Dysfunctional cortical inhibition in adult ADHD: neural correlates in auditory event-related potentials.

In recent times, the relevance of an accurate diagnosis of attention-deficit/hyperactivity disorder (ADHD) in adults has been the focus of several studies. No longer considered a pathology exclusive to children and adolescents, and taking into account its social implications, developing enhanced support tools for the current diagnostic procedure becomes a priority. Here we present a method for the objective assessment of ADHD in adults using chirp-evoked, paired auditory late responses (ALRs) combined with a two-dimensional ALR denoising scheme to extract correlates of intracortical inhibition. Our method allows for an effective single-sweep denoising, thus requiring less trials to obtain recognizable physiological features, useful as pointers of cortical impairment. Results allow an optimized diagnosis, reduction of data loss and acquisition time; moreover, they do not account exclusively for critical elements within clinical evaluations, but also allow studying the pathophysiology of the condition by providing objective information regarding impaired cortical functions.

Photoemission spectroscopy study of the lanthanum lutetium oxide/silicon interface.

Rare earth oxides are promising candidates for future integration into nano-electronics. A key property of these oxides is their ability to form silicates in order to replace the interfacial layer in Si-based complementary metal-oxide field effect transistors. In this work a detailed study of lanthanum lutetium oxide based gate stacks is presented. Special attention is given to the silicate formation at temperatures typical for CMOS processing. The experimental analysis is based on hard x-ray photoemission spectroscopy complemented by standard laboratory experiments as Rutherford backscattering spectrometry and high-resolution transmission electron microscopy. Homogenously distributed La silicate and Lu silicate at the Si interface are proven to form already during gate oxide deposition. During the thermal treatment Si atoms diffuse through the oxide layer towards the TiN metal gate. This mechanism is identified to be promoted via Lu-O bonds, whereby the diffusion of La was found to be less important.

Discussion paper: The naming of Potato virus Y strains infecting potato.

Potato virus Y (PVY) strain groups are based on host response and resistance gene interactions. The strain groups PVY(O), PVY(C) and PVY(N) are well established for the isolates infecting potato in the field. A switch in the emphasis from host response to nucleotide sequence differences in the virus genomes, detection of isolates recombining sequences of different strains, and the need to recognize isolates that cause necrotic symptoms in potato tubers have led to the assignment of new acronyms, especially to isolates of the PVY(N) strain group. This discussion paper proposes that any newly found isolates should be described within the context of the original strain groups based on the original methods of distinguishing strains (i.e., tobacco and potato assays involving use of 'differential' potato cultivars). Additionally, sequence characterization of the complete genomes of isolates is highly recommended. However, it is acceptable to amend the names of PVY isolates with additional, specific codes to show that the isolate differs at the molecular, serological or phenotypic level from the typical strains within a strain group. The new isolates should preferably not be named using geographical, cultivar, or place-association designations. Since many new variants of PVY are being discovered, any new static classification system will be meaningless for the time being. A more systematic investigation and characterization of PVY from potato at the biological and molecular levels should eventually result in a biologically meaningful genetic strain concept.

[Bacterial spectra and antibiotics in odontogenic infections. Renaissance of the penicillins?]. / Keimspektren und Antibiotika bei odontogenen Infektionen. Renaissance der Penicilline?

BACKGROUND: The role played by odontogenic infection in dental, oral, and maxillofacial surgery is not to be underestimated even at the present time. An extensive, standardized, prospective study was performed with the intention of verifying the bacterial spectrum of odontogenic infections to evaluate antibiotic sensitivity. MATERIAL AND METHODS: Bacterial spectra and resistograms of 65 patients with an odontogenic infection were analyzed in a prospective study under standardized conditions for specimen collection and transport. RESULTS: A total of 226 bacterial strains were analyzed. The ratio between anaerobes and aerobes was approximately 2:1. The most frequent aerobes were members of the genera Streptococcus (46 isolates), Staphylococcus (10 isolates), and Neisseria (9 isolates), respectively. The anaerobic gram-positive spectrum was dominated by members of the genera Eubacterium (19 isolates), Peptostreptococcus (16 isolates), and Actinomyces (12 isolates). The most frequently isolated gram-negative anaerobes were Prevotella (46 isolates), and Fusobacterium (21 isolates). The overall resistance to antibiotics was very low: only 7.3% of all bacteria were resistant to penicillin G/V, and 8.8% showed resistance to ampicillin. The resistance rates to other beta-lactam antibiotics were 4.4% to piperacillin and 0.6% to imipenem, respectively. Penicillin G presented the highest antimicrobial activity among aerobes: only 4.5% of anaerobic strains were resistant of penicillin G. The other resistance rates of anaerobic bacteria to antibiotics were as follows: ampicillin 24%, doxycycline 34%, erythromycin 18%, and clindamycin 9.3%. Penicillin G was also highly antimicrobially active to anaerobes. The resistance rates were: penicillin G 8.1%, ampicillin 2.6%, doxycycline 9.2%, erythromycin 10.2%, and clindamycin 1.4%, respectively.

Complete nucleotide sequence and molecular probing of potato virus S genome.

Complete genomes of three isolates of Potato virus S (PVS) were cloned and sequenced. The PVS ORF-1 was characterized for the first time. It encodes a putative replication protein (RPT) that shares the highest homology (about 52%) with that of Blueberry scorch virus (BlScV). ORF-1 motifs, characteristic for carlaviruses were found for methyltransferase (MTR), helicase (HEL) and RNA-dependent RNA polymerase (RdRp). The complete sequence of PVS genome enabled to develop an immunocapture RT-PCR probing of the PVS genome. Using this system, the sequence variability of 11 genome zones was examined for 34 PVS isolates including 15 PVS-CS variants that caused a systemic infection in Chenopodium quinoa. A broad variability between PVS isolates and diverse sequence variants was found. cDNA fragments covering the coat protein (CP) leader and CP-coding region (approx. 420 bp) were pooled for PVS-O and Chenopodium-systemic PVS isolates (PVS-CS) and corresponding cDNA libraries were screened for sequence variants. Both cDNA pools differred mainly in the 5'-end of the CP gene. Methionine at the position 17 in combination with serine at the position 34 were frequently associated with the CS character of PVS. In general, hydrophobic and polar amino acids were characteristic for the positions 17 and 34, respectively in PVS-CS isolates. Genome probing and evolutionary distances suggested that the PVS-CS isolates analyzed were close to the ordinary European isolates of ordinary strain of PVS (PVS-O) but distant to the original Andean strain of PVS (PVS-A).

B group vitamins and cleft lip and cleft palate.

B group vitamins including folic acid supplementation during pregnancy have been shown to be effective in preventing cleft lip and palate (CLP) in humans. The clinical trials for the prevention of malformation have been mostly empirically based. The aim of the present study was directed toward the elucidation of the mechanisms underlying the preventive measures. The teratogenic potency of vitamin deficiency over the whole period of gestation (days 1-18) and of food restriction during the critical period of palatogenesis (days 12 and 13) were investigated in the genetically different strains of NMRI and A/WySn mice. Furthermore the potential benefit of vitamin B supplementation/treatment in the genetically susceptible CLP strain was demonstrated for comparison with former work on a teratogenetically induced cleft palate model. The results illustrate the higher susceptibility of the NMRI strain to the teratogenic action of deficiency (increase of the CP rate from 3.8% to 25%) in contrast to A/WySn mice, which actually have a high spontaneous but relative teratogenic-resistant clefting rate (28-44%). A deficiency of each of the individual B vitamins is teratogenic, however total B group deficiency has the strongest effect in the case of deficiency of all B vitamins. This produces up to 25% cleft palates in the NMRI strain. Alternatively, vitamin B group treatment in pregnant A/WySn mice did not substantially influence the clefting rate in contrast to our former experience in Halle:AB mice. The results may help to elucidate the interplay of genetic conditions and exogenous (nutritional) factors in both the aetiology and prevention of CLP. This may further clarify the role of the B vitamins in empiric preventive clinical trials.

The variability of hop latent viroid as induced upon heat treatment.

We have previously shown that heat treatment of hop plants infected by hop latent viroid (HLVd) reduces viroid levels. Here we investigate whether such heat treatment leads to the accumulation of sequence variability in HLVd. We observed a negligible level of mutated variants in HLVd under standard cultivation conditions. In contrast, the heat treatment of hop led to HLVd degradation and, simultaneously, to a significant increase in sequence variations, as judged from temperature gradient-gel electrophoresis analysis and cDNA library screening by DNA heteroduplex analysis. Thirty-one cDNA clones (9.8%) were identified as deviating forms. Sequencing showed mostly the presence of quadruple and triple mutants, suggesting an accumulation of mutations in HLVd during successive replication cycles. Sixty-nine percent of base changes were localised in the left half and 31% in the right half of the secondary structure proposed for this viroid. No mutations were found in the central part of the upper conserved region. A "hot spot" region was identified in a domain known as a "pathogenicity domain" in the group representative, potato spindle tuber viroid. Most mutations are predicted to destabilise HLVd secondary structure. All mutated cDNAs, however, were infectious and evolved into complex progeny populations containing molecular variants maintained at low levels.

In vitro generation of human CD86+ dendritic cells from CD34+ haematopoietic progenitors by PMA and in serum-free medium.

The cytokine requirements to differentiate CD34+ progenitor cells from different origins either cord blood (CB) or peripheral blood (PB) into dendritic cells (DC) are known to be different. In addition to DC, macrophages and neutrophils are generated. On the other hand, phorbol esters such as PMA induce primary human CD34+ bone marrow (BM) progenitor cells to differentiate into functional DC and no other lineages are generated. In addition, FCS is used as culture supplement in most of the protocols described which contains additional foreign antigens potentially skewing the resulting immune response. Therefore, we evaluated the ability to differentiate CB- and PB-CD34+ progenitor cells into DC with PMA and under serum-free conditions. In this study, we delineate the maturation of cultured human blood DC by analysis of expression co-stimulatory molecule B7-2 (CD86). Human mature DC with typical morphology and surface antigen phenotype (CD1a-, CD83+ and CD86+) were obtained from CB- and PB-CD34+ progenitor cells after 1 week of culture in serum-free medium upon stimulation with PMA alone. The same result was obtained from ex vivo-expanded BM-CD34+ cells. CD86+ yield was increased by PMA compared to cytokine cocktails (28.0% +/- 7.0 versus 15.3% +/- 5.6 for CB and 44.6% +/- 7.5 versus 28.1% +/- 7.5 for PB, respectively). CD86 was most up-regulated in the presence of the calcium ionophore ionomycin. However, the number of viable cells after differentiation was decreased by PMA plus ionomycin (P < 0.05) or plus TNF-alpha (P > 0.05) as compared with that in PMA alone. We conclude that PMA is a potent activator to differentiate human CD34+ cells into mature DC in serum-free medium. This may be used for in vitro studies of primed or genetically modified DC against infectious and tumour-associated antigens.

The male chronic pelvic pain syndrome.

Suffering chronic pain is a common and debilitating problem that significantly impairs the quality of life of affected patients. Because we continue to struggle with chronic pelvic pain disorders both diagnostically and therapeutically, a neuro-behavioral perspective should be used in an attempt to explain pathways and neurophysiological mechanisms, and to improve diagnostics and treatment of male pelvic pain. First, however, malignant and acute/chronic bacterial disease has to be excluded as a cause of chronic pain in every single case. Then diagnostic approaches should screen for lower urinary tract dysfunction, pelvic floor functional disorders, and disturbed reflex integrity within the pelvic area. Treatment approaches for the male chronic pelvic pain syndrome could be divided into causal and symptomatic. Causal treatment approaches try to influence basic mechanisms generating and supporting chronic pain. In most cases a symptomatic approach is needed to relieve pain immediately. Because generally accepted treatment protocols and studies are missing, the following approach in the individual patient is recommended: (1) symptomatic treatment for immediate pain relief, (2) diagnostic work-up, (3) causal treatment trial.

Sacral nerve stimulation for pain relief in interstitial cystitis.

A 60-year-old woman was treated for severe interstitial cystitis pain using sacral nerve stimulation. Pain and accompanying bladder dysfunction were improved by temporary and permanent sacral nerve stimulation. Six months after implantation of a sacral neuromodulator the patient is pain free and significantly improved on bladder dysfunction. Interstitial cystitis may be an indication for functional electrostimulation.

Analysis of variability of P1 gene region of N strain of potato virus Y using temperature-gradient gel electrophoresis and DNA heteroduplex analysis.

Reaction conditions specific for reverse taranscription-polymerase chain reaction (RT-PCR) of potato virus Y strain NTN (PVYNTN) were used to amplify a 394 bp fragment of the P1 gene from selected PVY isolates with the aim to study the PVY variability within this genomic region. The P1 gene fragment from the Nicola isolate (Nicola P1/1 clone) was sequenced and characterized by temperature-gradient gel electrophoresis (TGGE). The Nicola P1/1 clone differed from that from the Hungarian isolate by double point mutation resulting in two changes at the deduced amino acid level. The clone showed simple transition from double-stranded to single-stranded form with two characteristic melting end points of about 41 degrees C and 48 degrees C. A more complicated TGGE pattern was, however, found for the whole P1 cDNA library of the Nicola isolate, suggesting accumulation of some minor sequence variants of PVY in this isolate. Based on the TGGE pattern, 46 degrees C was selected as the standard temperature for electrophoretic analysis of heteroduplex DNAs formed with the Nicola P1/1 DNA as reference. More than 40 other PVY isolates from PVYN group were analysed using this method. In most cases only minor fractions of electrophoretically distinguishable DNA heteroduplexes were found, however, in most isolates of PVYN-Wilga type, mixtures of the major sequence variants were observed. Two of these variants from the hybrid 220-5 (Czech Republic) were sequenced. Both of them differed from the Nicola P1/1 clone by 6 point mutations, which led to several changes at the amino acid level.

Effective analgesia for extracorporeal shock wave lithotripsy: transcutaneous electrical nerve stimulation.

OBJECTIVES: Extracorporeal shock wave lithotripsy (ESWL) has revolutionized the treatment of urinary stone disease. However, the most appropriate analgesia offering pain-free treatment, minimal side effects, and adequate cost effectiveness remains to be established. This prospective study was performed to evaluate the efficacy of transcutaneous electrical nerve stimulation (TENS) during ESWL using third-generation lithotripters. METHODS: Two pairs of stimulator electrodes were placed paravertebrally at L1 and near the lithotripter shock tube before ESWL. Treatment was carried out as follows: (a) shock wave administration was begun (no current = sham TENS); (b) in the case of severe pain, TENS was begun; and (c) if patients experienced no pain relief, analgesic drugs were given intravenously. RESULTS: Of 149 patients, 92 (62%) did not need any analgesia (neither TENS nor medication). In 42 (72%) of the remaining 57 patients, a TENS-related, pain-relieving response was observed. ESWL-induced pain could be reduced by 39.2%. The degree of fragmentation assessed by two urologists was found to be 90% for patients receiving TENS compared with a retrospectively analyzed control group (94%, n = 100). CONCLUSIONS: Two different theories explaining TENS-related analgesia are known: segmental (spinal) and supraspinal (central) inhibition. Since we did not observe any analgesic effect in patients having both pairs of electrodes attached around the shock tube (n = 30), supraspinal inhibition obviously accounts for the abovementioned pain relief. We conclude that TENS is a noninvasive, cost-effective method to achieve side-effect-free analgesia in ESWL using third-generation lithotripters.

31P-magnetic resonance spectroscopy (31P-MRS) of human allografts after renal transplantation.

BACKGROUND: 31P-Magnetic resonance spectroscopy (31P-MRS) can be used as a non-invasive tool for measuring the relative intracellular concentrations of several phosphorus metabolites in different organs. Various pathological conditions are characterized by different metabolic patterns. We studied the value of 31P-MRS after renal transplantation with both an uneventful and a clinically complicated course. METHODS: We determined the relative concentrations of phosphate-containing metabolites in renal allografts of humans with 31P-MRS (1.5 Tesla) in the first few weeks after transplantation; 18 patients with an uneventful clinical course and 10 patients who required dialysis after transplantation were examined. Six patients with a stable allograft function 2-3 months after transplantation served as controls. RESULTS: In patients with primary allograft function, we found a significant correlation between the phosphomonoester/phosphodiester-ratio (PME/PDE) (r = 0.66, r < 0.01) and the time after transplantation, but no correlation between the nucleoside triphosphate (beta-NTP)-concentration (r = -0.11) and the time course. In the patients with primary or early allograft dysfunction caused by histologically proven rejection (n=5), we found a low beta-NTP compared to patients with an uncomplicated clinical course (0.09+/-0.01 vs 0.15+/-0.03), but no differences in the PME/PDE ratio (0.73+/-0.21 vs 0.80+/-0.21). In contrast, the PME/PDE ratio was lowered in three patients with delayed graft function caused by acute tubular necrosis (0.45+/-0.07 vs 0.80+/-0.21), but the beta-NTP concentration was not reduced (0.15+/-0.003 vs 0.15+/-0.03). The 31P-MR spectrum of two patients with cyclosporin A damage was not altered compared to the controls. CONCLUSIONS: 31P-MRS can be used in patients in the early period after renal transplantation. A significant correlation between the PME/PDE ratio and the time course but no change in the beta-NTP concentration was found in patients with primary allograft function in the first 4 weeks after renal transplantation. Different patterns of 31P-MR spectra were observed depending on the different causes of primary and early transplant dysfunction.

Ceramic coagulation tip for interstitial thermoablation of the prostate: first experiments.

A direct electrically heated ceramic coagulation tip for interstitial thermoablation has been developed. Both the coagulation tip and a laser system (Medilas 4060) were tested in vitro to compare their efficacies. We have obtained coagulation necroses of similar sizes. The electrical coagulation tip as opposed to laser coagulation is a new therapeutic option for the therapy of high risk patients with symptomatic benign prostatic hyperplasia. Because of the materials used and the principle of heating involved, certain economic and safety advantages over the laser system are offered.

Breaking the mold: expanding options for reproductive health awareness: the CARE experience.

The early years of the CARE family planning and reproductive health program were geared primarily toward modern methods of contraception and providing services. However, new and fresh opportunities to address reproductive health awareness and natural family planning are now emerging as important options. In these programs, coordination and collaboration with other sectors such as food and nutrition, children's health and natural resource management, combined with more sophisticated approaches for assessing need and reaching communities with information, has resulted in more people being reached than ever before with appropriate options and opportunities for reproductive health awareness and care. There are examples of CARE projects from India, Peru and Nepal where activities which feature working across development sectors and engaging communities to address their individual and collective RH needs are featured. Ways to disseminate information about reproductive health are being broadened to include creative combinations of interpersonal, mass and folk media', whether it be an informal one-to-one counseling session with flipcharts, a community mobilization event, a multi-media campaign, or any combination thereof. Likewise, the target audience need not always be the women of reproductive age, not should the RH messengers always be the medical and public health professionals. What is critical in all of these instances is to craft strategies based on appropriate research and need, continuously monitor progress, refine approaches as necessary, track results and evaluate the process and impact of interventions leading to behavior change. The challenge is not insignificant, but the rewards to be reaped through the improved programs are clearly worth striving for.

Affected paroxysmal nocturnal hemoglobinuria T lymphocytes harbor a common defect in assembly of N-acetyl-D-glucosamine inositol phospholipid corresponding to that in class A Thy-1- murine lymphoma mutants.

Deficient expression of glycoinositol phospholipid (GPI) anchored proteins in affected paroxysmal nocturnal hemoglobinuria (PNH) cells has been traced to a defect in GPI anchor assembly. In a previous study (Schubert, J., Schmidt, R. E., and Medof, M. E. (1993) J. Biol. Chem., in press) we characterized the biosynthesis of putative Man-containing GPI anchor precursors in normal peripheral blood lymphocytes and investigated assembly of these intracellular GPI intermediates in CD48- affected and CD48+ unaffected T and natural killer cell lines of PNH patients. We found that affected T cells from five patients exhibited a uniform defect in which dolichol-phosphoryl-Man was synthesized but no GPI mannolipids were expressed. In this study, membranes of patients' affected T cells were labeled with UDP-[3H]GlcNAc to evaluate earlier steps in GPI synthesis, and intact cells were fused to Thy-1- murine lymphoma mutants harboring different defects in early GPI assembly to test for the presence of corresponding or complementary lesions. In all cases, affected cell membranes failed to assemble GlcNAc-inositol phospholipid, the initial precursor of GPI anchor structures, and the intact cells failed to complement class A mutants while complementing other classes. Affected polymorphonuclear leukocytes from three additional patients of different origin were then labeled with [3H]Man and the labeling patterns found to correspond to those obtained with the T lymphocytes. Taken together the data indicate that the genetic lesion in PNH cells resides in a DNA element which: 1) encodes a product required for the synthesis of GlcNAc-inositol phospholipid, 2) corresponds to that altered in class A Thy-1- murine lymphoma mutants, and 3) is commonly affected in different patients.

Further studies on protective effects of vitamins in cyclophosphamide-induced cleft palate.

The effects of vitamins B1, B6, and E administered 1 day before and simultaneously with an embryotoxic dose of cyclophosphamide (CPM) were studied using random-bred mice ICR (VELAZ). A single dose of 20 mg/kg CPM administered i.p. or i.m. on day 12 of pregnancy induced in the foetuses cleft palate and malformations of the upper and lower limbs. Both vitamins B1 and B6 decreased nonsignificantly the overall proportion of malformed foetuses and changed the spectrum of malformations, the decrease in foetuses with malformed upper limbs being statistically significant. In the groups supplemented with vitamins the mean foetal weight was higher in litters without malformed upper limbs than in litters with malformed upper limbs and those of both types in the control group. Similar effects of vitamin E were statistically nonsignificant. It is most likely that vitamins influence the pharmacokinetics of cyclophosphamide or its metabolites. The data provided offer no explanation for the claimed beneficial effects of vitamins for preventing the occurrence of orofacial clefts in patients at risk.