One consensual depression diagnosis tool to serve many countries: a challenge! A RAND/UCLA methodology.

OBJECTIVE: From a systematic literature review (SLR), it became clear that a consensually validated tool was needed by European General Practitioner (GP) researchers in order to allow multi-centred collaborative research, in daily practice, throughout Europe. Which diagnostic tool for depression, validated against psychiatric examination according to the DSM, would GPs select as the best for use in clinical research, taking into account the combination of effectiveness, reliability and ergonomics? A RAND/UCLA, which combines the qualities of the Delphi process and of the nominal group, was used. GP researchers from different European countries were selected. The SLR extracted tools were validated against the DSM. The Youden index was used as an effectiveness criterion and Cronbach's alpha as a reliability criterion. Ergonomics data were extracted from the literature. Ergonomics were tested face-to-face. RESULTS: The SLR extracted 7 tools. Two instruments were considered sufficiently effective and reliable for use: the Hospital Anxiety and Depression Scale and the Hopkins Symptoms Checklist-25 (HSCL-25). After testing face-to-face, HSCL-25 was selected. A multicultural consensus on one diagnostic tool for depression was obtained for the HSCL-25. This tool will provide the opportunity to select homogeneous populations for European collaborative research in daily practice.

The concept of ferrofluid preheating in the treatment of cancer by magnetic hyperthermia of tissues.

The frequency dependence of the complex magnetic susceptibility, χ(ω) = χ'(ω) - i χ″(ω), of a water-based magnetic fluid with magnetite particles, over the frequency range 500 kHz to 2 MHz and at three different temperatures of 30 °C, 40 °C and 50 °C are presented. Based on these experimental measurements, the dependence on frequency, f = (ω/2π) Hz, of the heating rate, ΔT/Δt, of the ferrofluid has been evaluated at these stated temperatures and alternating magnetic field of different amplitudes, Ho = 200 A/m, 400 A/m, 600 A/m, 800 A/m and 1 kA/m. The results show that the preheating of the ferrofluid sample at the desired operating temperature has the advantage of using lower levels of H0 during over a shorter time period, as opposed to the case of an unheated sample. This concept of preheating a sample, has major significance for the treatment of cancer by magnetic hyperthermia in that the patient is subjected to lower values of H0, over the time period of the treatment.

Kinematic magnetic resonance imaging study of the brain stem and cervical cord by dynamic neck motion.

BACKGROUND: The aim was to examine the position of the brain stem and cervical cord following the neck flexion and extension. MATERIALS AND METHODS: The serial sagittal T2-weighted magnetic resonance imaging (MRI) sections of the cervical cord and brain stem were made in 6 volunteers. The images were mainly used to measure certain distances and angles of the brain stem and cervical cord in the neutral position, and then following the head and neck flexion and extension. RESULTS: The measurements showed that the pons is slightly closer to the clivus following the neck flexion; the medulla oblongata is somewhat distant to the basion but closer to the odontoid process. At the same time, the spino-medullary angle diminishes in size. On the other hand, the upper cervical cord slightly approaches the posterior wall of the spinal canal, the lower cervical cord is closer to the anterior wall, while the angle between them is significantly larger in size. After the cervical cord extension, the rostral pons is somewhat distant to the clivus, whereas the caudal pons and the medulla are slightly closer to the clivus and the basion. At the same time, the spino-medullary angle diminishes in size. The cervical cord is mainly closer to the posterior wall of the spinal canal, whilst its angle is significantly smaller. CONCLUSIONS: The obtained results regarding the brain stem and cervical cord motion can be useful in the kinetic MRI examination of certain congenital disorders, degenerative diseases, and traumatic injuries of the craniovertebral junction and the cervical spine.

A 3 tesla magnetic resonance imaging volumetric analysis of the hippocampal formation: dependence on handedness and age.

BACKGROUND: The hippocampal formation (HF) is one of the most important parts of the brain in the magnetic resonance imaging (MRI) volumetric analysis in various domains, but not completely from all aspects, including the handedness. The aim of our study was to evaluate the possible differences in the volume of the right and left HF among the healthy right-handed and left-handed subjects, and to determine whether the volume differences are age related. MATERIALS AND METHODS: The MRI of this prospective study was performed using T1 fast field echo (FFE) sequence. The 124 subsequent coronal slices (thickness 1.5 mm) were performed in each participant. The obtained HF volumes were normalised and statistically compared. Volunteers comprised 30 persons aged 22.0 years, 12 of whom were the left-handed, and 30 persons aged 75.2 years on average, 9 of whom were the left-handed. RESULTS: The right and left HF volumes averaged 2.986 cm3 and 2.858 cm3 in the right-handed, and 2.879 cm³ and 3.020 cm³ in the left-handed young volunteers, as well as 2.728 cm³ and 2.650 cm³ in the right-handed, and 2.617 cm³ and 2.780 cm³ in the left-handed elderly persons. The HF volume ratios in the young left-handed participants showed a significant left-greater-than-right asymmetry. A significant difference was also noticed within the right-to-left volume ratios of the right- and left-handed young and elderly participants. The latter reduction in the HF volume within the aged group can be interpreted as a slight atrophy of the HF. CONCLUSIONS: There is a significant difference in the volumes of the left and right HF of the left-handed young participants. The age related HF volume differences were proven between the groups of the young and elderly volunteers. The obtained data should be included into the future MRI studies of the HF volumes in various clinical domains.

What research agenda could be generated from the European General Practice Research Network concept of Multimorbidity in Family Practice?

BACKGROUND: Multimorbidity is an intuitively appealing, yet challenging, concept for Family Medicine (FM). An EGPRN working group has published a comprehensive definition of the concept based on a systematic review of the literature which is closely linked to patient complexity and to the biopsychosocial model. This concept was identified by European Family Physicians (FPs) throughout Europe using 13 qualitative surveys. To further our understanding of the issues around multimorbidity, we needed to do innovative research to clarify this concept. The research question for this survey was: what research agenda could be generated for Family Medicine from the EGPRN concept of Multimorbidity? METHODS: Nominal group design with a purposive panel of experts in the field of multimorbidity. The nominal group worked through four phases: ideas generation phase, ideas recording phase, evaluation and analysis phase and a prioritization phase. RESULTS: Fifteen international experts participated. A research agenda was established, featuring 6 topics and 11 themes with their corresponding study designs. The highest priorities were given to the following topics: measuring multimorbidity and the impact of multimorbidity. In addition the experts stressed that the concept should be simplified. This would be best achieved by working in reverse: starting with the outcomes and working back to find the useful variables within the concept. CONCLUSION: The highest priority for future research on multimorbidity should be given to measuring multimorbidity and to simplifying the EGPRN model, using a pragmatic approach to determine the useful variables within the concept from its outcomes.

Brain and art: illustrations of the cerebral convolutions. A review.

BACKGROUND: Aesthetics and functional significance of the cerebral cortical relief gave us the idea to find out how often the convolutions are presented in fine art, and in which techniques, conceptual meaning and pathophysiological aspect. MATERIALS AND METHODS: We examined 27,614 art works created by 2,856 authors and presented in art literature, and in Google images search. RESULTS: The cerebral gyri were shown in 0.85% of the art works created by 2.35% of the authors. The concept of the brain was first mentioned in ancient Egypt some 3,700 years ago. The first artistic drawing of the convolutions was made by Leonardo da Vinci, and the first colour picture by an unknown Italian author. Rembrandt van Rijn was the first to paint the gyri. Dozens of modern authors, who are professional artists, medical experts or designers, presented the cerebralc onvolutions in drawings, paintings, digital works or sculptures, with various aesthetic, symbolic and metaphorical connotation. Some artistic compositions and natural forms show a gyral pattern. The convolutions, whose cortical layers enable the cognitive functions, can be affected by various disorders. Some artists suffered from those disorders, and some others presented them in their artworks. CONCLUSIONS: The cerebral convolutions or gyri, thanks to their extensive cortical mantle, are the specific morphological basis for the human mind, but also the structures with their own aesthetics. Contemporary authors relatively often depictor model the cerebral convolutions, either from the aesthetic or conceptual aspect. In this way, they make a connection between the neuroscience and fineart.

Heart in anatomy history, radiology, anthropology and art.

BACKGROUND: Anthropologic, artistic and medical significance of heart inspired usto undertake this multidisciplinary study. MATERIALS AND METHODS: Amongst the 24 obtained echocardiograms and phonograms, 1 was used for a Photoshop processing. In addition, over 20,000 art work reproductions were examined in this study. RESULTS: Artistic and symbolic presentation of heart started some 15,000 years ago. First heart models were made by the Egyptian and Olmec civilisations. Ancient cultures regarded heart as the seat of the soul, spirit and intelligence. First anatomical and artistic images of heart were created by Leonardo da Vinci in the15th century, and first wax models by the Italian anatomists in the 17th century. Mediaeval religious symbolism of heart was replaced in the Renaissance and later on mainly by its role in the romantic love. Anatomical heart art continued in the 18th and 19th centuries through the works of Sénac, Cloquet, Hirschfeldand Bourgery. Some modern artists, such as Dalí, Kahlo, Rivera, Warhol, Ivanjicki, Vital, Kober and Mastrlova, created the anatomical heart images or sculptures, whereas some others, such as Duchamp, Klee, Miró, Matisse and Dine, presented heart symbol in their artworks. New radiologic technologies produce fine images of heart, some of which are similar to the works of modern artists. CONCLUSIONS: Heart biology and symbolism have had a tremendous influence on our culture, including art and medical sciences. New radiologic techniques and computer technology have produced such images of heart, which substantially improved diagnosis, but also enhanced the heart aesthetics.

Structure and immunohistochemistry of the human lenticulostriate arteries.

BACKGROUND: Data about the structure and immunohistochemistry of the lenticulostriate arteries (LSAs), although very important for medical research and clinical practice, have been rarely reported in literature. MATERIALS AND METHODS: Fourty serially sectioned LSAs were stained with hematoxilin and eosin, and prepared for immunohistochemistry. RESULTS: Our examination revealed a typical endothelial lining and a narrow subendothelial space with subintimal smooth muscle cells occasionally. The internal elastic lamina was fragmented or absent in the smallest LSAs branches. The mediacoat, with a mean diameter of 148.5 µm, contained typical smooth muscle cells which formed 14.2 layers on average and showed a positive immune reactions for alfa-actin, desmine, laminin and collagen IV. The thin adventitial coat contained fibroblasts, collagen fibers, and nerve bundles, with the strongest immunopositivity to thyrosin hydroxilase. The immune reactions against CD31 and CD34 proteins,endothelial nitric oxide synthase, S 100 protein, neurofilament protein and synaptophysin,seem to be performed in the LSAs wall for the first time. Similarly,the thickness of the LSAs wall and its coats have never been reported, nor the number of the smooth muscle cell layers. CONCLUSIONS: Our results related to the structure and immunohistochemistry of the LSAs could be important in cerebrovascular pathology, neurology and neurosurgery.

[Retrospective calculation of the workload in emergency departments in case of a mass accident. An analysis of the Love Parade 2010]. / Retrospektive Abschätzung der Belastung einer Notaufnahme beim MANV. Eine Analyse am Beispiel der Loveparade 2010.

BACKGROUND: For the clinical planning of mass events the emergency departments are of critical importance, but there are still no data available for the workload in these cases. As this is essential for an effective medical preparation, we calculated the workload based on the ICD codes of the vicitims at the Loveparade 2010 in Duisburg. MATERIAL AND METHODS: Based on the patient data of the Loveparade 2010 we used a filter diagnosis to estimate the number of shock room patients, regular admittances, surgical wound treatments, applications of casts or splints, and diagnosis of drug abuse. In addition every patient was classified to a Manchester Triage System category. This resulted in a chronological and quantitative work-load profile of the emergency department, which was evaluated by the clinical experiences of the departmental medical staff. RESULTS: The workload profile as a whole displayed a realistic image of the real true situation on July 24, 2010. While only the number, diagnosis and chronology of medical surgical patients was realistic, the MTS classification was not. The emergency department had a maximum of 6 emergency room admittances, 6 regular admittances, 4-5 surgical wound treatments, 3 casts and 2 drug abuse patients per hour. CONCLUSION: The calculation of workload from the ICD data is a reasonable tool for retrospective estimation of the workload of an emergency department, the data can be used for future planning. The retrospective MTS grouping is at present not suitable for a realistic calculation. Retrospective measures in the MTS groups are at present not sufficiently suitable for valid data publication.

Paramount levels of ergothioneine transporter SLC22A4 mRNA in boar seminal vesicles and cross-species analysis of ergothioneine and glutathione in seminal plasma.

Ergothioneine (ET) is a unique natural antioxidant which mammalia acquire exclusively from their food. Recently, we have discovered an ET transporter (ETT; gene symbol SLC22A4). The existence of a specific transporter suggests a beneficial role for ET; however, the precise physiological purpose of ET is still unclear. A conspicuous site of high extracellular ET accumulation is boar seminal plasma. Here, we have investigated whether ETT is responsible for specific accumulation of ET in the boar reproductive tract. The putative ETT from pig (ETTp) was cloned and validated by functional expression in 293 cells. The highest levels of ETTp mRNA were detected by real-time RT-PCR in seminal vesicles, eye, and kidney; much less was present in bulbourethral gland, testis, and prostate. By contrast, there was virtually no ETT mRNA in rat seminal vesicles. ET content in boar reproductive tissues, determined by LC-MS/MS, closely matched the ETT expression profile. Thus, strong and specific expression of ETTp in boar seminal vesicles explains high accumulation of ET in this gland and hence also in seminal plasma. Previous reports suggest that the glutathione (GSH) content of seminal plasma correlates directly with ET content; however, a comprehensive analysis across several species is not available. We have measured ET and GSH in seminal plasma from human, boar, bull, stallion, and rabbit by LC-MS/MS. GSH levels in seminal plasma do not correlate with ET levels. This suggests that the function of ET, at least in this extracellular context, does not depend on redox cycling with GSH.

Enhanced human papillomavirus type 8 oncogene expression levels are crucial for skin tumorigenesis in transgenic mice.

Human papillomavirus 8 (HPV8) is involved in skin cancer development in epidermodysplasia verruciformis patients. Transgenic mice expressing HPV8 early genes (HPV8-CER) developed papillomas, dysplasias and squamous cell carcinomas. UVA/B-irradiation and mechanical wounding of HPV8-CER mouse skin led to prompt papilloma induction in about 3 weeks. The aim of this study was to analyze the kinetics and level of transgene expression in response to skin irritations. Transgene expression was already enhanced 1 to 2 days after UVA/B-irradiation or tape-stripping and maintained during papilloma development. The enhanced transgene expression could be assigned to UVB and not to UVA. Papilloma development was thus always paralleled by an increased transgene expression irrespective of the type of skin irritation. A knock-down of E6 mRNA by tattooing HPV8-E6-specific siRNA led to a delay and a lower incidence of papilloma development. This indicates that the early increase of viral oncogene expression is crucial for induction of papillomatosis.

Uterine tumour resembling an ovarian sex cord tumour.

Endometrial stromal sarcomas account for 0.25% of all uterine malignancies. These tumours were originally divided into low grade and high grade stromal sarcomas, but the recent World Health Organisation classification (2003) recognises low grade stromal sarcoma and undifferentiated endometrial sarcoma. Low grade sarcomas may exhibit other forms of differentiation, including smooth muscle and sex cord differentiation. In the latter form, the tumour contains epithelial-like or sex cord-like elements often with epithelioid appearance, arranged in nests, cords, trabeculae, solid, or tubular structures. If this element predominates, the tumour is considered to be a uterine tumour resembling ovarian sex cord tumour, and may cause diagnostic difficulties. This case report describes the histological and immunohistochemical features of a uterine stromal sarcoma showing exclusively a pattern reminiscent of ovarian sex cord tumour.

Oral status, aesthetic materials and frequency of crowns and bridges in patients with fixed prosthetic appliances living in the Metkovic region.

The aim of the study was to examine oral status in patients of the Metkovic region with fixed prosthodontic appliances. The aim was also to evaluate aesthetic materials used, and difference between the frequency of crowns and bridges dependent on patient's age and frequency of visits to dentist. The examination was performed on 212 dental patients with fixed prosthetic appliances, from the Public Health Center "Metkovic". A questionnaire was created for the purpose of this study and was filled in by the patients. The dentist registered oral status. Descriptive statistics and chi 2 tests were used for the data analysis. Following conclusions were made: 1. The examined patients had relatively high caries (tooth decay), gangrene and residual roots prevalence, the oral hygiene was not appropriate, calculus and gingivitis were diagnosed in all patients (100%) and these facts point out to the insufficient preventive oral health care in the Metkovic region, as well as to the insufficient self-perception on the proper oral hygiene maintenance. 2. Patients who visit their dentist regularly (once a year or more) have significantly more crowns than bridges than the patients who visit their dentist irregularly or when in pain (p < 0.01). 3. Almost all fixed prosthetic appliances not older than 10 years were made of porcelain (98%), while acrylic veneer crowns (or chromasite) were more frequent in appliances older than 10 or 15 years (p < 0.01). There was no gender difference dependent on the material used (p > 0.05). High frequency of porcelain was attributed to the high economic status of this region, as well as to a dentist's preference.

Patients' views on the professional behaviour of family physicians.

BACKGROUND: Patient satisfaction is an important part and a measure of the quality of health care. Patient satisfaction with family physicians was studied within the project 'Analysis of Transition of Health Care System in Croatia'. OBJECTIVES: The aim of this study was to explore patient satisfaction with family physicians through evaluation of some characteristics of physician behaviour. The specific goals of this study were to determine whether there were differences in the evaluation of patient satisfaction with physician behaviour with regard to some sociodemographic characteristics of the respondents. METHODS: The study group consisted of 1217 respondents: 479 (39.4%) men and 738 (60.6%) women. Medical students interviewed the respondents 'face-to-face' immediately after their consultation with the physician. An anonymous questionnaire was created providing answers to 10 questions on patient satisfaction. Data on sociodemographic characteristics and the reason for encounter of the respondents were also collected. RESULTS: The average positive rating over 10 questions on patient satisfaction was 85.3%. There was a statistically significant difference in age distribution between geographic areas (P < 0.001). Differences in answers were found regarding sex, age, educational level (P < 0.001) and reason for encounter (P < 0.01). Two factors were obtained by factor analysis: the first could be called physician's competence/expertise estimated by respondents, and the other physician's empathy evaluated by respondents. The respondents were divided into two groups based on the reason for encounter as a criterion for discriminant analysis: acute (symptoms and complaints, injuries; n = 553) and other reasons (n = 664). The discriminant function obtained was statistically significant (P < 0.01). Younger respondents, regardless of sex, whose reason for encounter was an acute condition, were less satisfied with the physician's expertise, agreeableness during the consultation, physician's interest in what they were saying and physician's friendliness. CONCLUSION: Considering the difficulties present in the health systems of countries in transition, the results of our study were surprisingly encouraging, showing that the respondents were satisfied with the physician's behaviour and that the physicians fulfilled the basic elements of professional behaviour.

The rat beta (b miny)-globin promoter: nuclear protein factors and erythroid-specific induction of transcription.

We show that the rat adult beta (b miny)-globin gene is transcriptionally active. The - 100-bp promoter region contains control elements that are important for the induction of transcription in rat erythroleukemia (REL) cells. By using DNaseI footprinting and gel mobility shift assays, we have shown that the CCAAT box, a regulatory element from an analyzed promoter region, binds NF-Y and GATA-1 transcription factors. Another regulatory element from this region, betaDRE, binds erythroid-specific and ubiquitous factors from REL cells. Although both the CCAAT box region and betaDRE element bind the same protein factors before and after induction of REL cells, we show by South-Western blot analysis that the concentrations of 150-kDa, 70-kDa and 60-kDa factors binding to the betaDRE are increased in DMSO-induced REL cells.

The influence of selenium and neuroleptics on the rat brain nuclear regulatory mechanism in carcinogenesis.

The potential clinical benefit of the antitumor effect of selenium (Se) has recently been confirmed in tumor-bearing animals and human tumor cells in culture. In clinical medicine, the reduced incidence of cancer among schizophrenic patients was attributed to neuroleptic medication. However, there has been little information on the effect of Se, carcinogen, and neuroleptic on the brain cells. This investigation was carried out on the brains of male Wistar rats treated with inorganic Se, 9,10-dimethyl-1,2-benzanthracene, and chlorpromazine. Chromatin was prepared and purified from isolated brain cell nuclei. Various protein species (histones and nonhistone proteins), RNA, and DNA were extracted by different extraction procedures. A higher relative content of nonhistone proteins was found in the group of animals treated with Se alone, carcinogen alone, and Se plus carcinogen administered simultaneously when compared with other experimental and control groups. The ratio of nonhistone proteins and histones of < 1.0 in the group of animals treated with neuroleptic + carcinogen or with neuroleptic indicates a lower content of nonhistone proteins when compared to histones. We obtained a more pronounced susceptibility to degradation by DNase I in the group of animals treated with neuroleptic + carcinogen or with neuroleptic compared to chromatin in the animals treated with carcinogen alone. We conclude that neuroleptic increases protein synthesis, as well as chromatin susceptibility to enzymatic degradation, thus achieving an opposite effect of carcinogen.

Alpha- and beta-globins of the anemic Belgrade laboratory rat. I. Status of alpha- and beta-globins in bone marrow and spleen.

In this study we have demonstrated that the bone marrow of the anemic Belgrade laboratory (b/b) rat, as the primary site of erythropoiesis, has a decreased globin polypeptide synthesis in total protein cell extracts. Therefore, it is the source of red blood cells containing decreased amounts of globin mRNAs and polypeptides. In spite of the fact that the b/b rat shows a splenomegaly, the spleen is not capable of compensating for the anemic state. Spleen erythroid cells are defective in differentiation and contain a decreased share of globin polypeptides in total protein cell extracts compared to the control. Spleen cells are also characterized by a drastic imbalance of alpha- to beta-globin resulting in the beta-globin chains surplus.

Alpha- and beta-globins of the anemic Belgrade laboratory rat. II. The effect of hemin and iron-dextran treatment.

We have studied the changes in bone marrow and spleen globin chain levels after in vivo hemin and iron-dextran treatment of hereditarily anemic Belgrade laboratory (b/b) rats. The increase of globin chains was detected in the bone marrow and in the spleen when b/b animals were treated with either iron or hemin. The analysis of changes in alpha- and beta-globin chain ratios revealed the distinctive role of these molecules in regulating globin chain status. Iron-dextran, as expected, ameliorated the imbalance of alpha- and beta-globin chains in the b/b rat spleen. On the other hand, hemin, as we have hypothesized in the accompanying paper, leads to a surplus of beta-globin chains in the bone marrow, similar to the one detected in the b/b rat spleen. Therefore, an iron-rich microenvironment has a stimulatory effect, while a hemin-rich microenvironment has an inhibitory effect on erythropoiesis.

[Melkersson-Rosenthal syndrome]. / Melkerson-Rozentalov sindrom.

Melkersson-Rosenthal's syndrome is characterized by recurrent or persistent oedema of the lips or the face; the fissured tongue, and intermittent paralysis of the facial nerve. Oligosymptomatic forms are more common than the triad. The syndrome is rarely encountered, it is aetiologycally obscure, the laboratory findings are not specific, but differential diagnosis is very complex, especially in conditions of recurrent and hereditary angioedema. The authors report two cases of the syndrome: the first with the triad and mild neurological symptoms, and the second with two syndrome elements, oedema of the lips and the fissured tongue. Pathohistological results of the biopsy samples of oral mucosa revealed the advanced phase with granulomatous lesions in one case, and early phase with oedema of the connective tissue and perivascular lymphocyte infiltration in the second. Allergic genesis was ruled out, based on negative results of numerous laboratory and clinical tests. Glycocorticoid therapy with antihistaminics and anabolica resulted in clinical improvement.

[Angioimmunoblastic lymphadenopathy with dysproteinemia and hypothyreosis]. / Angioimunoblastna limfadenopatija s disproteinemijom i hipotireoza.

A patient with angioimmunoblastic lymphadenopathy with disproteinemia is presented. The diagnosis is made on the basis of lymph node hystology and laboratory findings of typical immunologic aberrations. The patient had signs of developed primary hypothyreosis with cardiac failure at the same time. The two diagnsis were made in the late stages of diseases, two years after the first findings of generalised lymphadenopathy and clinical signs of hypothyreosis, with developed complications in the form or cardiac, respiratory and renal failure. The disease had terminated lethaly before the pathohystologic diagnosis was known.