A surgical model for determination of true absorption and biliary excretion of manganese in conscious swine fed commercial diets

Some trace elements, such as Mn, Cu and Zn, are absorbed and quickly resecreted into the gut through the bile. When this occurs, the unabsorbed nutrient and the absorbed and resecreted nutrient may mix in the gut, preventing quantitative calculation of either. We have developed a surgical model that prevents this complication. Pigs (20-40 kg) were fitted with cannulas in the bile duct, lumen of the duodenum, portal vein, ileocolic vein and jugular vein. After recovery for 6-8 d, pigs were given an oral dose of 9.25 mBq of 54Mn. The flow rate of blood past the portal vein was determined by infusion of P-amino hippuric acid into the ileocolic vein. Absorption was quantified by multiplying the concentration of 54Mn in the portal blood by the flow rate. Biliary excretion was determined by quantitative collection of bile, and previously collected bile was reinfused into the gut lumen. Urine and feces were also quantitatively collected. A postoperative time of 6-8 d was sufficient for pigs to recover from the effects of surgery and anesthesia, as assessed by several measures of metabolic function and food and water intake. True absorption was calculated to be 0.5%. 54Mn in the urine and bile began to increase after 4 d. When the pigs were killed after 12 d, only 0.5% of the 54Mn remained in the carcass. Results of this study show that pigs surgically modified by the described procedure can recover fully and can serve as a model to study intestinal absorption and biliary excretion of nutrients. Furthermore, initial studies using 54Mn showed that the model is applicable to studying Mn metabolism and suggest the need for a more detailed study of Mn absorption and biliary excretion.     

Cost-effective reduction of neuromuscular-blocking drug expenditures

BACKGROUND: Anesthetic drug expenditures have been a focus of cost-containment efforts. The aim of this study was to determine whether expenditures for neuromuscular-blocking agents could be reduced without compromising outcome, and to determine whether such a cost-effective pattern of neuromuscular blocker use could be sustained. METHODS: Education, practice guidelines, and paperwork barriers were used to persuade anesthesiologists to substitute low-cost neuromuscular-blocking drugs (pancuronium or a metocurine-pancuronium combination) for a more costly neuromuscular-blocking drug (vecuronium). Neuromuscular-blocking drug use in all patients during a historical control period (6 months; n = 4,804) was compared with that during two consecutive 1-yr periods of intervention (n = 9,761/n = 10,695). Expenditures for vecuronium and for all neuromuscular-blocking drugs were compared for the control and intervention periods. The rate of complications related to neuromuscular-blocking drugs was determined by an ongoing continuous quality improvement program. RESULTS: Vecuronium use decreased by 76% during the first and second yr of intervention, compared with the historical period (P < 0.01). The cost of neuromuscular-blocking drugs decreased by 31% (P < 0.01) and 47% (P < 0.01) for the first and second yr, respectively. The complication rate related to neuromuscular-blocking drugs was 0.081% in the historical period and 0.11% and 0.093% during the intervention periods (P = 0.29 and 0.41). CONCLUSION: Practice guidelines, education, and paperwork barriers used together substantially reduced the expenditures for neuromuscular-blocking drugs for 2 yr without adversely affecting clinical outcome.     

Management guidelines for progressive chronic renal failure. New Zealand Nephrologists Consensus Group

Consensus guidelines are provided for the conservative management of adult patients with chronic and progressive renal failure, together with a brief review of the evidence relating to various treatable complications. Blood pressure control, diet, hyperlipidaemia, calcium and phosphate metabolism, anaemia and acidosis are considered.     

Fathers of persons with mental illness: a preliminary study of coping capacity and service needs

The effects of a single dose of caffeine on specific information processing operations were examined by using a visual selective attention task in which subjects were asked to select between a left and right hand response on the basis of two different target letters. The target was presented on a predefined position in the visual field and was either presented alone or with flanker letters, calling for the correct, the incorrect or no specific response. A dose of 3 mg/kg body weight caffeine or lactose, dissolved in a cup of decaffeinated coffee, was administered double blind and deceptively to overnight abstinence coffee drinkers. Behavioural measures were supplemented by psychophysiological measures. The present results replicated the basic findings obtained in this paradigm. The results indicated that the time to localise the target decreased and response preparation started earlier after caffeine than after placebo. These caffeine effects did not interact with the time subjects spent on the task or with the reaction time distribution, which might be due to a high level of practice.     

MAD analysis of FHIT, a putative human tumor suppressor from the HIT protein family

BACKGROUND: The fragile histidine triad (FHIT) protein is a member of the large and ubiquitous histidine triad (HIT) family of proteins. It is expressed from a gene located at a fragile site on human chromosome 3, which is commonly disrupted in association with certain cancers. On the basis of the genetic evidence, it has been postulated that the FHIT protein may function as a tumor suppressor, implying a role for the FHIT protein in carcinogenesis. The FHIT protein has dinucleoside polyphosphate hydrolase activity in vitro, thus suggesting that its role in vivo may involve the hydrolysis of a phosphoanhydride bond. The structural analysis of FHIT will identify critical residues involved in substrate binding and catalysis, and will provide insights into the in vivo function of HIT proteins. RESULTS: The three-dimensional crystal structures of free and nucleoside complexed FHIT have been determined from multiwavelength anomalous diffraction (MAD) data, and they represent some of the first successful structures to be measured with undulator radiation at the Advanced Photon Source. The structures of FHIT reveal that this protein exists as an intimate homodimer, which is based on a core structure observed previously in another human HIT homolog, protein kinase C interacting protein (PKCI), but has distinctive elaborations at both the N and C termini. Conserved residues within the HIT family, which are involved in the interactions of the proteins with nucleoside and phosphate groups, appear to be relevant for the catalytic activity of this protein. CONCLUSIONS: The structure of FHIT, a divergent HIT protein family member, in complex with a nucleotide analog suggests a metal-independent catalytic mechanism for the HIT family of proteins. A structural comparison of FHIT with PKCI and galactose-1-phosphate uridylyltransferase (GaIT) reveals additional implications for the structural and functional evolution of the ubiquitous HIT family of proteins.