Biomedical subjects

M J Allison

Publications and source records attributed to M J Allison.

At least 19 recordsLinked to original sources

PubMed2005

Pharmacokinetic interaction between verapamil and everolimus in healthy subjects.

AIMS: We sought to define the influence of verapamil, an inhibitor of CYP3A and P-glycoprotein, on the pharmacokinetics of everolimus, a substrate of this enzyme and transporter. METHODS: This was a two-period, single-sequence, crossover study in 16 healthy subjects. In period 1 subjects received a single 2 mg oral dose of everolimus. In period 2 they received verapamil 80 mg three times daily for a total of 6 days and a single 2 mg dose of everolimus co-administered on the second day of verapamil therapy. RESULTS: During verapamil co-administration, everolimus C(max) increased 2.3-fold (90% CI, 1.9, 2.7) from 21 +/- 8 to 47 +/- 18 ng ml(-1) and AUC increased 3.5-fold (90% CI, 3.1, 3.9) from 115 +/- 45 to 392 +/- 142 ng ml(-1) h. Everolimus half-life was only prolonged to a minor extent (32 +/- 6 vs. 37 +/- 6 h). Verapamil predose concentrations doubled from 32 +/- 16 to 74 +/- 42 ng ml(-1) after single dose administration of everolimus. CONCLUSIONS: Multiple dosing with verapamil increased blood concentrations of everolimus after a single dose by an average 3.5-fold. During verapamil treatment, dose reduction for everolimus should be made guided by blood monitoring and for verapamil by blood pressure monitoring.

Analysis of Variance↗

PubMed2001

Diseases of the spine in South American mummies.

OBJECTIVE: The skulls and spinal columns of people from ancient civilizations, which frequently are found in a preserved state at archeological sites, can provide a large amount of information about these individuals' physical condition through paleopathological investigation. METHODS: This study represents the examination of more than 700 human remains dating back more than 8000 years that were recovered from archaeological excavations in the Andean region of southern Peru and northern Chile. RESULTS: Examples of congenital malformations, degenerative processes, infectious diseases, neoplasias, and traumatic diseases were discovered. Congenital anomalies such as spina bifida occulta were relatively common in these populations. No cases of meningomyelocele were discovered. The most common pathological findings were degenerative changes of the vertebral bodies. Large cervical and lumbar osteophytes were identified in some remains. Several cases of cervical spondylosis were determined to be the result of an occupational disease resulting from carrying heavy loads on the back. These heavy loads were supported by wearing around the forehead a tumpline, known as a capacho. The most common infectious disease process in the spine was due to tuberculosis. The diagnosis was made by radiological and histopathological studies, and in several cases the organism Mycobacterium tuberculosis was identified in the soft tissues. Metastatic lesions on the vertebral bodies were identified in a single case. Examples of traumatic spinal injury were rare. Compression fractures were noted infrequently. CONCLUSION: Diseases of the spinal column in the ancient inhabitants of the Andean region of South America were similar to those that affect the present-day population of that area.

Adult↗

PubMed2001

Rapid reversal of hyperoxaluria in a rat model after probiotic administration of Oxalobacter formigenes.

PURPOSE: The gut inhabiting bacterium Oxalobacter formigenes may be a negative risk factor in recurrent calcium oxalate kidney stone disease that apparently maintains oxalic acid homeostasis in its host via the degradation of dietary oxalate. The possibility of using this bacterium as probiotic treatment to reduce urinary oxalate was investigated in a rat model. MATERIALS AND METHODS: Male Sprague-Dawley rats were placed on a diet supplemented with ammonium oxalate to induce a state of severe hyperoxaluria. Subgroups of these rats received an esophageal gavage of 1 x 10(3), 10(5), 10(7) or 10(9) O. formigenes per feeding for a 2-week period. Each rat was followed for general health and changes in urinary oxalate. RESULTS: Rats with chronic hyperoxaluria resulting from high dietary oxalate that were treated with O. formigenes showed decreased urinary oxalate within 2 days of initiating probiotic supplementation. The amount of the decrease in a 2-week period proved directly proportional to the dose of bacteria. Urinary oxalate in rats receiving higher amounts of O. formigenes returned to almost normal. Throughout the study the rats remained healthy with no signs of toxicity, antibody development or a histopathological condition. CONCLUSIONS: Probiotic treatment of hyperoxaluric rats with O. formigenes may significantly and rapidly reduce the level of oxalate in the urine. This probiotic treatment appears to be safe and well tolerated. The approach may be feasible for treating calcium oxalate kidney stone disease.

Animals↗

PubMed2000

Denitrobacterium detoxificans gen. nov., sp. nov., a ruminal bacterium that respires on nitrocompounds.

A new group of anaerobic, Gram-positive, high G + C (56-60 mol%) bacteria was isolated from the bovine rumen. Of four strains characterized, all were non-motile and none produced spores. The isolates did not produce indole or H2S and did not hydrolyse gelatin. Cells of each strain exhibited similar rod-shaped morphology (0.5-1.0 x 1.0-1.5 microns) although bulbous ends were sometimes present. None of the four strains were able to grow via oxidation of a variety of potentially fermentable substrates but rather obtained energy for growth via anaerobic respiration processes, oxidizing hydrogen, formate or lactate for reduction of various oxidized nitrogen compounds. Trimethylamine oxide and DMSO were also used as electron acceptor. All four strains shared greater than 99% 16S rRNA gene sequence identity. The closest match found between the 16S rRNA gene sequence of all four strains, NPOH1T, NPOH2, NPOH3 and MAJ1, to sequences available in GenBank was that of Coriobacterium glomerans (86% sequence similarity), a phenotypically dissimilar anaerobe within the class Actinobacteria. To accommodate these bacteria the creation of a new genus and species, Denitrobacterium detoxificans, for placement within the family Coriobacteriaceae is proposed. The type strain, NPOH1T (ATCC 700546T), grew equally well over a narrow range of incubation temperatures tested (32-39 degrees C).

Actinomycetaceae↗

PubMed2000

Enzyme, bacterial inoculant, and formic acid effects on silage composition of orchardgrass and alfalfa.

We evaluated the effects of cellulase (from Trichoderma longibrachiatum) application rates on neutral detergent fiber (NDF) concentration and fermentation products of orchardgrass (Dactylis glomerata L.) and alfalfa (Medicago sativa L.) silages harvested with decreasing dry matter (DM) digestibility. Additionally, the impacts of inoculant (Lactobacillus plantarum and Pediococcus cerevisiae), pectinase (from Aspergillus niger), or formic acid on silage composition were studied. Forages wilted to a DM content of about 320 g/kg were ensiled in laboratory silos for 60 d. Cellulase, combined with inoculant, was applied at 2, 10, and 20 ml/kg of herbage (at least 2500 IU/ml). Cellulase at 10 ml/kg was also applied alone or in combination with pectinase and inoculant or formic acid. The NDF concentration of orchardgrass silage decreased with increasing cellulase up to 20 ml/kg, at which NDF content was decreased by 30%. The NDF concentration of alfalfa silage decreased with increasing cellulase application up to 10 ml/kg, at which NDF content was decreased by 13%. Immature plants were more responsive to cellulase treatment than mature plants. Cellulase at 2 ml/kg combined with inoculant improved fermentation characteristics of the silages but generally, there was no effect on silage fermentation by higher cellulase applications, resulting in an accumulation of sugar. The improved fermentation of orchardgrass treated with cellulase and inoculant was mostly related to the effect of inoculant, whereas cellulase alone improved fermentation characteristics of alfalfa silage and this effect was enhanced by addition of inoculant. Decreased NDF and increased sugar concentrations did not improve the in vitro DM digestibility of cellulase-treated silages.

Aspergillus niger↗

PubMed1999

Further studies on fecal parasites in antiquity.

This is a continuation study of the survival of antigenic material over the centuries using mummified human remains from the Andean area of South America. The fluorescent antibody kit from Meridian Diagnostics (Cincinnati, OH) was used to identify some Cryptosporidium species and Giardia species found in feces from the intestines of mummies 500 to 3,000 years old. The specimens that were positive by direct visualization using fluorescent antibody were then tested with an enzyme-linked immunosorbent assay reaction using a Meridian kit just released on the market. Since all of the feces used were formed, it would seem that the organisms found were from carriers rather than active cases of disease. Similar fecal specimens were shown to harbor antigens from Helicobacter pylori almost 3,000 years old.

Animals↗

PubMed1999

Direct quantification of the enteric bacterium Oxalobacter formigenes in human fecal samples by quantitative competitive-template PCR.

Homeostasis of oxalic acid appears to be regulated, in part, by the gut-associated bacterium Oxalobacter formigenes. The loss of this bacterium from the gut flora is associated with an increased susceptibility to hyperoxaluria, a condition which can lead to the formation of calcium oxalate crystalluria and kidney stones. In order to identify and quantify the presence of O. formigenes in clinical specimens, a quantitative-PCR-based assay system utilizing a competitive DNA template as an internal standard was developed. This quantitative competitive-template PCR test allows for the rapid, highly specific, and reproducible quantification of O. formigenes in fecal samples and provides a prototype for development of DNA-based quantitative assays for enteric bacteria.

Bacteria↗

PubMed1998

Length of stay for specialized pediatric urologic care.

BACKGROUND: Pediatric urologic specialists have been excluded from many recent managed care contracts because they are believed to be more expensive and of no better quality than general urologists in managing common urologic problems in children. We believed this to be inaccurate. OBJECTIVES: To compare the length of stay at the University of California, San Francisco Medical Center for 2 common pediatric urologic operative procedures with data from other northern California hospitals and to document our results and patient satisfaction. DESIGN: Retrospective analysis of HCIA statewide database (HCIA Inc, Orange, Conn). SETTING: Northern California, 1995. SUBJECTS: Children younger than 12 years undergoing surgery for repair of an obstruction of the ureteropelvic junction or vesicoureteral reflux. MAIN OUTCOME MEASURE: Length of stay. RESULTS: The length of stay in our hospital was similar to that observed in other hospitals in which other full-time pediatric urologic specialists practiced and was significantly less than that observed in other northern California hospitals, even when adjusted for risk. In fact, a savings of 279 hospital days would have been realized if all patients had the same length of stay as that achieved at University of California, San Francisco Medical Center. In the 38 patients operated on at our center, there was uniform surgical success. Of the parents, 92% (11/ 12) were satisfied with their child's care and 92% (11/ 12) believed they received enough information to know what to expect and how to care for their child at home. There were no data available evaluating quality from other northern California hospitals for comparison. CONCLUSIONS: Our finding that actual and risk-adjusted length of stay were shorter when patients were treated by full-time pediatric urologists, while excellent quality was maintained, suggests that these specialists achieve their results with more efficiency and lower resource utilization than do general urologists. The implication of these results is that exclusive contracting that prevents patients from receiving care from full-time specialists results in overuse of valuable resources and possibly reduced quality. If our results are generalizable, they have important implications for health care reform in the United States.

Academic Medical Centers↗

PubMed1998

Diseases of the skull in pre-Columbian South American mummies.

OBJECTIVE: The majority of paleopathological investigations focus on the study of the skull. This is because the skull is the most frequently preserved part of the human body recovered from archaeological excavations. From studying the skull, a variety of information can be obtained regarding the individual, such as sex, age, nutritional status, and other disease processes, if present. METHODS: This study represents the examination of more than 700 human skulls recovered from archaeological excavations from the Andean region of southern Peru and northern Chile and dating back more than 8000 years. RESULTS: A variety of skull abnormalities were encountered. The nonmetric variables of Huschke's foramina and palatine tori were common. Cranial deformation was observed in more than 85% of the cases. There were two cases of sagittal synostosis. Iron deficiency anemia resulting in porotic hyperostosis of the skull was evident in certain cultures. Exostoses of the external auditory canal resulting from chronic otitis was evident only among coastal populations. One skull demonstrated a periostitis consistent with Treponema infection. Trephination was encountered only in the skulls from Peru. Fifty-four cases of skull fractures were observed, half of which showed evidence of healing. Finally, only two cases of neoplastic skull lesions were encountered. CONCLUSION: The study of the human skull alone provides a large amount of information regarding the health and diseases of ancient populations.

Adult↗

PubMed1997

Ultrastructure of a well-preserved lymphocyte from a mummified human.

A well-preserved lymphocyte was found during the electron microscopic examination of the cerebral material recovered from a naturally preserved male mummy from northern Chile dating back over 500 years. The cytoplasmic structures were easily recognizable. This study represents one of the best ultrastructural analyses of mummified human peripheral blood elements.

Adult↗

PubMed1997

Characteristics of a nitropropanol-metabolizing bacterium isolated from the rumen.

We report some characteristics of a ruminal bacterium (strain NPOH1) that metabolizes 3-nitropropanol, the toxic principle of various milk vetchs that are distributed worldwide. The gram-positive bacterium was nonmotile and did not produce spores. Growth of strain NPOH1 occurred under anaerobic conditions and was supported by the electron acceptors 3-nitropropanol, 3-nitropropionate, nitrate, 2-nitropropanol, nitroethane, nitroethanol, or 3-nitro-1-propyl-beta-D-glucopyranoside (miserotoxin). Other potential electron acceptors, namely sulfate, sulfite, azide, chlorate, perchlorate, nitrite, fumarate, 2-nitrobutane, or nitrobenzene, did not support growth. Formate, lactate, and H2 stimulated growth of strain NPOH1 in the presence of the appropriate nitrocompound, whereas a variety of other potential H2 donors did not. When grown in medium containing both nitrate and either 3-nitropropanol or 3-nitropropionate, nitrate was the preferred acceptor. Strain NPOH1 reduced nitrate to nitrite and, when grown with excess reductant, nitrite was further reduced to ammonia. The products formed during the metabolism of 3-nitropropanol and 3-nitropropionate by mixed ruminal populations, 3-aminopropanol and beta-alanine, were not found in culture fluids of strain NPOH1. Analysis of total cellular fatty acid profiles and of the mole percent guanine plus cytosine suggests that strain NPOH1 is a novel bacterium. The capacity of strain NPOH1 to metabolize 3-nitropropanol suggests that this organism may play an important role in detoxification of 3-nitropropanol in the rumen.

Animals↗

PubMed1996

A quality improvement team on autologous and directed-donor blood availability.

BACKGROUND: Until 1985, volunteer donors provided blood for almost all transfusions and donated blood was rarely restricted for transfusion to a specific patient. With the AIDS (Acquired Immunodeficiency Syndrome) crisis, autologous (blood from oneself) and directed (blood from families and friends) donations increased, calling for handling of far greater complexity. At the University of California at San Francisco Medical Center, the demand for special donations superseded the development of systems to meet the demand and autologous and/or directed donations were often not available when needed. After a rapid rise in incident reports and complaints from physicians, nurses, patients, and families, a quality improvement (QI) team was formed in mid-1991 to improve blood availability. METHOD: Meetings were held to analyze the processes involved in blood donation and transfusion, identify and categorize problems, develop interventions, test and implement solutions, and monitor improvements. Educational efforts were implemented throughout the medical center, recruitment for a special donations co-ordinator began, and changes were made in the blood bank's internal systems. RESULTS: In two years, with stable numbers of transfused units, the number of incident reports regarding blood availability decreased from 19 to 2 per year-an improvement that has been sustained for more than three years. The QI team continues to meet regularly to design and implement additional improvements. CONCLUSION: A QI team has improved the availability of autologous and directed-donor blood to patients and has extended the impact of the QI methodology throughout the medical center as a whole.

Academic Medical Centers↗

PubMed1996

Enrichment and isolation of a nitropropanol-metabolizing bacterium from the rumen.

A bacterium capable of metabolizing nitropropanol, nitropropionate, and nitrate has been isolated from a mixed ruminal population enriched for enhanced rates of nitropropanol metabolism. The numbers of nitropropanol-metabolizing bacteria in mixed populations increased > 10,000-fold during enrichment; the rates of nitropropanol metabolism increased 8-fold. Hydrogen and phytone were important nutrients for nitropropanol metabolism.

1-Propanol↗

PubMed1996

Generation of a proton motive force by the anaerobic oxalate-degrading bacterium Oxalobacter formigenes.

The generation of transmembrane ion gradients by Oxalobacter formigenes cells metabolizing oxalate was studied. The magnitudes of both the transmembrane electrical potential (delta psi) and the pH gradient (internal alkaline) decreased with increasing external pH; quantitatively, the delta psi was the most important component of the proton motive force. As the extracellular pH of metabolizing cells was increased, intracellular pH increased and remained alkaline relative to the external pH, indicating that O. formigenes possesses a limited capacity to regulate internal pH. The generation of a delta psi by concentrated suspensions of O. formigenes cells was inhibited by the K+ ionophore valinomycin and the protonophore carbonyl cyanide-m-chlorophenylhydrazone, but not by the Na+ ionophore monensin. The H+ ATPase inhibitor N,N'-dicyclohexyl-carbodiimide inhibited oxalate catabolism but did not dissipate the delta psi. The results support the concept that energy from oxalate metabolism by O. formigenes is conserved not as a sodium ion gradient but rather, at least partially, as a transmembrane hydrogen ion gradient produced during the electrogenic exchange of substrate (oxalate) and product (formate) and from internal proton consumption during oxalate decarboxylation.

Biodegradation, Environmental↗

PubMed1996

Anabolic Incorporation of Oxalate by Oxalobacter formigenes.

Cell-free lysates of the strict anaerobe Oxalobacter formigenes contained the following enzymatic activities: oxalyl coenzyme A reductase, glyoxylate carboligase, tartronic semialdehyde reductase, and glycerate kinase. NAD(P)-linked formate dehydrogenase, serine-glyoxylate aminotransferase, and NAD(P) transhydrogenase activities were not detected. These results support the hypothesis that O. formigenes assimilates carbon from oxalate by using the glycerate pathway, whereby oxalate is reduced to 3-phosphoglycerate before entering common biosynthetic pathways.

Journal Article↗

PubMed1996

Assimilation of oxalate, acetate, and CO2 by Oxalobacter formigenes.

Oxalobacter formigenes is the only well-documented oxalate-degrading bacterium isolated from the gastrointestinal tract of animals. The production of ATP by Oxalobacter formigenes is centered around oxalate metabolism and oxalate is required for growth. A small amount of acetate (0.5 mM) is also required. Oxalate is decarboxylated to formate plus CO2 in nearly equimolar amounts. Experiments were conducted to determine which potential carbon sources (oxalate, acetate, formate, CO2) were assimilated by Oxalobacter formigenes and which metabolic pathways were operative in carbon assimilation. Measurements of the specific activities of total cell carbon after growth with different 14C-labeled precursors indicated that at least 54% of the total cell carbon was derived from oxalate and at least 7% was derived from acetate. Carbonate was also assimilated, but formate was not a significant source of cell carbon. Labeling patterns in amino acids from cells grown in [14C]oxalate or 14CO3 were different; however, in both cases 14C was widely distributed into most cellular amino acids. Carbon from [14C]acetate was less widely distributed and detected mainly in those amino acids known to be derived from alpha-ketoglutarate, oxaloacetate, and pyruvate. Cell-free extracts contained citrate synthase, isocitrate dehydrogenase, and malate dehydrogenase activities. The labeling observed in amino acids derived from acetate is in agreement with the function of these enzymes in biosynthesis and indicates that the majority of acetate carbon entered into amino acid biosynthesis via well-known pathways.

Acetates↗

PubMed1994

Lachnospira pectinoschiza sp. nov., an anaerobic pectinophile from the pig intestine.

Pectinophiles are bacteria that utilize pectin and only a few related compounds as substrates. Obligately anaerobic pectinophiles have been isolated from the intestinal tracts and gingivae of humans and from the rumina of cattle. We isolated three strains of pectinophilic bacteria from colonic contents of pigs but were unable to isolate pectinophiles from the rumen contents of four sheep, even when the animals were fed a high-pectin diet. The pectinophiles isolated from pigs were strictly anaerobic, motile, gram-positive rods (0.36 to 0.56 by 2.4 to 3.1 microns). Pectin, polygalacturonic acid, and gluconate were the only substrates that supported rapid growth. All three strains grew slowly on either lactose or cellobiose and fermented fructose after a lag of several days. Pectin was degraded by means of an extracellular pectin methylesterase and a Ca(2+)-dependent exopectate lyase. A comparison of the 16S rRNA sequences of these isolates with the 16S rRNA sequences of other gram-positive bacteria revealed a specific relationship with Lachnospira multipara (level of similarity, 94%). The Gram reaction, formation of spore-like structures, and the utilization of lactose and cellobiose differentiated the pig isolates from previously described pectinophiles. The pig isolates represent a previously undescribed species of the genus Lachnospira, for which we propose the name Lachnospira pectinoschiza.

Animals↗

PubMed1993

Amino acid utilization by the ruminal bacterium Synergistes jonesii strain 78-1.

The ruminal bacterium Synergistes jonesii strain 78-1, which is able to degrade the pyridinediol toxin in the plant Leucaena leucocephala, was studied for its ability to utilise amino acids. The organism used arginine, histidine and glycine from a complex mixture of amino acids, and both arginine and histidine supported growth in a semi-defined medium. The products of (U-14C)-arginine metabolism were CO2 acetate, butyrate, citrulline and ornithine. The labelling pattern of end products from (U-14C)-histidine metabolism differed in that carbon also flowed into formate and propionate. Arginine was catabolised by the arginine deiminase pathway which was characterised by the presence of arginine deiminase, ornithine transcarbamylase and carbamate kinase. This is the first report of a rumen bacterium that uses arginine and histidine as major energy yielding substrates.

Amino Acids↗