GDNF-induced seminomatous tumours in mouse--an experimental model for human seminomas?

Glial-cell-line-derived neurotrophic factor (GDNF) is a distant member of the transforming growth factor superfamily. It binds to and activates a receptor complex consisting of GFR-alpha1 and Ret receptor tyrosine kinase. In testis, GDNF is expressed by Sertoli cells. We have shown by transgenic loss- and gain-of-function mouse models that GDNF regulates the cell fate decision of undifferentiated spermatogonia. In the GDNF +/- mice, the spermatogonia differentiate in excess leading to the depletion of germ cells. In the mice overexpressing GDNF in testes, undifferentiated spermatogonia accumulate in the tubules, no sperm is produced, and the mice are infertile. After a year, the GDNF overexpressing mice frequently (89%) develop testicular tumours, and most of them are bilateral (56%). All these tumours show the same histological pattern. They are composed of round spermatogonial/gonocytic cells with only a scant cytoplasm. The tumours are locally invasive but do not metastasise. They express germ line markers, are positive for alkaline phosphatase, and aneuploid with a triploid peak. Thus, by several histological, molecular, and histochemical characteristics, the GDNF-induced tumours mimic classical seminomas in men, but the precursor lesions are apparently different in mouse and man.     

Epidemiology and health for all

Summary World Health Organization's goal Health for All is the starting point for a most ambitious health policy ever. The paper analyzes the role of epidemiology in the Organization's work, particularly in the Health for All development. During WHO's early years, epidemiology helped to design and carry out major public health campaigns against such scourges of the humanity as yaws, tuberculosis, malaria and small pox. When the Organization during the 1960s began to emphasize the need to develop the infrastructure of health care, health services research partly replaced epidemiology as WHO's main scientific allay. After the Health for All policy was launched in 1987, epidemiology has again played a major role in establishing the scientific background of the policy. The European experiences show how the epidemiologists can help WHO to identify the most important health problems and set achievable and measurable targets for them. The paper concludes that epidemiology serves to identify problems, show ways to solve them, monitor the changes in the situation and evaluate the achievements.

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Zusammenfassung Das Ziel der Weltgesundheitsorganisation Gesundheit für alle ist Ausgangspunkt für die ehrgeizigste Gesundheitspolitik, die je definiert wurde. Der vorliegende Artikel analysiert die Rolle der Epidemiologie in der Arbeit der Organisation, insbesondere bei der Entwicklung von Gesundheit für alle. Während der frühen Jahre der WHO half die Epidemiologie bei der Planung und Ausführung der grossen Gesundheitskampagnen gegen Geisseln der Menschheit wie Frambösie, Tuberkulose, Malaria und Pocken. In den 60er Jahren begann die WHO, die Wichtigkeit der Entwicklung von Infrastrukturen für die Gesundheitsversorgung zu betonen, Gesundheitswesensforschung ersetzte in der Folge teilweise Epidemiologie als wichtigsten wissenschaftlichen Bereich der WHO. Seit 1987 aber Gesundheit für alle in Angriff genommen wurde, spielt die Epidemiologie wieder eine wichtige Rolle in der Erarbeitung des wissenschaftlichen Hintergrundes dieser Politik. Die europäische Erfahrung zeigt, wie Epidemiologen der WHO helfen können, die wichtigsten Gesundheitsprobleme zu erkennen und erreichbare und messbare Ziele für sie zu setzen. Der vorliegende Artikel schliesst, dass die Epidemiologie dazu dient, Gesundheitsprobleme zu identifizieren, Wege aufzuzeigen, wie sie zu lösen sind, Änderungen der Situation zu überwachen und die Erfolge zu evaluieren.

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Résumé Pour l'OMS (Organisation mondiale de la santé), le programme «Santé pour tous» doit être le point de départ d'une action de santé sans précédent. Cet article analyse le rôle de l'épidémiologie à l'OMS, en particulier dans le cadre de ce programme. Au début de l'existence de l'OMS l'épidémiologie a permis de planifier et de conduire les grandes campagnes contre des maladies telles que la tuberculose, la malaria et la variole. Dans les années 60, l'OMS a insisté sur le développement de l'infrastructure des soins, la recherche sur les services de santé remplaçant en partie le rôle conducteur de l'épidémiologie. Avec le lancement du programme «Santé pour tous» en 1987, l'épidémiologie joue à nouveau un rôle central pour fonder le programme scientifique de l'OMS. L'expérience européenne montre de quelle façon les épidémiologistes peuvent aider l'OMS pour identifier les problèmes les plus importants et établir des buts raisonnables et mesurables. L'article montre comment l'épidémiologie sert à identifier les problèmes, établir des façons de les résoudre et évaluer l'impact de ces programmes.

     

Prevalence of restless legs symptoms according to depressive symptoms and depression type: a cross-sectional study

Background: Restless legs syndrome is a sensorimotor disorder and it is associated with several other diseases especially mental illnesses.

Aims: To analyze the relationship between the symptoms of restless legs syndrome and the severity of depressive symptoms and the prevalence of restless legs symptoms in depression subtypes.

Methods: A cross-sectional study of primary care patients in the Central Finland Hospital District. The prevalence of restless legs symptoms was studied in 706 patients with increased depressive symptoms and 426 controls without a psychiatric diagnosis by using a structured questionnaire. The depressive symptoms were evaluated with the Beck Depression Inventory (BDI) and the psychiatric diagnosis was confirmed by means of a diagnostic interview (Mini-International Neuropsychiatric Interview). The subjects with increased depressive symptoms were divided into three groups (subjects with depressive symptoms without a depression diagnosis, melancholic depression and non-melancholic depression).

Results: In the whole study population, the prevalence of restless legs symptoms increased with the severity of depressive symptoms. The prevalence of restless legs symptoms was highest in the melancholic and non-melancholic depressive patients (52 and 46%, respectively) and then in subjects with depressive symptoms without a depression diagnosis (43.4%), but the prevalence was also substantial (24.6%) in subjects without a psychiatric diagnosis.

Conclusions: Restless legs symptoms are very common in primary care among subjects with depression, regardless of the depression type. The prevalence of restless legs symptoms increased with increasing severity of depressive symptoms, regardless of the diagnosis. These findings should be considered in clinical evaluation and treatment of patients visiting their physician due to restless legs or depressive symptoms.     

Use of prescription drugs in athletes

Although athletes are young and generally healthy, they use a variety of non-doping classified medicines to treat injuries, cure illnesses and obtain a competitive edge. Athletes and sports medicine physicians try to optimize the treatment of symptoms related to extreme training during an elite athlete's active career. According to several studies, the use of antiasthmatic medication is more frequent among elite athletes than in the general population. The type of training and the kind of sport influence the prevalence of asthma. Asthma is most common among those competing in endurance events, such as cycling, swimming, cross-country skiing and long-distance running. Recent studies show that athletes use also NSAIDs and oral antibacterials more commonly than age-matched controls, especially athletes competing in speed and power sports. Inappropriately high doses and concomitant use of several different NSAIDs has been observed. All medicines have adverse effects that may have deleterious effects on elite athletes' performance. Thus, any unnecessary medication use should be minimized in elite athletes. Inhaled beta(2)-agonists may cause tachycardia and muscle tremor, which are especially harmful in events requiring accuracy and a steady hand. In experimental animal models of acute injury, especially selective cyclo-oxygenase-2 inhibitors have been shown to be detrimental to tissue-level repair. They have been shown to impair mechanical strength return following acute injury to bone, ligament and tendon. This may have clinical implications for future injury susceptibility. However, it should be noted that the current animal studies have limited translation to the clinical setting. Adverse effects related to the CNS and gastrointestinal adverse reactions are commonly reported in connection with NSAID use also in elite athletes. In addition to the potential for adverse effects, recent studies have shown that NSAID use may negatively regulate muscle growth by inhibiting protein synthesis. Physicians and pharmacists taking care of athletes' medication need to be aware of the medicines that an athlete is taking and how those medicines interact with performance, exercise, environment and other medicines. Sport associations should repeatedly monitor not only the use of banned substances, but also the trends of use of legal medicines in athletes. Not only physicians and pharmacists, but also athletes and coaches should be better educated with respect to potential benefits and risks, and how each agent may affect an athlete's performance. The attitudes and beliefs leading to ample use of legal medicines in athletes is an interesting area of future research.     

Prognostic value of various staging and grading systems in proximal colon cancer.

OBJECTIVE: To compare the ability of various methods of staging and grading to predict survival in proximal colon cancer. DESIGN: Retrospective study. SETTING: University hospital, Finland. SUBJECTS: 153 patients with primary proximal colon cancer. MAIN OUTCOME MEASURES: Staging by four classification systems, grading by two grading systems, and survival analysis based on Kaplan-Meier survival curves. RESULTS: In all staging systems the survival curves of different stages differed significantly from each other. The modified Dukes' classification was still the best predictor of survival. Grade of tumours had no significant effect on long term survival, but short term survival was affected adversely by the presence of anaplastic tissue. Tumours with no mucin had a worse prognosis than those that produced mucin. All staging methods were superior to either of the histological grading systems tested as prognosticators. Tumour depth correlated with the operator's clinical impression of radicality of operation, and also predicted survival. CONCLUSION: The clinicopathological modified Dukes' staging system was the most powerful prognosticator in proximal colonic cancer and its use in clinical practice should continue. Even a small amount of anaplastic tissue (> or = 5%) had an adverse effect on short term survival.     

Objective scar assessment—A new method using standardized digital imaging and spectral modelling

Introduction

Quantitative assessment of scars is needed in clinical practice and in scientific studies. To date, there have been no entirely objective methods available for these purposes. We introduce a new method developed for scar assessment combining standardized digital imaging (SDI) and spectral modelling (SpM). With this method, the estimated concentration changes (ECCs) of haemoglobin and melanin in the scar can be determined quantitatively.

Patient and methods

: In the current study, 22 skin graft donor site (SGDS) wounds were treated with two alternative dressing materials, Suprathel^® and Mepilex Transfer^®, side by side on the same wound. The SGSD scars were assessed using SDI and SpM. The scars were given subjective ratings by three surgeons using the POSAS and the Vancouver Scar Scale (VSS). The correlations between the ECCs of melanin and haemoglobin and the corresponding subjective ratings were calculated as well as the Intraclass Correlation Coefficient (ICC) of the subjective ratings.

Results

There was a statistically significant correlation between the ECCs of melanin and haemoglobin and the subjective ratings. A single observer could reliably assess pigmentation with the POSAS scale (ICC = 0.75) but not vascularity (ICC = 0.51). The reliability ratings of the VSS were unacceptably low.

Conclusions

The ECC values of haemoglobin and melanin give accurate documentation of the scar status. The results also show that the subjective ratings in this study were unreliable especially when interfering pigmentation and increased vascularity were both present at the same time.     

Bone Mineral Density in the Proximal Femur and Contralateral Knee After Total Knee Arthroplasty

Osteoarthrosis (OA) is often associated with pain and disability, which are relieved after total knee arthroplasty (TKA), but the nature of bone changes associated with OA is controversial. We examined preoperative hip and contralateral knee bone mineral density (BMD) in patients requiring TKA and monitored the BMD changes postoperatively. Sixty-nine patients, scheduled to have TKA for osteoarthrotic knees, had both hips and contralateral knee BMD measured by dual-energy X-ray absorptiometry (DXA) at the time of operation (baseline) and at 1 yr after operation. X-rays of the knee joints were also taken to evaluate the severity of OA. Preoperatively, 27% and 38% of the patients had total hip BMD Z-score more than 1 SD in the operated side and contralateral hips, respectively. In all regions of interest (ROI), the mean baseline BMD of the affected side proximal femur was significantly lower than that of the contralateral side (p < 0.0005-0.019). The severity of OA was not associated with BMD. During 1-yr follow-up, the postoperative knee status and the physical activity of the patients (AKS score) improved. However, neither the hip nor the nonoperated knee BMDs increased. Knee OA is associated with significantly lower BMD values in the affected side compared with the contralateral hip, and these levels remained similar or decreased during a 1-yr follow-up. We conclude that improved mobility after TKA does not improve the effects of preoperative disuse-associated bone loss in the short term.     

The effect of intravenous dopamine and dobutamine on blood circulation during a microvascular TRAM flap operation

A study was conducted to assess the effect of intraoperatively administered inotropic agents on blood flow in the recipient and donor vessels, during breast reconstruction with a muscle sparing free TRAM flap. Twenty-one consecutive patients were randomized into 3 groups receiving either dopamine, dobutamine, or placebo. When the flap and all vessels had been fully dissected but not yet divided, the study drug was administered intravenously for 15 minutes. Hemodynamic parameters and transit-time flow of the thoracodorsal and inferior epigastric arteries were monitored.Both dobutamine and dopamine infusions resulted in significant raises in cardiac output and mean arterial pressure. However, while dobutamine resulted in a higher cardiac output (P = 0.001) and a decrease in systemic vascular resistance (P = 0.028), the increase in mean arterial pressure was greater with dopamine (P = 0.002). Only the dobutamine group showed increased blood flow, in both the thoracodorsal (P = 0.043) and the inferior epigastric (P = 0.043) arteries.If vasoactive agents are needed during microvascular anesthesia, dobutamine seems to be more advantageous than dopamine.