HOST GENETIC CONTROL OF RECOVERY FROM FRIEND LEUKEMIA VIRUS-INDUCED SPLENOMEGALY : Mapping of a Gene Within the Major Histocompatability Complex

The influence of the major mouse histocompatibility gene complex (H-2) on the response of mice to Friend leukemia virus was studied in F₁ congenic mice differing only at genes within the H-2 complex. F₁ mice which were H-2^b/b had a high incidence of recovery from splenomegaly compared to H-2^b/d or H-2^b/a mice. In mice with recombinations within the H-2 complex a gene (designated RFV-1), responsible for the Friend virus recovery effect, was found to map near or within the D region of serologically detectable transplantation antigens. Because the incidence of recovery was much higher in F₁ H-2^b/b mice than in parental H-2^b/b mice, other non-H-2 host genetic factors also appear to be important to expression of recovery in H-2^b/b F₁ mice. The mechanisms of action of these genes remain unknown.     

Home-based video CBT for comorbid geriatric insomnia: a pilot study using secondary data analyses

Two recent studies showed that cognitive-behavioral treatment (CBT) is efficacious in treating insomnia in older adults with comorbid medical conditions. The authors extended these findings by comparing 12 older adults with comorbid insomnia who received a home-based video CBT program to the authors' previously published data on 24 participants who received classroom CBT or no treatment. All 36 participants were initially randomized within the same protocol, but the video arm was conducted 7 months after completion of the other two study arms. Compared to controls, the video CBT group demonstrated significant changes in five of eight self-report measures of sleep at posttreatment, including sleep latency, time awake after sleep onset, total time in bed, overall sleep quality, and dysfunctional beliefs and attitudes about sleep. Compared to controls, the video CBT group also had posttreatment improvements in daytime functioning, including mood, pain perception, social functioning, and energy-vitality. Although video CBT was not significantly different from classroom CBT on self-report measures, the attrition rate was higher (27% vs. 19%) and the number of participants who achieved clinically significant change was lower (50% vs. 73%). These preliminary findings suggest that delivering CBT in a home-based video format has the potential to serve as a first-line, cost-effective treatment for comorbid insomnia.     

Photorhabdus asymbiotica, a pathogen emerging on two continents that proves that there is no substitute for a well-trained clinical microbiologist

A 54-year-old ranch hand presented to the emergency room with an alleged spider bite and multiple abscesses. Both wound and blood cultures grew Photorhabdus asymbiotica, an enteric gram-negative rod that was initially misidentified by the hospital's rapid identification system. Clinical laboratories should be aware of the limitations of their rapid identification systems and always use them as an adjunct to analysis of morphological and phenotypic traits.     

Phylogenetic analysis of Taura syndrome virus isolates collected between 1993 and 2004 and virulence comparison between two isolates representing different genetic variants

Taura syndrome virus (TSV) is highly pathogenic to Litopenaeus vannamei (Pacific white shrimp) and has caused significant economic loss in the shrimp culture industry. It was first reported from Ecuador in 1992 and has since become widely distributed throughout the Americas and southeast Asia (SE Asia). To determine the genetic relationship among various geographic isolates, we amplified and sequenced a 1.3 kb fragment of the TSV capsid protein gene 2 (CP2) from each of 34 isolates collected from cultured penaeid shrimp stocks in Ecuador, Colombia, Honduras, USA, Mexico, Belize, Thailand, China, and Indonesia. An additional six CP2 sequences obtained from GenBank were included in the analysis. The results indicated low genetic variation (0--5.6% for nucleotide sequence and 0--7.0% for deduced amino acid sequence) among these 40 isolates. A phylogenetic analysis based on the deduced CP2 amino acid sequence revealed three distinct groups: Americas, Belize, and SE Asia. The Belize and SE Asia groups were separated from each other by a 4.7% difference in amino acid sequence. The Belize and Americas groups differed by 4.4%. The Americas and SE Asia groups were the closest, separated by a difference of only 3.3%. Comparison between Belize and Hawaii TSV (reference strain for Americas group) indicated that Belize TSV was more virulent than Hawaii TSV. In bioassays, the Belize isolate caused 50% mortality by 3 days, while the Hawaii isolate caused 50% mortality over 4--6 days. Based on the phylogenetic analysis and virulence comparison, the Belize TSV isolate should be considered as a new variant.     

Regulatory considerations for novel gene therapy products: a review of the process leading to the first clinical lentiviral vector

This review is intended to exemplify the roles and responsibilities of the two agencies under the Department of Health and Human Services, the National Institutes of Health and the Food and Drug Administration, that have oversight for human gene transfer clinical protocols, as seen through our experience of bringing a first-in-its-class lentiviral vector to clinical trials. In response to the changing circumstances in gene therapy research between 1999 and 2002, the concerns of these agencies regarding gene therapy have been evolving. This review provides an overview of the major safety concerns regarding insertional oncogenesis, the generation of a replication- competent lentivirus (RCL), and vector mobilization thought to be related to lentiviral vectors, which had to be addressed during the regulatory review process before initiating the clinical trial. Specific monitoring assays to address these concerns were established to test for RCL generation, vector mobilization, persistence of vector-modified cells, and abnormal clonal expansion of modified cells. We hope to provide a basic understanding and appreciation of the regulatory process and major safety concerns, toward providing useful insight to those presently embarking on the development of clinical application of lentiviral vectors.     

Depletion of B cells by a humanized anti-CD20 antibody PRO70769 in Macaca fascicularis

PRO70769 is a humanized IgG1 monoclonal antibody against the CD20 molecule that is present on normal and malignant B cells. PRO70769 is being evaluated for treatment of B-cell-mediated diseases and is in a phase 1 trial for rheumatoid arthritis. As part of the preclinical toxicology evaluation, B-cell depletion profiles and safety of PRO70769 were assessed in cynomolgus monkeys. Animals were administered drug (IV) on days 1 and 15 with 10, 50, or 100 mg/kg PRO70769 and killed 2 weeks after the second dose and after a 3-month recovery period. In a parallel study, animals were not necropsied but instead were retreated with a second cycle of PRO70769 administered under an identical regimen. PRO70769 suppressed B cells in the blood to undetectable levels and significantly reduced B cells in lymphoid tissues. Splenic B cells were depleted to a greater extent compared with lymph node B cells. A second cycle of treatment resulted in a greater extent of depletion in lymphoid tissues compared with the depletion observed after one cycle of treatment; however, residual B cells in lymphoid tissues were still detectable, even at the highest dose. The rate of B-cell recovery in peripheral blood appeared similar between one and two cycles of treatment. Upon depletion there was a change in the profile of lymph node B-cell subsets. After recovery, B-cell subsets were reconstituted to normal levels. Depletion of CD20-expressing cells and lymphoid follicular atrophy were the only treatment-related effects.     

Cost losses associated with the "PICC, stick, and run team" concept.

Covenant Healthcare System is a 500-bed facility in Saginaw, Michigan. A peripherally inserted central catheter (PICC) program was instituted there in 1990 when it was St. Lukes Hospital. Over the course of 17 years, 30 nurses had been trained to place PICCs in their spare time. A "PICC, stick, and run team" was established in 1998 but was unsuccessful. After a merger with Saginaw General Hospital, Covenant Healthcare created two full-time vascular access specialty positions. This nursing-based PICC program with full-time staffing has revitalized vascular access at Covenant Healthcare System. Currently, PICCs are placed proactively at the beginning of hospital stays. Peripheral catheter restarts have been replaced with reliable PICC access sites. Delayed discharge for PICC insertion is no longer an issue.     

Effect of individualized social activity on sleep in nursing home residents with dementia

OBJECTIVES: To test the efficacy of an individualized social activity intervention (ISAI) on decreasing daytime sleep, improving nighttime sleep, and lowering the day/night sleep ratio and to determine its cost. DESIGN: Pretest/posttest randomized with an experimental and control group. SETTING: Seven nursing homes. PARTICIPANTS: One hundred forty-seven residents with dementia. INTERVENTION: One to 2 hours of individualized social activities for 21 consecutive days. MEASUREMENTS: Twenty-four-hour sleep/wake patterns using an Actigraph. RESULTS: The ISAI group had significantly less daytime sleep (P=.001) and a lower day/night sleep ratio (P=.03) than the control group, after adjusting for baseline values. Because 40% of the sample slept 7 or more hours at night, a secondary analysis was conducted. When only those residents with a sleep efficiency of less than 50% (n=50) were included, the ISAI group (n=20) had less daytime sleep (P=.005), a lower day/night sleep ratio (P=.02), fell asleep faster (P=.03), and were awake less at night (P=.04) than the control group (n=30), after adjusting for baseline values. The weekly cost of the ISAI was roughly $70 per participant. Initial training and supply costs were $1,944. CONCLUSION: The ISAI provides an alternative to medications, without side effects.