Haemodynamic effects of atropine during halothane or isoflurane anaesthesia in infants and small children

In this study, two-dimensional and pulsed Doppler echocardiography were used to measure cardiovascular changes before and after IV atropine in 31 infants and small children during halothane (n = 15) or isoflurane (n = 16) anaesthesia. Prior to induction of anaesthesia heart rate (HR), mean blood pressure (MBP), and two0dimensional echocardiographic dimensions of the left ventricle and pulmonary artery bloodflow velocity were measured by pulsed Doppler echocardiography. Cardiovascular measurements were repeated while anaesthesia was maintained at 1.5 MAC halothane (n = 15) or isoflurane (n = 16). Atropine 0.02 mg·kg⁻¹ IV was then administered and two minutes later, a third set of cardiovascular data was obtained. Heart rate decreased during halothane anaesthesia but did not change significantly during isoflurane anaesthesia. Mean blood pressure, cardiac output (CO) and stroke volume (SV) decreased similarly during 1.5 MAC halothane or isoflurane anaesthesia. Ejection fraction (EF) decreased and left ventricular end-diastolic volume (LVEDV) increased significantly in bothgroups, but decreases in EF (32 ± 5 percentvs18 ± 5 per cent) and increases in LVEDV (18 ± 7 per cent vs7 ± 5 per cent) were significantly greater during halothane than during isoflurane anaesthesia. Following atropine, HR increased more in the patients maintained with halothane (31 ± 6 per cent), than during isoflurane anaesthesia (18 ± 5 per cent). Atropine increased CO in both groups of patients, but SV and EF remained unchanged. When compared with awake values, HR increased similarly and significantly (18 ± 4 per cent) following atropine in both groups, and CO returned to control levels. Halothane decreased EF and increased LVEDV more than isoflurane at 1.5 MAC end— expired anaesthetic levels. Atropine did not diminish the myocardial depression produced by halothane or isoflurane. The increase in CO following atropine during halothane and isoflurane anaesthesia in infants and small children is the result of increases in HR alone. Nous avons utilisé un appareil à échocardiographie bi-dimensionnelle couplé à un Doppler pulsé chez des bébés et de jeunes enfants pour évaluer l’impact hémodynamique de l’halothane (n = 15) et de l’isoflurane (n = 16) et la modification possible de ces effets par l’atropine. Nous avons mesure la frequence cardiaque (FC), la pression artérielle moyenne (PAM), la dimension de la cavité ventriculaire gauche (par écho bi-dimensionnelle) et la vélocité du flot sanguin pulmonaire (par Doppler) et ce, en trois occasions soit avant l’induction, après l’instauration de 1.5 MAC d’halothane ou d’isoflurane et finalement, deux minutes après l’injection IV de 0.02 mg·kg⁻¹ d’atropine. On ne nota une baisse de la frequence cardiaque qu’avec l’halothane tandis que la PAM, le débit cardiaque (DC) et le volume d’éjection (VE) diminuaient autant avec l’un ou l’autre anesthésique. La diminution de la fraction d’éjection (FE) et l’augmentation du volume télédiastolique du ventricule gauche (VTDVG) significatives pour les deux groupes, étaienl plus marqué avec l’halothane qu’avec l’isoflurane: FE 32 ± 5 pour cent vs18 ±5 pour cent; VTDVG 18 ± 7 pour cent vs 7 ± 5 pour cent. Avec l’atropine, la FC monta plus dans le groupe halothane (31 ± 6 pour cent) que dans le groupe isoflurane (18 ± 5 pour cent), le DC augmentant dans les deux groupes, alors que le VE et la FE demeuraient inchangés. Comparée aux mesures pré-induction, l’atropine amenait une hausse significative de la FC, semblable dans les deux groupes (18 ± 4 pour cent) et restaurait le DC. Donc, chez les bebes et les jeunes enfants, a 1.5 MAC, l’halothane diminue la FE et augmente le VTDVG plus que ne le fait l’isoflurane. L’atropine ne modifie pas la depression myocardique et elle ne restaure le DC que par une hausse de la FC.

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Supported by PHS Grant No. 8507300 from the College of Medicine, University of Iowa Hospital, Iowa City, IA.     

Phenotypic and functional characteristics of tumor-associated lymphocytes in patients with malignant ascites receiving intraperitoneal infusions of recombinant interleukin-2 (rIL-2)

In the course of a phase I trial, in which recombinant IL-2 (rIL-2) was infused intraperitoneally (i.p.) in patients with peritoneal carcinomatosis, we evaluated the effect on "tumor-associated lymphocytes" (TAL) isolated from the ascitic fluid. No major changes in the percentages of cells expressing the CD3, CD4, CD8, Leu-7, OKM1 and WT-31 antigens were detected either in TAL or in peripheral blood lymphocytes (PBL) after 7 days of rIL-2 infusion. In contrast the percentages of TAL (but not PBL) expressing surface IL-2 receptor (Tac), or LAK-1 antigen were sharply increased. Analysis of cytolytic functions showed a potentiation of the lytic activity against natural-killer (NK) sensitive K562 target cells and the de novo appearance of lytic activity against fresh melanoma cells. In one patient IFN-gamma was detected in the ascitic fluid following rIL-2 infusion. T-cell clones derived from the patient were analyzed for the IFN-gamma production. While only approximately 40% of PB-derived control clones produced medium to low amounts of IFN-gamma, all of the TAL-derived clones produced medium to high amounts of the lymphokine.     

The molecular basis of Natural Killer (NK) cell recognition and function

Natural Killer cells are likely to play an important role in the host defenses because they kill virally infected or tumor cells but spare normal self-cells. The molecular mechanism that explains why NK cells do not kill indiscriminately has recently been elucidated. It is due to several specialized receptors that recognize major histocompatibility complex (MHC) class I molecules expressed on normal cells. The lack of expression of one or more HLA class I alleles leads to NK-mediated target cell lysis. Different types of receptors specific for groups of HLA-C, HLA-B, and, very recently, HLA-A alleles have been identified. While in most instances, they function as inhibitory receptors, an activatory form of the HLA-C-specific receptors has been identified in some donors. Molecular cloning of HLA-C-, HLA-B- or HLA-A-specific receptors has revealed new members of the immunoglobulin superfamily with two or three Ig-like domains, respectively, in their extracellular portion. While the inhibitory form is characterized by a long cytoplasmic tail associated with a non-polar transmembrane portion, the activatory one has a short tail asociated with a Lys-containing transmembrane portion. Thus, these human NK receptors are different from the murine Ly49, that is a type II transmembrane protein characterized by a C-type lectin domain. A subset of activated T lymphocytes expresses NK-type class I-specific receptors. These receptors exert an inhibiting activity on T cell receptor-mediated functions and may provide an important mechanism of downregulation of T cell responses.     

Effects of enzyme replacement therapy on pain and health related quality of life in patients with Fabry disease: data from FOS (Fabry Outcome Survey)

Background: Fabry disease is an X linked lysosomal storage disease caused by deficiency of the lysosomal enzyme α-galactosidase A. This leads to accumulation of globotriaosylceramide in nearly all tissues, including the blood vessels, kidney, myocardium, and nervous system. Symptoms often begin in childhood and include acroparaesthesia, with burning or tingling pain that spreads from the extremities to more proximal sites.

Aims: This study set out to evaluate pain and its influence on quality of life in patients with Fabry disease receiving enzyme replacement therapy (ERT) with agalsidase alfa.

Methods: Data were obtained from the Fabry Outcome Survey. Pain was measured using the Brief Pain Inventory (BPI), and health-related quality of life (HRQoL) was documented with the European Quality of Life Questionnaire (EQ-5D).

Results: The mean (SD) score for "pain at its worst" on the BPI prior to ERT was 5.1 (2.7). One year after commencement of ERT, this had improved by 0.5, and improved by a further 0.6 after 2 years (p<0.05). Similar statistically significant improvements were seen for "pain on average" and "pain now" after 2 years of ERT. The mean HRQoL utility score prior to ERT was 0.66 (0.32). After 12 months of treatment with agalsidase alfa, this had improved to 0.74 (0.26; p<0.05); this improvement was maintained after 2 years.

Conclusions: ERT with agalsidase alfa significantly reduces pain and improves quality of life in patients with Fabry disease.

     

Application of an intragenic genomic probe to genetic counselling for haemophilia B in the west of Scotland.

Total ascertainment revealed 28 families with haemophilia B in the west of Scotland (prevalence 1/26 870 males). In 12 of these families more than one person was affected and 26 living obligate carriers were identified and tested. Of these, 42% were heterozygous for a DNA polymorphism recognised by a factor IX genomic probe. No recombination was observed in 11 phase known and four phase unknown informative meioses. Definitive genetic counselling was possible for 14 of 42 females at risk, 11 could not be traced, in 10 the probe was not informative, and in seven paternal absence prevented interpretation. Linkage disequilibrium was apparent for this restriction fragment length polymorphism and haemophilia B in the west of Scotland.     

Extensive cytological damage caused by measles in African children

The occurrence of mitotic and chromosomal aberrations was examined in cultured lymphocytes from 25 African children suffering from acute measles at an early stage (0-5 days after onset of rash).

In eight cases the mitotic response to phytohaemagglutinin was impaired. In two cases extensive changes were observed, involving the formation of giant polykaryotic syncytia with chromosome pulverization. It is suggested that the development of giant cells in vivo and the damage to epithelial membranes characteristic of severe measles in the tropics are to be correlated with these changes.

A varying incidence of minor chromosome aberrations, mostly small gaps, was found in 15 cases of measles as well as in controls. The specific relationship of this type of aberration to the virus is questionable.

Mitotic activity was induced in two replicate lymphocyte cultures in the absence of phytohaemagglutinin.

The possible oncogenic potential of the measles virus is discussed in connection with the fusion-pulverization phenomenon.

     

Immunohistochemical labelling of cytokines in lung lesions of pigs naturally infected with Mycoplasma hyopneumoniae

Mycoplasma hyopneumoniae (Mh) is the primary agent of porcine enzootic pneumonia (PEN), a chronic respiratory disease endemic to pig farms, and characterized histologically by infiltration of mononuclear cells in airways and prominent hyperplasia of the bronchus-associated lymphoid tissue (BALT). To gain further insight into the pathogenesis of PEN, cytokine expression in the lung, with particular attention to the BALT, was examined immunohistochemically in pigs naturally infected with Mh. An increase (P < 0.05) in proinflammatory and immunoregulatory cytokines (especially interleukin [IL]-2, IL-4 and tumour necrosis factor [TNF]-alpha, and to a lesser extent IL-1 [alpha and beta] and IL-6) was detected in the BALT, which showed intense lymphoid hyperplasia. IL-1beta and TNF-alpha were also detected in the bronchoalveolar exudate of infected pigs, and IL-6 and IL-8 were demonstrated in mononuclear cells of the alveolar septa. The results showed that in Mh infection, macrophage and lymphocyte activation results in the expression of a number of cytokines capable of inducing lung lesions and lymphoreticular hyperplasia of the BALT.