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R Sandyk

Publications and source records attributed to R Sandyk.

At least 19 recordsLinked to original sources

The pineal gland and the clinical course of multiple sclerosis.

Clinical, epidemiological, biochemical, immunological, and radiological studies suggest that the pineal gland may be implicated in the pathophysiology of multiple sclerosis (MS). The following communication is concerned with the association among MS, pregnancy, the postpartum period, and melatonin secretion and illustrates, based on a clinical case report, the influence of the pineal gland on the clinical course of MS. This association is noteworthy since MS may worsen during the postpartum period and melatonin secretion is reported to be altered most dramatically by pregnancy and delivery. Since melatonin secretion is cyclical, undergoing diurnal, weekly, seasonal, and annual variations, it is proposed that the pineal gland may be the "prime mover" underlying the spontaneous exacerbations and remissions in MS.

Calcinosis

Is the pineal gland involved in the pathogenesis of endometrial carcinoma.

The pathogenesis of endometrial carcinoma, which is the most common malignant neoplasm of the female genital tract, is unknown. It is believed that a prolonged period of increased estrogenic exposure unopposed by progesterone may underlie the malignant transformation of the endometrial cells. In the following communication, we propose that deficient melatonin functions may be an additional endocrine factor implicated in the pathogenesis of endometrial carcinoma. This hypothesis is based on the observations that: (a) melatonin has antiestrogenic properties; (b) melatonin stimulates progesterone production which opposes the action of estrogens; (c) an increased rate of endometrial hyperplasia, a premalignant condition, has been noted during the winter, a time of year associated with diminished melatonin secretion; (d) an increased incidence of anovulatory cycles, which is a risk factor for endometrial carcinoma, occurs in the winter; (e) melatonin secretion decreases sharply during the menopause, a period associated with an increased risk of endometrial carcinoma; (f) obesity, which is a major risk factor for endometrial carcinoma, is associated with impaired circadian melatonin secretion; (g) diabetes mellitus, which is an additional risk factor for endometrial carcinoma, is associated with decreased melatonin secretion and an increased rate of pineal calcification; and (h) the prevalence of endometrial carcinoma is lower in the black population compared to the white population. Similarly, the incidence of pineal calcification, which reflects the secretory activity of the gland, is significantly lower in the African and American black populations as compared to the white population.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Abnormal EEG and calcification of the pineal gland in schizophrenia.

Computed tomographic (CT) studies of the brain in schizophrenic patients have demonstrated a variety of structural abnormalities. We reported recently an association between pineal calcification (PC) and cortical and prefrontal cortical atrophy, and third ventricular size on CT scan in chronic schizophrenic patients. These findings indicate that in schizophrenia PC is associated with the morphological brain abnormalities associated with the disease. If PC is, indeed, related to organic cerebral pathology, then one would expect a higher prevalence of pineal gland pathology among patients with electroencephalographic (EEG) abnormalities by comparison to those with a normal EEG. To investigate this hypothesis, we studied the prevalence of PC on CT scan in a sample of 52 neuroleptic-treated schizophrenic patients (29 men, 23 women, mean age: 51.3 years SD = 9.1), of whom 10 (19.2%) had an abnormal EEG. The prevalence of PC in patients with EEG abnormalities was significantly greater by comparison to those with a normal EEG (90.0% vs. 54.8%, X2 = 4.24, p < .05). Since both groups did not differ on any of the historical and demographic data, and since PC was unrelated to neuroleptic exposure, these findings suggest that in schizophrenia PC may be related to the disease process and that it may be a marker of subcortical pathology.

Adult

Is postmenopausal osteoporosis related to pineal gland functions?

There is currently considerable interest in the pathogenesis of postmenopausal osteoporosis, which is the most common metabolic bone disease. Osteoporosis affects approximately 20 million persons in the United States, 90% of whom are postmenopausal women. Although there is evidence that estrogen deficiency is an important contributory factor, the pathogenesis of osteoporosis is multifactorial and presently poorly understood. There is evidence that pineal melatonin is an anti-aging hormone and that the menopause is associated with a substantial decline in melatonin secretion and an increased rate of pineal calcification. Animal data indicate that pineal melatonin is involved in the regulation of calcium and phosphorus metabolism by stimulating the activity of the parathyroid glands and by inhibiting calcitonin release and inhibiting prostaglandin synthesis. Hence, the pineal gland may function as a "fine tuner" of calcium homeostasis. In the following communication, we propose that the fall of melatonin plasma levels during the early stage of menopause may be an important contributory factor in the development of postmenopausal osteoporosis. Consequently, plasma melatonin levels taken in the early menopause could be used as an indicator or perhaps as a marker for susceptibility to postmenopausal osteoporosis. Moreover, light therapy, administration of oral melatonin (2.5 mg at night) or agents which induce a sustained release of melatonin secretion such as 5-methoxypsoralen, could be useful agents in the prophylaxis and treatment of postmenopausal osteoporosis. Finally, since application of external artificial magnetic fields has been shown to synchronize melatonin secretion in experimental animals and humans, we propose that treatment with artificial magnetic fields may be beneficial for postmenopausal osteoporosis.

Aged

The pineal gland and spontaneous abortions: implications for therapy with melatonin and magnetic field.

Spontaneous abortion, the termination of pregnancy prior to 20 weeks of gestation, is estimated to occur in 40%-50% of all pregnancies and in 12%-15% of identified pregnancies. The causes of spontaneous abortion can be divided into two main categories: those arising from chromosomal anomalies and those arising from abnormalities in the intrauterine environment. In the following communication, we propose that deficient pineal melatonin functions in early pregnancy may be causally related to the development of spontaneous abortions in cases where chromosomal anomalies or structural abnormalities of the uterus have been excluded. This hypothesis is based on the findings that: (a) melatonin plasma levels normally increase by 200%-300% in the first 20 weeks of pregnancy; (b) melatonin decreases uterine contractility in the rat; (c) melatonin stimulates the secretion of progesterone, which decreases uterine contractility and prevents immunological rejection of the trophoblast; (d) melatonin inhibits the synthesis of prostaglandins, which are potent inducers of uterine contractility and labor, and (e) pinealectomy increases the number of spontaneous abortions in pregnant rats. In addition, since melatonin is a hormone with immunosuppressant properties, we propose that the increased melatonin production in early pregnancy may contribute to a state of "transplantation immunity" to the paternal histocompatibility antigens preventing immunological rejection of the trophoblast. If this hypothesis is correct, then plasma melatonin, levels during early pregnancy could be used as an indicator for increased risk of spontaneous abortions.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Spontaneous

Seasonal panic disorder: a possible variant of seasonal affective disorder.

The present communication concerns a 30 year-old female patient with panic disorder in whom panic attacks appeared to be seasonally-related. Characteristically, attacks were more frequent and severe during the months of October to May with spontaneous remissions during the months of June to September. Since 70% of patients with seasonal affective disorder (SAD), a variant of affective illness characterized by recurrent winter depressions with remissions in summer, suffer from anxiety disorders, we propose that seasonal panic disorder may be a variant of SAD. Since SAD is associated with phase delay of circadian rhythms, some forms of panic disorder may be related to phase instability of circadian rhythms. Moreover, since administration of artificial bright light therapy is currently the most effective treatment for SAD, it is suggested that patients with panic disorder should be questioned as to whether their symptoms are seasonally related. If a positive association is established, these patients should be offered treatment with light therapy prior to or coincident with the institution of pharmacotherapy.

Adult

Melatonin and maturation of REM sleep.

The discovery in 1953 of rapid eye movement (REM) sleep and the appreciation that sleep is a heterogeneous physiological state stimulated major research into sleep disorders. Electroencephalographic studies have shown that the amount of REM sleep changes with age. While newborns spend almost 50% of their sleep time in REM, the percentage of REM sleep decreases to 30% by the age of 3 months and to 20% by the age of 6 months. In addition, newborns enter REM sleep soon after the initiation of sleep, but by the age of 4 months entry into sleep assumes the adult pattern in which a significant period of non-REM sleep precedes the onset of REM sleep. Since reduction in the amount of REM sleep is associated with cerebral maturation and since the pineal gland has been implicated both in cerebral development and in the organization of REM sleep, the pineal gland may be involved in the maturation of the adult REM sleep pattern. Prior to the age of 3 months melatonin plasma levels are low and the characteristic circadian rhythms of melatonin are absent. Thereafter, melatonin secretion increases and circadian rhythmicity of melatonin becomes apparent. Thus, the abundance of REM sleep during the first 3 months of infancy is associated with deficient pineal melatonin functions, while the decline in the percentage of REM sleep coincides with the emergence of melatonin secretion coincident with the maturation of the pineal gland. I propose, therefore, that a state of low melatonin secretion is permissive for REM sleep and that maturation of the pineal gland retards REM sleep. This hypothesis is supported by the findings that melatonin suppresses REM sleep in cats and that in rats and humans pinealectomy induces a narcoleptic-like pattern of REM sleep which strikingly resembles that of the newborn and which is reversed by the administration of melatonin. A further hypothesis is advanced to explain the pathophysiology of narcolepsy in terms of a maturational defect of the pineal gland in infancy.

Body Temperature

Melatonin as a proconvulsive hormone in humans.

The pineal gland and melatonin exert a major influence in the control of brain electrical activity and have been shown to be involved in seizure and sleep mechanisms. Since pinealectomy has been reported to result in seizures in experimental animals, it is assumed that melatonin has anticonvulsant properties. Indeed, limited studies in humans with temporal lobe epilepsy indicate that melatonin attenuates seizure activity. In the present communication we present evidence, based on magnetoencephalographic (MEG) brain measurements, that melatonin may exert proconvulsive activity in humans as well. The proconvulsive properties of melatonin may explain several phenomena associated with epilepsy such as the increased occurrence of seizures at night when melatonin plasma levels are 5 to 8-fold higher than during the day and the observed exacerbation of seizures premenstrually and during pregnancy as well as the attenuation of seizures in the menopause. Furthermore, our findings suggest that anticonvulsants which decrease melatonin secretion, such as the benzodiazepines, may exert their antiepileptic activity by attenuating nocturnal melatonin secretion. Finally, we propose that patients with nocturnal epilepsy or those experiencing exacerbation of seizures premenstrually may benefit from the administration of agents which block the secretion or action of melatonin.

Adult

Magnetic fields in the treatment of Parkinson's disease.

Levodopa-induced dyskinesias are a common complication of chronic dopaminergic therapy in patients with Parkinson's disease (PD). The overall prevalence of levodopa-induced dyskinesias ranges from 40%-90% and is related to the underlying disease process, pharmacologic factors, and to the duration of high dose levodopa therapy. The mechanisms underlying the emergence of levodopa-induced dyskinesias are unknown, although most investigators favor the theory that striatal dopamine receptor supersensitivity is directly responsible for the development of these abnormal movements. In laboratory animals, the pineal hormone melatonin has been shown to regulate striatal dopaminergic activity and block levodopa-induced dyskinesias (Cotzias et al., 1971). Since the pineal gland is known to be a magnetosensitive organ and as application of external magnetic fields has been shown to alter melatonin secretion, we studied the effects of application of external artificial weak magnetic fields in a Parkinsonian patient with severe levodopa-induced dyskinesias ("on-off"). Application of weak magnetic fields with a frequency of 2 Hz and intensity of 7.5 picotesla (pT) for a 6 minute period resulted in a rapid and dramatic attenuation of Parkinsonian disability and an almost complete resolution of the dyskinesias. This effect persisted for about 72 hours after which the patient regressed to his pretreatment state. To ascertain if the responses elicited in the laboratory were reproducible, the patient was instructed to apply magnetic fields of the same characteristics daily at home. These subsequent treatments paralleled the initial response with a sustained improvement being maintained during an observation period lasting at least one month. This case demonstrates the efficacy of weak magnetic fields in the treatment of Parkinsonism and motor complications of chronic levodopa therapy.

Combined Modality Therapy

The pineal gland and the menstrual cycle.

The menstrual cycle reflects the expression of a cyclical process involving the interaction between the hypothalamic-pituitary axis and the ovaries. This complex process requires an integrated neural and humoral control mechanism. It is now well established that a hypothalamic "transducer" located in the medial basal hypothalamus integrates neural and humoral information and translates it into an oscillatory signal which eventually results in the release of the gonadotropin releasing hormone (GnRH), triggering the secretion of gonadotropins from the pituitary gland. Recent animal studies indicate that melatonin influences the functions of the hypothalamic-pituitary-gonadal axis by modifying the firing frequency of the hypothalamic GnRH pulse generator. Consequently, the pineal gland, through the action of melatonin, may exert an important modulatory effect on the mechanisms controlling menstrual cyclicity. Furthermore, abnormal melatonin functions may be involved in the pathogenesis of several disorders of the menstrual cycle including some forms of hypothalamic amenorrhea such as exercise and malnutrition-induced amenorrhea. Consideration of pineal melatonin functions provides a new dimension into the understanding of the neuroendocrine mechanisms governing the cyclical phenomena of the female reproductive system.

Female

Alpha rhythm and the pineal gland.

Alpha rhythm is classically described as a bilateral posterior rhythm of substantially constant frequency in the range of 8-13 Hz which is enhanced by mental relaxation and blocked by attention. Since the full expression of alpha rhythm has been shown to occur coincident with puberty, it is possible that the establishment of alpha rhythm is subject to neuroendocrine influences which govern psychosexual maturation. There is ample evidence to indicate that the pineal gland is implicated in cerebral maturation and psychosexual development. Nocturnal plasma melatonin levels have been shown to decline progressively throughout childhood reaching a nadir at puberty. Since administration of melatonin has been reported to block alpha rhythm, it is proposed that the progressive decline in melatonin secretion during childhood facilitates the maturation of the alpha rhythm. Consequently, the presence of alpha rhythm could be used as a neurophysiological marker for the activity of the pineal gland and disorders associated with absent or delayed maturation of the alpha rhythm such as autism, dyslexia, personality disorders, epilepsy, Tourette's syndrome, and schizophrenia might be related to disturbances of pineal melatonin functions in early life. Moreover, since the EEG patterns associated with cerebral immaturity (i.e., slowing, absence of alpha activity) are more pronounced in the left hemisphere, this hypothesis implies differential influence of the pineal gland on hemispheric maturation potentially accounting for the vulnerability of the left hemisphere to cerebral insults.

Alpha Rhythm

Magnetic fields alter the circadian periodicity of seizures.

We have recently reported that application of external, weak magnetic fields attenuated seizures in epileptic patients (Anninos et al., 1991). However, the mechanisms by which magnetic stimulation reduces seizure activity are unknown. We present four non-selected epileptic patients the first to be rated by the senior author, in whom treatment with magnetic fields attenuated the severity of seizures and also altered the circadian occurrence of seizures. The first patient, a 27-year old woman, had generalized tonic-clonic seizures which occurred almost exclusively at night. Following treatment with magnetic fields she experienced attenuation of seizures which then occurred only after waking up in the morning. The second patient, a 42-year old man, had generalized tonic-clonic seizures which occurred randomly during the day and night. Treatment with magnetic fields resulted in disappearance of nocturnal seizures with seizures now occurring exclusively during the day. The third patient, a 21-year old woman had generalized tonic-clonic seizures which occurred randomly during the day. After treatment with magnetic fields she was free of seizures for 7 months, but recently experienced one attack in the morning hours while sleeping. The fourth patient, a 39-year old woman had secondary generalized seizures since the age of 12. Prior to treatment with magnetic fields she had 8-10 seizures daily which occurred randomly during the day and night hours. Magnetic treatment resulted in attenuation in seizure frequency (1-2/day) with seizures now occurring only during the day. We propose, therefore, that since the pineal gland is a magnetosensitive organ which "transduces" environmental information of the light-dark cycle and of the earth's magnetic field into an endocrine message mediated via the circadian release of melatonin, and since it is recognized that melatonin attenuates seizure activity, artificial magnetic fields attenuate seizure activity by altering the functions of the pineal gland.

Adult