Life-threatening hypokalaemia associated with ibuprofen-induced renal tubular acidosis.

Renal tubular acidosis is an underreported complication of ibuprofen misuse, and can result in life-threatening hypokalaemia. We describe four patients who presented with profound hypokalaemia and muscle weakness associated with excessive ibuprofen ingestion. Ibuprofen cessation and supportive management resulted in complete biochemical resolution within a few days. These cases remind practitioners about potential complications of unmonitored use of over-the-counter analgesics, including those with potential for misuse due to their codeine content.

Neuroblastoma with neuronal differentiation in the spinal cord in an Aberdeen Angus heifer calf.

A 5-month-old, female, Aberdeen Angus heifer presented to the veterinary medical teaching hospital for evaluation of slowly progressive hindlimb ataxia. The calf was clinically normal until 4 months of age, following routine pregnancy and delivery. Neurologic examination revealed marked symmetric spastic hindlimb paraparesis. Thoracolumbar radiographs and cerebrospinal fluid (CSF) analysis were unremarkable. A presumptive diagnosis of T3-L3 myelopathy was made, and neurologic status remained static for 3 months with broad-spectrum antibiotic and nonsteroidal anti-inflammatory therapy. Additional diagnostic tests were refused, and a necropsy was performed following euthanasia. A moderately well delineated, reddish-tan, soft mass 18 mm in diameter replaced 80% of the fourth lumbar spinal cord segment. Histologic examination revealed two distinct features: undifferentiated, primitive, polygonal-to-round cells with typical morphologic characteristics of primitive neuroectoderm; and interspersed areas containing myelinated axons and cells with neuronal differentiation. Immunohistochemical examination confirmed the presence of primitive neuroepithelium and cells with neuronal differentiation.

Mucosal co-administration of cholera toxin and influenza virus hemagglutinin-DNA in ponies generates a local IgA response.

We have previously demonstrated that equine influenza virus hemagglutinin (HA) DNA vaccination protects ponies from challenge infection, and induces protective IgGa and IgGb responses. However, this approach does not induce a nasal IgA response. The objective of this study was to examine the value of cholera toxin (CT) administration as an adjuvant for intranasal HA DNA vaccination, and to measure protection 3 months after DNA vaccination. After an immunogenic dose of CT was determined, ponies were immunized on two occasions by intranasal administration of HA DNA and cholera toxin, or HA DNA alone. Ponies in both groups received two additional HA DNA particle mediated vaccinations at skin and mucosal sites. Antibody responses, and protection from challenge infection 3 months after the last vaccination were studied and compared to an influenza virus naive control group. Ponies in both vaccination groups produced virus-specific IgG antibodies in serum following vaccination and showed clinical protection from challenge infection 3 months after the last vaccination. Co-administration of CT plus HA DNA vaccination induced a nasal IgA response. In addition, analysis of antibody titers in nasal secretions indicated local production of nasal IgGb, which was amplified by CT administration.

Identification of a locus involved in systemic dissemination of Yersinia enterocolitica.

A putative LysR-type transcriptional activator, Hre20, was identified previously in an in vivo expression technology screen designed to identify factors which are expressed early during infection by Yersinia enterocolitica (G. M. Young and V. L. Miller, Mol. Microbiol. 25:319-328, 1997). An insertion in hre20, now designated rscR, resulted in increased splenic dissemination of bacteria during infection in a BALB/c mouse model. A nonpolar mutation was generated in rscR, and examination of this strain in the BALB/c mouse model demonstrated that the mutation in rscR was responsible for the increased dissemination to the spleen that was seen in the original experiments. RscR is homologous to the LysR family of transcriptional regulators; thus, a screen was undertaken to identify genes regulated by RscR. A strain containing an insertion in the chromosomal rscR gene and carrying rscR on a plasmid under the control of the inducible araBAD promoter was mutagenized with an mTn5Km-2 transposon containing a promoterless lacZY. Eighteen insertions were identified which appeared to respond to levels of RscR, and these were classified into four allelic groups based on Southern blot hybridization analysis. Representative members were sequenced from three allelic groups. Sequencing revealed insertions in an ORF with no known homologues, a homologue of OmpF of Serratia marcescens, and a locus (designated rscBAC) with similarity to the hmwABC locus of Haemophilus influenzae. The hmwABC locus promotes adherence of H. influenzae to host cells (S. J. Barenkamp and J. W. St. Geme III, Infect. Immun. 62:3320-3328, 1994; J. W. St. Geme III, S. Falkow, and S. J. Barenkamp, Proc. Natl. Acad. Sci. USA 90:2875-2879, 1993). A strain containing a deletion mutant of rscA, the hmwA homologue, exhibits increased splenic dissemination of bacteria during infection in a BALB/c mouse model, similar to the rscR mutant. This suggests that the phenotype of an rscR mutant is due to the loss of RscA.

How to develop and implement a program to continuously demonstrate the value of clinical pharmacy services.

This paper summarizes key elements that support the success of clinical pharmacy services to continuously improve the quality of drug therapy. Five drivers identify a successful model for continuously demonstrating the value of clinical pharmacy services: knowing the organizational culture; providing leadership; recruiting pharmacy sponsors; showing tenacity; and acting with management courage. Difficulties encountered when communicating the value of clinical pharmacy services within a health care organization usually arise because of failure to include one of these drivers.

Local and systemic isotype-specific antibody responses to equine influenza virus infection versus conventional vaccination.

Inactivated alum-adjuvanted conventional equine influenza virus vaccines are of poor efficacy and offer limited short-term protection against infection. In sharp contrast, natural infection with equine influenza virus confers long-term protective immunity. In order to identify the protective immune responses to equine influenza virus, the influenza virus-specific IgA, IgGa, IgGb, IgGc and IgG(T) antibody responses in nasal secretions and serum induced by natural infection and a commercial vaccine were studied by ELISA. Two groups of four influenza-naive ponies were established. In the natural infection group, ponies received 10(8.5) EID50 of A/equine/Ky/1/81 by intranasal instillation, were allowed to recover, and then were rechallenged 100 days later. All four ponies exhibited clinical signs of influenza virus infection and viral shedding following primary infection, but were completely protected from challenge infection. Antibody responses to primary infection were characterized by nasal IgA and serum IgGa and IgGb responses. Ponies in the conventional vaccine group received a commercially available vaccine by intramuscular injection followed by a booster injection 3 weeks later. Challenge infection 100 days after vaccination resulted in clinical signs of infection and viral shedding. Antibody responses to vaccination were restricted to serum IgG(T) responses only. These results demonstrate that the protective immunity generated by natural equine influenza virus infection is associated with a mucosal IgA immune response and humoral IgGa and IgGb sub-isotype responses, and that this pattern of response is not generated by conventional vaccines.

Combined tubal and cornual pregnancy in a patient without risk factors. A case report.

BACKGROUND: Ectopic pregnancy is the leading cause of pregnancy-related death during the first trimester. Bilateral ectopic pregnancy is a rare phenomenon, varying in frequency between 1 per 725 and 1 per 1,580 ectopic pregnancies. We report the case of a bilateral ectopic pregnancy (ruptured right cornual and intact left ampullary) in a patient with no known risk factors for extrauterine gestation. CASE: A 33-year-old, black woman, gravida 2, para 1001, presented at approximately 7 weeks' gestation with the acute onset of abdominal pain. She had a rigid surgical abdomen but was hemodynamically stable. Her beta-human chorionic gonadotropin level was 6,398 mIU/mL, and transvaginal ultrasound failed to reveal an intrauterine gestation, adnexal mass or cul-de-sac fluid. Findings at laparotomy included a 500-mL hemoperitoneum and a ruptured right cornual and intact left ampullary pregnancy. Pathology of both specimens confirmed the presence of chorionic villi. CONCLUSION: Although rare, heterotopic pregnancies can occur even in patients without risk factors.

Immunogenicity and efficacy of baculovirus-expressed and DNA-based equine influenza virus hemagglutinin vaccines in mice.

Two fundamentally different approaches to vaccination of BALB/c mice with the hemagglutinin (HA) of A/Equine/Kentucky/1/81 (H3N8) (Eq/KY) were evaluated, that is, administration of HA protein vs administration of HA-encoding DNA. Each vaccine was tested for its immunogenicity and ability to provide protection from homologous virus challenge. HA protein was synthesized in vitro by infection of Sf21 insect cells with a recombinant baculovirus. Intranasal administration of this vaccine induced virus-specific antibodies, as measured by enzyme-linked immunosorbent assay (ELISA), but did not induce virus neutralizing (VN) antibodies. This route of administration provided partial protection from virus challenge, but interestingly, this protection was completely abrogated, rather than enhanced, by co-administration of 10 micrograms of cholera holotoxin. As a second approach, mice were directly vaccinated in vivo by Accell gene gun delivery of plasmid DNA encoding the Eq/KY HA gene. This approach induced VN antibodies as well as virus-specific ELISA antibodies. When two doses of DNA vaccine were administered 3 weeks apart, mice were not protected from challenge, although they cleared the infection more rapidly than control mice. However, when the second DNA vaccination was delayed until 9 weeks after the first, 9 out of 10 vaccinated mice were completely protected. These results indicate that the time between initial and booster DNA vaccinations may be an important variable in determining DNA vaccination efficacy.

Health care fraud and abuse. What physician executives need to know.

Fraud and abuse, which can occur in all industries, also exist in the health care industry. This problem is compounded by the reality that "American medicine, although undergoing evolution, now faces changes of a magnitude that has never before been encountered." These changes are creating new realities for physician executives and also new challenges. As there are changes in business practices, there will be changes in how fraud occurs in health care. Physician executives need to be sensitive to the possibility of fraud and abuse as an unwanted component in medical losses in managed care systems.

Nosocomial transmission of Cryptosporidium in a veterinary hospital.

An outbreak of cryptosporidiosis occurred at a veterinary hospital, involving multiple species, including humans. The index case was an infected dairy calf that presented with diarrhea. Several other cases of cryptosporidial diarrhea subsequently developed during a 1-month period. The key features of this outbreak were the multiple species affected, the increased morbidity in immunocompromised neonates, and the failure of implemented control measures to contain the disease.

What is the role of angiotensin-converting enzyme inhibitors in congestive heart failure and after myocardial infarction?

OBJECTIVE: To discuss the controversies surrounding the choice of angiotensin-converting enzyme (ACE) inhibitor, and the timing, dosage, and duration of ACE inhibitor therapy for congestive heart failure (CHF) and after myocardial infarction (MI). The beneficial effects of ACE inhibition in patients with CHF and after MI are reviewed. Human clinical trials are reviewed and their clinical implications are discussed. DATA SOURCES: MEDLINE searches (1985-1995) identified human clinical trials and review articles. DATA EXTRACTION: Landmark human clinical trials with morbidity and mortality end points were included. The validity of the study data were assessed on the basis of study methods, population characteristics, and statistical power. DATA SYNTHESIS: ACE inhibitors exert beneficial effects in patients with CHF by hemodynamic and neurohormonal mechanisms. The attenuation of ventricular remodeling that occurs with ACE inhibition does not fully explain the results of clinical trials in patients after MI. Routine determination of ejection fraction to guide ACE inhibitor therapy is not as important as the patient's clinical status. Clinicians should titrate the chosen ACE inhibitor on the basis of hemodynamic response to target doses used in major clinical trials. Because the beneficial effects of ACE inhibitors appear to be a class effect, choice of an agent should include cost considerations and the results of clinical trials. CONCLUSIONS: ACE inhibitor reduce morbidity and mortality in selected CHF and post-MI patients. Patients with symptomatic CHF benefit most from ACE inhibitor therapy, and it should be continued indefinitely. Treatment effects in asymptomatic patients are delayed. The role of ACE inhibitor therapy in preventing morbidity and morality in asymptomatic patients with preserved ventricular function requires further study.

Drug-related hospital admissions.

To describe the frequency and pattern of drug-related morbidity that results in hospital admission and the extent to which these admissions are avoidable, we prospectively reviewed the charts of 452 consecutive patients admitted to the intensive care unit or internal medicine service of a university-affiliated, county hospital. Of these, 73 (16.2%) were admitted due to drug-related morbidity. Forty patients (54.8%) experienced drug therapy failure, 24 (32.9%) had an adverse reaction, and 9 (12.3%) had overdoses. Thirty-six (49.3%) of these admissions were definitely avoidable. Compared with patients admitted for other reasons, these patients were more likely to report noncompliance with drug therapy (65.8% vs 15.7%, p < 0.0001) and were taking more drugs (p = 0.0037). We conclude that approximately half of drug-related hospital admissions are avoidable. Targeting patients taking several drugs and with a history of noncompliance may reduce this problem.

Relationship of standardized mitotic indices to other prognostic factors in breast cancer.

OBJECTIVE: To examine the relationship between mitotic index (MI), calculated from direct microscopic counts, and other prognostic features in breast cancer. DESIGN: Mitotic index was based on direct microscopic observations of mitotic figures in 10 consecutive microscopic fields, and the average cell number was determined by counts of population density in three of those fields. Tumor grade and type were established from tissue sections, whereas metastases were detected in lymph node biopsy, chest roentgenograms, and bone scan. Estrogen receptor (ER) and progesterone receptor (PgR) levels were determined by flow cytometry. RESULTS: The MI for 242 patients ranged from 0.2 to 37.6, with a mean of 5.8 mitoses per 1000 cells. More than 85% of the tumors with an MI below 1.0 were diploid and contained an S-phase fraction of 6.7% or less. In contrast, more than 75% of tumors with an MI above 5.0 were aneuploid with more than 6.7% of cells in S-phase. There was an inverse relationship between ER and PgR status and MI. Eighty percent of tumors with an MI less than 1.0 were both ER and PgR positive while only 25% of those with an MI above 10.0 were both ER and PgR positive. Receptor-positive tumors with high S-phase and MI values had ER and PgR levels below 100 fmol/mg. CONCLUSIONS: Lower MI values calculated from direct cell counts are correlated with negative node status, diploid DNA content, low S-phase fraction, and positive receptor status. Thus, there is a significant relationship between objective MI values and several other factors that predict the probability of breast tumor recurrence.

Effect of amino acid infusion on glucose production in trauma patients.

The relationship between precursor supply and hepatic glucose output (HGO) was examined in 8 control subjects and 12 trauma patients after a fasting period of approximately 60 hours. Glucose kinetics were measured with a primed-constant infusion of [U-14C]glucose and [6-3H]glucose. The basal rate of HGO was 5.45 +/- 0.22 micromol x kg-1 x min-1 in the controls and 13.16 +/- 0.76 micromol x kg-1 x min-1 following trauma (p < 0.001). Four hours after amino acid infusion of 1.3 g x kg-1 x 24 h-1, HGO in the controls was unchanged at 5.35 +/- 0.22 micromol x kg-1 x min-1 but it had decreased to 11.71 +/- 0.67 micromol x kg-1 after trauma (p < 0.001). We conclude that increasing the supply of gluconeogenic precursors does not stimulate HGO in normal subjects after fasting or after severe trauma and that factors other than to availability of amino acids are responsible for the enhanced rate of HGO in trauma patients.