Cognitive functioning in the schizophrenia prodrome

In the last decade, there has been an increasing interest in cognitive alterations during the early course of schizophrenia. From a clinical perspective, a better understanding of cognitive functioning in putative at-risk states for schizophrenia is essential for developing optimal early intervention models. Two approaches have more recently been combined to assess the entire course of the initial schizophrenia prodrome: the predictive "basic symptom at-risk" (BS) and the ultra high-risk (UHR) criteria. Basic symptoms are considered to be present during the entire disease progression, including the initial prodrome, while the onset of symptoms captured by the UHR criteria expresses further disease progression toward frank psychosis. The present study investigated the cognitive functioning in 93 subjects who met either BS or UHR criteria and thus were assumed to be at different points on the putative trajectory to psychosis. We compared them with 43 patients with a first episode of psychosis and to 49 help-seeking patient controls. All groups performed significantly below normative values. Both at-risk groups performed at intermediate levels between the first-episode (FE) group and normative values. The UHR group demonstrated intermediate performance between the FE and BS groups. Overall, auditory working memory, verbal fluency/processing speed, and declarative verbal memory were impaired the most. Our results suggest that cognitive impairments may still be modest in the early stages of the initial schizophrenia prodrome and thus support current efforts to intervene in the early course of impending schizophrenia because early intervention may prevent or delay the onset of frank psychosis and thus prevent further cognitive damage.     

Inhibitory effects of different galanin compounds and fragments on osmotically and histamine-induced enhanced vasopressin secretion in rats

The effects of rat, porcine and human galanin, and the human 1-16 and human 16-30 terminal galanin fragments on vasopressin secretion were studied in rat. The plasma vasopressin level was determined by radioimmunoassay (RIA). There were no changes in the basal vasopressin secretion after galanin administration. A significant increase in vasopressin concentration was detected following 2.5% NaCl or histamine administration. I.c.v. injected rat, porcine or human galanin or the 1-16 N-terminal galanin fragment prevented the plasma vasopressin level enhancement. Following the i.v. administration of rat galanin or the i.c.v. injected 16-30 C-terminal galanin fragment, the vasopressin concentration did not return to the normal level. Administration of the galanin antagonist galantid (M15) i.c.v. before the rat galanin i.c.v. injection prevented the inhibitory effect on the increased plasma vasopressin level following 2.5% NaCl solution or histamine administration. The results indicate that there is no significant difference in the inhibitory effect of rat, porcine or human galanin or the 1-16 galanin fragment on the enhanced plasma vasopressin secretion induced by hyperosmosis or histamine administration.Our findings suggest that galanin, as a peptide modulator, is physiologically involved in the regulation of vasopressin release following different forms of stimulation: an osmotic response or histamine administration.     

The attendance of the first screening round (2002-2003) of the Hungarian organized breast cancer screening program and its effect on the number of diagnostic and screening mammography

AIM: Organised, nationwide screening for breast cancer with mammography in the age group 45-65 years with 2 years screening interval started in Hungary in January 2002. The aim of this study is to analyze the attendance rate of breast screening programme, including the analysis of the ratio of screening and diagnostic mammography examinations. DATA AND METHODS: The data derive from the financial database of the National Health Insurance Fund Administration (NHIFA) covering the period 2000-2003. The ratio of women was calculated in the age group 45-65 years having either a screening mammography or a diagnostic mammography. The analysis was carried out for the years 2000-2001 (mainly opportunistic screening) before and 2002-2003 after the implementation of nationwide organized programme. RESULTS: In the years 2000-2001 7,26% of the women aged 45-65 had an opportunistic screening mammography while in 2002-2003 33,95% of the target population had screening mammography within the organized programme. During the same periods 19,67% (2000-2001) and 22,05% (2002-2003) of women aged 45-65 had a diagnostic mammography. Thus the total (screening and diagnostic) coverage of mammography increased from 25,85% (2000-2001) to 53,46% (2002-2003). CONCLUSIONS: The attendance of the Hungarian organized breast cancer screening programme - compared to the previous period before the implementation of the organized screening programme - is promising, although to achieve the expected results in mortality decrease a further improvement of the uptake is necessary.     

Analysis of health insurance costs in cases of patients under 60 years old with medial femoral neck fracture treated primarily with screw fixation or hip replacement

AIM: The aim of the study is to analyse the cost of patients under the age of 60 with medial femoral neck fracture up to 2 years follow up after the primary treatment including cost of acute and chronic inpatient care, outpatient care, sickness pay and changes in ability to work according to the most frequently used surgical methods and Garden classification. PATIENTS AND METHODS: Patients were identified from the financial database of the National Health Insurance Fund Administration and a questionnaire was used for further analysis. The costs of patients were analysed in three groups I) all patients, (II.) patients with further treatment because of complications, and (III.) patients cured by one primary treatment. RESULTS: Altogether 518 patients were included into the study: 413 (79.7%) with primary screw fixation and 48 (9.3%) with hip replacement. The average cost for all patients (I) for the 2 years follow up was 582.181 Hungarian Forint (HUF) with screw fixation and 545.300 HUF with hip replacement. The average cost per patients in the group with one primary surgical treatment (II) was (N = 337, 81.6%) 441.466 HUF with screw fixation and (N = 44, 91.6%) 561.027 HUF with hip replacement. The average cost per patients in the subgroup with further hospitalization because of complications (II) was (N = 76, 18.4%) 1.005.578 HUF with screw fixation and (N = 4, 8.4%) 775.640 HUF with hip replacement. The costs according to Garden classification (I-IV.) were as follows: patients without complications from 436.681 HUF to 659.160 HUF and patients with complications from 628.323 HUF to 1.192.564 HUF. CONCLUSION: The results suggest that patients (N = 76, 18.4%) having displaced fractures with screw fixation receiving further treatment should be treated - knowing the vitality of femoral head - with stable osteosynthesis or hip replacement in order to reduce further reoperations and finally, health insurance expenditures and patients' burden.     

Clinical effectiveness and safety of paroxetine in post-stroke depression: results from a phase 4, open label, multicenter clinical trial with 26 weeks of follow-up

INTRODUCTION: Prevalence of post-stroke depression ranges from 20% to 50%. Treatment of depression positively correlated with the success of rehabilitation, quality of life, and the post-stroke patient's independence. AIM: The primary goal of the study was to establish the therapeutic efficacy of paroxetine (measured by the changes of Hamilton Depression Scale Score) in post-stroke depression. Secondary outcomes were changes in clinical status (based on Clinical Global Impression), alterations of mental capabilities (by Mini-Mental State Examination) and changes in quality of life (based on Quality of Life values). METHOD: An estimation of the efficacy of paroxetine treatment of 788 patients with post-stroke depression (Hamilton Depression Scale Score > 18) was performed in an open-label phase IV multicenter trial, during a clinical (8 weeks) as well as a follow-up period (a total of 26 weeks). The applied doses of paroxetine were: 20, 30 or 40 mg per day, subject to their therapeutic effect. RESULTS: On the third week of the study (i.e.: at the 2nd visit) the mean Hamilton Depression Scale Score decreased significantly to 12.3 points; from a starting mean basic score of 24.8 points. At the conclusion of the clinical phase (by the end of the 8th week) we found an Hamilton Depression Scale Score of 8.6 points, which decreased further to 6.6 points by the end of the follow-up period (i.e.: the 26th week). At the end of the 3rd week 92% of the patients stated that paroxetine was effective while this number grew to 93.1% by the end the 8th week. Events related to secondary outcomes also showed significant improvements of similar size: by the end of the 8th week the clinical status of 92.8% of the patients improved (in 81.3% by a remarkable rate); mental output of the patients (based on Mini-Mental State Examination) grew significantly from a starting score of 26.7 to 27.9 and their Quality of Life values grew from 204 points to 238 points by the end of the 8th week and by the end of the 26th week it reached to 251 points; another indication of a significant improvement of their quality of life. In the course of the study 8.21% of the patients experienced side effects; the most frequent of these were: nausea/vomiting, dizziness, headaches and diarrhea. Serious adverse events occurred in 1.9% of the patients during the 26 weeks period of the study although these were unrelated to the taking of paroxetine. In the course of the study the patients' compliance was clearly good: by the end of the 8th week 94%, at the end of the 26th week 90.7% of them reported for control visitation, in other words, during the 6 months study their dropout rate was less than 10%. CONCLUSION: the selective serotonin-reuptake inhibitor paroxetine effectively improved the symptoms of depression, the functional and cognitive performance, as well as the quality of life of patients with post-stroke depression. The drug was safe and well tolerable.     

Occurrence of Tubuloreticular Inclusions in Acute Viral Hepatitis

Light and electron microscopy were used to study the liver needle-biopsy material of 20 patients with acute viral hepatitis. According to clinical and serologic data, 5 cases proved to be acute viral hepatitis type A, 13 were type B, and 2 were type non-A/non-B. In 2 of the hepatitis type A, in 6 of the hepatitis type B, and in one of the type non-A/non-B cases, tubuloreticular inclusions (TRI) were found in the endoplasmic reticulum of the sinusoidal endothelial cells of the liver.

These data support the possible presumption that the inclusions represent a characteristic reaction of the endoplasmic reticulum to different influences, as for example to viral infection, rather than to the virus itself.     

Adaptation of nasometry to Hungarian language and experiences with its clinical application

OBJECTIVES: (1) To adopt the nasometry for the Hungarian language and to obtain normative nasalance scores. (2) To compare our results with the data of other languages and to evaluate the correlation between nasalance scores and perceptual ratings of nasality. (3) To use the nasometry in various fields of the otolaryngological, phoniatric, and logopedic diagnostics, therapy and documentation. METHODS: (1) To determine the normative nasalance scores regarding the Hungarian language, we included 30 children aged 5-7 years and 45 adults in the 20-25 years age group. In the latter group 15 subjects were speech therapists and 30 phonetically untrained people-15 males and 15 females. Study design: phonation of isolated vowels, articulation of spirants, cyclical repetition of affricates, pronunciation of various (oral, nasal, mixed type) sentences and evaluation of the nasalance score in continuous speech. (2) Thirty-six persons (12 speech pathologists, 12 logopedic students, 12 phonetically uneducated individuals) evaluated the children's physiological and nasal speech recordings with a 3-point scale. (3) Two hundred and forty-eight children of kindergarten age were examined, 20 infants and 6 adult singers in the following fields: evaluation of hypernasality due to cleft palate or velopharyngeal insufficiency (VPI), and of the success of the therapy; examination of hyponasality in cases of enlarged adenoid and allergic rhinitis; evaluation of the speech of hard-of-hearing people; differentiation between nasal sigmatism and hyperrhinophony; testing of the resonance in professional singers; examination of infant cry; application of nasometry in the therapy. RESULTS: The mean value of the nasalance score using the oral sentence: "Zsuzsi kutyája ugat" is 11-13%, in the nasal sentence ("A majom banánt enne") 56%, while that of the mixed sentence representing the Hungarian language ("Jó napot kívánok!") falls in the 30-40% range. The resonance grows with aging and there is no significant difference between genders. The nasalance score is greater with phonetically trained people. Our data correlate with the values of other languages. The correlation is significant between the nasalance scores and perceived nasality (r=0.901). Practical results: Values above 40% in cases of VPI using mixed sentences may support the indication of velopharyngoplasty, together with the subjective evaluation of nasality and other tests. In cases with rhinitis and adenoid vegetation the nasalance score remains below 20%. The nasality value is increased in sensorineural hearing loss, and is decreased in cases with conducting hearing impairment. In nasal sigmatism not the vowels' but the nasality of consonants grow. The difference between the nasalance score of the cry in clefted and non-cleft infants is significant (26% versus 36%): this observation could give possibility in the future to screen babies with congenital hearing problems or hidden VPI. Alterations in nasalance can be documented with nasometry in professional singers when they increase the nasal resonance to grow the power capacity of their voice. The nasometry procedure is a significant help also in speech therapy through the real time visual and auditive control. CONCLUSIONS: The otolaryngological, phoniatric and logopedic diagnostics and therapy is significantly widened with nasometry which is a quick, non-invasive and objective procedure, measuring the nasal resonance of the speech.     

The human antimicrobial peptide LL-37 suppresses apoptosis in keratinocytes

The human cathelicidin antimicrobial peptide LL-37 is involved in various aspects of skin biology, including protection against infection, wound healing, and also in psoriasis. The tight regulation of apoptosis is critical in tissue repair and its deregulation is a part of the psoriasis phenotype. Despite being involved in cell death of several cell types, virtually nothing is known about the function of LL-37 in keratinocyte apoptosis. Here we report that LL-37 peptide protects primary human keratinocytes and HaCaT cells from apoptosis induced by the topoisomerase I inhibitor camptothecin (CAM). In particular, pretreatment with LL-37 significantly decreased caspase-3 activity after CAM-treatment. Expression profiling of keratinocytes treated with LL-37 identified the upregulation of cyclooxygenase-2 (COX-2) expression, a gene implicated in protection from apoptosis. In addition to inducing COX-2 expression, LL-37 stimulated the production of its product, prostaglandin E-2 (PGE-2). Moreover, LL-37 induced the expression of inhibitor of apoptosis-2 (IAP-2), implicated in the COX-2/PGE-2 antiapoptotic pathway. Pretreatment with a selective COX-2 inhibitor abolished the antiapoptotic effect of LL-37 and reduced IAP-2 expression implicating that the antiapoptotic effect of LL-37 in keratinocytes is mediated by a COX-2-dependent mechanism involving IAP-2. Thus, overexpression of LL-37 may contribute to reduced keratinocyte apoptosis in conditions such as psoriasis.     

Expression and function of Toll-like receptors 2 and 4 in human keratinocytes

Keratinocytes have the ability to kill pathogenic fungi and bacteria by producing antimicrobial substances. Recent studies suggest that microbial components use signaling molecules of the human Toll-like receptor (TLR) family to transduce signals in various cells. Here we provide evidence that keratinocytes express both TLR2 and TLR4 at the mRNA and protein levels, and show that TLR2 and TLR4 are present in the normal human epidermis in vivo and that their expression is regulated by microbial components. The expression of myeloid differentiation protein gene (MyD88), which is involved in the signaling pathway of many TLR, was also demonstrated in keratinocytes. LPS + IFN-gamma increased the expression of TLR2 and TLR4 50- and 5-fold respectively. Treatment of keratinocytes with Candida albicans, mannan, Mycobacterium tuberculosis or LPS with IFN-gamma resulted in the activation and nuclear translocation of NF-kappaB. Inhibition of NF-kappaB blocked the Candida-killing activity of keratinocytes, suggesting that the antimicrobial effect of keratinocytes requires NF-kappaB activation. LPS + IFN-gamma, C. albicans (4 Candida/KC), peptidoglycan (1 micro g/ml) or M. tuberculosis extract significantly increased IL-8 gene expression after 3 h of treatment (P < 0.05). The increases over the 0-h level were 15-, 8-, 10.8- and 7-fold, respectively. The microbial compound-induced increase in IL-8 gene expression could be inhibited by anti-TLR2 and anti-TLR4 neutralizing antibodies, suggesting that TLRs are involved in the pathogen-induced expression of this pro-inflammatory cytokine. Our findings stress the importance of the role of keratinocytes as a component of innate immunity.