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PubMed2001

An epidemiological study of HIV-infections in Frankfurt/Main and other major cities in Germany.

Epidemiological studies can help to understand the effects of medical treatment of HIV infections. Accordingly, this study was designed to discuss the most important parameters in Frankfurt/Main and other big German cities from 1984 to 2000. The number of HIV tests performed by Frankfurt's Virology has been decreasing continually since 1991. A decrease of new infections in men could be registered, whereas the number of HIV infected women rose. From 1985 to 2000 an annual mean value of 478 HIV infected men and 121 HIV infected women was registered in Frankfurt. The gender proportion was followed up for Frankfurt and Hamburg since 1985, for Berlin, Munich, and Cologne since 1993. All but one city showed a significant decline of infected males, only Berlin did not show any obvious changes in this proportion. Over the last twelve years the average age of men and women tested positive for the first time increased. An obvious shift could be discerned during the last two years concerning the distribution of risk groups. The percentage of HIV infected homosexuals and female i.v. drug addicts sank significantly over the last two years, the number of women infected by heterosexual contacts is still increasing when compared to data compiled from 1988 to 1992, and varies between 44% and 33%. During the same time-span a significant shift in first onset of AIDS-defining illnesses was observed. PCP (pneumocystis carinii pneumonia)--formerly represented with 35.5%--decreased and is now surpassed by tuberculosis with 25.5%. The general gender proportion (3:1) could not be reflected by AIDS-defining diseases of which NHL (non-Hodgkin-lymphoma) seems to have the shortest time-span (6.5 months) between the occurrence of illness and death.

AIDS-Related Opportunistic Infections↗
PubMed2004

Pseudo-periodic partitions of biological sequences.

MOTIVATION: Algorithm development for finding typical patterns in sequences, especially multiple pseudo-repeats (pseudo-periodic regions), is at the core of many problems arising in biological sequence and structure analysis. In fact, one of the most significant features of biological sequences is their high quasi-repetitiveness. Variation in the quasi-repetitiveness of genomic and proteomic texts demonstrates the presence and density of different biologically important information. It is very important to develop sensitive automatic computational methods for the identification of pseudo-periodic regions of sequences through which we can infer, describe and understand biological properties, and seek precise molecular details of biological structures, dynamics, interactions and evolution. RESULTS: We develop a novel, powerful computational tool for partitioning a sequence to pseudo-periodic regions. The pseudo-periodic partition is defined as a partition, which intuitively has the minimal bias to some perfect-periodic partition of the sequence based on the evolutionary distance. We devise a quadratic time and space algorithm for detecting a pseudo-periodic partition for a given sequence, which actually corresponds to the shortest path in the main diagonal of the directed (acyclic) weighted graph constructed by the Smith-Waterman self-alignment of the sequence. We use several typical examples to demonstrate the utilization of our algorithm and software system in detecting functional or structural domains and regions of proteins. A big advantage of our software program is that there is a parameter, the granularity factor, associated with it and we can freely choose a biological sequence family as a training set to determine the best parameter. In general, we choose all repeats (including many pseudo-repeats) in the SWISS-PROT amino acid sequence database as a typical training set. We show that the granularity factor is 0.52 and the average agreement accuracy of pseudo-periodic partitions, detected by our software for all pseudo-repeats in the SWISS-PROT database, is as high as 97.6%.

Algorithms↗
PubMed2000

Big issues, small systems: managing with information in medical research.

This subject of this article is the design of a database system for handling files related to the work of the Molecular Genetics Department of the International Blood Group Reference Laboratory. It examines specialist information needs identified within this organization and it indicates how the design of the Rhesus Information Tracking System was able to meet current needs. Rapid Applications Development prototyping forms the basis of the investigation, linked to interview, questionnaire, and observation techniques in order to establish requirements for interoperability. In particular, the place of this specialist database within the much broader information strategy of the National Blood Service will be examined. This unique situation is analogous to management activities in broader environments and a number of generic issues are highlighted by the research.

Blood Banks↗
PubMed1994

Pharmacological characterization of bosentan, a new potent orally active nonpeptide endothelin receptor antagonist.

The authors describe here the pharmacological properties of bosentan, a new nonpeptide mixed antagonist of endothelin (ET) receptors, obtained by structural optimization of the less potent Ro 46-2005 [Ro 46-2005 (4-tert-butyl-N-[6-(2-hydroxyethoxy)-5-(3-methoxy-phenoxy)-4-pyrimidinyl ]-benzenesulfonamide]. Bosentan (Ro 47-0203, 4-tert-butyl-N-[6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2,2'-bipyr imidin-4-yl]-benzenesulfonamide) competitively antagonized the specific binding of [125I]-labeled ET-1 on human smooth muscle cells (ETA receptors) with a Ki of 4.7 nM and on human placenta (ETB receptors) with a Ki of 95 nM. It also inhibited the binding of selective ETB ligands on porcine trachea. Contractions induced by ET-1 in isolated rat aorta (ETA) and by the selective ETB agonist sarafotoxin S6C in rat trachea were competitively inhibited by bosentan (pA2 = 7.2 and 6.0, respectively), as was the endothelium-dependent relaxation to sarafotoxin S6C in rabbit superior mesenteric artery (pA2 = 6.7). The binding of 40 other peptides, prostaglandins, ions and neurotransmitters was not significantly affected by bosentan, which shows its specificity for ET receptors. In vivo, bosentan inhibited the pressor response to big ET-1 both after i.v. and oral administration, with a long duration of action and no intrinsic agonist activity. It also inhibited the depressor and pressor effect of ET-1 and sarafotoxin S6C. Thus, bosentan is the most potent orally active antagonist of ET receptors described so far. Its pharmacological profile makes bosentan a potentially useful drug in the management of clinical disorders associated with vasoconstriction.

Administration, Oral↗
PubMed2003

Staphylococcal resistance revisited: community-acquired methicillin resistant Staphylococcus aureus--an emerging problem for the management of skin and soft tissue infections.

PURPOSE OF REVIEW: In the community non-localized or deep staphylococcal skin and soft tissue infections are typically managed with beta-lactamase stable penicillins. The aims of this review are (1) to evaluate the evidence for the emergence of new strains of community-acquired methicillin resistant Staphylococcus aureus (MRSA), (2) to identify the reasons for their significant association with cutaneous infections, and (3) to consider how they arose and how big a threat they pose to the management of such infections outside hospitals. RECENT FINDINGS: MRSA are emerging as significant community pathogens, especially in previously healthy children with no recognizable risk factors, and are predominantly associated with skin and soft tissue infections (especially abscesses and cellulitis). When present, risk factors are generally similar to those for infection with methicillin susceptible S. aureus. The MRSA isolates associated with such infections may not be entirely 'new', but could represent the displacement of some hospital clones (e.g. EMRSA-15 or variants thereof) to the community as well as the de-novo generation of novel MRSA clones by multiple horizontal transmissions of the mecA gene into methicillin susceptible S. aureus with different genetic backgrounds, some of which are already circulating globally. Community-acquired MRSA from diverse locations are non multiresistant and almost always contain the novel type IV SCCmec commonly found in coagulase-negative staphylococci, but also in hospital-associated gentamicin susceptible MRSA from France, the paediatric clone and in EMRSA-15. SUMMARY: More local data on CA-MRSA infections are needed so that dermatologists and community physicians can assess the risk of such infections amongst their patients and avoid the inappropriate administration of beta-lactams. No simple change in prescribing practices will entirely alleviate selective pressure for the spread of community-acquired MRSA and not exacerbate resistance in pyogenic streptococci, commonly found together with S. aureus in skin and soft tissue infections. The importance of hygiene in preventing the spread of community-acquired MRSA in the community must be reemphasized.

Adolescent↗
PubMed2002

Activation of big mitogen-activated protein kinase-1 regulates smooth muscle cell replication.

This study examined the activation of big mitogen-activated protein (MAP) kinase-1 (BMK1) in rat carotid smooth muscle cells (SMCs). Platelet-derived growth factor, fibroblast growth factor-2, sorbitol, and serum all increased the activation of BMK1 in rat carotid SMCs, whereas angiotensin II, phorbol esters, and tumor necrosis factor-alpha had only slight effects. With the exception of tumor necrosis factor-alpha, all these factors phosphorylated extracellular signal-regulated kinase (ERK)1/2. The MAPK kinase inhibitor (MEKI), U0126 (1 micromol/L), blocked ERK1/2 phosphorylation and at higher doses (5 micromol/L) blocked BMK1 phosphorylation. This inhibitor also blocked SMC DNA synthesis in a dose-dependent manner. When SMCs were transfected with an adenoviral construct expressing dominant mutant BMK1 and stimulated with fibroblast growth factor-2, a significantly smaller increase in cyclin D1 and cyclin A expression and in retinoblastoma factor phosphorylation was detected compared with the increase in cells transfected with an adenoviral construct expressing green fluorescent protein (GFP). SMC DNA synthesis was significantly blocked in the cells transfected with the dominant mutant BMK1. These data support the suggestion that BMK1 is important and necessary for mitogen-induced SMC proliferation.

Animals↗
PubMed2003

Tooth-by-tooth survival analysis of the first caries attack in different age cohorts and health centers in Finland.

The aims of this study were to test the hypothesis that existing patient records serve as a source of data for survival analysis of dental health and to develop a system for routinely conducted survival analysis of dental health from tooth eruption to first caries attack. Patient records for three cohorts were collected from four towns in Finland: Oulu, Turku, Kuopio, and Kemi. The study population comprised 2103 children born and living in these towns. The Kaplan-Meier curves for dental caries were drawn separately for each tooth and for the maxilla and mandible (for each age cohort). Placements of the first restoration of all teeth in each age cohort were investigated. The 1960 cohort had an extremely high post-eruptive morbidity in all teeth. The 1970 cohort had relatively high immediate post-eruptive morbidity in both molars, but much lower than that of the 1960 cohort. The filling increment rates for second molars were lower than those of the first molars in the 1970 cohort. Characteristic of the 1980 cohort was a rapid increase in the caries increment of the premolars and second molars 4 years after eruption. The results indicate a big difference in tooth-by-tooth dental health in Finland. A huge decline in caries attack was seen from the 1960 cohort to the 1980 cohort, but a deterioration of dental health in premolars and second molars is clearly seen in the 1980 cohort in the 1990s.

Adolescent↗
PubMed2003

Regulation of epidermal growth factor-induced connexin 43 gap junction communication by big mitogen-activated protein kinase1/ERK5 but not ERK1/2 kinase activation.

The gap junction protein, Cx43, plays a pivotal role in coupling cells electrically and metabolically, and the putative phosphorylation sites that modulate its function are reflected as changes in gap junction communication. Growth factor stimulation has been correlated with a decrease in gap junction communication and a parallel activation of ERK1/2; the inhibition of epidermal growth factor (EGF)-induced Cx43 gap junction uncoupling was observed by using the MEK1/2 inhibitor, PD98059. Because 1) BMK1/ERK5, another MAPK family member also activated by growth factors, possesses a phosphorylation motif similar to ERK1/2, and 2) it has been reported that PD98059 can inhibit not only MEK1/2-ERK1/2 but also MEK5-BMK1 activation, we investigated whether BMK1 can regulate EGF-induced Cx43 gap junction uncoupling and phosphorylation, comparing this to the role of ERK1/2 on Cx43 function and phosphorylation induced by EGF. Selective activation or inactivation of ERK1/2 by using a constitutively active form or a dominant negative form of MEK1 did not regulate Cx43 gap junction coupling. In contrast, we found that BMK1, selectively activated by constitutively active MEK5alpha, induced gap junction uncoupling, and the inhibition of BMK1 activation by transfection of dominant negative BMK1 prevented EGF-induced gap junction uncoupling. Activated BMK1 selectively phosphorylates Cx43 on Ser-255 in vitro and in vivo, but not on S279/S282, which are reported as the consensus phosphorylation sites for MAPK. Furthermore, by co-immunoprecipitation, we found that BMK1 directly associates with Cx43 in vivo. These data indicate that BMK1 is more important than ERK1/2 in EGF-mediated Cx43 gap junction uncoupling by association and Cx43 Ser- 255 phosphorylation.

Blotting, Western↗
PubMed1991

Structure of the precursor for vasoactive intestinal contractor (VIC): its comparison with those of endothelin-1 and endothelin-3.

Vasoactive intestinal contractor (VIC) is a member of the endothelin (ET) peptide family, which evokes a strong contractile response in the ileum, its gene being expressed only in the intestine. Using dot blot analysis, we carried out an interspecies comparison of the nucleotide and deduced amino acid sequences of the precursor for VIC with those of ET-1 and ET-3 to investigate the physiological significance of processing of the precursor for VIC. The highly conserved amino acid sequence was observed between the big form region (big VIC, big ET-1, and big ET-3) of about 40 amino acids and the like peptide region (VIC-like peptide, ET-1-like peptide, and ET-3-like peptide) of 15 amino acids downstream from the big form region. Sequence identity of amino acids of the precursors of ET-1 and ET-3 with that of VIC was 29 and 28%, respectively. Thus, the precursors for the three peptides might have arisen from a common progenitor gene. However, apparent cleavage sites of the like peptide regions are rather unique in the VIC-like peptide, i.e., it had dibasic amino acids at the amino and carboxy termini. Therefore, we suggest that the VIC-like peptide might be liberated from its precursor protein and play some role in the intestine in vivo.

Amino Acid Sequence↗
PubMed1990

Active site complementation in engineered heterodimers of Escherichia coli glutathione reductase created in vivo.

By directed mutagenesis of the cloned Escherichia coli gor gene encoding the dimeric flavoprotein glutathione reductase, Cys-47 (a cysteine residue forming an essential charge-transfer complex with enzyme-bound FAD) was converted to serine (C47S) and His-439 (required to facilitate protonation of the reduced glutathione) was converted to glutamine (H439Q). Both mutant genes were placed in the same plasmid, pHD, where each of them came under the control of a strong tac promoter. This was designed to achieve equal over-expression of both genes in the same E. coli cell. The parental homo-dimers show no (C47S) or very little (H439Q) activity as glutathione reductases. The formation in vivo of heterodimers, carrying one crippled and one fully functional active site, was detected by absorbance spectroscopy and fluorescence emission spectrometry of enzyme-bound FAD and by active site complementation. The fractional distribution of homo- and hetero-dimers was in accord with that expected for a random association of enzyme subunits. In a homo-dimer, the H439Q mutation leads to a big fall in the value of Km for NADPH which binds some 1.8 nm from the point of mutation (Berry, A., Scrutton, N.S. & Perham, R. N. Biochemistry 28, 1264-1269 (1989)). However, the one active site in the H439Q/C47S hetero-dimer exhibited kinetic parameters similar to those of the wild-type enzyme. Thus, the effect of the H439Q mutation must be retained within the active site that accommodates it and is not transmitted through the protein to the second active site across the subunit interface.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1990

Endothelins.

The endothelins (ETs) are a family of newly discovered peptides with potent vasoconstrictor properties. They were first discovered in cultured endothelial cells but ET expression has since been found in many other tissues such as brain and kidney. They are peptides with 21 amino acids formed by hydrolytic cleavage of a larger peptide, big ET. Release of ETs from cultured endothelial cells is modulated by a variety of chemical and physical stimuli and as no storage sites have been identified it is suggested that endothelin release is regulated at the level of transcription or translation. Both big ET and ET-1 are found circulating in the blood. The levels are elevated in shock, myocardial infarction and kidney failure indicative of enhanced formation in these diseases. The literature now abounds with reports on actions of the ETs in vitro and in vivo. The vasoconstrictor properties are powerful and long-lasting. Several studies also show a mitogenic effect, indicating a possible trophic role. It is likely that in the next few years the development of inhibitors of endothelin synthesis and/or action will be of importance in unravelling the role of the ETs.

Amino Acid Sequence↗
PubMed2004

Conflicts of interest in medical science: peer usage, peer review and 'CoI consultancy'.

In recent years, the perception has grown that conflicts of interest are having a detrimental effect on medical science as it influences health policy and clinical practice, leading medical journals to enforce self-declaration of potential biases in the attempt to counteract or compensate for the problem. Conflict of interest (CoI) declarations have traditionally been considered inappropriate in pure science since its evaluation systems themselves constitute a mechanism for eliminating the effect of individual biases. Pure science is primarily evaluated by 'peer usage', in which scientific information is 'replicated' by being incorporated in the work of other scientists, and tested by further observation of the natural world. Over the long-term, the process works because significant biases impair the quality of science, and bad science tends to be neglected or refuted. However, scientific evaluation operates slowly over years and decades, and only a small proportion of published work is ever actually evaluated. But most of modern medical science no longer conforms to the model of pure science, and may instead be conceptualized as a system of 'applied' science having different aims and evaluation processes. The aim of applied medical science is to solve pre-specified problems, and to provide scientific information ready for implementation immediately following publication. The primary evaluation process of applied science is peer review, not peer usage. Peer review is much more rapid (with a timescale of weeks or months) and cheaper than peer usage and (consequently) has a much wider application: peer review is a prospective validation while peer usage is retrospective. Since applied science consists of incremental advances on existing knowledge achieved using established techniques, its results can usually be reliably evaluated by peer review. However, despite its considerable convenience, peer review has significant limitations related to its reliance on opinion. One major limitation of peer review has proved to be its inability to deal with conflicts of interest, especially in a 'big science' context when prestigious scientists may have similar biases, and conflicts of interest are widely shared among peer reviewers. When applied medical science has been later checked against the slower but more valid processes of peer usage, it seems that reliance on peer review may allow damaging distortions to become 'locked-in' to clinical practice and health policy for considerable periods. Scientific progress is generally underpinned by increasing specialization. Medical journals should specialize in the communication of scientific information, and they have neither the resources nor the motivation to investigate and measure conflicts of interest. Effectively dealing with the problem of conflicts of interest in applied medical science firstly requires a more explicit demarcation between the communications media of pure medical science and applied medical science. Greater specialization of these activities would then allow distinctive aims and evaluation systems to evolve with the expectation of improved performance in both pure and applied systems. In future, applied medical science should operate with an assumption of bias, with the onus of proof on applied medical scientists to facilitate the 'data transparency' necessary to validate their research. Journals of applied medical science will probably require more rigorous processes of peer review than at present, since their publications are intended to be ready for implementation. But since peer review does not adequately filter-out conflicts of interest in applied medical science, there is a need for the evolution of specialist post-publication institutional mechanisms. The suggested solution is to encourage the establishment of independent 'CoI consultancy' services, whose role would be to evaluate conflicts of interest and other biases in published applied medical science prior to their implementation. Such services would be paid-for by the groups who intend to implement applied medical research.

Conflict of Interest↗
PubMed2005

[Cockroach hypersensitivity in children suffering from perennial allergic rhinitis].

UNLABELLED: The role of cockroach allergens in the etiology of allergic disorders is still not clear. Published studies show a high variability in frequency of hypersensitivity to cockroaches. The aim of our work was to study the possible role of cockroach allergy in children suffering from perennial allergic rhinitis. MATERIAL AND METHODS: The study group consisted of 97 children with symptoms of perennial rhinitis admitted to our Outpatient Clinic. The data about medical history, symptoms, incomes and accomodation were gathered using a questionnaire. Skin prick tests (SPT) with a set of allergens including cockroaches were performed. RESULTS: Sixty boys and 37 girls with mean age 9.15 +/- 3.48 years, with mean duration of symptoms of perennial rhinitis 2.92 +/- 1.86 years were included it the study. In 28 children (28.9% of the study group) had all SPT negative. At least one positive SPT was found in 69% of patients. The most frequent allergens were house dust mites (Der f--65.2%, Der p--60.9%), followed by grasses (58%) and moulds (46.%). Positive SPT with cockroaches was found in 16 children (23.2%). The most frequent symptom in our study group was nasal congestion (68.4%). 46.4% of children complained about deterioration of nasal symptoms during a day. Perennial rhinitis coexisted with diagnosed bronchial asthma in 28 patients (28.9%) and with atopic dermatitis in 14 patients (14.4%). Presence of cockroaches at home was noticed in 3 cases and at school in 1 case. We did not find correlation between type of housing, living in a big city, small city or countryside and allergy to cockroaches (chi2 test p = 0.75). Hypersensitivity to cockroaches did not correlate with severity of rhinitis (U-Mann-Whitney test p = 1.0). There was no correlation between low incomes and allergy to cockroaches (chi2 test p = 0.294). CONCLUSIONS: The results of our study show that in our region hypersensitivity to cockroaches is one of possible, but not leading factor responsible for the development of perennial rhinitis.

Allergens↗
PubMed1991

Neuro-ocular Lyme borreliosis.

Any patient who has a Bell's palsy (unilateral or bilateral), aseptic meningitis, chronic fatigue syndrome, atypical radiculoneuropathy, presenile dementia, atypical myopathy, or symptoms of atypical rheumatoid arthritis should be asked specifically about the following: visits to highly endemic areas, any known tick bites, any skin lesion suggestive of erythema migrans, any history of palpitations or of prior Bell's palsy, aching in joints (especially the knees), paresthesias, chronic fatigue and depression, forgetfulness, and eye problems. Any patient showing a chronic iritis with posterior synechiae, vitritis in one or both eyes, an atypical pars planitis-like syndrome, big blind spot syndrome, and swollen or hyperemic optic discs should be asked the same questions. The physician should send one red-top tube of blood containing 2 to 3 ml serum to Microbiology Reference Laboratory, 10703 Progress Way, Cypress, CA 90630-4714, requesting a Lyme/treponemal panel. For $90 the patient will receive an RPR test with titer, serum FTA-ABS test, serum Lyme IFA IgG and IgM, and a serum Lyme ELISA test. If these tests are within normal limits and the physician is still suspicious, a Western blot can be ordered on serum. A green top tube with fresh white blood cells sent out by overnight express on a Monday or Tuesday will produce a Lyme PCR and a lymphocyte stimulation test. Finally, R.K. Porschen, director of MRL Laboratory, will provide information on the urine antigen test on an investigational basis. A careful history with emphasis on the specific questions noted above, a complete neuro-ophthalmological and physical examination ruling out other causative problems, and the laboratory studies here discussed will usually provide sufficient data to choose therapy. Much further active research into Lyme borreliosis is an important priority in medicine.

Adult↗
PubMed1993

High variability of nitrosamine metabolism among individuals: role of cytochromes P450 2A6 and 2E1 in the dealkylation of N-nitrosodimethylamine and N-nitrosodiethylamine in mice and humans.

We undertook this study to answer several questions regarding nitrosamine metabolism. Kinetics of nitrosamine metabolism showed the involvement of at least two enzymes in the dealkylation of N-nitrosodiethylamine (NDEA) and N-nitrosodimethylamine (NDMA) in mouse liver microsomes. Coumarin inhibited both reactions competitively. On the other hand, microsomal coumarin 7-hydroxylase was inhibited by NDMA (Ki 2.7 mM) and NDEA (Ki 0.013 mM). The big difference in the Ki values suggests a higher affinity of NDEA than NDMA to Cyp2a-5 (mouse cytochrome P450coh). A specific antibody against Cyp2a-5 inhibited more of the microsomal NDEA (up to 90%) than NDMA (up to 40%) dealkylation. The converse was true with anti-Cyp2e-1 antibody. These results suggest that the primary substrate for Cyp2a-5 is NDEA and for Cyp2e-1, NDMA. Western blot analysis of human liver microsomes showed a great interindividual variation in the amounts of CYP2A6 (human cytochrome P450coh) and CYP2E1. Also, coumarin 7-hydroxylation and nitrosamine dealkylation varied greatly among individuals. A high correlation (r = 0.93, P < 0.001) was found between NDEA and coumarin metabolism. Both activities were associated with CYP2A6. On the other hand, little or no correlation was found between microsomal CYP2A6 and CYP2E1 or between CYP2E1 and NDEA dealkylation. Immunoinhibition of human microsomal NDEA metabolism by CYP2a-5 antibody varied greatly among individuals (10-90%), suggesting, as in the case of mice, that NDEA is metabolized primarily by CYP2A6, at least in some individuals. Taken together the data suggest that (1) the metabolic activation of nitrosamines in humans varies greatly among individuals; (2) different nitrosamines may partially be metabolized by different cytochrome P450 isozymes; and (3) because of similarities between nitrosamine metabolism in mice and humans, inbred strains of mice would be relevant experimental models for studying nitrosamine activation.

Animals↗
PubMed1989

Detailed assessment of big big prolactin in women with hyperprolactinemia and normal ovarian function.

Six women with elevated circulating levels of big big PRL (BBPRL) and apparently normal ovarian function were variously studied through a menstrual cycle and menstruation, through pregnancy and suckling, and during stimulation tests with TRH and suppression with bromocriptine. No significant changes in monomeric PRL were demonstrated during the menstrual cycle, but all subjects showed a small and significant rise in BBPRL during the preovulatory phase. High PRL levels were present in day 1 menstrual plasma, but BBPRL was only present in low concentrations. All subjects (n = 5) demonstrated a rise in both PRL and BBPRL during pregnancy, with a consistent tendency for PRL to increase to a proportionately greater extent than BBPRL. One subject exhibited a rise in PRL (by 93%), but not BBPRL, 30 min after suckling. TRH caused a brisk rise in PRL (by 363 +/- 116%) but only a sluggish rise in BBPRL (by 17.5 +/- 7.4%; n = 3). Bromocriptine rapidly suppressed PRL (by 81.8 +/- 34.4%), but only slowly suppressed BBPRL (by 21.0 +/- 8.7% after 6 h; n = 3). Plasma binding studies did not demonstrate any evidence of a circulating specific PRL-binding protein. These data indicate that plasma concentrations of BBPRL may vary under the influence of a number of factors, but are much less sensitive to TRH stimulation, bromocriptine suppression, pregnancy, and suckling than PRL. The occurrence of BBPRL does not seem to be due to a specific circulating binding protein.

Adult↗
PubMed2005

Short to long term mortality of patients hospitalised with heart failure in the Czech Republic--a report from the EuroHeart Failure Survey.

BACKGROUND AND AIM: The European Society of Cardiology initiated the EuroHeart Failure Survey to obtain more data about the quality of care in patients hospitalised with suspected heart failure (HF). The Czech Republic was 1 of the 24 European Society countries included in the survey. The aim of this report is to extend the original follow-up period of 12 weeks out to 4 years to assess mortality. METHODS: All admitted patients were screened according to the EuroHeart Survey Protocol, over a 6-week period in six hospitals in Pilsen, Prague and Brno in the year 2000. Annual mortality and cause of death were obtained from the Prague Institute for Health Statistical Information (UZIS Praha). RESULTS: A total of 2365 patients were screened and about 25% of all admitted patients fulfilled the criteria for HF. About 14% of patients died between admission and the 12-week follow-up, 36% of male and 42% of female patients died during the 4-year follow-up (2000-2003). Cardiovascular diseases were the main causes of death (92%). Deceased patients were significantly older, had lower haemoglobin and total plasma cholesterol level, and had renal insufficiency and higher levels of big endothelin and BNP than the survivors. Mortality risk was increased independently by positive history of previous myocardial infarction OR=2.39 (1.59-3.59), by age OR=1.03 (1.01-1.05) and by plasma creatinine level OR=1.04 (1.01-1.07). Treatment with diuretics and digoxin was associated with a higher risk of death; by contrast, a protective effect of beta-blockers and statins was found in these HF patients. CONCLUSION: Patients with HF were older and had a poor prognosis; approximately one third of the patients will die within 3 years.

Adrenergic beta-Antagonists↗
PubMed2006

Lack of patients? A hypothesis for understanding discrepancies between hospital resources and productivity.

BACKGROUND: Despite a substantial increase in hospital resources, increased hospital admissions and out-patient visits, long waiting lists have been a significant problem in Norwegian health care. A detailed analysis of the development in resource allocation and productivity at St. Olavs University Hospital in central Norway was therefore undertaken. METHODS: Resource allocation and patient volume was analysed during the period 1995 to 2001. Data were analysed both for emergency and elective admissions as well as outpatient visits specified into new referrals and follow-up consultations. RESULTS: Full time employee equivalents for doctors and nurses increased by 36.6% and 25.9%, respectively, and all employees by 28.1%. However, admitted patients, outpatient consultations and surgical procedures only increased by 10%, 15% and 8.3%, respectively. Thus, the productivity for each hospital employee, defined as operations pr. surgeon, outpatient consultations pr. doctor etc. was significantly reduced. A striking finding was that although the number of outpatient consultations increased, the number of new referrals actually went down and the whole increase in activity at the outpatient clinics could be explained by a substantial increase in follow-up consultations. This trend was more evident in the surgical departments, where some departments actually showed a reduction in total outpatient consultations. CONCLUSION: In view of the slow increase in hospital activity in spite of a significant increase in resources, it can be speculated that patient volume might be a limiting factor for hospital activity. The health market (patient population) might not be big enough in relation to the investments in increased production capacity (equipment and manpower).

Efficiency, Organizational↗