Effects of surgery on the pharmacokinetic parameters of drugs

As with other forms of stress, surgery is a time of fluctuating haemodynamics, physiological shifts, intense metabolic changes, and protein catabolism and anabolism. At times, these changes can occur within hours. There is a reasonable body of literature concerning the adverse effects of surgery on gastric emptying, but not on the effects of surgery on the distribution, metabolism and excretion of drugs. Gastric emptying is diminished or absent following major procedures, which prevent the delivery of orally administered drugs to their major site of absorption, the small bowel. Changes in the paracellular absorption of drugs may occur postoperatively, although transcellular absorption appears to be unimpaired. Distribution is affected by changes in blood volume, alterations in circulation, increases in the extracellular fluid and changes in the circulating plasma protein levels, such as albumin and alpha 1-acid glycoprotein. Little is known about alterations in drug metabolism following surgery. However, it has been shown that systemic hypoxia alters the function of some of the cytochrome P450 (CYP) system and increased levels of cytokines have an effect on the metabolism of at least 1 drug. In addition, the renal elimination of drugs is affected in patients postoperatively, although the effects of biliary clearance in this period are difficult to determine. Despite the lack of research into pharmacokinetics during the postoperative period, and given the immense and often sudden changes observed in patients post-surgery, it is reasonable to recommend vigilance with respect to drug therapy during this period.     

Anesthesia and analgesia for minor injuries to children

Today's children are rambunctious, playful, and aggressive and are provided through the miracles of modern technology with ample opportunities to injure themselves. As such, they are a source of both joy and terror to their parents. It is a "given" that many of them will injure themselves in the course of growing up. When they come to us in the ED waiting room, they are typically very frightened and usually in pain. We are fortunate that we have techniques and drugs to alleviate this pain and to attenuate their fear. It is our responsibility as anesthesiologists to ensure that these drugs and techniques are used appropriately and cause no further harm. We hope the information contained in this chapter may be of benefit in achieving this goal.     

Physiological compensation in antisense transformants: specific induction of an "ersatz" glucan endo-1,3-beta-glucosidase in plants infected with necrotizing viruses

Plant class I glucan endo-1,3-beta-glucosidases (beta-1,3-glucanase; 1,3-beta-D-glucan glucanohydrolase, EC 3.2.1.39) have been implicated in development and defense against pathogen attack. Nevertheless, beta-1,3-glucanase deficiencies generated by antisense transformation of Nicotiana sylvestris and tobacco have little biological effect. We report here that another beta-1,3-glucanase activity is induced in these deficient mutants after infection with necrotizing viruses. Induction of class I beta-1,3-glucanase was markedly inhibited in leaves of N. sylvestris and tobacco antisense transformants infected with tobacco necrosis virus and tobacco mosaic virus, respectively. A serologically distinct beta-1,3-glucanase activity was present in the infected antisense transformants but was absent in both healthy and infected control plants and in antisense transformants treated with the stress hormone ethylene. Immunoblot analyses, localization studies, and measurements of antibody specificity indicate that this compensatory beta-1,3-glucanase activity is an intracellular enzyme different from known tobacco beta-1,3-glucanases. Therefore, plants can compensate for a deficiency in enzyme activity by producing a functionally equivalent replacement--i.e., "ersatz"--protein or proteins. The fact that compensation for beta-1,3-glucanase activity occurs in response to infection argues strongly for an important role of these enzymes in pathogenesis.     

The psychological development of orphanage-reared infants: interventions with outcomes (Tehran)

This paper describes five successive interventions in the rearing of infants at an orphanage in Tehran, with their outcomes. The outcomes were assessed longitudinally. The first of the successive groups, here called "waves", numbered 15. These Ss constitute the controls. The only intervention consisted of examining the infants every other week during the first year and every fourth week thereafter with the ordinal, sensorimotor scales of Uzgiris and Hunt. The audio-visual intervention intended for the second wave of 10 infants was tape-recorded mother talk and music under the control of the infants and mobiles that the infants could activate. This plan was never adequately implemented because of inadequate supervision. The third wave of 10 infants got extra untutored human care. The fourth wave of 20 infants got the kind of audio-visual intervention originally intended for the second wave plus access to responsive inanimate materials. For the fifth wave, numbering 11, the infant-caretaker ratio was reduced to two or three to one and the caretakers were taught the Badger program supplemented with procedures to foster vocal imitation and semantic mastery of body parts, clothing, toys, and other objects and events regularly encountered. The results show that each successive wave, excepting the second, achieved the top steps of nearly all seven of the ordinal scales at mean ages younger than the preceding wave, and the fifth wave surpassed even home-reared American children from predominantly professional families in achieving the top steps on five of the seven scales. The findings show that infants need not advance along all branches simultaneously and that the kinds of experience encountered determine the branch along which advancement occurs. A number of theoretical implications are examined. Especially important is the idea that a dependable educational psychology for infancy and early childhood calls for much more knowledge than we now have of the kinds of experience that advance development along each of the various branches.     

增加折叠电流保护的电路

对许多需要数安培供电电流的应用而言，三端输出可调线性稳压器有易用．低成本和完全片上过载保护等特点，如美国国家半导体公司的LM317。增加数个元器件可以使三端稳压器具备一种高速度的短路限流能力，从而提高可靠性。限流器可将最大输出电流限制在一个安全的恒定水平IMAX上，避免稳压器的损坏。当出现一个故障状况时，传输晶体管上的功耗近似于VIN×IMAX。要让设计的稳压器能承受过载，就需要谨慎地选择元器件的额定值（经常是留了过大的余地），除非可以在故障发生时降低或折叠（foldback）输出电流。     

Orientation disruptor (ord): a recombination-defective and disjunction-defective meiotic mutant in Drosophila melanogaster

The effects of a semidominant autosomal meiotic mutant, orientation disruptor (symbol: ord), located at 2-103.5 on the genetic map and in region 59B-D of the salivary map, have been examined genetically and cytologically. The results are as follows. (1) Crossing over in homozygous females is reduced to about seven percent of controls on all chromosomes, with the reduction greatest in distal regions. (2) Crossing over on different chromosomes is independent. (3) Reductional nondisjunction of any given chromosome is increased to about thirty percent of gametes from homozygous females. The probability of such nondisjunction is the same among exchange and nonexchange tetrads with the exception that a very proximal exchange tends to regularize segregation. (4) Equational nondisjunction of each chromosome is increased to about ten percent of gametes in homozygous females; this nondisjunction is independent of exchange. (5) The distributive pairing system is operative in homozygous females. (6) In homozygous males, reductional nondisjunction of each chromosome is increased to about ten percent, and equational nondisjunction to about twenty percent, of all gametes. (7) Cytologically, two distinct meiotic divisions occur in spermatocytes of homozygous males. The first division looks normal although occasional univalents are present at prophase I and a few lagging chromosomes are seen at anaphase I. However, sister chromatids of most chromosomes have precociously separated by metaphase II. Possible functions of the ord(+) gene are considered.     

Intra-arterial sympathetic blockade in the treatment of clinical frostbite

Regional medical sympathectomy achieved by the intra-arterial injection of reserpine appeared to be of benefit in the treatment of five patients with acute or chronic frostbite injuries. Clinical improvement was associated with a significant increase in arteriographically determined regional perfusion.     

Cholesterogenesis: derepression in extrahepatic tissues with 4-aminopyrazolo (3,4-d) pyrimidine

Administration of 4-aminopyrazolo [3,4-d] pyrimidine decreased serum cholesterol levels in the rat to less than 5 milligrams per deciliter. Coincident with this change, there was a 2.1 - to 16.0-fold increase in the rate of sterol synthesis in seven extrahepatic tissues. This suggests that cholesterol carried in serum lipoproteins plays a major role in regulating sterol synthesis in many extrahepatic tissues.     

Effects of glutathione-oxidizing agents on microtubule assembly and microtubule-dependent surface properties of human neutrophils

In human peripheral blood polymorphonuclear leukocytes and lymphocytes, GSH-oxidizing agents promote the movement of surface-bound concanavalin A (Con A) into caps and inhibit the assembly of microtubules (MT) that is normally induced by Con A binding. Con A capping and inhibition of MT assembly occur when GSH levels in cell suspensions are decreased by 30-70%, and return to GSH to control levels is accompanied by the appearance of cytoplasmic MT and by inhibition of the capping response with Con A. Oxidation of GSH markedly stimulates the hexose monophosphate shunt, and regeneration of GSH occurs rapidly. The data indicate that MT cannot be assembled or maintained in the face of decreased GSH levels. Thus, GSH homeostasis becomes critical during physiological events such as phagocytosis which simultaneously induce the assembly of MT and the production of agents like H2O2 that can oxidize GSH.     

Derepressed alloantigen in transplacentally induced lung tumor coded for by H-2 linked gene

A transplacentally induced lung tumor of strain C3Hf mice grows progressively when transplanted to (C3Hf X A)F1 hybrid mice but not when transplanted to C3Hf recipients. Progressive tumor growth occurs in [(C3Hf X A)F1 X C3Hf] backcross mice inheriting the H-2a haplotype from the F1 parent. Furthermore, radioresistant immunity to the lung tumor can be induced in C3Hf mice by immunization with normal tissue of B10.A and B10.A(2R) but not of B10 or B10.A(5R) strain mice.