Risk factors for depression in later life; results of a prospective community based study (AMSTEL)

BACKGROUND: Depression in the elderly was found to be associated with a variety of risk-factors in cross sectional designs. Based on the vulnerability-stress model, etiologic pathways for depression have been suggested, with vulnerability modifying the effect of stress factors. The current prospective study tests an etiologic model for depression incidence, by assessing modifying effects of three types of vulnerability: genetic/familial vulnerability, organic vulnerability, and environmental vulnerability. METHODS: 1940 non-depressed community-living elderly were interviewed at baseline, and at follow-up three years later. Bivariate and multivariate relationships between risk factors and incident depression (GMS-AGECAT) were studied. RESULTS: Higher age, personal history of depression, death of spouse, health related factors and comorbid organic or anxiety syndrome showed significant bivariate associations with depression incidence. In multivariate analysis, the effect of stress factors on incident depression was not modified by a genetic/familial vulnerability, nor by an organic vulnerability. Effect modification by environmental factors was however evident; having a marital partner, and if unmarried having social support, significantly reduced the impact of functional disabilities on the incidence of depression. LIMITATIONS: The study consisted of two measurements with a three years interval, depressive episodes with a short duration may be under-represented. CONCLUSIONS: In the elderly, the effect of stress on incident depression is modified by environmental vulnerability. No evidence was found of effect modification by either genetic/familial or organic vulnerability. The results have implications for both recognition and treatment of late-life depression.     

Placental insufficiency decreases cell cycle activity and terminal maturation in fetal sheep cardiomyocytes

Umbilicoplacental embolization (UPE) in sheep has been used to investigate the effects of placental insufficiency on fetal development. However, its specific effects on the heart have been little studied. The aim of this study was to determine the effects of placental insufficiency, induced by UPE, on cardiomyocyte size, maturation and proliferation. Instrumented fetal sheep underwent UPE for either 10 or 20 days. Hearts were collected at 125 ± 1 days (10 day group) or 136 ± 1 days (20 day group) of gestation (term ∼145 days). Cell size, maturational state (as measured by the proportion of binucleated myocytes) and cell cycle activity (as measured by positive staining of cells for Ki-67) were determined in dissociated cardiomyocytes. UPE fetuses were hypoxaemic, but mean arterial pressures were not different from controls. UPE fetuses were lighter than control fetuses (10 days: −21%, P < 0.05; 20 days: −27%, P < 0.01) and had smaller hearts, but heart weight was appropriate for body weight. Neither lengths nor widths were different between control and UPE cardiomyocytes at either age. Ten days of UPE did not significantly alter the proportion of binucleated myocytes or cell cycle activity in either ventricle. However, 20 days of UPE reduced cell cycle activity in both ventricles by ∼70% ( P < 0.05); the proportion of binucleated myocytes was also lower in UPE fetuses at this age (left ventricle: 31.1 ± 12.0 versus 46.0 ± 6.6%, P < 0.05; right ventricle: 29.4 ± 12.3 versus 46.3 ± 5.3%, P < 0.05). It is concluded that in the absence of fetal arterial hypertension, placental insufficiency is associated with substantially depressed growth of the heart through suppressed proliferation and maturation of cardiomyocytes.     

Effect of Pyrimidine Nucleosides on Body Temperatures of Man and Rabbit in Relation to Pharmacokinetic Data

The effect of high-dose uridine on body temperatures of rabbits and man has been studied in relation to plasma concentrations of uridine and its catabolite uracil. Uridine induced fever in both rabbits and man. High-dose cytidine had no influence on body temperature in rabbits. Plasma concentrations of uridine were between 1 and 1.5 mM at 30 min after an iv bolus injection of 400 mg uridine/kg in rabbits and reached peak levels of 2 mM after a 1-hr infusion of 12 g uridine/m² in man. The plasma concentration of cytidine in rabbits was about 0.5 mM and that of uridine was 0.30 mM at 30 min after an iv bolus injection of 400 mg cytidine/kg. The mean residence time for uridine in patients and rabbits varied between 80 and 195 min. The area under the plasma concentration–time curve (AUC) for uridine in rabbits was 2.0 mmol · hr/liter, and that for cytidine was 0.6 mmol · hr/liter. A large AUC for uridine indicates a prolonged exposure of tissues to uridine, which might lead to extensive formation of degradation products. The administration of some of these catabolites, dihydrouracil (at 20–40 mg/kg), carbamyl--alanine (at 60 mg/kg), and -alanine (at 300–400 mg/kg), resulted in a significant increase in body temperature. It is concluded that the change in body temperature associated with uridine administration was not due to bacterial pyrogens but that one of the degradation products might be involved in thermoregulation.     

Longer Term Outcomes Following High Tibial Osteotomy for Osteoarthritis: A Prospective,Multi-Centre Observational Study Comparing Tomofix and OPTY-LINE Devices

PurposeAssessing surgical accuracy and patient-recorded outcome measures for patients fitted with either the OPTY-LINE intramedullary realignment system or the Tomofix plate for medial opening wedge high tibial osteotomy (HTO).Patients and methodsTwo matched case series of patients with symptomatic medial compartment osteoarthritis without other significant knee pathology. One group comprised of 19 patients receiving the Tomofix plate, whereas another comprised of 12 patients receiving the OPTY-LINE intramedullary nail. Patella-centred long leg alignment radiographs were assessed to calculate surgical accuracy in all cases. Patients completed knee injury osteoarthritis outcome scores (KOOS) and osteotomy surgery patient satisfaction questionnaires pre-operatively and at 24 months post-surgery.ResultsAbsolute surgical accuracy at 2 years post-surgery was a mean 4.2 [standard deviation 3.7] for OPTY-LINE versus 9.2 [SD 7.8] for Tomofix (p = 0.11, Mann–Whitney U test). On average, patients in either the OPTY-LINE or Tomofix cohort reported at least a minimal perceptible clinical improvement—minimum average improvement of 15—for all five KOOS themes. No significant difference in change of KOOS scores over time or patient satisfaction levels were observed between the two cohorts.ConclusionThe OPTY-LINE device for HTO performs to a similar level as the Tomofix device. Surgical accuracy data are promising for OPTY-LINE, but does not seem to readily translate into difference in patient-reported outcomes compared to Tomofix. Even longer follow-up periods, to measure survival rates, and true randomised trials on larger samples can elucidate if there is a benefit for using one device over the other.     

Major histocompatibility complex class II-restricted antigen presentation across a species barrier: conservation of restriction determinants in evolution.

The existence of at least three alleles of the HLA-DRB3 gene within the human population is evident. These alleles express DRw52 determinants and react with monoclonal antibody (mAb) 7.3.19.1. The polymorphic epitope recognized by 7.3.19.1 is not only present on human cells but is also expressed on chimpanzee (Pan troglodytes) class II-positive cells. The 7.3.19.1 determinant already existed before speciation of man and chimpanzee, and is at least 5,000,000 yr old. Two-dimensional gel electrophoresis demonstrated that the various HLA- and Patr-DRw52 molecules that are reactive with 7.3.19.1 exhibit isoelectric point differences due to primary amino acid heterogeneity, as was confirmed by sequencing data. Sequence comparison allowed us to map the binding site of mAb 7.3.19.1 to the alpha helix of the major histocompatibility complex (MHC) class II DRB1 domain surrounding the antigen-binding cleft. Despite MHC sequence variation, chimpanzee antigen-presenting cells can present antigen (purified protein derivative) to human T cell lines and vice versa. Only the HLA- and Patr-DRw52 molecules were shown to function as restriction elements for antigen presentation across this species barrier. It is concluded that these particular restriction determinants probably have been conserved in evolution. The HLA- and Patr-DRw52 molecules represent alleles displaying polymorphism that has been selected for in evolution. Such "biomutants" may thus be more useful to study the biological significance of MHC molecules than MHC variants that have been generated by in vitro mutagenesis experiments.     

Patients'' complaints and satisfaction 5 years after complete denture treatment

This study is based on an evaluation of patients' opinions of their dentures by means of a questionnaire. The patients had been provided with complete dentures at a university clinic. Of the original sample (n = 139) a test group of 92 patients remained available for the actual study 5 yr after treatment. The replies in the questionnaire were subjected to statistical processing and interpretation. Six clusters could be defined and these were introduced as "scales" representing the patients' score on a specific type of complaint. Apart from the six scales a score was achieved for each patient's overall satisfaction. The correlations between the various scales were calculated with the aid of a computer program. Finally, cross-tabulation was used to see if any significant (inter)correlations could be proved between complaints, satisfaction, and some of the patients' social data. It could be concluded that a correlation exists between complaints of pain and of functional aspects on the one hand and vague complaints on the other hand. There is also a correlation between complaints of looseness of the maxillary denture and complaints about aesthetic factors. Well-fitting and well-functioning dentures, absence of pain, and a socially acceptable appearance contribute much to the patients' satisfaction with dentures. Social variables such as type of insurance (public or private) and marital status influence denture appreciation to a certain extent.     

Epidermal growth factor receptor levels increase but epidermal growth factor receptor ligand levels decrease in mouse mammary tumors during progression from hormone dependence to hormone independence

Summary Twenty-six serially transplanted Grunder (GR) strain mouse mammary tumors were analyzed for epidermal growth factor receptor (EGFR) and EGFR-ligand levels, in addition to steroid hormone receptors (estrogen receptor, ER, progesterone receptor, PgR). In concordance with earlier studies, hormone dependent (HD) and hormone responsive (HR) tumors were found to be positive for both ER and PgR, whereas hormone independent (HI) tumors contained only 30% of the ER concentration that was found in the HD tumors. PgR was undetectable in HI tumors. HI tumors contained 2.5 to 3-fold higher EGFR levels than HD/HR tumors, an observation which shows remarkable concordance with studies on EGFR in human breast cancer. On the other hand, the level of EGFR-ligand(s) was positively associated with ER levels and was three-fold higher in HD/HR tumors than in HI tumors. The low EGFR in HD/HR tumors relative to HI tumors may be the result of downregulation by EGFR ligands produced under ER control. During progression to hormone independence this downregulation of EGFR is then abolished in absence of ER. The increase in EGFR may therefore be a secondary effect rather than a key event in the progression to hormone independence in this mouse mammary tumor model.Abbreviations EGF Epidermal Growth Factor - EGFR Epidermal Growth Factor Receptor - ER Estrogen Receptor - PgR Progesterone Receptor - HD Hormone Dependent - HR Hormone Responsive - HI Hormone Independent - HAP Hydroxylapatite - DCC Dextran Coated Charcoal - GR Grunder - TGF- Transforming Growth Factor-     

Factors Influencing the Growth in Knowledge of Trainees in General Practice

Objectives: The relation between the content of postgraduate training for general practice and the outcome in terms of the growth in knowledge of trainees was investigated. The training variables included were: (1) the number of patients seen per day, (2) the trainer, (3) the practice and (4) the theoretical curriculum.Methods: Subjects were 58 trainee-trainer pairs. Growth in knowledge was assessed by two written tests administered with eight months interval. Training variables were evaluated by means of questionnaires and logbook-registration. The correlation was explored between each of the training variables and the knowledge tests scores. To correct for interactional effects, a step-wise multiple regression analysis was performed with the second test as dependent variable and the first test as well as the training variables as independent variables.Results: Significant growth in knowledge was demonstrated. Non of all training variables investigated explained the variance in scores on the second test equally good or better than the scores on the entry test.Conclusions: The impact of the separate training-components on the growth in knowledge, remains unclear. We may speculate, that the sort of knowledge assessed with the written literature based true/false test is different from the sort of knowledge transferred during every day training: evidence based knowledge versus experience based knowledge. Equally valid is the conclusion that these findings fit into the theory that in adult learning the outcome is more learner than teacher dependent.This revised version was published online in September 2005 with corrections to the Cover Date.     

Thallium-201 single-photon emission computed tomography as an early predictor of outcome in recurrent glioma.

PURPOSE: With limited response rates and potential toxicity of chemotherapeutic treatment in patients with recurrent glioma, reliable response assessment is essential. Currently, the assessment of treatment response in glioma patients is based on the combination of radiologic and clinical findings. However, response monitoring with computed tomography (CT) or magnetic resonance imaging (MRI) is hampered by several pitfalls and is prone to interobserver variability. The aim of this study was to establish the value of thallium-201 single-photon emission computed tomography (201Tl-SPECT) as a predictor of overall survival and response to chemotherapy in recurrent glioma, and to compare the value of 201Tl-SPECT with that of CT and MRI. PATIENTS AND METHODS: We studied patients who underwent CT or MRI and 201Tl-SPECT before chemotherapy (n = 57), and patients who also had undergone CT or MRI and 201Tl-SPECT after two courses of chemotherapy (n = 44). The value of the radiologic variables (CT-MRI tumor size, 201Tl-SPECT tumor size, and maximal tumor intensity) at baseline and at follow-up in predicting overall survival, and the percentage of patients alive and progression-free at 6 months (APF6) were examined using Cox regression and logistic regression analysis. RESULTS: Both at baseline and at follow-up, 201Tl-SPECT maximal tumor intensity was the strongest predictive variable and was inversely related to overall survival and APF6. In particular, progression of maximal tumor intensity after two courses of chemotherapy was a powerful predictor of poor outcome. CONCLUSION: 201Tl-SPECT is superior to conventional CT-MRI in the early prediction of overall survival and response to chemotherapy in patients with recurrent glioma.     

''I found myself to be a down to earth Dutch girl'': a qualitative study into learning outcomes from international traineeships

OBJECTIVE: To explore learning outcomes from international traineeships for undergraduate medical students. METHODS: In-depth interviews were conducted with 24 undergraduate medical students at Maastricht University Medical School, The Netherlands. The 24 subjects were selected by purposeful sampling. RESULTS: Students reported meaningful learning outcomes in 6 domains: medical knowledge; skills; international health care organisation; international medical education; society and culture, and personal growth. DISCUSSION: International traineeships appear to provide good opportunities for students to meet the requirements of globalisation as well as some of the generic objectives of undergraduate medical education. The tentative findings of this study need to be confirmed by further studies.