Kaposi sarcoma herpes virus antibody response and viremia following highly active antiretroviral therapy in the Swiss HIV Cohort study.

OBJECTIVE: To describe the effect of HAART on Kaposi sarcoma herpes virus (KSHV) antibody response and viremia among HIV-positive MSM. DESIGN: A follow-up study of 272 HIV-positive MSM (including 22 with Kaposi sarcoma) who first initiated HAART between January 1996 and July 2004 in the Swiss HIV Cohort Study. METHODS: For each individual, two serum samples, one at HAART initiation and another 24 months later, were tested for latent and lytic KSHV antibodies using immunofluorescence assays, and for KSHV viremia using PCR. Factors associated with changes in KSHV antibody titers and viremia were evaluated. RESULTS: At HAART initiation, 69.1 and 75.0% of patients were seropositive to latent and lytic KSHV antibodies, respectively. Seropositivity was associated with the presence of Kaposi sarcoma, older age, lower CD8 cell count and higher CD4/CD8 ratio. Prevalence of KSHV viremia at HAART initiation was 6.4%, being significantly higher among patients with Kaposi sarcoma (35.0%), and those with HIV viral loads 100 000 copies/ml (11.7%) or higher. At 24-month follow-up, geometric mean titers (GMTs) among KSHV seropositive patients increased and antibody seroprevalence was higher. Having Kaposi sarcoma and/or CD4 cell counts less than 50 cells/microl at HAART initiation was associated both with higher probability for antibody titers to increase (including seroconversion) and larger increases in GMTs. Only one of 17 viremic patients at HAART initiation had viremia at 24-month follow-up. CONCLUSION: HAART increases KSHV-specific humoral immune response and clearance of viremia among HIV-infected MSM, consistent with the dramatic protection offered by HAART against Kaposi sarcoma.

Evaluation of prenatal ultrasound diagnosis of fetal abdominal wall defects by 19 European registries.

OBJECTIVES: To evaluate the current effectiveness of routine prenatal ultrasound screening in detecting gastroschisis and omphalocele in Europe. DESIGN: Data were collected by 19 congenital malformation registries from 11 European countries. The registries used the same epidemiological methodology and registration system. The study period was 30 months (July 1st 1996-December 31st 1998) and the total number of monitored pregnancies was 690,123. RESULTS: The sensitivity of antenatal ultrasound examination in detecting omphalocele was 75% (103/137). The mean gestational age at the first detection of an anomaly was 18 +/- 6.0 gestational weeks. The overall prenatal detection rate for gastroschisis was 83% (88/106) and the mean gestational age at diagnosis was 20 +/- 7.0 gestational weeks. Detection rates varied between registries from 25 to 100% for omphalocele and from 18 to 100% for gastroschisis. Of the 137 cases of omphalocele less than half of the cases were live births (n = 56; 41%). A high number of cases resulted in fetal deaths (n = 30; 22%) and termination of pregnancy (n = 51; 37%). Of the 106 cases of gastroschisis there were 62 (59%) live births, 13 (12%) ended with intrauterine fetal death and 31 (29%) had the pregnancies terminated. CONCLUSIONS: There is significant regional variation in detection rates in Europe reflecting different policies, equipment and the operators' experience. A high proportion of abdominal wall defects is associated with concurrent malformations, syndromes or chromosomal abnormalities, stressing the need for the introduction of repeated detailed ultrasound examination as a standard procedure. There is still a relatively high rate of elective termination of pregnancies for both defects, even in isolated cases which generally have a good prognosis after surgical repair.

Profile of a serial killer: cellular and molecular approaches to study individual cytotoxic T-cells following therapeutic vaccination.

T-cell vaccination may prevent or treat cancer and infectious diseases, but further progress is required to increase clinical efficacy. Step-by-step improvements of T-cell vaccination in phase I/II clinical studies combined with very detailed analysis of T-cell responses at the single cell level are the strategy of choice for the identification of the most promising vaccine candidates for testing in subsequent large-scale phase III clinical trials. Major aims are to fully identify the most efficient T-cells in anticancer therapy, to characterize their TCRs, and to pinpoint the mechanisms of T-cell recruitment and function in well-defined clinical situations. Here we discuss novel strategies for the assessment of human T-cell responses, revealing in part unprecedented insight into T-cell biology and novel structural principles that govern TCR-pMHC recognition. Together, the described approaches advance our knowledge of T-cell mediated-protection from human diseases.

An objective anisotropic elastic plastic model and Algorithm applicable to bone mechanics

The implicit projection algorithm of isotropic plasticity is extended to an objective anisotropic elastic perfectly plastic model. The recursion formula developed to project the trial stress on the yield surface, is applicable to any non linear elastic law and any plastic yield function.A curvilinear transverse isotropic model based on a quadratic elastic potential and on Hill's quadratic yield criterion is then developed and implemented in a computer program for bone mechanics perspectives. The paper concludes with a numerical study of a schematic bone-prosthesis system to illustrate the potential of the model.

Geochemistry of highly acidic mine water following disposal into a natural lake with carbonate bedrock

Acid mine drainage (AMD) from the Zn-Pb(-Ag-Bi-Cu) deposit of Cerro de Pasco (Central Peru) and waste water from a Cu-extraction plant has been discharged since 1981 into Lake Yanamate, a natural lake with carbonate bedrock. The lake has developed a highly acidic pH of similar to 1. Mean lake water chemistry was characterized by 16,775 mg/L acidity as CaCO(3), 4330 mg/L Fe and 29,250 mg/L SO(4). Mean trace element concentrations were 86.8 mg/L Cu, 493 mg/L Zn, 2.9 mg/L Pb and 48 mg/L As, which did not differ greatly from the discharged AMD. Most elements showed increasing concentrations from the surface to the lake bottom at a maximal depth of 41 m (e.g. from 3581 to 5433 mg/L Fe and 25,609 to 35,959 mg/L SO(4)). The variations in the H and 0 isotope compositions and the element concentrations within the upper 10 m of the water column suggest mixing with recently discharged AMD, shallow groundwater and precipitation waters. Below 15 m a stagnant zone had developed. Gypsum (saturation index, SI similar to 0.25) and anglesite (SI similar to 0.1) were in equilibrium with lake water. Jarosite was oversaturated (SI similar to 1.7) in the upper part of the water column, resulting in downward settling and re-dissolution in the lower part of the water column (SI similar to -0.7). Accordingly, jarosite was only found in sediments from less than 7 m water depth. At the lake bottom, a layer of gel-like material (similar to 90 wt.% water) of pH similar to 1 with a total organic C content of up to 4.40 wet wt.% originated from the kerosene discharge of the Cu-extraction plant and had contaminant element concentrations similar to the lake water. Below the organic layer followed a layer of gypsum with pH 1.5, which overlaid the dissolving carbonate sediments of pH 5.3-7. In these two layers the contaminant elements were enriched compared to lake water in the sequence As < Pb approximate to Cu < Cd < Zn = Mn with increasing depth. This sequence of enrichment was explained by the following processes: (i) adsorption of As on Fe-hydroxides coating plant roots at low pH (up to 3326 mg/kg As), (ii) adsorption at increasing pH near the gypsum/calcite boundary (up to 1812 mg/kg Pb, 2531 mg/kg Cu. and 36 mg/kg Cd), and (iii) precipitation of carbonates (up to 5177 mg/kg Zn and 810 mg/kg Mn: all data corrected to a wet base). The infiltration rate was approximately equal to the discharge rate, thus gypsum and hydroxide precipitation had not resulted in complete clogging of the lake bedrocks. (C) 2010 Elsevier Ltd. All rights reserved.

Severe rhabdomyolysis following venlafaxine overdose.

Venlafaxine is a recently developed serotoninergic antidepressant whose reported toxicity at overdose levels includes central nervous system depression, seizures, and cardiovascular toxicity. The authors now present a case of venlafaxine overdose in a young woman complicated by a rise in plasma creatine kinase activity up to 52,600 U/L. Immediate therapy with intravenous fluids, bicarbonate, and furosemide was administered, and there were no further complications, notably no renal failure. This case supports the notion that venlafaxine can induce direct skeletal muscle toxicity leading to severe rhabdomyolysis. Therefore, clinicians should monitor muscle enzymes in patients with venlafaxine overdose to detect the development of rhabdomyolysis at an early stage and to initiate appropriate therapy rapidly.

Transmission immunity in malaria: reflections on the underlying immune mechanisms during natural infections and following artificial immunization

Malaria transmission-blocking immunity has been studied in natural malaria infections in man, during infections in animals and following artificial immunization of animals with sexual stage malaria parasites. Effective immunity, which prevents infectivity of a malarial infection to mosquitoes, has been observed under all of these circumstances. Two general types of effector mechanism have been identified. One is an antibody mediated mechanism which acts against the extracellular sexual stages of the parasite within the midgut of a blood feeding mosquito. The other is a cytokine mediated mechanism which inactivates the gametocytes of the parasites while in the circulation of the vertebrate host. Both effects have been observed during natural infections and following artificial immunization. The basis of induction of transmission-blocking immunity, including the nature of the memory for such immunity, however, may be very different in different host/parasite systems and during natural infection of following artificial immunization. Following artificial immunization a strong immune memory for transmission blocking immunity has been observed in animal systems. By contrast, following natural infections in man immune memory for transmission blocking immunity has been found to be weak and short lived if it occurs at all. It is suggested that the immunogens which induce natural transmission blocking immunity may be CD4+ independent.

Magnetic resonance coronary lumen and vessel wall imaging.

Coronary magnetic resonance angiography (MRA) is a technique aimed at establishing a noninvasive test for the assessment of significant coronary stenoses. There are certain boundary conditions that have hampered the clinical success of coronary MRA and coronary vessel wall imaging. Recent advances in hardware and software allow for consistent visualization of the proximal and mid portions of the native coronary arteries. Current research focuses on the use of intravascular MR contrast agents and black blood coronary angiography. One common goal is to create a noninvasive test which might allow for screening for major proximal and mid coronary artery disease. These novel approaches will represent a major step forward in diagnostic cardiology.

Mini-review: the ultrasonographical and serological chanbges and their improvement after praziquantel treatment Schistosoma japonicum infected patients in Leyete, Philippines

We have identified the specific ultrasonographical (US) changes in Schistosoma japonicum infected patients with the serological changes in general liver function markers. The US examination with the following haematological and biochemical serum analysis was performed on 102 patients in Shistosomiasis Hospital, Leyte, Philippines. The US liver images were classified into 4 patterns according to the development of periportal fibrosis and the patterns of echogenic bands. Among various haematological and biochemical serum parameters of liver damage. The serum levels of total bile acid (TBA) and procollagen-III-peptide (P-III-P) correlated well with the development of hepatic fibrosis and the portal hypertension. These patients were subsequently treated with praziquantel (3 x 20 mg/kg), and improvement of the thickening of the portal vein wall and the dintensity of the echogenic band formation was detected 6 months after treatment. The significant US changes could not be detected in the patients with severe hepatic fibrosis caused in the long term infection. The results revealed that the US examination with the serum TBa level would provider a sensitive tool monitor the severity of the infection and also the improvement occured shortly after praziquantel treatment.

A numerical algorithm for finding solutions of a generalized Nash equilibrium problem

A family of nonempty closed convex sets is built by using the data of the Generalized Nash equilibrium problem (GNEP). The sets are selected iteratively such that the intersection of the selected sets contains solutions of the GNEP. The algorithm introduced by Iusem-Sosa (2003) is adapted to obtain solutions of the GNEP. Finally some numerical experiments are given to illustrate the numerical behavior of the algorithm.

The fourth transmembrane segment of the Na,K-ATPase alpha subunit: a systematic mutagenesis study.

The Na,K-ATPase is a major ion-motive ATPase of the P-type family responsible for many aspects of cellular homeostasis. To determine the structure of the pathway for cations across the transmembrane portion of the Na,K-ATPase, we mutated 24 residues of the fourth transmembrane segment into cysteine and studied their function and accessibility by exposure to the sulfhydryl reagent 2-aminoethyl-methanethiosulfonate. Accessibility was also examined after treatment with palytoxin, which transforms the Na,K-pump into a cation channel. Of the 24 tested cysteine mutants, seven had no or a much reduced transport function. In particular cysteine mutants of the highly conserved "PEG" motif had a strongly reduced activity. However, most of the non-functional mutants could still be transformed by palytoxin as well as all of the functional mutants. Accessibility, determined as a 2-aminoethyl-methanethiosulfonate-induced reduction of the transport activity or as inhibition of the membrane conductance after palytoxin treatment, was observed for the following positions: Phe(323), Ile(322), Gly(326), Ala(330), Pro(333), Glu(334), and Gly(335). In accordance with a structural model of the Na,K-ATPase obtained by homology modeling with the two published structures of sarcoplasmic and endoplasmic reticulum calcium ATPase (Protein Data Bank codes 1EUL and 1IWO), the results suggest the presence of a cation pathway along the side of the fourth transmembrane segment that faces the space between transmembrane segments 5 and 6. The phenylalanine residue in position 323 has a critical position at the outer mouth of the cation pathway. The residues thought to form the cation binding site II ((333)PEGL) are also part of the accessible wall of the cation pathway opened by palytoxin through the Na,K-pump.

Post operative epidural haematomas following spinal surgery : P58

Introduction: Compressive epidural haematomas occurring following spine surgery are very rare but can potentially lead to irreversible damage. The evacuation of the haematoma as an emergency procedure remains the only effective treatment providing though alerting signs are detected on time. Few studies exist on this subject probably due to its rarity. The etiological factors as well as the place of imaging studies prior to urgent haematoma evacuation remain controversial. Two cases of delayed post-operative compressive epidural haematomas following lumbar-spine surgery were detected in our unit between April 2003 and January 2009. In both cases new onset of pain, aggravation of existing neurological deficit or development of new deficit along with worsening of pre-existing walking difficulties were noted. Emergency computer tomography (CT) could not exclude compression in both cases due to important artefacts. Emergency surgery was performed confirming the presence of haematoma in both cases and leading to a complete neurological recovery following its evacuation. As only risk factors common to both cases we identified drain removal and resuming of thromboprophylaxis. Conclusion: Obstacles in early detection of post-operative compressive epidural haematomas occurring following spine surgery are patients presenting with multiple complaints as well as shift work pattern of staff who might not always be trained in detecting early changes in neurological status. We therefore established a checklist for post-operative neurological observations to be carried out on spine surgery patients during the postoperative period. We describe our adopted attitude considering the etiological factors observed in our unit. Further studies including in a multi centre setting would be necessary in order to ascertain our observations.

Thyroid hormone enhances transected axonal regeneration and muscle reinnervation following rat sciatic nerve injury.

Improvement of nerve regeneration and functional recovery following nerve injury is a challenging problem in clinical research. We have already shown that following rat sciatic nerve transection, the local administration of triiodothyronine (T3) significantly increased the number and the myelination of regenerated axons. Functional recovery is a sum of the number of regenerated axons and reinnervation of denervated peripheral targets. In the present study, we investigated whether the increased number of regenerated axons by T3-treatment is linked to improved reinnervation of hind limb muscles. After transection of rat sciatic nerves, silicone or biodegradable nerve guides were implanted and filled with either T3 or phosphate buffer solution (PBS). Neuromuscular junctions (NMJs) were analyzed on gastrocnemius and plantar muscle sections stained with rhodamine alpha-bungarotoxin and neurofilament antibody. Four weeks after surgery, most end-plates (EPs) of operated limbs were still denervated and no effect of T3 on muscle reinnervation was detected at this stage of nerve repair. In contrast, after 14 weeks of nerve regeneration, T3 clearly enhanced the reinnervation of gastrocnemius and plantar EPs, demonstrated by significantly higher recovery of size and shape complexity of reinnervated EPs and also by increased acetylcholine receptor (AChRs) density on post synaptic membranes compared to PBS-treated EPs. The stimulating effect of T3 on EP reinnervation is confirmed by a higher index of compound muscle action potentials recorded in gastrocnemius muscles. In conclusion, our results provide for the first time strong evidence that T3 enhances the restoration of NMJ structure and improves synaptic transmission.

Proterodiplostome Parasites (Digenea, Proterodiplostomidae) of the Caiman, Caiman crocodilus yacare (Reptilia, Crocodylia) in the Pantanal mato-Grossense, Brazil, with the description of two new species

Two new species are described from the caiman. Caiman crocodilus yacare. Proterodiplostomum breve n. sp. differs from all other species in the genus by the following chacacteristics: (1) the paraprostate gland is shorter and club-shaped; (2) the genital cone is, in average, eight times longer than that of P. medusae; (3) the genital atrium is larger and without pseudosuckers; (4) the oral sucker and pharynx are longer; and (5) there are larger numbers of papillae surrounding the tribocytic organ (40) against 20 in P. longum, 16 in p. tumidilum, 8 in P. ophidum, and 16-18 in P. medusae. Proterodiplostomum globulare n. sp. differs from all the other species in the fenus by the following characteristics: (1) from P. tumidilum, P. lomgum, P. medusae, and P. breve n. sp. for the absense of pseudosuckers or muscular bunches in the inferior wall of the genital atrium; (2) the shape of the paraprostate gland, which is globular and not cylindrical as in P. longum, P. tumidilum, P. medusae, and P. ophidum; (3) the size of the tribocytic organ 201-407 long, 183-495 wide, while is 138-270 long, 102-292 wide in P. medusae, and 138-270 long, 255 wide in P. ophidum; (4) the number of papillae in the tribocytic organ (18-20) in P. globulare and 16-18 in P. medusae, and 8 in P. ophidum. Specimens belonging to six other species of proterodiplostomes are recorded for the first time infecting the caiman, C. c. yacare in the Pantanal Mato-grossense, Brazil, namely: Proterodiplostomum medusae, P. tumidilum, Cystodiplostomum hollyi, Prolecithodiplostomum constrictum, Paradiplostomum abbreviatum, and Herpetodiplostomum caimancola.