Occult Cushing's syndrome in type-2 diabetes

Subclinical Cushing's syndrome (SCS) caused by adrenal incidentalomas is frequently associated with overweight and insulin resistance. Metabolic syndrome X may therefore be a clue to the presence of CS. However, the incidence of CS in this situation remains unknown. We have conducted a prospective study to evaluate the prevalence of occult CS in overweight, type-2 diabetic patients devoided of specific clinical symptoms of CS. Two hundred overweight, type-2 diabetic patients, consecutively referred for poor metabolic control (HbA(1C) > 8%), were studied as inpatients. A first screening step was performed with the 1-mg overnight dexamethasone suppression test (DST) using a revised criterion for cortisol suppression (60 nmol/liter) to maximize the sensitivity of the procedure. A second confirmatory step of biochemical investigations (midnight plasma cortisol concentration, plasma cortisol circadian rhythm, morning plasma ACTH concentration, 24-h urinary free cortisol, and 4-mg i.v. DST) was performed in patients with impaired 1-mg DST. A third step of imaging studies was performed according to the results of second-step investigations. Fifty-two patients had impaired 1-mg DST. Among these, 47 were further evaluated. Thirty were considered as false positives of the 1-mg DST, whereas 17 displayed at least one additional biological abnormality of the hypothalamic-pituitary-adrenal axis. Definitive occult CS was identified in four patients (2% of the whole series) with Cushing's disease (n = 3) and surgically proven adrenal adenoma (n = 1). Definitive diagnosis remains to be established in seven additional patients (3.5%) with mild occult CS associated with unsuppressed plasma ACTH concentrations and a unilateral adrenal tumor of 10-29 mm in size showing prevalent uptake at radiocholesterol scintigraphy. In conclusion, a relatively high prevalence of occult CS was found in our study. Further studies are needed to evaluate the impact of the cure of occult CS on obesity and diabetes mellitus in these patients. Such studies might provide a rationale for systematic screening of occult CS in this population.     

Self-reported management of pain in hospitalized patients: link between process and outcome

PURPOSE: Hospitalized patients commonly experience pain. We investigated the association between patients' reported use of recommended pain management practices and overall pain relief. METHODS: All adult patients discharged during a 1-month period from a Swiss teaching hospital were invited to complete a mailed survey that included the Picker patient experience questionnaire, questions on pain relief during hospitalization, and questions on various procedures that are recommended as standards of pain management. RESULTS: Of 2156 eligible patients, 1518 (70%) participated. Sixty-nine percent (n = 1050) had experienced pain during their hospital stay, of whom 71% (n = 697/978) reported complete pain relief. After adjustment for sex, age, general health, and hospital department, pain relief was associated independently with availability of physicians (odds ratio [OR] = 11; 95% confidence interval [CI]: 3.3 to 36 for excellent vs. poor availability), having received information about pain and its management (OR = 2.8; 95% CI: 1.8 to 4.2), regular pain assessment (OR = 1.8; 95% CI: 1.2 to 2.8), modification of pain treatment when ineffective (OR = 3.0; 95% CI: 1.6 to 5.6), and waiting less than 10 minutes for pain medications (OR = 3.5; 95% CI: 1.9 to 6.6). CONCLUSION: Patient reports that recommended pain management procedures had been used were associated with better self-reported pain relief among hospitalized patients.     

Proliferation of early human myeloid precursors induced by interleukin- 1 and recombinant soluble CD23

Low affinity Fc epsilon receptors (Fc epsilon RII/CD23) or their soluble fragments have various biologic effects on B- and T-cell lineages. In this study, we have assessed the effect of recombinant soluble CD23 (rsCD23) on the proliferation of human bone marrow (BM)- derived myeloid precursors with or without recombinant interleukin-1 (rIL-1) addition. Non-adherent CD2- or CD34+ BM cell subsets were used as target cells. Our results show that rsCD23 in synergy with rIL-1 displays an interleukin-3-like activity as it promotes the proliferation of multipotential marrow precursors. This effect was abolished by anti-CD23 addition to these cultures, but was not affected by anti-IL-3 monoclonal antibody. Furthermore, sequential study indicates that rIL-1 induces bone marrow cell responsiveness to rsCD23.     

In vivo and in vitro sensitivity of blastic plasmacytoid dendritic cell neoplasm to SL-401, an interleukin-3 receptor targeted biologic agent

Blastic plasmacytoid dendritic cell neoplasm is an aggressive malignancy derived from plasmacytoid dendritic cells. There is currently no accepted standard of care for treating this neoplasm, and therapeutic strategies have never been prospectively evaluated. Since blastic plasmacytoid dendritic cell neoplasm cells express high levels of interleukin-3 receptor α chain (IL3-Rα or CD123), antitumor effects of the interleukin-3 receptor-targeted drug SL-401 against blastic plasmacytoid dendritic cell neoplasm were evaluated in vitro and in vivo. The cytotoxicity of SL-401 was assessed in patient-derived blastic plasmacytoid dendritic cell neoplasm cell lines (CAL-1 and GEN2.2) and in primary blastic plasmacytoid dendritic cell neoplasm cells isolated from 12 patients using flow cytometry and an in vitro cytotoxicity assay. The cytotoxic effects of SL-401 were compared to those of several relevant cytotoxic agents. SL-401 exhibited a robust cytotoxicity against blastic plasmacytoid dendritic cell neoplasm cells in a dose-dependent manner. Additionally, the cytotoxic effects of SL-401 were observed at substantially lower concentrations than those achieved in clinical trials to date. Survival of mice inoculated with a blastic plasmacytoid dendritic cell neoplasm cell line and treated with a single cycle of SL-401 was significantly longer than that of untreated controls (median survival, 58 versus 17 days, P<0.001). These findings indicate that blastic plasmacytoid dendritic cell neoplasm cells are highly sensitive to SL-401, and support further evaluation of SL-401 in patients suffering from blastic plasmacytoid dendritic cell neoplasm.     

Secretory IgA as a vaccine carrier for delivery of HIV antigen to M cells

HIV transmission and spread in the host are based on the survival of the virus or infected cells present in mucosal secretions, and the virus' ability to cross the epithelial barrier and access immune target cells, which leads to systemic infection. Therefore, HIV‐specific immunity at mucosal sites is critical for control of infection. Although mucosal delivery would ensure the best onset of protective immunity, most candidate vaccines are administered through the parenteral route. Remarkably, secretory IgA (SIgA) interacts specifically with mucosal microfold (M) cells present in gut‐associated lymphoid tissues. Here we evaluate the feasibility of delivering chemically bound p24HIV antigen via SIgA into the intestinal mucosae in mice. After oral administration, p24–SIgA complexes are quickly delivered into the tissue and selectively captured by CX3CR1⁺ dendritic cells. Oral immunization with p24gag linked to SIgA (p24–SIgA) adjuvanted with E. coli heat labile enterotoxin (HLT) elicits both humoral and cellular immune responses against p24 at the systemic and mucosal levels and induces efficient protection against rectal challenge with a recombinant vaccinia virus encoding gag. This is the first study which underscores the remarkable potential of SIgA to serve as a vaccine carrier for an HIV antigen in mucosal administration targeting the gastrointestinal environment.     

Pressure sores in geriatric medicine: the role of nutrition

Malnutrition is frequent in geriatric patients: it affects 30 to 60% of elderly residents of institutions and 30 to 70% of patients admitted for short-term hospitalization. Malnutrition is a risk factor for developing pressure sores, and patients with them are more often and more severely malnourished than patients without them. In elderly subjects, multiple and interlinked factors may trigger or aggravate malnutrition; they may be physical, psychological or social and may be worsened by drugs and some diets. Malnutrition has been recognized as a risk factor for the onset and perpetuation of pressure sores. Of the dietary factors, protein intake seems most important. A low body mass index (BMI), low serum albumin, and weight loss are associated with an increased risk of pressure sores. A physician observing pressure sores must conduct a nutritional assessment, using clinical and laboratory screening tools. The criteria for malnutrition in elderly subjects are weight loss > or =5% in 3 months or > or =10% in 6 months, BMI<21 kg/m(2), serum albumin<35 g/L or a MNA (Mini Nutritional Assessment) score<17. Any one of these criteria is a sufficient basis for a diagnosis of malnutrition. Nutritional management is part of the prevention and treatment of pressure sores in geriatric medicine. It must be adapted for each patient. The recommended calorie intake in malnourished patients at risk of or with pressure sores is 30-40 kcal/kg/d, with 1.2-1.5 g of proteins/kg/d.