Analgesia for circumcision in a paediatric population: comparison of caudal bupivacaine alone with bupivacaine plus two doses of clonidine

BACKGROUND: Clonidine is often used to improve the duration and quality of analgesia produced by caudal epidural blockade, although the optimum dose of clonidine with bupivacaine remains uncertain. Methods: We compared the effect of clonidine, 1 and 2 microg x kg(-1), added to bupivacaine (1.25 mg x kg(-1)) with that of bupivacaine alone in 75 male children undergoing elective circumcision. RESULTS: There was a trend towards increasing duration of analgesia with increasing dose of clonidine [group B (bupivacaine) 280.7 (171.6) min, C1 (bupivacaine + clonidine 1 microg x kg(-1)) 327.8 (188.3) min and C2 (bupivacaine + clonidine 2 microg x kg(-1)) 382.0 (200.6) min], although this difference was not statistically significant. Mean time to arousal from anaesthesia was significantly prolonged with clonidine 2 microg kg(-1) (group C2 21.3 (13-36) min, group C1 14.0 (6-25) min and group B 14.4 (2-32) min. Supplementary analgesic requirements and incidence of adverse effects were low, with no differences between the groups. Conclusions: For paediatric circumcision, under general anaesthesia, the addition of clonidine 2 microg x kg(-1) to low volume (0.5 ml x kg(-1)) caudal anaesthetics has a limited clinical benefit for children undergoing circumcision.     

Proliferation of myofibroblasts in the stroma of epithelial hyperplastic lesions and squamous carcinoma of the larynx

OBJECTIVES: The immunohistochemical phenotype, distribution and significance of proliferation of myofibroblasts in laryngeal epithelial hyperplastic lesions (EHL) and squamous carcinoma (SC) were analyzed. METHODS: Samples of 42 resected larynxes and 40 laryngeal biopsies of EHL and SC were included. Immunohistochemistry was performed using antibodies against vimentin, alpha-smooth muscle actin (SMA), desmin and leukocyte common antigen. RESULTS: Myofibroblasts were vimentin- and SMA-positive, and were found exclusively in SC, indicating that invasion beyond the basement membrane is necessary to evoke a myofibroblastic stromal reaction. We observed two patterns of stromal reaction in SC: one was characterized by a marked proliferation of myofibroblasts and desmoplasia, with scarce lymphocytic infiltration; this pattern tended to be associated with well- or moderately differentiated SC. The other was characterized by few myofibroblasts, weak desmoplasia, and dense lymphocytic infiltration; the latter pattern tended to be associated with moderately or poorly differentiated SC. The degree of myofibroblast proliferation was inversely related to the density of lymphocytic infiltration. Antibodies against SMA also stained stromal blood vessels, demonstrating a gradual increase of vessel density as the grade of EHL increased. CONCLUSIONS: Immunohistochemical analysis of myofibroblasts provides useful information on the phenotypic characteristics of the stroma in laryngeal EHL and SC, and can serve as an additional marker of invasion.     

Leukocyte driven-decidual angiogenesis in early.pregnancy

Successful pregnancy and long-term, post-natal maternal and offspring cardiac, vascular and metabolic health require key maternal cardiovascular adaptations over gestation. Within the pregnant decidualizing uterus, coordinated vascular, immunological and stromal cell changes occur. Considerable attention has been given to the roles of uterine natural killer （uNK） cells in initiating decidual spiral arterial remodeling, a process normally completed by mid-gestation in mice and in humans. However, leukocyte roles in much earlier, region specific, decidual vascular remodeling are now being defined. Interest in immune cell-promoted vascular remodeling is driven by vascular aberrations that are reported in human gestational complications such as infertility, recurrent spontaneous abortion, preeclampsia （PE） and fetal growth restriction. Appropriate maternal cardiovascular responses during pregnancy protect mothers and their children from later cardiovascular disease risk elevation. One of the earliest uterine responses to pregnancy in species with hemochorial placentation is stromal cell decidualization, which creates unique niches for angiogenesis and leukocyte recruitment. In early decidua basalis, the aspect of the implantation site that will cradle the developing placenta and provide the major blood vessels to support mature placental functions, leukocytes are greatly enriched and display specialized properties. UNK cells, the most abundant leukocyte subset in early decidua basalis, have angiogenic abilities and are essential for normal early decidual angiogenesis. The regulation of uNK cells and their roles in determining maternal and progeny cardiovascular health over ore~nancv and PostPartum are discussed.     

Autoplex versus proplex: a controlled, double-blind study of effectiveness in acute hemarthroses in hemophiliacs with inhibitors to factor VIII

In view of uncontrolled observations and anecdotal reports suggesting that the activated PCC, Autoplex, was much more effective than standard (non-activated) PCC in controlling bleeding in hemophiliacs with inhibitors, a controlled double-blind study was designed to compare the effectiveness of Autoplex and Proplex. Acute hemarthrosis was chosen for study as this common but non-life-threatening lesion lends itself well to controlled study. A single dose of "unknown" product (Autoplex 75 FECU/kg; Autoplex 50 FECU/kg; or Proplex 75 FIX U/kg) was given, and effectiveness was judged at 6 hr. By all criteria of efficacy, there were no significant differences between the products. It is noteworthy that a single dose of PCC was judged effective in 50% of episodes, a figure that is consistent with other published clinical trials. In this model, no additional benefit was derived from using the activated PCC, Autoplex, in either dosage.     

Acute virulent infection with Plasmodium chabaudi does not impair the generation of a protective immune response

We have investigated whether a protective immune response occurred in mice infected with a virulent cloned strain of Plasmodium chabaudi. Animals inoculated intravenously with 10(7) parasitized erythrocytes (PE) showed an exponentially increasing parasitaemia and died by day 6 of the infection, presenting a pronounced anaemia. Smaller inocula produced a longer pre-patent period but did not change the lethal course of infection, since mice injected with 100 parasites died on day 12. When anaemia was compensated for by red blood cell (RBC) transfusion, infected mice recovered and thereafter exhibited a strong immunity, comparable to that of mice immunized by a drug-controlled infection. The immune response was P. chabaudi specific, as the mice were fully susceptible to a challenge by P. yoelii. Three transfusions of 5 x 10(9) RBC per mouse at 2-day intervals were necessary before all the animals were able to control the infection. Transfusion of a larger number of RBC resulted in a lower anaemia and a delay in reticulocytaemia but, paradoxically, the expression of the immune response was delayed. Three transfusions of 1.2 x 10(10) RBC enabled three out of eight mice to survive the infection, while six transfusions enabled all the mice to survive. The data suggest that parasitized immature RBC could play an important role in triggering the protective immune response.     

Intensive leukapheresis as initial therapy for chronic granulocytic leukemia

Intensive leukapheresis has been used as the initial treatment of chronic granulocytic leukemia (CGL) in six patients. The number of leukaphereses ranged from 3 in 7 days to 13 in 39 days (mean, 8 in 22 days). The procedures were well tolerated, and in all patients there was improvement in hematologic values, in most cases with considerable reduction in the peripheral leukocytosis and thrombocytosis and in the proportion of immature granulocytic cells in the circulation. Splenomegaly decreased considerably in the four patients who had more than four leukaphereses. Symptoms of sweating, malaise, and pain due to splenomegaly were rapidly relieved. Problems due to hyperuricemia did not occur, but four patients required blood transfusions for correction of anemia. This method of initial treatment of CGL appears to give more rapid relief of symptoms than does conventional chemotherapy; it incurs no risk of hyperuricemia and lessens that associated with thrombocytosis. In addition, large quantities of granulocyte-rich plasma are made available for the treatment of infections in neutropenic patients. Intensive leukapheresis deserves more widespread evaluation as the initial treatment of CGL.