Radwan Zaidan

Melatonin is able to influence its secretion in humans : description of a phase-response curve

A single physiological dose of melatonin (20 micrograms 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.

Pharmacokinetics of melatonin in man after intravenous infusion and bolus injection

SummaryThe pharmacokinetics of melatonin during the day-time has been studied in 4 healthy subjects after a bolus i.v. injection of 5 or 10 μg/person and after a 5 h infusion of 20 μg 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 β 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.

Thrombosis complicating high dose intravenous immunoglobulin: report of three cases and review of the literature.

High dose intravenous immunoglobulin (IVG) is increasingly used in a broad range of immune mediated diseases. Thrombosis was exceptionaly 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.

Myasthenia gravis: presentation and outcome in 104 patients managed in a single institution.

BACKGROUND AND OBJECTIVES Few studies have attempted to delineate the clinical profile of myasthenia gravis (MG) among people of Arab ancestry. Therefore, we sought to clarify the clinical profile, the outcome of treatment and the role of thymectomy in non-thymomatous MG in Saudi Arabia. PATIENTS AND METHODS We retrospectively studied 104 patients followed over a mean period of 7.2 years (range, 1 to 22 years) at the King Khaled University Hospital, Riyadh, Saudi Arabia. Disease outcomes were compared among thymectomized and non-thymectomized patients according to the post-intervention status criteria of the Myasthenia Gravis Foundation of America (MGFA). RESULTS Age of onset was 22.5±9.3 years (mean±SD) in females and 28.2±15.9 years in males, with peaks in the second and third decades among females and the third and fourth decades among males. At diagnosis, a majority of patients had moderate generalized weakness, equivalent to MGFA class III severity. After medical treatment with or without thymectomy, 9.6% of all patients had achieved complete stable remission, 3.8% had pharmacological remission, 27.9% had minimal manifestations, 23.1% were improved, 20.2% were unchanged and 15.4% were worse. Only thymectomized patients without a thymoma achieved remission, a significant benefit over those who had no thymectomy (P=.02). CONCLUSION MG presents at a younger age among Saudi Arabs compared to other racial groups. Thymectomy conferred significant benefits towards achievement of remission.

event-related evoked potentials in chronic respiratory encephalopathy

Background: Cognitive event-related potential (P300) is an index of cognitive processing time. It was found to be prolonged in dementia, renal, and hepatic encephalopathies, but was not extensively assessed in respiratory failure. Objective: To evaluate P300 changes in patients with respiratory failure, and especially those with mild or subclinical hypoxic–hypercapnic encephalopathy. Methods: Auditory event-related evoked potential P300 latency was measured using an oddball paradigm in patients with respiratory failure due to any cause (partial pressure of oxygen in arterial blood (PO2) should be 75 mm/Hg or less). Apart from blood gases measurement, patients underwent the Mini-Mental State Examination (MMSE). Patient performances were compared with that of matched normal control. Patients were admitted into the study from outpatient clinics and wards at King Khalid University Hospital and Sahara Hospital. Results: Thirty-four patients (12 women, 22 men) were admitted to the study. Ages ranged from 19–67 years with a mean of 46.1 years. Respiratory failure was severe or very severe in 11 patients (33%), and mild or moderate in the rest (66%). Mean value for PO2 and partial pressure of carbon dioxide in arterial blood (PCO2) were 63.7 and 45.2 mm/Hg, respectively. pH mean was 7.4 and O2 saturation was 90.7%. P300 latency ranged from 218 to 393 milliseconds, with a mean of 338.4 milliseconds. In comparison with control (309.9 milliseconds), there was a significant difference (P = 0.007). P300 amplitude differences were not significant. No significant difference in MMSE was noted between mild and severe respiratory failure. Results of detailed neuropsychological assessment were clearly abnormal but were limited by the small number of tested patients. P300 latency changes correlated significantly with age as well as severity of respiratory failure. P300 was also significantly delayed whether hypoxia occurred with or without hypercapnia. Conclusion: Results show a significant delay of P300 latency in patients with severe and mild respiratory failure. This was associated with subclinical encephalopathy in most patients, evidenced by a near-normal MMSE score. Apart from confirming the importance of P300 latency measurement as a marker of respiratory encephalopathy, this study asserts the causal relationship between hypoxemia and cognitive derangement. Furthermore, it promotes the early use of oxygen therapy in a selected group of patients with mild or moderate respiratory failure, who have responsibilities which involve taking rapid critical decisions.

A rare homozygous missense mutation in ATP7B exon 19 in a case of Wilson disease

Introduction Wilson disease (WD), an autosomal recessive disorder of copper transport, is characterized by impaired biliary excretion and deficient incorporation of copper into ceruloplasmin [1]. This leads to toxic accumulation of copper in the liver and subsequent overflow and accumulation in the brain, kidney and cornea. Thus, excess accumulation of copper can cause tissue damage leading to hepatic, neurological and psychiatric disturbances or a combination of these [1, 2]. Patients with liver disease generally present in childhood or adolescence. Neurological and psychiatric symptoms begin at the age of 12 years or later [2]. WD occurs in populations of every geographic and ethnic origin. The worldwide prevalence of WD is estimated to be 1 in 30,000, with a corresponding gene frequency of 0.56% and a carrier frequency of about 1/90 [1, 2]. ATP7B, the gene mutated in WD, has 21 exons and encodes a protein of 1,465 amino acids [1]. The protein is a copper-transporting P-type ATPase. To date more than 100 mutations have been detected in the ATP7B gene, few of which are common to several populations, the majority being population specific [3–5]. In this report, we present a patient with WD caused by a novel homozygous missense mutation associated with severe neurological and psychiatric disturbances leading to his death.

Severe intermittent anxiety attacks. A diagnosis challenge in temporal lobe epilepsy

Psychiatric symptoms are frequently reported with epilepsy. Anxiety symptoms are the most common psychiatric expressions of temporal lobe epilepsy (TLE). Longer duration of the epileptic manifestation can be mistaken for psychiatric diseases, particularly when psychiatric symptoms are the only manifestations of the disorder. Here we introduce a case of a 27-year-old Saudi man presented to our clinic with a history of sudden and severe anxiety attacks over the prior 2 years, each lasting for 2-3 days. The attacks recurred monthly without clear triggers, and he recovered his normal clinical state between them. His condition worsened with antidepressants and improved with antiepileptic. Later follow ups and work ups supported the diagnosis of temporal lobe epilepsy. Diagnosis after such presentation may be challenging and we tried, in this case, to enhance awareness of such an unusual presentation.