A quantitative framework for a multi-group model of Schistosomiasis japonicum transmission dynamics and control in Sichuan,China

A quantitative framework is presented for the site-specific characterization of schistosomiasis transmission with the object of developing local control strategies. Central to the framework is a worm-burden model using ordinary differential equations of disease transmission in risk groups defined by residence and occupation. The model incorporates temperature- and precipitation-dependent seasonality of infectious stages, snail population dynamics, and seasonal patterns of human water contact specific to the local agricultural setting. The model's parameters are separated into two main subsets, those associated with the general biology of the parasite and its life cycle in the human and the snail and those associated with directly measurable features of disease status in the local population or relevant aspects of the local environment. In this regard, the model is structured and parameterized to take maximum advantage of data that can be collected in rural China by conventional methods. For example, it includes a statistical model for egg excretion to the environment by each risk group which is based on local population surveys of the prevalence and intensity of infection. The second element of the framework of analysis relates to the strategy for parameter estimation and calibration to local conditions. We propose a Bayesian approach in which parameter estimates are refined over time by methods employing extensive computer simulations. An early analysis of data collected between 1987 and 1989 in endemic villages near Xichang City in southwestern Sichuan provides encouragement that parametric uncertainty can be reduced to levels adequate to explore effective control strategies.     

Stage-specific expression of c-kit protein by murine hematopoietic progenitors

We have analyzed c-kit expression by hematopoietic progenitors from normal and 5-fluorouracil (5-FU)-treated mice by staining with monoclonal anti-c-kit antibody ACK-4. Marrow cells that were enriched for progenitors by a combination of metrizamide density separation and negative immunomagnetic selection with lineage-specific monoclonal antibodies (MoAbs) were separated into three populations based on the level of c-kit expression, c-kit(high), c-kit(low), and c-kit-. The majority of colony-forming cells from normal mice were in c-kit(high) population, whereas most of the progenitors from 5-FU-treated mice were in the c-kit(low) population. Optimal colony formation from c-kit(low) cells from 5-FU-treated mice required the interactions of at least two factors among interleukin-3 (IL-3), IL-11 and steel factor (SF) whereas colony formation from c-kit(high) cells of normal mice was supported well by IL-3 alone. Blast cells that were derived from 5-day culture of c-kit(low) post 5-FU cells were c-kit(high). These observations suggest that the primitive hematopoietic progenitors in cell cycle dormancy are c-kit(low) whereas actively cell cycling maturer progenitors are c- kit(high). Mature cells, with the exception of mast cells, derived from secondary culture of the c-kit(high) blast cells expressed little, if any, c-kit. These results are consistent with a model in which c-kit expression progresses from low levels on primitive, dormant multipotent progenitors to high levels on later, actively cycling progenitors, and finally, decreases to very low or undetectable levels on most mature blood cells, with the exception of mast cells.     

Necessary but not sufficient

Objective: To consider the impact on primary care patient outcomes of using both a screener to determine elevated anxiety levels among patients with previously undetected anxiety and a physician intervention to inform physicians of their patients’ conditions. Design: Participating physicians were randomized to either the demonstration or the control arm, and patients were assigned to a study arm based on the randomization of their physicians. The patients were followed for change in outcome measures during the five-month study period. Setting: A mixed-model health maintenance organization serving approximately 110,000 enrollees in central Colorado. Patients/participants: 573 patients who had unrecognized and untreated anxiety identified from the approximately 8,000 patients who completed the waiting room screening questionnaire. Interventions: A physician intervention served the dual function of 1) providing an educational demonstration of anxiety in the primary care setting and 2) providing a reporting system for summarizing the anxiety symptom levels and functioning status of the patients enrolled in the study. Measurements and main results: Patient outcomes were measured as changes in global anxiety scores, functioning and well-being, and patients’ reports of global improvements. Conclusions: The findings indicate that this method of reporting symptoms and functioning status to primary care physicians did not significantly change patient outcomes. Improvement in outcomes appeared to be more closely associated with the patient’s severity of psychological distress. Preliminary data from this study were presented at the Seventh Annual National Institute of Mental Health International Research Conference on Mental Health Problems in the General Health Care Sector, September 20–22, 1993, McLean, Virginia, and at the first Annual Symposium of Contributed Papers on Quality of Life at the Drug Information Association Workshop, April 26–27, 1993, Charleston, South Carolina. Supported by a grant from the Upjohn Company, Kalamazoo, Michigan, and Take Care, Colorado. (Note: Dr. Buesching is a former employee of the Upjohn Company but owns no stock or option to purchase further stock in the company. Ms. Mathias, Dr. Fifer, Dr. Mazonson, Dr. Lubeck, and Dr. Patrick own no stock or option in the Upjohn Company.)     

Bone marrow transplantation (BMT) in Europe for primary immunodeficiencies other than severe combined immunodeficiency: a report from the European Group for BMT and the European Group for Immunodeficiency

Bone marrow (BM) transplantations performed between 1977 and 1991 at 13 European centers in 149 patients with 11 different primary immunodeficiency (ID) diseases (excluding severe combined immunodeficiency) were analyzed retrospectively. Overall survival among recipients of HLA genetically identical BM (n = 56) was 66%. Since October 1985, the date of a previous survey, a significant improvement in survival has been achieved in most ID diseases (overall survival, 81.5% v 51.7%; P < .01), primarily because of a decrease in the frequency of infectious complications. In long-term survivors, disease correction is excellent, with minimal sequelae in most patients. In 22 patients who received closely matched BM (ie, from phenotypically identical related donors, matched unrelated donors, or one HLA-ag- mismatched related donors), the survival rate (45.5%) was not significantly better than among 71 recipients of BM with 2 or 3 mismatched HLA antigens (38%). In the latter group, favorable outcome was associated with younger age, with transplantation since October 1985 (47% v 25%; P < .0001), and with a diagnosis of leukocyte adhesion deficiency. The improvement in outcome was mainly because of a higher engraftment rate and a decrease in the frequency of infections, although Epstein-Barr virus-induced B-lymphocyte proliferative disorders occurred in 16 patients (mainly those with Wiskott-Aldrich syndrome), 10 of whom died. The improvement in engraftment corresponded to the introduction of treatment in vivo with anti-LFA-1 antibody to prevent rejection of T-cell-depleted grafts (74% engraftment and 45% survival in 38 treated patients versus 37.5% and 21%, respectively, in 24 untreated patients.     

The formation of Ca++-dependent complexes of platelet membrane glycoproteins IIb and IIIa in solution as determined by crossed immunoelectrophoresis

Triton X-100 soluble proteins from 125I-labeled human platelets were studied by crossed immunoelectrophoresis employing a multispecific rabbit antibody raised against whole normal platelets. Emphasis was placed upon an analysis of immunoprecipitates containing 125I-labeled major membrane glycoproteins, and in particular, a prominent immunoprecipitate containing a glycoprotein antigen (s) previously designated as protein 16. SDS-polyacrylamide gel electrophoresis of protein 16 precipitated by a monospecific alloantibody. IgG L . . . , confirmed the presence of both glycoproteins IIb and IIIa. 125I-IgG L . . . , at concentration below that capable of precipitating protein 16 by itself, bound specifically to the precipitate containing protein 16 produced by the multispecific rabbit antibody. No other precipitates formed by the rabbit antibody contained either glycoprotein IIb or IIIa. When platelet proteins, incubated with optimum concentrations of ethylenediamine tetraacetic acid (EDTA) or ethyleneglycol bis (B- aminoethylether) NN1-tetraacetic acid (EGTA), were electrophoresed against the rabbit antibody, previously unobserved immunoprecipitates that contained either free glycoprotein IIb or free glycoprotein IIIa were detected. Upon readdition of excess Ca++, but not Mg++, to the same protein samples, a single immunoprecipitate containing both glycoproteins was once again observed. It is thus demonstrated that glycoproteins IIb and IIIa can form Ca++-dependent complexes (protein 16) in Triton X-100 extracts of normal platelets. The potential significance of the reversible association of these glycoproteins to normal platelet function is discussed.     

Early colonoscopy for acute lower GI bleeding predicts shorter hospital stay: a retrospective study of experience in a single center

BACKGROUND: Appropriate management of lower-GI hemorrhage remains controversial largely because outcomes data are lacking. It is our hypothesis that clinical factors, such as comorbidity, hemodynamic instability, and timing of colonoscopy, are associated with hospital lengths of stay. METHODS: Medical records of patients hospitalized for lower-GI hemorrhage from 1993 to 2000 were reviewed and abstracted, and a Cox regression model was constructed to explore associations between time to discharge (i.e., length of stay) and clinical parameters. RESULTS: A total of 565 hospitalizations for acute lower-GI hemorrhage were examined in which mean length of stay was 6.7 days. Colonoscopy was performed during 415 hospitalizations. Approximately a third of patients were discharged within 48 hours after colonoscopy. In the regression model, hemodynamic instability, higher comorbidity, performance of a tagged red blood cell nuclear scan, and surgery for hemostasis were significantly associated with a decreased likelihood of discharge. Having a colonoscopy was associated with an increased likelihood of being discharged compared with not having a colonoscopy at any given time point during hospitalization (hazard ratio 1.5: 95% CI[1.2, 1.8]. The mean lengths of stay for patients having colonoscopy within 24 hours of hospitalization was shorter than those having colonoscopy after 24 hours of hospitalization (5.4 vs. 7.2 days; p<0.008). CONCLUSIONS: In patients with lower-GI hemorrhage, earlier colonoscopy predicted earlier hospital discharge. However, colonoscopy did not necessarily lead to expedited post-procedural discharge. Although early colonoscopy appears to shorten hospital length of stay, prospective studies of inpatient colonoscopy are needed to determine the impact of this approach on outcomes.