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.     

P300, Disinhibited Personality, and Early-Onset Alcohol Problems

BACKGROUND: Recent research suggests that a reduced P300 amplitude of the event-related potential is associated with a vulnerability to alcoholism. This study tested the hypothesis that reductions in the P300 amplitude would be associated with specific dimensions of disinhibited personality (social deviance proneness and impulsivity) and that these personality traits would mediate the association between P300 and alcohol problems in a young adult sample that varied widely in disinhibitory traits. METHODS: Alcohol problems, personality (impulsivity, social deviance, harm avoidance, and excitement seeking), and event-related potentials were measured in a sample of 190 subjects (87 men, 103 women) with a mean age of 20.7 +/- 1.9 years. RESULTS: Social deviance, impulsivity, and alcohol problems were associated with reductions in the P300, but only in male subjects. A structural model suggested that social deviance, impulsivity, and alcohol problems were all strongly related to P300 amplitude at Fz. Further analyses indicated that for male subjects, social deviance mediated the association between P300 at Fz and alcohol problems as well as the association between impulsivity and alcohol problems. CONCLUSIONS: This study suggests that reduced P300s are strongly associated with a general tendency toward antisocial, defiant, and impulsive traits, which might, in turn, increase the risk for alcohol abuse. The lack of an association between reduced P300s and personality or alcohol problems in women was unexpected and deserves further study.     

Elevated C-reactive protein levels are associated with endothelial dysfunction in chronic cocaine users

OBJECTIVE: To examine the relationship of the serum C-reactive protein (CRP) and endothelial function and their associations with coronary artery calcification, lipid profile and cardiac changes. METHODS: The analyses for serum lipids and CRP, echocardiography, spiral computed tomography scans and endothelial function assay were performed in 53 participants with a history of chronic cocaine use. RESULTS: There were no statistically significant differences in demographic characteristics and drug use between CRP normal (<1.9 mg/l) and abnormal groups. The brachial artery diameter percentage changes in the third scan (immediately after deflation of cuff) and the fourth scan (90 s after deflation of cuff) were significantly associated with the CRP levels (the third: beta=-0.054, S.E.=0.027; P=0.028; the fourth: beta=-0.065, S.E.=0.026; P=0.016). The multiple regression models showed that CRP was the only significant predictor of artery diameter changes (%) in these two scans. The CRP abnormal group had more coronary artery calcification (calcium scores >5, 16.7 vs. 0%; P=0.036) and more cardiac diastolic dysfunction expressed as deceleration time >240 ms (16.7 vs. 0%; P=0.036). CONCLUSIONS: Elevated serum CRP levels are associated with endothelial dysfunction, coronary artery calcification and cardiac diastolic dysfunction in chronic cocaine users.     

Long-term Fracture Risk in Patients with Celiac Disease: A Population-Based Study in Olmsted County,Minnesota

Celiac disease is associated with decreased bone density, but there are conflicting data regarding fracture risk. We determined the fracture incidence relative to matched controls in a population-based cohort with celiac disease before and after diagnosis. Olmsted County residents with celiac disease (n = 83) diagnosed between 1950 and 2002 were compared with 166 gender and age matched controls. Fracture histories were ascertained from each subject’s medical records. Celiac disease is linked to an increased fracture risk before and after diagnosis. Before the index date, cases had a fracture rate twice that of controls (CI: 1.0–3.9, P = 0.045) and 2.5-fold greater after the index date (CI: 1.1–5.6, P = 0.026). Appendicular and axial fractures were 2.5 (CI: 0.9–6.5) and 3.2 times more likely (CI: 1.0–10.5) after the index date. These observations support a rationale for earlier detection of celiac disease, and active management of bone disease before bone effects have occurred, to reduce the persistent risk of fractures.     

Intensive care unit readmission after elective coronary artery bypass grafting

Prospective data of 3,120 consecutive patients who had elective coronary artery bypass were analyzed to identify patient profile, cost, outcome and predictors of those readmitted to the intensive care unit. Group A (n=3,002) had a single intensive care unit admission and group B (n=118) were readmitted within 30 days after surgery. Parsonnet score, EuroSCORE, age, body mass index, chronic obstructive airway disease, peripheral vascular disease, renal dysfunction, unstable angina, congestive cardiac failure, and poor left ventricular function were higher in group B. Bypass and crossclamp times were longer, and the prevalence of inotropic and balloon pump support, arrhythmias, myocardial infarction, re-exploration, blood loss and transfusion, cerebrovascular accident, wound infection, sternal dehiscence, and multisystem failure were higher in group B. Despite a 4-fold increase in cost of care, the mortality rate (32.4%) of patients readmitted to intensive care was 23-times higher than routine patients (1.4%). Crossclamp time>80 min, Parsonnet score>10, EuroSCORE>9, sternal dehiscence, ventricular arrhythmias, and renal failure predicted readmission.     

Clinical and angiographic variables affecting the progression of coronary artery disease as determined by quantitative angiography

To assess by serial quantitative angiography, the significance of clinical and angiographic variables that affect the progression of coronary artery disease (CAD). Progression of disease by sequential angiography is unpredictable and the role of clinical risk factors controversial. Various intervention trials have demonstrated less progression and even regression in hyperlipidemic patients. Correlates of progression have included a younger age, unstable angina, and greater involvement of the coronary arteries, with few studies looking at angiographic features of individual lesions. Serial angiograms on 74 patients were analyzed by computer assisted quantitative angiography using absolute measurements. A total of 99 diseased segments were analyzed for progression defined as an absolute reduction of 20% in luminal cross-sectional area. A preliminary correlation coefficient was calculated for each of the clinical and angiographic variables to detect any association with progression, and the odds ratio determined.The presence of any of the clinical risk factors-diabetes, hypertension, serum cholesterol, smoking, and a family history of coronary disease could not predict progression. The use of beta blockers was three times less likely to be associated with progression (odds ratio 0.33). While the presence of distal disease was associated with progression of a more proximal lesion (odds ratio 2.4), eccentricity, branch point location, lesion length, calcification, thrombus, or the presence of collaterals did not influence progression of disease in an individual segment. In conclusion, the presence of any of the clinical risk factors could not predict progression of disease in an individual coronary segment as determined by serial quantitative angiography, and the use of beta blockers and the absence of coexistent distal disease was associated with less progression of disease in an individual coronary segment. This may be related to changes in wall stress, reduced platelet interactions, and the integrity and permeability of the vascular endothelium to lipids.     

Colorectal Polyps in Carriers of the APC I1307K Polymorphism

PURPOSE The probability of colorectal cancer is moderately increased among carriers of the APC I1307K polymorphism. However, it is not known if endoscopic surveillance of this high-risk group is warranted. The prevalence of polyps and adenomas in specimens of colorectal cancer who are carriers and noncarriers of the APC I1307K polymorphism is compared. METHOD Prevalence of adenomatous polyps in the pathology specimens of the study participants, stratified by their APC I1307K polymorphism status, was studied in 900 consecutive cases of colorectal cancer diagnosed in northern Israel between 1998 and 2002, within the framework of a population-based, case-controlled study (MECC Study). RESULTS The APC I1307K mutation was detected in 78 colorectal cancer cases (8.7 percent) of the study population. Prevalence was higher among Ashkenazi Jews (11.2 percent) than among non-Ashkenazi Jews (2.7 percent) or Arabs (3.1 percent). After adjustment for age, APC I1307K carriers were significantly more likely than noncarriers to have polyps in their surgical specimen (51.3 percent vs. 32.6 percent, P = 0.002). Adenomas with a tubular component (either tubular adenomas or tubulovillous adenomas), but not villous adenomas, were significantly more frequent among carriers (37.2 percent vs. 23.6 percent, P = 0.005). CONCLUSION Together with former evidence of I1307K being a risk factor for colorectal cancer, these data suggest that colonoscopic surveillance for colorectal adenomas and cancer may be warranted in I1307K carriers, even in the absence of other identifiable risk factors. Supported by the National Institutes of Health grant RO1-CA81488 to S.B.G. and G.R.