T-cell receptor excision circle and T-cell dynamics after allogeneic stem cell transplantation are related to clinical events

It is generally believed that homeostatic responses regulate T-cell recovery after peripheral stem cell transplantation (PSCT). We studied in detail immune recovery in relation to T-cell depletion and clinical events in a group of adult patients who underwent PSCT because of hematologic malignancies. Initially, significantly increased proportions of dividing naive, memory, and effector CD4(+) and CD8(+) T cells were found that readily declined, despite still very low numbers of CD4(+) and CD8(+) T cells. After PSCT, increased T-cell division rates reflected immune activation because they were associated with episodes of infectious disease and graft-versus-host disease (GVHD). T-cell receptor excision circles (TRECs) were measured to monitor thymic output of naive T cells. Mean TREC content normalized rapidly after PSCT, long before naive T-cell numbers had significantly recovered. This is compatible with the continuous thymic production of TREC(+) naive T cells and does not reflect homeostatic increases of thymic output. TREC content was decreased in patients with GVHD and infectious complications, which may be explained by the dilution of TRECs resulting from increased proliferation. Combining TREC and Ki67 analysis with repopulation kinetics led to the novel insight that recovery of TREC content and increased T-cell division during immune reconstitution after transplantation are related to clinical events rather than to homeostatic adaptation to T-cell depletion. (Blood. 2002;99:3449-3453)     

Air pollution exposure estimation using dispersion modelling and continuous monitoring data in a prospective birth cohort study in the Netherlands

Background

High temperature and humidity conditions are associated with short-term elevations in the mortality rate in many United States cities. Previous research has quantified this relationship in an aggregate manner over large metropolitan areas, but within these areas the response may differ based on local-scale variability in climate, population characteristics, and socio-economic factors.

Methods

We compared the mortality response for 48 Zip Code Tabulation Areas (ZCTAs) comprising Philadelphia County, PA to determine if certain areas are associated with elevated risk during high heat stress conditions. A randomization test was used to identify mortality exceedances for various apparent temperature thresholds at both the city and local scale. We then sought to identify the environmental, demographic, and social factors associated with high-risk areas via principal components regression.

Results

Citywide mortality increases by 9.3% on days following those with apparent temperatures over 34°C observed at 7:00 p.m. local time. During these conditions, elevated mortality rates were found for 10 of the 48 ZCTAs concentrated in the west-central portion of the County. Factors related to high heat mortality risk included proximity to locally high surface temperatures, low socioeconomic status, high density residential zoning, and age.

Conclusions

Within the larger Philadelphia metropolitan area, there exists statistically significant fine-scale spatial variability in the mortality response to high apparent temperatures. Future heat warning systems and mitigation and intervention measures could target these high risk areas to reduce the burden of extreme weather on summertime morbidity and mortality.     

Prevalence and incidence of shoulder pain in the general population; a systematic review

OBJECTIVE: To investigate the incidence and prevalence of shoulder complaints in the general population. METHOD: A systematic review of the literature was conducted. Medline, Embase, and Cinahl were searched for relevant studies. RESULTS: Eighteen studies on prevalence and one study on incidence met the inclusion criteria. Incidence figures of 0.9-2.5% were found for different age groups. Prevalence figures differed from 6.9 to 26% for point prevalence, 18.6-31%, for 1-month prevalence, 4.7-46.7% for 1-year prevalence and 6.7-66.7% for lifetime prevalence. Prevalence rates decreased when the case definition was restricted, in terms of duration of pain or the presence of limited movements, and increased when the location for pain was enlarged. CONCLUSION: The reported prevalence figures on shoulder complaints diverged strongly. Health professionals and policymakers who estimate the amount of medical care needed and related costs should be aware of the variations in prevalence rate and the underlying reasons for these differences.     

Detection of Early Anti-p24 HIV Responses in EIA- and Immunoblot-Negative Individuals

A sensitive and specific radioimmunoprecipitation assay was developed for the detection and analysis of anti-HIV antibody response in human sera with the use of 125I-labelled purified HIV proteins with subsequent sodium-dodecylsulfate gel electrophoresis (125I-RIPA). The 125I-RIPA was shown to be as specific but at least 1 log more sensitive with respect to the detection of gp41env and p24gag than the immunoblot analysis as tested in serum samples from several risk groups. Sequential sera were obtained from 9 individuals who seroconverted for HIV antibodies. In 4 individuals, antibody to p24gag was detected in earlier serum samples by the 125I-RIPA than by EIA or immunoblot; in the other 5 individuals, the detection of p24gag concorded in enzyme-linked immunosorbent assay (EIA), immunoblot and 125I-RIPA. Moreover, in one of 78 randomly chosen EIA-negative sera from individuals at high risk, antibodies to p24gag could be detected by the 125I-RIPA. This early seroconversion was confirmed 3 months later by means of immunoblotting and EIA. The specificity of the 125I-RIPA was further demonstrated by analyzing sequential EIA-negative serum samples from 10 individuals at risk for AIDS, collected during 2 years at 3-monthly intervals. All 80 serum samples were found to be negative in the 125I-RIPA and the individuals revealed no signs of HIV infection. The 125I-RIPA technique may be a valuable confirmatory assay in the serology of HIV infections. The sensitivity of this test provides a reliable measure of effective sensitivity when new-generation screening tests are evaluated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Response of canine ileocolonic sphincter to intraluminal acetic acid and colonic distension

The aim was to determine the effect of intraluminal acetic acid and proximal colonic distension on canine ileocolonic sphincter pressure, ileal motility, and coloileal reflux. In six conscious dogs with an isolated ileocolonic loop, basal pressure of the ileocolonic sphincter was similar during ileal perfusion with 100 mM acetic acid at 1 ml/min (mean±sem=18±0.4 mm Hg) and with saline (18±0.5 mm Hg;P=0.81). Discrete clustered ileal contractions were more frequent with acetic acid, however, and when they propagated across the sphincter, sphincter pressure increased from 18±0.4 mm Hg to 36±1.3 mm Hg (P=0.002). Sphincter pressure was also greater during colonic perfusion with acetic acid (32±0.7 mm Hg) than during ileal perfusion with acetic acid or saline (P<0.017). Moreover, sphincter pressure gradually increased as the colon was distended with saline (slope=0.8 mm Hg/cm H₂O,P<0.017) or acetic acid (slope=0.5 mm Hg/cm H₂O,P<0.017), but the increase did not prevent coloileal reflux. In conclusion, ileal clustered contractions, colonic perfusion of acetic acid, and colonic distension all increased canine ileocolonic sphincter pressure.     

Interleukin 1 induces human marrow stromal cells in long-term culture to produce granulocyte colony-stimulating factor and macrophage colony- stimulating factor

Pure interleukin 1 (IL 1) was found to stimulate established human bone marrow stromal layers in long-term culture to produce colony- stimulating activity (CSA). Maximal concentrations in the culture medium were reached 24 hours after a single IL 1 pulse. The effect could be neutralized by a specific rabbit anti-IL 1 antiserum. Stromal layers, once stimulated by IL 1, continued to release CSA into the culture medium in the absence of exogenous IL 1. A second IL 1 pulse induced CSA release in an identical manner, as did the primary stimulation, indicating that the CSA released was actively produced. Using specific immunologic assays, both granulocyte colony-stimulating factor (G-CSF) and macrophage CSF (M-CSF) could be identified in the culture supernatants, and production of both factors was inducible by IL 1. Shortly after initiation of the long-term marrow cultures "spontaneous" G-CSF and M-CSF release occurred. The release of G-CSF diminished following addition of the anti-IL 1 antiserum, indicating that endogenous production of IL 1 by stromal cells had contributed to this effect. These results further support the role of IL 1 as an important modulator of CSF production by cells of the hematopoietic microenvironment.     

Transvaginal cholecystectomy without laparoscopic support using prototype flexible endoscopic instruments in a porcine model

Background

Transvaginal cholecystectomy with laparoscopic assistance has been performed safely in humans. The next goal was to develop a natural orifice transluminal endoscopic surgery (NOTES) technique to perform cholecystectomy without laparoscopic instruments using one flexible endoscope and flexible accessories. The aim of the study was to test the feasibility of the procedure in a survival porcine model.

Methods

Cholecystectomies were attempted in five 88–130-lb. pigs with a planned 2-week survival. Prototype flexible instruments (NOTES Toolbox, Ethicon Endo-Surgery, Inc.) were used to aid in access, dissection, and removal of the gallbladder via the transvaginal route.

Results

Cholecystectomy could be completed without abdominal incision using prototype instruments in four out of five pigs. The cystic duct could be exposed with a flexible hook knife and clips applied. The steerable trocar improved stability and the precision of the dissection. The critical view was established in all five pigs. Dissection of the gallbladder off the liver bed was imprecise resulting in gallbladder perforation in all pigs and liver hemorrhage in two. At necropsy, all clips on the cystic duct were secure and no bile leak, bowel injury, or adhesions were present.

Conclusions

NOTES cholecystectomy without laparoscopic support is feasible but challenging using prototype flexible endoscopic devices. A prototype clip applier was effective in controlling the cystic duct. Further improvements in instrument design to ensure precision and safety are needed before flexible devices should be used for pure NOTES procedures in humans.     

Hair tourniquet syndrome

A 6-year-old girl presented with necrosis of the left labium minus. An encircled hair at the base of the lesion was seen, and the diagnosis genital hair tourniquet syndrome was made. Genital hair tourniquet syndrome in children is a rare but potentially severe syndrome that requires immediate medical attention to prevent resulting necrosis.