Genitourinary Tract Infection Due to Mycobacterium avium intracellulare Complex Infection in Pretransplant Setting With Recurrence Following Transplant: A Case Report.

Genitourinary (GU) tract infection with Mycobacterium avium intracellulare complex (MAI) is very rare and, to our knowledge, has never been reported in the solid organ transplant literature. CASE DESCRIPTION: A 61-year-old Somali-born woman had a history of liver cirrhosis due to chronic hepatitis C infection. She was diagnosed as having and treated for latent tuberculosis infection and GU tract infection due to MAI. She received a total of 17 months antimycobacterial therapy consisting of azithromycin, ethambutol, and moxifloxacin. Within 5 months of the initiation of antimicrobial therapy, there was documented sterilization of urine mycobacterial cultures. Liver and kidney transplant was performed 3 months after finishing the treatment course. One year following transplant, GU tract infection due to MAI recurred. She declined further diagnostic testing as well as mycobacterial therapy. She died 15 months following transplant for reasons not related to infections. CONCLUSION: The treatment of MAI infection in solid organ transplant candidates and recipients is challenging, and the duration of therapy in this population is not known. The recurrence of infection following transplant in this case may argue in favor of a duration that extends beyond the date of transplant. The combination of a fluoroquinolone and ethambutol may successfully prevent reactivation of tuberculosis in patients with history of latent tuberculosis infection and deserves further evaluation.

GCKR and PPP1R3B identified as genome-wide significant loci for plasma lactate: the Atherosclerosis Risk in Communities (ARIC) study.

AIM: To investigate the genetic influence of circulating lactate level, a marker of oxidative capacity associated with diabetes. METHODS: We conducted a genome-wide association study of log-transformed plasma lactate levels in 6901 European-American participants in the Atherosclerosis Risk in Communities study. For regions that achieved genome-wide significance in European-American participants, we conducted candidate region analysis in African-American subjects and tested for interaction between metformin use and the index single nucleotide polymorphisms for plasma lactate in European-American subjects. RESULTS: The genome-wide association study in European-American subjects identified two genome-wide significant loci, GCKR (rs1260326, T allele ß=0.08; P=1.8×10(-47) ) and PPP1R3B/LOC157273 (rs9987289, A allele ß=0.06; P=1.6×10(-9) ). The index single nucleotide polymorphisms in these two loci explain 3.3% of the variance in log-transformed plasma lactate levels among the European-American subjects. In the African-American subjects, based on a region-significant threshold, the index single nucleotide polymorphism at GCKR was associated with plasma lactate but that at PPP1R3B/LOC157273 was not. Metformin use appeared to strengthen the association between the index single nucleotide polymorphism at PPP1R3B/LOC157273 and plasma lactate in European-American subjects (P for interaction=0.01). CONCLUSIONS: We identified GCKR and PPP1R3B/LOC157273 as two genome-wide significant loci of plasma lactate. Both loci are associated with other diabetes-related phenotypes. These findings increase our understanding of the genetic control of lactate metabolism.

Combined admixture mapping and association analysis identifies a novel blood pressure genetic locus on 5p13: contributions from the CARe consortium.

Admixture mapping based on recently admixed populations is a powerful method to detect disease variants with substantial allele frequency differences in ancestral populations. We performed admixture mapping analysis for systolic blood pressure (SBP) and diastolic blood pressure (DBP), followed by trait-marker association analysis, in 6303 unrelated African-American participants of the Candidate Gene Association Resource (CARe) consortium. We identified five genomic regions (P< 0.001) harboring genetic variants contributing to inter-individual BP variation. In follow-up association analyses, correcting for all tests performed in this study, three loci were significantly associated with SBP and one significantly associated with DBP (P< 10(-5)). Further analyses suggested that six independent single-nucleotide polymorphisms (SNPs) contributed to the phenotypic variation observed in the admixture mapping analysis. These six SNPs were examined for replication in multiple, large, independent studies of African-Americans [Women's Health Initiative (WHI), Maywood, Genetic Epidemiology Network of Arteriopathy (GENOA) and Howard University Family Study (HUFS)] as well as one native African sample (Nigerian study), with a total replication sample size of 11 882. Meta-analysis of the replication set identified a novel variant (rs7726475) on chromosome 5 between the SUB1 and NPR3 genes, as being associated with SBP and DBP (P< 0.0015 for both); in meta-analyses combining the CARe samples with the replication data, we observed P-values of 4.45 × 10(-7) for SBP and 7.52 × 10(-7) for DBP for rs7726475 that were significant after accounting for all the tests performed. Our study highlights that admixture mapping analysis can help identify genetic variants missed by genome-wide association studies because of drastically reduced number of tests in the whole genome.

Perspectives from the clinic: will the average physician embrace personalized medicine?

In 1961, Richard Asher argued that the clinical question regarding a particular intervention is not "should it work?" but rather "does it work?". Since that time, clinical trials have become the cornerstone of clinical science, providing physicians access to an expanding pharmacopeia of therapeutic options. The new capacity to change the course of illness has transformed patients' lives as well as the clinical encounter. The recent call for personalized medicine is an attempt to further our therapeutic effectiveness.

The coming epidemic: hypertension in rural Kyrgyzstan, Central Asia.

Eastern Europe is experiencing an epidemic of cardiovascular disease far outpacing rates in Western Europe. This epidemic was heralded by a precipitous rise in hypertension prevalence. The former Soviet states of Central Asia may be facing a similar epidemic. In order to access this threat, we performed a retrospective analysis of data generated during humanitarian medical visits to two villages in Kyrgyzstan, Central Asia. The age-adjusted prevalence of hypertension was 39%. Hypertension was much more common among men than women (46 vs 33%, respectively). In addition, the rise in blood pressure with age was striking, surpassing the experience in Western countries. This epidemic of hypertension may herald a coming epidemic of cardiovascular disease in Central Asia.

Testing shelled corn for aflatoxin, Part II: modeling the observed distribution of aflatoxin test results.

The suitability of several theoretical distributions to predict the observed distribution of aflatoxin test results in shelled corn was investigated. Fifteen positively skewed theoretical distributions were each fitted to 18 empirical distributions of aflatoxin test results for shelled corn. The compound gamma distribution was selected to model aflatoxin test results for shelled corn. The method of moments technique was chosen to estimate the parameters of the compound gamma distribution. Mathematical expressions were developed to calculate the parameters of the compound gamma distribution for any lot aflatoxin concentration and test procedure. Observed acceptance probabilities were compared to operating characteristic curves predicted from the compound gamma distribution, and all 18 observed acceptance probabilities were found to lie within a 95% confidence band. The parameters of compound gamma were used to calculate the fraction of aflatoxin-contaminated kernels in contaminated lots. At 20 ppb, it was estimated that about 6 in 10,000 kernels are contaminated.

Testing shelled corn for aflatoxin, Part III: evaluating the performance of aflatoxin sampling plans.

The effects of changes in sample size and/or sample acceptance level on the performance of aflatoxin sampling plans for shelled corn were investigated. Six sampling plans were evaluated for a range of sample sizes and sample acceptance levels. For a given sample size, decreasing the sample acceptance level decreases the percentage of lots accepted while increasing the percentage of lots rejected at all aflatoxin concentrations, and decreases the average aflatoxin concentration in lots accepted and lots rejected. For a given sample size where the sample acceptance level decreases relative to a fixed regulatory guideline, the number of false positives increases and the number of false negatives decreases. For a given sample size where the sample acceptance level increases relative to a fixed regulatory guideline, the number of false positives decreases and the number of false negatives increases. For a given sample acceptance level, increasing the sample size increases the percentage of lots accepted at concentrations below the regulatory guideline while increasing the percentage of lots rejected at concentrations above the regulatory guideline, and decreases the average aflatoxin concentration in the lots accepted while increasing the average aflatoxin concentration in the rejected lots. For a given sample acceptance level that equals the regulatory guideline, increasing the sample size decreases misclassification of lots, both false positives and false negatives.

Testing shelled corn for aflatoxin, Part I: estimation of variance components.

The variability associated with testing lots of shelled corn for aflatoxin was investigated. Eighteen lots of shelled corn were tested for aflatoxin contamination. The total variance associated with testing shelled corn was estimated and partitioned into sampling, sample preparation, and analytical variances. All variances increased as aflatoxin concentration increased. With the use of regression analysis, mathematical expressions were developed to model the relationship between aflatoxin concentration and the total, sampling, sample preparation, and analytical variances. The expressions for these relationships were used to estimate the variance for any sample size, subsample size, and number of analyses for a specific aflatoxin concentration. Test results on a lot with 20 parts per billion aflatoxin using a 1.13 kg sample, a Romer mill, 50 g subsamples, and liquid chromatographic analysis showed that the total, sampling, sample preparation, and analytical variances were 274.9 (CV = 82.9%), 214.0 (CV = 73.1 %), 56.3 (CV = 37.5%), and 4.6 (CV = 10.7%), respectively. The percentage of the total variance for sampling, sample preparation, and analytical was 77.8, 20.5, and 1.7, respectively.

Diagnosis and follow-up of acute promyelocytic leukemia by detection of PML-RAR alpha gene rearrangement.

BACKGROUND: Rapid and accurate diagnosis of acute promyelocytic leukemia (APL) is essential for management of the disease, as all-trans retinoic acid (ATRA) therapy only induces complete remission in patients whose leukemic cells harbor a t(15;17) translocation, resulting in promyelocytic-retinoic acid receptor alpha (PML-RAR alpha) fusion transcripts. Moreover, a positive reverse transcriptase-polymerase chain reaction (RT-PCR) of PML-RAR alpha is reported to be a sensitive predictor of relapse in APL. This prompted us to use RT-PCR for rapid diagnosis and monitoring of minimal residual disease in APL patients. METHODS: A nested RT-PCR technique was applied to detect the unique PML-RAR alpha fusion transcript in 13 APL patients. The test was applied to help clarify the diagnosis and monitor minimal residual disease after treatment. RESULTS: All 13 APL patients had a positive test result: five patients with the S-form, seven patients with the L-form and one patient with the V-form of mRNA fusion transcripts. Minimal residual disease was prospectively monitored using this technique in six patients. Although in clinical remission, all four patients treated with ATRA alone were persistently PCR positive. Of the six patients receiving various forms of consolidation chemotherapy, one was persistently PCR positive while in remission and relapsed four months after the positive PCR test. Five patients were PCR negative. One of the five negative patients relapsed six months after a negative PCR test. The other four patients remained in remission, with a follow-up period of 25 to 46 months after the negative test. PCR was performed in two patients who had been in continuous remission for 3.5 and seven years, respectively. They both had negative PCR tests. CONCLUSIONS: Nested RT-PCR is valuable for confirming the diagnosis of APL and in monitoring minimal residual disease. However, we found that negative test cannot absolutely exclude the possibility of future relapse.

The early regulation of figs in the United States.

When the Food and Drugs Act became law in 1906, the commercial fig industry in California had just become established. Domestic figs began to compete with imported figs, especially from Turkey and Greece. Fig culture, both in the Near East and the American West, was beset by many threats, especially insect pests. The Bureau of Chemistry in the U.S. Department of Agriculture (USDA), enforcer of the 1906 law, undertook to protect consumers from spoiled figs from overseas and in interstate commerce. Simultaneously the USDA helped both domestic and Turkish growers to counter infestation. Through the State Department, sanitary controls in Smyrna were enhanced. Scientific experts from Agriculture educated American growers and packers in protective techniques. A high point of both legal actions and educational endeavors came in the late 1920s. In the 1930s, the state of California assumed the role of guiding inspection and helping dispose of substandard figs. World War II brought retrogression in fig quality, requiring a new corrective campaign by the Food and Drug Administration, successor to the Bureau of Chemistry, to prevent spoiled figs from reaching the market. By the 1950s, the need for such legal actions was rare.

Bilateral choroidal metastases as the initial presentation of a small breast carcinoma: a case report.

Most ocular tumors metastasize from systemic origins in breast carcinoma in females, and bronchial carcinoma in males. Here, we report a case of choroidal carcinoma metastasis from the breast with visual problems being the only initial manifestations. In this case, both eyes were involved at almost the same time, with initial manifestation of blurred vision which progressed to complete visual loss. At first, the patient was diagnosed with malignant melanoma, and enucleation of the right eye was performed in another hospital. However, the tumor had already metastasized rapidly to numerous organs, including the lungs, brain and bone, although it had not affected the liver. Clinical presentations were, therefore, not compatible with those of malignant melanoma, which has usually been reported to metastasize to the liver. Persistent hypercalcemia and raised carcinoembryonic antigen (CEA) concentrations prompted investigations into the possibility of systemic malignancy. A very small breast nodule was finally located by thorough physical examination, and a lumpectomy was performed. A detailed review of the histopathology showed the tumors from the breast and the right eye to have the same origin. Simultaneous bilateral choroidal metastases from other malignancies is not uncommon; however, it is quite rare for breast carcinoma to present with visual problems as a first manifestation. Detailed history taking and physical examination are therefore essential when searching for a primary tumor, so that appropriate therapy can be given earlier.

Pharmaceutical services in the United States Air Force.

The status of pharmaceutical services in the United States Air Force medical service is described. Air Force pharmacy is adopting new programs, staffing standards, inventory methods, and roles for pharmacists and technicians. One of the most visible changes is TRICARE, an interservice program that provides improved access to care. Many Air Force medical treatment facilities have been closed; prescription mail-out programs and networks of community pharmacies are filling the gap. The Air Force pharmacy team consists of more than 1300 pharmacists and technicians. Air Force pharmacists are military officers first. Great emphasis is placed on medical readiness training and continuing education. Some Air Force pharmacies are very small outpatient operations filling fewer than 300 prescriptions per day; others fill well over 4000. Many hospitals are being considered for more outpatient-focused operations. Because of anticipated minor reductions in pharmacist staffing, Air Force pharmacists will have to maximize efficiencies to maintain or improve current levels of service. More and better patient information will be provided and distributive processes streamlined. A greater role for technicians is anticipated. The future includes pharmacists serving in a wide variety of leadership and staff positions, improving the use of computers, and incorporating new technologies. Air Force pharmacy is changing to ensure uninterrupted fulfillment of its responsibilities.