a greater dose increase than in previous pediatric TPM studies.16,48...
[]
first reported that TPM might be effective as a first-line therapy for infantile spasm.19 The dose titration schedule of that study was 2-4 times faster, it was rapidly titrated over four weeks, and it was increased up to a dosage of 24 mg/kg per day, a greater dose increase than in previous pediatric TPM studies.16,48...
false
true
false
true
false
7,218
5
DISCUSSION
1
19
[ "B19", "B16", "B48", "B49", "B50", "B51" ]
16,941,739
pmid-9860068|pmid-10227615|pmid-12694931|pmid-10768307|pmid-15519117|pmid-11248537
In those studies, the mean dose of TPM during stabilization was 15.0 ± 5.7 mg/kg per day.
[ "19", "16", "48", "49", "50", "51" ]
89
41,840
0
false
In those studies, the mean dose of TPM during stabilization was 15.0 ± 5.7 mg/kg per day.
[]
In those studies, the mean dose of TPM during stabilization was 15.0 ± 5.7 mg/kg per day.
true
true
true
true
true
7,218
5
DISCUSSION
1
19
[ "B19", "B16", "B48", "B49", "B50", "B51" ]
16,941,739
pmid-9860068|pmid-10227615|pmid-12694931|pmid-10768307|pmid-15519117|pmid-11248537
These studies showed that 45% of patients became spasm free and 9 of 11 patients experienced a ≥ 50% reduction in spasm frequency.
[ "19", "16", "48", "49", "50", "51" ]
130
41,841
0
false
These studies showed that 45% of patients became spasm free and 9 of 11 patients experienced a ≥ 50% reduction in spasm frequency.
[]
These studies showed that 45% of patients became spasm free and 9 of 11 patients experienced a ≥ 50% reduction in spasm frequency.
true
true
true
true
true
7,218
5
DISCUSSION
1
19
[ "B19", "B16", "B48", "B49", "B50", "B51" ]
16,941,739
pmid-9860068|pmid-10227615|pmid-12694931|pmid-10768307|pmid-15519117|pmid-11248537
The slow dose titration of TPM allowed assessment of the patients' responses and increased patient tolerability to the drug.50
[ "19", "16", "48", "49", "50", "51" ]
126
41,842
0
false
The slow dose titration of TPM allowed assessment of the patients' responses and increased patient tolerability to the drug.50
[]
The slow dose titration of TPM allowed assessment of the patients' responses and increased patient tolerability to the drug.50
true
true
false
true
false
7,218
5
DISCUSSION
1
19
[ "B19", "B16", "B48", "B49", "B50", "B51" ]
16,941,739
pmid-9860068|pmid-10227615|pmid-12694931|pmid-10768307|pmid-15519117|pmid-11248537
The dose range of TPM is 1.2-12 mg/kg once or twice daily, and a slow titration of 0.5-2 mg/kg/day every 2 weeks was well tolerated and resulted in only mild to moderate adverse effects.51 In our study, TPM was initiated at 1 mg/kg per day and it was slowly titrated over 12 weeks up to a dosage of 12 mg/kg per day.
[ "19", "16", "48", "49", "50", "51" ]
316
41,843
0
false
The dose range of TPM is 1.2-12 mg/kg once or twice daily, and a slow titration of 0.5-2 mg/kg/day every 2 weeks was well tolerated and resulted in only mild to moderate adverse effects.51 In our study, TPM was initiated at 1 mg/kg per day and it was slowly titrated over 12 weeks up to a dosage of 12 mg/kg per day.
[]
The dose range of TPM is 1.2-12 mg/kg once or twice daily, and a slow titration of 0.5-2 mg/kg/day every 2 weeks was well tolerated and resulted in only mild to moderate adverse effects.51 In our study, TPM was initiated at 1 mg/kg per day and it was slowly titrated over 12 weeks up to a dosage of 12 mg/kg per day.
true
true
true
true
true
7,218
5
DISCUSSION
1
19
[ "B19", "B16", "B48", "B49", "B50", "B51" ]
16,941,739
pmid-9860068|pmid-10227615|pmid-12694931|pmid-10768307|pmid-15519117|pmid-11248537
Our results showed that the mean dose of TPM during stabilization was 9.1 ± 3.1 mg/kg per day, and 70% of the subjects achieved a ≥ 50% reduction in spasm frequency, including six patients who became spasm-free.
[ "19", "16", "48", "49", "50", "51" ]
211
41,844
0
false
Our results showed that the mean dose of TPM during stabilization was 9.1 ± 3.1 mg/kg per day, and 70% of the subjects achieved a ≥ 50% reduction in spasm frequency, including six patients who became spasm-free.
[]
Our results showed that the mean dose of TPM during stabilization was 9.1 ± 3.1 mg/kg per day, and 70% of the subjects achieved a ≥ 50% reduction in spasm frequency, including six patients who became spasm-free.
true
true
true
true
true
7,218
5
DISCUSSION
1
19
[ "B19", "B16", "B48", "B49", "B50", "B51" ]
16,941,739
pmid-9860068|pmid-10227615|pmid-12694931|pmid-10768307|pmid-15519117|pmid-11248537
These results suggested that the maximal therapeutic dose and mean dose of stabilization are lower than those reported by previous studies.
[ "19", "16", "48", "49", "50", "51" ]
139
41,845
0
false
These results suggested that the maximal therapeutic dose and mean dose of stabilization are lower than those reported by previous studies.
[]
These results suggested that the maximal therapeutic dose and mean dose of stabilization are lower than those reported by previous studies.
true
true
true
true
true
7,218
5
DISCUSSION
1
19
[ "B19", "B16", "B48", "B49", "B50", "B51" ]
16,941,739
pmid-9860068|pmid-10227615|pmid-12694931|pmid-10768307|pmid-15519117|pmid-11248537
Despite these differences, there were no differences in the observed effects of TPM between the reports.
[ "19", "16", "48", "49", "50", "51" ]
104
41,846
0
false
Despite these differences, there were no differences in the observed effects of TPM between the reports.
[]
Despite these differences, there were no differences in the observed effects of TPM between the reports.
true
true
true
true
true
7,218
6
DISCUSSION
1
46
[ "B46", "B52", "B5" ]
16,941,739
pmid-9579944|pmid-7788106|pmid-10757471
Although several reports displayed findings contrary to the current textbook findings, patients with cryptogenic infantile spasm responded better to TPM than did the symptomatic patients.46,52
[ "46", "52", "5" ]
192
41,847
0
false
Although several reports displayed findings contrary to the current textbook findings, patients with cryptogenic infantile spasm responded better to TPM than did the symptomatic patients.46,52
[]
Although several reports displayed findings contrary to the current textbook findings, patients with cryptogenic infantile spasm responded better to TPM than did the symptomatic patients.46,52
true
true
false
true
false
7,219
6
DISCUSSION
1
46
[ "B46", "B52", "B5" ]
16,941,739
pmid-9579944|pmid-7788106|pmid-10757471
Our data is similar to above the textbook features.
[ "46", "52", "5" ]
51
41,848
0
false
Our data is similar to above the textbook features.
[]
Our data is similar to above the textbook features.
true
true
true
true
true
7,219
6
DISCUSSION
1
46
[ "B46", "B52", "B5" ]
16,941,739
pmid-9579944|pmid-7788106|pmid-10757471
Four of eight cryptogenic patients (50%) had a normalized EEG and were spasm-free, whereas only 2 of 12 symptomatic patients (17%) responded.
[ "46", "52", "5" ]
141
41,849
0
false
Four of eight cryptogenic patients had a normalized EEG and were spasm-free, whereas only 2 of 12 symptomatic patients (17%) responded.
[ "50%" ]
Four of eight cryptogenic patients had a normalized EEG and were spasm-free, whereas only 2 of 12 symptomatic patients (17%) responded.
true
true
true
true
true
7,219
6
DISCUSSION
1
46
[ "B46", "B52", "B5" ]
16,941,739
pmid-9579944|pmid-7788106|pmid-10757471
The observed efficacy of TPM in our study is similar that observed for VGB in cryptogenic and symptomatic patients (62% and 29%, respectively).5
[ "46", "52", "5" ]
144
41,850
0
false
The observed efficacy of TPM in our study is similar that observed for VGB in cryptogenic and symptomatic patients (62% and 29%, respectively).5
[]
The observed efficacy of TPM in our study is similar that observed for VGB in cryptogenic and symptomatic patients.5
true
true
false
true
false
7,219
7
DISCUSSION
1
53
[ "B53", "B53", "B54", "B55", "B56", "B57", "B58" ]
16,941,739
pmid-9360061|pmid-9360061|pmid-11218053|pmid-8641242|pmid-11346412|pmid-12760427|pmid-12366731
The reported side effects of TPM include central nervous system problems,53 behavioral and cognitive problems,53 gastrointestinal effects,54 weight loss,55 acute angle-closure glaucoma,56 oligohydrosis57 and kidney stones.58
[ "53", "53", "54", "55", "56", "57", "58" ]
224
41,851
0
false
The reported side effects of TPM include central nervous system problems,53 behavioral and cognitive problems,53 gastrointestinal effects,54 weight loss,55 acute angle-closure glaucoma,56 oligohydrosis57 and kidney stones.58
[]
The reported side effects of TPM include central nervous system problems,53 behavioral and cognitive problems,53 gastrointestinal effects,54 weight loss,55 acute angle-closure glaucoma,56 oligohydrosis57 and kidney stones.58
true
true
false
true
false
7,220
7
DISCUSSION
1
53
[ "B53", "B53", "B54", "B55", "B56", "B57", "B58" ]
16,941,739
pmid-9360061|pmid-9360061|pmid-11218053|pmid-8641242|pmid-11346412|pmid-12760427|pmid-12366731
Although five patients in this study manifested adverse effects, they were mild to moderate in severity.
[ "53", "53", "54", "55", "56", "57", "58" ]
104
41,852
0
false
Although five patients in this study manifested adverse effects, they were mild to moderate in severity.
[]
Although five patients in this study manifested adverse effects, they were mild to moderate in severity.
true
true
true
true
true
7,220
7
DISCUSSION
1
53
[ "B53", "B53", "B54", "B55", "B56", "B57", "B58" ]
16,941,739
pmid-9360061|pmid-9360061|pmid-11218053|pmid-8641242|pmid-11346412|pmid-12760427|pmid-12366731
The side effect profile mainly involved the central nervous system, and these problems were generally short-lived.
[ "53", "53", "54", "55", "56", "57", "58" ]
114
41,853
0
false
The side effect profile mainly involved the central nervous system, and these problems were generally short-lived.
[]
The side effect profile mainly involved the central nervous system, and these problems were generally short-lived.
true
true
true
true
true
7,220
7
DISCUSSION
1
53
[ "B53", "B53", "B54", "B55", "B56", "B57", "B58" ]
16,941,739
pmid-9360061|pmid-9360061|pmid-11218053|pmid-8641242|pmid-11346412|pmid-12760427|pmid-12366731
None of the patients in our study developed weight loss, acute angle-closure glaucoma, or kidney stones.
[ "53", "53", "54", "55", "56", "57", "58" ]
104
41,854
0
false
None of the patients in our study developed weight loss, acute angle-closure glaucoma, or kidney stones.
[]
None of the patients in our study developed weight loss, acute angle-closure glaucoma, or kidney stones.
true
true
true
true
true
7,220
8
DISCUSSION
0
null
null
16,941,739
null
In conclusion, our results demonstrate that TPM might be both effective and well tolerated as a first-line therapy for infantile spasm.
null
135
41,855
0
false
null
null
In conclusion, our results demonstrate that TPM might be both effective and well tolerated as a first-line therapy for infantile spasm.
true
true
true
true
true
7,221
8
DISCUSSION
0
null
null
16,941,739
null
We believe that slow dose titration and a low maximal dose of TPM should be considered when starting monotherapy in patients with infantile spasm.
null
146
41,856
0
false
null
null
We believe that slow dose titration and a low maximal dose of TPM should be considered when starting monotherapy in patients with infantile spasm.
true
true
true
true
true
7,221
8
DISCUSSION
0
null
null
16,941,739
null
Yet further studies involving a larger numbers of patients are warranted and will be required to determine the long-term outcome of the TPM responders.
null
151
41,857
0
false
null
null
Yet further studies involving a larger numbers of patients are warranted and will be required to determine the long-term outcome of the TPM responders.
true
true
true
true
true
7,221
0
INTRODUCTION
1
1
[ "B1", "B2" ]
19,429,891
pmid-9568909|pmid-11152613
Genome-wide estimations indicate that alpha-helical transmembrane (TM) proteins comprise roughly 20–30% of the genes in a typical organism (1,2).
[ "1", "2" ]
145
41,858
0
false
Genome-wide estimations indicate that alpha-helical transmembrane (TM) proteins comprise roughly 20–30% of the genes in a typical organism.
[ "1,2" ]
Genome-wide estimations indicate that alpha-helical transmembrane (TM) proteins comprise roughly 20–30% of the genes in a typical organism.
true
true
true
true
true
7,222
0
INTRODUCTION
1
1
[ "B1", "B2" ]
19,429,891
pmid-9568909|pmid-11152613
These proteins are essential for vital biological functions such as cell communication and signaling, active and passive transport of molecules across the membrane, energy-transduction and cell–cell adhesion.
[ "1", "2" ]
208
41,859
0
false
These proteins are essential for vital biological functions such as cell communication and signaling, active and passive transport of molecules across the membrane, energy-transduction and cell–cell adhesion.
[]
These proteins are essential for vital biological functions such as cell communication and signaling, active and passive transport of molecules across the membrane, energy-transduction and cell–cell adhesion.
true
true
true
true
true
7,222
1
INTRODUCTION
0
null
null
19,429,891
null
Prediction of membrane protein topology (i.e.
null
45
41,860
0
false
null
null
Prediction of membrane protein topology (i.e.
true
true
true
true
true
7,223
1
INTRODUCTION
0
null
null
19,429,891
null
the positions and in/out orientation of the membrane-spanning regions) serves to quickly obtain fundamental structural knowledge of TM proteins in silico.
null
154
41,861
0
false
null
null
the positions and in/out orientation of the membrane-spanning regions) serves to quickly obtain fundamental structural knowledge of TM proteins in silico.
false
true
true
true
false
7,223
1
INTRODUCTION
0
null
null
19,429,891
null
For TM proteins, computational methods are particularly important since structural knowledge is difficult to attain experimentally.
null
131
41,862
0
false
null
null
For TM proteins, computational methods are particularly important since structural knowledge is difficult to attain experimentally.
true
true
true
true
true
7,223
1
INTRODUCTION
0
null
null
19,429,891
null
Therefore, a correctly predicted topology provides an excellent template for further studies in the laboratory and might facilitate and improve functional and structural classification of protein sequences on a genomic level.
null
225
41,863
0
false
null
null
Therefore, a correctly predicted topology provides an excellent template for further studies in the laboratory and might facilitate and improve functional and structural classification of protein sequences on a genomic level.
true
true
true
true
true
7,223
2
INTRODUCTION
1
2
[ "B2", "B3", "B4", "B5", "B6 B7 B8" ]
19,429,891
pmid-11152613|pmid-15111065|pmid-16844984|pmid-11119716|pmid-7828069|pmid-15215417|pmid-17274768
A number of different methods have been developed over the last decades that predict topology with high accuracy.
[ "2", "3", "4", "5", "6–8" ]
113
41,864
0
false
A number of different methods have been developed over the last decades that predict topology with high accuracy.
[]
A number of different methods have been developed over the last decades that predict topology with high accuracy.
true
true
true
true
true
7,224
2
INTRODUCTION
1
4
[ "B2", "B3", "B4", "B5", "B6 B7 B8" ]
19,429,891
pmid-11152613|pmid-15111065|pmid-16844984|pmid-11119716|pmid-7828069|pmid-15215417|pmid-17274768
Many of these methods are freely available as web servers, both individually (2,3) and combining the results from several methods (4).
[ "2", "3", "4", "5", "6–8" ]
134
41,865
1
false
Many of these methods are freely available as web servers, both individually and combining the results from several methods.
[ "2,3", "4" ]
Many of these methods are freely available as web servers, both individually and combining the results from several methods.
true
true
true
true
true
7,224
2
INTRODUCTION
1
2
[ "B2", "B3", "B4", "B5", "B6 B7 B8" ]
19,429,891
pmid-11152613|pmid-15111065|pmid-16844984|pmid-11119716|pmid-7828069|pmid-15215417|pmid-17274768
With prediction algorithms based on different principles, it is not a surprising observation that for a fair amount of proteins, different prediction methods disagree about the final result, causing uncertainty about the correct topology.
[ "2", "3", "4", "5", "6–8" ]
238
41,866
0
false
With prediction algorithms based on different principles, it is not a surprising observation that for a fair amount of proteins, different prediction methods disagree about the final result, causing uncertainty about the correct topology.
[]
With prediction algorithms based on different principles, it is not a surprising observation that for a fair amount of proteins, different prediction methods disagree about the final result, causing uncertainty about the correct topology.
true
true
true
true
true
7,224
2
INTRODUCTION
1
5
[ "B2", "B3", "B4", "B5", "B6 B7 B8" ]
19,429,891
pmid-11152613|pmid-15111065|pmid-16844984|pmid-11119716|pmid-7828069|pmid-15215417|pmid-17274768
Earlier studies have stated, for example, that topology predictions are more likely to be correct when individual methods agree in their prediction than when they do not (5), but so far only a few attempts have been made at combining individual topology predictions into one consensus prediction (6–8).
[ "2", "3", "4", "5", "6–8" ]
302
41,867
1
false
Earlier studies have stated, for example, that topology predictions are more likely to be correct when individual methods agree in their prediction than when they do not, but so far only a few attempts have been made at combining individual topology predictions into one consensus prediction.
[ "5", "6–8" ]
Earlier studies have stated, for example, that topology predictions are more likely to be correct when individual methods agree in their prediction than when they do not, but so far only a few attempts have been made at combining individual topology predictions into one consensus prediction.
true
true
true
true
true
7,224
3
INTRODUCTION
0
null
null
19,429,891
null
Here we present TOPCONS, a fundamental algorithm that combines an arbitrary number of topology predictions into one consensus prediction and quantifies the reliability of the prediction based on the level of agreement between the underlying methods, both on the protein level and on the level of individual TM regions.
null
318
41,868
0
false
null
null
Here we present TOPCONS, a fundamental algorithm that combines an arbitrary number of topology predictions into one consensus prediction and quantifies the reliability of the prediction based on the level of agreement between the underlying methods, both on the protein level and on the level of individual TM regions.
true
true
true
true
true
7,225
4
INTRODUCTION
1
9
[ "B9", "B10", "B11" ]
19,429,891
pmid-18474507|pmid-15215532|pmid-18477697
We also present an implementation of TOPCONS as a web-server based on the individual topology prediction methods OCTOPUS (9), PRO-TMHMM and PRODIV-TMHMM (10), SCAMPI-single and SCAMPI-multi (11).
[ "9", "10", "11" ]
195
41,869
1
false
We also present an implementation of TOPCONS as a web-server based on the individual topology prediction methods OCTOPUS, PRO-TMHMM and PRODIV-TMHMM, SCAMPI-single and SCAMPI-multi.
[ "9", "10", "11" ]
We also present an implementation of TOPCONS as a web-server based on the individual topology prediction methods OCTOPUS, PRO-TMHMM and PRODIV-TMHMM, SCAMPI-single and SCAMPI-multi.
true
true
true
true
true
7,226
4
INTRODUCTION
1
9
[ "B9", "B10", "B11" ]
19,429,891
pmid-18474507|pmid-15215532|pmid-18477697
During the development a large set of combinations using many different topology predictors as an input to TOPCONS was tested.
[ "9", "10", "11" ]
126
41,870
0
false
During the development a large set of combinations using many different topology predictors as an input to TOPCONS was tested.
[]
During the development a large set of combinations using many different topology predictors as an input to TOPCONS was tested.
true
true
true
true
true
7,226
4
INTRODUCTION
1
9
[ "B9", "B10", "B11" ]
19,429,891
pmid-18474507|pmid-15215532|pmid-18477697
However, no combination performed significantly better than the one used here and therefore we decided to only use methods developed in house in the current version of the TOPCONS webserver.
[ "9", "10", "11" ]
190
41,871
0
false
However, no combination performed significantly better than the one used here and therefore we decided to only use methods developed in house in the current version of the TOPCONS webserver.
[]
However, no combination performed significantly better than the one used here and therefore we decided to only use methods developed in house in the current version of the TOPCONS webserver.
true
true
true
true
true
7,226
0
INTRODUCTION
1
1
[ "B1", "B2" ]
17,984,072
pmid-16381881|pmid-14681417
xBASE grew out of coliBASE, CampyDB and several similar projects, which were restricted to selected taxonomic groups of bacteria (1,2).
[ "1", "2" ]
135
41,872
0
false
xBASE grew out of coliBASE, CampyDB and several similar projects, which were restricted to selected taxonomic groups of bacteria.
[ "1,2" ]
xBASE grew out of coliBASE, CampyDB and several similar projects, which were restricted to selected taxonomic groups of bacteria.
false
true
true
true
false
7,227
0
INTRODUCTION
1
1
[ "B1", "B2" ]
17,984,072
pmid-16381881|pmid-14681417
In its initial implementation, xBASE was simply an umbrella term applied to a set of distinct databases that relied on a similar schema.
[ "1", "2" ]
136
41,873
0
false
In its initial implementation, xBASE was simply an umbrella term applied to a set of distinct databases that relied on a similar schema.
[]
In its initial implementation, xBASE was simply an umbrella term applied to a set of distinct databases that relied on a similar schema.
true
true
true
true
true
7,227
0
INTRODUCTION
1
1
[ "B1", "B2" ]
17,984,072
pmid-16381881|pmid-14681417
In creating xBASE2, we have developed a new integrated, comprehensive bacterial genomes database, with greatly increased coverage, many new features and an improved user interface and code base.
[ "1", "2" ]
194
41,874
0
false
In creating xBASE2, we have developed a new integrated, comprehensive bacterial genomes database, with greatly increased coverage, many new features and an improved user interface and code base.
[]
In creating xBASE2, we have developed a new integrated, comprehensive bacterial genomes database, with greatly increased coverage, many new features and an improved user interface and code base.
true
true
true
true
true
7,227
0
INTRODUCTION
1
An et al., 1996
[ "bib2", "bib10", "bib15", "bib29" ]
12,601,084
NA|NA|NA|NA
Investigation of ion channel defects associated with the long QT syndrome (LQTS)* has provided new insights into fundamental mechanisms through which ion channel activity and its modulation by drugs control the duration of the cardiac ventricular action potential and consequently the QT interval of the electrocardiogra...
[ "An et al., 1996", "Dumaine and Kirsch, 1998", "Kambouris et al., 2000", "Viswanathan et al., 2001" ]
328
41,875
0
false
Investigation of ion channel defects associated with the long QT syndrome (LQTS)* has provided new insights into fundamental mechanisms through which ion channel activity and its modulation by drugs control the duration of the cardiac ventricular action potential and consequently the QT interval of the electrocardiogra...
[]
Investigation of ion channel defects associated with the long QT syndrome (LQTS)* has provided new insights into fundamental mechanisms through which ion channel activity and its modulation by drugs control the duration of the cardiac ventricular action potential and consequently the QT interval of the electrocardiogra...
true
true
true
true
true
7,228
0
INTRODUCTION
1
An et al., 1996
[ "bib2", "bib10", "bib15", "bib29" ]
12,601,084
NA|NA|NA|NA
In particular, the unanticipated discovery of mutations in SCN5A, the gene coding for the α subunit of the heart voltage–gated Na+ channel, associated with LQTS variant 3 (LQT-3) and the use of Na+ channel blockers to control QT prolongation in LQT-3 mutation carriers has renewed interest into the fundamental mechanism...
[ "An et al., 1996", "Dumaine and Kirsch, 1998", "Kambouris et al., 2000", "Viswanathan et al., 2001" ]
459
41,876
0
false
In particular, the unanticipated discovery of mutations in SCN5A, the gene coding for the α subunit of the heart voltage–gated Na+ channel, associated with LQTS variant 3 (LQT-3) and the use of Na+ channel blockers to control QT prolongation in LQT-3 mutation carriers has renewed interest into the fundamental mechanism...
[ "An et al., 1996; Dumaine and Kirsch, 1998; Kambouris et al., 2000; Viswanathan et al., 2001" ]
In particular, the unanticipated discovery of mutations in SCN5A, the gene coding for the α subunit of the heart voltage–gated Na+ channel, associated with LQTS variant 3 (LQT-3) and the use of Na+ channel blockers to control QT prolongation in LQT-3 mutation carriers has renewed interest into the fundamental mechanism...
true
true
true
true
true
7,228
1
INTRODUCTION
1
Brugada et al., 1999
[ "bib6", "bib5", "bib6" ]
12,601,084
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
Flecainide, the prototypical Class 1c antiarrhythmic agent, is of particular interest because it has been shown to be more effective than lidocaine, a prototypical Class 1b agent, in the management of QT prolongation in some LQT-3 mutation carriers (Brugada et al., 1999; Benhorin et al., 2000).
[ "Brugada et al., 1999", "Benhorin et al., 2000", "Brugada et al., 1999" ]
295
41,877
0
false
Flecainide, the prototypical Class 1c antiarrhythmic agent, is of particular interest because it has been shown to be more effective than lidocaine, a prototypical Class 1b agent, in the management of QT prolongation in some LQT-3 mutation carriers.
[ "Brugada et al., 1999; Benhorin et al., 2000" ]
Flecainide, the prototypical Class 1c antiarrhythmic agent, is of particular interest because it has been shown to be more effective than lidocaine, a prototypical Class 1b agent, in the management of QT prolongation in some LQT-3 mutation carriers.
true
true
true
true
true
7,229
1
INTRODUCTION
1
Brugada et al., 1999
[ "bib6", "bib5", "bib6" ]
12,601,084
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
Additionally, flecainide is used in diagnostic tests to identify patients at risk for the Brugada syndrome, an inherited form of idiopathic ventricular fibrillation that too is associated with SCN5A mutation (Brugada et al., 1999).
[ "Brugada et al., 1999", "Benhorin et al., 2000", "Brugada et al., 1999" ]
231
41,878
1
false
Additionally, flecainide is used in diagnostic tests to identify patients at risk for the Brugada syndrome, an inherited form of idiopathic ventricular fibrillation that too is associated with SCN5A mutation.
[ "Brugada et al., 1999" ]
Additionally, flecainide is used in diagnostic tests to identify patients at risk for the Brugada syndrome, an inherited form of idiopathic ventricular fibrillation that too is associated with SCN5A mutation.
true
true
true
true
true
7,229
1
INTRODUCTION
1
Brugada et al., 1999
[ "bib6", "bib5", "bib6" ]
12,601,084
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
Clearly, understanding fundamental differences between the mechanisms of action of flecainide and lidocaine has significance, not only from the point of view of the fundamental molecular pharmacology of the cardiac Na+ channel, but also for its importance in detecting and treating these inherited arrhythmias.
[ "Brugada et al., 1999", "Benhorin et al., 2000", "Brugada et al., 1999" ]
310
41,879
0
false
Clearly, understanding fundamental differences between the mechanisms of action of flecainide and lidocaine has significance, not only from the point of view of the fundamental molecular pharmacology of the cardiac Na+ channel, but also for its importance in detecting and treating these inherited arrhythmias.
[]
Clearly, understanding fundamental differences between the mechanisms of action of flecainide and lidocaine has significance, not only from the point of view of the fundamental molecular pharmacology of the cardiac Na+ channel, but also for its importance in detecting and treating these inherited arrhythmias.
true
true
true
true
true
7,229
2
INTRODUCTION
1
Hille, 1977a
[ "bib12", "bib3", "bib21", "bib17", "bib17" ]
12,601,084
NA|NA|NA|NA|NA
Flecainide and lidocaine have similar chemical structures but markedly different effects on sodium channel activity.
[ "Hille, 1977a", "Anno and Hondeghem, 1990", "Ragsdale et al., 1996", "Liu et al., 2002", "Liu et al., 2002" ]
116
41,880
0
false
Flecainide and lidocaine have similar chemical structures but markedly different effects on sodium channel activity.
[]
Flecainide and lidocaine have similar chemical structures but markedly different effects on sodium channel activity.
true
true
true
true
true
7,230
2
INTRODUCTION
1
Hille, 1977a
[ "bib12", "bib3", "bib21", "bib17", "bib17" ]
12,601,084
NA|NA|NA|NA|NA
Both drugs promote tonic and use channel state–dependent block (block that increases with channel activity) of Na+ channels.
[ "Hille, 1977a", "Anno and Hondeghem, 1990", "Ragsdale et al., 1996", "Liu et al., 2002", "Liu et al., 2002" ]
124
41,881
0
false
Both drugs promote tonic and use channel state–dependent block (block that increases with channel activity) of Na+ channels.
[]
Both drugs promote tonic and use channel state–dependent block of Na+ channels.
true
true
true
true
true
7,230
2
INTRODUCTION
1
Hille, 1977a
[ "bib12", "bib3", "bib21", "bib17", "bib17" ]
12,601,084
NA|NA|NA|NA|NA
The affinity of lidocaine is higher for inactivated compared with resting channels, and hence the stabilization of inactivated lidocaine-bound channels has been shown to underlie its state-dependent Na+ channel block (Hille, 1977a).
[ "Hille, 1977a", "Anno and Hondeghem, 1990", "Ragsdale et al., 1996", "Liu et al., 2002", "Liu et al., 2002" ]
232
41,882
1
false
The affinity of lidocaine is higher for inactivated compared with resting channels, and hence the stabilization of inactivated lidocaine-bound channels has been shown to underlie its state-dependent Na+ channel block.
[ "Hille, 1977a" ]
The affinity of lidocaine is higher for inactivated compared with resting channels, and hence the stabilization of inactivated lidocaine-bound channels has been shown to underlie its state-dependent Na+ channel block.
true
true
true
true
true
7,230
2
INTRODUCTION
1
Hille, 1977a
[ "bib12", "bib3", "bib21", "bib17", "bib17" ]
12,601,084
NA|NA|NA|NA|NA
In contrast with lidocaine, flecainide requires channels to open before it causes use-dependent block (UDB) and consequently has been associated with block of open channels (Anno and Hondeghem, 1990; Ragsdale et al., 1996; Liu et al., 2002).
[ "Hille, 1977a", "Anno and Hondeghem, 1990", "Ragsdale et al., 1996", "Liu et al., 2002", "Liu et al., 2002" ]
241
41,883
0
false
In contrast with lidocaine, flecainide requires channels to open before it causes use-dependent block (UDB) and consequently has been associated with block of open channels.
[ "Anno and Hondeghem, 1990; Ragsdale et al., 1996; Liu et al., 2002" ]
In contrast with lidocaine, flecainide requires channels to open before it causes use-dependent block (UDB) and consequently has been associated with block of open channels.
true
true
true
true
true
7,230
2
INTRODUCTION
1
Hille, 1977a
[ "bib12", "bib3", "bib21", "bib17", "bib17" ]
12,601,084
NA|NA|NA|NA|NA
However, investigation of disease-associated mutant cardiac Na+ channels recently has provided evidence that although necessary, channel openings are not sufficient to explain flecainide UDB.
[ "Hille, 1977a", "Anno and Hondeghem, 1990", "Ragsdale et al., 1996", "Liu et al., 2002", "Liu et al., 2002" ]
191
41,884
0
false
However, investigation of disease-associated mutant cardiac Na+ channels recently has provided evidence that although necessary, channel openings are not sufficient to explain flecainide UDB.
[]
However, investigation of disease-associated mutant cardiac Na+ channels recently has provided evidence that although necessary, channel openings are not sufficient to explain flecainide UDB.
true
true
true
true
true
7,230
2
INTRODUCTION
1
Liu et al., 2002
[ "bib12", "bib3", "bib21", "bib17", "bib17" ]
12,601,084
NA|NA|NA|NA|NA
Instead, like lidocaine, flecainide block may be determined by preferential interaction with inactivated channels (Liu et al., 2002).
[ "Hille, 1977a", "Anno and Hondeghem, 1990", "Ragsdale et al., 1996", "Liu et al., 2002", "Liu et al., 2002" ]
133
41,885
1
false
Instead, like lidocaine, flecainide block may be determined by preferential interaction with inactivated channels.
[ "Liu et al., 2002" ]
Instead, like lidocaine, flecainide block may be determined by preferential interaction with inactivated channels.
true
true
true
true
true
7,230
2
INTRODUCTION
1
Hille, 1977a
[ "bib12", "bib3", "bib21", "bib17", "bib17" ]
12,601,084
NA|NA|NA|NA|NA
Further, the results of that study suggested that differential access to a common receptor might account for differences between these two drugs.
[ "Hille, 1977a", "Anno and Hondeghem, 1990", "Ragsdale et al., 1996", "Liu et al., 2002", "Liu et al., 2002" ]
145
41,886
0
false
Further, the results of that study suggested that differential access to a common receptor might account for differences between these two drugs.
[]
Further, the results of that study suggested that differential access to a common receptor might account for differences between these two drugs.
true
true
true
true
true
7,230
3
INTRODUCTION
1
Hille, 1977a
[ "bib12", "bib27", "bib26", "bib12", "bib8" ]
12,601,084
NA|NA|NA|NA|NA
Investigation into differential access to a common receptor has been hampered by differences in the physical chemical properties of the two drugs.
[ "Hille, 1977a", "Strichartz et al., 1990", "Strichartz, 1973", "Hille, 1977a", "Chernoff and Strichartz, 1990" ]
146
41,887
0
false
Investigation into differential access to a common receptor has been hampered by differences in the physical chemical properties of the two drugs.
[]
Investigation into differential access to a common receptor has been hampered by differences in the physical chemical properties of the two drugs.
true
true
true
true
true
7,231
3
INTRODUCTION
1
Hille, 1977a
[ "bib12", "bib27", "bib26", "bib12", "bib8" ]
12,601,084
NA|NA|NA|NA|NA
Lidocaine has a pKa between 7.8–8.6 and thus may be up to 50% neutral at physiological pH.
[ "Hille, 1977a", "Strichartz et al., 1990", "Strichartz, 1973", "Hille, 1977a", "Chernoff and Strichartz, 1990" ]
90
41,888
0
false
Lidocaine has a pKa between 7.8–8.6 and thus may be up to 50% neutral at physiological pH.
[]
Lidocaine has a pKa between 7.8–8.6 and thus may be up to 50% neutral at physiological pH.
true
true
true
true
true
7,231
3
INTRODUCTION
1
Hille, 1977a
[ "bib12", "bib27", "bib26", "bib12", "bib8" ]
12,601,084
NA|NA|NA|NA|NA
In contrast, flecainide has a pKa of ∼9.3, resulting in >99% of the drug in ionized and <1% in neutral forms at pH 7.4 (Hille, 1977a;
[ "Hille, 1977a", "Strichartz et al., 1990", "Strichartz, 1973", "Hille, 1977a", "Chernoff and Strichartz, 1990" ]
133
41,889
0
false
In contrast, flecainide has a pKa of ∼9.3, resulting in >99% of the drug in ionized and <1% in neutral forms at pH 7.4 (Hille, 1977a;
[]
In contrast, flecainide has a pKa of ∼9.3, resulting in >99% of the drug in ionized and <1% in neutral forms at pH 7.4 (Hille, 1977a;
true
true
false
true
false
7,231
3
INTRODUCTION
1
Hille, 1977a
[ "bib12", "bib27", "bib26", "bib12", "bib8" ]
12,601,084
NA|NA|NA|NA|NA
Strichartz et al., 1990).
[ "Hille, 1977a", "Strichartz et al., 1990", "Strichartz, 1973", "Hille, 1977a", "Chernoff and Strichartz, 1990" ]
25
41,890
0
false
Strichartz et al., 1990).
[]
Strichartz et al., 1990).
true
true
true
true
true
7,231
3
INTRODUCTION
1
Hille, 1977a
[ "bib12", "bib27", "bib26", "bib12", "bib8" ]
12,601,084
NA|NA|NA|NA|NA
Thus, the charge on flecainide is likely to restrict access of the drug to a receptor site, confer the dependence of use-dependent block on channel openings, and account for most of the differences between it and lidocaine (Strichartz, 1973; Hille, 1977a; Chernoff and Strichartz, 1990).
[ "Hille, 1977a", "Strichartz et al., 1990", "Strichartz, 1973", "Hille, 1977a", "Chernoff and Strichartz, 1990" ]
287
41,891
0
false
Thus, the charge on flecainide is likely to restrict access of the drug to a receptor site, confer the dependence of use-dependent block on channel openings, and account for most of the differences between it and lidocaine.
[ "Strichartz, 1973; Hille, 1977a; Chernoff and Strichartz, 1990" ]
Thus, the charge on flecainide is likely to restrict access of the drug to a receptor site, confer the dependence of use-dependent block on channel openings, and account for most of the differences between it and lidocaine.
true
true
true
true
true
7,231
3
INTRODUCTION
1
Hille, 1977a
[ "bib12", "bib27", "bib26", "bib12", "bib8" ]
12,601,084
NA|NA|NA|NA|NA
However, a direct test of this possibility has not been possible because of the marked differences in distribution between neutral and charged forms of each compound.
[ "Hille, 1977a", "Strichartz et al., 1990", "Strichartz, 1973", "Hille, 1977a", "Chernoff and Strichartz, 1990" ]
166
41,892
0
false
However, a direct test of this possibility has not been possible because of the marked differences in distribution between neutral and charged forms of each compound.
[]
However, a direct test of this possibility has not been possible because of the marked differences in distribution between neutral and charged forms of each compound.
true
true
true
true
true
7,231
4
INTRODUCTION
0
null
null
12,601,084
NA|NA|NA|NA|NA|NA|NA|NA|NA
Here we employed two custom-synthesized flecainide analogues, NU-FL and QX-FL, to investigate the molecular determinants of flecainide activity.
null
144
41,893
0
false
null
null
Here we employed two custom-synthesized flecainide analogues, NU-FL and QX-FL, to investigate the molecular determinants of flecainide activity.
true
true
true
true
true
7,232
4
INTRODUCTION
0
null
null
12,601,084
NA|NA|NA|NA|NA|NA|NA|NA|NA
NU-FL has nearly identical hyrophobicity and very similar three-dimensional structure compared with flecainide, but has a very different pKa.
null
141
41,894
0
false
null
null
NU-FL has nearly identical hyrophobicity and very similar three-dimensional structure compared with flecainide, but has a very different pKa.
true
true
true
true
true
7,232
4
INTRODUCTION
0
null
null
12,601,084
NA|NA|NA|NA|NA|NA|NA|NA|NA
As measured by titration, NU-FL has an approximate pKa value of 6.4.
null
68
41,895
0
false
null
null
As measured by titration, NU-FL has an approximate pKa value of 6.4.
true
true
true
true
true
7,232
4
INTRODUCTION
0
null
null
12,601,084
NA|NA|NA|NA|NA|NA|NA|NA|NA
Consequently, it should be nearly 90% neutral at physiological pH, thus more closely resembling the ionization profile of lidocaine.
null
132
41,896
0
false
null
null
Consequently, it should be nearly 90% neutral at physiological pH, thus more closely resembling the ionization profile of lidocaine.
true
true
true
true
true
7,232
4
INTRODUCTION
0
null
null
12,601,084
NA|NA|NA|NA|NA|NA|NA|NA|NA
QX-FL shares a very similar three-dimensional structure with the parent compound flecainide, but is fully charged at physiological pH, and thus is well suited to discriminate between hydrophilic and hydrophobic access to its receptor.
null
234
41,897
0
false
null
null
QX-FL shares a very similar three-dimensional structure with the parent compound flecainide, but is fully charged at physiological pH, and thus is well suited to discriminate between hydrophilic and hydrophobic access to its receptor.
true
true
true
true
true
7,232
4
INTRODUCTION
0
null
null
12,601,084
NA|NA|NA|NA|NA|NA|NA|NA|NA
We compared the effects of flecainide, NU-FL, QX-FL, and lidocaine on human heart (hH1) sodium channels expressed in human embryonic kidney (HEK) 293 cells to better understand the specific mechanism of block by flecainide.
null
223
41,898
0
false
null
null
We compared the effects of flecainide, NU-FL, QX-FL, and lidocaine on human heart (hH1) sodium channels expressed in human embryonic kidney (HEK) 293 cells to better understand the specific mechanism of block by flecainide.
true
true
true
true
true
7,232
4
INTRODUCTION
0
null
null
12,601,084
NA|NA|NA|NA|NA|NA|NA|NA|NA
Our results indicate that like lidocaine, the tertiary flecainide analogue (NU-FL) interacts preferentially with inactivated channels without prerequisite channel openings, while flecainide (and QX-FL) is ineffective in blocking channels that inactivate without first opening.
null
276
41,899
0
false
null
null
Our results indicate that like lidocaine, the tertiary flecainide analogue (NU-FL) interacts preferentially with inactivated channels without prerequisite channel openings, while flecainide (and QX-FL) is ineffective in blocking channels that inactivate without first opening.
true
true
true
true
true
7,232
4
INTRODUCTION
0
null
null
12,601,084
NA|NA|NA|NA|NA|NA|NA|NA|NA
Ionized flecainide underlies UDB.
null
33
41,900
0
false
null
null
Ionized flecainide underlies UDB.
true
true
true
true
true
7,232
4
INTRODUCTION
0
null
null
12,601,084
NA|NA|NA|NA|NA|NA|NA|NA|NA
Our results show marked UDB of channels by internally, but not externally, applied QX-FL, with voltage and time-dependent characteristics consistent with intracellular access to a common receptor for local anesthetic molecules.
null
227
41,901
0
false
null
null
Our results show marked UDB of channels by internally, but not externally, applied QX-FL, with voltage and time-dependent characteristics consistent with intracellular access to a common receptor for local anesthetic molecules.
true
true
true
true
true
7,232
4
INTRODUCTION
0
null
null
12,601,084
NA|NA|NA|NA|NA|NA|NA|NA|NA
QX-FL block requires the open conformation of the channel, suggesting that channel openings unmask a preferred intracellular access route allowing QX-FL to bind to the LA receptor site in the inner mouth of the channel pore.
null
224
41,902
0
false
null
null
QX-FL block requires the open conformation of the channel, suggesting that channel openings unmask a preferred intracellular access route allowing QX-FL to bind to the LA receptor site in the inner mouth of the channel pore.
true
true
true
true
true
7,232
4
INTRODUCTION
0
null
null
12,601,084
NA|NA|NA|NA|NA|NA|NA|NA|NA
Further, because the slow recovery of channels from QX-FL block was impeded by outer pore block by tetrodotoxin, our data also suggest that drug can diffuse away from channels via the outer pore even in the absence transitions into the open state.
null
247
41,903
0
false
null
null
Further, because the slow recovery of channels from QX-FL block was impeded by outer pore block by tetrodotoxin, our data also suggest that drug can diffuse away from channels via the outer pore even in the absence transitions into the open state.
true
true
true
true
true
7,232
4
INTRODUCTION
0
null
null
12,601,084
NA|NA|NA|NA|NA|NA|NA|NA|NA
Our data strongly suggest that it is the difference in degree of ionization (pKa) between lidocaine and flecainide, rather than differences in their gross structural features, that determines distinction in block of cardiac Na+ channels.
null
237
41,904
0
false
null
null
Our data strongly suggest that it is the difference in degree of ionization (pKa) between lidocaine and flecainide, rather than differences in their gross structural features, that determines distinction in block of cardiac Na+ channels.
true
true
true
true
true
7,232
4
INTRODUCTION
0
null
null
12,601,084
NA|NA|NA|NA|NA|NA|NA|NA|NA
The data also suggest that the two drugs share a common receptor, but, as outlined in the modulated receptor hypothesis, reach this receptor by distinct routes.
null
160
41,905
0
false
null
null
The data also suggest that the two drugs share a common receptor, but, as outlined in the modulated receptor hypothesis, reach this receptor by distinct routes.
true
true
true
true
true
7,232
0
DISCUSSION
0
null
null
12,601,084
NA|NA|NA|NA
The results of this study show for the first time that the degree of ionization of flecainide molecules at physiological pH defines the mechanism of action of the drug and confers upon the drug molecules the prerequisite, during repetitive activity, that channels must first open before channel block can accumulate (UDB...
null
322
41,906
0
false
null
null
The results of this study show for the first time that the degree of ionization of flecainide molecules at physiological pH defines the mechanism of action of the drug and confers upon the drug molecules the prerequisite, during repetitive activity, that channels must first open before channel block can accumulate (UDB...
true
true
true
true
true
7,233
0
DISCUSSION
0
null
null
12,601,084
NA|NA|NA|NA
Reduction of the pKa of the drug molecule from 9.3 to 6.4 yielded a flecainide analogue (NU-FL) for which 90% of the drug molecules are neutral at pH 7.4, compared with <1% neutral flecainide molecules at the same pH.
null
217
41,907
0
false
null
null
Reduction of the pKa of the drug molecule from 9.3 to 6.4 yielded a flecainide analogue (NU-FL) for which 90% of the drug molecules are neutral at pH 7.4, compared with <1% neutral flecainide molecules at the same pH.
true
true
true
true
true
7,233
0
DISCUSSION
0
null
null
12,601,084
NA|NA|NA|NA
With this change in drug structure, the molecular pharmacology of the custom synthesized drug was remarkably similar to the well-characterized Na+ channel blocker lidocaine.
null
173
41,908
0
false
null
null
With this change in drug structure, the molecular pharmacology of the custom synthesized drug was remarkably similar to the well-characterized Na+ channel blocker lidocaine.
true
true
true
true
true
7,233
1
DISCUSSION
1
Rosen et al., 1975
[ "bib22", "bib23", "bib33", "bib12", "bib14", "bib25", "bib12", "bib14", "bib25", "bib12", "bib35", "bib26", "bib31" ]
12,601,084
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
UDB by LA drugs is the hallmark of their antiarrhythmic activity, it enables these drugs to be more effective when the frequency of action potentials is high, such as in ventricular tachycardia (Rosen et al., 1975; Rosen and Wit, 1983; Wit and Rosen, 1983).
[ "Rosen et al., 1975", "Rosen and Wit, 1983", "Wit and Rosen, 1983", "Hille, 1977a", "Hondeghem and Katzung, 1977", "Starmer et al., 1984", "Hille, 1977a", "Hondeghem and Katzung, 1977", "Starmer et al., 1984", "Hille, 1977a", "Yeh and Tanguy, 1985", "Strichartz, 1973", "Wang et al., 1995" ]
257
41,909
0
false
UDB by LA drugs is the hallmark of their antiarrhythmic activity, it enables these drugs to be more effective when the frequency of action potentials is high, such as in ventricular tachycardia.
[ "Rosen et al., 1975; Rosen and Wit, 1983; Wit and Rosen, 1983" ]
UDB by LA drugs is the hallmark of their antiarrhythmic activity, it enables these drugs to be more effective when the frequency of action potentials is high, such as in ventricular tachycardia.
true
true
true
true
true
7,234
1
DISCUSSION
1
Rosen et al., 1975
[ "bib22", "bib23", "bib33", "bib12", "bib14", "bib25", "bib12", "bib14", "bib25", "bib12", "bib35", "bib26", "bib31" ]
12,601,084
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
During UDB, channel block accumulates because of incomplete recovery of drug-bound channels during diastole (interstimulus intervals).
[ "Rosen et al., 1975", "Rosen and Wit, 1983", "Wit and Rosen, 1983", "Hille, 1977a", "Hondeghem and Katzung, 1977", "Starmer et al., 1984", "Hille, 1977a", "Hondeghem and Katzung, 1977", "Starmer et al., 1984", "Hille, 1977a", "Yeh and Tanguy, 1985", "Strichartz, 1973", "Wang et al., 1995" ]
134
41,910
0
false
During UDB, channel block accumulates because of incomplete recovery of drug-bound channels during diastole (interstimulus intervals).
[]
During UDB, channel block accumulates because of incomplete recovery of drug-bound channels during diastole.
true
true
true
true
true
7,234
1
DISCUSSION
1
Rosen et al., 1975
[ "bib22", "bib23", "bib33", "bib12", "bib14", "bib25", "bib12", "bib14", "bib25", "bib12", "bib35", "bib26", "bib31" ]
12,601,084
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
Slowed recovery of drug-bound channels can be explained by a combination of the modulated-receptor hypothesis and the guarded-receptor model (Hille, 1977a; Hondeghem and Katzung, 1977; Starmer et al., 1984).
[ "Rosen et al., 1975", "Rosen and Wit, 1983", "Wit and Rosen, 1983", "Hille, 1977a", "Hondeghem and Katzung, 1977", "Starmer et al., 1984", "Hille, 1977a", "Hondeghem and Katzung, 1977", "Starmer et al., 1984", "Hille, 1977a", "Yeh and Tanguy, 1985", "Strichartz, 1973", "Wang et al., 1995" ]
207
41,911
0
false
Slowed recovery of drug-bound channels can be explained by a combination of the modulated-receptor hypothesis and the guarded-receptor model.
[ "Hille, 1977a; Hondeghem and Katzung, 1977; Starmer et al., 1984" ]
Slowed recovery of drug-bound channels can be explained by a combination of the modulated-receptor hypothesis and the guarded-receptor model.
true
true
true
true
true
7,234
1
DISCUSSION
1
Rosen et al., 1975
[ "bib22", "bib23", "bib33", "bib12", "bib14", "bib25", "bib12", "bib14", "bib25", "bib12", "bib35", "bib26", "bib31" ]
12,601,084
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
The modulated receptor hypothesis proposes that higher affinity for LA drugs during activated and inactivated gating states slows unbinding of drug and, consequently, recovery of the drug-bound channels (Hille, 1977a; Hondeghem and Katzung, 1977).
[ "Rosen et al., 1975", "Rosen and Wit, 1983", "Wit and Rosen, 1983", "Hille, 1977a", "Hondeghem and Katzung, 1977", "Starmer et al., 1984", "Hille, 1977a", "Hondeghem and Katzung, 1977", "Starmer et al., 1984", "Hille, 1977a", "Yeh and Tanguy, 1985", "Strichartz, 1973", "Wang et al., 1995" ]
247
41,912
0
false
The modulated receptor hypothesis proposes that higher affinity for LA drugs during activated and inactivated gating states slows unbinding of drug and, consequently, recovery of the drug-bound channels.
[ "Hille, 1977a; Hondeghem and Katzung, 1977" ]
The modulated receptor hypothesis proposes that higher affinity for LA drugs during activated and inactivated gating states slows unbinding of drug and, consequently, recovery of the drug-bound channels.
true
true
true
true
true
7,234
1
DISCUSSION
1
Starmer et al., 1984
[ "bib22", "bib23", "bib33", "bib12", "bib14", "bib25", "bib12", "bib14", "bib25", "bib12", "bib35", "bib26", "bib31" ]
12,601,084
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
The guarded-receptor model emphasized that a state-dependent availability of the drug access path to and from the binding site influence apparent binding and unbinding kinetics (Starmer et al., 1984).
[ "Rosen et al., 1975", "Rosen and Wit, 1983", "Wit and Rosen, 1983", "Hille, 1977a", "Hondeghem and Katzung, 1977", "Starmer et al., 1984", "Hille, 1977a", "Hondeghem and Katzung, 1977", "Starmer et al., 1984", "Hille, 1977a", "Yeh and Tanguy, 1985", "Strichartz, 1973", "Wang et al., 1995" ]
200
41,913
1
false
The guarded-receptor model emphasized that a state-dependent availability of the drug access path to and from the binding site influence apparent binding and unbinding kinetics.
[ "Starmer et al., 1984" ]
The guarded-receptor model emphasized that a state-dependent availability of the drug access path to and from the binding site influence apparent binding and unbinding kinetics.
true
true
true
true
true
7,234
1
DISCUSSION
1
Rosen et al., 1975
[ "bib22", "bib23", "bib33", "bib12", "bib14", "bib25", "bib12", "bib14", "bib25", "bib12", "bib35", "bib26", "bib31" ]
12,601,084
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
Both of these hypotheses suggest that there is common binding site for tertiary amine LAs.
[ "Rosen et al., 1975", "Rosen and Wit, 1983", "Wit and Rosen, 1983", "Hille, 1977a", "Hondeghem and Katzung, 1977", "Starmer et al., 1984", "Hille, 1977a", "Hondeghem and Katzung, 1977", "Starmer et al., 1984", "Hille, 1977a", "Yeh and Tanguy, 1985", "Strichartz, 1973", "Wang et al., 1995" ]
90
41,914
0
false
Both of these hypotheses suggest that there is common binding site for tertiary amine LAs.
[]
Both of these hypotheses suggest that there is common binding site for tertiary amine LAs.
true
true
true
true
true
7,234
1
DISCUSSION
1
Rosen et al., 1975
[ "bib22", "bib23", "bib33", "bib12", "bib14", "bib25", "bib12", "bib14", "bib25", "bib12", "bib35", "bib26", "bib31" ]
12,601,084
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
In this study, our data clearly showed that UDB develops predominantly by the charged forms of both flecainide and NU-FL.
[ "Rosen et al., 1975", "Rosen and Wit, 1983", "Wit and Rosen, 1983", "Hille, 1977a", "Hondeghem and Katzung, 1977", "Starmer et al., 1984", "Hille, 1977a", "Hondeghem and Katzung, 1977", "Starmer et al., 1984", "Hille, 1977a", "Yeh and Tanguy, 1985", "Strichartz, 1973", "Wang et al., 1995" ]
121
41,915
0
false
In this study, our data clearly showed that UDB develops predominantly by the charged forms of both flecainide and NU-FL.
[]
In this study, our data clearly showed that UDB develops predominantly by the charged forms of both flecainide and NU-FL.
true
true
true
true
true
7,234
1
DISCUSSION
1
Rosen et al., 1975
[ "bib22", "bib23", "bib33", "bib12", "bib14", "bib25", "bib12", "bib14", "bib25", "bib12", "bib35", "bib26", "bib31" ]
12,601,084
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
What are the explanations for the weakness of UDB of Na+ channels by the neutral form of flecainide?
[ "Rosen et al., 1975", "Rosen and Wit, 1983", "Wit and Rosen, 1983", "Hille, 1977a", "Hondeghem and Katzung, 1977", "Starmer et al., 1984", "Hille, 1977a", "Hondeghem and Katzung, 1977", "Starmer et al., 1984", "Hille, 1977a", "Yeh and Tanguy, 1985", "Strichartz, 1973", "Wang et al., 1995" ]
100
41,916
0
false
What are the explanations for the weakness of UDB of Na+ channels by the neutral form of flecainide?
[]
What are the explanations for the weakness of UDB of Na+ channels by the neutral form of flecainide?
true
true
true
true
true
7,234
1
DISCUSSION
1
Rosen et al., 1975
[ "bib22", "bib23", "bib33", "bib12", "bib14", "bib25", "bib12", "bib14", "bib25", "bib12", "bib35", "bib26", "bib31" ]
12,601,084
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
First, the neutral form may occupy a binding site that is distinct from the binding site for charged form of flecainide.
[ "Rosen et al., 1975", "Rosen and Wit, 1983", "Wit and Rosen, 1983", "Hille, 1977a", "Hondeghem and Katzung, 1977", "Starmer et al., 1984", "Hille, 1977a", "Hondeghem and Katzung, 1977", "Starmer et al., 1984", "Hille, 1977a", "Yeh and Tanguy, 1985", "Strichartz, 1973", "Wang et al., 1995" ]
120
41,917
0
false
First, the neutral form may occupy a binding site that is distinct from the binding site for charged form of flecainide.
[]
First, the neutral form may occupy a binding site that is distinct from the binding site for charged form of flecainide.
true
true
true
true
true
7,234
1
DISCUSSION
1
Rosen et al., 1975
[ "bib22", "bib23", "bib33", "bib12", "bib14", "bib25", "bib12", "bib14", "bib25", "bib12", "bib35", "bib26", "bib31" ]
12,601,084
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
However, our data didn't support the existence of a separate neutral LA binding site apart from the charged form binding site.
[ "Rosen et al., 1975", "Rosen and Wit, 1983", "Wit and Rosen, 1983", "Hille, 1977a", "Hondeghem and Katzung, 1977", "Starmer et al., 1984", "Hille, 1977a", "Hondeghem and Katzung, 1977", "Starmer et al., 1984", "Hille, 1977a", "Yeh and Tanguy, 1985", "Strichartz, 1973", "Wang et al., 1995" ]
126
41,918
0
false
However, our data didn't support the existence of a separate neutral LA binding site apart from the charged form binding site.
[]
However, our data didn't support the existence of a separate neutral LA binding site apart from the charged form binding site.
true
true
true
true
true
7,234