Demonstration of the feasibility of emergency department immunization against influenza and pneumococcus

STUDY OBJECTIVE: To demonstrate the feasibility of systematic immunization against influenza and pneumococcus in a public emergency department. METHODS: This was a demonstration project conducted from October 21, 1996, through December 2, 1996, at Cook County Hospital, an inner-city hospital with a 1996 adult ED census of 120,449. Seventy-eight percent of patients are uninsured; 92% are people of color; 73% deny having a primary physician. Only 15% have emergency complaints. Nurses received standing orders that all nonemergency adult patients meeting Centers for Disease Control and Prevention criteria for high risk should be offered immunization against influenza and pneumococcus at triage. Cash prizes were offered to nurses appropriately immunizing the most patients. The date of immunization was entered into the computerized patient registration system, available to all providers within the county system. From November 4 through November 18, an extra nurse was assigned to triage to test for improvement in immunization rates. A time-motion study determined the time required per immunization on the basis of a convenience sample of 8 nurses drawn from all 3 shifts. RESULTS: Only 3% of identified high-risk patients reported previous pneumococcal immunization. Despite extreme variation in nurse performance, 2,631 patients (24% of patients triaged) were screened, and 716 high-risk patients were identified (27% of patients screened). A total of 1234 patients were immunized against influenza, and 241 patients were appropriately immunized against pneumococcus. Sixty-one percent of high-risk patients with no contraindication to influenza immunization were immunized against influenza. Thirty-five percent of high-risk patients not previously immunized against pneumococcus were immunized against pneumococcus. Immunizations per shift per triage nurse varied from 0 to 24. Median time for all activities related to immunization was 4 minutes (range, 2 to 10 minutes). There was no increase in immunization rates with the addition of an extra nurse at triage (95% confidence interval for odds ratio, .929 to 1.153). CONCLUSION: Systematic immunization against influenza and pneumococcus is both needed and feasible in a public ED. "Buy-in" by nurses is variable. Increased staffing alone does not improve immunization rates.     

CT-guided spinal biopsy in spondylodiscitis

Since February 1987 percutaneous CT-guided spine biopsy was performed in 18 patients with spondylodiscitis at the X-ray Department of Bispebjerg Hospital. Eleven cases were spontaneous and seven followed spinal surgery. The infection was located in five cases in the thoracic spine and in 13 cases in the lumbar spine. Only one biopsy was performed during general anaesthesia, the rest under local anaesthesia. No complications were observed. The bioptic material was cultivated immediately beside the patient and incubated for 14 days. The infective organism was isolated in 12 cases (67%). Thus, material obtained through a fine needle was satisfactory for microbiological investigation. A biopsy is crucial for establishing a microbiological diagnosis and thereby enabling prompt adequate treatment.     

Heuristic lipophilicity potential for computer-aided rational drug design

In this contribution we suggest a heuristic molecular lipophilicity potential (HMLP), which is a structure-based technique requiring no empirical indices of atomic lipophilicity. The input data used in this approach are molecular geometries and molecular surfaces. The HMLP is a modified electrostatic potential, combined with the averaged influences from the molecular environment. Quantum mechanics is used to calculate the electron density function rho(r) and the electrostatic potential V(r), and from this information a lipophilicity potential L(r) is generated. The HMLP is a unified lipophilicity and hydrophilicity potential. The interactions of dipole and multipole moments, hydrogen bonds, and charged atoms in a molecule are included in the hydrophilic interactions in this model. The HMLP is used to study hydrogen bonds and water-octanol partition coefficients in several examples. The calculated results show that the HMLP gives qualitatively and quantitatively correct, as well as chemically reasonable, results in cases where comparisons are available. These comparisons indicate that the HMLP has advantages over the empirical lipophilicity potential in many aspects. The HMLP is a three-dimensional and easily visualizable representation of molecular lipophilicity, suggested as a potential tool in computer-aided three-dimensional drug design.     

CVT-313, a specific and potent inhibitor of CDK2 that prevents neointimal proliferation

The activity of cyclin-dependent kinase 2 (CDK2) is essential for progression of cells from G1 to the S phase of the mammalian cell cycle. CVT-313 is a potent CDK2 inhibitor, which was identified from a purine analog library with an IC50 of 0.5 microM in vitro. Inhibition was competitive with respect to ATP (Ki = 95 nM), and selective CVT-313 had no effect on other, nonrelated ATP-dependent serine/threonine kinases. When added to CDK1 or CDK4, a 8.5- and 430-fold higher concentration of CVT-313 was required for half-maximal inhibition of the enzyme activity. In cells exposed to CVT-313, hyperphosphorylation of the retinoblastoma gene product was inhibited, and progression through the cell cycle was arrested at the G1/S boundary. The growth of mouse, rat, and human cells in culture was also inhibited by CVT-313 with the IC50 for growth arrest ranging from 1.25 to 20 microM. To evaluate the effects of CVT-313 in vivo, we tested this agent in a rat carotid artery model of restenosis. A brief intraluminal exposure of CVT-313 to a denuded rat carotid artery resulted in more than 80% inhibition of neointima formation. These observations suggest that CVT-313 is a promising candidate for evaluation in other disease models related to aberrant cell proliferation.     

Differential expression of two functional serine/threonine protein kinases from soybean that have an unusual acidic domain at the carboxy terminus

Two soybean cDNA clones, SPK-3 and SPK-4, encoding putative protein kinases were isolated and characterized. Both cDNAs encoded approximately 40-kDa serine/threonine kinases with unusual stretches of acidic amino acids in their carboxy-terminal regions, which are highly homologous to PKABA1 from wheat and ASKs from Arabidopsis. These kinases are encoded by one- or two-copy genes in the soybean genome. Notably, SPK-3 and -4 showed different patterns of expression in various soybean tissues. SPK-3 is highly expressed in dividing and elongating tissues of young seedlings but relatively weakly in tissues of mature plants. In contrast, SPK-4 showed relatively high and constitutive expression in all the tissues examined except for leaf tissues of mature plants. Although various stressors, such as dehydration and high salinity, increased the expression of both genes, the induction kinetics were different. The two genes also differed in their response to abscisic acid (ABA). SPK-3 was induced but SPK-4 was not affected by exogenously supplied abscisic acid. In accordance with these expression data analysis of the activity of a chimeric SPK-3 promoter::beta-glucuronidase (GUS) reporter gene by transient expression in tobacco leaves confirmed the inducibility of SPK-3 by salt and ABA. Polyclonal antibodies raised against a recombinant SPK-4 protein produced in Escherichia coli specifically recognized both recombinant SPK-3 and -4 proteins. Kinase assays using affinity-purified SPK-4/ antibody complexes with crude soybean extracts as substrate identified specific phosphorylation of two 41 and 170 kDa soybean proteins that were phosphorylated on serine residues. Taken together, our results suggest that SPK-3, and/or SPK-4 are functional serine protein kinase(s). Furthermore, SPK-3 and -4 may play different roles in the transduction of various environmental stresses.     

Pancreatic cancer and comparison of a hospital-based tumor registry with a National Cancer Data Base

BACKGROUND: The Commission on Cancer of the American College of Surgeons has called upon institutions providing cancer care to compare practice patterns and outcomes with the National Cancer Data Base (NCDB). Using data from the Virginia Mason Tumor Registry (VMTR), we sought to compare our pancreatic cancer care patterns with those reported nationally, while critically evaluating the accuracy and usefulness of our registry. METHODS: A review of the 906 computerized patient files in the VMTR from 1973 to 1995 was performed, with more detailed data on patients from the last 5 years retrieved from 224 manual abstracts. These data were compared with the 1991 NCDB for pancreatic cancer. RESULTS: The percent of cases according to AJCC stage in the NCDB (n = 9,715) versus the VMTR (n = 149), respectively, with cases of unknown stage excluded, were stage I 22% versus 22%, stage II 9% versus 12%, stage III 17% versus 28% (P <0.05) stage IV 52% versus 38% (P <0.05). One-third of the cases in the VMTR 1991 to 1995 were of unknown stage; number of cases with unknown stage for NCDB was 26.6%. The percent of surgical procedures for the NCDB (n = 7,802) versus the VMTR (n = 224), respectively, was pancreatectomy 14% versus 11%, local excision 1% versus 0%, no cancer-directed surgery 83% versus 89% (P <0.05), unknown 2% versus 0% (P <0.05). The actuarial relative survival rates for the 1991 NCDB versus 1987 to 1995 VMTR was 3-year 18% versus 38%, and 5-year 14% versus 35%. CONCLUSIONS: In comparison with the NCDB, VMTR may have fewer stage IV pancreatic cancers, but improvement is needed in decreasing the number of patients for whom the stage is unknown, as many of these likely represent late stage disease. We have a similar resection rate and a higher survival compared with the NCDB, but a mechanism is not in place to statistically compare our survival data with those of the NCDB. Even though all accredited hospitals are required to have a tumor registry, our data were difficult to compare with those of the NCDB because of coding and reporting deficiencies and inability to statistically compare survival data. Before our practice patterns and outcomes can be compared with national standards, both the VMTR and the NCDB must have standardized data collection and better access to the data.