Failure of Hemodialysis to Diminish Psychotic Behavior in Schizophrenia: Behavioral and Psychophysiological Evaluation

In a double-blind sham replacement study, eight drug-free schizophrenic patients underwent 10 active and 10 sham hemodialysis for 20 weeks. At the end of the 10 active dialyses, none of the patients appeared to be improved in psychotic, affective, or social symptoms. Active dialysis was associated with a "startle" response in heart rate and skin conductance to auditory stimuli, while sham dialysis was associated with an "orienting" response. Night-recorded sleep electroencephalography was unaffected by active dialysis. Spinal fluid beta-endorphin-like immunoreactivity levels were unchanged after active treatment. The behavioral improvements reported in other studies may be related to "stress," psychotherapeutic support, spontaneous remissions, neuroleptic withdrawal, denial of symptoms, or diagnostic differences. This study did not confirm the claims for hemodialysis as a specific therapeutic intervention in schizophrenia.     

The influence of a hydrogen peroxide and glycerol containing mouthrinse on plaque accumulation: a 3-day non-brushing model

Abstract: Aim: To evaluate the inhibition of plaque growth by an experimental mouthrinse (BioXyl^®) based on hydrogen peroxide/glycerol. Design: It was a double‐blind, randomized study involving 40 volunteers in good general health. At the start of the trial, all participants received a dental prophylaxis to remove all plaque deposits. During the next 3 days subjects refrained from any mechanical oral hygiene procedure, except for the allocated mouthrinse being either the hydrogen peroxide (H₂O₂; 0.013% H₂O₂/0.004% glycerol) or the placebo without H₂O₂. At the third day of appointment, plaque levels were assessed at six sites per tooth. Results: The test group had a mean overall plaque score of 2.66 and the placebo group of 2.70. The difference in plaque scores between the two groups was not statistically significant. Conclusions: The results of this pilot study showed that there was no statistically significant difference between the H₂O₂/glycerol group and the placebo group with respect to plaque inhibition within this study design.     

Comparison of hematopoietic progenitor cells in human umbilical cord blood collected from neonatal infants who are small and appropriate for gestational age

BACKGROUND: Cord blood has been used for transplantation. The purpose of this study was to compare numbers of hematopoietic progenitors in cord blood collected from neonatal infants who are small for their gestational age and those who are normal. STUDY DESIGN AND METHODS: Sixteen pregnant women diagnosed with intrauterine growth restriction were prospectively identified. Cord blood was collected at delivery. Fourteen cord blood samples were obtained from gestational age-matched, appropriately grown newborns. In vitro assays for hematopoietic progenitors were performed and results of the two compared. Comparisons were also made with numbers of hematopoietic progenitor cells previously found by this laboratory in samples collected with the possibility of use for transplantation. RESULTS: Gestational age, the women's pregnancy and delivery histories, maternal risk factors for intrauterine growth restriction, maternal age, delivery method, umbilical cord blood gases, and 5-minute Apgar scores were similar in the two groups. Newborns who were small for their gestational age had significantly lower birth weights and longer stays in the neonatal intensive care unit with no evidence for viral infections in the immediate neonatal period. The mean number of progenitors per collection of cord blood in the small newborns was about half that per collection from appropriately grown newborns, but in most cases, these differences were not significant in the two groups, and many numbers in the small newborns fell within the range associated with successfully engrafting cord blood collections. CONCLUSION: Hematopoietic progenitor cells in the small newborns may be adequate for transplantation purposes in many cases. Their possible use in this context should, however, involve careful consideration of the numbers of progenitors collected as well as of possible viral or other contamination.     

Interleukin-12 regulates natural killer cell-dependent Propionibacterium acnes-primed, lipopolysaccharide-induced liver injury.

Aim: Interleukin (IL)-12, produced primarily by macrophage/monocytes, modulates mature T and natural killer (NK) cell functions, including cytotoxicity and cytokine production. Methods: To determine the role of IL-12 in Propionibacterium acnes (P. acnes)-primed, lipopolysaccharide (LPS)-induced liver injury, mice were injected with an anti-IL-12 monoclonal antibody (mAb) 1 and 2 days before P. acnes injection (day 0) or 5 and 6 days before LPS challenge (day 7). The survival rates, plasma cytokine levels, and liver mononuclear cell phenotypes were evaluated for the mice treated with and without anti-IL-12 mAb. Results: The observed mortality with P. acnes-primed, LPS-induced liver injury in C57BL/6 (B6) mice was 100%, but was reduced to 0% in interferon (IFN)-gamma receptor-deficient mice and B6 mice treated with anti-IL-12 mAb on 1 and 2 days before P. acnes exposure (day 0). The plasma IFN-gamma levels weresignificantly lower (P < 0.05), and significantly less ( approximately 90% reduction) hepatic infiltrating mononuclear and NK1.1 cells were also found in the IL-12 mAb-treated, P. acnes-primed mice. The plasma cytokine levels after LPS challenge and in vitro cytokine release by liver mononuclear cells were significantly lower (P < 0.05) in the mice treated with anti-IL-12 mAb prior to P. acnes exposure. The in vivo administration of anti-NK1.1 mAb also improved survival in this liver injury model. Conclusion: IL-12-regulated IFN-gamma production is crucial during the priming phase by P. acnes, but not at the time of the subsequent LPS challenge. NK1.1(+)CD3(-)CD4(-) NK or NK1.1(+)CD3(+)CD4(-) NKT cells are important in this model of liver injury.     

Human umbilical vein endothelial cells display high-affinity c-kit receptors and produce a soluble form of the c-kit receptor

Stem cell factor (SCF) is a hematopoietic growth factor produced by fibroblasts and endothelial cells that stimulates the growth of primitive hematopoietic cells. SCF triggers cell growth by binding to the c-kit receptor. Because endothelial cells can respond to certain hematopoietic growth factors, we tested human umbilical vein endothelial cells for display of the c-kit receptor and examined the effect of SCF on endothelial cell proliferation, adhesion molecule expression, and production of tissue factor. Quantitative binding experiments with 125I-SCF showed both high-affinity (Kd = 42 pmol/L) and low-affinity (Kd = 1.7 nmol/L) c-kit receptors. There were approximately 1,100 high-affinity c-kit receptors, and 5,400 low- affinity c-kit receptors per endothelial cell. Enzyme immunoassays showed that endothelial cells released soluble c-kit receptor and SCF. The transmembrane form of SCF was detected by indirect immunofluorescence analysis using monoclonal or polyclonal anti-SCF receptor antibodies. The addition of SCF (100 ng/mL) did not alter endothelial cell proliferation over a 7-day period. Similarly, there was no change in the release of tissue factor or expression of inducible endothelial adhesion molecules (intercellular adhesion molecule-1, endothelial-leukocyte adhesion molecule-1, and vascular cell adhesion molecule-1) measured by enzyme-linked immunosorbant assay at 4 and 24 hours after SCF addition. The neutralizing anti-c-kit receptor monoclonal antibody SR-1 blocked binding of 125I-SCF to the c- kit receptor by 98% but did not alter endothelial cell proliferation or adhesion-molecule expression. c-kit receptors were also detected on adult endothelial cells lining small blood vessels in normal human lymph nodes. These data indicate that normal human endothelial cells produce SCF and show high-affinity c-kit receptors that have the capacity to dimerize. The lack of response to exogenous SCF may be because of intracellular activation of the c-kit receptor via autocrine production of SCF. Alternatively, SCF and c-kit may play a role other than stimulation of proliferation, adhesion-molecule display, or tissue factor production by endothelial cells. The production of soluble c-kit receptors by normal human endothelial cells may serve to regulate the bioactivity of SCF within the bone marrow microenvironment.     

The use of multiattribute decision models in evaluating triptan treatment options in migraine

Background The physician treating patients with migraine is now able to choose from among seven triptans–almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan and zolmitriptan. These differ, to greater or lesser degrees, on a range of clinical attributes important for treatment selection. Objective To outline the basic principles of Multiattribute Decision Making (MADM) and describe how one such method–TOPSIS (Technique for Order Preference by Similarity to the Ideal Solution)–can be applied to evaluate the currently available triptans. Methods In an example application, summary data from a recent meta–analysis of 53 published and unpublished placebo–controlled trials of the oral triptans were combined in TOPSIS models with computer–generated attribute importance weights representing the entire range of possible values, That is, the relative performance of the triptans was explored across all logically possible combinations of relative importance of the treatment attributes available from the meta–analysis, and uncertainty was assessed based on the confidence intervals from the meta–analysis. Results When compared across the entire range of values for relative attribute importance, almotriptan, eletriptan and rizatriptan were more similar to a hypothetical ideal triptan and were more likely to appear in the top three closest to the hypothetical ideal, than were naratriptan, sumatriptan, and zolmitriptan. Conclusion Using the TOPSIS model, almotriptan, eletriptan and rizatriptan were more likely to appear in the top three closest to the hypothetical ideal triptan.