Safety of rush immunotherapy using a modified schedule: a cumulative experience of 893 patients receiving multiple aeroallergens.

Conventional immunotherapy (IT) is effective in treating allergic rhinitis, allergic asthma, and chronic rhinosinusitis. Disadvantages include poor compliance, delayed efficacy, and patient frustration. Rush IT, or rapid desensitization, offers the advantages of rapid response, improved compliance, and cost-effectiveness. Although premedication with corticosteroids and antihistamines dramatically reduces systemic reactions, safety remains a primary concern. Two separate half-day schedules with minor differences were used to rapidly desensitize 893 patients (aged 1.5-77 years) in two typical outpatient settings equipped to treat anaphylaxis. All patients exhibited positive skin-prick tests to perennial and seasonal allergens. Diagnoses included allergic rhinitis (857/96%), allergic asthma (505/57%), and chronic rhinosinusitis (384/43%). Five hundred sixty-eight patients were premedicated with prednisone and HI-antihistamine for 3 days. Three hundred twenty-five patients were premedicated for 3 days with prednisone and H1- and H2-blockade. The protocol's final dose ranged from 0.1 to 0.5 mL of a 1:1000 dilution of extracts manufactured by ALK and Greer Laboratories. Patients continued on to higher doses by resuming a conventional schedule. Eighteen patients (2.0%) experienced a mild systemic reaction. All responded to subcutaneous epinephrine and/or nebulized albuterol and were sent home after observation. One patient (0.1%) experienced true anaphylaxis and received appropriate treatment and observation. Our experience with rush IT confirms that maintenance IT can be reached quickly and safely under careful supervision. Caution must be exercised when using this procedure because anaphylaxis does occur. Systemic reactions occur less frequently using a lower targeted final dose than previously described in the literature.     

Failure of atriopeptin II to cause arterial vasodilation in the conscious rat

The cardiovascular actions of the synthetic natriuretic peptide, atriopeptin II, were examined in conscious unrestrained spontaneously hypertensive rats and normotensive Wistar-Kyoto rats. The animals were chronically instrumented with miniaturized pulsed Doppler flow probes to allow measurement of regional blood flow, or with an electromagnetic flow probe on the ascending aorta to facilitate the measurement of cardiac output in the conscious rat. Intravenous infusion of increasing doses of atriopeptin II (0.25-4 micrograms/kg per min) caused a dose-dependent fall in mean arterial pressure in the hypertensive and normotensive rats. Blood flow in the renal, mesenteric, and hindquarters vascular beds was markedly decreased during the infusion of atriopeptin II, and regional vascular resistance was significantly increased in both groups of rats. Heart rate was significantly elevated (47 +/- 14 beats/min) in the spontaneously hypertensive rats during atriopeptin II infusion, but no change in heart rate was observed in the Wistar rats. In the hypertensive rats, atriopeptin II caused a marked dose-dependent decrease in cardiac output (maximal decrease = -39 +/- 4%) and stroke volume (maximal decrease = -48 +/- 4%). Central venous pressure and left atrial pressure were also significantly reduced during atriopeptin II infusion. Total peripheral resistance was increased over the infusion protocol by 26 +/- 3%. These data suggest that atriopeptin II infusion markedly attenuated cardiac output in the conscious spontaneously hypertensive rats. Total and regional vascular resistances were increased, possibly through reflex compensatory mechanisms, to maintain arterial pressure in the face of decreased cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)     

Impact of baseline renal function on mortality after percutaneous coronary intervention with sirolimus-eluting stents or bare metal stents

Renal impairment is an important predictor of mortality after percutaneous coronary intervention and may increase the restenosis rate. However, the relation between restenosis and the risk of death in patients who have renal impairment remains unclear. We evaluated the incidences of repeat revascularization and mortality in patients who had renal impairment and those who did not and who received sirolimus-eluting stents or bare stents. A total of 1,080 consecutive patients treated for 1 year had available data to calculate baseline creatinine clearance. Patients received bare stents (first 6 months, n = 543) or sirolimus-eluting stents (last 6 months, n = 537) and were grouped according to the presence or absence of renal impairment (creatinine clearance <60 ml/min). Patients who had renal impairment had a higher mortality rate at 1 year (7.6% vs 2.5%, hazard ratio 3.14, 95% confidence interval 1.68 to 5.88, p <0.01), with no differences in mortality between patients who received bare stents and those who received sirolimus-eluting stents (hazard ratio 0.91, 95% confidence interval 0.49 to 1.68, p = 0.8). The incidence of target vessel revascularization decreased significantly in patients who were treated with sirolimus-eluting stents and did not have renal impairment (hazard ratio 0.59, 95% confidence interval 0.39 to 0.90, p = 0.01) and in those who had decreased renal function (hazard ratio 0.37, 95% confidence interval 0.15 to 0.90, p = 0.03). Thus, sirolimus-eluting stents compared with conventional stents decreased clinical restenosis in patients who had renal impairment. However, this benefit was not paralleled by a decrease in the risk of death in this population. It seems unlikely that restenosis could be a contributing factor that influenced the increased mortality of patients who had impaired renal function.     

Early cognitive impairment in a subset of patients with presumed low-grade glioma

We investigated the presence of cognitive impairment, in adults with presumed low-grade glioma at early stage of disease prior to major treatments, in relation to neurological symptoms and radiological characteristics of the tumour. Sixteen patients were evaluated. A subset of patients was identified with clearly impaired cognition. Patients with cognitive impairment often had large tumours in the left frontal lobe, were relatively young, and most of them were males. We conclude that cognitive dysfunction may be present already at early stage of disease, and that early identification of patients at risk is warranted.     

Selection of probiotic bacteria for prevention of allergic diseases: immunomodulation of neonatal dendritic cells

Modification of intestinal microbiota early in life by administration of probiotic bacteria may be a potential approach to prevent allergic disease. To select probiotic bacteria for in vivo purposes, we investigated the capacity of probiotic bacteria to interact with neonatal dendritic cells (DC) and studied the ensuing T cell polarizing effect. Immature DC were generated from cord blood-derived monocytes and maturation was induced by maturation factors (MF), lipopolysaccharide (LPS) plus MF and Bifidobacterium bifidum, B. infantis, Lactobacillus salivarius, Lactococcus lactis alone or combined with MF. After 12 days of co-culture with DC and Staphylococcus aureus enterotoxin B (SEB) as antigenic stimulus, cytokine production by autologous T cells was determined by intracellular cytokine staining. Additionally, cells were stimulated with CD3 and CD28 monoclonal antibodies and cytokines were measured in supernatants by multiplex assay. The probiotic strains induced partial maturation of DC. Full maturation of DC was induced for all strains tested when MF was added. The percentage of interleukin (IL)-4 producing T cells was lower in T cell cultures stimulated with B. bifidum matured DC compared to MF and LPS matured DC, which coincided with a higher percentage of interferon (IFN)-gamma-producing T cells. Furthermore, T cells stimulated by B. bifidum matured DC produced significantly more IL-10 compared to MF matured DC. Selected species of the Bifidobacterium genus prime in vitro cultured neonatal DC to polarize T cell responses and may therefore be candidates to use in primary prevention of allergic diseases.     

Does pretreatment testing for serotonin transporter polymorphisms lead to earlier effects of drug treatment in patients with major depression? A decision-analytic model

BACKGROUND: An estimated 30% to 40% of patients with depression do not sufficiently respond to treatment with selective serotonin reuptake inhibitors (SSRIs) and the period in which treatment efficacy can be assessed is relatively long. Therefore, a test to identify potential nonresponders could be useful in the treatment of depression. Serotonin transporter gene (SLC6A4) variations have been reported to account for differences in the way individuals respond to SSRI treatment. OBJECTIVE: A decision-analytic model was used to assess whether pretreatment genetic testing for 5-HTTLPR, a polymorphism of the SLC6A4 genotype, could be an efficient tool in the treatment of depression. METHODS: A theoretical clinical decision-analytic model was constructed to compare the current treatment strategy in The Netherlands with an alternative strategy for the treatment of depression. Under treatment guidelines in The Netherlands, all patients with depression receive SSRI treatment (nontesting strategy). Under the alternative strategy, genetic testing would be performed to identify which class of antidepressant would be the best choice for initiation of treatment (genetic testing strategy). Probabilities (predicted results) for this model were based on data from previous studies and the opinions of experts in the field of psychopharmacology. To test the robustness of the model, 6- and 12-week remission rates for patients treated with SSRIs were varied in a sensitivity analysis using a predetermined range that was established based on expert opinion. Threshold analyses were performed on the parameters of serotonin transporter genotype frequency and response and nonresponse rates for patients receiving SSRIs, serotonin-norepinephrine reuptake inhibitors (SNRIs), and tricyclic antidepressants (TCAs) to determine the value for a variable at which it could be concluded that a change in treatment strategy would be preferred. RESULTS: When genetic testing was performed before an antidepressant was prescribed, 64.6% of patients were predicted to be in remission after 6 weeks of treatment compared with 60.0% of patients who did not receive genetic testing. After 12 weeks, 79.5% of patients in the testing group who received an SNRI as initial treatment and 83.2% of those who received a TCA initially were predicted to be in remission compared with 76.7% of patients in the nontesting group. Sensitivity analyses indicated that the model was robust to variation of probability estimates within their plausible ranges. However, these findings were based on a theoretic model and did not include cost assessment. Pretreatment genetic testing must be evaluated further in randomized clinical trials and costs must be assessed before implementing this strategy in routine psychiatric practice can be recommended. CONCLUSIONS: The findings of this study suggest that performing genetic testing before prescribing antidepressant treatment may lead to greater numbers of patients experiencing remission early in treatment.