Adolescent Transition to Adult Care in Solid Organ Transplantation: a consensus conference report.

Transition of care from pediatric to adult-oriented health care providers is difficult for children with special health care needs. Children who have received solid organ transplants and their providers experience the same difficulties and frustrations as children with other major illnesses. A consensus conference was organized by several transplant organizations to identify major issues in this area and recommend possible approaches to easing the process of transition for solid organ transplant recipients. This report summarizes the discussions and recommendations.

Selective inhibition of initial polyadenylation in isolated nuclei by low levels of cordycepin 5"-triphosphate.

The effect of cordycepin 5'-triphosphate on poly(A) synthesis was investigated in isolated rat hepatic nuclei. Nuclei were incubated in the absence and presence of exogenous primer in order to distinguish the chromatin-associated poly(A) polymerase from the "free" enzyme (Jacob, S.T., Roe, F.J. and Rose, K.M. (1976) Biochem. J. 153, 733--735). The chromatin-bound enzyme, which adds adenylate residues onto the endogenous RNA, was selectively inhibited at low concentrations of cordycepin 5'-triphosphate, 50% inhibition being achieved at 2microng/ml. At least 80 times more inhibitor was required for 50% reduction in the "free" nuclear poly(A) polymerase activity. Inhibition of DNA-dependent RNA synthesis also required higher concentrations of the nucleotide analogue. These data not only offer a mechanism for the selective inhibition of initial polyadenylation of heterogeneous nuclear RNA in vivo by cordycepin, but also provide a satisfactory explanation for the indiscriminate effect of the inhibitor on partially purified or "free" poly(A) and RNA polymerases.

One-year follow-up of weight, total body potassium, and total body nitrogen in obese adolescents treated with the protein-sparing modified fast.

Seventeen obese adolescents were treated with the protein-sparing modified fast (PSMF), a high-protein, low-carbohydrate, low-calorie diet, for approximately 3 mo and then followed for a total of 12 mo. The diet provided a mean of 880 kcal.kg-1. d-1 and 2.5 g protein. kg IBW-1. d-1. Body composition was determined using four skinfold measurements, total body potassium (TBK), and total body nitrogen (TBN) at baseline, 3 mo, and 12 mo. Twelve subjects returned for follow-up at 1 y (71%) and 48% had sustained weight loss with the percentage ideal body weight for height decreased from 154 to 125 over the year. Six subjects had TBK and TBN measured and TBK decreased 13.0% and TBN decreased 14.3% over the year. This reflected a change toward normalization of the predicted TBK from 121 to 102% and TBN from 119 to 102%.

Women, food and HIV.

AIDS: Women with HIV need to consider their diet and how it relates to their medical treatment with anti-HIV drug regimens. Unplanned weight loss, called AIDS-related wasting syndrome, is a common factor with HIV disease, and is among the leading causes of death for HIV-positive women and men. Currently, diets for women with HIV are largely based on research conducted for other disorders or research based on male participants. Only three trials over the last ten years reflected nutritional research specific to women and wasting, and the data showed fundamental differences between the effect of the syndrome on women versus men. The use and benefits of anabolic steroids, such as oxandrolone, to assist women in maintaining lean body mass are discussed. Greater emphasis needs to be placed on proper nutrition and its benefits of promoting the body's response to restore and maintain energy. Tables are provided that give guidance for healthy food choices and suggestions for incorporating healthy eating into an individual's lifestyle.^ieng

Immunization mall programs.

This descriptive survey provided the Health Department and its CHNs with data heretofore unexamined. The survey provided a beginning analysis and description of three major areas which assisted the County Health Department in establishing vital base line information regarding: (a) where people usually went for immunizations, (b) how they heard about the mall program, and (c) whether they would return to future mall programs. Recommendations from the survey demonstrate the need for the county health department and CHNs to increase the number and length of programs and to meet client demand. The survey has implications for all public health departments and CHNs as they examine the most cost effective strategies to promote and provide immunizations for vaccine preventable disease to clients of all ages.

The influence of age on the distribution, metabolism and excretion of methoxyflurane in Fischer 344 rats: a possible relationship to nephrotoxicity.

Age as a factor in methoxyflurane nephrotoxicity was evaluated in Fischer 344 rats of various ages by determination of: 1) serum inorganic fluoride and methoxyflurane concentrations, and urinary inorganic fluoride excretion in methoxyflurane-exposed rats; 2) liver microsomal methoxyflurane defluorinase activity; and 3) distribution of injected sodium fluoride. Only rats in the youngest age group (6 weeks) did not develop nephrotoxicity after anesthesia. Older rats had a biphasic rather than a monophasic decay in serum methoxyflurane concentration and also had increased serum inorganic fluoride concentration and urinary inorganic fluoride excretion. Older rats also excreted a greater proportion of an injected dose of sodium fluoride compared to young rats. Microsomal methoxyflurane defluorinase specific activity was similar among rats of all ages. It is likely that increased availability of methoxyflurane due to its greater storage in fat led to more inorganic fluoride production in older compared to younger rats. Bone sequestration of inorganic fluoride in younger rats probably accounts for decreased serum inorganic fluoride levels in that group. Both factors cause significant differences in renal exposure to inorganic fluoride; thus the risk of nephrotoxicity is less in younger animals.

Specific inhibition of chromatin-associated poly(A) synthesis in vitro by cordycepin 5'-triphosphate.

It has been established that many eukaryotic mRNAs contain poly(adenylic acid) tracts at their 3'-termini. The polyadenylation of mRNA occurs post-transcriptionally in the nucleus as a rapid, initial addition of 100-200 adenylate residues to the pre-mRNA (ref. 1). Subsequently, a slower chain extension (6-8 bases) of the poly(A) tail seems to occur both in the nucleus and in the cytoplasm. The initial polyadenylation reaction can be specifically inhibited by the drug cordycepin (3'-deoxyadenosine) in cell culture, presumably by its conversion to the triphosphate analogue which acts as a competitive inhibitor of poly(A) polymerase. Cordycepin, however, has little effect on the slower poly(A) extension reaction or on the formation of mRNA precursor molecules; but it can inhibit rRNA synthesis. Contrary to the in vitro observations, cordycepin 5'-triphosphate (3'dATP) is not a specific inhibitor of poly(A) synthesis in vivo, relative to RNA synthesis, and RNA polymerase I (which synthesises rRNA) is actually less sensitive to inhibition by 3'dATP than RNA polymerase II (ref. 10) (which is presumed to be involved in the synthesis of mRNA). Since nuclear poly(A) polymerase occurs in two functional states as 'free' and 'chromatin-bound' forms, we reasoned that if the chromatin-associated poly(A) polymerase were involved in the initial polyadenylation of mRNA, it might be selectively inhibited by 3'dATP. The present studies, designed to test such an idea, demonstrate that, as in vivo, the initial polyadenylation reaction can be selectively inhibited in vitro by low levels of 3'dATP. These data also show that higher levels of 3'dATP can inhibit RNA synthesis, 'chromatin-bound' RNA polymerase I activity being significantly more sensitive than the 'bound' RNA polymerase II activity.

Ultrastructural localisation of alkaline phosphatase in adult human large intestine.

The localisation of alkaline phosphatase in human large intestine was investigated at the ultrastructural level. Alkaline phosphatase was found in the mature absorptive cells of the surface, upper, and middle crypt epithelium; the reaction product was localised in the glycocalyx coat of the microvilli, the Golgi apparatus, and the rough endoplasmic reticulum. Slight activity was found in the immature absorptive cells of the middle and lower regions of the crypts. The undifferentiated cells and the enterochromaffin cells were negative. In the lamina propria, alkaline phosphatase was localised in the plasma membrane of the endothelial cells of the venules, in the rough endoplasmic reticulum of the plasma cells, and the cell membrane of macrophages. These results are consistent with the role of alkaline phosphatase in membrane transport.

Effect of halothane-oxygen anesthesia on the pharmacokinetics of diazepam and its metabolites in rats.

Inhalation anesthetics have been shown to substantially diminish the clearance of several drugs eliminated by hepatic routes. The purpose of the present study was to determine the influence of halothane-oxygen anesthesia on the hepatic metabolism of diazepam and its proximate metabolites in anesthetized rats whose physiologic status was monitored and maintained. The portal vein, femoral artery and bile duct of male Sprague-Dawley rats 370 to 395 g, were cannulated under pentobarbital anesthesia. After a 2-hr recovery period, [14C]diazepam was administered in to the portal vein as a 0.25-mg/kg bolus followed immediately by a 0.25-mg/kg/hr infusion by the same route. After the attainment of steady state, the halothane group (seven rats) received 1% halothane in oxygen whereas the control group (six rats) continued to breathe room air. The diazepam infusion was maintained for an additional 3 hr. Concentrations of diazepam, N-desmethyldiazepam, 4-hydroxyphenyldiazepam and 3-hydroxydiazepam were determined in plasma; these metabolites as well as oxazepam and N-desmethyl-4-hydroxyphenyldiazepam were also determined in bile. Radioactivity in bile was approximately 98% conjugated; radioactivity in plasma was approximately 30% conjugated. Halothane anesthesia caused an increase in the concentrations of diazepam and its metabolites in plasma, but the steady-state ratios of the concentration of the individual metabolites in plasma to diazepam concentration were not changed. The intrinsic clearance of diazepam was decreased by 42%, P less than .01, and the ratio of formation to elimination clearance of the metabolites measured in plasma was not changed. Halothane anesthesia also decreased the excretion rate of 14C into bile.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Distributed Growth of Saccharomyces cerevisiae Cells Immobilized in Polyacrylamide Gel.

A technique is described for the quantitative determination of the distributed growth of Saccharomyces cerevisiae immobilized in polyacrylamide gel. Gel specimens were embedded in paraffin or gelatin and paraffin before sectioning and staining. Photomicrographs of specimen sections were enlarged, and cell microcolony volumes were determined as a function of position in the gel by grid transparency analysis. Overall cell densities within the gel were calculated for a quantitative comparison with values measured by a second spectrophotometric method. The results show good agreement and demonstrate the sigmoidal growth of the immobilized cells, reaching a maximum steady-state value. The technique shows promise as a general method for following the transient growth of organisms immobilized within gel particles.

A heparin-sensitive nuclear protein kinase. Purification, properties, and increased activity in rat hepatoma relative to liver.

A cyclic-nucleotide independent heparin-sensitive nuclear protein kinase (NII) from the Morris hepatoma 3924A has been purified by a combination of ion exchange and affinity chromatographic procedures and velocity gradient centrifugation. The purified kinase had a molecular weight of 140,000 as determined by gel filtration. Two polypeptides (Mr = 42,000 and 25,600) were present in the purified preparation in approximately equimolar concentrations. The protein kinase employed Mg2+ and Co2+ as divalent ion and preferred the nonhistone proteins, casein or phosvitin, as protein acceptors. In the presence of Mg2+, it utilized both ATP and GTP as substrates and transferred the terminal nucleotide phosphate to serine and threonine residues of the protein acceptor. Phosphorylation of casein was stimulated by polyamines, particularly spermine. This polyamine preferentially enhanced phosphate transfer to threonine. The enzyme was inhibited by several compounds including heparin, the o-n-octyloxime of rifamycin (AF/013), 3'-dATP, o-phenanthroline, polynucleotides, and ADP. Of these inhibitors, heparin was the most potent and completely abolished kinase activity at a concentration of 0.1 micrograms/ml. The kinase could be autophosphorylated by incubation with Mg2+ and [gamma-32P]ATP; under these conditions phosphorylation was confined to the polypeptide of Mr = 24,600 and was completely inhibited by heparin. Based on the unique properties of NII protein kinase (ability to use GTP, stimulation by spermine, sensitivity to heparin), a selective assay was developed which could measure NII activity in the presence of other nuclear kinases. Under the optimal assay conditions, the nuclear extract of hepatoma 3924A was found to contain at least five times more NII kinase activity than that of normal adult liver. Analysis of extensively purified preparations from the two sources confirmed these results. After purification 11 times more NII protein kinase activity was obtained from hepatoma 3924A than from liver. Although hepatoma and liver protein kinases exhibited many common properties, they displayed distinct nucleotide saturation kinetics. The apparent Km for ATP was 10 microM for hepatoma protein kinase and 24 microM for the liver enzyme.

Caudal anesthesia with lidocaine or bupivacaine: plasma local anesthetic concentration and extent of sensory spread in old and young patients.

Continuous caudal peridural anesthesia with 2% lidocaine (6 mg/kg) or 0.75% bupivacaine (2.2 mg/kg), both with epinephrine 1:200,000, was studied in two groups of male patients, younger than 40 or older than 55 yr old, respectively. Patients receiving lidocaine in the younger group (n = 6) were 32 +/- 5.2 (mean +/- SD) yr old and weighed 75 +/- 12 kg, while those in the older group (n = 16) were 66 +/- 5.3 yr old and weighed 72 +/- 8.2 kg. Patients receiving bupivacaine in the respective groups were 27 +/- 7.0 yr old (n = 5), and 76 +/- 10 kg compared to 69 +/- 10 yr (n = 14) and 75 +/- 10 kg. Anesthesia was satisfactory in all patients. Extent of sensory anesthesia, peak plasma lidocaine or bupivacaine concentrations, and area under the plasma concentration-time curves were independent of age. No local anesthetic toxicity was observed and peak drug concentrations were below those commonly associated with toxicity.

Reversible encephalopathy associated with tacrolimus in pediatric renal transplants.

Neurological complications post transplant have been described with the use of calcineurin inhibitors. Although tacrolimus may be a better immunosuppressant than cyclosporine, its neurological side effects may be worse. Two children, living-related kidney transplant recipients, were treated with antibody induction, mycophenolate mofetil, prednisone, and tacrolimus. Soon after transplant, they each developed an encephalopathy, which when visualized by magnetic resonance imaging showed that it affected both white and grey matter of the brain. Although the encephalopathy was associated with the use of tacrolimus, there was a complete neurological recovery without cessation of the drug.