Kearns-Sayre's syndrome developing in a boy who survived Pearson's syndrome caused by mitochondrial DNA deletion

Documenta Ophthalmologica 1992, Volume 82, Issue 1-2, pp 73-79 Kearns-Sayre's syndrome developing in a boy who survived Pearson's syndrome caused by mitochondrial DNA deletion Dr H. J. Simonsz, K. Bärlocher, A. Rötig … show all 3 hide » Download PDF (2,322 KB) Abstract A 7-year-old boy presented with bilateral ptosis and atypical retinitis pigmentosa. Before age two, he had had an Fe-refractory anemia, with neutropenia and thrombopenia. Just prior to the ophthalmic examination, the patient developed lactate acidosis, muscular hypotonia, ataxia and increased protein in the spinal fluid. Pancytopenia, pancreas dysfunction and growth retardation are the main features of Pearson's syndrome, most children not surviving beyond age three. The cause of Pearson's syndrome in our patient turned out to be a 5 kb deletion in the mitchondrial DNA. Similar deletions have been described in the Kearns-Sayre syndrome. It seems that children who survive the initial phase of Pearson's syndrome, may develop Kearns-Sayre syndrome

Confronting the issues of patient safety and investigator conflict of interest in an international clinical trial of myocardial reperfusion

The Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) trial is a large scale international trial of new myocardial reperfusion strategies. The primary hypothesis is that early and sustained coronary artery recanalization will be associated with a significant reduction in mortality. The four regimens that are being tested are 1) streptokinase with subcutaneous heparin; 2) streptokinase with intravenous heparin; 3) accelerated recombinant tissue-type plasminogen activator (rt-PA) with intravenous heparin; and 4) combination streptokinase, rt-PA and intravenous heparin. The planned recruitment of 41,600 patients in 1,500 sites from 15 countries is expected to be completed by December 1992 and will enable detection of a 15% reduction or 1% absolute difference in mortality compared with that associated with standard therapy (streptokinase and subcutaneous heparin). In designing the trial, two important issues were directly addressed. First, a strategy was developed to provide assurance of patient safety during large scale investigational use of an aggressive thrombolytic regimen. This includes fascimile transmission of a one-page safety summary form to the Data Coordinating Center within 24 h of death or discharge, acceptance of the concept of "net clinical benefit" and close surveillance of the trial's progress by the independent Data and Safety Monitoring Committee. S

Energy expenditure during sleep, sleep deprivation and sleep following sleep deprivation in adult humans

Sleep has been proposed to be a physiological adaptation to conserve energy, but little research has examined this proposed function of sleep in humans. We quantified effects of sleep, sleep deprivation and recovery sleep on whole-body total daily energy expenditure (EE) and on EE during the habitual day and nighttime. We also determined effects of sleep stage during baseline and recovery sleep on EE. Seven healthy participants aged 22 ± 5 years (mean ± s.d.) maintained ∼8 h per night sleep schedules for 1 week before the study and consumed a weight-maintenance diet for 3 days prior to and during the laboratory protocol. Following a habituation night, subjects lived in a whole-room indirect calorimeter for 3 days. The first 24 h served as baseline – 16 h wakefulness, 8 h scheduled sleep – and this was followed by 40 h sleep deprivation and 8 h scheduled recovery sleep. Findings show that, compared to baseline, 24 h EE was significantly increased by ∼7% during the first 24 h of sleep deprivation and was significantly decreased by ∼5% during recovery, which included hours awake 25–40 and 8 h recovery sleep. During the night time, EE was significantly increased by ∼32% on the sleep deprivation night and significantly decreased by ∼4% during recovery sleep compared to baseline. Small differences in EE were observed among sleep stages, but wakefulness during the sleep episode was associated with increased energy expenditure. These findings provide support for the hypothesis that sleep conserves energy and that sleep deprivation increases total daily EE in humans

A critical review of smaller state diplomacy

In The Peloponnesian War, Thucydides (1972: 402) highlights the effects of the general, overall weakness of smaller states vis-à-vis larger, more powerful ones in a key passage, where the Athenians remind the Melians that: “… since you know as well as we do that, as the world goes, right is only in question between equals in power. Meanwhile, the strong do what they can and the weak suffer what they must.” Concerns about the vulnerability of small, weak, isolated states have echoed throughout history: from Thucydides, through the review by Machiavelli (1985) of the risks of inviting great powers to intervene in domestic affairs, through 20th century US-led contemporary political science (Vital, 1971; Handel, 1990) and Commonwealth led scholarship (Commonwealth Secretariat, 1985). In the context of 20th century ‘Balkanization’, the small state could also prove unstable, even hostile and uncooperative, a situation tempting enough to invite the intrusion of more powerful neighbours: a combination, according to Brzezinski (1997: 123-124) of a power vacuum and a corollary power suction2: in the outcome, if the small state is ‘absorbed’, it would be its fault, and its destiny, in the grand scheme of things. In an excellent review of small states in the context of the global politics of development, Payne (2004: 623, 634) concludes that “vulnerabilities rather than opportunities are the most striking consequence of smallness”. It has been recently claimed that, since they cannot defend or represent themselves adequately, small states “lack real independence, which makes them suboptimal participants in the international system” (Hagalin, 2005: 1). There is however, a less notable and acknowledged but more extraordinary strand of argumentation that considers ‘the power of powerlessness’, and the ability of small states to exploit their smaller size in a variety of ways in order to achieve their intended, even if unlikely, policy outcomes. The pursuance of smaller state goals becomes paradoxically acceptable and achievable precisely because such smaller states do not have the power to leverage disputants or pursue their own agenda. A case in point concerns the smallest state of all, the Vatican, whose powers are both unique and ambiguous, but certainly not insignificant (The Economist, 2007). Smaller states have “punched above their weight” (e.g. Edis, 1991); and, intermittently, political scientists confront their “amazing intractability” (e.g. Suhrke, 1973: 508). Henry Kissinger (1982: 172) referred to this stance, with obvious contempt, as “the tyranny of the weak”3. This paper seeks a safe passage through these two, equally reductionist, propositions. It deliberately focuses first on a comparative case analysis of two, distinct ‘small state-big state’ contests drawn from the 1970s, seeking to infer and tease out the conditions that enable smaller ‘Lilliputian’ states (whether often or rarely) to beat their respective Goliaths. The discussion is then taken forward to examine whether similar tactics can work in relation to contemporary concerns with environmental vulnerability, with a focus on two other, small island states. Before that, the semiotics of ‘the small state’ need to be explored, since they are suggestive of the perceptions and expectations that are harboured by decision makers at home and abroad and which tend towards the self-fulfilling prophecy.peer-reviewe

Sleep, vigilance, and thermosensitivity

The regulation of sleep and wakefulness is well modeled with two underlying processes: a circadian and a homeostatic one. So far, the parameters and mechanisms of additional sleep-permissive and wake-promoting conditions have been largely overlooked. The present overview focuses on one of these conditions: the effect of skin temperature on the onset and maintenance of sleep, and alertness. Skin temperature is quite well suited to provide the brain with information on sleep-permissive and wake-promoting conditions because it changes with most if not all of them. Skin temperature changes with environmental heat and cold, but also with posture, environmental light, danger, nutritional status, pain, and stress. Its effect on the brain may thus moderate the efficacy by which the clock and homeostat manage to initiate or maintain sleep or wakefulness. The review provides a brief overview of the neuroanatomical pathways and physiological mechanisms by which skin temperature can affect the regulation of sleep and vigilance. In addition, current pitfalls and possibilities of practical applications for sleep enhancement are discussed, including the recent finding of impaired thermal comfort perception in insomniacs