On pulmonary rehabilitation and the flight of the bumblebee: the ATS/ERS Statement on Pulmonary Rehabilitation.
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Europe↗
Biomedical subjects
E Wouters
Publications and source records attributed to E Wouters.
Variant t(2;11)(p11;q13) associated with the IgK-CCND1 rearrangement is a recurrent translocation in leukemic small-cell B-non-Hodgkin lymphoma.
Classical t(11;14)(q13;q32) involving IGH-CCND1 is typically associated with aggressive CD5-positive mantle cell lymphoma (MCL). Recently, we identified the IGK variant of this translocation, t(2;11)(p11;q13), in three patients with a leukemic small-cell B-non-Hodgkin lymphoma. In all cases, rearrangements of the IGK and CCND1 genes were demonstrated by fluorescence in situ hybridization. Moreover, we mapped the 11q13 breakpoint of this variant translocation in the 3' region of CCND1 which contrasts with the 5' breakpoints in a standard t(11;14)(q13;q32). Expression of cyclin D1 was shown in two cases analyzed either at diagnosis or during disease progression. All three patients were asymptomatic at presentation and no initial therapy was required. One patient died of a progressive disease 58 months from diagnosis, and two patients showed stable disease after 12 months of follow-up. In two analyzed cases, mutated IGVH genes were identified. Our findings indicate that variant t(2;11)(p11;q13) does not typify a classical MCL but possibly a more indolent leukemic lymphoma originating from an antigen experienced (mutated) B cell.
Adult↗
Sustained, clonal karyotype abnormalities in the Philadelphia chromosome negative cells of CML patients successfully treated with Imatinib.
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Adult↗
Early clinical investigation of Viozan (sibenadet HCl), a novel D2 dopamine receptor, beta2-adrenoceptor agonist for the treatment of chronic obstructive pulmonary disease symptoms.
Viozan, (Sibenadet HCl, AR-C68397AA) is a dual D2 dopamine receptor, beta2-adrenoceptor agonist that combines bronchodilator activity with the sensory afferent modulating effects associated with D2-receptor agonism. Investigation in animal models of key chronic obstructive pulmonary disease (COPD) symptoms has demonstrated that sibenadet effectively inhibits sensory nerve activity, thereby reducing reflex cough, mucus production and tachypnoea. The results of the early clinical evaluation of this novel agent are reported. An initial proof of concept study (Study 1) aimed to determine the clinical potential of this novel agent by assessing the effects of three doses of sibenadet therapy relative to placebo, with two commonly used bronchodilators, intended to provide a benchmark against which sibenadet activity could be judged. In all, 701 patients were randomized to one of three sibenadet dose groups (400, 600 or 1000 microg ex valve), salbutamol 200 microg, ipratropium bromide (IB) 40 microg or placebo, all three times daily via pressurized metered dose inhaler (pMDI) for 4 weeks. Once the results of Study 1 had been evaluated, a dose-ranging, study (Study 2) involving 872 patients randomized to receive sibenadet (45, 270, or 495 microg ex actuator), or placebo all three times daily via pMDI, for 6 weeks commenced. Both studies were preceded by a 2-week baseline phase and followed by a 2-week follow up period.The primary efficacy variable identified changes in key COPD symptoms over the treatment period (compared with baseline data) as determined by the novel Breathlessness, Cough and Sputum Scale (BCSS). In addition, data on lung function, health-related quality of life and adverse events were collected. Patients receiving sibenadet therapy three times daily exhibited statistically significantly greater improvements in BCSS total score than those receiving placebo or bronchodilator therapy alone. A clear dose-response was evident in Study 2. Symptom improvement in this study was also accompanied by improved lung function and health-related quality of life. Sibenadet therapy was well tolerated with an adverse events profile comparable to current bronchodilator therapy. These data were viewed as extremely encouraging, warranting further, large-scale clinical investigation.
Administration, Inhalation↗
Fatigue associated with obstructive sleep apnea in a patient with sarcoidosis.
Many patients with sarcoidosis suffer from persistent constitutional symptoms such as fatigue and general weakness, even though physiological measures of disease activity returned within normal limits. The following case report demonstrates a sarcoidosis patient with recurring fatigue caused by an obstructive sleep apnea syndrome developed during the course of the disease.
Adrenal Cortex Hormones↗
Alpha-glycosidase activity in seminal plasma: predictive value for outcome in intrauterine insemination and in vitro fertilization.
OBJECTIVE: To test the hypothesis that alpha-glycosidase activity in seminal plasma can predict the outcome of both IUI and IVF. DESIGN: A retrospective cohort study. SETTING: Tertiary fertility center in a university hospital. PATIENT(S): Eighty-three subfertile couples who underwent IUI and 125 subfertile couples who underwent IVF. INTERVENTION: None. MAIN OUTCOME MEASURE(S): Determination of the alpha-glycosidase activity in seminal plasma before an IUI or IVF attempt, correlation of alpha-glycosidase activity and other semen parameters, and prediction of pregnancy using alpha-glycosidase activity in seminal plasma. RESULT(S): Alpha-glycosidase activity correlated with sperm count. In the IUI group, alpha-glycosidase activity of >23.9 mU/mL predicted pregnancy with a sensitivity of 100% and a specificity of 55.2%. In the IVF group, the outcome could not be predicted with use of any of the semen parameters. CONCLUSION(S): Alpha-glycosidase activity measured in mU/mL probably can be used as a predictor for IVF and pregnancy in an IUI program but has no predictive value with regard to pregnancy rate in an IVF program.
Adult↗
Sperm morphology assessment: diagnostic potential and comparative analysis of strict or WHO criteria in a fertile and a subfertile population.
This prospective study compared the diagnostic and predictive potential of sperm morphology assessments in a fertile vs. a subfertile population, evaluated in three different laboratories. The fertile population included 144 men who had recently fertilized their partners. As subfertile controls, 136 men with a history of subfertility for more than 12 months were used. All semen samples (280) were evaluated in three different centres in a blind fashion, without any patient information. The evaluation of sperm morphology was performed according to the criteria normally used in the different laboratories: WHO (1992) criteria for laboratory A, and Tygerberg strict criteria for laboratories B and C. Using ROC analysis, the predictive power of sperm morphology turned out to be different in the three laboratories (area under ROC curve: 69% for lab A, 72% for lab B and 78% for lab C). Using percentile 10 of the fertile population as the cut-off value for normality, we obtained the following results: 2, 1 and 5% for laboratories A, B and C, respectively. Using ROC analysis cut-off values with optimal specificity and sensitivity were 6, 1 and 10%, respectively. Although our data highlight a reasonable predictive power of sperm morphology in centres using different or the same criteria, cut-off values for normality were different, even when the same criteria were applied. These results stress the importance of standardization in sperm morphology evaluation and the need for examining a reference population in estimating the real threshold value in different laboratories.
Fertility↗
Appetite-suppressant drugs and the risk of primary pulmonary hypertension. International Primary Pulmonary Hypertension Study Group.
BACKGROUND: Recently, a cluster of patients was observed in France in whom primary pulmonary hypertension developed in patients exposed to derivatives of fenfluramine in appetite suppressants (anorexic agents), which are used for weight control. We investigated the potential role of anorexic agents and other suspected risk factors for primary pulmonary hypertension. METHODS: In a case-control study, we assessed 95 patients with primary pulmonary hypertension from 35 centers in France, Belgium, the United Kingdom, and the Netherlands and 355 controls recruited from general practices and matched to the patients' sex and age. RESULTS: The use of anorexic drugs (mainly derivatives of fenfluramine) was associated with an increased risk of primary pulmonary hypertension (odds ratio with any anorexic-drug use, 6.3; 95 percent confidence interval, 3.0 to 13.2). For the use of anorexic agents in the preceding year, the odds ratio was 10.1 (95 percent confidence interval, 3.4 to 29.9). When anorexic drugs were used to a total of more than three months, the odds ratio was 23.1 (95 percent confidence interval, 6.9 to 77.7). We also confirmed an association with several previously identified risk factors: a family history of pulmonary hypertension, infection with the human immunodeficiency virus, cirrhosis, and use of cocaine or intravenous drugs. CONCLUSIONS: The use of anorexic drugs was associated with the development of primary pulmonary hypertension. Active surveillance for this disease should be considered, particularly since their use is expected to increase in the near future.
Adolescent↗
Febrile reactions to platelet transfusion: the effect of increased interleukin 6 levels in concentrates prepared by the platelet-rich plasma method.
BACKGROUND: A relation between febrile reactions to platelet transfusion and high cytokine levels in platelet concentrates (PCs) was found previously. The levels of cytokines such as interleukin (IL)-6 are related to the while cell content of the PC during storage. Therefore, early removal of white cells should prevent reactions. STUDY DESIGN AND METHODS: This prospective study was set up to compare methods for the preparation of random PCs, the platelet-rich plasma method (PRP-PCs), which results in a high white cell content, and the buffy coat method (BC-PCs), which results in a low white cell content, with regard to the frequency and severity of reactions to platelet transfusion and the IL-6 level of the PC. IL-6 was chosen because it is the major mediator of the acute-phase response. White cells were reduced in all PCs before transfusion. RESULTS: Platelet transfusions (n = 584) in 64 patients were studied. An overall reaction frequency of 7.2 percent was observed. Transfusion reactions were seen predominantly in patients who received PRP-PCs (PRP-PCs: 9.3% vs. BC-PCs: 2.7%, p = 0.007). Allergic reactions were limited to transfusions of PRP-PCs. The following PRP-PC characteristics were significantly correlated with febrile transfusion reactions: IL-6 level (p < 0.0001), initial white cell count (p = 0.001), and storage time (p = 0.02). In this group, reactions were less frequent in patients receiving pretransfusion medication (p < 0.001). In the PRP-PC group, IL-6 content (p = 0.01) and initial white cell count (p = 0.04) were also significantly correlated with allergic reactions, which indicated that these or associated factors might have an effect on the outcome of this type of reaction. CONCLUSION: Febrile reactions are highly correlated with IL-6 levels in PCs. The low white cell content of BC-PCs is associated with undetectable IL-6 levels and a reduced frequency of febrile as well as allergic reactions in recipients. The BC method is the preferable one for the production of random-donor PCs.
Acute-Phase Reaction↗
Alcohol and a high-fat diet: a combination favoring overfeeding.
The effects of alcohol and dietary fat on spontaneous energy and macronutrient intakes were investigated in eight male subjects who participated in a protocol including four randomly assigned 2-d sessions during which they ate ad libitum. In each session they had free access to either high- or low-fat foods, with alcohol or a placebo. The high-fat diet was associated with a substantial increase in daily energy intake. Alcohol had no inhibitory effect on food intake and its energy content was thus associated with an additional increase in energy intake. The enhancing effects of alcohol and dietary fat on daily energy intake were additive so that overfeeding was maximal (2.8 MJ/d) under the high-fat diet+alcohol condition. To further examine the effects of alcohol on energy and macronutrient intakes, reported food intake was studied in 351 men and 360 women who had been tested in the Québec Family Study. The results showed that a high alcohol intake was associated with a high daily energy intake and had no inhibitory effect on lipid intake. In conclusion, a dietary regimen providing a high fraction of energy as alcohol and fat increases the risk for positive energy balance under free-living conditions.
Adult↗
Cryptorchidism and extragonadal germ cell tumor.
A patient with an extragonadal germ cell tumor and a history of bilateral cryptorchidism is reported. The rarity of this concurrence in a single patient is discussed. The necessity for thorough investigation of the cryptorchid testes in patients with metastatic germ cell cancer remains essential.
Adult↗
Nodular sclerosing Hodgkin's disease of the thymus gland.
An asymptomatic anterior mediastinal mass in a 22-year-old man proved to be nodular sclerosing Hodgkin's disease of the thymus gland. Complete excision was possible via a left posterolateral thoracotomy. Postoperative chemotherapy was given. Follow-up after 1 year showed no residual disease. Nodular sclerosing Hodgkin's disease is an uncommon tumor of the thymus gland and should be incorporated in the differential diagnosis of anterior mediastinal tumors. Multimodality treatment is advocated.
Adult↗
Increased tumor necrosis factor alpha (TNF alpha), interleukin 1, and interleukin 6 (IL-6) levels in the plasma of stored platelet concentrates: relationship between TNF alpha and IL-6 levels and febrile transfusion reactions.
Increased interleukin 6 (IL-6) levels were found in 8 of 12 platelet concentrates (PCs) after 3 days of storage and in 10 of 12 PCs after 5 and 7 days of storage. Most of the PCs with an increased IL-6 level also showed increased tumor necrosis factor alpha (TNF alpha) and interleukin 1 beta (IL-1 beta) levels. Levels of IL-6 increased by 3 log10 over the base level during storage. Increased levels were found when the PC white cell count exceeded 3 x 10(9) per L. A linear correlation was found among the levels of TNF alpha, IL-1 beta, IL-1 alpha, and IL-6 in the PCs (r > 0.885). Comparison of the TNF alpha, IL-1 beta, and IL-6 levels in samples taken at various storage times indicates that the increased levels are the result of an active synthesis and release of interleukins during storage. In a second part of the study, 45 transfusions of white cell-reduced PCs were studied. Six transfusions were complicated by a febrile reaction. These reactions were related to high levels of IL-6 and TNF alpha in the PCs (p < 0.0001). These cytokines are known as endogenous pyrogens. These findings indicate that transfusion reactions might be due to the intravenous administration of plasma with high cytokine levels and might not always result from an antigen-antibody reaction.
Blood Platelets↗
Isolated posterior dislocation of the radial head without fracture of the ulna in a child.
An isolated posterior dislocation of the radial head is a rare injury. We present a case report on an 11-year-old boy with a traumatic posterior radial head dislocation without fracture or bending of the ulna. The diagnosis can be difficult and should be supported with good radiographic images, since clinically the injury can be missed or misdiagnosed.
Child↗
Hypoplastic acute leukemia: description of eight cases and search for hematopoietic inhibiting activity.
Hypoplastic acute leukemia (HAL) is characterized by pancytopenia and by hypocellularity of the bone marrow. The marrow contains equal to or more than 30% myeloblasts. Absence of tissue infiltrates and/or tumor masses is mandatory. Eight patients are described here. They do not fit into the FAB classification for either acute nonlymphocytic leukemia (ANLL) or myelodysplastic syndrome (MDS), except for one patient who subsequently proved to have a chronic myelomonocytic leukemia (CMML). The median age is 65 years. Two patients, including the CMML patient, are alive, 22 and 6 months from diagnosis. Six patients have died. The median survival is 8 months. Normal bone marrow cells cultured either with HAL sera or with HAL peripheral blood mononuclear cells as feeders and exogenous GM-CSF yielded subnormal CFU-GM counts. This might indicate inhibitory activity of HAL serum and defective stimulatory activity of HAL peripheral blood mononuclear cells.
Acute Disease↗
Reactions to platelet transfusion: the effect of the storage time of the concentrate.
Random platelet concentrates were pooled and depleted of leucocytes by centrifugation immediately prior to transfusion. The incidence and severity of reactions to 570 leucocyte-poor platelet transfusions in 74 patients were studied. An overall transfusion reaction rate of 13.7% was observed. The reaction rate to platelets stored for less than 3 days (8.7%) was significantly different from the reaction rate to platelets stored for 3 days or more (17.6%). Minor reactions as well as moderate and severe reactions were more frequent in the latter group. As most of the white blood cells were removed prior to transfusion, it is suggested that the reactions result from the transfusion of pyrogenic and/or vasoactive substances accumulated in the plasma of the concentrate during storage.
Adolescent↗
Tumor lysis syndrome in a patient with metastatic Merkel cell carcinoma.
A first course of combination chemotherapy for large volume metastatic disease in a patient with Merkel cell carcinoma resulted in a tumor lysis syndrome. After this course a nearly complete response was documented. This case report extends further the chemosensitivity of Merkel cell carcinoma and demonstrates the need for tumor lysis syndrome prophylaxis in patients with bulky disease or fast-growing tumors.
Aged↗
Transcutaneous oxygen saturation and carbon dioxide tension during meals in patients with chronic obstructive pulmonary disease.
The effect on transcutaneous SaO2 and transcutaneous carbon dioxide tension (PtCO2) of eating was assessed in 44 patients with severe COPD (FEV1 less than 50 percent). The SaO2, PtCO2, and heart rate (HR) were measured every minute before, during, and until 30 minutes after a standardized meal (445 kcal) was consumed. All patients were measured twice on the same day, while eating a meal with high (80 percent) and low (28 percent) carbohydrate content, respectively. The mean meal desaturation (delta SaO2) was less than 1 percent in normoxemic patients but was -3.2 +/- 0.7 percent (p less than 0.001) in hypoxemic (PaO2 less than 7.3 kPa) patients. Significant differences between hypoxemic patients with a delta SaO2 greater than 4 percent and less than or equal to 4 percent, respectively, were found in FEV1 (16 +/- 3 percent and 29 +/- 8 percent; p less than 0.001), respiratory muscle strength (3.9 +/- 1.2 kPa and 5.9 +/- 1.2 kPa; p less than 0.01), HR (112 +/- 12 beats per minute and 90 +/- 18 beats per minute; p less than 0.001), body weight (54.9 +/- 7.5 kg and 74.7 +/- 10.4 kg; p less than 0.001), and fat-free mass (42.0 +/- 6.6 kg and 52.6 +/- 5.8 kg; p less than 0.005) but not in baseline SaO2 and PtCO2. The decrease in SaO2 and the increase in HR were less during the carbohydrate-rich meal. No significant fluctuations in PtCO2 were found after either meal. Meal-related oxygen desaturation cannot explain weight loss in normoxemic patients with COPD but may contribute to a limited dietary intake in a subgroup of hypoxemic patients exhibiting marked oxygen desaturation during meals. A single carbohydrate-rich meal does not have an immediate impact on PtCO2 in stable COPD.
Carbon Dioxide↗