Impact of metabolic syndrome on clinical outcomes after new generation drug-eluting stent implantation: the 'obesity paradox' phenomenon is still apparent.

BACKGROUND AND AIM: New generation drug-eluting stents (DES) have improved clinical outcomes. However, their impact on patients with metabolic syndrome (MS) is still unclear as there is no sufficient data. Therefore, we evaluated the impact of the new generation DES on patients with an isolated lesion in the proximal segment of the left anterior descending artery (pLAD) suffering from MS. METHODS AND RESULTS: We evaluated 511 patients with a pLAD lesion. Of these, 147 patients had MS. The major adverse cardiac events (MACE) including death, non-fatal myocardial infarction (MI) and target lesion revascularization (TLR) were defined as primary end points. Stent thrombosis was also evaluated. MACEs had a trend to be higher in non-MS group (8.24% vs 3.40%, p = 0.05) during 20 months mean follow-up period. Rates of cardiac death (1.37% vs 0.68%, p = 0.67), non-fatal MI (1.92% vs 0.0%, p = 0.20), TLR (4.94% vs 2.04% MS, p = 0.21) and thrombosis (3.29% vs 1.36%, p = 0.36) were not significantly different in non-MS and MS group. The Kaplan-Meier curve revealed: MS group: 96.59% vs non-MS group: 91.75% (p = 0.04). MS was a favorable independent predictor for MACE (hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.12-0.93, p < 0.03). In addition, independent predictors for MACE were BMI ≥ 30 kg/m(2) (HR 0.87 95% CI 0.79-0.96 p = 0.008) and diabetes mellitus (HR 2.01 95% CI 0.99-4.11, p = 0.05). CONCLUSION: The 'obese paradox' phenomenon is found in the era of new generation DES. In order to investigate the underlying mechanism for this phenomenon further studies are required.

What is the appropriate shunt system for normal pressure hydrocephalus?

Normal pressure hydrocephalus (NPH) represents a common disorder among older people with mild elevation of cerebrospinal fluid pressure and certain clinical manifestations. We present a patient with such a disorder in whom a programmable valve was implanted. With the use of a lower opening pressure, the patient developed a subdural hematoma although the symptoms subsided. After evacuating the hematoma and by setting the valve pressure higher, the patient recovered without any symptomatology. We observed that only the higher pressure was the right one, although in two different pressure values the symptoms had subsided.

Benign cerebral aqueductal stenosis in an adult.

We present a patient with partial stenosis of aqueduct of Sylvius which was an incidental finding without any clinical symptoms. That in our opinion means that the ventricular brain system has many reserves that are being activated before symptoms appear.

Severe aseptic inflammation caused by long distance running (246 km) does not increase procalcitonin.

BACKGROUND: The Spartathlon ultra distance running race (246 kilometres) is an exhausting physical exercise leading to a state of systemic inflammation associated with dramatic elevation of interleukin-6 and acute-phase reactants to levels seen only in critically ill or patients near death. We sought to study the effect of this severe inflammatory response on the levels of serum procalcitonin. MATERIALS AND METHODS: Fifteen healthy endurance-trained runners who participated in the 2006 Spartathlon were studied. Blood samples were taken the day before the race, within 15 min after the end of the race and 48 h after the end of the race. Serum interleukin-6, serum amyloid A protein, C-reactive protein, tumour necrosis factor-alpha and procalcitonin concentrations were determined. RESULTS: Serum interleukin-6, serum amyloid A protein and C-reactive protein were dramatically increased after the end of the race (150-, 116- and 10,470- fold increase of the mean values, respectively). Procalcitonin levels remained within normal range (mean +/- standard error of mean, 0.27 +/- 0.02 microg L(-1), 0.26 +/- 0.02 microg L(-1) and 0.27 +/- 0.02 microg L(-1) before, at the end, and 48 h after the race, respectively). Tumour necrosis factor-alpha measurements revealed no significant changes. CONCLUSIONS: This study provides strong evidence that Spartathlon, a prolonged endurance exercise resulting in severe stimulation of inflammatory mediators followed by muscle and liver damage, does not induce procalcitonin secretion. The findings cannot directly be applied to other causes of aseptic inflammation.

Dolichoectatic cervical arteries (carotid and vertebral arteries) heralded by recurrent cerebral ischemia: case illustration.

A case of a 61-year-old man with recurrent episodes of cerebral transient ischemic attacks is reported. The patient had a history of cigarette smoking, hypertension, hypercholesterolemia, and diabetes mellitus. Before these episodes, the patient had no clinical symptoms and signs of cerebral pathology. Brain magnetic resonance imaging revealed microvascular lesions in the white matter of the cerebral hemispheres. Digital subtraction arteriogram revealed the aortic arch dolichoic shape and course of the great vessels originating from it, whereas there were no pathological findings from the intracranial vessels. This study describes a case of the existence of distal dolichoectasia of the vertebral and carotid arteries without intracranial dolichoectasia. It seems that such a type of dolichoectasia does not influence the performance status of a patient, but when a critical point is crossed, patients suffer from cerebrovascular disease.

Risks to health and risks to science: the need for a responsible "bioevidential" scrutiny.

Ethical issues of evidence relevant for risk policy are not adequately addressed if divorced from issues of the responsible interpretation of the risk evidence itself. Evidence for hormetic hypotheses are based on data that disagree with a null hypothesis asserting H0: zero (0) improvement (at low doses). We critically evaluate some of the reasoning and the procedures used by leading proponents of hormesis, and suggest how potential errors may be avoided.

New aspects on the kinetics of activation of ribosomal peptidyltransferase-catalyzed peptide bond formation by monovalent ions and spermine.

The effect of NH4+ and K+ ions on the activity of ribosomal peptidyltransferase was investigated in a model system derived from Escherichia coli, in which AcPhe-puromycin is produced by a pseudo-first-order reaction between the preformed AcPhe-tRNA-poly(U)-ribosome complex (complex C) and excess puromycin. Detailed kinetic analysis suggests that both NH4+ and K+ ions act as essential activators of peptidyltransferase by filling randomly, but not cooperatively, multiple sites on the ribosome. With respect to the NH4+ effect at 25 degrees C. the values of the molecular interaction coefficient (n), the dissociation constant (KA), and the apparent catalytic rate constant (kmax) of peptidyltransferase at saturating levels of NH4+ and puromycin are 1.99, 268.7 mM and 24.8 min(-1), respectively. The stimulation of peptidyltransferase by K+ ions at 25 degrees C (n = 4.38, KA = 95.5 mM, kmax = 9.6 min[-1]) is not as marked as that caused by NH4+ ions. Furthermore, it is evident that NH4+ at high concentration (200 mM) is effective in filling regulatory sites of complex C, which are responsible for the modulatory effect of spermine. The combination of NH4+ ions (200 mM) with spermine (300 microM) produces an additive increase in peptidyltransferase activity. Taken together, these findings suggest the involvement of two related pathways in the regulation of peptidyltransferase activity, one mediated by specific monovalent cations and the other mediated by spermine.

Structural and functional architecture of the yeast cell-cycle transcription factor swi6.

The structural and functional organisation of Swi6, a transcriptional regulator of the budding yeast cell cycle has been analysed by a combination of biochemical, biophysical and genetic methods. Limited proteolysis indicates the presence of a approximately 15 kDa N-terminal domain which is dispensable for Swi6 activity in vivo and which is separated from the rest of the molecule by an extended linker of at least 43 residues. Within the central region, a 141 residue segment that is capable of transcriptional activation encompasses a structural domain of approximately 85 residues. In turn, this is tightly associated with an adjacent 28 kDa domain containing at least four ankyrin-repeat (ANK) motifs. A second protease sensitive region connects the ANK domain to the remaining 30 kDa C-terminal portion of Swi6 which contains a second transcriptional activator and sequences required for heteromerisation with Swi4 or Mbp1. Transactivation by the activating regions of Swi6 is antagonised when either are combined with the central ankyrin repeat motifs. Hydrodynamic measurements indicate that an N-terminal 62 kDa fragment comprising the first three domains is monomeric in solution and exhibits an unusually high frictional coefficient consistent with the extended, multi-domain structure suggested by proteolytic analysis.

The Ustilago maydis pyr3 gene: sequence and transcriptional analysis.

The pyr3 gene of Ustilago maydis encodes a 391-amino acid (aa) polypeptide. The sequence has identifies with dihydro-orotases (DHOases) from other organisms, but is most related to sequences of other monofunctional enzymes. The polypeptide contains the three domains conserved in other DHOases. The polypeptide encoded by the pyr3-1 allele has an aa change seven residues away from the C-terminal conserved domain. Transcription start point (tsp) is 58 nucleotides upstream from the start codon, and is in a region characterised by CTTT and CATC motifs. In the absence of TATA and CAAT boxes, these motifs might be important in transcriptional regulation. Gene disruption experiments suggest that the pyr3 gene product might have another function in addition to that in pyrimidine biosynthesis.

The Ustilago maydis nar1 gene encoding nitrate reductase activity: sequence and transcriptional regulation.

The nar1 gene was cloned from Ustilago maydis and the 908-amino-acid (aa) sequence of the encoded protein found to have strong identities with other nitrate reductases from fungi and plants. This was especially so in three domains which define enzyme cofactor-binding sites. The gene was isolated alone and in association with the nir1 gene, suggesting that the two genes are closely linked on the chromosome. The phenotype of a strain in which nar1 had been disrupted was consistent with the only role of nar1 being in nitrate reduction. Nitrate ions induced a 90-fold increase in nar1 transcript levels, while ammonium ions repressed transcript levels.

Developmental expression of a neuron-specific beta-tubulin in frog (Xenopus laevis): a marker for growing axons during the embryonic period.

In mammals, there are seven classes of beta-tubulin genes, one of which, class III, is neuron specific. Using class-specific monoclonal antibodies, class III beta-tubulin protein could not be detected in frog embryos or in adults with either Western blotting or immunohistochemical techniques. In contrast, the class II beta-tubulin protein, which is predominant in mammalian brain but is also expressed in other tissues, is expressed only in neurons in frog embryos. Protein was detected only in neurons from late stages of neural tube closure through premetamorphic stages. At stages 21-28, the pioneering axons of Rohon-Beard, commissural, primary motor, and trigeminal ganglion neurons were distinctly stained in the axon scaffolds that they formed in the embryonic brain and the peripheral mesenchyme. Nonneuronal cells, both outside the nervous system and within it (e.g., radial glia, Müller glia, roof plate, and floor plate cells) were not immunoreactive. Throughout swimming and premetamorphic stages, neuronal cells in all brain regions became immunoreactive as they differentiated and extended axons. Whereas many embryonic neurons became postmitotic during gastrulation stages, neurons expressed detectable levels of class II beta-tubulin protein only beginning at the onset of overt axon outgrowth. These observations demonstrate that the neuron-specific beta-tubulin in frog is a different gene from that in mammals, and its protein product is detectable at the time of axonogenesis rather than neurogenesis.

The calmodulin antagonist trifluoperazine provides mild prophylactic protection against cerebral vasospasm after subarachnoid hemorrhage, but no therapeutic value.

In vitro studies of the canine basilar artery have demonstrated that calmodulin antagonism can effectively inhibit cerebral arterial smooth muscle contractility. The prophylactic and therapeutic effectiveness of a potent calmodulin antagonist, the phenothiazine compound trifluoperazine (TFP), was investigated in vivo over a wide range of doses in the well-documented "double-subarachnoid hemorrhage" canine model of cerebral vasospasm. The compound is perhaps more well-known under its trade name, Stelazine, as a classic antipsychotic drug. The drug demonstrated no therapeutic relief of preexisting chronic cerebral vasospasm at any time during 2 days of systemic administration at any practical dose. At doses far in excess of the normally accepted therapeutic range in humans, a prophylactic regimen reduced the severity of chronic cerebral vasospasm after subarachnoid hemorrhage by approximately 35% compared to untreated dogs.

Persistent symptoms after whiplash injuries implications for prognosis and management.

The incidence of whiplash injuries of the neck has been increasing in recent years as a result of the use of seat belts, changes in automobile design, and growth in traffic loads. Physicians see many patients with this problem, a significant proportion of whom suffer from persistent symptoms. Many patients present a puzzling array of cognitive, neurologic, and musculoskeletal symptoms that challenge the clinician and are further confused by legal and compensation claims. Management is based almost completely on empirical approaches, and much research is needed to clarify this neglected problem. This article reviews and attempts to analyze the current information about the epidemiology, etiology, management, and prognostic issues of persistent whiplash injuries.

A revalidation of the Thurstone Test of Mental Alertness as a brief measure of intelligence through comparison with the Wechsler Adult Intelligence Scale-III.

In earlier research, Rossini, Wygonik, Barrett, and Friedman (1994) demonstrated that the Thurstone Test of Mental Alertness (TMA) is a valid, brief measure of intelligence by comparing it to the Wechsler Scale of Adult Intelligence-Revised, which was at that time the "gold standard" of IQ assessment. Since that study, the WAIS has again been revised and reissued in a third edition, the WAIS-III. We assessed the relationship between scores on the Thurstone Test of Mental Alertness and this latest WAIS test to see if there is still a predictive relationship between the two tests. Correlations between the two tests and the accuracy of TMA point estimates of IQ indicate that the Thurstone Test of Mental Alertness remains a viable brief measure of adult intelligence.

Thecaloscopy through sacral bone approaches, cadaver study: further anatomic landmarks.

Endoscopy of the spinal canal, for interventional studies, diagnosis and therapy, is a scientific topic that has attracted the interest of neurosurgeons, anesthesiologists and orthopedic surgeons for the past twenty years. Endoscopy of the thecal sac was assumed to be less important than endoscopy of the ventricular system by neurosurgeons. Nevertheless, during the last years it has attained increasing scientific interest, firstly because of the introduction of small diameter flexible endoscopes and secondly due to the growing interest for minimal invasive diagnostic and therapeutic procedures in modern neurosurgery. Until now thecaloscopy was performed by the ISGT (International Study Group for Thecaloscopy) using co-axial downward orientated approaches. We have examined transsacral approaches to facilitate the navigation of flexible scopes in the lumbosacral subarachnoid space, and thus we now introduce further recognizable endoscopic anatomic landmarks.