Phosphatemic control during acute renal failure: intermittent hemodialysis versus continuous hemodiafiltration

BACKGROUND: Achieving "adequacy of dialysis" includes the maintenance of normal serum phosphate concentrations and is an important therapeutic goal in the treatment of acute renal failure (ARF). It is unknown whether this goal is best achieved with intermittent or continuous renal replacement therapy. METHODS: We compared the effects of continuous veno-venous hemodiafiltration (CVVHDF) and intermittent hemodialysis (IHD) on serum phosphate concentrations using daily morning blood tests in 88 consecutive intensive care patients half of which were treated with IHD and half with CRRT RESULTS: Mean patient age was 54+/-14 years for IHD and 60+/-14 years for CVVHDF (NS). However, patients who received CVVHDF were more critically ill (mean APACHE II scores: 24.4+/-5.1 for IHD vs. 29.2+/-5.7 for CVVHDF, p<0.003). Before treatment, the serum phosphate concentration was 2.04+/-0.16 mmoll L for IHD and 1.96+/-0.17 mmoll L for CVVHDF (NS), with abnormal values in 79.4% of IHD patients and in 64.8% of CVVHDF patients (NS). During treatment, CVVHDF induced a greater reduction in serum phosphate (p=0.02) during the first 48 hours and conferred superior subsequent control of hyperphosphatemia (achieved in 64.6% of observations during CVVHDF vs. 41.8% during IHD; p<0.0001). The serum phosphate concentration was also more likely to be within the normal range during CVVHDF (55.3% vs.36.2%; p<0.0001). There was a trend toward more frequent hypophosphatemia (9.3% vs. 5.6%; P<0.1) during CVVHDF CONCLUSIONS: Abnormal serum phosphate concentrations are frequent in ARF patients before and during renal replacement, however, normalization of phosphatemia is achieved more frequently with CVVHDF.     

Comparative Analysis of Haemophilus influenzae hifA (Pilin) Genes

Adherence of Haemophilus influenzae to epithelial cells plays a central role in colonization and is the first step in infection with this organism. Pili, which are large polymorphic surface proteins, have been shown to mediate the binding of H. influenzae to cells of the human respiratory tract. Earlier experiments have demonstrated that the major epitopes of H. influenzae pili are highly conformational and immunologically heterogenous; their subunit pilins are, however, immunologically homogenous. To define the extent of structural variation in pilins, which polymerize to form pili, the pilin genes (hifA) of 26 type a to f and 16 nontypeable strains of H. influenzae were amplified by PCR and subjected to restriction fragment length polymorphism (RFLP) analysis with AluI and RsaI. Six different RFLP patterns were identified. Four further RFLP patterns were identified from published hifA sequences from five nontypeable H. influenzae strains. Two patterns contained only nontypeable isolates; one of these contained H. influenzae biotype aegyptius strains F3031 and F3037. Another pattern contained predominantly H. influenzae type f strains. All other patterns were displayed by a variety of capsular and noncapsular types. Sequence analysis of selected hifA genes confirmed the 10 RFLP patterns and showed strong identity among representatives displaying the same RFLP patterns. In addition, the immunologic reactivity of pili with antipilus antisera correlated with the groupings of strains based on hifA RFLP patterns. Those strains that show greater reactivity with antiserum directed against H. influenzae type b strain M43 pili tend to fall into one RFLP pattern (pattern 3); while those strains that show equal or greater reactivity with antiserum directed against H. influenzae type b strain Eagan pili tend to fall in a different RFLP pattern (pattern 1). Sequence analysis of representative HifA pilins from typeable and nontypeable H. influenzae identified several highly conserved regions that play a role in bacterial pilus assembly and other regions with considerable amino acid heterogeneity. These regions of HifA amino acid sequence heterogeneity may explain the immunologic diversity seen in intact pili.     

Characterization of knitted polymeric scaffolds for potential use in ligament tissue engineering

Different scaffolds have been designed for ligament tissue engineering. Knitted scaffolds of poly-L-lactic acid (PLLA) yarns and co-polymeric yarns of PLLA and poly(glycolic acid) (PLGA) were characterized in the current study. The knitted scaffolds were immersed in medium for 20 weeks, before mass loss, molecular weight, pH value change in medium were tested; changes in mechanical properties were evaluated at different time points. Results showed that the knitted scaffolds had 44% porosity. There was no significant pH value change during degradation, while there was obvious mass loss at initial 4 week, as well as smooth molecular weight drop of PLLA. PLGA degraded more quickly, while PLLA kept its integrity for at least 20 weeks. Young's modulus increased while tensile strength and strain at break decreased with degradation time; however, all of them could maintain the basic requirements for ACL reconstruction. It showed that the knitted polymeric structures could serve as potential scaffolds for tissue-engineered ligaments.     

The effects of butterbur on the histamine and allergen cutaneous response.

BACKGROUND: Butterbur or Petasites hybridus is an herbal remedy that exhibits antihistamine and antileukotriene activity and has been shown to attenuate the response to adenosine monophosphate challenge in patients with allergic rhinitis and asthma. However, no data are available regarding its effects on the histamine and allergen cutaneous response. OBJECTIVE: To evaluate the effects of butterbur compared with fexofenadine and montelukast on the histamine and allergen wheal and flare cutaneous responses. METHODS: Atopic patients were randomized into a double-blind, double-dummy, crossover study to receive for 1 week butterbur, 50 mg twice daily (8 AM and 10 PM); fexofenadine, 180 mg once daily (10 PM), and placebo once daily (8 AM); montelukast, 10 mg once daily (10 PM), and placebo once daily (8 AM); or placebo twice daily (8 AM and 10 PM). Patients attended the department at 10 AM and had measurements of the cutaneous wheal and flare responses to histamine, allergen, and saline control at 10-minute intervals for 60 minutes. RESULTS: Twenty patients completed the study. The mean +/- SE histamine wheal and flare responses, respectively, were significantly attenuated (P < .05) by fexofenadine (9.4 +/- 1.8 mm2 and 13.5 +/- 3.2 mm2) compared with placebo (15.5 +/- 3.3 mm2 and 179.8 +/- 74.3 mm2) but not by butterbur (16.4 +/- 2.1 mm2 and 297.7 +/- 121.2 mm2) or montelukast (19 +/- 1.9 mm2 and 240.2 +/- 66.6 mm2). The allergen wheal and flare responses, respectively, were also significantly attenuated (P < .05) by fexofenadine (31.1 +/- 6.3 mm2 and 256.9 +/- 86.5 mm2) compared with placebo (65.4 +/- 15.2 mm2 and 1,014.5 +/- 250.0 mm2) but not by butterbur (50.4 +/- 9.2 mm2 and 1,110.3 +/- 256.1 mm2) or montelukast (58.8 +/- 9.1 mm2 and 1,463.6 +/- 295.6 mm2). CONCLUSIONS: Butterbur did not produce any significant effects on the histamine and allergen cutaneous response compared with placebo, whereas mediator antagonism with fexofenadine but not montelukast produced significant attenuation. This finding would suggest that butterbur may not be effective in allergic skin disease.     

Knowledge representation model for systems-level analysis of signal transduction networks

A Petri-net based model for knowledge representation has been developed to describe as explicitly and formally as possible the molecular mechanisms of cell signaling and their pathological implications. A conceptual framework has been established for reconstructing and analyzing signal transduction networks on the basis of the formal representation. Such a conceptual framework renders it possible to qualitatively understand the cell signaling behavior at systems-level. The mechanisms of the complex signaling network are explored by applying the established framework to the signal transduction induced by potent proinflammatory cytokines, IL-1beta and TNF-alpha The corresponding expert-knowledge network is constructed to evaluate its mechanisms in detail. This strategy should be useful in drug target discovery and its validation.     

Assessing the effect of visual and tactile distractors on the perception of auditory apparent motion

In this study we investigated the effect of the directional congruency of tactile, visual, or bimodal visuotactile apparent motion distractors on the perception of auditory apparent motion. Participants had to judge the direction in which an auditory apparent motion stream moved (left-to-right or right-to-left) while trying to ignore one of a range of distractor stimuli, including unimodal tactile or visual, bimodal visuotactile, and crossmodal (i.e., composed of one visual and one tactile stimulus) distractors. Significant crossmodal dynamic capture effects (i.e., better performance when the target and distractor stimuli moved in the same direction rather than in opposite directions) were demonstrated in all conditions. Bimodal distractors elicited more crossmodal dynamic capture than unimodal distractors, thus providing the first empirical demonstration of the effect of information presented simultaneously in two irrelevant sensory modalities on the perception of motion in a third (target) sensory modality. The results of a second experiment demonstrated that the capture effect reported in the crossmodal distractor condition was most probably attributable to the combined effect of the individual static distractors (i.e., to ventriloquism) rather than to any emergent property of crossmodal apparent motion.     

Hemopoietic stem cell transplantation in rheumatic diseases--an update

Hematopoietic stem cell transplant (HSCT) for autoimmune diseases has been recognized as a potential treatment for patients who have failed conventional therapy. Autologous (self) donor cells have been preferred over allogeneic (HLA-matched) cells for rescue after high dose immunotherapy, given the previous higher rates of mortality, graft versus host disease (GVHD), and the need for more intense myeloablation associated with the latter. The European Group for bone Marrow Transplantation in Basel Switzerland (EBMT) and various groups within the US funded by the NIH (including the Autologous Blood and Marrow Transplant Registry (ABMTR)) have been pivotal in maintaining registries on patients transplanted as well as promoting homogeneity for future studies including Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE) and Systemic Sclerosis (SSc). Although, patients transplanted for RA show initial success, relapse of the disease is common. In many, however, a second positive result can be obtained with the addition of DMARD therapy to which they were previously unresponsive, suggesting a "debulking" of disease by HSCT. SLE patients also have a high rate of success after HSCT, although current mortality rates appear high. Transplant in SSc patients has offered durable responses with improving transplant-related mortality related to careful patient selection.     

Molecular genetics of pseudoxanthoma elasticum: type and frequency of mutations in ABCC6

Pseudoxanthoma elasticum (PXE) is a systemic heritable disorder that affects the elastic tissue in the skin, eye, and cardiovascular system. Mutations in the ABCC6 gene cause PXE. We performed a mutation screen in ABCC6 using haplotype analysis in conjunction with direct sequencing to achieve a mutation detection rate of 97%. This screen consisted of 170 PXE chromosomes in 81 families, and detected 59 distinct mutations (32 missense, eight nonsense, and six likely splice-site point mutations; one small insertion; and seven small and five large deletions). Forty-three of these mutations are novel variants, which increases the total number of PXE mutations to 121. While most mutations are rare, three nonsense mutations, a splice donor site mutation, and the large deletion comprising exons 23-29 (c.2996_4208del) were identified as relatively frequent PXE mutations at 26%, 5%, 3.5%, 3%, and 11%, respectively. Chromosomal haplotyping with two proximal and two distal polymorphic markers flanking ABCC6 demonstrated that most chromosomes that carry these relatively frequent PXE mutations have related haplotypes specific for these mutations, which suggests that these chromosomes originate from single founder mutations. The types of mutations found support loss-of-function as the molecular mechanism for the PXE phenotype. In 76 of the 81 families, the affected individuals were either homozygous for the same mutation or compound heterozygous for two mutations. In the remaining five families with one uncovered mutation, affected showed allelic compound heterozygosity for the cosegregating PXE haplotype. This demonstrates pseudo-dominance as the relevant inheritance mechanism, since disease transmission to the next generation always requires one mutant allelic variant from each parent. In contrast to other previous clinical and molecular claims, our results show evidence only for recessive PXE. This has profound consequences for the genetic counseling of families with PXE.     

A history of Combined-Integrated doctoral training in psychology

The history of doctoral training in psychology is reviewed, with special emphasis on the development of training models for applied psychology. Among applied psychology doctoral programs, most label themselves as being one of the three currently recognized practice areas: clinical, counseling, and school psychology; however, since the 1970s, APA also has accredited "combined" programs. The history of the development of the combined model is traced, including information from the programs themselves about the manner in which each evolved. Recently, new interest in the combined category -or Combined-Integrated (C-I) as these programs wish to become known-has emerged, and an organization representing these programs has formed. The C-I model is described, and the potential that the model may serve as a template for the future of professional training in psychology is discussed.     

Detection of human T-lymphotropic virus (HTLV) tax sequences in New York City blood donors seronegative for HTLV types 1 and 2

A potential public health concern is the reported detection of the human T-lymphotropic virus (HTLV) tax gene in the lymphocytes of up to 11% of a low-risk group of New York City blood donors (NYBD). This study aimed to independently confirm the prevalence of HTLV tax sequences in 293 NYBD. All NYBD tested negative for antibodies to HTLV types 1 and 2 and HTLV Tax. HTLV tax sequences were not detected in the NYBD lymphocytes. These data demonstrate the lack of HTLV-1 tax in this group of NYBD at low risk for HTLV infection.