- Email: [email protected]
Entrainment of free-running circadian rhythms by melatonin in blind people
T
melatonin was measured as a marker of the circadian time (phase), and sleep was monitored by polysomnography. At base line, the subjects had free-running circadian rhythms with distinct and predictable cycles averaging 24.5 hours (range, 24.2-24.9). These rhythms were unaffected by the administration of placebo. In six of the seven subjects the rhythm was entrained to a 24.0-hour cycle during melatonin treatment (P⬎0.001). After entrainment, the subjects spent less time awake after the initial onset of sleep (P⫽0.05) and the efficiency of sleep was higher (P⫽0.06). Three subjects subsequently participated in a trial in which a 10-mg dose of melatonin was given daily until entrainment was achieved. The dose was then reduced to 0.5 mg per day over a period of three months; the entrainment persisted, even at the lowest dose. The authors concluded that administration of melatonin could entrain circadian rhythms in most blind people who have free-running rhythms.—Nancy J. Newman
HE IRREVERSIBLE LOSS OF VISUAL ACUITY IN MACULAR
edema is usually attributed to permanent loss of photoreceptor cells. The purpose of this study was to assess photoreceptor function in various stages of macular edema and to relate the findings to visual acuity and angiographic changes. Directional sensitivity (optical Stiles–Crawford effect) and visual pigment density of foveal cones was measured with a custom-built scanning laser ophthalmoscope (SLO) in 19 eyes of 19 patients. Twelve eyes exhibited macular edema: five of inflammatory origin, and seven of diabetic origin. Seven eyes with an intraocular inflammatory disease without clinical or angiographic evidence of edema were also included. Results of SLO measurements were related to findings using fluorescein angiography and Snellen visual acuity, both assessed at the time of SLO measurement and six months thereafter. Eyes with macular edema exhibited diminished directional sensitivity of photoreceptor cells in the fovea compared with eyes without edema (P ⫽ 0.02). Visual pigment density of eyes with macular edema was decreased and associated with both initial and follow-up visual function and with the angiographic macular edema grade at follow-up. Abnormal directional sensitivity and pigment density were already present in eyes with slight edematous changes and normal visual acuity. The authors conclude that eyes with inflammatory or diabetic macular edema showed decreased directional sensitivity and visual pigment density in the macular area. These findings may support a role for SLO measurements in detecting retinal damage due to macular edema.—Thomas J. Liesegang.
*Mail Code L-469, Oregon Health Sciences University, Portland, OR 97201. E-mail: [email protected]
●
Antioxidant Therapy in Neurologic Disease. Delanty N,* Dichter MA. Arch Neurol. 2000;57:1265–1270.
F
mental mechanism underlying a number of human neurologic diseases. Therapy using free radical scavengers (antioxidants) has the potential to prevent, delay, or ameliorate many neurologic disorders. The biochemistry of oxidative pathobiology is complex, and optimum antioxidant therapeutic options may vary and need to be tailored to individual diseases. The authors review the results of several antioxidant trials in neurology. In vitro and animal model studies support the potential beneficial role of various antioxidant compounds in neurologic disease. The results of clinical trials using various antioxidants, including vitamin E, tirilazad, N-acetylcysteine, and ebselen, however, have been mixed. Potential reasons for these mixed results include lack of pretrial dose-finding studies and failure to appreciate and characterize the individual unique oxidative processes occurring in different diseases. Therapy with antioxidants may need to be given early in chronic insidious neurologic disorders to achieve an appreciable clinical benefit. Predisease screening and intervention in at-risk individuals may also need to be considered in the near future.—Thomas J. Liesegang
*Department of Ophthalmology, F. C. Donders Institute, University Hospital Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands. E-mail: [email protected]
● Entrainment of free-running circadian rhythms by melatonin in blind people. Brandes RW,* Kendall AR, Lewy AJ. N Engl J Med 2000;343:1070 –1077.
T
HE ENDOGENOUS CIRCADIAN PACEMAKER OSCILLATES
with a period that is slightly longer than 24 hours and therefore requires synchronization, or entrainment, to the 24-hour day. Most totally blind people have circadian rhythms that are “free-running” (i.e., that are not synchronized to environmental time cues). This condition causes recurrent insomnia and daytime sleepiness when the rhythms drift out of phase with the normal 24-hour cycle. This study investigated whether a daily dose of melatonin could entrain their circadian rhythms to a normal 24-hour cycle. Seven totally blind subjects who had free-running circadian rhythms were involved in a crossover study in which the subjects were given 10 mg of melatonin or placebo daily, one hour before their preferred bedtime, for three to nine weeks. They were then given the other treatment. The timing of the production of endogenous
288
AMERICAN JOURNAL
REE RADICAL OR OXIDATIVE INJURY MAY BE A FUNDA-
*Department of Clinical Neurological Sciences, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin 9, Ireland. E-mail: [email protected]
●
Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy. Delettre C, Lenaers G, Griffoin J-M, Gigarel N, OF
OPHTHALMOLOGY
FEBRUARY 2001
melatonin was measured as a marker of the circadian time (phase), and sleep was monitored by polysomnography. At base line, the subjects had free-running circadian rhythms with distinct and predictable cycles averaging 24.5 hours (range, 24.2-24.9). These rhythms were unaffected by the administration of placebo. In six of the seven subjects the rhythm was entrained to a 24.0-hour cycle during melatonin treatment (P⬎0.001). After entrainment, the subjects spent less time awake after the initial onset of sleep (P⫽0.05) and the efficiency of sleep was higher (P⫽0.06). Three subjects subsequently participated in a trial in which a 10-mg dose of melatonin was given daily until entrainment was achieved. The dose was then reduced to 0.5 mg per day over a period of three months; the entrainment persisted, even at the lowest dose. The authors concluded that administration of melatonin could entrain circadian rhythms in most blind people who have free-running rhythms.—Nancy J. Newman
HE IRREVERSIBLE LOSS OF VISUAL ACUITY IN MACULAR
edema is usually attributed to permanent loss of photoreceptor cells. The purpose of this study was to assess photoreceptor function in various stages of macular edema and to relate the findings to visual acuity and angiographic changes. Directional sensitivity (optical Stiles–Crawford effect) and visual pigment density of foveal cones was measured with a custom-built scanning laser ophthalmoscope (SLO) in 19 eyes of 19 patients. Twelve eyes exhibited macular edema: five of inflammatory origin, and seven of diabetic origin. Seven eyes with an intraocular inflammatory disease without clinical or angiographic evidence of edema were also included. Results of SLO measurements were related to findings using fluorescein angiography and Snellen visual acuity, both assessed at the time of SLO measurement and six months thereafter. Eyes with macular edema exhibited diminished directional sensitivity of photoreceptor cells in the fovea compared with eyes without edema (P ⫽ 0.02). Visual pigment density of eyes with macular edema was decreased and associated with both initial and follow-up visual function and with the angiographic macular edema grade at follow-up. Abnormal directional sensitivity and pigment density were already present in eyes with slight edematous changes and normal visual acuity. The authors conclude that eyes with inflammatory or diabetic macular edema showed decreased directional sensitivity and visual pigment density in the macular area. These findings may support a role for SLO measurements in detecting retinal damage due to macular edema.—Thomas J. Liesegang.
*Mail Code L-469, Oregon Health Sciences University, Portland, OR 97201. E-mail: [email protected]
●
Antioxidant Therapy in Neurologic Disease. Delanty N,* Dichter MA. Arch Neurol. 2000;57:1265–1270.
F
mental mechanism underlying a number of human neurologic diseases. Therapy using free radical scavengers (antioxidants) has the potential to prevent, delay, or ameliorate many neurologic disorders. The biochemistry of oxidative pathobiology is complex, and optimum antioxidant therapeutic options may vary and need to be tailored to individual diseases. The authors review the results of several antioxidant trials in neurology. In vitro and animal model studies support the potential beneficial role of various antioxidant compounds in neurologic disease. The results of clinical trials using various antioxidants, including vitamin E, tirilazad, N-acetylcysteine, and ebselen, however, have been mixed. Potential reasons for these mixed results include lack of pretrial dose-finding studies and failure to appreciate and characterize the individual unique oxidative processes occurring in different diseases. Therapy with antioxidants may need to be given early in chronic insidious neurologic disorders to achieve an appreciable clinical benefit. Predisease screening and intervention in at-risk individuals may also need to be considered in the near future.—Thomas J. Liesegang
*Department of Ophthalmology, F. C. Donders Institute, University Hospital Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands. E-mail: [email protected]
● Entrainment of free-running circadian rhythms by melatonin in blind people. Brandes RW,* Kendall AR, Lewy AJ. N Engl J Med 2000;343:1070 –1077.
T
HE ENDOGENOUS CIRCADIAN PACEMAKER OSCILLATES
with a period that is slightly longer than 24 hours and therefore requires synchronization, or entrainment, to the 24-hour day. Most totally blind people have circadian rhythms that are “free-running” (i.e., that are not synchronized to environmental time cues). This condition causes recurrent insomnia and daytime sleepiness when the rhythms drift out of phase with the normal 24-hour cycle. This study investigated whether a daily dose of melatonin could entrain their circadian rhythms to a normal 24-hour cycle. Seven totally blind subjects who had free-running circadian rhythms were involved in a crossover study in which the subjects were given 10 mg of melatonin or placebo daily, one hour before their preferred bedtime, for three to nine weeks. They were then given the other treatment. The timing of the production of endogenous
288
AMERICAN JOURNAL
REE RADICAL OR OXIDATIVE INJURY MAY BE A FUNDA-
*Department of Clinical Neurological Sciences, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin 9, Ireland. E-mail: [email protected]
●
Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy. Delettre C, Lenaers G, Griffoin J-M, Gigarel N, OF
OPHTHALMOLOGY
FEBRUARY 2001