NXF1 and CRM1 nuclear export pathways orchestrate nuclear export, translation and packaging of murine leukaemia retrovirus unspliced RNA.

Cellular mRNAs are exported from the nucleus as fully spliced RNAs. Proofreading mechanisms eliminate unprocessed and irregular pre-mRNAs to control the quality of gene expression. Retroviruses need to export partially spliced and unspliced full-length RNAs to the cytoplasm where they serve as templates for protein synthesis and/or as encapsidated RNA in progeny viruses. Genetically complex retroviruses such as HIV-1 use Rev-equivalent proteins to export intron-retaining RNA from the nucleus using the cellular CRM1-driven nuclear export machinery. By contrast, genetically simpler retroviruses such as murine leukaemia virus (MLV) recruit the NXF1 RNA export machinery. In this study, we reveal for the first time that MLV hijacks both NXF1 and CRM1-dependent pathways to achieve optimal replication capacity. The CRM1-pathway marks the MLV full-length RNA (FL RNA) for packaging, while NXF1-driven nuclear export is coupled to translation. Thus, the cytoplasmic function of the viral RNA is determined early in the nucleus. Depending on the nature of ribonucleoprotein complex formed on FL RNA cargo in the nucleus, the FL RNA will be addressed to the translation machinery sites or to the virus-assembly sites at the plasma membrane.

Mutations in a new gene encoding a protein of the hair bundle cause non-syndromic deafness at the DFNB16 locus.

Hearing impairment affects about 1 in 1,000 children at birth. Approximately 70 loci implicated in non-syndromic forms of deafness have been reported in humans and 24 causative genes have been identified (see also http://www.uia.ac.be/dnalab/hhh). We report a mouse transcript, isolated by a candidate deafness gene approach, that is expressed almost exclusively in the inner ear. Genomic analysis shows that the human ortholog STRC (so called owing to the name we have given its protein-stereocilin), which is located on chromosome 15q15, contains 29 exons encompassing approximately 19 kb. STRC is tandemly duplicated, with the coding sequence of the second copy interrupted by a stop codon in exon 20. We have identified two frameshift mutations and a large deletion in the copy containing 29 coding exons in two families affected by autosomal recessive non-syndromal sensorineural deafness linked to the DFNB16 locus. Stereocilin is made up of 1,809 amino acids, and contains a putative signal petide and several hydrophobic segments. Using immunohistolabeling, we demonstrate that, in the mouse inner ear, stereocilin is expressed only in the sensory hair cells and is associated with the stereocilia, the stiff microvilli forming the structure for mechanoreception of sound stimulation.

Use of self-expandable metal stents for the treatment of esophageal perforations and anastomotic leaks.

BACKGROUND: Esophageal perforations and extensive anastomotic leaks after esophageal resection or gastrectomy are surgical emergencies with high mortality rates. In recent years, the use of self-expanding metallic stents (SEMS) has emerged as a promising treatment alternative for bridging and sealing the damage. This study aimed to evaluate the role of covered SEMS for the management of esophageal perforations and anastomotic leaks. METHODS: All esophageal stent placement procedures (174 procedures for 157 patients) at the authors' unit between January 1999 and April 2008 were assessed by a retrospective chart review. Of the 157 patients, 10 (6.4%) were treated with SEMS for sealing of an iatrogenic esophageal perforation (n = 4), a spontaneous esophageal rupture in Boerhaave's syndrome (n = 4), or an anastomotic leakage (n = 2). RESULTS: The median time from perforation or anastomotic leak to stent insertion was 13 days (range, 2 h to 48 days). The esophageal leak was totally sealed for 8 (80%) of 10 patients. The overall mortality rate was 50% (n = 5), and three (30%) of the five deaths were related to the perforation (n = 2) or leakage (n = 1). In both of the perforation cases, the diagnosis and treatment were substantially delayed. One patient with an anastomotic leak after gastrectomy died of the complication despite successful operative and SEMS treatment. Two of the deaths were unrelated to the perforation. In both cases, the cause of death was a disseminated malignant disease. CONCLUSIONS: Traumatic perforations and anastomotic leaks can be treated effectively with covered SEMS together with adequate drainage of the thoracic cavity even in cases of severely ill patients with inveterate esophageal perforations and leaks.

Severe and fatal complications after ERCP: analysis of 2555 procedures in a single experienced center.

BACKGROUND AND STUDY AIMS: The majority of recent large series on endoscopic retrograde cholangiopancreatography (ERCP) complications have been multicenter studies reflecting varying degrees of experience and ERCP volume; major ERCP complications are associated with low case volume. The aim of this study was to report and analyze the frequency of severe and fatal complications associated with ERCP at a single specialized surgical high-volume referral center (Turku University Central Hospital). METHODS: All scheduled ERCP procedures (n = 2788) at our unit between January 1997 and December 2005 were included and the procedure-related severe and fatal complications were assessed by retrospective chart review. Complications were classified as severe or fatal according to standardized guidelines. RESULTS: The number of ERCP procedures performed was 2555, of which 71% were therapeutic and 29% were diagnostic. Seventeen (0.8%) severe complications were identified in 16 patients, of whom 15 underwent a therapeutic endoscopic procedure. Of the 17 severe complications, perforation constituted five cases (0.2%), pancreatitis occurred in five patients (0.2%), bleeding in five cases (0.2%), and two patients suffered from purulent cholangitis (0.1%). Procedure-related mortality was 0.08% (n = 3). CONCLUSIONS: In our study the rate of severe or fatal complications of ERCP is low in experienced hands at a high-volume center, comparing favorably to corresponding complication rates of multicenter series, which further supports the importance of centralizing ERCP procedures in high-volume advanced centers.

Surgeons' experience with laparoscopic fundoplication after the early personal experience: does it have an impact on the outcome?

BACKGROUND: The adverse outcomes of laparoscopic fundoplication are more likely during the initial 20 cases performed by each individual surgeon. This study aimed to evaluate the impact of substantial surgical experience versus experience beyond the learning curve on the early and late objective and subjective results. METHODS: The patients were divided into two groups according to the surgeon. In group 1 (n = 230), all the patients underwent surgery by a surgeon with substantial experience in laparoscopic fundoplication. In group 2 (n = 118), the patients were treated by a total of seven surgeons whose personal experience exceeded the individual learning curve, but was distinctively less than that of the group 1 surgeon. RESULTS: The conversion rate was 2.2% in group 1 and 4.4% in group 2. The median operating time was 65 min in group 1 and 70 min in group 2 (p = 0.0020). The occurrence of immediate complications was 3.5% in group 1 and 7.6% in group 2 (p = 0.0892). At 6 months after surgery, 7.4% of the patients in group 1 and 16.1% of the patients in group 2 reported that dysphagia disturbed their daily lives (p = 0.0115). The late subjective results, including postoperative symptoms and evaluation of the surgical result, were similar in the two groups. CONCLUSIONS: Substantial experience with the procedure is associated with a shorter operating time and somewhat fewer complications, conversions, and early dysphagia episodes. This supports the provision of expert supervision even after the initial learning phase of 20 individual procedures. The patients' long-term subjective symptomatic outcome was similar in the two groups. Substantial experience does not provide better late results than surgical experience beyond the learning curve.

Needle-knife assisted ERCP.

BACKGROUND: During endoscopic retrograde cholangiopancreatography (ERCP), incising through the wall of the major papilla with an electrocautery needle-knife is a method for achieving access into the bile duct. This procedure, often referred to as a "precut," may be used when cannulation attempts via the orifice of the papilla are unsuccessful. Potential complications include hemorrhage, duodenal perforation, and acute pancreatitis. METHODS: The 172 patients who underwent an attempt of a needle-knife assisted ERCP during the years 1997-2003 at our institution were retrospectively evaluated. RESULTS: A selective bile duct cannulation was achieved after needle-knife incision in 148 out of 172 patients (86%) at the primary session. In 10 additional patients (6%), a repeated procedure proved successful for cannulation. In the remaining 14 patients (8%), the biliary cannulation failed and was not attempted again. Complications after needle-knife assisted ERCP occurred as follows: three patients (2%) presented with late bleeding after the ERCP and three patients (2%) developed acute pancreatitis. None of the patients required operative treatment for complications. There was no mortality. CONCLUSION: The use of the needle-knife markedly improves the success rate of selective biliary cannulation in ERCP without increasing the rate of complications.

Serum adhesion molecules and interleukin-2 receptor as markers of tumour load and prognosis in advanced cutaneous melanoma.

Cell adhesion molecules are cell surface glycoproteins that may act as mediators in the metastatic process. Soluble interleukin-2 receptor (sIL-2R) is an immunological marker that may also serve as an indicator of tumour progression. Normal and neoplastic cells are capable of releasing these molecules into circulation. We evaluated the association between pretreatment serum levels of soluble intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule 1 (sVCAM-1) and sIL-2R and metastases and survival in 50 patients with advanced melanoma. The patients with liver and/or bone metastases had significantly higher sICAM-1 levels than those with soft tissue and/or lung involvement (P=0.002). In addition, there was a trend towards higher sIL-2R levels in patients with more metastatic sites (P=0.07). In univariate analysis, the number of metastatic sites (P=0.0001, odds ratio (OR) 3.0, 95% confidence interval (CI): 1.7-5.3), the metastatic site (P=0.01, OR 2.3, 95% CI: 1.2-4.4) and the levels of sICAM-1 (P=0.011, OR 2.5, 95% CI: 1.2-5.0), sVCAM-1 (P=0.036, OR 2.1, 95% CI: 1.0-4.3) and sIL-2R (P=0.0016, OR 3.0, 95% CI: 1.5-6.0) were found to be statistically significant prognostic factors for survival. In multivariate analysis, the number of metastatic sites was the dominant prognostic indicator. After it was excluded from the analysis, the sIL-2R level and the metastatic site were found to be significant. It can be concluded, that high sICAM-1 levels suggest liver metastases and sIL-2R seems to serve as a marker of tumour load in metastatic melanoma. Furthermore, the sIL-2R level appears to add to clinical data predicting the patient's outcome.

Antiphospholipid and antinuclear antibodies in patients with epilepsy or new-onset seizure disorders.

PURPOSE: The increased prevalence of autoantibodies in patients with epilepsy has been traditionally regarded to be a consequence of antiepileptic drugs. The purpose of this study was to measure autoantibodies in well-defined groups of patients with seizures to determine the effects of epilepsy and antiepileptic medications on the presence of autoantibodies. PATIENTS AND METHODS: We studied the frequency of antinuclear antibodies, anti-beta2-glycoprotein I antibodies, and anticardiolipin antibodies in 50 patients with therapy-resistant localization-related epilepsy, 50 patients with generalized epilepsy syndromes, 52 patients with a newly diagnosed seizure disorder but no antiepileptic medication, and 83 healthy controls. RESULTS: Compared with controls, newly diagnosed patients had a significantly greater prevalence of immunoglobulin (Ig) G class anticardiolipin antibodies (21% versus 7%); the prevalence was 14% in patients with localization-related epilepsy and 8% in patients with generalized epilepsy. The prevalence of IgM class anticardiolipin antibodies was significantly greater in all seizure groups (60% in localization-related epilepsy, 42% in generalized epilepsies, and 33% in newly diagnosed patients) compared with controls (7%). Antinuclear antibodies were significantly more common in newly diagnosed patients (21%) and localization-related epilepsy (24%) compared with controls (12%). When patients with generalized epilepsy (8%) were used as the reference group, antinuclear antibodies were also significantly more frequent in localization-related epilepsy (relative risk [RR] = 2.9, 95% confidence interval [CI]: 1.1 to 8.2) and newly diagnosed seizures (RR = 3.4, 95% CI: 1.2 to 9.3). There were no consistent associations between autoantibodies and specific antiepileptic medications. CONCLUSIONS: The prevalence of autoantibodies is greater in patients with epilepsy, including newly diagnosed seizure disorder. The increased prevalence of autoantibodies is more strongly associated with epilepsy than with antiepileptic drugs, perhaps indicating that immune dysregulation may be commonly associated with epilepsy.

Towards automatic detection of point mutations: use of scintillating microplates in solid-phase minisequencing.

Simplification of molecular genetic techniques is one of the main features of large-scale clinical applications of mutation analysis. The solid-phase minisequencing method, which is based on single-nucleotide primer extension by a DNA polymerase on a solid support, is an easy way of detecting point mutations of previously known locations. Here the procedure was further simplified by the use of microplates made of scintillating plastics, a microplate format scintillation counter and an automatic microplate washer. DNA samples from patients with either a hereditary aspartylglucosaminidase (AGA) gene point mutation or an acquired N-ras gene mutation were analyzed by three different minisequencing detection procedures utilizing tritiated nucleotides. The new counting method with scintillating plates was compared to traditional liquid scintillation counting in scintillation vials or to another microplate format procedure, which requires addition of scintillation liquid. In all three methods, normal individuals, heterozygous carriers of the AGA mutation and homozygous patients could be unequivocally discriminated. The N-ras mutation in leukemic blasts could also be detected with high resolution. The coefficients of variation and reproducibility of the scintillating microplate method were almost identical to those of the traditional liquid scintillation assay, which was used as a reference method. The technical innovations adopted here for performing minisequencing assays reduce significantly the labor required without affecting the quality of the results.

Cardioprotective effect of adenosine pretreatment in coronary artery bypass grafting.

OBJECTIVE: There are several reports of the use of adenosine as a cardioprotective agent during cardiac surgery. Adenosine treatment might affect neutrophils and inflammatory mediators. The present prospective randomized study was designed to investigate the effect of adenosine pretreatment on myocardial recovery and inflammatory response in patients undergoing elective coronary artery bypass surgery. DESIGN: A prospective, randomized, controlled study. SETTING: Operative unit and ICU in a university hospital in Finland. PATIENTS: Thirty male patients undergoing primary, elective coronary revascularization. INTERVENTIONS: Patients in the adenosine group received a 7-min infusion of adenosine (total, 650 microg/kg) before the initiation of cardiopulmonary bypass. MEASUREMENTS: Postoperative creatine kinase (CK)-MB release and hemodynamics were recorded. Perioperative leukocyte and cytokine release were measured. RESULTS: Adenosine pretreatment resulted in less CK-MB release and an improved postbypass cardiac index. Similar leukocyte counts and cytokine responses were seen in both groups perioperatively. Neutrophil counts were similar between the groups before and after myocardial ischemia when measured simultaneously in arterial and coronary sinus blood. CONCLUSIONS: The present results support the hypothesis that adenosine pretreatment is cardioprotective in humans, but the present dose failed to regulate the inflammatory responses after coronary artery bypass grafting.

Thyroid antibodies in association with thyroid malignancy. I. Simultaneous occurrence of thyroiditis and thyroid malignancy.

Occurrence of thyroid antibodies and thyroiditis in association with thyroid malignancy, suspected malignancy or other thyroid diseases was studied in 177 patients. Retrospective clinical analysis revealed that 137 patients had thyroid carcinoma (108 papillary carcinomas, 10 occult papillary carcinomas, 14 follicular carcinomas, and 5 other carcinomas) and 40 had other thyroid diseases. Thyroid microsomal (AMC) and thyroglobulin antibodies (ATG) were measured by the particle agglutination method. Clinically significant thyroid antibody titers and histological or clinical features of thyroiditis were seen in nine patients with thyroid carcinoma, being equally prevalent in follicular and papillary carcinomas. Taking into account the prevalence of positive AMC antibodies and thyroid carcinoma in Finland, the highest predicted prevalence of simultaneously occurring thyroid carcinoma and thyroiditis in the under 40 age group should be 0.002% and in the over 40 age group 0.006%. In the present material the observed occurrences in corresponding age groups were unexpectedly high (4.7% and 5.2%). The results may partly be due to patient selection, but they also suggest that there might be a link between thyroiditis and thyroid carcinoma.

Evaluation of the new Behring Nephelometer in the measurement of M proteins.

The Behring Nephelometer is a new automatic analyzer designed for the measurement of specific proteins. The authors evaluated the nephelometer in the determination of M proteins as compared with immunodiffusion and cellulose acetate electrophoresis. In addition, the effects of sample dilution and antigen excess on the nephelometric measurement of M proteins were studied in 24 patient samples containing a single monoclonal IgG, IgA, or IgM M component. Immunodiffusion cannot be recommended for the determination of M proteins. Nephelometry and protein electrophoresis gave similar results with few exceptions. Sera with immunoglobulin monomer-oligomer pairs involve difficulties in serum electrophoresis. In certain cases, special care must be taken to adjust the nephelometric measurement of the M protein to the most accurate part of the calibration curve. All in all, the new Behring Nephelometer proved precise and reliable in M protein determination without risk of antigen excess.

Opsonising immunoglobulins and mannan-binding lectin in chronic lymphocytic leukemia.

We investigated the influence of plasma concentrations of immunoglobulin G (IgG), IgA, IgM, IgG subclasses and mannan-binding lectin (MBL) on susceptibility to infection in patients with chronic lymphocytic leukemia (CLL). Of 28 patients with CLL, increased susceptibility to infection was recorded in nine. Four of them (44%) had hypogammaglobulinemia as opposed to only one (5%) of the 19 patients without increased susceptibility to infection (OR 14.4; 95% CI, 1.6-130). When the effect of IgG subclasses contributing to hypogammaglobulinemia was studied, only the decreased concentrations of IgG4 and IgG2 were associated with increased susceptibility to infection. They, in turn, were intercorrelated and also highly correlated with the concentration of IgA. In fact, when these parameters were studied by a multivariable model, only the decreased concentration of IgA was shown as an independent risk factor for infection (P = 0.03). The mean concentration of MBL was significantly higher in patients with infections than in those without (6.54 mg/l and 2.75 mg/l, respectively; P = 0.001). The monitoring of its concentrations might be useful in the follow-up of infectious morbidity in CLL.

Cholecystokinin in the early course of acute post-ERCP pancreatitis.

BACKGROUND: A high dose of cholecystokinin (CCK) agonist cerulein can induce acute pancreatitis in animals. The role of CCK in the induction of acute pancreatitis in humans is unclear. We investigated basal plasma CCK levels before and after induction of post-ERCP pancreatitis to determine CCK levels in the early course of the disease. STUDY DESIGN: We determined plasma CCK concentrations in four groups of patients who underwent ERCP: (1) post-ERCP pancreatitis patients (n = 23); (2) patients with post-ERCP hyperamylasemia without pancreatitis (n = 5); (3) patients with post-ERCP abdominal pain without hyperamylasemia (n = 18); and (4) patients with an uneventful post-ERCP period (n = 43). Plasma samples were taken before ERCP, 4 to 8 hours, 10 to 16 hours, and 24 hours after ERCP. Plasma CCK concentrations were determined by a specific and sensitive radioimmunoassay using CCK antiserum (Euro-Diagnostica, Malmö, Sweden). RESULTS: Plasma CCK levels increased five-fold early in the course in post-ERCP pancreatitis patients, but not in post-ERCP hyperamylasemia patients or in uncomplicated ERCP patients, where CCK levels temporarily decreased after ERCP. In patients with abdominal pain, CCK levels did not change. After the early increase, plasma CCK levels declined to almost unmeasurable levels one day after the onset of symptoms in post-ERCP pancreatitis. In other groups CCK levels were close to the pre-ERCP level. CONCLUSIONS: It remains to be shown whether CCK is important in the pathogenesis of post-ERCP pancreatitis or merely a secondary phenomenon. There is a rationale to test CCK antagonists in preventing post-ERCP pancreatitis.

Lipid peroxidation is increased in paraoxonase L55 homozygotes compared with M-allele carriers.

Human serum paraoxonase (PON) is an antioxidative enzyme, which circulates on high-density lipoproteins and appears to use oxidized phospholipids as physiological substrates. PON M/L55 substitution changes the ability of PON to prevent lipid oxidation. Urinary 8-iso-PGF(2alpha) (one of F2 -isoprostanes) may represent a non-invasive in vivo index of free radical generation and we propose that PON might influence the biosynthesis of 8-iso-PGF(2alpha) in the vasculature. We studied the urinary excretion of 8-iso-PGF(2alpha) and related it to PON M/L55 genotypes in patients with type 2 diabetes mellitus (n = 55) and non-diabetic control subjects (n = 55). Urinary 8-iso-PGF(2alpha) was determined by competitive ELISA and the PON genotype by a PCR based restriction enzyme digestion method. LL homozygotes were compared to M-allele carriers (ML heterozygotes and MM homozygotes). The urinary excretion of 8-iso-PGF(2alpha) among non-diabetic non-smoking LL homozygotes was 3995.5 +/- 3352.8 ng/24-hour and among M-allele carriers 1689.8 +/- 1051.3 ng/24-hour (p = 0.017, ANCOVA; gender, hypertension, total cholesterol, triglycerides and LDL cholesterol as covariates). The excretion of 8-iso-PGF(2alpha), was increased in type 2 diabetes mellitus compared to non-diabetic control subjects. PON may thus protect against oxidative stress by destroying some biologically active lipids. Excretion of 8-iso-PGF(2alpha) is increased in type 2 diabetes, which may reflect oxidant injury.

Normal CSF neuron-specific enolase and S-100 protein levels in patients with recent non-complicated tonic-clonic seizures.

PURPOSE: Increased concentrations of the nervous-system-specific proteins neuron-specific enolase (NSE) and S-100 protein (S-100) have been measured with lesions in the CNS. Elevated levels of serum NSE (s-NSE) have been found in status epilepticus, but also after single epileptic seizures. Because larger studies addressing cerebrospinal fluid (CSF) levels of NSE or S-100 have not been performed, we measured CSF NSE and S-100 after tonic-clonic seizures to search for evidence of neuronal and glial damage. METHODS: 22 consecutive patients with single, previously undiagnosed and untreated tonic-clonic seizures were studied. Serum and CSF samples were collected within 24 h after seizure. 18 serum and CSF samples were measured from a control group. RESULTS: The mean CSF NSE was 8.9 ng/ml (range 0-28 ng/ml) and s-NSE 8.2 ng/ml (range 5-15 ng/ml) in the patient group. The mean concentrations in the control group were 13.1 ng/ml (range 3-24 ng/ml) and 8.0 ng/ml (range 5-12 ng/ml) respectively. The mean CSF S-100 was 3.17 microg/l (range 1.45-7.02 microg/l) and serum S-100 0.05 microg/l (range 0-0.32 microg/l), and in controls 3.19 microg/l (range 1.52-5.13 microg/l) and 0.08 microg/l (range 0-0.28 microg/l). CONCLUSION: There were no significant differences between the mean concentrations of NSE or S-100 in CSF and serum between the epileptic group and controls. These results do not confirm the previous observation of elevated NSE-levels after tonic-clonic seizures, which argues against neuronal or glial damage after uncomplicated tonic-clonic seizures in unmedicated patients.

The value of serum S-100beta and interleukins as tumour markers in advanced melanoma.

Recently serum S-100beta has shown promise as a tumour marker in melanoma; however, its use as a prognostic marker in the advanced stage needs to be confirmed. Interleukins (ILs) may mediate regression or progression of cancer. In order to study their relation to the metastatic profile and survival, we evaluated the association between pretreatment serum levels of S-100beta, IL-6, IL-10 and IL-12 and metastatic site and survival in 50 patients with advanced melanoma who were to receive chemoimmunotherapy. Patients with liver and/or bone metastases had significantly higher median concentrations of S-100beta, IL-6 and IL-10 than those with only skin, nodal and/or lung involvement. The differences in IL-12 levels were unremarkable. Using univariate analysis, the S-100beta level and metastatic profile were found to be statistically significant prognostic factors for survival. Using multivariate analysis the S-100beta level was the most powerful prognostic indicator, while the metastatic profile was found to be significant after exclusion of S-100beta. The findings suggest that elevated serum levels of S-100beta, IL-6 and IL-10 reflect concurrent liver or bone metastases in melanoma. S-100beta is also an independent prognostic marker. Pretreatment IL levels were not associated with outcome.

Visualization of fluid-bed granulation with self-organizing maps.

The degree of the instrumentation of pharmaceutical unit operations has increased. This instrumentation provides information of the state of the process and can be used for both process control and research. However, on-line process data is usually multidimensional, and is difficult to study with traditional trends and scatter plots. The Self-Organizing Map (SOM) is a recognized tool for dimension reduction and process state monitoring. The basics of the SOM and the application to on-line data collected from a fluid-bed granulation process are presented. As a batch process, granulation traversed through a number of process states, which was visualized with SOM as a two-dimensional map. In addition, it is demonstrated how the differences between granulation batches can be studied. The results suggest that SOM together with new in-line process analytical solutions support the in-process control of the pharmaceutical unit operations. Further, a novel research tool for understanding the phenomena during processing is achieved.

Self-determination in nursing students: an empirical investigation.

The purpose of this descriptive study was to examine nursing students' perceptions of student self-determination in a Finnish health-care institute and to find out whether background data were in any way associated with these perceptions. To do this we developed a 56-item Students Self-Determination Questionnaire (SSDQ), which was completed by 435 nursing students. The results showed that self-determination is important for nursing students and that they are willing to exercise self-determination in their training. In practice, however, the students were not very active in this respect, nor did they feel that they were getting very much support from teaching staff. The meaning of self-determination increased with age and with increasing experience.