Activated protein C resistance, factor V Leiden and assessment of thrombotic risk.

Venous thromboembolism comprises deep vein thrombosis (DVT) and pulmonary embolism (PE). Acute venous thromboembolism (VTE) is a serious and potentially fatal disorder which often complicates the course of hospitalized patients, but also affects ambulatory and otherwise healthy people. The annual incidence of venous thromboembolism is 1 to 2 cases per 1000 person and the risk of the disorder rises exponentially with age, from an annual rate of less than 5 per 100,000 children to greater than 400 per 100,000 adults older than 80 years.

Coagulase-negative staphylococcal contamination of whole blood and its components: the effects of WBC reduction.

BACKGROUND: Most bacteria present in blood components are normal skin flora, particularly Staphylococcus epidermidis and other coagulase-negative staphylococci. Growth patterns of these bacteria and the effects of different methods of component preparation may depend on variations in behavior between different isolates of the same species. STUDY DESIGN AND METHODS: Whole-blood units were inoculated with 19 different coagulase-negative staphylococcus (CNS) isolates at 1 to 10 and 10 to 100 CFUs per mL. After overnight holding at 22 degrees C, the units were processed into components. The components were cultured before inoculation and during processing, including before and after WBC reduction. RESULTS: At low inoculum levels, CNS was detected in 15 (79%) of 19 whole-blood units and in 12 (63%) of 19 RBCs after separation; after filtration, bacteria were detected in 3 (16%) of 19 (p = 0.0069). For platelet concentrates, 6 (32%) of 19 grew bacteria before filtration and 1 of 18 after filtration (difference not statistically significant). Three (16%) of 19 plasmas were positive before and after freezing. At high inoculum levels, 16 (89%) of 18 whole-blood samples and RBCs were positive before filtration; 6 (33%) of 18 RBCs were positive after filtration (p = 0.0002); 8 (44%) of 18 platelets were positive before filtration; 3 (17%) of 18 were positive after filtration (difference not statistically significant), and 7 (37%) of 18 plasma samples were positive before and after freezing. CONCLUSION: The growth characteristics of CNS in blood components vary with differences either in the subtype of bacteria or in the donor blood. Filtration reduces but does not eradicate contamination of RBCs and platelets by CNS. Plasma may act as a reservoir for CNS infection.

Impact of an easy-access VA clinic-based program for patients with bipolar disorder.

OBJECTIVE: The study examined the impact of easy access to ambulatory services for patients with bipolar disorder in a clinic-based program at a Veterans Affairs medical center. Core program components included medication administration based on treatment algorithms, standardized psychoeducation, and easy access to a single primary nurse provider to enhance continuity of care. The program had no community outreach or extensive rehabilitation components. METHODS: The study used a mirror-image design to compare patients' data from the year before program entry when patients received standard clinical care with data for the first year in the program. Process and outcome data from the first 103 patients to complete one year are reported. RESULTS: The findings indicated increased patient satisfaction and increased intensity of medication treatment without increased side effects at one year. Although scheduled ambulatory clinic visits increased as expected, use of the emergency room and the psychiatric triage team decreased significantly. Patients who were high utilizers of care before program entry experienced significant reductions in psychiatric hospital days and total mental health expenditures. CONCLUSIONS: Easy access to ambulatory care, even if limited to clinic-based services, may have beneficial effects on important process and outcome measures for bipolar disorder. These effects may be attributable to on-demand access to services, continuity of care with a single primary provider, or improved medication delivery to reduce the "efficacy-effectiveness gap" for patients with bipolar disorder. Results indicate that augmenting, rather than limiting, access to ambulatory care for patients with major mental illnesses such as bipolar disorder may reduce overall mental health expenditures.

High affinity type I interleukin 1 receptor antagonists discovered by screening recombinant peptide libraries.

Two families of peptides that specifically bind the extracellular domain of the human type I interleukin I (IL-1) receptor were identified from recombinant peptide display libraries. Peptides from one of these families blocked binding of IL-lalpha to the type I IL-1 receptor with IC50 values of 45-140 microM. Affinity-selective screening of variants of these peptides produced ligands of much higher affinity (IC50 approximately 2 nM). These peptides block IL-1-driven responses in human and monkey cells; they do not bind the human type II IL-1 receptor or the murine type I IL-1 receptor. This is the first example (that we know of) of a high affinity peptide that binds to a cytokine receptor and acts as a cytokine antagonist.

Cloning and targeted gene disruption of XYL1, a beta 1,4-xylanase gene from the maize pathogen Cochliobolus carbonum.

The gene, XYL1, encoding the major extracellular endo-beta 1,4-xylanase from the maize pathogen Cochliobolus carbonum was cloned using a synthetic, degenerate oligonucleotide based on a tryptic fragment from the purified enzyme. The deduced product of XYL1 has a M(r) of 20,869 and a predicted pI of 9.1, in good agreement with the measured M(r) and pI of the purified enzyme. The XYL1 product has strong amino acid identity to seven endo-beta 1,4-xylanases from six prokaryotes but no obvious similarity to 10 other prokaryotic endoxylanases or a yeast endoxylanase. An internal fragment of the gene was used to create a specific xylanase mutant by transformation-mediated gene disruption via homologous recombination. Total extracellular xylanase activity in the mutant was reduced by 85-94%. When analyzed by cation exchange HPLC, culture filtrates of the mutant and wild type had identical protein profiles, but the mutant lacked the major peak of UV absorption corresponding to the major xylanase activity. Xylanase II activity was also missing in the mutant, but xylanase III activity was still present. The XYL1 mutant grew as well as the wild type on sucrose, on corn cell walls, and on xylan. The pathogenicity of the mutant was indistinguishable from the wild type, indicating that XYL1 is not required for pathogenicity.

Fairness in prospective payment: a clustering approach.

Problems of fairness in prospective payment have existed since the inception of this regulatory method in the early 1980s. While prospective payment ostensibly has sought to reward efficient producers and provide disincentives for inefficient producers of health care, many hospitals have been penalized financially as a consequence of facing systematic factors beyond their control. This article defines homogenous peer groups of Department of Veterans Affairs providers for the purpose of establishing competitive prospective reimbursement rates. An econometric analysis classifies hospitals into six categories: small affiliated, small general, midsize affiliated/tertiary, large affiliated/tertiary, midsize general, and psychiatric. The Department of Veterans Affairs adopted this classification to alter its prospective payment system in 1988.

Medical informatics and health care organizations.

A dialogue between upper management and operational elements over an organization's informatics policies and procedures could take place in an environment in which both parties could succeed. Excellent patient care practices can exist in organizational settings where upper management is not concerned with the specifics of the medical care process. But as the medical care process itself becomes costly, complex, and part of the purview of upper management, solutions to ambiguous informatics policies and practices need to be found. As the discussion of cost determination suggests, a comprehensive "top-down" solution may not be feasible. Allowing patient care expertise to drive the design and implementation of clinical computing modules without unduly restrictive specifications from above is probably the best way to proceed. But if the organization needs to know the specifics of a treatment episode, then the informatics definitions specific to treatment episodes need to be unambiguous and consistently applied. As the discussion of Social Security numbers suggests, communication of information across various parts of the organization not only requires unambiguous data structure definitions, but also suggests that the communication process not be dependent on the content of the messages. Both ideas--consistent data structure definitions for essential data and open system communication architectures--are current in the medical informatician's vocabulary. The same ideas are relevant to the management and operation of large and diffuse health care enterprises. The lessons we are learning about informatics policy and practice controls in clinical computing need to be applied to the enterprise as a whole.

When Infections Co-exist: Infectious Mono and Diphtheria.

Infectious mononucleosis was tentatively diagnosed in a patient who presented with a temperature of 39.5°C, red throat and enlarged nodes in the neck. He was given amoxycillin 250 mg tid and was admitted to hospital, where his clinical symptoms of diphtheria were investigated. Medication was switched to penicillin V 300 mg tid. On the fifth hospital day the laboratory reported a culture of a toxigenic strain of C. diphtheriae from an initial throat swab.On the same day, he developed an erythematous, highly pruritic maculopapular rash which was probably caused by the initial use of amoxycillin. The rash initially became generalized and slowly resolved in 7-9 days. He apparently had infectious mononucleosis and a coincidental pharyngeal infection with toxigenic C. diphtheriae.No indication exists for the use of antibiotics in infectious mononucleosis, unless throat cultures reveal bacterial pathogens. In that case, an appropriate antibiotic other than ampicillin-amoxycillin can be chosen.

Listerial meningitis and renal allografts: a life-threatening affinity.

Two cases of Listeria monocytogenes infection in patients receiving immunosuppressive treatment after kidney transplantation are described. In the first, the infection, which occurred soon after transplantation and was accompanied by signs of mild chronic rejection, was the immediate cause of death. The other case occurred in a patient whose transplanted kidney had been functioning well for more than four years; this patient recovered. These cases, plus a review of 40 similar cases in the literature, point out the importance of anticipating possible listerial infection when septic meningitis arises in a patient with a transplanted kidney.

Tetanus in a 67-year-old man.

A fatal case of generalized tetanus in a 67-year-old man is presented. The incubation period following finger damage was short, and the diagnosis was confirmed by the isolation of Clostridium tetani. Subsequently, a partial surgical amputation of the infected finger during the clinically active stage of the disease did not remove all the infecting organisms. Although convincing evidence of any previous active immunization was lacking, no form of tetanus antitoxin was given at the time of injury. This case illustrates the potential dangers of unfamiliarity with tetanus owing to its low incidence in developed countries.

Observations and comments concerning the isolation of group B beta-hemolytic streptococci from human sources.

A marked increase in the isolation of Group B streptococci from patients in the University Hospital, Saskatoon, has been noted over the past four years, and no change in technical methods has been found to explain this increase. Group B streptococci have been isolated from 242 patients, in 53 of whom the streptococcus was considered the cause of the infection. Infections occurred predominantly in the urinary tract, female genital tract and upper respiratory tract. There was a low incidence of infections in newborn infants, and only four infections were in patients under 1 year old. Infections were more frequent in women than men and in patients over 40 years of age. No particular affinity of Group B streptococci for diabetics was demonstrated.