R Luboshitzky

Ha'Emek Medical Center, Naẕerat, Northern District, Israel

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Publications (111)379.29 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: To elucidate whether pineal melatonin secretion is affected by changes in day length, we determined the concentration of melatonin in human pineal glands obtained at autopsy from 66 male subjects, aged 16–84 years over a period of 12 consecutive months. Based on the time of death, a day–night difference in pineal melatonin levels was evident only in the long photoperiod (April–September) with significantly higher melatonin concentrations occurring at night (2200–1000 h). Nighttime values in the long photoperiod were significantly higher than the nighttime values during the short photoperiod (October–March). During the short photoperiod, the data suggested a possible phase-delay in melatonin secretion. Day–night difference was evident in young subjects (30–60 years), but not in elderly subjects (61–84 years). Elderly subjects had lower total melatonin levels (day and night values) although statistically not significant. Therefore, melatonin levels did not decline with age and when the data were analyzed by age there was no significant day–night difference in melatonin levels. These data indicate that the concentration of melatonin in the human pineal is augmented only during the long photoperiod. The results suggest a partial effect of photoperiod on melatonin secretion in humans. This may result from living in an artificial light environment or due to other nonphotic signals involved in generating melatonin rhythm.
    Brain Research Bulletin 11/1998; · 2.94 Impact Factor
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    R Luboshitzky, G Qupti, A Ishai, M Dharan
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    ABSTRACT: A 27-year-old woman with no previous personal or family history of thyroid disease was referred to us for the evaluation of thyroid nodule, five months postpartum. Thyroid scintigraphy demonstrated a left cold nodule. Fine needle aspiration cytology of the nodule showed a mixture of colloid, follicular cells and lymphocytes, suggesting lymphocytic thyroiditis. Thyroid function tests were normal and thyroid autoantibodies were negative. After two months the thyroid nodule was not palpated and thyroid scintigraphy returned to normal. Thyroid function tests remained normal twelve months after delivery. These findings suggest that postpartum thyroiditis may present as a localized transient form and should be considered in the differential diagnosis of painless solitary nodule that appears postpartum.
    European Journal of Endocrinology 06/1998; 138(5):562-4. · 3.14 Impact Factor
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    Acta Cytologica - ACTA CYTOL. 01/1998; 42:791-795.
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    ABSTRACT: Synovial sarcoma (SS), a malignant mesenchymal tumor, has a biphasic growth pattern characteristically. Histologically and cytologically the tumor can pose diagnostic difficulty when the epithelial component is predominant. A 22-year-old female presented with a rapidly enlarging mass on the lower left side of the neck. Fine needle aspiration of the tumor yielded abundant, discohesive round-oval cells mingled with amorphous hyaline material, raising a suspicion of medullary carcinoma of the thyroid. In addition, air-dried, Giemsa-stained smears demonstrated rosettelike structures with central magenta globular material, mimicking adenoid cystic carcinoma. However, histologic examination of the excised tumor, including immunohistochemical and ultrastructural studies, proved it to be a typical SS with copious basement membrane accumulations. The cytologic appearance of SS can be confusing. However, a false diagnosis may be avoided if adequate needle sampling is ensured and clinical correlation considered.
    Acta cytologica 01/1998; 42(3):791-5. · 0.69 Impact Factor
  • A Ishay, R Luboshitzky
    Harefuah 01/1998; 133(12):632-4.
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    ABSTRACT: We describe two male patients, aged 17 and 47 years, with clinical and biochemical features of pheochromocytoma. Both patients had normal-sized adrenal glands on abdominal CT scan and abnormal unilateral uptake of I-123 metaiodobenzylguanidine (MIBG) on scintigraphy. The surgical adrenalectomy revealed normal macroscopic glands in both patients. Histological examination showed adrenal medullary hyperplasia with adrenal cortico-medullary ratios of 2:1 and 4:1. Unilateral adrenalectomy resulted in amelioration of symptoms and normalization of catecholamines excretion. DNA examination for RET protooncogene revealed no mutations in exons 10, 11, 13, 14 and 16. Our results suggest that diffuse adrenal medullary hyperplasia may be the initial pathological change in the adrenal gland leading, subsequently, to the development of nodular hyperplasia and adrenal medullary tumor. These results indicate that the syndrome of pheochromocytoma may occur as an unilateral adrenal medullary hyperplasia in patients without evidence for multiple endocrine neoplasia.
    Clinical Endocrinology 12/1997; 47(5):613-7. · 3.40 Impact Factor
  • R Luboshitzky, O Wagner, S Lavi, P Herer, P Lavie
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    ABSTRACT: We have recently demonstrated that GnRH deficient male patients have increased nocturnal melatonin secretion, whereas hypergonadotrophic hypogonadal males have decreased melatonin levels. We were interested in determining whether testosterone (T) treatment (when T levels were well matched with pubertal control values) has an effect on melatonin secretory profiles in these patients. Prospective, controlled. Six male patients with idiopathic hypogonadotrophic hypogonadism (IGD), six males with hypergonadotrophic hypogonadism due to Klinefelter's syndrome (KS) and seven controls. Patients were examined before and during the administration of 250 mg testosterone enanthate/month for four months. Serum samples for melatonin levels were obtained every 15 minutes from 1990 to 0700 h in a controlled light-dark environment. The results of FSH, LH, T and oestradiol (E2) (determined at hourly intervals) and melatonin profiles, were compared with the pre-treatment values in each group, and with values obtained in the control group. All 12 patients had low pre-treatment T levels (1.4 +/- 0.7 in IGD and 2.0 +/- 0.4 in KS vs. 19.8 +/- 2.3 nmol/l in controls) and attained normal levels after four months of T treatment (19.5 +/- 7 in IGD and 22.7 +/- 3.8 nmol/l in KS). Serum LH, FSH and E2 levels (11 +/- 4 IU/l, 24 +/- 10 IU/l and 113 +/- 12 pmol/l, respectively) were still elevated in KS during T treatment as compared with values in controls (2 +/- 1 IU/l, 2 +/- 1 IU/l and 67 +/- 4 pmol/l, respectively). In IGD, serum LH (0.12 +/- 0.1 IU/l) and FSH (0.16 +/- 0.2 IU/l) levels during T treatment were suppressed. Pretreatment melatonin levels in IGD were greater than those in age-matched pubertal controls while in KS, melatonin levels were lower than values in controls. Melatonin levels were equal in all 12 hypogonadal patients and controls when T levels were well matched. Mean (+/- SD) dark-time melatonin levels decreased from 286 +/- 18 to 157 +/- 26 pmol/l in IGD and increased from 92 +/- 19 to 183 +/- 48 pmol/l in KS (vs 178 +/- 59 pmol/l in controls). The integrated melatonin values decreased in IGD (from 184 +/- 14 to 102 +/- 21 pmol/min. 1 x 10(3)) and increased in KS (from 64 +/- 13 to 123 +/- 40, vs. 116 +/- 39 pmol/min. 1 x 10(3) in controls). No correlations were found between melatonin and LH, FSH or E2 levels. These data indicate that male patients with GnRH deficiency have increased nocturnal melatonin secretion while in hypergonadotrophic hypogonadal males melatonin secretion is decreased. Testosterone treatment normalized melatonin concentrations in these patients. Taken together, the results suggest that GnRH, gonadotrophins and gonadal steroids modulate pineal melatonin in humans.
    Clinical Endocrinology 11/1997; 47(4):463-9. · 3.40 Impact Factor
  • T Shochat, R Luboshitzky, P Lavie
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    ABSTRACT: In this study, we used the "ultrashort sleep-wake paradigm" (7/13), which measures sleep propensity three times an hour for 29 h, from 0700 to 1200 the next day, on 6 healthy male subjects concomitantly with melatonin plasma level. Melatonin was measured once an hour during the morning and early afternoon of the first day and three times an hour from 1600 to 1000 the following morning. Rectal temperature was measured continuously for four subjects. Subjects underwent the 7/13 paradigm three times, and in all three sessions consistent phase relationships were found between the nocturnal onset of melatonin secretion and opening of the nocturnal sleep gate; also, there was an inverse relationship between melatonin and core body temperature and an almost perfect out-of-phase relationship between sleep propensity and temperature, with the temperature peak falling precisely in the middle of the "forbidden zone" for sleep, i.e., the early evening nadir in sleepiness. On the basis of these phase relationships and previous findings from our laboratory on the effects of exogenous melatonin on the sleep propensity function, we conclude that melatonin participates in sleep-wake regulation in humans.
    The American journal of physiology 08/1997; 273(1 Pt 2):R364-70. · 3.28 Impact Factor
  • R Luboshitzky, P Herer, P Lavie
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    ABSTRACT: Recently, we have demonstrated that male patients with gonadotropin-releasing hormone (GnRH) deficiency had increased nocturnal melatonin secretion that decreased to normal levels during testosterone treatment. The purpose of the current study was to examine if the abnormally increased melatonin levels in these patients were associated with pulsatile secretory patterns, and, if these were modified during testosterone administration. Characteristics of nocturnal melatonin and luteinizing hormone (LH) secretion were compared in six normal young males, six males with idiopathic hypogonadotropic hypogonadism (IGD), and in six males with constitutional delayed puberty (DP). Patients were examined in the untreated state and following the administration of 250 mg testosterone enanthate/month for 4 months. Serum samples for melatonin and LH levels were obtained every 15 min from 19.00 hr to 07.00 hr in a controlled light-dark environment. Pulse detection and pulse characteristics were determined by the program ULTRA. In comparison with normal controls, untreated IGD patients showed significantly higher pulse frequency, lower relative increments and shorter half-life times for melatonin. Similar findings were observed in DP patients, although statistically of borderline significance. Treatment with testosterone normalized melatonin pulse characteristics in both IGD and DP patients. The secretory pattern of LH release in these patients was characterized by significantly higher relative and absolute increments and shorter half-life time without any significant change in the number of LH pulses. Taken together, these data suggest that melatonin is secreted in a pulsatile pattern in normal adult males and in male patients with GnRH deficiency. The abnormally increased nocturnal melatonin secretion observed in these patients may indicate that the pineal pulse generator is expressing an altered activity pattern within its normal capabilities. Testosterone administration normalized melatonin secretory patterns in IGD and DP patients. The lack of relationship between the pulsatile LH and melatonin secretory patterns suggest an independent signal for the nocturnal pulsatile melatonin and LH secretions.
    Journal of Pineal Research 04/1997; 22(2):95-101. · 7.30 Impact Factor
  • R Luboshitzky, M Dharan, D Goldman, Y Hiss, P Herer, P Lavie
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    ABSTRACT: Recently, we demonstrated that melatonin secretion was increased in male patients with GnRH deficiency and decreased to normal levels during testosterone treatment. These data suggested that gonadal steroids modulate melatonin secretion, probably by activating specific receptors in the pineal gland. We used immunohistochemistry to localize gonadotropin (LH and FSH) and gonadal steroid (androgens and estrogens) receptors in human pineal glands. Tissues were obtained at autopsy from 25 males, aged 19-87 yr, and five prepubertal children, aged 0.2-10 yr. Positive staining for all four types of receptors (LH, FSH, androgen, and estrogen) in the pineal parenchymal cells, pinealocytes, was evident in all 30 glands examined. Double staining revealed that nuclear receptors (androgen or estrogen) co-existed with cytoplasmatic receptors (LH or FSH) in the same cells. The results demonstrate the presence of gonadotropin and gonadal steroid receptors in human pinealocytes from infancy to old age.
    Journal of Clinical Endocrinology &amp Metabolism 04/1997; 82(3):977-81. · 6.43 Impact Factor
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    ABSTRACT: Recently abnormal melatonin secretion was demonstrated in hypogonadal male patients which was normalized during testosterone administration. These results suggested that both gonadal steroids and gonadotropins may modulate melatonin secretion, probably by activating specific receptors in the pineal gland. We used immunohistochemistry to localize luteinizing hormone, follicle stimulating hormone, estrogen and androgen receptors in human pineal glands. Tissues were obtained at autopsy from 53 adult males (aged 19–94 years) over a period of 1 year. Positive staining for the four types of receptors was evident in all 53 specimens examined. The percent of positively stained cells revealed a significant seasonal variation of gonadotropin receptors with higher values in the winter than in the summer. Day-night difference was evident only for follicle stimulating hormone-receptors during the summer and winter, with higher values at night. Androgen receptors and estrogen receptors were present in all specimens but did not reveal day-night or seasonal variations. These data demonstrate the presence of gonadotropin and gonadal steroid receptors in the human pineal gland. Gonadotropin receptors exhibited seasonal variation with higher values in the winter.
    Brain Research Bulletin 02/1997; · 2.94 Impact Factor
  • R Luboshitzky, R Hardoff
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    ABSTRACT: We describe a 13 year-old Ethiopian girl with vitamin D deficiency rickets. Hypercalcemia, increased serum alkaline phosphatase and PTH levels, together with low serum levels of 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D suggested the co-existence of primary hyperparathyroidism. The surgical removal of a parathyroid adenoma led to bone healing and normalization of blood chemistry. We conclude that vitamin D deficiency masked the hyperparathyroidism and hypercalcemia, while excess PTH secretion delayed the cure of rickets until successful parathyroidectomy had been carried out.
    Journal of pediatric endocrinology & metabolism: JPEM 01/1997; 10(2):237-41. · 0.75 Impact Factor
  • Source
    Rafael Luboshitzky
    01/1997;
  • Physics Letters B 01/1997; 396(1). · 4.57 Impact Factor
  • R Luboshitzky, O Wagner, S Lavi, P Herer, P Lavie
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    ABSTRACT: We have recently demonstrated that GnRH deficient male patients have increased nocturnal melatonin secretion which decreases to normal levels during testosterone treatment. The results suggested that sex steroids, rather than LH, modulate pineal melatonin in an inverse fashion. The purpose of this study was to characterize circulating melatonin levels in untreated males with hypergonadotrophic hypogonadism due to Klinefelter's syndrome (KS). Prospective, controlled. Eleven patients with Klinefelter's syndrome and seven controls. Patients were subdivided into two groups: (1) with low testosterone, and (2) with normal testosterone levels. Serum samples for melatonin concentrations were obtained every 15 minutes from 1900 to 0700 h in a controlled light-dark environment. All patients had elevated FSH, LH and oestradiol (E2) levels. Mean (+/-SD) dark time nocturnal melatonin levels were significantly lower in low testosterone KS (92 +/- 19 pmol/l) compared with 146 +/- 42 pmol/l in normal testosterone KS and 179 +/- 59 pmol/l in controls (P < 0.02). A similar pattern was observed for the mean (+/-SD) peak melatonin levels (165 +/- 41, 236 +/- 59 and 293 +/- 89 pmol/l) in low testosterone KS, normal testosterone KS and controls, respectively (P < 0.01). Integrated nocturnal melatonin secretion values (AUC) were also lower in low testosterone KS (64 +/- 13) compared with 96 +/- 26 in normal testosterone KS and 116 +/- 39 pmol/min 1 x 10(3) in controls (P < 0.02). The time of melatonin peak and the time of the nocturnal melatonin rise as well as the light-time mean (+/-SD) serum melatonin levels were similar in all three groups. No correlations were found between melatonin and LH, FSH, or E2 levels. Melatonin secretion is decreased in male patients with low testosterone hypergonadotrophic hypogonadism whereas in normal testosterone Klinefelter's syndrome patients, melatonin secretory profiles are normal. The results suggest that the suppression of melatonin secretion in these patients is mediated by GnRH (either directly or indirectly) and/or oestradiol.
    Clinical Endocrinology 12/1996; 45(6):749-54. · 3.40 Impact Factor
  • S Atar, R Luboshitzky
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    ABSTRACT: Hypokalemic periodic paralysis is an uncommon complication of thyrotoxicosis, and very rare as a presenting symptom. It is most frequent in east Asian and Japanese males, but extremely rare in others. Only 1 case has previously been reported from Israel. We present a 29-year-old Arab man who presented with sudden paralysis of both legs. Physical examination revealed signs of thyrotoxicosis, and laboratory tests showed profound hypokalemia. Oral potassium resulted in rapid disappearance of symptoms, and after restoration of the euthyroid state, there were no further attacks. This case shows that thyrotoxic hypokalemic periodic paralysis is not confined to males of east Asian and Japanese origin, and that adequate treatment with oral potassium and antithyroid drugs is successful, and should be given as soon as possible.
    Harefuah 08/1996; 131(1-2):21-2, 70.
  • R Luboshitzky, S Lavi, I Thuma, P Herer, P Lavie
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    ABSTRACT: To clarify whether disorders of gonadotropin releasing hormone (GnRH) deficiency are associated with altered melatonin and pituitary hormones secretory patterns, we studied male patients with hypogonadotropic hypogonadism (IGD; n = 6), delayed puberty (DP; n = 7) and age-matched pubertal controls (n = 7). Serum samples for the determination of melatonin, luteinizing hormone (LH), prolactin and cortisol levels were obtained at 15 min intervals from 1900 to 0700 in a controlled light-dark environment, complete bed-rest and fasting with simultaneous sleep recordings. Mean (+/- SD) dark-time melatonin levels were significantly higher in IGD (286 +/- 26 pmol/L) and DP (205 +/- 44 pmol/L) compared with 178 +/- 64 pmol/L in controls (P < 0.003). So were the mean (+/- SD) peak melatonin levels (453 +/- 63, 346 +/- 106 and 292 +/- 96 pmol/L) in IGD, DP and controls, respectively (P < 0.03). Integrated nocturnal melatonin (AUC) values were also higher in IGD and DP (184 +/- 15 and 134 +/- 28 pmol/min/L x 10(3)) compared with 116 +/- 42 pmol/min/L x 10(3) in controls (P < 0.003). The time of onset of the nocturnal melatonin rise was observed earlier in IGD and DP patients as compared to controls. No correlations were found between melatonin and LH levels, between melatonin and prolactin levels, or between melatonin and cortisol levels. These data indicate that melatonin secretion is enhanced in male patients with GnRH deficiency. The lack of correlation between melatonin and LH suggest that circulating gonadal steroids, rather than LH, modulate melatonin secretion in a reverse fashion.
    Journal of Pineal Research 08/1996; 21(1):49-54. · 7.30 Impact Factor
  • R Luboshitzky, S Lavi, I Thuma, P Lavie
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    ABSTRACT: To examine the role of melatonin in pathological hyperprolactinemia we compared untreated young females (N = 5) with hyperprolactinemic amenorrhea owing to pituitary microadenoma to healthy female controls (N = 6). Serum samples for melatonin, prolactin, and luteinizing hormone (LH) concentrations were obtained every 15 min from 1900 hr to 0700 hr in a controlled light-dark environment with simultaneous sleep recordings. The mean (+/- SD) light-time period, dark-time period, and the integrated nocturnal melatonin secretion values (area under the curve, or AUC) in patients (51 +/- 11 pmol/L, 157 +/- 33 pmol/L, and 102 +/- 19 pmol/min.L x 10(3), respectively) were similar to the values obtained in controls (79 +/- 39, 165 +/- 44, 111 +/- 31, respectively). The onset of the nocturnal melatonin rise, peak level, and peak time were similar in the two groups. A significant nocturnal prolactin rise was observed in patients (112 +/- 9 vs. 65 +/- 11 micrograms/L, P < 0.006) and controls (19 +/- 2 vs. 10 +/- 3 micrograms/L, P < 0.006). The time of prolactin peak was similar in patients and controls (0424 +/- 3:36 vs. 0350 +/- 2:21) and paralleled that of melatonin (0354 +/- 1:46 vs. 0337 +/- 1:30). The mean +/- SD light-time period, dark-time period, and the AUC values of LH were similar in patients and controls. The number of LH pulses in patients (7.2 +/- 1.9 per 12 hr) were not different from those in controls (7.7 +/- 2.1). The LH pulse interval was 100 +/- 22 min in patients compared with 94 +/- 23 min in controls. The mean (+/- SD) nocturnal estradiol (E2) levels were significantly lower in patients (84 +/- 15 pmol/L) than in controls (224 +/- 77) (P < 0.005). Analysis of LH and melatonin secretory profiles revealed significant pulses for both hormones. No significant relationship was observed between the LH and melatonin pulses. However, a negative correlation between LH pulse amplitude and the number of melatonin pulses (P < 0.04) and a positive correlation between LH amplitude and duration of melatonin pulses (P < 0.04) were observed. Taken together, these data suggest that the suppression of normal ovarian cycles in women with hyperprolactinemic amenorrhea owing to pituitary microadenoma may be mediated by blocking of gonadotropin action by prolactin at the ovarian level; yet it remains possible that chronically elevated prolactin might prevent the LH surge and thus lead to amenorrhea. Pulsatile melatonin secretion is unaltered in these patients, and frequent occurrence of amenorrhea in this population is not mediated by melatonin.
    Journal of Pineal Research 03/1996; 20(2):72-8. · 7.30 Impact Factor
  • R Luboshitzky, S Lavi, I Thuma, P Lavie
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    ABSTRACT: Recently, we demonstrated that melatonin secretion is increased in untreated male patients with GnRH deficiency. As testosterone (T) can be aromatized to estradiol (E2), and both T and E2 increase during T enanthate treatment, we were interested in determining whether T treatment (when T and E2 levels were well matched with pubertal control values) has an effect on melatonin levels in these patients. We measured nocturnal serum melatonin levels during the administration of 250 mg testosterone enantale/month for 4 months in 12 male patients with idiopathic hypogonadotropic hypogonadism (IGD; n = 6) and delayed puberty (DP; n = 6). Serum samples for melatonin and LH determinations were obtained every 15 min from 1900-0700 h in a controlled light-dark environment. The results of melatonin profiles were compared with the pretreatment values in each group and with values obtained in six normal pubertal male controls. After 4 months of testosterone treatment, all patients attained normal serum testosterone (19.5 +/- 3.7 in IGD vs. 20.8 +/- 4.1 nmol/L in DP) and E2 levels (83 +/- 12 in IGD vs. 84 +/- 9 pmol/L in DP). Serum LH levels were suppressed in all patients during T treatment (0.12 +/- 0.1 in IGD vs. 0.12 +/- 0.2 IU/L in DP). Before T treatment, patient melatonin levels were greater than those in age-matched pubertal controls. Melatonin levels were equal in patients and controls when T and E2 levels were well matched. Mean (+/- SD) dark-time melatonin levels decreased from 286 +/- 23 to 157 +/- 36 pmol/L in IGD and from 217 +/- 32 to 133 +/- 47 pmol/L in DP (vs. 183 +/- 64 pmol/L in controls). The integrated melatonin values decreased to normal (from 184 +/- 16 to 102 +/- 21 in IGD and from 142 +/- 19 to 90 +/- 26 pmol/min.L x 10(3) in DP vs. 119 +/- 61 pmol/min.L x 10(3) in controls). The intraindividual variations in melatonin levels ranged from 7.2-14.5%. These data indicate that male patients with GnRH deficiency have increased nocturnal melatonin secretion. T treatment decreased melatonin secretion to normal levels. The results suggest that in GnRH-deficient male patients, sex steroids, rather than LH, modulate pineal melatonin in a reverse fashion.
    Journal of Clinical Endocrinology &amp Metabolism 03/1996; 81(2):770-4. · 6.43 Impact Factor
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    ABSTRACT: A child with a germ cell tumor involving the pineal region had marked suppression of melatonin secretion associated with severe insomnia. Exogenous melatonin (3 mg in the evening) for 2 weeks restored sleep continuity, as demonstrated by objective monitoring of rest-activity cycles. This case report provides direct evidence of the essential role of melatonin in normal sleep.
    Neurology 02/1996; 46(1):261-3. · 8.25 Impact Factor

Publication Stats

1k Citations
379.29 Total Impact Points

Institutions

  • 2005–2012
    • Ha'Emek Medical Center
      Naẕerat, Northern District, Israel
  • 1997–2012
    • Technion - Israel Institute of Technology
      • Ruth and Bruce Rappaport Faculty of Medicine
      H̱efa, Haifa District, Israel
  • 2001–2009
    • Meir Medical Center
      Kafr Saba, Central District, Israel
  • 1978–2001
    • Rambam Medical Center
      • Department of Pediatrics
      H̱efa, Haifa District, Israel
  • 1979–1980
    • Shaare Zedek Medical Center
      Yerushalayim, Jerusalem District, Israel