Unhealthy alcohol use, HIV infection and risk of liver fibrosis in drug users with hepatitis C

Aim To analyze alcohol use, clinical data and laboratory parameters that may affect FIB-4, an index for measuring liver fibrosis, in HCV-monoinfected and HCV/HIV-coinfected drug users. Patients and Methods Patients admitted for substance abuse treatment between 1994 and 2006 were studied. Socio-demographic data, alcohol and drug use characteristics and clinical variables were obtained through hospital records. Blood samples for biochemistry, liver function tests, CD4 cell count, and serology of HIV and HCV infection were collected at admission. Multivariate linear regression was used to analyze the predictors of FIB-4 increase. Results A total of 472 (83% M, 17% F) patients were eligible. The median age at admission was 31 years (Interquartile range (IQR) 27–35 years), and the median duration of drug use was 10 years (IQR 5.5–15 years). Unhealthy drinking (>50 grams/day) was reported in 32% of the patients. The FIB-4 scores were significantly greater in the HCV/HIV-coinfected patients (1.14, IQR 0.76–1.87) than in the HCV-monoinfected patients (0.75, IQR 0.56–1.11) (p<0.001). In the multivariate analysis, unhealthy drinking (p = 0.034), lower total cholesterol (p = 0.042), serum albumin (p<0.001), higher GGT (p<0.001) and a longer duration of addiction (p = 0.005) were independently associated with higher FIB-4 scores in the HCV-monoinfected drug users. The effect of unhealthy drinking on FIB-4 scores disappeared in the HCV/HIV-coinfected patients, whereas lower serum albumin (p<0.001), a lower CD4 cell count (p = 0.006), higher total bilirubin (p<0.001) and a longer drug addiction duration (p<0.001) were significantly associated with higher FIB-4 values. Conclusions Unhealthy alcohol use in the HCV-monoinfected patients and HIV-related immunodeficiency in the HCV/HIV-coinfected patients are important risk factors associated with liver fibrosis in the respective populations.

Aggressive Behaviour of Different Social and Demographic Groups in Post-Totalitarian Society

The project looked at aggressiveness in different age and social groups of modern post-totalitarian society, beginning with the hypotheses that the greatest risk groups are teenagers and the unemployed, and that there is a link between aggression and the level of meaningfulness of life. The groups studied comprised about 200 persons from urban areas of eastern Ukraine, including schoolchildren, students, white collar workers, self-employed persons, the unemployed and pensioners. Workers in industry were not included as this group has virtually disappeared in Ukraine at present since most enterprises have ceased to work and most workers have moved into the groups of the unemployed or self-employed. Participants were divided into age groups of 13-14, 16-17, 18-22, 24-45, 46-60 and over 60, with each group including approximately equal number of men and women. Research methods included Buss-Darky techniques, the "hand test" (E. Wagner), the "non-existent animal" technique, a Rozenzweig picture frustration study, purpose-in-life tests and an interview. The Buss-Darky test showed that schoolchildren have the highest level of aggression, followed by students. These groups have high indexes in virtually all types of aggression, including its open form. The self-employed have relatively lower indexes, although they are more likely to manifest it openly, while such open manifestations are less likely among white-collar workers, pensioners and the unemployed. The least aggressive were the unemployed and pensioners, although the latter had a relatively high level of hostility. In terms of age, aggression was shown to decrease with age, which Ms. Ivanova attributes to the still imperfect control mechanisms of teenagers and their less mature personalities. Among the younger groups girls showed a slightly higher level of aggression, although this situation was reversed among older people. The risk groups inclined to manifest open forms of aggressiveness can therefore be seen to be teenagers and students. Other tests used show aggressiveness as a feature of the current state, rather than as an inherent feature and the results obtained were somewhat different. In the interviews, all adults referred to the increased aggressiveness in society and most stated that they themselves had become more aggressive and bad-tempered. The ability of individuals to adapt to their social environment was also investigated and schoolchildren turned out to have the lowest adaptation index and the unemployed the highest. MS. Ivanova attributes that latter, rather surprising, result to the fact that the constant frustrations facing the unemployed force them to actively seek ways and means of adapting in order to survive. The final aspect considered was the possible connection between human aggressiveness and the meaningfulness of life. Here the groups with the most meaningful lives were the self-employed and pensioners. The latter result, again rather surprising, was attributed to the desire of people who have already lived the greater part of their lives to place more weight on what they have already done, in order to prove to themselves that they have not lived in vain. The hypothesis that aggressiveness is conversely related to the meaningfulness of life was only partially confirmed. In the two extreme cases (schoolchildren and pensioners) this was indeed the case, but the remaining groups did not show any such connection. From the data obtained, Ms. Ivanova concluded that life in modern post-totalitarian society does indeed foster a rise in people's aggressiveness, and this was supported by the fact that indexes of aggressiveness proved to be higher than the norm. Her original hypothesis as to the groups in society most at risk from open aggression confirmed in the case of teenagers but not of the unemployed, who had relatively low aggressiveness indexes and the highest degree of adaptation.

The Social Desintegration of an Ethnical German Group from Romanian Village Community Comparative with a Romanian Group and Hungarian Group from some Village Their Integration into the German Society

Zarna is witness to the disappearance of the Swabian community in Santana, a process which seems to date back to before the major changes in Central and Eastern Europe. His project showed how a strong German ethnic community, formed more than 250 years ago, has virtually disappeared from the village of Santana (Romania). Zarna presents the causes leading to the loss of their ethnic identity, of their culture, traditions and of the collective reproduction of their ethnicity, although the last Swabians remaining in the village have preserved their individual identity and not let themselves be assimilated. The policy of the former communist regime is not sufficient to explain the decline of the German ethnic group, nor is the present international context with its varying effects on the form and reproduction of their ethnic identity. Zarna has analysed the origins of the Swabian community, its development, historical changes (both desired and imposed) and the disappearance of elements that determined their German culture and their pride in being German. The Germans have demobilised more rapidly than other ethnic groups in Romania, partly because of Germany's pro-emigration policy over the last two decades. Many of the emigrants were however, poorly prepared for emigration and have not been able to recreate the prosperous financial situation which they left. The prevalent feeling among those interviewed was disappointment and this increases with age and education.

Aldosterone deficiency adversely affects pregnancy outcome in mice

Circulating aldosterone levels are increased in human pregnancy. Inadequately low aldosterone levels as present in preeclampsia, a life-threatening disease for both mother and child, are discussed to be involved in its pathogenesis or severity. Moreover, inactivating polymorphisms in the aldosterone synthase gene have been detected in preeclamptic women. Here, we used aldosterone synthase-deficient (AS(-/-)) mice to test whether the absence of aldosterone is sufficient to impair pregnancy or even to cause preeclampsia. AS(-/-) and AS(+/+) females were mated with AS(+/+) and AS(-/-) males, respectively, always generating AS(+/-) offspring. With maternal aldosterone deficiency in AS(-/-) mice, systolic blood pressure was low before and further reduced during pregnancy with no increase in proteinuria. Yet, AS(-/-) had smaller litters due to loss of fetuses as indicated by a high number of necrotic placentas with massive lymphocyte infiltrations at gestational day 18. Surviving fetuses and their placentas from AS(-/-) females were smaller. High-salt diet before and during pregnancy increased systolic blood pressure only before pregnancy in both genotypes and abolished the difference in blood pressure during late pregnancy. Litter size from AS(-/-) was slightly improved and the differences in placental and fetal weights between AS(+/+) and AS(-/-) mothers disappeared. Overall, an increased placental efficiency was observed in both groups paralleled by a normalization of elevated HIF1α levels in the AS(-/-) placentas. Our results demonstrate that aldosterone deficiency has profound adverse effects on placental function. High dietary salt intake improved placental function. In this animal model, aldosterone deficiency did not cause preeclampsia.

Importance of the sampled milk fraction for the prediction of total quarter somatic cell count

This study investigated the changes in somatic cell counts (SCC) in different fractions of milk, with special emphasis on the foremilk and cisternal milk fractions. Therefore, in Experiment 1, quarter milk samples were defined as strict foremilk (F), cisternal milk (C), first 400 g of alveolar milk (A1), and the remaining alveolar milk (A2). Experiment 2 included 6 foremilk fractions (F1 to F6), consisting of one hand-stripped milk jet each, and the remaining cisternal milk plus the entire alveolar milk (RM). In Experiment 1, changes during milking indicated the importance of the sampled milk fraction for measuring SCC because the decrease in the first 3 fractions (F, C, and A1) was enormous in milk with high total quarter SCC. The decline in SCC from F to C was 50% and was 80% from C to A1. Total quarter SCC presented a value of approximately 20% of SCC in F or 35% of SCC in C. Changes in milk with low or very low SCC were marginal during milking. Fractions F and C showed significant differences in SCC among different total SCC concentrations. These differences disappeared with the alveolar fractions A1 and A2. In Experiment 2, a more detailed investigation of foremilk fractions supported the findings of Experiment 1. A significant decline in the foremilk fractions even of F1 to F6 was observed in high-SCC milk at concentrations >350 x 10(3) cells/mL. Although one of these foremilk fractions presented only 0.1 to 0.2% of the total milk, the SCC was 2- to 3-fold greater than the total quarter milk SCC. Because the trait of interest (SCC) was measured directly by using the DeLaval cell counter (DCC), the quality of measurement was tested. Statistically interesting factors (repeatability, recovery rate, and potential matrix effects of milk) proved that the DCC is a useful tool for identifying the SCC of milk samples, and thus of grading udder health status. Generally, the DCC provides reliable results, but one must consider that SCC even in strict foremilk can differ dramatically from SCC in the total cisternal fraction, and thus also from SCC in the alveolar fraction.

[Follow-up in a boy with Leydig cell tumor after selective surgery]

A 8(6/12) year-old-boy presented with precocious puberty and a slightly enlarged left testis. After a detailed examination a Leydig cell tumour was diagnosed. Surgical exploration revealed an encapsulated tumour, 2.7 cm in length, which was selectively removed without orchidectomy. Within one year the clinical signs of pubertal precocity disappeared, the bone age did not further advance and height velocity declined from 8.2 cm / year (+3.9 SDS) to 4.1 cm/year (-1.0 SDS). Physiologically, he entered puberty at the chronological age of twelve years, presenting at that age, in comparison to his peer group, a slightly decreased pubertal growth spurt. However, bearing in mind that being precocious in puberty he started in fact his pubertal growth spurt at a far earlier age, therefore, this acceleration of height before operation has to be added to the centimetres gained during pubertal development thereafter resuiting consequently in an absolute normal pubertal growth spurt. This underlines the fact that the individual growth spurt and, therefore, the total amount of centimetres gained is very much robust. Ten years later, the patient ended up well within his familial target height and remained free of disease. We report on a long-term follow-up of a prepubertal boy after testis-sparing surgery for Leydig-cell-tumour.

UMTS base station-like exposure, well-being, and cognitive performance

BACKGROUND: Radio-frequency electromagnetic fields (RF EMF) of mobile communication systems are widespread in the living environment, yet their effects on humans are uncertain despite a growing body of literature. OBJECTIVES: We investigated the influence of a Universal Mobile Telecommunications System (UMTS) base station-like signal on well-being and cognitive performance in subjects with and without self-reported sensitivity to RF EMF. METHODS: We performed a controlled exposure experiment (45 min at an electric field strength of 0, 1, or 10 V/m, incident with a polarization of 45 degrees from the left back side of the subject, weekly intervals) in a randomized, double-blind crossover design. A total of 117 healthy subjects (33 self-reported sensitive, 84 nonsensitive subjects) participated in the study. We assessed well-being, perceived field strength, and cognitive performance with questionnaires and cognitive tasks and conducted statistical analyses using linear mixed models. Organ-specific and brain tissue-specific dosimetry including uncertainty and variation analysis was performed. RESULTS: In both groups, well-being and perceived field strength were not associated with actual exposure levels. We observed no consistent condition-induced changes in cognitive performance except for two marginal effects. At 10 V/m we observed a slight effect on speed in one of six tasks in the sensitive subjects and an effect on accuracy in another task in nonsensitive subjects. Both effects disappeared after multiple end point adjustment. CONCLUSIONS: In contrast to a recent Dutch study, we could not confirm a short-term effect of UMTS base station-like exposure on well-being. The reported effects on brain functioning were marginal and may have occurred by chance. Peak spatial absorption in brain tissue was considerably smaller than during use of a mobile phone. No conclusions can be drawn regarding short-term effects of cell phone exposure or the effects of long-term base station-like exposure on human health.

Spastin in the human and mouse central nervous system with special reference to its expression in the hippocampus of mouse pilocarpine model of status epilepticus and temporal lobe epilepsy

In the present in situ hybridization and immunocytochemical studies in the mouse central nervous system (CNS), a strong expression of spastin mRNA and protein was found in Purkinje cells and dentate nucleus in the cerebellum, in hippocampal principal cells and hilar neurons, in amygdala, substantia nigra, striatum, in the motor nuclei of the cranial nerves and in different layers of the cerebral cortex except piriform and entorhinal cortices where only neurons in layer II were strongly stained. Spastin protein and mRNA were weakly expressed in most of the thalamic nuclei. In selected human brain regions such as the cerebral cortex, cerebellum, hippocampus, amygdala, substania nigra and striatum, similar results were obtained. Electron microscopy showed spastin immunopositive staining in the cytoplasma, dendrites, axon terminals and nucleus. In the mouse pilocarpine model of status epilepticus and subsequent temporal lobe epilepsy, spastin expression disappeared in hilar neurons as early as at 2h during pilocarpine induced status epilepticus, and never recovered. At 7 days and 2 months after pilocarpine induced status epilepticus, spastin expression was down-regulated in granule cells in the dentate gyrus, but induced expression was found in reactive astrocytes. The demonstration of widespread distribution of spastin in functionally different brain regions in the present study may provide neuroanatomical basis to explain why different neurological, psychological disorders and cognitive impairment occur in patients with spastin mutation. Down-regulation or loss of spastin expression in hilar neurons may be related to their degeneration and may therefore initiate epileptogenetic events, leading to temporal lobe epilepsy.

Reorganization of CA3 area of the mouse hippocampus after pilocarpine induced temporal lobe epilepsy with special reference to the CA3-septum pathway

We showed that when CA3 pyramidal neurons in the caudal 80% of the dorsal hippocampus had almost disappeared completely, the efferent pathway of CA3 was rarely detectable. We used the mouse pilocarpine model of temporal lobe epilepsy (TLE), and injected iontophoretically the anterograde tracer phaseolus vulgaris leucoagglutinin (PHA-L) into gliotic CA3, medial septum and the nucleus of diagonal band of Broca, median raphe, and lateral supramammillary nuclei, or the retrograde tracer cholera toxin B subunit (CTB) into gliotic CA3 area of hippocampus. In the afferent pathway, the number of neurons projecting to CA3 from medial septum and the nucleus of diagonal band of Broca, median raphe, and lateral supramammillary nuclei increased significantly. In the hippocampus, where CA3 pyramidal neurons were partially lost, calbindin, calretinin, parvalbumin immunopositive back-projection neurons from CA1-CA3 area were observed. Sprouting of Schaffer collaterals with increased number of large boutons in both sides of CA1 area, particularly in the stratum pyramidale, was found. When CA3 pyramidal neurons in caudal 80% of the dorsal hippocampus have almost disappeared completely, surviving CA3 neurons in the rostral 20% of the dorsal hippocampus may play an important role in transmitting hyperactivity of granule cells to surviving CA1 neurons or to dorsal part of the lateral septum. We concluded that reorganization of CA3 area with its downstream or upstream nuclei may be involved in the occurrence of epilepsy.

Incidental task sequence learning: perceptual rather than conceptual?

In four experiments we investigated whether incidental task sequence learning occurs when no instructional task cues are available (i.e. with univalent stimuli). We manipulated task sequence by presenting three simple binary-choice tasks (colour, form or letter case decisions) in regular repeated or random order. Participants were required to use the same two response keys for each of the tasks. We manipulated response sequence by ordering the stimuli so as to produce either a regular or a random order of left versus right-hand key presses. When sequencing in both, or either, separate stream (i.e. task sequence and/or response sequence) was changed to random, only those participants who had processed both sequences together showed evidence of sequence learning in terms of significant response time disruption (Experiments 1-3). This effect disappeared when the sequences were uncorrelated (Experiment 4). The results indicate that only the correlated integration of task sequence and response sequence produced a reliable incidental learning effect. As this effect depends on the predictable ordering of stimulus categories, it suggests that task sequence learning is perceptual rather than conceptual in nature.

Benign paroxysmal positional vertigo in mountain bikers

We evaluated 4 men who had benign paroxysmal positional vertigo (BPPV) that occured several hours after intensive mountain biking but without head trauma. The positional maneuvers in the planes of the posterior and horizontal canals elicited BPPV, as well as transitory nystagmus. This was attributed to both the posterior and horizontal semicircular canals (SCCs) on the left side in 1 patient, in these 2 SCCs on the right side in another patient, and to the right posterior SCC in the other 2 patients. The symptoms disappeared after physiotherapeutic maneuvers in 2 patients and spontaneously in the other 2 patients. Cross-country or downhill mountain biking generates frequent vibratory impacts, which are only partially filtered through the suspension fork and the upper parts of the body. Biomechanically, during a moderate jump, before landing, the head is subjected to an acceleration close to negative 1 g, and during impact it is subjected to an upward acceleration of more than 2g. Repeated acceleration-deceleration events during intensive off-road biking might generate displacement and/or dislocation of otoconia from the otolithic organs, inducing the typical symptoms of BPPV. This new cause of posttraumatic BPPV should be considered as an injury of minor severity attributed to the practice of mountain biking.

Nitric oxide is protective in listeric meningoencephalitis of rats

The bacterium Listeria monocytogenes causes meningoencephalitis in humans. In rodents, listeriosis is associated with granulomatous lesions in the liver and the spleen, but not with meningoencephalitis. Here, infant rats were infected intracisternally to generate experimental listeric meningoencephalitis. Dose-dependent effects of intracisternal inoculation with L. monocytogenes on survival and activity were noted; 10(4) L. monocytogenes organisms induced a self-limiting brain infection. Bacteria invaded the basal meninges, chorioid plexus and ependyme, spread to subependymal tissue and hippocampus, and disappeared by day 7. This was paralleled by recruitment and subsequent disappearance of macrophages expressing inducible nitric oxide synthase (iNOS) and nitrotyrosine accumulation, an indication of nitric oxide (NO.) production. Treatment with the spin-trapping agent alpha-phenyl-tert-butyl nitrone (PBN) dramatically increased mortality and led to bacterial numbers in the brain 2 orders of magnitude higher than in control animals. Treatment with the selective iNOS inhibitor L-N(6)-(1-iminoethyl)-lysine (L-NIL) increased mortality to a similar extent and led to 1 order of magnitude higher bacterial counts in the brain, compared with controls. The numbers of bacteria that spread to the spleen and liver did not significantly differ among L-NIL-treated, PBN-treated, and control animals. Thus, the infant rat brain is able to mobilize powerful antilisterial mechanisms, and both reactive oxygen and NO. contribute to Listeria growth control.

[Chronic anterior tibial syndrome]

In two young athletic men we made the diagnosis of chronic tibialis anterior syndrome. Pain during strenuous exercise was localized in the anterolateral aspect of both calves. After stopping exercise the complaints disappeared within 15-20 minutes and not in 2-3 minutes as it would be typical for patients with atherosclerotic peripheral arterial occlusive disease. Diagnosis is based on patient history, normal clinical examination (systolic ankle pressure determined by Doppler-Sonography, electronic segmental oscillography) and increased intramuscular pressure at rest (> 10 mmHg) and after exercise (42 and 35 mmHg). Bilateral fasciotomy was performed in both patients. They are free of pain after 3 respectively 6 months postoperatively.

Rotational atherectomy followed by drug-eluting stent implantation (Rota-DES): a rational approach for complex calcified coronary lesions

Rotational atherectomy has been regaining interest over the last couple of years after it almost has disappeared from most interventional catheterization laboratories for several years due to failure to prove its original concept of improving long term results of percutaneous coronary interventions (PCI) as was repeatedly shown in studies in the 1990s. Its revival coupled the introduction of drug-eluting stents (DES); these devices have led to treating much more complex lesions and high-risk patients by PCI. However, real-world experience suggested that off-label use of DES is associated with a higher rate of early and late stent thrombosis. Therefore, more attention is now being paid to the initial implantation technique of DES including aggressive lesion preparation to facilitate stent delivery and expansion. The limited studies with rot-ablation and DES showed promising results with no long term safety concerns. In these studies, a subtle observation was made suggesting that rot-ablation prior to DES implantation in such lesions may have an add-on effect on long term outcome compared to DES alone. An ongoing multicenter study is investigating such effect among complex calcified coronary lesions. Even if this additive benefit does not prove true, rot-ablation remains an efficient tool for preparing certain lesions to facilitate effective and safe DES implantation. Therefore, interventional training programs should focus on this difficult technique to bridge the gap of experience which resulted from neglecting it for several years. In this regard, dedicated courses at experienced sites as well as medical simulation may be appropriate.

Percutaneous closure of patent foramen ovale for migraine headaches refractory to medical treatment

BACKGROUND: Patent foramen ovale (PFO) has been linked to migraine, and several retrospective studies reported an improvement in migraine prevalence or frequency after PFO closure for other reasons, mostly for secondary prevention of paradoxical embolism or following diving accidents. We investigated the outcome of patients undergoing PFO closure solely for migraine headaches refractory to medical treatment. METHODS: Seventeen patients (age 44 +/- 12 years; 76% female; one atrial septal aneurysm) underwent percutaneous PFO closure using the Amplatzer PFO Occluder (AGA Medical Corporation, Golden Valley, MN). An 18-mm device was used in two patients, a 25-mm device in 13, and a 35-mm device in two. The interventions were solely guided by fluoroscopy, without intraprocedural echocardiography. RESULTS: All implantation procedures were successful. There were no peri-procedural complications. Contrast transesophageal echocardiography after Valsalva maneuver at 6 months showed complete PFO closure in 16 patients (94%), whereas a minimal residual shunt persisted in one (6%). During 2.7 +/- 1.5 years of follow-up, no deaths and no embolic events occurred. After PFO closure, migraine headaches disappeared in four patients (24%), and improved in eight additional patients (47%). Three patients (18%) reported a decrease of their headaches by 75%, three patients (18%) a decrease of 50%, and two patients (12%) a decrease of 25%, while headaches remained unchanged in five patients (29%). No patient experienced worsening headaches. Moreover, the prevalence of migraine with aura decreased from 82 to 24% (P = 0.002). CONCLUSIONS: These results suggest that percutaneous PFO closure durably alters the spontaneous course of shunt associated migraine.