The pharmacokinetics of melatonin during the day-time has been studied in 4 healthy subjects after a bolus i.v. injection of 5 or 10 micrograms/person and after a 5 h infusion of 20 micrograms per person in 6 healthy subjects. In addition, a pinealomectomized patient whose nocturnal plasma melatonin had been abolished was investigated after the i.v. infusion--once during the night and once during the day. The clearance of melatonin from blood showed a biexponential decay. The pharmacokinetic parameters in the two studies were similar, except for the disappearance rate constant beta and the apparent volume of distribution at steady-state (Vss). Supplementary peaks or troughs were superimposed on the plateau and the falling part of the profile. They were not due to stimulation of endogenous secretion, because they were also seen in the pinealomectomized patient. During the melatonin infusion, the plasma hormone level reached a steady-state after 60 and 120 min, and when it was equal to the nocturnal level. The infusion regime may be valuable in replacing blunted hormonal secretion in disease states.

A single physiological dose of melatonin (20 µg for 3 h given intravenously at different times of the day (04.00–12.00, 16.00 and 20.00 h) was able to shift the endogenous plasma melatonin profile of healthy volunteers under entrained conditions according to a phase-response curve (PRC). ANOVA showed an effect of the time of administration on the onset, the acrophase or the offset of the melatonin profiles. These profiles were significantly delayed when the infusion was administered at 12.00 h and advanced when the infusion was given at 20.00 h. Further, the AUCs evaluated on the nocturnal melatonin profiles were increased after the 04.00 h infusion (+20.5%, p < 0.05), whereas they were decreased after the 12.00 h infusion (–20%, p < 0.05). Lastly, no alteration was observed for cortisol rhythm, whatever the time of melatonin administration. These results, which show that according to a PRC the system regulating melatonin secretion is sensitive to a single short-term administration of the hormone given at a low dose, support the paradigm of the endogenous synchronizer melatonin.

High dose intravenous immunoglobulin (IVG) is increasingly used in a broad range of immune mediated diseases. Thrombosis was exceptionally reported as a complication of this therapy. We describe three cases of thrombotic complications during or soon after IVIG treatment: myocardial infarction in a man and cerebral infarctions in an elderly man, associated with peripheral ischemia in a woman. In addition we review the published cases in the literature and discuss the possible etiologic factors.

S Al-Rajeh, A Ogunniyi, A Awada, A Daif, R Zaidan, Preliminary Assessment of an Arabic Version of the MiniMental State Examination. 1999; 19(2): 150-152 The Mini-Mental State Examination (MMSE) is one of the most widely used instruments for quantitative assessment of cognitive functions and for dementia screening.1,2 It assesses many cognitive domains, including orientation, memory, language, calculation and visual construction. The test, however, shows educational as well as cultural bias, and appears to be more suited to Western culture. [2][3][4] The use of the MMSE in other cultures, therefore, entails translation into the specific languages, modification and/or substitution of some of the items with culturally relevant ones, and pilot-testing these for reliability, sensitivity and specificity. There are many versions and translations of the MMSE, including Chinese, German, Spanish and Nigerian, which have been used for studies in the respective cultures. [4][5][6][7] An Arabic version of the MMSE was developed and pilot-tested on Saudi patients. The results are presented in this report. Materials and MethodsThe MMSE was translated into the Arabic language, with many items left unchanged from the original version. The names of the area of the Kingdom and its location were substituted for the name of the country and the particular state, which appear in the original version. Date (a popular palm produce), chair and money, were the three items most often used. We used serial subtraction of 3s from 100 for assessing calculation, attention and concentration. We omitted spelling "world" backwards because the concept appeared difficult in a predominantly illiterate population. The expression "no ifs, ands or buts" was replaced by an Arabic phrase. The Arabic version produced was then translated back into English to ensure consistency of the items. The questionnaire was then administered by the same interviewer to 33 subjects, comprising 27 males and 6 females, who volunteered to take part in the study. The participants were mainly relations of inpatients at the King Khalid University Hospital, Riyadh (KKUH), who had no evidence of central nervous system dysfunction and were not on medications that could depress cognitive function or alertness. The responses were recorded as either correct or incorrect. The educational status of the individuals was obtained at the end of the administration of the questionnaire. Individuals who had not attended school or had spent less than six years in school were regarded as uneducated.Using sequential analysis, the questionnaire was administered by the same interviewer to four clinically diagnosed demented patients (based on DSM-IV criteria) 8 being managed at KKUH, for the determination of its psychometric properties. The dementia diagnoses were vascular (two cases), probable Alzheimer's disease (one case) and dementia associated with meningioma (one case). The patients included three females and one male, with a mean age of 69.8±11.2 years (range, 54-80 years), who were uned...

The plasma melatonin profile was significantly disturbed (phase-shift of the maximum melatonin level) in four out of six female sufferers from status migrainosus, compared with nine healthy controls. The number of secretion peaks was similar in both groups. A nocturnal 20 micrograms melatonin infusion (from 21.00 to 01.00 h) evoked plasma melatonin levels slightly higher than a physiological secretion peak. During infusion, the episodes of secretion were reinforced and the endogenous plasma profile was phase-advanced in two patients displaying a phase-delay. These data suggest impaired pineal function in migraine. In the absence of side effects of melatonin infusion, the relief of certain migraine symptoms described by our patients might support a controlled trial of melatonin in migraine.