Letter to the editor. The delivery of influenza vaccinations and the role of pharmacists.
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Humans↗
Biomedical subjects
M S Hayney
Publications and source records attributed to M S Hayney.
Effect of influenza immunization on CYP3A4 activity.
A number of clinical reports of drug interactions with influenza vaccine have been made. We hypothesized that CYP3A4 activity would decrease following influenza immunization. Fifteen healthy subjects had erythromycin breath tests (ERMBT) and influenza antibody titer hemagglutinin inhibition assay (HIA) before and after receiving influenza vaccine. The mean age of the subjects was 31.9 years (S.D. 10.2). The change in ERMBT following influenza immunization was not significant (mean -4%, S.D. 17%, P=0.25). Influenza immunization does not significantly change CYP3A4 activity. Changes in serum drug concentrations noted previously after influenza immunization are either due to very small changes in CYP3A4 activity or other pharmacokinetic interactions.
Adult↗
Immunology of Varicella Immunization in the elderly.
OBJECTIVE: To review the varicella-zoster virus (VZV) and herpes zoster disease and to summarize published reports on the use of the live-attenuated varicella zoster vaccine to enhance cell-mediated immunity in elderly individuals. DATA SOURCE: A MEDLINE search (1966-August 1999) for English-language clinical studies and review articles pertaining to VZV and the live-attenuated varicella vaccine was conducted; references obtained from these publications were subsequently reviewed for additional relevant articles. STUDY SELECTION AND DATA EXTRACTION: Representative clinical trials were summarized and relevant information was selected to assist in the understanding of VZV, the subsequent immune response, and the live-attenuated varicella vaccine. DATA SYNTHESIS: The physiologic, age-related decline in VZV cell-mediated immunity has been shown to be restored on administration of live-attenuated varicella vaccine. Various studies report serum anti-VZV antibody concentrations, and production of interferon-gamma were increased following vaccination. Concentrations subsequently returned to baseline one year after vaccination. Increase in responder cell frequency, a measure of cell-mediated immunity, has been reported to last up to four years after vaccination, at concentrations similar or superior to those observed following herpes zoster. CONCLUSIONS: Enhancement of cell-mediated immune response in elderly individuals through vaccination with live-attenuated varicella vaccine is a possible measure to protect this population from herpes zoster and to attenuate its complications. A summary of immunogenicity studies to identify the immune response to live-attenuated varicella vaccine in the elderly is presented. The absolute clinical significance, as well as appropriate administration guidelines of this prophylactic intervention, will become evident following forthcoming large, masked, placebo-controlled trials.
Aged↗
A novel method for assigning TAP1 genotype using restriction enzyme plus PASA methodology.
The function of the TAP gene products appears to be the transport of antigenic peptides into the lumen of the endoplasmic reticulum where peptides are loaded onto HLA molecules. The polymorphisms within the TAP genes and potential disease associations are the subject of intense current study. While several methods have been described for TAP1 genotyping, most of these methods are unable to definitively assign TAP1 genotypes to individuals heterozygous at more than one polymorphic position. A combination named TAP1U was observed in approximately 25% of study subjects. We developed a restriction enzyme based method that allows definitive TAP1 genotypes assignment to 100% of subjects. We also further developed and optimized TAP genotyping by PCR amplification of specific alleles (PASA) that resulted in significant time and cost savings. Hence, we report a novel method for assigning TAP genotypes for TAP1U subjects and the modified PASA reactions. These improvements facilitate the rapid and efficient assignment of TAP genotypes useful for large human disease-gene association studies.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Angiotensin-converting enzyme gene polymorphism: is there a link to nephropathy in patients with type 1 diabetes?
OBJECTIVE: To evaluate the association between the angiotensin-converting enzyme (ACE) gene polymorphism and diabetic nephropathy in patients with type 1 diabetes. DATA SOURCES: Citations were selected using the MEDLINE database. Only those citations involving human subjects and available in English were selected. Key search words included angiotensin-converting enzyme (ACE), polymorphism, nephropathy, and type 1 diabetes. STUDY SELECTION: Selection criteria consisted of all MEDLINE-referenced clinical trials, review articles, and editorial comments assessing the potential link between the ACE gene polymorphism and diabetic nephropathy in insulin-dependent diabetes mellitus published between January 1990 and February 1998. DATA SYNTHESIS: Because diabetic nephropathy is a serious complication of type 1 diabetes, focus has been placed on the early identification of and intervention with patients genetically susceptible to this complication. Because the ACE gene polymorphism has an effect on plasma ACE concentration variations among individuals, it has been investigated as a potential genetic marker for diabetic nephropathy. The best studies to date are reviewed in order to assess the utility of the ACE polymorphisms as a genetic marker of diabetic nephropathy in patients with type 1 diabetes, and to determine what implications this holds for drug treatment. CONCLUSIONS: Although the ACE gene polymorphism's potential link to diabetic nephropathy in patients with type 1 diabetes has been debated, the most definitive studies show that an association exists. Large epidemiologic studies must now be conducted to determine the implications this polymorphism holds for the best treatment strategies in the care of these patients.
Clinical Trials as Topic↗
Lyme disease prevention and vaccine prophylaxis.
OBJECTIVE: To provide a comprehensive review of the epidemiology, diagnosis, and prevention of Lyme disease with a focus on the Lyme disease vaccine. DATA SOURCE: A computerized search of MEDLINE (January 1996-December 1998) was used to identify articles regarding Lyme disease, Borrelia burgdorferi, epidemiology, prevention, and vaccine. DATA SYNTHESIS: Lyme disease is a condition caused by infection with B. burgdorferi. The organism is carried by certain species of Ixodes ticks and is the most common tick-borne disease in the US. In patients with clinical manifestations of Lyme disease, various pharmacotherapeutic approaches have proven effective in treatment of the clinical features. Prevention strategies exist; however, their application is sometimes difficult. A vaccine for the prevention of Lyme disease is available, and another is being considered for approval. The recombinant outer surface protein A (OspA) vaccines to prevent Lyme disease are immunogenic and have an acceptable adverse effect profile. These vaccines are highly efficacious for the prevention of Lyme disease. CONCLUSIONS: Lyme disease is the most common tick-borne disease in the US. The infection, caused by B. burgdorferi, results in dermatologic, neurologic, cardiovascular, and musculoskeletal manifestations. Until recently, tick bite prevention strategies were the only means of decreasing the risk of acquiring the infection. The OspA vaccines are efficacious for the prevention of infection. Although universal immunization with these vaccines is unlikely, the availability of effective vaccines represents an important tool for the prevention of Lyme disease in endemic regions of the US.
Bacterial Vaccines↗
Polymorphisms of the TAP2 gene may influence antibody response to live measles vaccine virus.
The transporter associated with antigen processing (TAP) gene products transport peptides from the cytosol to the endoplasmic reticulum for processing by the immune system. We hypothesized that polymorphisms within the TAP genes may influence measles vaccine antigen processing and hence antibody response. TAP genotypes were determined for subjects who were measles vaccine nonresponders (n = 32) and hyper-responders (n = 28). TAP1 and TAP2 alleles were determined by PCR amplification of specific alleles (PASA). Measles vaccine nonresponders were more likely to be homozygous at TAP2 position 665 than were hyper-responders (OR = 5.0, P = 0.016). Lastly, a trend was found in the overall distribution of all TAP2 genotype frequencies between hyper-responders and nonresponders (P = 0.08). No association was found between TAP1 polymorphisms and vaccine response. These data reveal an association between TAP2 genotype and measles vaccine antibody response which may explain one mechanism behind vaccine failure.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Azathioprine and allopurinol: the price of an avoidable drug interaction.
OBJECTIVE: To report the price of a drug interaction between azathioprine and allopurinol that resulted in pancytopenia in a patient who had undergone a heart transplant. CASE SUMMARY: A 63-year-old white man who received an orthotopic heart transplant in 1987 was hospitalized in June 1991 with a diagnosis of pancytopenia. His immunosuppressive medications on admission included cyclosporine 125 mg bid, azathioprine (AZA) 200 mg/d, and prednisone 2.5 mg/5 mg every other day. Six weeks prior to admission, the patient's local physician prescribed allopurinol for left wrist pain suspected to be gout. It was determined that the pancytopenia was caused by the drug interaction between AZA and allopurinol, both of which were withheld on admission. During hospitalization, the patient's white blood cell count dropped to 1.1 x 10(3)/mm3 with an absolute neutrophil count of less than 0.5 x 10(3)/mm3, a platelet count of less than 20 x 10(3)/mm3, and a hemoglobin of 3.7 g/dL. Four units of packed red blood cells were transfused and regramostim (GM-CSF) therapy was begun on hospital day 3 to speed the marrow recovery process. The patient was discharged on hospital day 8 and AZA, which had been withheld since admission, was restarted. The dosage was titrated to 200 mg/d over the following 2 weeks. The price of this patient's hospital stay was $13,042. DISCUSSION: Not included in this price was the effect this drug interaction had on the patient's quality of life. Even after discharge from the hospital, it was estimated that it would take up to 3 months for the patient to fully recover his previous level of strength and functional capability. This interaction between AZA and allopurinol could easily have been avoided. Both the physician and the pharmacist missed this well-documented and potentially life-threatening drug interaction. Also, the patient failed to notify the transplant team when allopurinol was prescribed by his local physician. The importance of patient responsibility for medication therapy must be stressed to help avoid unnecessary drug interactions. CONCLUSIONS: Undetected drug interactions can be life-threatening to patients as well as costly to the healthcare system. Drug interactions also can have a profound negative effect on the patients' quality of life, the price of which cannot be measured in dollars alone. It is vital that the physician, pharmacist, and patient work together to optimize therapeutic outcomes and avoid unnecessary drug interactions.
Allopurinol↗
The influence of the HLA-DRB1*13 allele on measles vaccine response.
BACKGROUND: Measles remains a public health threat in the United States with over 50,000 cases being reported from 1989 through 1991 with continued smaller outbreaks. Measles vaccine failure is in part to blame for these large-scale outbreaks. The human leukocyte antigen (HLA) genes are important determinants of immune response to measles virus and vaccine. To examine the influence that HLA polymorphisms may have on measles vaccine antibody response, we compared the distribution of HLA-DRB1 alleles between measles vaccine nonresponders and hyper-responders. METHODS: We determined the seroprevalence of measles antibody in 881 school children immunized with measles-mumps-rubella-II at age 15 months using a whole virus IgG EIA. We performed class II HLA-DR typing by PCR with sequence specific primers (PCR-SSP) on 81 nonresponders (IgG seronegative) and 65 hyper-responders (from the upper 10th percentile of IgG levels of all subjects). We then compared the distribution of alleles between nonresponders and hyper-responders. RESULTS: The distribution of HLA-DRB1 alleles among nonresponders compared to hyper-responders was significantly different (p = 0.014). Nonresponders were significantly less likely to carry the HLA-DRB1*13 alleles than were hyper-responders (7.4% vs 16.2%;p = 0.02). Nonresponders also had an excess of HLA-DRB1*07 alleles (15.4% vs 6.2%; p = 0.015). CONCLUSIONS: The absence of HLA-DRB1*13 alleles is associated with measles vaccine nonresponse. The absence of this allele has also been associated with susceptibility to other infectious diseases. The role of this gene in the immunogenetic response to infectious diseases requires further study.
Alleles↗
Utility of a "swish and spit" technique for the collection of buccal cells for TAP haplotype determination.
OBJECTIVE: To demonstrate the utility of a "swish and spit" technique as a nucleated cell source for transporter associated with antigen processing (TAP) haplotype determination by molecular methods in large-scale clinical trials. DESIGN: Twenty normal volunteers were recruited for this prospective feasibility study. From each subject, buccal or blood cells (or both) were collected for use in TAP haplotype assignment by molecular methods and subjected to various storage conditions. MATERIAL AND METHODS: As an alternative to use of lymphocytes obtained by venipuncture, we developed a swish and spit technique for collecting buccal cells for assigning TAP haplotype. For this technique, the subject vigorously swishes isotonic saline in the mouth and expectorates it into a collection container. DNA is extracted from the buccal cells by proteinase K digestion, phenol-chloroform extraction, and ethanol precipitation. In addition, we compared DNA extracted from mouthwash specimens stored under various conditions to which a specimen might be exposed if mailed. RESULTS: DNA extracted from buccal cells obtained by the swish and spit technique provided excellent templates for the polymerase chain reaction (PCR), and subject acceptance of this method was universal. In all cases, assigning TAP haplotype by PCR amplification of specific alleles with use of buccal or blood-derived specimens was successful. The integrity of the specimens was unaffected by storage at -20 degrees C, 4 degrees C, 25 degrees C, or 37 degrees C, and we were able to use the DNA from cells stored under any of these conditions for TAP haplotying. CONCLUSION: We conclude that DNA from buccal cells collected by the swish and spit technique for TAP haplotype assignment is an excellent substitute for DNA obtained from nucleated blood cells, and the technique is useful for large-scale clinical studies that require DNA from subjects geographically distant from the research site.
DNA↗
Practices of cardiothoracic transplant centers regarding hepatitis C-seropositive candidates and donors.
The purpose of this survey was to determine current practices of cardiothoracic transplant centers regarding transplantation of hearts and lungs into hepatitis C (HCV)-seropositive candidates and the use of organs from HCV-seropositive donors. A telephone survey of 48 cardiothoracic transplant centers was conducted in October 1992. Questions included the center's policy for listing HCV-seropositive candidates; if, and under what conditions, organs from HCV-seropositive donors would be used; and which HCV assays were used. Forty-five programs responded; 75% will list an HCV-seropositive candidate, either directly or by lack of routine screening to exclude such patients; only 16% will not accept HCV-seropositive candidates; 9% had no policy. Overall, 69% will accept organs from HCV-seropositive donors, at least for selected recipients (22% for any recipient, 45% for HCV-seropositive and/or status I recipients; 2% do not screen donors). A total of 27% will never accept organs from an HCV-seropositive donor, and 4% had no policy. Thirty centers provided information on HCV methodology. All but one use a second generation ELISA or EIA as a first-line test. A positive result will be followed by a confirmatory assay/liver biopsy in 42%. The variation in practices reflects the ambiguity in the literature. Adequate evaluation of morbidity and mortality due to HCV infection in this population has not yet been possible, although currently available reports do not show a substantial increase. Prospective controlled trials in cardiothoracic transplant patients are necessary.
Data Collection↗
Relationship of HLA-DQA1 alleles and humoral antibody following measles vaccination.
BACKGROUND: The human leukocyte antigen (HLA)-DQA1 locus is only moderately polymorphic compared to other HLA class II loci; however, we hypothesized that these polymorphisms could be important in determining the humoral antibody response to measles vaccine virus. METHODS: The seroprevalence of measles antibody was determined in 881 school children who had been immunized with MMR-II at age approximately 15 months. All subjects resided in a geographic area with no circulating measles virus. The IgG antibody levels were determined by a measles-specific whole virus enzyme immunoassay (EIA) (BioWhittaker, Walkersville, MD). Subjects who were nonresponders (IgG seronegative or equivocal) (n = 46) and hyperresponders (upper 10th percentile of IgG levels of all subjects) (n = 64) were HLA-DQA1 typed using polymerase chain reaction with sequence-specific primers (PCR-SSP). The HLA-DQA1 allele frequencies, as well as homozygosity rates, were compared between the nonresponders and hyperresponders. RESULTS: The overall allele frequency distribution of alleles between the nonresponders and hyperresponders was significantly different (P = 0.05), with nonresponders having an excess of HLA-DQA1*05 alleles (P = 0.017) and hyperresponders having an excess of HLA-DQA1*01 alleles (P = 0. 016). The homozygosity rate among nonresponders was significantly higher than among hyperresponders (23.9% vs. 9.4%, P = 0.037). CONCLUSION: HLA-DQA1 alleles have important associations with the antibody response to measles vaccine. Specifically, the carriage of the HLA-DQA1*05 alleles is associated with nonresponse and that of HLA-DQA1*01 alleles with hyperresponse. In addition, HLA-DQA1 homozygosity is significantly associated with poor antibody response to measles vaccine.
Adolescent↗
A noninvasive 'swish and spit' method for collecting nucleated cells for HLA typing by PCR in population studies.
Buccal-cell-derived DNA collected by a 'swish and spit' technique and blood-derived DNA were compared for ease of collection, participant acceptance, utility and accuracy for HLA class II DR typing by the polymerase chain reaction with sequence-specific primers (PCR-SSP). The HLA class II DR typing results determined from DNA extracted by proteinase K digestion followed by phenol/chloroform extraction and ethanol precipitation from buccal cells and blood cells were identical for all subjects we studied (n = 10). Class II typing by PCR-SSP using DNA extracted from buccal cells stored at -20, 4, 25 or 37 degrees C for 1 week was successful. The samples can be collected without medical supervision and are not affected by exposure to a variety of temperature conditions for up to 1 week. The stability of the buccal cell specimens to these extreme conditions demonstrates the utility of this 'swish and spit' technique for collecting nucleated cells for geographically dispersed large-scale population studies. Buccal-cell-derived DNA collected by a simple 'swish and spit' mouthwash technique is an excellent and practical substitute for blood-derived DNA.
Cell Separation↗