Seasonal Reactivity: Attentional Bias and Psychophysiological Arousal in Seasonal and Nonseasonal Depression

Individuals diagnosed with seasonal depression (MDD-SAD), nonseasonal depression (MDD), and controls completed a modified Stroop task and viewed winter and summer content scenes while skin conductance levels were recorded. Participants in the MDD-SAD and MDD groups took longer than controls to color name dark and depressive content words; however, individuals in the MDD group took longer than controls to color name all words. In reaction to winter scenes, individuals in the MDD-SAD group exhibited a greater frequency of significant skin conductance responses and greater amplitude of skin conductance responses than individuals in the MDD and control groups. These results add to a growing literature on seasonal reactivity which suggests that there may be specific features that distinguish seasonal and nonseasonal depression. Portions of this article were presented at the annual meeting of the Association for the Advancement of Behavior Therapy, Reno, Nevada, November 2002.     

A rapid and inexpensive method for anticipating severe toxicity to fluorouracil and fluorouracil-based chemotherapy

Dihydropyrimidine dehydrogenase (DPD) deficiency leads to dramatic overexposure to fluorouracil (5-FU), resulting in a potentially lethal outcome in patients treated with standard doses. The aim of this study was to validate, in a routine clinical setting, a simple and rapid method to determine the DPD status in a subset of cancer patients, all presenting with life-threatening toxicities following 5-FU or capecitabine intake. In this study, 80 out of 615 patients (13%) suffered severe toxicities, including 5 lethal ones (0.8%), during or after chemotherapy with a fluoropyrimidine drug. Patients with severe toxicities were treated with 5-FU (76 patients) or capecitabine-containing protocols (4 patients). Simplified uracil to di-hydrouracil (U/UH2) ratio determination in plasma was retrospectively performed in these 80 patients, as a surrogate marker of DPD activity. When possible, 5-FU Css determination was performed, and screenings for the canonical IVS14+1G>A mutation were systematically carried out. Comparison of the U/UH2 ratios with a reference, non-toxic population, showed abnormal values suggesting impaired DPD activity in 57 out of the 80 toxic patients (71%) included in this study, and in 4 out of 5 patients (80%) with a fatal outcome. Similarly, drug exposures up to 15 times higher than the range observed in the non-toxic population were also observed. Importantly, no IVS14+1G>A mutation was found in these patients, including those displaying the most severe or lethal toxicities. These data warrant systematic detection of DPD-deficient patients prior to fluoropyrimidine administration, including when oral capecitabine (Xeloda) is scheduled. Finally, the simplified methodology presented here proved to be a low cost and rapid way to identify routinely patients at risk of toxicity with 5-FU or capecitabine.     

Diagnostically Usable Skin Lesions in Candida Septicaemia Diagnostisch verwertbare Hautverinderungen bei Candida-Septikämie

We present three patients with hematological malignancies, all neutropenic and febrile despite broadspectrum antibiotics. They all developed a sparse rash with purpuric maculopapules with a violaceous hue centrally. These skin lesions were associated with systemic Candida infections and responded well to antifungal treatment. They appeared to be a short-cut to the diagnosis of systemic Candida infections for both the hematologist and the dermatologist.     

Sleep and metabolic function

Evidence for the role of sleep on metabolic and endocrine function has been reported more than four decades ago. In the past 30 years, the prevalence of obesity and diabetes has greatly increased in industrialized countries, and self-imposed sleep curtailment, now very common, is starting to be recognized as a contributing factor, alongside with increased caloric intake and decreased physical activity. Furthermore, obstructive sleep apnea, a chronic condition characterized by recurrent upper airway obstruction leading to intermittent hypoxemia and sleep fragmentation, has also become highly prevalent as a consequence of the epidemic of obesity and has been shown to contribute, in a vicious circle, to the metabolic disturbances observed in obese patients. In this article, we summarize the current data supporting the role of sleep in the regulation of glucose homeostasis and the hormones involved in the regulation of appetite. We also review the results of the epidemiologic and laboratory studies that investigated the impact of sleep duration and quality on the risk of developing diabetes and obesity, as well as the mechanisms underlying this increased risk. Finally, we discuss how obstructive sleep apnea affects glucose metabolism and the beneficial impact of its treatment, the continuous positive airway pressure. In conclusion, the data available in the literature highlight the importance of getting enough good sleep for metabolic health.     

Lack of benefit of 3‐month intensification with enfuvirtide plus optimized background regimen (OBR) versus OBR alone in patients with multiple therapeutic failures: The INNOVE study

The objective of the present study was to evaluate the virological efficacy of a 3‐month short‐course intensification with enfuvirtide (ENF) associated with an optimized background regimen (OBR) in treatment‐experienced patients infected with HIV‐1 with multiple therapeutic failures. This was a prospective, randomized, open‐label multicenter trial including patients infected with HIV‐1 and harboring a multi‐resistant virus that was still susceptible to at least 2 active compounds. Patients were randomized (1:1) to receive OBR + ENF or OBR alone. ENF was discontinued at Week 12. The primary endpoint was the proportion of patients with plasma viral load <50 copies/ml at Week 24. Fifteen patients were randomized into the OBR group and 14 into the OBR + ENF group with a median viral load of 4.1 log₁₀ copies/ml and a median CD4+ cell count of 346 cells/mm³. The primary endpoint was achieved in 93% (14/15) and 79% (11/14) of patients, respectively. Eighty‐seven percent (13/15) of patients had a viral load <50 copies/ml as soon as Week 12 in the OBR group and 79% (11/14) in the OBR + ENF group. At Week 12, the median CD4+ cell count was 327 in the OBR and 437 in the OBR + ENF groups and at Week 24 they were comparable. Intensification with ENF had no significant impact on PBMCs HIV‐DNA levels. A 3‐month short‐course intensified treatment with ENF did not improve Week‐24 virological response in treatment‐experienced patients infected with HIV‐1 harboring resistant viruses that were still susceptible to two antiretroviral drugs. J. Med. Virol. 84:1710–1718, 2012. © 2012 Wiley Periodicals, Inc.     

Activity-related dyspnea is not modified by psychological status in people with COPD, interstitial lung disease or obesity

Sensory (physiological) and affective (psychological) dimensions of dyspnea have been described but the usefulness of measuring psychological status in addition to ventilatory capacity (spirometry, lung volumes) in the assessment of exertional dyspnea remains controversial. We hypothesized that activity-related dyspnea would not be modified by psychological status. Principal component analysis (PCA) was used to reduce the number of parameters (psychological or functional) to fewer independent dimensions in 328 patients with altered ventilatory capacity: severe obesity (BMI ≥ 35, n = 122), COPD (n = 128) or interstitial lung disease (n = 78). PCA demonstrated that psychological status (Hospital Anxiety-Depression, Fatigue Impact scales) and dyspnea (Medical Research Council [MRC] scale) were independent dimensions. Ventilatory capacity was described by three main dimensions by PCA related to airways, volumes, and their combination (specific airway resistance, FEV(1)/FVC), which were weakly correlated with dyspnea. In conclusion, in patients with COPD, interstitial lung disease or severe obesity, psychological status does not modify activity-related dyspnea rating as evaluated by the MRC scale.     

Dismal prognostic value of monosomal karyotype in elderly patients with acute myeloid leukemia: a GOELAMS study of 186 patients with unfavorable cytogenetic abnormalities

The prognosis of acute myeloid leukemia (AML) is very poor in elderly patients, especially in those classically defined as having unfavorable cytogenetics. The recent monosomal karyotype (MK) entity, defined as 2 or more autosomal monosomies or combination of 1 monosomy with structural abnormalities, has been reported to be associated with a worse outcome than the traditional complex karyotype (CK). In this retrospective study of 186 AML patients older than 60 years, the prognostic influence of MK was used to further stratify elderly patients with unfavorable cytogenetics. CK was observed in 129 patients (69%), and 110 exhibited abnormalities according to the definition of MK (59%). MK(+) patients had a complete response rate significantly lower than MK(-) patients: 37% vs 64% (P = .0008), and their 2-year overall survival was also decreased at 7% vs 22% (P < .0001). In multivariate analysis, MK appeared as the major independent prognostic factor related to complete remission achievement (odds ratio = 2.3; 95% confidence interval, 1-5.4, P = .05) and survival (hazard ratio = 1.7; 95% confidence interval, 1.1-2.5, P = .008). In the subgroup of 129 CK(+) patients, survival was dramatically decreased for MK(+) patients (8% vs 28% at P = .03). These results demonstrate that MK is a major independent factor of very poor prognosis in elderly AML.