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Biomedical subjects

G Collins

Publications and source records attributed to G Collins.

At least 19 recordsLinked to original sources

Broadband dielectric function of nonequilibrium warm dense gold.

We report on the first single-state measurement of the broadband (450-800 nm) dielectric function of gold isochorically heated by a femtosecond laser pulse to energy densities of 10(6) - 10(7) J/kg. A Drude and an interband component are clearly seen in the imaginary part of the dielectric function. The Drude component increases with energy density while the interband component shows both enhancement and redshift. This is in strong disagreement with predictions of a recent calculation of dielectric function based on limited Brillouin zone sampling.

Journal Article↗

Application and biomolecular monitoring of psychrophilic anaerobic digestion.

Thirteen anaerobic hybrid expanded granular sludge bed-anaerobic filter bioreactors were used for psychrophilic (15-18 degrees C) anaerobic digestion of a variety of synthetic and non-synthetic wastewaters, including: food-processing, dairy, aromatic- and aliphatic-containing and brewery discharges. Specific methanogenic activity assays were employed to assess temporal physiological activity dynamics. Terminal restriction fragment length polymorphism genetic fingerprinting and fluorescent in situ hybridization were used to monitor shifts in the structure of the microbial communities in the bioreactors in response to operating conditions. Treatment efficiencies obtained were comparable to previous mesophilic (37 degrees C) trials. Methanogenic activity developed under psychrophilic conditions and putative psychrophilic populations were detected within otherwise psychrotolerant mesophilic communities. Shifts in the population structure of archaeal (methanogenic) communities were more indicative of process disruption than bacterial communities. Biomolecular techniques were demonstrated as valuable tools for anaerobic wastewater treatment plant monitoring.

Biomass↗

Experience with minimally invasive esophagectomy.

BACKGROUND: Minimally invasive esophagectomy (MIE) is an evolving surgical alternative to traditional open esophagectomy. Despite considerable technical challenges, it was hypothesized that MIE could be performed effectively by surgeons experienced in open esophageal resection and advanced laparoscopic surgery. The authors report their experience with 25 patients who underwent MIE for esophageal disease. METHODS: A multidisciplinary esophageal cancer team evaluated all the patients enrolled in this institutional review board-approved retrospective review study. Over an 18-month period, 25 consecutive patients (22 men and 3 women; mean age, 62 years; range, 48-77 years) with resectable esophageal cancer underwent MIE. Six patients were treated with neoadjuvant chemoradiotherapy. The preoperative diagnoses were adenocarcinoma (64%, n = 16), high-grade dysplasia (20%, n = 5), and squamous cell cancer (16%, n = 4). The outcomes evaluated included operative course, hospital and intensive care unit lengths of stay, pathologic stage, morbidity, and mortality. RESULTS: Two patients required conversion to open esophagectomy. Operative mortality was 4% (n = 1). The mean operative time was 350 min (range, 300-480), and the average blood loss was 200 ml. The patients remained ventilated for a median of 12 h, and the median intensive care unit utilization was 1 day. The median hospital length of stay was 9 days (range, 6-33 days). Major complications occurred in 32% of the patients. The anastomotic leak rate was 12%. Minor pulmonary complications occurred in 32% and atrial fibrillation in 16% of the patients. An anastomotic stricture developed in 24% of all the patients. One patient showed a positive proximal margin in the final pathology results. CONCLUSIONS: Minimally invasive esophagectomy is a technically challenging procedure that can be performed safely at the Virginia Piper Cancer Institute. Optimal results require appropriate patient selection and a multidisciplinary team experienced in the management of esophageal cancer.

Adenocarcinoma↗

Assessment of anaerobic wastewater treatment failure using terminal restriction fragment length polymorphism analysis.

AIMS: The suitability of genetic fingerprinting to study the microbiological basis of anaerobic bioreactor failure is investigated. METHODS AND RESULTS: Two laboratory-scale anaerobic expanded granular sludge bed bioreactors, R1 and R2, were used for the mesophilic (37 degrees C) treatment of high-strength [10 g chemical oxygen demand (COD) l(-1)] synthetic industrial-like wastewater over a 100-day trial period. A successful start up was achieved by both bioreactors with COD removal over 90%. Both reactors were operated under identical parameters; however, increased organic loading during the trial induced a reduction in the COD removal of R1, while R2 maintained satisfactory performance (COD removal >90%) throughout the experiment. Specific methanogenic activity measurements of biomass from both reactors indicated that the main route of methane production was hydrogenotrophic methanogenesis. Terminal restriction fragment length polymorphism (TRFLP) analysis was applied to the characterization of microbial community dynamics within the system during the trial. The principal differences between the two consortia analysed included an increased abundance of Thiovulum- and Methanococcus-like organisms and uncultured Crenarchaeota in R1. CONCLUSIONS: The results indicated that there was a microbiological basis for the deviation, in terms of operational performance, of R1 and R2. SIGNIFICANCE AND IMPACT OF THE STUDY: High-throughput fingerprinting techniques, such as TRFLP, have been demonstrated as practically relevant for biomonitoring of anaerobic reactor communities.

Anaerobiosis↗

Equation of state data for iron at pressures beyond 10 Mbar.

We present equation of state points for iron, in the pressure range 10-45 Mbar, the first obtained with laser-driven shock waves. The experiment has been performed with the high energy laser Phebus, optically smoothed with Kinoform phase plates. Our results double the set of existing experimental data at very high pressures showing good agreement with the predictions of the quotidian equation of state model and with previous results.

Journal Article↗

Statistical methodology of phase III cancer clinical trials: advances and future perspectives.

The methodology for conducting cancer clinical trials has undergone enormous changes over the past 25-30 years since the EORTC Data Center was created. The purpose of this paper is to highlight and to provide a historical perspective for the main methodological concepts, both practical and theoretical, which form the basis for the design and analysis of phase III cancer clinical trials within the EORTC Data Center. Some statistical aspects of other associated topics such as quality of life, health economics, meta-analysis and treatment outcome will also be briefly discussed. Finally, some future perspectives and topics for further statistical methodological research will be presented in order to spur statisticians to meet the challenge of efficiently designing and analysing the clinical trials of tomorrow.

Clinical Trials, Phase III as Topic↗

Increasing antioxidant levels in tomatoes through modification of the flavonoid biosynthetic pathway.

Flavonoids are a diverse group of phenolic secondary metabolites that occur naturally in plants and therefore form an integral component of the human diet. Many of the compounds belonging to this group are potent antioxidants in vitro and epidemiological studies suggest a direct correlation between high flavonoid intake and decreased risk of cardiovascular disease, cancer and other age-related diseases. Enhancing flavonoid biosynthesis in chosen crops may provide new raw materials that have the potential to be used in foods designed for specific benefits to human health. Using genetic modification, it was possible to generate several tomato lines with significantly altered flavonoid content and to probe the role and importance of several key enzymatic steps in the tomato flavonoid biosynthetic pathway. Most notably an up to 78-fold increase in total fruit flavonols was achieved through ectopic expression of a single biosynthetic enzyme, chalcone isomerase. In addition, chalcone synthase and flavonol synthase transgenes were found to act synergistically to up-regulate flavonol biosynthesis significantly in tomato flesh tissues.

Acyl Coenzyme A↗

Molecular mobility and fragility in indomethacin: a thermally stimulated depolarization current study.

PURPOSE: To show that thermally stimulated depolarization currents (TSDC), which is a dielectric experimental technique relatively unknown in the pharmaceutical scientists community, is a powerful technique to study molecular mobility in pharmaceutical solids, below their glass transition temperature (Tg). Indomethacin (Tg = 42 degrees C) is used as a model compound. METHODS: TSDC is used to isolate the individual modes of motion present in indomethacin, in the temperature range between -165 degrees C and +60 degrees C. From the experimental output of the TSDC experiments, the kinetic parameters associated with the different relaxational modes of motion were obtained, which allowed a detailed characterization of the distribution of relaxation times of the complex relaxations observed in indomethacin. RESULTS: Two different relaxational processes were detected and characterized: the glass transition relaxation, or alpha-process, and a sub-Tg relaxation, or secondary process. The lower temperature secondary process presents a very low intensity, a very low activation energy, and a very low degree of cooperativity. The fragility index (Angell's scale) of indomethacin obtained from TSDC data is m = 64, which can be compared with other values reported in the literature and obtained from other experimental techniques. CONCLUSIONS: TSDC data indicate that indomethacin is a relatively strong glass former (fragility similar to glycerol but lower than sorbitol, trehalose, and sucrose). The high-resolution power of the TSDC technique is illustrated by the fact that it detected and characterized the secondary relaxation in indomethacin, which was not possible by other techniques.

Calorimetry↗

RESEARCH: Assessing Uncertainty in Estimates of Nitrogen Loading to Estuaries for Research, Planning, and Risk Assessment.

/ There can be considerable uncertainty associated with calculations of nutrient loading to estuaries from their watersheds, arising from uncertainty in the variables used in the calculation. Analysis of uncertainty is particularly important in the context of planning and management, where such information can be useful in helping make decisions about development in the coastal zone and in risk assessment, where probability of worse-case extremes may be relevant. This fact has been largely ignored when loading calculations have been made, presumably because both uncertainty estimates for the input variables and a standard method were lacking. Parametric (propagation for normal error estimates) and nonparametric methods (bootstrap and enumeration of combinations) to assess the uncertainty in calculated rates of nitrogen loading were compared, based on the propagation of uncertainty observed in the variables used in the calculation. In addition, since such calculations are often based on literature surveys rather than random replicate measurements for the site in question, error propagation was also compared using the uncertainty of the sampled population (e.g., standard deviation) as well as the uncertainty of the mean (e.g., standard error of the mean). Calculations for the predicted nitrogen loading to a shallow estuary (Waquoit Bay, MA) were used as an example. The previously estimated mean loading from the watershed (5,400 ha) to Waquoit Bay (600 ha) was 23,000 kg N yr(-1). The mode of a nonparametric estimate of the probability distribution differed dramatically, equaling only 70% of this mean. Repeated observations were available for only 8 of the 16 variables used in our calculation. We estimated uncertainty in model predictions by treating these as sample replicates. Parametric and nonparametric estimates of the standard error of the mean loading rate were 12-14%. However, since the available data include site-to-site variability, as is often the case, standard error may be an inappropriate measure of confidence. The standard deviations were around 38% of the loading rate. Further, 95% confidence intervals differed between the nonparametric and parametric methods, with those of the nonparametric method arranged asymmetrically around the predicted loading rate. The disparity in magnitude and symmetry of calculated confidence limits argue for careful consideration of the nature of the uncertainty of variables used in chained calculations. This analysis also suggests that a nonparametric method of calculating loading rates using most frequently observed values for variables used in loading calculations may be more appropriate than using mean values. These findings reinforce the importance of including assessment of uncertainty when evaluating nutrient loading rates in research and planning. Risk assessment, which may need to consider relative probability of extreme events in worst-case scenarios, will be in serious error using normal estimates, or even the nonparametric bootstrap. A method such as our enumeration of combinations produces a more reliable distribution of risk.

Journal Article↗

Randomized, controlled trial of caloric supplements in HIV infection. Terry Beirn Community Programs for Clinical Research on AIDS.

OBJECTIVE: To compare the efficacy of three nutritional regimens in the prevention of weight loss. DESIGN: A three-arm randomized controlled trial with primary outcome measure percent change in weight over four months. PATIENTS: A total of 536 patients with CD4 count <200 cells/mm3 and stable weight, defined as <5% weight loss as determined by a weight measurement 3 to 6 months before randomization were recruited at fourteen administrative units in the United States, each unit consisting of multiple primary care sites. INTERVENTION: The three arms were 500 kcal daily of caloric supplement with peptides and medium-chain triglycerides plus a multivitamin and mineral supplement, 500 kcal of a caloric supplement with whole protein and long-chain triglycerides plus a multivitamin and mineral supplement, and a multivitamin and mineral supplement only. RESULTS: There were no significant differences among the three regimens in the percent change in weight (p = .74) and body cell mass (p = .63). On average, 65% of the recommended 500 kcal/day of caloric supplements containing peptides with medium-chain triglycerides and 82% of the 500 kcal/day of the caloric supplement containing whole protein and long-chain triglycerides were consumed. CONCLUSIONS: Caloric supplements do not promote increases in average weight or body cell mass in weight-stable, HIV-infected adults beyond that offered by a multivitamin and mineral supplement.

Adult↗

Linkage analysis of Dermatophagoides pteronyssinus-specific IgE responsiveness with polymorphic markers on chromosome 6p21 (HLA-D region) in Caucasian families by the transmission/disequilibrium test. Collaborative Study on the Genetics of Asthma (CSGA).

BACKGROUND: Recently, we have obtained evidence for linkage between Der p 1-specific IgE antibodies and markers on chromosome 6p21 (HLA-D region) in a genome-wide screening in Caucasian families recruited as a part of the Collaborative Study on the Genetics of Asthma (CSGA). OBJECTIVE: Specific IgE antibodies toward different Dermatophagoides pteronyssinus (Der p) polypeptides were detected by immunoblotting analysis, and the transmission/disequilibrium test (TDT) was performed between specific IgE responsiveness toward each different Der p polypeptide and markers on chromosome 6p21 to better clarify the genetic contribution of HLA-D genes. METHODS: We studied 299 individuals in 45 Caucasian families participating in the CSGA. Serum samples from 137 individuals that showed elevated specific IgE antibodies toward the Der p crude allergen (> -0.5 log IU/mL) by ACCESS immunoassay were subjected to immunoblotting analysis. TDT was conducted between the presence of specific IgE antibodies toward each of 12 different Der p polypeptides and 4 polymorphic markers on chromosome 6p21. RESULTS: The 196-bp allele of D6S1281 and the 104-bp allele of DQCAR showed significant excess transmission to specific IgE responders toward a particular Der p polypeptide (120 kd, 55 kd, 45 kd, or 37 kd). In contrast, the 200-bp allele of D6S1281 and the 204-bp allele of D6S291 showed significantly decreased transmission to specific IgE responders toward a particular Der p polypeptide (120 kd, 90 kd, 52 kd, or 45 kd). Deviation from the expected 50% transmission in heterozygous parents was statistically significant after correcting for multiple comparisons. CONCLUSION: This study supported our previous findings that genes on chromosome 6p21 (HLA-D region) may influence the expression of Der p-specific IgE responsiveness in this Caucasian population. Our results, however, reveal the complexity of genetic regulations of Der p-specific IgE responsiveness by HLA-D genes, suggesting the strong influence of non-HLA loci and perhaps environmental factors for the development of Der p-specific IgE responsiveness.

Alleles↗

Failure to control the airway in a patient with Hunter's syndrome.

Hunter's syndrome is due to recessively inherited mucopolysaccharide storage diseases. The anaesthetic complications in this syndrome are related to the organs involved in the disease, but pertain especially to upper airway obstruction problems. We report a patient with Hunter's syndrome who, while under general anaesthesia for a simple procedure (the introduction of bilateral grommets), suffered a fatal outcome.

Adolescent↗

Postoperative outcome in high-risk infants undergoing herniorrhaphy: comparison between spinal and general anaesthesia.

The incidence of inguinal hernia is higher in premature infants, particularly in low birth weight neonates. This latter group may also incur increased postoperative respiratory complications and inpatient admissions. The purpose of this study was to compare the effects of general and spinal anaesthesia on postoperative respiratory morbidity and on the length of hospital stay in high-risk infants undergoing inguinal herniorrhaphy. Forty patients, all high-risk infants who underwent unilateral or bilateral herniorrhaphies, were randomly assigned to receive general anaesthesia (n = 20) or spinal anaesthesia (n = 20). There was a significant difference in respiratory morbidity between the two groups, as well as a significant difference in the inpatient hospital stay. The present study suggests that spinal anaesthesia can be used safely for high-risk infants, preterm or formerly preterm, undergoing inguinal hernia repair.

Anesthesia, General↗

Liver transplantation from non-heart beating donors in rats: influence of viscosity and temperature of initial flushing solutions on graft function.

BACKGROUND: We evaluated the effect of warm (37 degrees C) versus cold (4 degrees C) solutions as the initial flush for liver preservation from non-heart beating donors in rats. METHODS: An initial flush was performed just before donor hepatectomy with cold or warm University of Wisconsin solution (UW), UW without hydroxyethyl starch, sodium lactobionate sucrose solution, or lactated Ringer's solution as the control group. A separate group also used as control received no initial flushing. Liver transplantation was performed, and the graft function was determined by survival and assessment of enzyme release. The viscosity of each solution and the vascular resistance of the graft were measured. RESULTS: The 7-day survival rate was 83% and 100% in the warm and cold sodium lactobionate sucrose solution groups and 60% and 50% in the warm and cold lactated Ringer's solution groups, respectively. In the no-initial-flush group, rats did not survive. The 7-day survival rate was 67% and 0% in the warm and cold UW groups, respectively. Eliminating the hydroxyethyl starch from the cold UW improved the survival to 67%. Serum alanine aminotransferase levels 1 day after transplantation in the no-initial-flush and the cold UW groups were significantly higher than those of the remaining groups. At 4 degrees C the viscosity was higher in the UW (86.2 cp) compared to hydroxyethyl starch-free UW solution (30.9 cp), lactated Ringer's solution (24.5 cp), and sodium lactobionate sucrose solution (32.7 cp). The viscosity of UW at 37 degrees C was 34.7 cp. Vascular resistance correlated well with the viscosity. Livers flushed with solutions with a low viscosity showed lower vascular resistance than those flushed with cold UW and led to better survival. CONCLUSIONS: These data suggest that the viscosity of the initial flushing solution may play an important role in determining the outcome of organ procurement from non-heart beating donors.

Adenosine↗

Zidovudine alone or in combination with didanosine or zalcitabine in HIV-infected patients with the acquired immunodeficiency syndrome or fewer than 200 CD4 cells per cubic millimeter. Investigators for the Terry Beirn Community Programs for Clinical Research on AIDS.

BACKGROUND: We compared two combinations of nucleosides with zidovudine alone in patients with advanced human immunodeficiency virus (HIV) infection. METHODS: A total of 1102 patients with the acquired immunodeficiency syndrome or fewer than 200 CD4 cells per cubic millimeter were randomly assigned to receive zidovudine alone or zidovudine combined with either didanosine or zalcitabine. Disease progression, survival, toxic effects, and the CD4 cell response were assessed. RESULTS: After a median follow-up of 35 months, disease progression or death occurred in 62 percent of the 363 patients assigned to zidovudine plus didanosine, 63 percent of the 367 assigned to zidovudine plus zalcitabine, and 66 percent of the 372 assigned to zidovudine only (P=0.24). As compared with zidovudine therapy, treatment with zidovudine plus didanosine was associated with a relative risk of disease progression or death of 0.86 (95 percent confidence interval, 0.71 to 1.03), and treatment with zidovudine plus zalcitabine was associated with a relative risk of 0.92 (95 percent confidence interval, 0.76 to 1.10). Survival was similar in the three groups. In a subgroup analysis, combination therapy delayed disease progression or death in patients who had previously received zidovudine for 12 months or less. Therapy with zidovudine plus didanosine resulted in more gastrointestinal adverse effects, and treatment with zidovudine plus zalcitabine, more neuropathy. The mean increases in CD4 cell counts at two months were higher with combination therapy than with zidovudine alone. CONCLUSIONS: In patients with advanced HIV infection, combination therapy with zidovudine and either didanosine or zalcitabine is not superior to zidovudine therapy alone. However, these combinations may be more effective than zidovudine monotherapy in patients with little or no previous zidovudine treatment.

Acquired Immunodeficiency Syndrome↗

Refractoriness to mammary carcinogenesis in the parous mouse is reversible by hormonal stimulation induced by pituitary isografts.

We have previously reported that mouse mammary epithelial cells transformed in vitro yield tumors which vary qualitatively and quantitatively as a function of the mitogenic environment in which the cells are propagated at the time of carcinogen treatment. One milieu supportive of transformation in vitro was medium supplemented with progesterone and prolactin as the mitogens. We have performed parallel studies in which virgin mice were isografted with pituitaries resulting in elevated serum titers of progesterone and prolactin. After carcinogen treatment, these mice developed mammary tumors which included those identical genotypically and phenotypically to tumors induced in vitro in cells grown in progesterone and prolactin during carcinogen exposure. Our current working hypothesis is that the mitogenic environment around the time of carcinogen administration can modulate the incidence and phenotype of the resultant tumors. To further test this hypothesis, we have evaluated the susceptibility of hormonally-stimulated parous mice to chemically induced mammary carcinogenesis since parity is known to significantly reduce the susceptibility of the mouse mammary gland to carcinogenesis. Virgin or multiparous BALB/c mice were isografted with two pituitaries. Five weeks after surgery, the mice were injected with N-methyl-N-nitrosourea (MNU; 50 micrograms/g i.v.). Mammary carcinomas arose in 85% (11/13) with a median latency of 22.8 weeks and 1.9 tumors per virgin mouse and 80% (24/30) with a median latency of 22.1 weeks at a frequency of 1.9 tumors per parous mouse. Only 14% (2/14) of the non-isografted, age-matched parous controls developed tumors when injected with MNU. Fourteen parous mice receiving only pituitary isografts (no MNU), did not develop mammary carcinomas within the 7-month period of the study. These results demonstrate that parous BALB/c mice are refractory to MNU-induced mammary carcinogenesis and that this refractoriness is not permanent, but can be overcome by hormonal stimulation mediated by pituitary isografts.

Adenocarcinoma↗

In vivo growth stimulation of collagen gel embedded normal human and mouse primary mammary epithelial cells.

A new system for studying growth of normal human mammary epithelial cells in an in vivo environment using athymic nude mice is described. Human mammary epithelial cells dissociated from reduction mammoplasty specimens were embedded within collagen gels and subsequently transplanted subcutaneously into nude mice. Histological sections of recovered collagen gels showed epithelial cells arranged as short tubules with some branching. Proliferation of mammary epithelial cells was quantitated in vivo by 3 days' continuous infusion with 5 bromo-2'-deoxy-uridine followed by immunostaining of sections from recovered gels. Ovarian steroids administered to the host animals, resulting in blood serum levels normally found in the human female, had little or no effect on the proliferation of human mammary epithelial cells. Collagen gel embedded mouse mammary epithelial cells, mouse mammary explants, and host mammary glands all responded similarly to ovarian steroids, suggesting that the unresponsiveness of the human mammary epithelial cells under these conditions was not due to dissociation per se. However, an increased dose of 17 beta-estradiol or a growth factor combination containing epidermal growth factor, cholera toxin, and cortisol significantly stimulated the proliferation of human outgrowths. The growth factor response was dependent on the location of the cells, with the greatest response seen in the part of the gel proximal to the osmotic pump delivering the growth factors and the effect gradually waning in area more distal to the pump. The effect was especially striking since the mitotic figures could be easily identified and the labeling index was as high as 75%. The host mouse mammary gland also responded to growth factors, resulting in ductal hyperplasia. The proliferative and morphogenetic effects of various agents on normal human mammary epithelial cells embedded in collagen gel can be studied in vivo in nude mice.

Adolescent↗