[The (im?)possibility of a biological substrate for mental disorders]. / Een biologisch substraat voor psychische stoornissen: gouden toekomst of gouden bergen?

BACKGROUND: The constructivist position is often used for psychiatric diseases, in contrast with the general medical view. In the medical view a biological substrate is decisive for a classification as 'disease', which is not the case in the constructivist position.
AIM: We investigate how both positions relate to each other in psychiatric diseases.
METHOD: Analysis based on a conceptual analysis of Ian Hacking's book The Social Construction of What? (1999).
RESULTS: Different objects ought to be distinguished in a constructivist analysis of psychiatric diseases; the disease itself and the idea or concept of that disease. These different objects interact with each other. These interactions can be made explicit by distinguishing interactive kinds from indifferent kinds. Doing so makes it clear that even if a disease is not determined by a biological substrate, this does not imply that a biological substrate is something completely separate from that disease.
CONCLUSION: Hacking's philosophy makes it possible to move beyond the opposition between the medical and the constructivist account of psychiatric diseases by combining both accounts.

Short-Course Radiotherapy Followed by Neoadjuvant Bevacizumab, Capecitabine, and Oxaliplatin and Subsequent Radical Treatment in Primary Stage IV Rectal Cancer: Long-Term Results of a Phase II Study.

BACKGROUND: In a Dutch phase II trial conducted between 2006 and 2010, short-course radiotherapy followed by systemic therapy with capecitabine, oxaliplatin, and bevacizumab as neoadjuvant treatment and subsequent radical surgical treatment of primary tumor and metastatic sites was evaluated. In this study, we report the long-term results after a minimum follow-up of 6 years. METHODS: Patients with histologically confirmed rectal adenocarcinoma with potentially resectable or ablatable metastases in liver or lungs were eligible. Follow-up data were collected for all patients enrolled in the trial. Overall and recurrence-free survival were calculated using the Kaplan-Meier method. RESULTS: Follow-up data were available for all 50 patients. After a median follow-up time of 8.1 years (range 6.0-9.8), 16 patients (32.0%) were still alive and 14 (28%) were disease-free. The median overall survival was 3.8 years (range 0.5-9.4). From the 36 patients who received radical treatment, two (5.6%) had a local recurrence and 29 (80.6%) had a distant recurrence. CONCLUSIONS: Long-term survival can be achieved in patients with primary metastatic rectal cancer after neoadjuvant radio- and chemotherapy. Despite a high number of recurrences, 32% of patients were alive after a median follow-up time of 8.1 years.

Foreign body reaction triggered by cytotoxic T lymphocyte-associated protein 4 blockade 25 years after dermal filler injection.

Foreign body reactions are regularly seen as a late complication of cosmetic treatment with synthetic dermal fillers. Often this foreign body reaction is triggered by a systemic infection, but other systemic triggers are also reported. In this case report, we present a woman in her 60s who was treated with ipilimumab for metastatic melanoma. After two courses of treatment she developed painless facial nodules. A foreign body reaction to dermal fillers was suspected because the patient had received cosmetic treatment with dermal fillers 25 years previously. This reaction was confirmed by excision and histological examination. In the absence of other known triggers, this case revealed immunotherapy (ipilimumab) and subsequent activation of the adaptive immune system as potential triggers of foreign body reactions to dermal fillers. Immunotherapy is increasingly used as anticancer treatment for an increasing number of tumour types. Furthermore, synthetic dermal fillers have frequently been used in the past. Therefore, physicians should be aware of this late-occurring complication of synthetic filler treatment in patients who develop skin lesions during immunotherapy.

Consequence of restaging after neoadjuvant treatment for locally advanced rectal cancer.

BACKGROUND: Locally advanced rectal cancer is customarily treated with neoadjuvant chemoradiotherapy (CRT) followed by a total mesorectal excision. During the course of CRT, previously non-detectable distant metastases can appear. Therefore, a restaging CT scan of the chest and abdomen was performed prior to surgery. The aim of this study was to determine the frequency of a change in treatment strategy after this restaging CT scan. METHODS: Patients treated with neoadjuvant CRT for locally advanced rectal cancer between January 2003 and July 2013 were included retrospectively. To determine the value of the restaging CT scan, the surgical treatment as planned before CRT was compared with the treatment ultimately received. RESULTS: A total of 153 patients (91 male) were eligible, and median age was 62 (32-82) years. The restaging CT scan revealed the presence of distant metastases in 19 patients (12.4, 95 % confidence interval [CI] 7.0-17.8). In 17 patients (11.1, 95 % CI 6.1-16.1), a change in treatment strategy occurred due to the detection of metastases with a restaging CT scan. CONCLUSION: A restaging CT scan after completion of neoadjuvant CRT may detect newly developed metastases and consequently alter the initial treatment strategy. This study demonstrated the added value of the restaging CT scan prior to surgery.

Rational use of 18F-FDG PET/CT in patients with advanced cutaneous melanoma: A systematic review.

18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is increasingly used in patients with advanced melanoma. Immune checkpoint inhibitors and BRAF/MEK-targeted therapy have transformed the therapeutic landscape of metastatic melanoma. Consequently, a need for markers predicting (early) response to treatment and for monitoring treatment (toxicity) has arisen. This systematic review appraises the current literature evidence for rational use of 18F-FDG PET/CT scans in staging, clinical decision-making, treatment monitoring and follow-up in advanced melanoma. 18F-FDG PET/CT has high overall accuracy for detection of distant metastases and is, combined with cerebral MRI, the preferred imaging strategy for staging metastatic melanoma. In contrast, strong evidence supporting the standard use of 18F-FDG PET/CT for predicting and monitoring therapy response and toxicity is currently lacking. Essential for determining the position of 18F-FDG PET/CT during treatment course in advanced melanoma are well-designed studies with standardized scanning protocols, incorporation of clinical parameters and comparison with contrast-enhanced CT alone.

Is there a competition for oxygen availability between respiratory and limb muscles?

If a competition between the oxygen demands of limb and respiratory muscles happens, hypoxia may favor redistribution of blood flow from peripheral to respiratory muscles during heavy exercise. This hypothesis was tested in eighteen lowlanders and 27 highlanders at 4350m altitude. During an incremental exercise, the regional tissue oxygen saturation (rSO2) and tissue hemoglobin concentration ([Hbt]) of the intercostal muscles and vastus medialis were monitored simultaneously by NIRS. The intercostal and vastus medialis rSO2 values were lower at altitude than at sea level (-10%, p<0.001) and decreased similarly during incremental exercise (p<0.001) while [Hbt] values increased. At maximal exercise, the intercostal rSO2 was lower than the vastus medialis rSO2 in lowlanders (-7%, p<0.001). In highlanders the time patterns were similar but intercostal rSO2 was less decreased at exercise (p<0.05). Maximal exercise performed in hypoxia did not alter the kinetics of rSO2 and [Hbt] in peripheral muscles. These findings do not favor the hypothesis of blood flow redistribution.

Airway tone during exercise in healthy subjects: effects of salbutamol and ipratropium bromide.

In healthy subjects changes in airway calibre during exercise are conflicting and smaller than in asthmatics. Methodological differences could explain the discrepancies between the results obtained in healthy subjects. Therefore, our aim was to assess during exercise the changes in airway diameter and the effects of 200 microg salbutamol (SAL) or 40 microg ipratropium bromide (IPR) inhalations versus placebo (PLA), using spirometry and respiratory resistance (Rrs). Eight non-asthmatic subjects exercised 9 min at 70 % of their maximal aerobic power after inhalation of 200 microg SAL, 40 microg IPR, or PLA. Maximal flow-volume curves were obtained before and after inhalations, at 3 (E3) and 6 (E6) minutes of exercise, and during recovery. Rrs were measured by impulse oscillometry before and after inhalation, and immediately at the end of exercise. At rest, FEV (1) increased significantly after inhalation of SAL and IPR. Rrs decreased only after SAL. During exercise FEV (1) increased significantly from rest with SAL and IPR while forced mid expiratory flow (FEF (25 - 75)) increased significantly for all conditions. At E6 the rise of FEV (1) and FEF (25 - 75) were greater with SAL compared to PLA and IPR. In all conditions Rrs increased significantly immediately at the end of exercise as compared to rest but less than during flow-matched hyperpnea. It is concluded that a similar bronchodilation was observed during exercise with and without anticholinergic drug which suggests a withdrawal of parasympathetic control of airways during exercise in healthy subjects. Nevertheless, the bronchodilation observed during exercise is not maximal since it can be reinforced by beta (2)-mimetic drug.

Expiratory flow limitation and obstruction in the elderly.

Elderly people commonly suffer from dyspnoea, which may stem from expiratory flow limitation (EFL). The relationship between EFL, as assessed by the negative expiratory pressure method and spirometric indices, was investigated in an elderly French population. Subjects, aged 66-88 yrs, filled in socio-demographic and standardised questionnaires, which dealt with: medical history, smoking status and respiratory symptoms. EFL measurements and forced expiratory manoeuvres were performed. Validated measurements were obtained in 750 out of 1,318 subjects: 47% were EFL+ (EFL >0), with a higher prevalence in females than in males. EFL and forced expiratory volume in one second (FEV1) were correlated with age. A total of 116, from the 750 subjects, with no medical history and no symptoms, served as a healthy group. The prevalence of EFL+ subjects increased with the grade of dyspnoea and was highest in respiratory and cardiac patients when compared with the healthy subjects. EFL did not correlate with FEV1/forced vital capacity (FVC), the usual index of obstruction. Some elderly subjects (15%) with dyspnoea but with no medical history, mainly females with small FVC and normal FEV1/FVC, had a greater EFL than the healthy subjects. In elderly people, expiratory flow limitation measurements, along with the usual forced expiratory volume in one second/ forced vital capacity ratio, may be of value for the interpretation of dyspnoea.

Reduction of exercise-induced asthma in children by short, repeated warm ups.

AIM: To study the effect of a warm up schedule on exercise-induced asthma in asthmatic children to enable them to engage in asthmogenic activities. METHOD: In the first study, peak flows during and after three short, repeated warm up schedules (SRWU 1, 2, and 3), identical in form but differing in intensity, were compared in 16 asthmatic children. In the second study the efficiency of the best of these SRWU schedules was tested on 30 young asthmatic children. Children performed on different days a 7 minute run alone (EX1) or the same run after an SRWU (EX2). RESULTS: The second study showed that for most children (24/30) the fall in peak flow after EX2 was less than that after EX1. The percentage fall in peak flow after EX2 was significantly correlated with the percentage change in peak flow induced by SRWU2 (r = 0.68). The children were divided into three subgroups according to the change in peak flow after SRWU2: (G1: increase in peak flow; G2: < 15% fall in peak flow; G3: > 15% fall in peak flow). Only the children in the G3 subgroup did not show any gain in peak flow after EX2 compared with EX1. CONCLUSION: The alteration in peak flow at the end of the SRWU period was a good predictor of the occurrence of bronchoconstriction after EX2. An SRWU reduced the decrease in peak flow for most of the children (24/30) in this series, thus reducing subsequent post-exercise deep bronchoconstriction.