Genetic polymorphisms of UDP-glucuronosyltransferases (UGTs) are involved in individual and ethnic differences in drug metabolism. To reveal co-occurrence of the UGT1A polymorphisms, we first analyzed haplotype structures of the entire UGT1A gene complex using the polymorphisms from 196 Japanese subjects. Based on strong linkage disequilibrium between UGT1A8 and 1A10, among 1A9, 1A7, and 1A6, and between 1A3 and 1A1, the complex was divided into five blocks, Block 8/10, Block 9/6, Block 4, Block 3/1, and Block C, and the haplotypes for each block were subsequently determined/inferred. Second, using pyrosequencing or direct sequencing, additional 105 subjects were genotyped for 41 functionally tagged polymorphisms. The data from 301 subjects confirmed the robustness of block partitioning, but several linkages among the haplotypes with functional changes were found across the blocks. Thus, important haplotypes and their linkages were identified among the UGT1A gene blocks (and segments), which should be considered in pharmacogenetic studies.

Asian People↗

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Cytomegalovirus-induced gastritis in a bone marrow transplant patient.

Cytomegalovirus (CMV)-induced interstitial pneumonitis is a well-known lethal complication in bone marrow recipients. CMV is also known to cause gastroenteritis. We report the first case of a bone marrow recipient who developed CMV-induced gastritis which is verified both histologically and virologically. The gastritis preceded the interstitial pneumonitis which was detected in an early stage and was successfully treated. We propose that bone marrow recipients who show signs and symptoms of gastritis undergo an endoscopic examination, and that biopsied specimens should be scrutinized for CMV by both histological examination and culture investigation.

Bone Marrow Transplantation↗

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Support workers in Japan.

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Humans↗

PubMedDate not supplied

Physiologically based pharmacokinetic model for cefazolin in rabbits and its preliminary extrapolation to man.

In the present study, the physiologically based pharmacokinetic model, which succeeded previously in predicting the pharmacokinetics of beta-lactam antibiotics in rats [A. Tsuji, T. Yoshikawa, K. Nishide, H. Minami, M. Kimura, E. Nakashima, T. Terasaki, E. Miyamoto, C.H. Nightingale, and T. Yamana: Physiologically based pharmacokinetic model for beta-lactam antibiotics. I: tissue distribution and elimination in rats. J. Pharm. Sci. 72, 1239-1252 (1983)], was applied to cefazolin pharmacokinetics in rabbits and man. After iv bolus dosing in normal rabbits, the time courses of cefazolin concentration in plasma and various tissues (lung, heart, muscle, skin, bone, gut, liver, and kidney) were found to be very similar to those in rats. The values of physiological parameters (tissue plasma flows, tissue volumes, tissue/plasma albumin ratio) and biochemical parameters determined in this study (for nonlinear plasma protein binding, intrinsic renal clearance of active secretion and reabsorption) were incorporated into mass balance equations derived from the model. There was reasonable agreement between the model predictions and the observed data for cefazolin and inulin in rabbits. The model was also successful in the prediction of cefazolin disposition in rabbits with renal failure. Using available information reported for cefazolin in man, a preliminary extrapolation from the present model was attempted, and the overall predicted results after iv administration of 1 g cefazolin in man were compared with the serum and bone tissue data. The length of the effective antibacterial period for the drug is also discussed in terms of its predicted concentration unbound with proteins in various tissue interstitial fluids in man.

Animals↗

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High frequency chest wall compression and carbon dioxide elimination in obstructed dogs.

High frequency chest wall compression (HFCWC) was studied as a method of assisting ventilation in six spontaneously breathing anesthetized dogs. Under a constant level of anesthesia, the dogs became hypercapneic after airflow obstruction was created by metal beads inserted in the airways. HFCWC was achieved by a piston pump rapidly oscillating the pressure in a modified double blood pressure cuff wrapped around the lower thorax. Thirty minute periods of spontaneous ventilation were alternated with thirty minute periods of spontaneous breathing plus HFCWC at 3, 5 or 8 Hz. The superimposition of HFCWC to spontaneous ventilation resulted in little change in the PaO2. The PaCO2, however, was reduced in every case from a mean of 6.55 +/- 0.59 to 4.72 +/- 0.32 kPa at 3 Hz (p less than 0.05), 6.92 +/- 0.57 to 3.9 +/- 0.45 kPa at 5 Hz (p less than 0.01) and 7.10 +/- 0.65 to 4.56 +/- 0.59 kPa at 8 Hz (p less than 0.05). This occurred despite a decrease in spontaneous minute ventilation. We conclude that HFCWC can assist in elimination of CO2 in obstructed spontaneous breathing dogs with hypercapnea.

Animals↗

PubMedDate not supplied

[Understanding of environmental impact with inpatients based on structural modeling].

This study examined how inpatients perceive environmental impacts using the ISM(Interpretive Structural Modeling)method. 18 new items among inpatients perceiving the environmental impacts were selected through a discussion with three researchers, two nurses, and six patients. This was applied to two inpatients who were not in the same ambulatory state in order to establish the validity of the structural models. As a result, the structuring models showed the difference depending on each patient. Therefore the structuring model is effective to assess the environmental impacts on individuals.

Humans↗