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Biomedical subjects

L G Miller

Publications and source records attributed to L G Miller.

At least 19 recordsLinked to original sources
PubMed2006

Dissimilatory arsenate and sulfate reduction in sediments of two hypersaline, arsenic-rich soda lakes: Mono and Searles Lakes, California.

A radioisotope method was devised to study bacterial respiratory reduction of arsenate in sediments. The following two arsenic-rich soda lakes in California were chosen for comparison on the basis of their different salinities: Mono Lake (approximately 90 g/liter) and Searles Lake (approximately 340 g/liter). Profiles of arsenate reduction and sulfate reduction were constructed for both lakes. Reduction of [73As]arsenate occurred at all depth intervals in the cores from Mono Lake (rate constant [k] = 0.103 to 0.04 h(-1)) and Searles Lake (k = 0.012 to 0.002 h(-1)), and the highest activities occurred in the top sections of each core. In contrast, [35S]sulfate reduction was measurable in Mono Lake (k = 7.6 x10(4) to 3.2 x 10(-6) h(-1)) but not in Searles Lake. Sediment DNA was extracted, PCR amplified, and separated by denaturing gradient gel electrophoresis (DGGE) to obtain phylogenetic markers (i.e., 16S rRNA genes) and a partial functional gene for dissimilatory arsenate reduction (arrA). The amplified arrA gene product showed a similar trend in both lakes; the signal was strongest in surface sediments and decreased to undetectable levels deeper in the sediments. More arrA gene signal was observed in Mono Lake and was detectable at a greater depth, despite the higher arsenate reduction activity observed in Searles Lake. A partial sequence (about 900 bp) was obtained for a clone (SLAS-3) that matched the dominant DGGE band found in deeper parts of the Searles Lake sample (below 3 cm), and this clone was found to be closely related to SLAS-1, a novel extremophilic arsenate respirer previously cultivated from Searles Lake.

Arsenates↗
PubMed2001

Empirical therapy for uncomplicated urinary tract infections in an era of increasing antimicrobial resistance: a decision and cost analysis.

Infectious Diseases Society of America guidelines state that uncomplicated urinary tract infections (UTIs) should be treated empirically with trimethoprim-sulfamethoxazole (TMP-SMZ), unless the community resistance among uropathogens exceeds 10%-20%, in which case a fluoroquinolone (FQ) should be used. However, the data to support this threshold are limited. We performed a cost-minimization and sensitivity analysis to determine what level of TMP-SMZ resistance in a community should trigger FQ use. The mean cost of empirical treatment with TMP-SMZ was US$92 when the proportion of resistant Escherichia coli was 0%, $106 when it was 20%, and $120 when it was 40%. The mean cost of empirical FQ treatment was $107 at current levels of FQ resistance. When >22% of E. coli in a community are TMP-SMZ-resistant, empirical FQ therapy becomes less costly than TMP-SMZ therapy. Treatment guidelines for empirical treatment of UTIs may need modification, and the threshold trigger for empirical FQ use should be raised to >20% TMP-SMZ resistance.

Anti-Infective Agents↗
PubMed2001

A comparison study of multiple measures of adherence to HIV protease inhibitors.

BACKGROUND: Poor adherence to HIV protease inhibitors may compromise the effectiveness of treatment. Few studies have compared methods for measuring adherence or have related adherence measures to a clinical outcome. OBJECTIVE: To examine the relationship among a composite score of adherence, the three primary measures of adherence, and HIV virologic response. DESIGN: Longitudinal cohort study. SETTING: Public HIV clinic. PATIENTS: 108 HIV-infected adults receiving protease inhibitors or non-nucleoside reverse transcriptase inhibitors who were monitored for 666 monthly intervals. MEASUREMENTS: Medication Event Monitoring System (MEMS), pill count, and interview combined into a composite adherence score (CAS), and HIV viral load. RESULTS: Mean antiretroviral adherence differed by adherence measure (MEMS, 0.63; pill count, 0.83; interview, 0.93; and CAS, 0.76). Composite adherence score decreased significantly over time. Composite adherence score, MEMS values, pill values, and interview values were statistically significantly associated with achievement of an undetectable viral load within 6 months of initiating therapy. Composite adherence score showed the strongest predictive relationship (odds ratios for a 10% increase in adherence for CAS, MEMS, pill count, and interview, respectively, were 1.26 [95% CI, 1.16 to 1.37], 1.13 [CI, 1.06 to 1.21], 1.10 [CI, 1.02 to 1.19], and 1.35 [CI, 0.94 to 1.94]). CONCLUSIONS: Different measures applied to the same patient suggest different levels of adherence. Adherence may be underestimated by MEMS and overestimated by pill count and interview. A summary measure combining several measures is more strongly related to a clinical response, but more practical measurement methods are needed for clinical use.

Adult↗
PubMed2001

Large carbon isotope fractionation associated with oxidation of methyl halides by methylotrophic bacteria.

The largest biological fractionations of stable carbon isotopes observed in nature occur during production of methane by methanogenic archaea. These fractionations result in substantial (as much as approximately 70 per thousand) shifts in delta(13)C relative to the initial substrate. We now report that a stable carbon isotopic fractionation of comparable magnitude (up to 70 per thousand) occurs during oxidation of methyl halides by methylotrophic bacteria. We have demonstrated biological fractionation with whole cells of three methylotrophs (strain IMB-1, strain CC495, and strain MB2) and, to a lesser extent, with the purified cobalamin-dependent methyltransferase enzyme obtained from strain CC495. Thus, the genetic similarities recently reported between methylotrophs, and methanogens with respect to their pathways for C(1)-unit metabolism are also reflected in the carbon isotopic fractionations achieved by these organisms. We found that only part of the observed fractionation of carbon isotopes could be accounted for by the activity of the corrinoid methyltransferase enzyme, suggesting fractionation by enzymes further along the degradation pathway. These observations are of potential biogeochemical significance in the application of stable carbon isotope ratios to constrain the tropospheric budgets for the ozone-depleting halocarbons, methyl bromide and methyl chloride.

Bacteria↗
PubMed2001

Continuous flow stable isotope methods for study of delta(13)C fractionation during halomethane production and degradation.

Gas chromatography/mass spectrometry/isotope ratio mass spectrometry (GC/MS/IRMS) methods for delta(13)C measurement of the halomethanes CH(3)Cl, CH(3)Br, CH(3)I and methanethiol (CH(3)SH) during studies of their biological production, biological degradation, and abiotic reactions are presented. Optimisation of gas chromatographic parameters allowed the identification and quantification of CO(2), O(2), CH(3)Cl, CH(3)Br, CH(3)I and CH(3)SH from a single sample, and also the concurrent measurement of delta(13)C for each of the halomethanes and methanethiol. Precision of delta(13)C measurements for halomethane standards decreased (+/-0.3, +/-0.5 and +/-1.3 per thousand) with increasing mass (CH(3)Cl, CH(3)Br, CH(3)I, respectively). Given that carbon isotope effects during biological production, biological degradation and some chemical (abiotic) reactions can be as much as 100 per thousand, stable isotope analysis offers a precise method to study the global sources and sinks of these halogenated compounds that are of considerable importance to our understanding of stratospheric ozone destruction.

Biodegradation, Environmental↗
PubMed2000

A population-based survey of tuberculosis symptoms: how atypical are atypical presentations?

There is scant information on tuberculosis symptoms from a population-based perspective. We prospectively identified 526 tuberculosis cases reported in Los Angeles County over a 6-month period. Of 313 persons who completed our questionnaire, 72.7% had cough, 48.2% for >2 weeks, and 52.3% had fever, 29.4% for >2 weeks. Among those with pulmonary disease, only 52.4% had cough for >2 weeks. In a multivariate model, persons with significant symptoms typical of tuberculosis disease (defined as cough or fever for >2 weeks, weight loss, or hemoptysis) were associated with lack of medical insurance, negative tuberculin skin test, diagnosis during a process other than screening, and non-Asian race. In summary, classic symptoms of prolonged cough and fever are insensitive predictors of tuberculosis. Our data suggest that Asians may need to be added to the list of persons who present with tuberculosis atypically. We believe that the Infectious Diseases Society of America guidelines for community-acquired pneumonia should emphasize demographic features in addition to clinical symptoms when suggesting which patients require evaluation for Mycobacterium tuberculosis.

Adult↗
PubMed2000

White paper on herbal products. American College of Clinical Pharmacy.

Individuals increasingly are taking a more active role in their health care, and herbal products have emerged as a common choice among self-care therapies. Pharmacists are active participants in the care of patients who are taking herbal products. Currently, most pharmacists are not educated adequately about herbal products and other types of alternative medicine. Furthermore, good information about many of these products is not available. These combined factors present a challenge for pharmacists as they seek to provide optimal care and counseling to patients who use herbs or supplements. We recommend the following actions to place pharmacists in better positions as effective agents protecting public safety: Regulations should be implemented at a federal level to require basic levels of standardization and quality control in the manufacture of herbal products. Indexing terms in medical bibliographic systems should be expanded to target herbal products. Funding should be increased for scientific research evaluating herbal products. Pharmacy schools should include a competency statement in their curricula regarding herbal medicines. Continuing education in herbal products should be available and encouraged for all pharmacists. Pharmacists should approach the use of all therapeutic interventions with scientific rigor, whether they are traditional or complementary in nature. Patients will benefit as more information is known and widely disseminated. By actively embracing the responsibility for counseling individuals on the appropriate use of herbal products, pharmacists will become a recognized source of expert information in this rapidly growing area, yielding important improvements in the quality of care.

Humans↗
PubMed2000

Adherence to combination antiretroviral therapy: synthesis of the literature and clinical implications.

Adherence to combination antiretroviral therapy has a strong impact on virologic response and emergence of viral resistance. However, monitoring adherence in the clinic is difficult. What a patient says or a clinician believes about a patient's adherence may be misleading. Patients with suboptimal adherence may have reduced or undetectable viral loads. On the other hand, viral load may not decrease in patients with perfect adherence because of pretreatment resistance, poor drug metabolism, or other factors. A multidisciplinary approach involving patients, health care professionals, family, and friends may optimize adherence. This article reviews the literature on adherence to antiretroviral therapy, critiques the various adherence measures used by researchers and clinicians, and discusses the clinical implications of adherence to antiretroviral therapy.

Anti-HIV Agents↗
PubMed1999

High-risk sexual behavior in Los Angeles: who receives testing for HIV?

No recent population-based data on HIV testing in people with high-risk sexual behavior are available. We sought predictors of testing using data from the 1997 Los Angeles County Health Survey, a random-digit telephone survey of 8004 county households. An estimated 2.3 million (35.5%) adults were tested for HIV in the past 2 years and approximately 370,000 (5.6%) engaged in high-risk sexual behavior (defined as having > or =2 partners in the past 12 months and not always using condoms). Among high-risk persons, an estimated 46% of heterosexual men, 56% of heterosexual women, and 72% of men who had sex with men (MSM) were tested for HIV. In a multivariable model of high-risk people, both heterosexual men (odds ratio [OR], 0.31; 95% confidence interval [CI], 0.16-0.61) and women (OR, 0.41; 95% CI, 0.19-0.87) had significantly lower proportions of testing than MSM. Although African Americans and Hispanics had significantly higher testing proportions than whites overall among all county residents, those reporting high-risk sexual behavior did not test at higher proportions. We conclude that the proportion of adults with high-risk sexual behavior tested for HIV is higher than almost a decade ago. However, testing among this group remains suboptimal. Future public health campaigns should intensify efforts to encourage HIV testing among this population.

AIDS Serodiagnosis↗
PubMed1998

Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions.

Herbal medicinals are being used by an increasing number of patients who typically do not advise their clinicians of concomitant use. Known or potential drug-herb interactions exist and should be screened for. If used beyond 8 weeks, Echinacea could cause hepatotoxicity and therefore should not be used with other known hepatoxic drugs, such as anabolic steroids, amiodarone, methotrexate, and ketoconazole. However, Echinacea lacks the 1,2 saturated necrine ring associated with hepatoxicity of pyrrolizidine alkaloids. Nonsteroidal anti-inflammatory drugs may negate the usefulness of feverfew in the treatment of migraine headaches. Feverfew, garlic, Ginkgo, ginger, and ginseng may alter bleeding time and should not be used concomitantly with warfarin sodium. Additionally, ginseng may cause headache, tremulousness, and manic episodes in patients treated with phenelzine sulfate. Ginseng should also not be used with estrogens or corticosteroids because of possible additive effects. Since the mechanism of action of St John wort is uncertain, concomitant use with monoamine oxidase inhibitors and selective serotonin reuptake inhibitors is ill advised. Valerian should not be used concomitantly with barbiturates because excessive sedation may occur. Kyushin, licorice, plantain, uzara root, hawthorn, and ginseng may interfere with either digoxin pharmacodynamically or with digoxin monitoring. Evening primrose oil and borage should not be used with anticonvulsants because they may lower the seizure threshold. Shankapulshpi, an Ayurvedic preparation, may decrease phenytoin levels as well as diminish drug efficacy. Kava when used with alprazolam has resulted in coma. Immunostimulants (eg, Echinacea and zinc) should not be given with immunosuppressants (eg, corticosteroids and cyclosporine). Tannic acids present in some herbs (eg, St John wort and saw palmetto) may inhibit the absorption of iron. Kelp as a source of iodine may interfere with thyroid replacement therapies. Licorice can offset the pharmacological effect of spironolactone. Numerous herbs (eg, karela and ginseng) may affect blood glucose levels and should not be used in patients with diabetes mellitus.

Drug Interactions↗
PubMed1998

Staphylococcus aureus meningitis in a patient with acquired immunodeficiency syndrome.

Meningitis due to Staphylococcus aureus is well described but uncommon. Most cases arise as a complication of neurosurgical interventions or head trauma, although some arise spontaneously. To our knowledge, no case of S. aureus meningitis has been previously reported in a person with the acquired immunodeficiency syndrome (AIDS). Herein we describe a case of S. aureus meningitis in a person with AIDS who had no history of a neurosurgical procedure, head trauma, or overwhelming bacteremia. Treatment of this infection was successful. S. aureus should be added to the list of potential pathogens that can cause spontaneous meningitis in people with AIDS.

AIDS-Related Opportunistic Infections↗
PubMed1997

Bacterial oxidation of methyl bromide in fumigated agricultural soils.

The oxidation of [(sup14)C]methyl bromide ([(sup14)C]MeBr) to (sup14)CO(inf2) was measured in field experiments with soils collected from two strawberry plots fumigated with mixtures of MeBr and chloropicrin (CCl(inf3)NO(inf2)). Although these fumigants are considered potent biocides, we found that the highest rates of MeBr oxidation occurred 1 to 2 days after injection when the fields were tarped, rather than before or several days after injection. No oxidation of MeBr occurred in heat-killed soils, indicating that microbes were the causative agents of the oxidation. Degradation of MeBr by chemical and/or biological processes accounted for 20 to 50% of the loss of MeBr during fumigation, with evasion to the atmosphere inferred to comprise the remainder. In laboratory incubations, complete removal of [(sup14)C]MeBr occurred within a few days, with 47 to 67% of the added MeBr oxidized to (sup14)CO(inf2) and the remainder of counts associated with the solid phase. Chloropicrin inhibited the oxidation of MeBr, implying that use of this substance constrains the extent of microbial degradation of MeBr during fumigation. Oxidation was by direct bacterial attack of MeBr and not of methanol, a product of the chemical hydrolysis of MeBr. Neither nitrifying nor methane-oxidizing bacteria were sufficiently active in these soils to account for the observed oxidation of MeBr, nor could the microbial degradation of MeBr be linked to cooxidation with exogenously supplied electron donors. However, repeated addition of MeBr to live soils resulted in higher rates of its removal, suggesting that soil bacteria used MeBr as an electron donor for growth. To support this interpretation, we isolated a gram-negative, aerobic bacterium from these soils which grew with MeBr as a sole source of carbon and energy.

Journal Article↗
PubMed1997

The NMDA receptor competitive antagonist CPP modulates benzodiazepine tolerance and discontinuation.

Benzodiazepine discontinuation is characterized by a syndrome of increased activity and reduced seizure threshold that is similar to effects mediated by the glutamatergic system. To elucidate the involvement of the glutamatergic system in benzodiazepine tolerance and discontinuation, we administered lorazepam, the NMDA antagonist CPP, and the combination of these compounds either concomitantly or consecutively to mice via osmotic pumps and evaluated pentylenetetrazole-induced seizure threshold, open-field activity, and benzodiazepine receptor binding during and after chronic administration. Animals receiving lorazepam alone developed partial tolerance at 7 days and complete tolerance at 14 days to the anticonvulsant effects of lorazepam. This effect was partly attenuated by CPP coadministration with lorazepam. This combination produced only partial tolerance. A reduction in seizure threshold was observed 4 days after discontinuation of lorazepam alone. This effect was abolished by coadministration of CPP with lorazepam and by CPP administration during the withdrawal period. Benzodiazepine binding in most structures examined was significantly reduced at 14 days during chronic lorazepam administration (versus 1 day), and coadministration of CPP did not alter this decrement. After lorazepam discontinuation, binding was increased at 4 and 7 days versus chronically treated animals and versus vehicle within the cerebral cortex. This effect was abolished by coadministration of CPP as well as by CPP administration during the lorazepam withdrawal period. These data support the involvement of the glutamatergic system in benzodiazepine tolerance and discontinuation.

Animals↗