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Problems with drugs in Croatia.

Croatia has 4.8 million inhabitants, 11,800 physicians, 2000 pharmacists, two now shareholding, pharmaceutical companies (about 6500 employees, total sales of about 350 million US dollars). There are a number of problems due to the war (GNP fell from 3800 to about 1500 US dollars), occupation of 25% of its territory, 0.5 million refugees and lack of resources (139 US dollars/capita for health, about 40 US dollars i.e. 30%!! for drugs)--about three times less than before the aggression. The drug situation is controlled with the help of: (1) donations (approximate value of 600 million US dollars since 1991 from Europe and US), (2) (essential) drug formularies--250 for outpatients, and 580 generic names for various levels of hospital use, (3) special efforts to purchase drugs of good quality at a reasonable price (a kind of tender), (4) control of prescribing (prescriptions, specialists referral) especially by GPs. A new Medicines Act is in preparation and about 1000 generic names are on the market. DRUG EDUCATION: Pharmaca: the Croatian journal of pharmacotherapy has been published since 1962, there are several Drug bulletins (one published since 1975); special chapters on clinical pharmacology in textbooks, translation of three editions of Laurence's textbook with special commentary and adaptation to local needs; ADR spontaneous and intensive monitoring (WHO programme) with a personal feedback to the reporters and regular articles on drug use in a number of periodicals. Data on drug consumption indicates that there is room for improvement of prescribing. There is an enthusiasm for 'vasoactive drugs'--after dipirydamole came oxpentifylline and antimicrobials are always overprescribed. All these problems will hopefully decrease when the war finally stops and when industry (especially tourism) starts being fruitful again. In any case the importance of teaching of pharmacotherapy at the under- and postgraduate level should be recognized.

Journal Article↗

Privatization and the allure of franchising: a Zambian feasibility study.

Efforts to privatize portions of the health sector have proven more difficult to implement than had been anticipated previously. One common bottleneck encountered has been the traditional organizational structure of the private sector, with its plethora of independent, single physician practices. The atomistic nature of the sector has rendered many privatization efforts difficult, slow and costly-in terms of both organizational development and administration. In many parts of Africa, in particular, the shortages of human and social capital, and the fragile nature of legal institutions, undermine the appeal of privatization. The private sector is left with inefficiencies, high prices and costs, and a reduced effective demand. The result is the simultaneous existence of excess capacity and unmet need. One potential method to improve the efficiency of the private sector, and thereby enhance the likelihood of successful privatization, is to transfer managerial technology--via franchising--from models that have proven successful elsewhere. This paper presents a feasibility analysis of franchizing the successful Bolivian PROSALUD system's management package to Zambia. The assessment, based on PROSALUD's financial model, demonstrates that technology transfer requires careful adaptation to local conditions and, in this instance, would still require significant external assistance.

Efficiency, Organizational↗

A new and rapid method for visualising DNA replication in spread DNA by immunofluorescence detection of incorporated 5-iododeoxyuridine.

We have developed a new and rapid immunofluorescent method for visualisation of replicated regions on fixed DNA fibers. Using this method we have found in 5-fluorodeoxyuridine (FrdU)-blocked human cells distinct replication units covering about 60 kb of DNA and corresponding in size to single replicons or chromatin loops. Our results also suggest that nonadjacent replicons within a replicon cluster may be activated after FrdU arrest and that the method may be adapted for localization on fibers of specific DNA sequences.

Chromosomes, Human↗

Variation in tooth morphology of Gorilla gorilla.

Gorilla gorilla exemplifies a species that shows considerable variation in habitat, behaviour, genetic structure and morphology. This study examines variation of dental morphology in gorillas. Despite the marked size dimorphism, there are no significant shape differences between the sexes within subspecies. Differences in dental morphology, including tooth cusp proportions between the western G. g. gorilla and the eastern G. g. beringei are considerable. Although more similar to G. g. beringei than to the western G. g. gorilla, G. g. graueri also shows distinct morphological features. This indicates that the morphology of G. g. graueri is not merely intermediate, and genetic isolation between the two eastern subspecies could have had a substantial influence. Such extensive variation in dental morphology in Gorilla gorilla can be considered to be the result of an interesting combination of factors, including local dietary adaptations.

Animals↗

17O-decoupled (1)H spectroscopy and imaging with a surface coil: STEAM decoupling.

(17)O-decoupled (1)H spin-echo imaging has been reported as a means of indirect (17)O detection, with potential application to measurement of blood flow and metabolism. In its current form, (17)O decoupling requires large RF amplitudes and a 180 degrees refocusing pulse, complicating its application in volume and surface coils, respectively. To overcome this problem, we have developed an (17)O-decoupled proton stimulated echo sequence ("STEAM decoupling") to allow (17)O detection with a surface coil. A high B(1) amplitude is easily generated, allowing complete decoupling of (17)O and (1)H. Slice-selective, (17)O-decoupled (1)H imaging is readily performed and the sequence is easily adapted for localized spectroscopy. Intrinsic correction for variations in B(1) and further compensation for B(1) inhomogeneity are discussed.

Animals↗

Provision of supplementary fluids to breast fed infants and later breast feeding success.

It has been shown that altering hospital policies in a way to avoid interference of routine prescriptions with initiation of breast feeding and to provide active encouragement to mothers and personnel can result in significant benefit for later breast feeding success. It is less clear, however, which of the elements of a promotional programme such as UNICEF/WHO's "ten steps to successful breast feeding" are absolutely essential and which can be adapted to local cultural habits. We performed an open randomized multicenter study in Switzerland to evaluate, whether restriction of supplementary fluids for breast fed infants in the first week of life and strict avoidance of artificial teats and pacifiers affects later breast feeding success. Follow up to 6 months was ensured by mailed questionnaires. 602 mother infant pairs were enrolled. Of 294 infants in the intervention group 39% were excluded from the final analysis because of protocol violations, mainly maternal request for the use of pacifiers or bottles. Though the number of dextrin maltose supplements during the first two days (1.7 vs. 2.2 on day 1, 2.2 vs. 2.6 on day 2) and the percentage of infants receiving any supplement (85% vs. 96.6%) was significantly smaller in the intervention group, the difference was disappointingly small. The prevalence of breast feeding was 100% vs. 99% at day 5, 88% vs. 88% at 2 months, 75% vs. 71% at 4 months and 57% vs. 55% at 6 months, none of the differences being significant. We conclude that rigorous adherence to all of the ten steps may encounter obstinate resistance from cultural habits even in a population highly favourable to breast feeding. An improvement in adherence does not necessarily lead to better breast feeding success. The results of the few comparable studies in the literature show also that cultural practices during the first months of life may influence profoundly the long term effects of interventions during the first days of life.

Breast Feeding↗

Inversion polymorphism in species of the Drosophila nasuta subgroup from Thailand.

Thailand populations of three species of the D. nasuta complex have been analysed for the presence of paracentric inversions. D. albomicans and D. sulfurigaster albostrigata were collected from Phuket, Chiang Mai and the River Kwai, whilst D. kohkoa was found only in Phuket and the River Kwai. Chromosomal polymorphism was studied in respect to geographical distribution. The Phuket populations of all three species proved to be highly polymorphic by comparison with the River Kwai and Chiang Mai populations. The heterozygosity frequencies of inversions were calculated and the variations interpreted as a result of adaptation to local ecogeographical conditions. Shared polymorphisms revealed that D. kohkoa and D. s. albostrigata are more closely related to D. albomicans than they are to each other.

Animals↗

[The stress of the human hip joint. VI. A functional analysis of the cartilage thickness in the human femoral head (author's transl)].

The distribution of cartilage thickness was ascertained in 11 femoral heads. The greatest thickness of cartilage was always found lateral of the fovea capitis at the medial margin of the pressure area ("Druckbündelzone") of the cancellous bone, whereas the dorsomedial part of the head showed a zone of thinning, extending to the medial margin of the fovea capitis. The decrease in cartilage thickness occurred less rapidly in the lateral part of the joint than in the medial part. In the case of coxa vara, a changed pattern of cartilage thickness was observed, with a maximum thickness located more towards the lateral edge of the cartilage and a reduction in cartilage at the lateral margin of the fovea. The results are put in relation to the stress of the hip joint and are explained according to Pauwels' conceptions of the causal histogenesis and preservation of the mesenchymal supporting tissues. Differences in cartilage thickness are discussed as being a functional adaptation to local stress.

Adult↗

Changes in onset of blood lactate accumulation (OBLA) and muscle enzymes after training at OBLA.

Eight well-trained middle and long distance male runners added to their regular training program a weekly 20-min treadmill run at a velocity calculated to elicit a blood lactate concentration of 4 mmol X 1-1. VO2 max, the running velocity eliciting 4 mmol X 1-1 blood lactate (VOBLA), and the activities of citrate synthase (CS), phosphofructokinase (PFK), lactate dehydrogenase (LDH) and LDH isozymes in the M. vastus lateralis were determined before and after 14 weeks of this training. Significant increases were observed in VOBLA and the relative fraction of heart-specific LDH, while the activity of PFK and the ratio of PFK/CS decreased after training. The change in VOBLA was negatively correlated to the mean rate of blood lactate accumulation during the last 15 min of the treadmill training runs, and positively correlated to the percentage of slow twitch fibers in the M. vastus lateralis. The data support the hypothesis that a steady state training intensity which approximates VOBLA will increase VOBLA, and will result in measureable local metabolic adaptations in the active skeletal muscles of well-trained runners without a significant change in maximal aerobic power. Muscle fiber type composition may be an indicator of the "trainability" of the musculature.

Adolescent↗

Immunolocalization of 15-kDa membrane proteins in the kidneys of normal and acidotic rats.

Proteins with apparent molecular masses between 15 kDa and 17 kDa were enriched from rat renal brush-border membranes by preparative gel electrophoresis and used for immunization of rabbits. The serum of one of the rabbits reacted in Western blots of separated renal brush-border proteins with a single 15-kDa band. A comparably strong reaction is seen with a 15-kDa band of renal endosomal proteins. Basolateral membranes show a much weaker reaction. In light- and electron-microscopic studies the serum stains brush-border membranes and endosomes in rat proximal tubule cells, but not mitochondria and basolateral membranes. In cortical collecting ducts, principal cells are not stained with the antiserum. alpha-type (H(+)-secreting) intercalated cells bind the antibodies at apical tubulovesicles. The luminal membrane is scarcely labelled. Conversely, beta-type (HCO3(-)-secreting) intercalated cells exhibit antibody binding to their basolateral membrane. Thus, the antiserum detects 15-kDa proteins differently sorted in alpha- and beta-intercalated cells. After induction of an acute (6 h) metabolic acidosis, the antibody-binding pattern changes only in intercalated cells, type alpha, and occurs at the markedly enlarged luminal plasma membrane. The amount of alpha-type intercalated cells with enlarged luminal membrane ("secreting cell") increases at the expense of alpha cells with apical tubulovesicles ("resting cell"). Taken together, the antiserum detects 15-kDa proteins, the localization and adaptive changes to metabolic acidosis of which are similar to H(+)-ATPases. The functional role of the 15-kDa proteins needs to be established in further studies.

Acidosis↗

Comparative rheology of nucleated and non-nucleated red blood cells. I. Microrheology of avian erythrocytes during capillary flow.

Deformation and dynamic flow behaviour of nucleated duck erythrocytes were compared to those of nonnucleated human cells during steady flow (at wall shear stresses up to 3 N.m-2) through glass capillaries (diameter between 5 micrometer and 12 micrometer). While the deformation process of both cell species is qualitatively similar, significant quantitative differences demonstrate a lower deformability of the nucleated erythrocytes. In comparison to human cells, the avian red cells exhibit significantly lower stability of orientation during capillary flow. Viscometric measurements show that, in contrast to human red cell suspensions, the relative viscosity of nucleated cell suspensions does not decrease with increasing suspending medium viscosity. The results indicate that the hydrodynamic disturbance caused by avian erythrocytes in the flow of the suspending fluid is more pronounced than that of the mammalian cells. This is due to their lower ability to adapt to local shear forces.

Animals↗

Developing a Chinese version of the psychoeducational profile (CPEP) to assess autistic children in Hong Kong.

The Psychoeducational Profile (PEP) has been used to assess the developmental functioning and behavior of autistic children in the West. To examine its suitability for assessing autistic children in Hong Kong, the PEP was translated into Chinese and certain items were adapted for local conditions. The Chinese version of the PEP (CPEP) was administered to 23 autistic children and 40 children with normal development, ranging in age from 3 to 7 years. Some of the children were also given the Merrill-Palmer Scale of Mental Tests. Results indicated that CPEP scores correlated significantly with Merrill Palmer scores, demonstrating criterion-related validity. Significant positive correlations were also found between age and CPEP scores for children with normal development, verifying that the CPEP has properties of a developmental scale. There was also a significant difference between children with normal development and children with autism on the Pathology scale, suggesting that the scale has discriminant validity.

Autistic Disorder↗

Times to exhaustion at 100% of velocity at VO2max and modelling of the time-limit/velocity relationship in elite long-distance runners.

The aim of this study was to measure running times to exhaustion (Tlim) on a treadmill at 100% of the minimum velocity which elicits VO2max (vVO2max in 38 elite male long-distance runners (VO2max = 71.4 +/- 5.5 ml.kg-1.min-1 and vVO2max = 21.8 +/- 1.2 km.h-1). The lactate threshold (LT) was defined as a starting point of accelerated lactate accumulation around 4 mM and was expressed in %VO2max. Tlim value was negatively correlated with vVO2max (r = -0.362, p < 0.05) and VO2max (r = -0.347, p < 0.05) but positively with LT (% vVO2max) (r = 0.378, p < 0.05). These data demonstrate that running time to exhaustion at vVO2max in a homogeneous group of elite male long-distance runners was inversely related to vVO2max and experimentally illustrates the model of Monod and Scherrer regarding the time limit-velocity relationship adapted from local exercise for running by Hughson et al. (1984).

Adult↗

[Swiss Confederation cooperation in health development: beginnings, experiences and present projects].

The types of medical and health activities in the first ten years of the Swiss Confederation's development aid program (1961-71) are examined in a critical light. In that period such aid was primarily in support of missionary hospitals in Africa and came to 3% of the total aid program of Switzerland. In the seventies guidelines for health programs were established and these have since been systematically applied. The principal aspects are: creation of basic health services, adaptation to local conditions, integration into the overall economic and social development efforts, training of health personnel. In conclusion, the article lists geographically those health projects, which are at present financed and/or staffed by DEH.

Developing Countries↗

Transfer effects in endurance exercise. Adaptations in trained and untrained muscles.

The effects of 8 weeks of bicycle endurance training (5 X /week for 30 min) on maximal oxygen uptake capacity (VO2max) during arm and leg ergometry, and on the ultrastructure of an untrained arm muscle (m. deltoideus), and a trained leg muscle (m. vastus lateralis) were studied. With the training, leg-VO2max for bicycling increased by +13%, while the capillary per fiber ratio and the volume density of mitochondria in m. vastus lateralis increased by +15% and +40%, respectively. In contrast, the untrained m. deltoideus showed an unchanged capillary per fiber ratio and a decreased mitochondrial volume density (-17%). Despite this decrease of mitochondrial volume arm-VO2max increased by +9%. It seems unlikely that the observed discrepancy can be explained by cardiovascular adaptations, since arm cranking did not fully tax the cardiovascular system (arm-VO2max/leg-VO2max: 0.74 and 0.71 before and after training, respectively). Thus neither cardiovascular adaptations nor local structural changes in the untrained muscles could explain the increased arm-VO2max. However, the enhanced capacity for lactate clearance after endurance training could be sufficient to account for the larger VO2max during arm cranking. We propose that an increased net oxidation of lactate might be responsible for the increased arm-VO2max found after bicycle endurance training.

Adult↗

Computational simulations of stress shielding and bone resorption around existing and computer-designed orthopaedic screws.

Failure of an orthopaedic fixation due to stress shielding and consequent screw loosening is a major concern among surgeons: the loosened screws could not only interfere with the healing process but also endanger adjacent anatomical structures. In this study, the effect of the screw's engineering design (dimensions, profile shape and material properties) on the load sharing with adjacent bone and consequent bone resorption was tested, using a set of two-dimensional computational (finite element) models. An algorithm simulating local bone adaptation to strain energy density (SED) mechanical stimuli was developed and used to evaluate the biomechanical performances of different commercial screws. Two new designs, a 'graded-stiffness' composite screw, with a reduced-stiffness titanium core and outer polymeric threads, and an active-compression hollow screw that generates compressive stresses on the surrounding bone, were also evaluated. A dimensionless set of stress transfer parameters (STPs) were utilised for ranking the performances of the different screws according to the expected screw-bone load sharing and its evolution with adaptation of the surrounding tissue. The results indicated that commercial wide (6 mm thread diameter) trapezoidal and rectangular screw profiles have superior biomechanical compatibility with bone (i.e. predicted to be stable after 2 years). The graded-stiffness and active-compression screws provided the best biomechanical performances: bone loading around them was predicted to decrease by no more than 15% after 3 years, compared with a decrease of 55-70% in bone loading around commercially available screws. Computer simulations of bone adaptation around orthopaedic screws are demonstrated to be effective means for objective and quantitative evaluation of the biomechanical aspects of implant-tissue compatibility.

Bone Resorption↗

[Clinical pathways in psychiatry and psychotherapy].

BACKGROUND: Implementing evidence-based clinical guidelines by means of clinical pathways is one of the key elements of continuous quality management at the University Hospital of Marburg. This paper explains how clinical pathways for suicidal ideation and suicide attempts were developed. METHODS: Based upon a review of existing guidelines and literature, optimal standards of care were defined. Step-by-step analysis of the process of care and results of a questionnaire were used to describe the actual processes. A problem-orientated comparison of the actual and the optimal process of care was the basis for developing these pathways. A consensus was achieved with all persons involved in the respective process of care taking into consideration local resources as well as barriers. The most important decisions and interventions were defined and presented as a patient-oriented process. RESULTS: The lack of explicit "how to do it"-recommendations of the guidelines for the entire care processes required specific, locally tailored adaptations. Potentials for improvement were identified in the following areas: transfer of patients, consultation, information and coordination within the team, and diagnosis of suicide risk. The pathways include care-oriented algorithms, checklists and assignments of responsibility. CONCLUSIONS: The development of clinical pathways as part of quality management and transsectoral integrated care in psychiatry and psychotherapy is feasible. The concept presented incorporates the potential of increasing transparency, efficiency and efficacy of care, and of improving satisfaction of those involved. It offers psychiatric hospitals the chance to guarantee optimal quality of care in face of increasing workload and costs.

Critical Pathways↗

RAPD and pedigree-based genetic diversity estimates in cultivated diploid potato hybrids.

In this study, RAPD and pedigree data were used to investigate the genetic relationships in a group of 45 diploid hybrid potato clones used in the breeding and genetics program of the Agriculture and Agri-Food Canada Potato Research Centre in Fredericton, New Brunswick, and used for the potato after-cooking darkness program at the Nova Scotia Agricultural College. These hybrids were derived from crossing primitive cultivated South American diploid species such as Solanum phureja or Solanum stenotomum and wild diploid species such as Solanum chacoense and other wild Argentine species with haploids of Solanum tuberosum. These hybrids have subsequently undergone up to 30 years of breeding and selection, for adaptation to local growing and storage conditions, processing traits and pest resistances. The objectives of this study were to estimate the level of genetic similarity (GS) among these sets of clones and to investigate the correlation between RAPD-based GS and f, based on pedigree information. Genetic similarity coefficients varied from 0.29 to 0.90 with a mean of 0.65 when based on the RAPD data, whereas the coefficient of parentage varied from zero to 0.75 with a mean of 0.11. The degree of relationship between the similarity matrices based on RAPD and pedigree was measured by comparing the similarity matrices with the normalized Mantel test. A low positive correlation (R = 0.104, p = 0.999) between the two matrices was observed. Cluster analysis using GS divided the clones into many subgroups that did not correspond well with the grouping based on pedigree. The level of genetic variation present in this set of potato clones is very high. Rigorous selection pressure aimed at different breeding purposes may result in the genetic differentiation of the clones from the same origin.

DNA, Plant↗