European survey on national training activities in clinical research.

BACKGROUND: Investigator-initiated clinical studies (IITs) are crucial to generate reliable evidence that answers questions of day-to-day clinical practice. Many challenges make IITs a complex endeavour, for example, IITs often need to be multinational in order to recruit a sufficient number of patients. Recent studies highlighted that well-trained study personnel are a major factor to conduct such complex IITs successfully. As of today, however, no overview of the European training activities, requirements and career options for clinical study personnel exists. METHODS: To fill this knowledge gap, a survey was performed in all 11 member and observer countries of the European Clinical Research Infrastructure Network (ECRIN), using a standardised questionnaire. Three rounds of data collection were performed to maximize completeness and comparability of the received answers. The survey aimed to describe the landscape of academic training opportunities, to facilitate the exchange of expertise and experience among countries and to identify new fields of action. RESULTS: The survey found that training for Good Clinical Practice (GCP) and investigator training is offered in all but one country. A specific training for study nurses or study coordinators is also either provided or planned in ten out of eleven countries. A majority of countries train in monitoring and clinical pharmacovigilance and offer specific training for principal investigators but only few countries also train operators of clinical research organisations (CRO) or provide training for methodology and quality management systems (QMS). Minimal requirements for study-specific functions cover GCP in ten countries. Only three countries issued no requirements or recommendations regarding the continuous training of study personnel. Yet, only four countries developed a national strategy for training in clinical research and the career options for clinical researchers are still limited in the majority of countries. CONCLUSIONS: There is a substantial and impressive investment in training and education of clinical research in the individual ECRIN countries. But so far, a systematic approach for (top-down) strategic and overarching considerations and cross-network exchange is missing. Exchange of available curricula and sets of core competencies between countries could be a starting point for improving the situation.

Resistance band training or general exercise in multidisciplinary rehabilitation of low back pain? A randomized trial.

Multidisciplinary biopsychosocial rehabilitation has been recommended for chronic low back pain (LBP), including physical exercise. However, which exercise modality that is most advantageous in multidisciplinary biopsychosocial rehabilitation is unclear. In this study, we investigated whether multidisciplinary biopsychosocial rehabilitation could be more effective in reducing pain-related disability when general physical exercise was replaced by strength training in the form of progressive resistance training using elastic resistance bands. In this single-blinded (researchers), randomized controlled trial, 99 consenting adults with moderate-to-severe non-specific LBP were randomized to three weeks of multidisciplinary biopsychosocial rehabilitation with either general physical exercise or progressive resistance band training and were then instructed to continue with their respective home-based programs for nine additional weeks, in which three booster sessions were offered. The primary outcome was between-group difference in change on the Oswestry Disability Index (ODI) at 12 weeks. Due to early dropouts, data from 74 participants (mean age: 45 years, 57% women, mean ODI: 30.4) were obtained at baseline, 61 participants were followed-up at 3 weeks, and 46 at 12 weeks. There was no difference in the change in ODI score between groups at 12 weeks (mean difference 1.9, 95% CI: -3.6, 7.4, P = .49). Likewise, the change in secondary outcomes did not differ between groups, except for the patient-specific functional scale (0-10), which favored general physical exercise (mean difference 1.4, 95% CI: 0.1, 2.7, P = .033). In conclusion, this study does not support that progressive resistance band training compared to general physical exercise improve outcomes in multidisciplinary biopsychosocial rehabilitation for patients with non-specific LBP.

Combined aerobic and resistance training improves physical capacity in women treated for gynecological cancer.

PURPOSE: The purpose of this study was to evaluate the effects of 16 weeks combined aerobic and resistance training, twice a week, on the physical performance in women treated for gynecological cancer. METHODS: Sixty women (56.9 ± 13.3 years) who had completed curative treatment for gynecological cancer were divided into two groups: a physical training group (PT) (n = 29) or a control group (C) (n = 31). The PT group performed two sessions of combined aerobic and resistance training weekly for 16 weeks. Peak oxygen consumption (V̇O2peak) and one repetition maximum (1RM) of leg press, leg extension, and chest press were measured before group assignment, after 16 weeks and at the 1-year follow-up. RESULTS: A significant increase in V̇O2peak (ml min-1 kg-1) (29.7 ± 8.0 vs. 31.3 ± 8.3, p = .009), leg press (kg) (113.0 ± 27.3 vs. 116.7 ± 29.2, p = .047), leg extension (kg) (44.2 ± 10.1 vs. 48.0 ± 10.6, p < .001), and chest press (kg) (24.5 ± 7.5 vs. 26.9 ± 8.2, p = .001) was seen in the PT group from pre- to post-measurement. The PT group maintained the improved aerobic condition and muscle strength 1 year after the training intervention. In the C group, there were no significant differences between pre- and post-measurements, but a significant decrease (28.2 ± 7.5 vs. 27.0 ± 7.3, p = .040) in the V̇O2peak from post to 1-year follow-up measurements. CONCLUSIONS: Combined aerobic and resistance training twice a week in 16 weeks improves V̇O2peak and maximal strength in women treated for gynecological cancer. The training effects were sustained after 1 year in the PT group.

Differences and similarities between mothers and fathers of premature children: a qualitative study of parents' coping experiences in a neonatal intensive care unit.

BACKGROUND: The aim of this study was to explore and describe the coping experiences of parents to children admitted to a neonatal unit. METHODS: A qualitative research approach was chosen, using in-depth interviews with eight fathers and eight mothers. RESULTS: The main findings were that parents with previous complicated births had more difficulties in coping compared to those parents with no experience with complications. Coping seemed easier where parents' opinions were heard regarding their baby's care and when both parents were present in the neonatal intensive care unit (NICU). The main similarities between mothers and fathers were the reluctance to speak their opinions on childcare, and both experienced a sense of alienation and problems in bonding with the baby. They also needed a limitation on the number of visitors in the NICU. Differences between mothers and fathers were that fathers tried hard to be the strong partner in the relationship, and were more concerned with the mother if she was seriously ill postpartum, while mothers were more concerned for their baby. Mothers' postpartum period was felt as more stressful if the father was not present, but mothers were also better at welcoming support from the health personnel. CONCLUSION: This study highlights the parent's coping experiences in NICUs. Coping seemed easier where parents' opinions were heard. Nurses in the NICU should take the former experiences of the parents into consideration when nursing in the NICU and planning for discharge.

Structural brain changes after 4 wk of unilateral strength training of the lower limb.

Strength training enhances muscular strength and neural drive, but the underlying neuronal mechanisms remain unclear. This study used magnetic resonance imaging (MRI) to identify possible changes in corticospinal tract (CST) microstructure, cortical activation, and subcortical structure volumes following unilateral strength training of the plantar flexors. Mechanisms underlying cross-education of strength in the untrained leg were also investigated. Young, healthy adult volunteers were assigned to training (n = 12) or control (n = 9) groups. The 4 wk of training consisted of 16 sessions of 36 unilateral isometric plantar flexions. Maximum voluntary isometric contraction torque was tested pre- and posttraining. MRI investigation included a T1-weighted scan, diffusion tensor imaging and functional MRI. Probabilistic fiber tracking of the CST was performed on the diffusion tensor imaging images using a two-regions-of-interest approach. Fractional anisotropy and mean diffusivity were calculated for the left and right CST in each individual before and after training. Standard functional MRI analyses and volumetric analyses of subcortical structures were also performed. Maximum voluntary isometric contraction significantly increased in both the trained and untrained legs of the training group, but not the control group. A significant decrease in mean diffusivity was found in the left CST following strength training of the right leg. No significant changes were detected in the right CST. No significant changes in cortical activation were observed following training. A significant reduction in left putamen volume was found after training. This study provides the first evidence for strength training-related changes in white matter and putamen in the healthy adult brain.

Clinical differences between immigrants voluntarily and involuntarily admitted to acute psychiatric units: a 3-year prospective study.

Involuntary psychiatric admissions are widespread among patients with an immigrant background. According to a study in Norway, involuntary admissions are about 75% of admissions among immigrants compared to roughly 50% among ethnic Norwegians. The aim of the present study was to compare clinical and demographic characteristics of immigrant patients with involuntary or voluntary admissions to two acute psychiatric units. A 3-year prospective study of 94 immigrant patients involuntarily and voluntarily admitted to acute psychiatric units was carried out. Sixty-two patients (66.0%) were voluntarily and 30 (31.9%) involuntarily admitted. Involuntary admissions were significantly higher among men (22, 73.3%) compared to women (8, 26.7%; χ(2) = 4.507, d.f. = 1, P= 0.03). The mean length of stay for voluntary and involuntary patients were 7.8 (SD = 6.6) and 21.6 (SD = 27.3; t=-2.7, d.f. = 88, P= 0.01). Patients diagnosed with schizophrenia and psychotic disorder were more often admitted involuntarily (63.0%; χ(2) = 17.83, P= 0.001). This study confirms that immigrant patients diagnosed with psychotic disorders are more often involuntarily than voluntarily admitted. Comparing the clinical and demographic characteristics of immigrants helps identify the reasons behind involuntary admissions and might improve efforts towards reducing such admissions in the future.

Side effects of flux enhancing chemicals in membrane bioreactors (MBRs): study on their biological toxicity and their residual fouling propensity.

Soluble and colloidal materials like soluble microbial products (SMP) or extracellular polymeric substances (EPS) are considered to be major foulants in membrane bioreactors (MBRs). Removing these fouling causing substances is thus thought to reduce the fouling of the membrane in general. In addition to traditional strategies for fouling prevention which mostly try to remedy the effects of fouling by air scour, etc., the new and promising method of adding chemicals is being investigated here. Previous tests with 30 different substances have shown that several of these reduce SMP concentration in the supernatant and enhance filtration. Nevertheless, additive dosing might have unknown side effects in filtration systems. Results presented in this study indicate that these additives may themselves cause severe fouling on different membranes if they remain unbound in the liquid phase. Therefore, the thorough control of the dosing rate of these chemicals will be of paramount importance in full scale applications. Biological toxicity of additives was measured in terms of respiration. OUR tests did not show inhibiting effects for most additives. Chitosan even showed an enhanced OUR due to biodegradability. Oxygen transfer could be enhanced for 25% with the addition of a polymer.

Continuous measurement and control of fouling active compounds in membrane bioreactor systems.

For a more effective fouling reduction in membrane bioreactors (MBR) the approach of continuous measurement and control of protein and polysaccharide concentrations is followed. So called extra-cellular polymer substances (EPS) can be partially measured by a newly developed protein sensor based on sequential injection analysis. The sensor is validated by real MBR pilot data, stating the feasibility of the technique for continuous monitoring. Parallel to EPS, other fouling active compounds such as organic bio-polymer were determined in two parallel MBR pilot lines by size exclusion chromatography, proving desired comparable conditions in both lines for later parallel testing. The daily variation of EPS in MBR operation are moderate, where protein changes tend to react more pronounced to operational changes than polysaccharides. This was also the case for the organic bio-polymer fraction, especially in manipulated bench experiments at abruptly changing redox conditions.

Low-level laser therapy can reduce lipopolysaccharide-induced contractile force dysfunction and TNF-alpha levels in rat diaphragm muscle.

Our objective was to investigate if low-level laser therapy (LLLT) could improve respiratory function and inhibit tumor necrosis factor (TNF-alpha) release into the diaphragm muscle of rats after an intravenous injection of lipopolysaccharide (LPS) (5 mg/kg). We randomly divided Wistar rats in a control group without LPS injection, and LPS groups receiving either (a) no therapy, (b) four sessions in 24 h with diode Ga-AsI-Al laser of 650 nm and a total dose of 5.2 J/cm2, or (c) an intravenous injection (1.25 mg/kg) of the TNF-alpha inhibitor chlorpromazine (CPZ). LPS injection reduced maximal force by electrical stimulation of diaphragm muscle from 24.15+/-0.87 N in controls, but the addition of LLLT partly inhibited this reduction (LPS only: 15.01+/-1.1 N vs LPS+LLLT: 18.84+/-0.73 N, P<0.05). In addition, this dose of LLLT and CPZ significantly (P<0.05 and P<0.01, respectively) reduced TNF-alpha concentrations in diaphragm muscle when compared to the untreated control group.

High-dose, short-term, anti-inflammatory treatment with dexamethasone reduces growth and augments the effects of 5-fluorouracil on dimethyl-alpha-benzanthracene-induced mammary tumors in rats.

OBJECTIVE: To evaluate the effects of dexamethasone (DXM) alone or in combination with 5-fluorouracil (5-FU) on dimethyl-alpha-benzanthracene (DMBA)-induced mammary tumors in rats. MATERIAL AND METHODS: Female Sprague-Dawley rats were divided into 4 groups receiving: 1) saline (controls), 2) DXM (3 mg/kg), 3) 5-FU (1.5 mg/kg) and 4) DXM and 5-FU combined. The drugs were given i.p. every day for 4 days. Interstitial fluid pressure (Pif) and tumor growth were determined in all tumors on days 1, 5 and 7 using the "wick-in-the needle" technique and by external size measurements, respectively. Vessel density and inflammatory cell infiltration of tumor tissue were analyzed by immunohistochemistry. RESULTS: DXM treatment significantly retarded tumor growth and reduced Pif. Treatment with a combination of DXM and 5-FU reduced tumor size significantly more than any of the agents alone (p<0.01-0.001). Enhanced uptake of 5-FU by DXM treatment was demonstrated by microdialysis. There were no differences in the density of CD31-positive vessels after DXM or 5-FU treatment, but inflammatory cell infiltration of tumor tissue was significantly reduced after DXM treatment. CONCLUSIONS: Our data suggest that DXM may be beneficial as an adjuvant to chemotherapy in the treatment of mammary cancer by increasing the uptake of 5-FU in the tumor.

Low level laser therapy partially restores trachea muscle relaxation response in rats with tumor necrosis factor alpha-mediated smooth airway muscle dysfunction.

BACKGROUND AND OBJECTIVE: It is unknown if the decreased ability to relax airway smooth muscles in asthma and other inflammatory airways disorders can be influenced by low level laser therapy (LLLT) irradiation. To investigate if LLLT could reduce impairment in inflamed trachea smooth muscles (TSM) in rats. STUDY DESIGN/MATERIALS AND METHODS: Controlled rat study where trachea was dissected and mounted in an organ bath apparatus with or without a TNF-alpha solution. RESULTS: Low level laser therapy administered perpendicularly to a point in the middle of the dissected trachea with a wavelength of 655 nm and a dose of 2.6 J/cm(2), partially restored TSM relaxation response to isoproterenol. Tension reduction was 47.0 % (+/-2.85) in the laser-irradiated group compared to 22.0% (+/-2.21) in the control group (P < 0.01). Accumulation of cAMP was almost normalized after LLLT at 22.3 pmol/mg (+/-2.1) compared to 17.6 pmol/mg (+/-2.1) in the non-irradiated control group (P < 0.01). CONCLUSION: Low level laser therapy partially restores the normal relaxation response in inflamed TSM and normalizes accumulation of cAMP in the presence of isoproterenol.

Effects of a psychiatric intensive care unit in an acute psychiatric department.

Psychiatric acute units use different levels of segregation to satisfy needs for containment and decrease in sensory input for behaviourally disturbed patients. Controlled studies evaluating the effects of the procedure are lacking. The aim of the present study was to compare effects in acutely admitted patients with the use of a psychiatric intensive care unit (PICU) and not in a psychiatric acute department. In a naturalistic study, one group of consecutively referred patients had access only to the PICU, the other group to the whole acute unit. Data were obtained for 56 and 62 patients using several scales. There were significant differences in reduction of behaviour associated with imminent, threatening incidents (Broset Violence Checklist), and actual number of such incidents (Staff Observation Aggression Scale-Revised) in favour of the group that was treated in a PICU. The principles of patient segregation in PICUs have favourable effects on behaviours associated with and the actual numbers of violent and threatening incidents.

Low-level laser therapy induces dose-dependent reduction of TNFalpha levels in acute inflammation.

OBJECTIVE: The aim of this study was to investigate if low-level laser therapy (LLLT) can modulate acute inflammation and tumor necrosis factor (TNFalpha) levels. BACKGROUND DATA: Drug therapy with TNFalpha-inhibitors has become standard treatment for rheumatoid arthritis, but it is unknown if LLLT can reduce or modulate TNFalpha levels in inflammatory disorders. METHODS: Two controlled animal studies were undertaken, with 35 male Wistar rats randomly divided into five groups each. Rabbit antiserum to ovalbumin was instilled intrabronchially in one of the lobes, followed by the intravenous injection of 10 mg of ovalbumin in 0.5 mL to induce acute lung injury. The first study served to define the time profile of TNFalpha activity for the first 4 h, while the second study compared three different LLLT doses to a control group and a chlorpromazine group at a timepoint where TNFalpha activity was increased. The rats in LLLT groups were irradiated within 5 min at the site of injury by a 650-nm Ga-Al-As laser. RESULTS: There was a time-lag before TNFalpha activity increased after BSA injection. TNFalpha levels increased from < or =6.9 (95% confidence interval [CI], 5.6-8.2) units/mL in the first 3 h to 62.1 (95% CI, 60.8-63.4) units/mL (p < 0.001) at 4 h. An LLLT dose of 0.11 Joules administered with a power density of 31.3 mW/cm(2) in 42 sec significantly reduced TNFalpha level to 50.2 (95% CI, 49.4-51.0), p < 0.01 units/mL versus control. Chlorpromazine reduced TNFalpha level to 45.3 (95% CI, 44.0-46.6) units/mL, p < 0.001 versus control. CONCLUSION: LLLT can reduce TNFalpha expression after acute immunocomplex lung injury in rats, but LLLT dose appears to be critical for reducing TNFalpha release.

A randomised, placebo controlled trial of low level laser therapy for activated Achilles tendinitis with microdialysis measurement of peritendinous prostaglandin E2 concentrations.

BACKGROUND: Low level laser therapy (LLLT) has gained increasing popularity in the management of tendinopathy and arthritis. Results from in vitro and in vivo studies have suggested that inflammatory modulation is one of several possible biological mechanisms of LLLT action. OBJECTIVE: To investigate in situ if LLLT has an anti-inflammatory effect on activated tendinitis of the human Achilles tendon. SUBJECTS: Seven patients with bilateral Achilles tendinitis (14 tendons) who had aggravated symptoms produced by pain inducing activity immediately before the study. METHOD: Infrared (904 nm wavelength) LLLT (5.4 J per point, power density 20 mW/cm2) and placebo LLLT (0 J) were administered to both Achilles tendons in random blinded order. RESULTS: Ultrasonography Doppler measurements at baseline showed minor inflammation through increased intratendinous blood flow in all 14 tendons and measurable resistive index in eight tendons of 0.91 (95% confidence interval 0.87 to 0.95). Prostaglandin E2 concentrations were significantly reduced 75, 90, and 105 minutes after active LLLT compared with concentrations before treatment (p = 0.026) and after placebo LLLT (p = 0.009). Pressure pain threshold had increased significantly (p = 0.012) after active LLLT compared with placebo LLLT: the mean difference in the change between the groups was 0.40 kg/cm2 (95% confidence interval 0.10 to 0.70). CONCLUSION: LLLT at a dose of 5.4 J per point can reduce inflammation and pain in activated Achilles tendinitis. LLLT may therefore have potential in the management of diseases with an inflammatory component.

Changes in plasma protein extravasation in rat skin during inflammatory challenges evaluated by microdialysis.

Docetaxel and prostaglandin E1 (PGE1) increase transcapillary albumin extravasation and reduce interstitial fluid pressure in the skin. In this study the microdialysate concentration (Cm) of 125I-labeled human serum albumin (125I-HSA) and different-sized endogenous plasma proteins (EPP) was compared to evaluate changes in transcapillary extravasation of plasma proteins. 125I-HSA was also used to estimate changes in the specific activity of albumin. Extravasation of 125I-HSA and EPP from plasma to interstitium in the rat skin was compared during continuous administration of docetaxel and PGE1 by using microdialysis in anesthetized rats. Also, 20 ml of Ringer solution (RS) were injected intravenously during 10 min in a separate group. Two hollow plasmapheresis fibers (3 cm, cut off 3,000 kDa), one acting as control, were placed subcutaneously on the back skin and perfused with RS (5 microl/min, 140 min, collected every 10 min). The size of the different EPP was estimated to be 73, 65, 56, 47, and 39 A, separated by a size-exclusion high-performance liquid chromatography column and quantified by UV detection (280 nm). Docetaxel (0.5 mg/ml, n = 5) increased Cm of 125I-HSA and EPP of sizes 73, 65, 56, and 39 A significantly (P < 0.05) compared with control. PGE1 (20 microg/ml, n = 6) increased Cm of 125I-HSA significantly (P < 0.05) but none of the different-sized EPP was increased compared with control. Intravenous RS (20 ml, n = 6) increased Cm of 125I-HSA and increased all the different-sized EPP significantly (P < 0.05) compared with control. Although the microdialysis method is able to monitor qualitative changes in capillary permeability, a quantitative determination of the capillary reflection coefficient or permeability-surface area product was not possible, because steady state between plasma and dialysate was not achieved during the measurement period. The different pattern of extravasation of EPP and 125I-HSA after docetaxel, PGE1, and RS indicates increased interstitial transport rate and/or increased capillary permeability after docetaxel and RS, whereas PGE1 seems to increase transcapillary fluid flux without altering the permeability.

Platelet activating factor (PAF) increases plasma protein extravasation and induces lowering of interstitial fluid pressure (P) in rat skin.

AIM: To investigate the ability of the microdialysis technique to measure capillary selectivity of different sized plasma proteins induced by local administration of platelet activating factor (PAF). METHODS: We used hollow plasmapheresis fibres with 3 cm membrane (cut off 3000 kDa) placed on the back of anaesthetized rats. RESULTS: Platelet activating factor (50 microg mL(-1)) administered locally via the fibre, increased extravasation of radiolabelled 125I-HSA from plasma to the microdialysis fibre by approximately 900% compared both to baseline and the control fibre within 70 min (n = 6, P < 0.05). The extravasation in the control fibre did not change over time. HPLC measurement of plasma proteins in the microdialysis perfusate also demonstrated decreased capillary selectivity for proteins in the diameter range of 73 A, 56 A and 39 A after local administration of PAF (n = 6, P < 0.05). PAF also significantly lowered interstitial fluid (P(if)) pressure after subcutaneous administration (50 microg mL(-1)). Mean arterial pressure (MAP) after intravenous injection of PAF (0.4 microg kg(-1)) fell instantly by about 50 mmHg, and stabilized at 50 mmHg after 15 min (n = 6). MAP was unaltered when PAF was given through the microdialysis fibre (n = 4). Both total tissue water (TTW) and extravasation of albumin, measured as the plasma-to-tissue clearance (E-alb) showed a significant increase after PAF (n = 7, P < 0.05). CONCLUSIONS: The present study demonstrates that PAF induces plasma protein extravasation and decrease capillary selectivity of different sized plasma proteins. It also increases transcapillary fluid flux, and lowers P(if), indicating a role for PAF in the interstitium for generation of transcapillary transport of water and large molecules followed by formation of oedema.

Continuous measurements of plasma protein extravasation with microdialysis after various inflammatory challenges in rat and mouse skin.

This study describes the use of microdialysis technique for continuous measurement of plasma protein extravasation (PPE) in rat and mouse skin with drug application either intravenously or via the microdialysis fiber. Hollow plasmapheresis fibers (3-cm length, 0.4-mm diameter, cutoff 3,000 kDa) were placed subcutaneously on the back of anesthetized mice and rats. Intravenous injection of dextran (Macrodex, 60 mg/ml) increased PPE by 355% from baseline within 30 min in rats with ligated kidneys (n = 6; P < 0.05) but not in animals with intact kidneys. Phalloidin (500 microg/kg iv 40 min before dextran, n = 6; P < 0.05) did not change the response to dextran in either group. Animals receiving PGE1, compound 48/80 (mice), paclitaxel, docetaxel, and cremophor EL via the microdialysis fiber were also provided with a control fiber receiving vehicle. Both rats and mice had constant PPE in the control fiber, and there was no change in PPE in the NaCl-treated groups (rats, n = 4; mice, n = 6). Application via the fiber of PGE1 (20 microg/ml), compound 48/80 (mice; 4 mg/ml), and docetaxel (0.5 mg/ml) increased PPE compared with baseline within 60 min by 139% (n = 6; P < 0.05), 273% (n = 6; P < 0.05), and 325% (n = 5; P < 0.05), respectively. Phalloidin alone did not increase PPE (n = 5; P < 0.05). Pretreatment with phalloidin did not inhibit the increase after PGE1 or compound 48/80 but inhibited that after docetaxel (n = 6). Paclitaxel (0.6 mg/ml, n = 5) or vehicle (Cremophor) (n = 5) gave no increase in PPE. The results demonstrate that microdialysis can be used to continuously measure changes in PPE after inflammatory challenges in skin of rats and mice.

PGE1 induced transcapillary transport of 51Cr-EDTA in rat skin measured by microdialysis.

Interstitial fluid pressure (P(if)) is a key determinant in increasing the transcapillary driving pressure, pulling fluid from the microcirculation into the interstitial space at the onset of acute inflammatory reactions and the oedema formation associated with these. Prostaglandin E1 (PGE1) induces lowering of P(if) in rat skin which increases transcapillary transport of 51Cr-EDTA into the center of a tumor as measured by microdialysis. The aim of this study was twofold: First, to evaluate and develop the microdialysis technique thoroughly with regard to its suitability for investigating transcapillary water transport in rat skin using 51Cr-EDTA as a tracer. Secondly, to evaluate the effect of PGE1 on transcapillary transport of 51Cr-EDTA. This study demonstrates that PGE1 increases transcapillary transport of 51Cr-EDTA into skin interstitium. There were no significant differences between the experimental probe and the control probe when calculations from the entire experiment (90 min) were compared. On the other hand, significant differences were observed by examining the experiment in smaller time intervals. PGE1 increased transcapillary transport of 51Cr-EDTA during the first 15 min when administered through the microdialysis probe. This observation suggests that increased blood flow and/or permeability-surface area product are responsible for raising the transcapillary transport of 51Cr-EDTA, i.e. the transport is diffusion limited. Administration of PGE1 through the probe rather than around the probe resulted in less scatter between experiments than when PGE1 was injected subcutaneously around the probe.

[Diagnostic activity in general practice. 3. Diagnosis of breast diseases]. / Diagnostisk aktivitet i almen praksis. 3. Mammadiagnostisk aktivitet.

A random sample of 483 women from five practices representing a basic population of 4,867 women over the age of 35 years was selected in order to assess the examination activity for cancer of the breast. The examination activity in practice decreased with increasing age simultaneously with increase in the incidence of cancer of the breast. The possibility for a 93% total screening per five years is present but does not appear to be practically feasible. All of the positive findings occur in women seeking advice on account of symptoms. Instruction in self-examination will probably result in an increased number of referrals for this reason. Among the possibilities for teaching self-examination and regular control, women receiving hormonal contraception and women receiving substitution therapy at the menopause are suggested as possible clienteles. In both of these cases, annual examination of the breast should be performed in advance.

[Diagnostic activity in general practice. 2. Frequency of examination of urinary glucose and blood pressure determination among patients in general practice]. / Diagnostisk aktivitet i almen praksis. 2. Hyppigheden af urinundersøgelse for glukose og blodtryksmåling blandt praktiserende laegers patienter.

In order to estimate how frequently examinations of urine for glucosuria and blood pressure measurements are performed in the primary health care sector to detect common incapacitating diseases such as diabetes and hypertension, the authors carried out a study in five general practices in Denmark for a period of five years. The study was retrospective because it is not possible to study one's own behaviour prospectively. Nearly 1,000 persons aged 30 years or more were involved. 9% of the group had no contact with the health care sector during the period. In 49%, the urine had been tested at least once for glucose; 58% where women were concerned but only 40% of the men. Men under the age of 55 years were significantly underrepresented. Examination of the urine was only undertaken in 51% of the persons aged 55-74 years. Twelve new cases of diabetes were discovered, nine of these were diagnosed in general practice. Hypertension had been diagnosed in 52 patients before the registration period. 60% of the remainder had blood pressure measurements on at least one occasion during the period. Men under 55 years were significantly underrepresented (42%). Sixty-four new cases of hypertension were discovered, 59 of these in general practice. Screening for common diseases such as these is primarily performed by general practitioner. Several other works from general practice where no special efforts were made to systematize screening for diabetes or hypertension did not reveal any better results. It is estimated that 25% of diabetic patients and 50% of hypertensive patients remain undiagnosed. The present rather random screening for these diseases is insufficient.(ABSTRACT TRUNCATED AT 250 WORDS)