Coinheritance of mutated SMN1 and MECP2 genes in a child with phenotypic features of spinal muscular atrophy (SMA) type II and Rett syndrome.

Spinal muscular atrophy (SMA) is a neuromuscular autosomal recessive disease characterized by progressive muscle weakness and atrophy combined with motor neuron degeneration caused by mutations in the SMN 1 gene locus (5q11.2-13.2). Rett syndrome (RS) is an X-linked dominant neurodevelopmental disorder caused by mutations in MECP2 (Xq28) and characterized by normal development until 6-12 months of age, followed by regression with loss of acquired skills, gradual onset of microcephaly, stereotypic hand movements and psychomotor delay. We report a 6-year-old girl who, at 2 years of age, presented with hypotonia, psychomotor delay, amyotrophy and areflexia of the lower extremities. Molecular DNA analysis (PCR-RFLP's) for SMA type II revealed that both exons 7 and 8 of SMN 1 gene were deleted. Over the past 4 years, onset of stereotypic hand-washing movements, epileptic seizures, microcephaly, hyperventilation/breath-holding attacks and severe psychomotor delay raised the suspicion of the coexistence of RS. DNA analysis (DGGE and sequencing) identified the hotspot missense mutation R306C (c.916C>T) in exon 4 of the MECP2 gene. The coinheritance of SMA and RS, two rare monogenic syndromes in the same patient, has not been previously reported. Thorough clinical evaluation in combination with DNA analysis, allowed accurate diagnosis, providing valuable information for the genetic counseling of the family.

The penalty of mutilation for crimes in the Byzantine era (324-1453 A.D.).

Mutilation was a common punishment in Byzantium, which in all probability was introduced from the East. In legislation it was first featured in the "Eclogi" collection of laws of the Emperor Leo Isavrus III (717-741 A.D.). There are, however, indications that this punishment was already established and widespread in the time of Justinian I (527-565 A.D.), because some chroniclers of that era state that this was used for gamblers using dice and for homosexuals. The collection of laws of Leo VI the Wise (886-912 A.D.), the well-known "Hexabiblos", applied this punishment to a variety of offences such as theft, incest, adultery, attempted murder, sacrilege and the like. This punishment, furthermore, was the main penalty used against rebels and against Byzantine emperors and members of the royal family when they were removed from the throne after a successful insurrection. The basis of the latter punishment was that a mutilated person was excluded from the throne of Byzantium because the emperor was expected to fulfil the customary ideal presupposition of "perfection". No matter how curious it sounds, this barbaric penalty was imposed for reasons of leniency, i.e., to avert the heavier death penalty.

Defensive medicine: two historical cases.

Two characteristic historical examples of defensive medicine are referred to and analysed. The first of them relates to the behaviour of the eminent and experienced physician Critobulus, a member of the family of Asclepiades of Cos Island, native island of Hippocrates, who hesitated to undertake the operation on the severely wounded Alexander the Great, who was hurt during the siege of a town of the Mallians in India (326 BC). The second case refers to the Byzantine Emperor, Justin II (578 AD), when his physicians hesitated to undertake an operation for a possible wedging of a stone in the urethra, which caused painful inflammation. In both cases, the physicians proceeded to the operation after being reassured by their illustrious patients that they would not be punished in the event of failure. Furthermore, in the second case, of the mentally unbalanced Justin II, the physicians requested, obviously in the presence of witnesses, their immunity from punishment with the symbolic gesture of the handing over of the scalpel to them by the patient. This act symbolised the agreement of the patient to the operation.

Medical responsibility in Greece: analysis of a case of medical negligence.

A case of medical negligence is presented involving both surgical injury and failure to diagnose the fault and provide appropriate corrective treatment.

Vision-based absence seizure detection.

In order to diagnose epilepsy, neurologists rely on their experience, performing an equal assessment of the electroencephalogram and the clinical image. Since misdiagnosis reaches a rate of 30% and more than one-third of all epilepsies are poorly understood, a need for leveraging diagnostic precision is obvious. With the aim at enhancing the clinical image assessment procedure, this paper evaluates the suitability of certain facial expression features for detecting and quantifying absence seizures. These features are extracted by means of time-varying signal analysis from signals that are gained by applying computer vision techniques, such as face detection, dense optical flow computation and averaging background subtraction. For the evaluation, video sequences of four patients with absence seizures are used. The classification performance of a C4.5 decision tree shows accuracies of up to 99.96% with a worst percentage of incorrectly classified instances of 0.14%.

A short proximal promoter and the distal hepatic control region-1 (HCR-1) contribute to the liver specificity of the human apolipoprotein C-II gene. Hepatic enhancement by HCR-1 requires two proximal hormone response elements which have different binding specificities for orphan receptors HNF-4, ARP-1, and EAR-2.

We have identified the regulatory elements, some of the factors and potential regulatory mechanisms which determine the tissue specificity of the human apoC-II gene. The -545/+18 apoC-II promoter directs high levels of expression of the reporter CAT gene in cells of hepatic origin (HepG2), low levels of expression in cells of intestinal origin (CaCo-2) and basal expression in HeLa cells. Deletion analysis identified negative regulatory elements within the -545/-388 region and positive regulatory elements within the -388/-55 region. Linkage of different apoC-II promoter segments to the hepatic control region-1 (HCR-1) enhanced the promoter activity 2.5-11-fold in HepG2 cells but did not affect its activity in CaCo-2 or COS-1 cells. DNase I footprinting analysis using rat liver nuclear extracts identified five protected regions within the -545/+18 apoC-II promoter as follows: CIIA (-74/-44), CIIB (-102/-81), CIIC (-159/-116), CIID (-288/-265), and CIIE (-497/-462). Elements CIIB and CIIC contain hormone response elements. CIIB is recognized by hepatic nuclear factor-4 (HNF-4) but not ARP-1 or EAR-2, whereas CIIC is recognized by ARP-1 and EAR-2 but not by HNF-4. HNF-4 transactivated the apoC-II promoter or the apoC-II promoter linked to the HCR-1 in COS-1 cells. A double mutation in elements CIIB and CIIC that eliminated binding of HNF-4 or ARP-1 and EAR-2, respectively, to these sites abolished the enhancer activity of HCR-1. The combined data suggest that the apoC-II promoter/HCR-1 cluster can direct expression in cells of hepatic origin and that optimal enhancer activity requires synergistic interactions between factors bound to the distal HCR-1 and nuclear receptors bound to the two proximal hormone response elements.

Satisfying patients' rights: a hospital patient survey.

The aim of this project was to study the way in which patients' rights are being exercised in everyday hospital practice in Greece. Data were collected by using questionnaires and structured interviews with 600 patients. These patients were found to ignore the fact that special regulations exist regarding their rights. They considered their right to information was being respected, albeit to different degrees. Many patients allowed their doctors to make decisions. The right to confidentiality was not considered as a major priority by these patients because they doubted its applicability. They hesitated to protest when their rights were being violated. They thought that the most effective way of protecting their rights is either through the existence of someone with specialized knowledge or an internal hospital committee. These Greek patients appeared to be relatively satisfied with the way in which their rights were being exercised in hospital. However, a number of improvements could increase patient satisfaction regarding this issue.

Is consent in medicine a concept only of modern times?

Although the issue of consent in medical practice has grown immensely in recent years, and it is generally believed that historical cases are unknown, our research amongst original ancient Greek and Byzantine historical sources reveals that it is a very old subject which ancient philosophers and physicians have addressed. Plato, in ancient Greece, connected consent with the quality of a free person and even before him, Hippocrates had advocated seeking the patient's cooperation in order to combat the disease. In Alexander the Great's era and later on in Byzantine times, not only was the consent of the patient necessary but physicians were asking for even more safeguards before undertaking a difficult operation. Our study has shown that from ancient times physicians have at least on occasion been driven to seek the consent of their patient either because of respect for the patient's autonomy or from fear of the consequences of their failure.

Psychological stress and fatal heart attack: the Athens (1981) earthquake natural experiment.

The effects of acute and subacute psychological stress caused by a sudden general disaster on mortality from atherosclerotic heart disease (underlying cause) and cardiac events (proximate cause) were investigated by comparing total and cause-specific mortality during the days after a major earthquake in Athens in 1981 with the mortality during the surrounding month and the corresponding periods of 1980 and 1982. There was an excess of deaths from cardiac and external causes on the days after the major earthquake, but no excess of deaths from cancer and little, if any, excess of deaths from other causes. The excess mortality was more evident when atherosclerotic heart disease was considered as the underlying cause (5, 7, and 8 deaths on the first three days, respectively; background mean deaths per day 2.6; upper 95th centile 5) than when cardiac events in general were considered as the proximate cause (9, 11, and 14 deaths on the first three days, respectively; background mean 7.1, upper 95th centile 12).

An evaluation of the effectiveness of tobacco-control legislative policies in European Community countries.

The purpose of this paper was to assess the effectiveness of anti-tobacco smoking legislation from 1948 onwards in reducing actual per capita tobacco consumption in the twelve countries of the European Economic Community (EEC). In order to undertake these assessments a score was assigned to every legislative measure, indicating the a priori likely impact of this measure on tobacco consumption. Two approaches were then utilized. In the first, it was found that the cumulative anti-tobacco legislative score correlates well in time with a reduction of tobacco consumption. In the second, cross-sectional data from the EEC countries and multiple regression modelling were used to estimate the elasticities of tobacco price, per capita income and cumulative anti-tobacco legislation score; it was found that legislation has an impact on tobacco consumption which, although considerably smaller than the corresponding impact of tobacco price levels, is nominally significant and potentially important. The evaluative approaches utilized in this paper are based on observational data of ecologic nature and can provide only weak evidence about the causal nature of the reported associations. Nevertheless, this limited evidence suggests that legislative measures may be effective both by affecting price levels and through other mechanisms, including health education and the formation of a more general anti-smoking ethos.

Attitudes of a Mediterranean population to the truth-telling issue.

The attitudes of the Greeks, a Mediterranean population, to the issue of telling the truth to the patient have been studied. There is no clear answer to the question: 'Do the Greeks wish to be informed of the nature of their illness?'. The answer is: 'It depends'. It depends on age, education, family status, occupation, place of birth and residence and on whether or not they are religious people. However, it does not depend on their sex--men and women have similar reactions to the issue of truth-telling. Although the present study shows lower percentages of those who wish to know the truth than studies on other populations, the conclusion is that, emphasising the need for good communication between doctors and patients, doctors should not lie, but should disclose to their patients the part of the truth they are ready to accept.