The effects of pregnancy on the pharmacokinetics of infliximab and adalimumab in inflammatory bowel disease.

BACKGROUND: Transplacental transfer of infliximab and adalimumab results in detectable drug levels in the cord blood and infant. AIM: To determine if pregnancy influenced the pharmacokinetics of anti-TNF agents in women with inflammatory bowel disease. METHODS: Twenty-five women from the University of Calgary inflammatory bowel disease(IBD) pregnancy clinic on maintenance infliximab or adalimumab were recruited prospectively with serum bio-banking performed each trimester. Infliximab trough and adalimumab steady-state levels were the outcomes of interest and were analysed using the ANSER infliximab and adalimumab assays. Multivariate linear mixed-effects models were constructed to assess infliximab and adalimumab drug levels during pregnancy adjusting for the clinical covariates of albumin, BMI and CRP. RESULTS: Fifteen women (eight Crohn's disease, seven ulcerative colitis) received infliximab and 10 women with 11 pregnancies were treated with adalimumab. Median age was 29.6 years (IQR: 27.6-31.2 years). Median disease duration was 9.2 years (IQR: 3.16-15.0 years). Median trough infliximab concentrations were 8.50 µg/mL (IQR: 7.23-10.07 µg/mL), 10.31 µg/mL (IQR: 7.66-15.63 µg/mL) and 21.02 µg/mL (IQR: 16.01-26.70 µg/mL) at trimesters 1, 2 and 3 respectively. Significant changes in albumin and BMI (P < 0.05) but not CRP (P > 0.05) were documented throughout pregnancy. After adjusting for albumin, BMI and CRP, infliximab trough levels increased during pregnancy, by 4.2 µg/mL per trimester (P = 0.02), while adalimumab drug levels remained stable (P > 0.05). CONCLUSIONS: Infliximab levels rise during pregnancy, whereas adalimumab levels remain stable after accounting for changes in albumin, BMI and CRP. Therapeutic drug monitoring in the second trimester may be useful in guiding dosing in the third trimester.

Reinvestigating 2,5-di(pyridin-2-yl)pyrazine ruthenium complexes: selective deuteration and Raman spectroscopy as tools to probe ground and excited-state electronic structure in homo- and heterobimetallic complexes.

The mono- (1) and dinuclear (2) ruthenium(II) bis(2,2'-bipyridine) complexes of 2,5-di(pyridin-2-yl)pyrazine (2,5-dpp), for which the UV/Vis absorption and emission as well as electrochemical properties have been described earlier, are reinvestigated here by resonance, surface enhanced and transient resonance Raman spectroscopy together with selective deuteration to determine the location of the lowest lying excited metal to ligand charge transfer ((3)MLCT) states. The ground state absorption spectrum of both the mono- and dinuclear complexes are characterised by resonance Raman spectroscopy. The effect of deuteration on emission lifetimes together with the absence of characteristic bipy anion radical modes in the transient Raman spectra for both the mono- and dinuclear complexes bridged by the 2,5-dpp ligand confirms that the excited state is 2,5-dpp based; however DFT calculations and the effect of deuteration on emission lifetimes indicate that the bipy based MLCT states contribute to excited state deactivation. Resonance Raman and surface enhanced Raman spectroscopic (SERS) data for 1 and 2 are compared with that of the heterobimetallic complexes [Ru(bipy)(2)(2,5-dpp)PdCl(2)](2+)3 and [Ru(bipy)(2)(2,5-dpp)PtCl(2)](2+)4. The SERS data for 1 indicates that a heterobimetallic Ru-Au complex forms in situ upon addition of 1 to a gold colloid.

Ciprofloxacin: drug of choice in the treatment of malignant external otitis (MEO).

Ciprofloxacin, a fluorinated quinolone with high efficacy against Pseudomonas aeruginosa, was used in the treatment of 10 consecutive patients with malignant external otitis. All patients had skull base osteomyelitis documented by nuclear and computed tomography (CT) scans. Dosages of 1.5 g of ciprofloxacin daily were used for a mean average of 10 weeks. All patients were considered cured with a minimum follow-up of 18 months after completion of therapy. A new classification of malignant external otitis (MEO) is presented.

Management of congenital pediatric cholesteatomas.

During the past 10 years discrete middle ear congenital cholesteatomas have been detected with greater frequency in young children. The increased recognition of this condition is probably related to the pediatricians' greater awareness of this defect, their improved facility with pneumatic otoscopy, and effective audiometric and tympanometric screening procedures. This early detection while the lesions are small and localized facilitates their surgical removal. Clinically, it would appear that congenital cholesteatomas can be subdivided into two categories according to their anatomic locations. The anterior lesions present as an isolated pearl that arise from an area on the anterior surface of the malleus, are usually associated with normal hearing, and have pneumatized mastoids. The posterior lesions do not seem to originate from a clearly defined anatomic area, have a higher incidence of sclerotic mastoids, and erode the ossicular chain commonly producing a hearing loss. The anterior middle ear cholesteatoma probably arises from a persistent epidermoid formation, a structure that normally is present during fetal development of involutes by the 33rd week of gestation. The origin of cholesteatomas arising in the posterior middle ear space remains more controversial.

The vitamin D status of East Indian Punjabi immigrants to Canada.

1. Serum 25-hydroxyvitamin D (25-OHD), calcium and alkaline phosphatase (EC 3.1.3.1) levels and vitamin D intakes (from 3 d weighed dietary records) were determined in a cohort of fifty-nine male East Indian Punjabi immigrants (37.7 (SD 10.5) years) and fifty-four females (33.3 (SD 7.4) years). 2. Females had somewhat lower mean serum 25-OHD levels (12.3 (SD 5.0) v. 14.2 (SD 5.1) ng/ml, P less than 0.05) and serum Ca levels (88 (SD 8) v. 91 (SD 6) mg/l) than males (P less than 0.05) whereas serum alkaline phosphatase values (males 167 (SD 63), females 169 (SD 43) IU/l) and dietary vitamin D intakes (males 3.5 (SD 1.8), females 3.3 (SD 2.0) micrograms/d) were similar. 3. 22% of the females and 12% of the males had serum 25-OHD levels below 9.0 ng/ml but none had serum 25-OHD levels within the range associated with clinically overt disease. 4. In the males, serum 25-OHD levels were negatively correlated with dietary fibre intakes (g/d; r -0.29; P less than 0.05). 5. Multiple-regression analysis indicated that log serum 25-OHD levels were not related to dietary vitamin D intakes. Instead they were associated with sex and dietary fibre intakes (g/MJ) (F 3.71; P = 0.03). These two variables explained 8% of the variance.

Iron status of predominantly lacto-ovo vegetarian East Indian immigrants to Canada: a model approach.

Iron status of East Indian predominantly lacto-ovo vegetarian immigrants (59 males, mean age 37.7 +/- 10.5 yr; 55 females, mean age 33.3 +/- 7.4 yr) was assessed using dietary and biochemical-iron indices, including a Tri-index (TI) model. Iron deficiency was higher among females than males: 33% vs 5%, respectively, via the TI model (serum ferritin, serum-transferrin saturation, and mean corpuscular-hemoglobin concentration) and 18-42% vs 2-22%, respectively, via individual biochemical-iron indices. Rates of anemia calculated via the TI model in combination with low hemoglobin and mixed-distribution analysis (MDA) were similar and higher for the females (TI + Hb = 16%; MDA = 12%) than for the males (TI + Hb = 5%; MDA = 3%). High prevalence among females was attributed to low available iron intakes, concomitant with high intakes of dietary fiber, phytate, and tannins. We recommend the TI-model approach to estimate relative prevalence of iron deficiency in small surveys.

Mineral intakes of predominantly lacto-ovo vegetarian East Indian adults.

Daily energy, protein, calcium (Ca), phosphorus (P), zinc (Zn), copper (Cu), manganese (Mn), and dietary fiber intakes of East Indian Punjabi immigrants consuming predominantly lacto-ovo vegetarian diets [59 males (M), mean age 37.7±10.5 yr. and 53 females (F), mean age 33.3±7.4 yr] were assessed by calculation from 3-d weighted dietary records, using food composition values and by chemical analysis of 30 1-d diet composites. Mean daily calculated intakes wer: energy, M=2374±713 and F=1708±552 kcal; protein, M=95.8±35.1 and F=68.0±28.9g; Ca, M=990±468 and F=837±393 mg; M=2034±778 and F=1489±551 mg; Zn, M=12.2±4.9 and F=8.8±3.9 mg; Cu, M=2.4±0.9 and F=1.7±0.6 mg; and Mn, M=7.7±3.3 and F=5.7±2.4 mg. The mean daily Ca intakes for M and F were 124 and 105%, respectively, of the Canadian Recommended Nutrient Intake (RNI). In contrast, average P intakes were much higher, 254 and 213% of the RNI for M and F, respectively, so that the mean Ca:P ratios were 1:2.0 for M and 1:1.8 for F. Forty-eight percent of the F compared to 19% of the M had Zn intakes below the current RNI, whereas 28% of the M and 77% of the F received Cu intakes below the suggested US safe and adequate range. Mean daily Mn intakes were higher than those for subjects consuming omniverous North American diets and none of the subjects had Mn intakes below the US safe and adequate range.