The effects of a small-dose naloxone infusion on opioid-induced side effects and analgesia in children and adolescents treated with intravenous patient-controlled analgesia: a double-blind, prospective, randomized, controlled study

Opioids are frequently associated with side effects such as nausea, vomiting, and pruritus. We hypothesized that a prophylactic, continuous small-dose naloxone infusion would reduce the incidence of opioid-induced side effects without affecting analgesia or opioid consumption. In this prospective, double-blind, randomized, controlled clinical trial, we studied 46 postoperative patients (M:F, 21:25), averaging 14 +/- 2.5 yr and 53 +/- 17 kg, at the start of morphine IV patient-controlled analgesia. Patients were randomized to either saline (control, n = 26) or naloxone 0.25 microg . kg(-1) . h(-1) (n = 20). We found that the incidence and severity of pruritus (77% versus 20%; P < 0.05) and nausea (70% versus 35%; P < 0.05) was significantly more frequent in the placebo group compared with the naloxone group. Morphine consumption (1.02 +/- 0.41 mg . kg(-1) . d(-1) versus 1.28 +/- 0.61 mg . kg(-1) . d(-1)), pain scores at rest (4 +/- 2 versus 3 +/- 2), and pain scores with coughing (6 +/- 2 versus 6 +/- 2) were not different. We conclude that, in children and adolescents, a small-dose naloxone infusion (0.25 microg . kg(-1) . h(-1)) can significantly reduce the incidence and severity of opioid-induced side effects without affecting opioid-induced analgesia. When initiating morphine IV patient-controlled analgesia for the treatment of moderate to severe pain, clinicians should strongly consider starting a concomitant small-dose naloxone infusion.     

Immunogold study of effects of prenatal exposure to lipopolysaccharide and/or valproic acid on the rat blood-brain barrier vessels

The involvement of blood microvessels, representing the anatomic site of the blood-brain barrier (BBB), in brain damage induced by prenatal exposure to lipopolysaccharide (LPS) and/or valproic acid (VPA) was studied in four-week-old rats. The immunogold procedure was applied for localization at the ultrastructural level of endogenous albumin and glucose transporter (GLUT-1) in three brain regions: cerebral cortex, cerebellum and hippocampus. Four groups of rats were used: (1) untreated control, (2) prenatally VPA-treated, (3) prenatally LPS-treated, and (4) prenatally LPS- and VPA-treated. The functional state of the BBB was evaluated as follows: (a) by its tightness, i.e., permeability to blood-borne albumin, and (b) by the expression of GLUT-1 in the endothelial cells (ECs). Using morphometry, the labelling density for GLUT-1 was recorded over luminal and abluminal plasma membranes of the ECs, also providing information on their functional polarity. No extensive increase of vascular permeability and/or any considerable dysfunction of the BBB in experimental groups nos. 2 and 3 were observed, although in solitary vascular profiles, increased endocytosis or even transcytosis of albumin by ECs was noted. In experimental group no. 4, some vascular profiles showed scanty leakage (microleakage), manifested by the presence of immunosignals for albumin in the perivascular area. Although some fluctuations in the expression of GLUT-1 occurred in all experimental groups, especially in group no. 3, a most pronounced and significant diminution of the labelling density, in all three regions of the brain, was observed in group no. 4. This finding suggests the synergistic action of prenatally applied LPS and VPA that affects specific transport functions of glucose in the microvascular endothelium. The diminished or disturbed supply of glucose to selected brain regions can be one of the factors leading to previously observed behavioral disturbances in similarly treated rats.     

Scintigraphic diagnosis of tricuspid regurgitation

The authors describe a simple technique for diagnosis of tricuspid regurgitation. Red blood cells were labeled in vivo with 99mTc and 22 patients were studied with ECG-gated blood-pool imaging of the liver. A single region of interest was manually drawn around the liver and a time-activity curve obtained. The per cent change in liver counts during the cardiac cycle was found to be significantly higher in the 12 patients with tricuspid regurgitation (Group I) (mean, 4.04 +/- 1.6%; range, 1.3-21.4%) compared with the 10 controls (Group II) (mean, 0.35 +/- 0.16%; range, 0.013-1.3%) (p less than 0.05). Using a 1% change in liver counts as the criterion of a positive study, all 12 cases in Group I were diagnosed correctly, but there was one false positive in Group II; thus the sensitivity was 100% and the specificity 90%.     

Types of mesenchymal reactions in the carcinoma of uterine cervix.

In the cervical cancer stroma three essential types of mesenchymal reaction: myxoid, fibrogenic with angioplasia and fibroblastic low-differentiated were disclosed. The border membrane of cancer foci is composed of fibroblast layer and ground substance abundant in Ac-MPS of the hyaluronic acid type. This substance is the basal immunosuppressive factor of cancer cells in situ (TIS). Similar activity is exhibited by the pathologic mesenchymal proteins of fibrynoid and hyaline type. The level of chemical differentiation of the mesenchyma, changes according to the maturity of cellular factor in connective tissue. Ac-MPS of the hyaluronic acid type prevail in the ground substance of the myxoid and fibroblastic mesenchyma, while the substances containing sulfuric groups predominate in the tissue matrix exhibiting fibrogenic tendencies.     

Familial osteochondritis dissecans: A dysplasia of articular cartilage?

Two cases of osteochondritis dissecans in a boy and his mother are described. In the son only the knee and elbow joints and the epiphysis of the right second metacarpal were involved, whereas the mother showed early generalised degenerative joint disease associated with many large loose bodies in one knee. The authors speculate that familial osteochondritis dissecans is a dysplasia of articular cartilage caused by abnormal chondrocyte metabolism.     

Forty-two supernumerary marker chromosomes (SMCs) in 43,273 prenatal samples: chromosomal distribution, clinical findings, and UPD studies

Fluorescence in situ hybridization (FISH) analyses were performed on supernumerary marker chromosomes (SMCs) detected in 43,273 prenatal diagnoses over a period of 11 years, 1993-2003. A total of 42 pregnancies with SMC were identified, indicating a prevalence of one in 1032. A total of 15 SMCs were endowed with detectable euchromatin (prevalence, 1/2884), including six SMCs containing the cat eye critical region (CECR) on chromosome 22q11.21 (1/7212). De novo SMCs were found in 29 pregnancies (1/1492), including 14 euchromatic SMCs (48.2%). Follow-up studies were available for 24 cases. Nine pregnancies (37.5%) were terminated; two children (8.3%) were born with Pallister-Killian syndrome and cat eye syndrome (CES), respectively; 13 children (54.1%) showed apparently normal development. Familial SMCs were identified in 13 pregnancies (1/3328) from 11 unrelated women. They were all acrocentric. In all, 10 were heterochromatic and one was an extra der(22)t(11;22) chromosome. A total of 12 cases were available for follow-up. One pregnancy was terminated due to anhydramnios, spina bifida, and cystic-dysplastic kidneys; one child suffered from a der(22) syndrome; 10 children (83.3%) appeared unaffected. Studies for uniparental disomy were performed on seven pregnancies and revealed a case of maternal heterodisomy for chromosome 22. So far this is the largest FISH study of prenatally ascertained SMCs and the first study with detailed data on the prevalence. Findings illustrate the spectrum and clinical outcomes of prenatally diagnosed SMCs, and indicate a higher frequency of SMCs than generally assumed.     

Surface plasmon resonance analysis of antipolysaccharide antibody specificity: responses to meningococcal group C conjugate vaccines and bacteria

Antibody (Ab) responses to polysaccharides (PS), such as Neisseria meningitidis group C PS (MCPS), are characterized as being thymus independent and are restricted with regard to clonotype and isotype expression. PS conjugated to proteins, e.g., MCPS coupled with tetanus toxoid or the diphtheria toxin derivative CRM197, elicit thymus-dependent responses. The present study developed a surface plasmon resonance approach to evaluate Ab responses to MCPS conjugate vaccines, including either O-acetylated (OAc+) or de-O-acetylated (OAc-) forms of the PS. The results were generally consistent with those obtained by enzyme-linked immunosorbent assay and showed that sera from mice immunized with conjugate vaccines contain Abs that bind more effectively to OAc+ and OAc- MCPS than sera from mice immunized with fixed bacteria. The data suggest a critical shared or overlapping epitope recognized by all the conjugate vaccine immune sera and strategies for assessing polyclonal Ab avidity.     

Factors for consideration in the development and implementation of an online RN-BSN course. Faculty and student perceptions

An online "issues in nursing" course was developed over the summer 2000 and subsequently implemented over a 4-semester time period in an RN-BSN program. Student and faculty anecdotal evaluation records were compiled and reviewed to determine universal needs and concerns associated with online learning for this particular population. Seven themes emerged from student course evaluation data and 5 "factors for faculty consideration" were identified by the course facilitator.     

Differential effects of pyrethroids on volume-sensitive anion and organic osmolyte pathways

1. There are no effective ways of screening for potential modulators of volume-regulated anion channels in their native cell type. Generally, cell lines are used for this purpose. Using HeLa and C6 glioma cells, we identified the pyrethroids as a novel class of compounds that inhibit taurine efflux through volume-regulated anion transport pathways in these cells. Subsequently, we examined their effects on volume-regulated anion channels in guinea-pig ventricular myocytes to determine whether results obtained using cell lines could be extrapolated to other tissues. 2. Tetramethrin inhibited taurine efflux in both HeLa and C6 glioma cells with Ki values of approximately 26 and 16 micro mol/L, respectively. Bioallethrin and fenpropathrin inhibited volume-sensitive taurine efflux from C6 glioma cells, but not from HeLa cells. The Ki values for bioallethrin and fenpropathrin were 70 and 59 micro mol/L, respectively. 3. Volume-sensitive I- efflux was observed in HeLa cells but not in C6 glioma cells, suggesting that the taurine efflux pathway in C6 glioma cells may be different to that of the I- efflux pathway. Cyfluthrin, tetramethrin, fenpropathrin, tefluthrin and bioallethrin all significantly inhibited volume-sensitive I- efflux from HeLa cells at 100 micro mol/L. 4. Patch-clamp experiments have shown inhibition of ICl,vol in guinea-pig ventricular myocytes by fenpropathrin, but not tetramethrin or cypermethrin, at 100 micro mol/L. This revealed that further differences exist between ICl,vol in guinea-pig ventricular myocytes and the anion transport pathways in C6 glioma and HeLa cells. 5. In conclusion, we have shown that pyrethroids differentially inhibit volume-regulated anion and taurine efflux in a number of cell types. Because these compounds have different effects in different cells, it is likely that: (i) more than one pathway is involved in the volume-sensitive transport of anions and organic osmolytes; and (ii) the molecular identities of the channels underlying anion transport are different. Finally, for the reasons given above, care should be taken when extrapolating data from one cell type to another. However, in the absence of an existing high-throughput screen, taurine efflux still represents a viable route for the identification of potential modulators of volume-regulated ion channels.