Serum gastrin levels during long-term omeprazole treatment

Serum gastrin was determined in 33 patients during treatment with the proton pump inhibitor omeprazole. After 4 weeks of therapy, gastrin levels increased to a median of 55 pg/ml compared to 15 pg/ml prior to omeprazole (P less than 0.001). There was a close correlation (r = 0.939; P less than 0.001) between pre-treatment gastrin and levels at 4 weeks. Comparison of serum gastrin concentrations at 1 month of omeprazole with levels at 6 (n = 21) and 12 months (n = 12) continuous therapy revealed a close correlation (r = 0.961 and r = 0.882, respectively; P less than 0.001) despite dose adjustment. In marked hypochlorhydria documented by continuous pH monitoring, serum gastrin varied from normal up to profound hypergastrinaemia. These results demonstrate that the serum gastrin increase under powerful acid-inhibitory drug therapy depends upon a number of variables. (a) Only in patients with elevated gastrin levels, prior to omeprazole treatment, can moderate to marked hypergastrinaemia during omeprazole be expected. (b) Gastrin increases reached during the initial period of omeprazole treatment remain constant during long-term therapy. (c) Acid inhibition itself is not necessarily associated with an increase in serum gastrin in every patient, which suggests that the individual sensitivity of the gastrin cell to acid inhibition is more important for serum gastrin changes than the degree of acid inhibition itself.     

Fourteen-Day Inhalation Study in Rats, Using Aged and Diluted Sidestream Smoke from a Reference Cigarette: I. Inhalation Toxicology and Histopathology

Sprague-Dawley rats were exposed 6 hr per day for 14 consecutivedays to aged and diluted sidestream smoke (ADSS), used as asurrogate for Environmental Tobacco Smoke (ETS), at concentrationsof 0.1 (typical), 1 (extreme), or 10 (exaggerated) mg of particulatesper cubic meter. Animals were exposed nose-only, inside whole-bodychambers, to ADSS from the 1R4F reference cigarette. End-pointsincluded histopathology, CO-ox-imetry plasma nicotine and cotinine,clinical pathology, and organ and body weights. The only pathologicalresponse observed was slight to mild epithelial hyperplasiaand inflammation in the most rostral part of the nasal cavity,in the high-exposure group only. No effects were noted at mediumor low exposures. The minimal changes noted were reversible,using a subgroup of animals kept without further treatment foran additional 14 days. Overall, the end-points used in the studydemonstrated that there was no detectable biological activityof ADSS at typical or even 10-fold ETS concentrations and thatthe activity was only minimal at very exaggerated concentrations(particle concentrations 100 times higher than typical real-worldconcentrations).     

Impact of AV Conduction Disorders on SafeR Mode Performance

Purpose: CAN-SAVE R is a Canadian multicenter study that compares the effects of a new pacing mode algorithm designed to minimize right ventricular (V) pacing versus DDD mode with a long atrioventricular (AV) delay in a general population of pacemaker (PM) recipients .
Study Participants: Patients with permanent atrial fibrillation (AF) or high-degree AV block (AVB) were excluded. We present preliminary data collected in 208 patients (mean age = 71 ± 11 years, 68% men), for the 2-month baseline period during which all PM were programmed in the new pacing mode. The pacing indications were sinus node disease (SND) without AVB in 39%, AVB without SND in 30%, SND and AVB in 16%, and miscellaneous in 15% of patients.
Results: The mean percent V pacing in the overall population was 9.5 ± 23.8% (range = 0–100%, median <1%), ranging between 0.5 ± 1.5% (median = 0) in patients without AVB and 18.7 ± 31.2% in patients (median = 1) with AVB. Adverse events potentially related to the new pacing mode were observed in two patients with AVB.
Conclusions: A new pacing mode was effective and safe in a general population of PM recipients without permanent AVB and was associated with an overall <1% median V pacing. CAN-SAVE R will compare the long-term effects of the new pacing mode with DDD with a long AV delay on clinical outcomes and cardiac function.     

Specific lgG1 and lgG2 antibody responses of dogs to Leishmania infantum and other parasites

Sera from dogs naturally infected with Leishmania infantum were analysed for the IgG subclass specificity of their antibody response by ELISA. Dogs infected with L. infantum produced both IgGl and IgG2 antibodies with IgG2 being associated with asymptomatic infections and IgGl being associated with disease (symptomatic dogs, non- or low-responsive to chemotherapy). The differential responses of IgG] and IgGl serum antibodies in asymptomatic and symptomatic dogs may indicate a dichotomous immune response to infection with L. infantum. To confirm this, on a broader scale, sera from dogs naturally exposed to an asymptomatic protozoan infection, Toxoplasma gondii, were also analysed as were sera from dogs exposed to the helminths, Dirofilaria immitis and Toxocara canis. Antibodies specific for T. gondii antigen detected in sera from 17 dogs were of the IgG2 subclass only. Both IgGl and IgG2 antibodies to D. immitis andl. canis were present in the sera of naturally infected dogs but IgGl appeared to be the predominant subclass. Furthermore, in dogs experimentally infected with T. canis, selective regulation ofIgG2 and IgGl responses was apparent since production of the two subclasses occurred at different times following infection, with IgGl levels declining as IgGl levels rose. Thus, the analysis of IgG subsets in parasitized dogs provides evidence of a dichotomous response to infection: IgGl is associated with asymptomatic protozoan infections and IgGl is associated with helminth infections and disease caused by protozoan infection.