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Biomedical subjects

K Berry

Publications and source records attributed to K Berry.

At least 19 recordsLinked to original sources

Shoot meristem: an ideal explant for Zea mays L. transformation.

We report on a rapid high-frequency somatic embryogenesis and plant regeneration protocol for Zea mays. Maize plants were regenerated from complete shoot meristem (3-4 mm) explants via organogenesis and somatic embryogenesis. In organogenesis, the shoot meristems were directly cultured on a high-cytokinin medium comprising 5-10 mg x L(-1) 6-benzylaminopurine (BAP). The number of multiple shoots produced per meristem varied from six to eight Plantlet regeneration through organogenesis resulted in just four weeks. Callus was induced in five days of incubation on an auxin-modified Murashige and Skoog (MS) medium. Prolific callus, with numerous somatic embryos, developed within 3-4 weeks when cultured on an auxin medium containing 5 mg 2,4-dichlorophenoxyacetic acid x L(-1). The number of multiple shoots varied from three to six per callus. Using R23 (Pioneer, Hi-Bred, Johnston, Iowa), the frequency of callus induction was consistently in excess of 80% and plant regeneration ranged between 47 and 64%. All regenerated plantlets survived in the greenhouse and produced normal plants. Each transgenic plant produced leaves, glumes, and anthers that uniformly expressed green fluorescent protein (GFP). The GFP gene segregated in the pollen. Based on this data it is concluded that the transgenics arose from single-cell somatic embryos. The rate of transfer DNA (T-DNA) transfer to complete shoot meristems of Zea mays was high on the auxin medium and was independent of using super-virulent strains of Agrobacterium.

2,4-Dichlorophenoxyacetic Acid↗

Comparative audit of intravenous lorazepam and diazepam in the emergency treatment of convulsive status epilepticus in children.

There is little evidence on which to judge the optimal treatment for convulsive status epilepticus (CSE) in children. This study compares the effect of intravenous (iv) lorazepam with iv diazepam as the first line of treatment of CSE. We studied all children with prolonged seizures arriving in the Accident and Emergency (A&E) Department in two separate periods. In the first 6-month period iv diazepam was used as standard treatment, in the second 1-year period iv lorazepam was used. We measured latency to stopping of seizure and any adverse events. A successful treatment was defined as one in which the seizure clinically ceased within 15 minutes after siting the iv cannula, requiring no further treatment.Intravenous diazepam (0.32 mg kg (-1)) was used in 17 of 26 patients, whilst iv lorazepam (0.13 mg kg (-1)) was used in 31 of 59. There were no differences between the two groups regarding age, sex and seizure type.The seizure was successfully controlled 15 minutes after siting the iv cannula in 11 (65%) patients treated with diazepam (median time of 3 minutes) and in 20 (65%) patients treated with lorazepam (median time of 5 minutes). These preliminary results suggest that iv lorazepam may be as effective as iv diazepam.

Anticonvulsants↗

Haemorrhage into an arachnoid cyst: a serious complication of minor head trauma.

Arachnoid cysts are infra-arachnoidal cerebrospinal fluid collections that are usually asymptomatic. However, they can become acutely symptomatic because of haemorrhage and cyst enlargement, which may result from minor head trauma. The range of symptoms is wide and many are "soft" signs. Diagnosis is important as cysts causing mass effect require surgery. A case is reported of a child presenting with localised headaches after minor head trauma. Computed tomography demonstrated an arachnoid cyst with evidence of haemorrhage, which required surgical intervention. Other cases of arachnoid cyst presenting to our hospital or reported in the literature are reviewed with respect to presenting symptoms and signs. Localised headaches, behavioural or cognitive changes and ataxia are more commonly associated with this disorder than nausea, vomiting, visual disturbances or seizures. This range of symptomatology following minor head trauma may warrant computed tomography when other criteria for this investigation are not met.

Accidental Falls↗

Differing effects of low-dose estrogen-progestin therapy and pravastatin in postmenopausal hypercholesterolemic women.

BACKGROUND: Most studies examining the potential cardioprotective effects of postmenopausal estrogen have been undertaken in healthy women, with doses that may not be appropriate for long-term intervention. New low-dose estrogen-progestin regimens alleviate postmenopausal symptoms with a favorable side-effect profile; however, little is known of the impact of such regimens in women at increased risk of cardiovascular disease. Hence, we have evaluated the effects of low-dose oral estrogen-progestin therapy on serum lipoprotein lipids, brachial artery reactivity and fibrinogen in hypercholesterolemic postmenopausal women in direct comparison with the effects of pravastatin, a lipid-lowering agent known to reduce cardiovascular events in women. METHODS: In a randomized, double-blind, double-dummy, parallel trial, we studied the effects of continuous combined estrogen-progestin therapy (1 mg 17beta-estradiol with 500 micro g norethisterone acetate daily) or pravastatin (20 mg daily) in 72 postmenopausal women with fasting serum low-density lipoprotein (LDL) cholesterol levels greater than 124 mg/dl after an 8-week run-in diet, over a 24-week period. The primary end-point was percentage change in LDL cholesterol from baseline. RESULTS: The intention-to-treat population comprised 65 women, mean age 59 +/- 6.3 years, and 29 in each group completed the trial. Diet alone reduced LDL cholesterol significantly in both treatment groups, in association with a reduction in weight during this period. Compared with respective baseline values, pravastatin decreased LDL cholesterol and total cholesterol to a greater extent than hormone therapy (p = 0.0001 and 0.003 for difference between treatments, respectively). High-density lipoprotein (HDL) cholesterol levels decreased with hormone therapy, but did not change with pravastatin (p = 0.01). Lipoprotein(a) decreased significantly with hormone therapy only (-14%, 95% confidence interval (CI) -21 to -6%, p = 0.01 for difference between groups). Brachial artery flow-mediated dilatation (FMD) was impaired at baseline, and this increased with hormone therapy (absolute mean change in artery diameter as percentage units 2.07, 95% CI 0.57-3.57, p = 0.009) versus no change with pravastatin (0.19, 95% CI -1.1 to 1.5, p = 0.78), with a near-significant difference between the two groups (p = 0.058). A significant correlation between improved brachial artery FMD and reduction in LDL cholesterol was not observed. Fibrinogen decreased significantly in both treatment groups with no difference between treatments. CONCLUSIONS: In postmenopausal hypercholesterolemic women, pravastatin and hormone therapy exhibited divergent effects. The former lowered total and LDL cholesterol more effectively, whereas hormone therapy lowered lipoprotein(a) significantly and improved brachial artery endothelium-dependent dilatation, independent of the reduction in LDL cholesterol. The modest increase in brachial artery FMD seen is consistent with hypercholesterolemia compromising endothelial integrity, and suggests that the important effect of estrogen on the endothelial microenvironment may be attenuated in women with endothelial dysfunction.

Aged↗

Cost-effectiveness of microsatellite instability screening as a method for detecting hereditary nonpolyposis colorectal cancer.

BACKGROUND: The National Cancer Institute has published consensus guidelines for universal screening for hereditary nonpolyposis colorectal cancer (HNPCC) in patients with newly diagnosed colorectal cancer. OBJECTIVE: To determine the cost-effectiveness of screening compared with standard care in eligible patients with colorectal cancer and their siblings and children. DESIGN: Cost-effectiveness analysis. DATA SOURCES: National colorectal cancer registry data, the Creighton International Hereditary Colorectal Cancer Registry, Medicare claims records, and published literature. TARGET POPULATION: Patients with newly diagnosed colorectal cancer and their siblings and children. TIME HORIZON: Lifetime (varies depending on age at screening). PERSPECTIVE: Societal. INTERVENTIONS: Initial office-based screening to determine eligibility (based on personal and family cancer history), followed by tumor testing for microsatellite instability. Those with microsatellite instability were offered genetic testing for HNPCC. Siblings and children of patients with cancer and the HNPCC mutation were offered genetic testing, and those who were found to carry the mutation received lifelong colorectal cancer screening. MEASUREMENTS: Life-years gained. RESULTS OF BASE-CASE ANALYSIS: When only the patients with cancer were considered, cost-effectiveness of screening was $42 210 per life-year gained. When patients with cancer and their siblings and children were considered together, cost-effectiveness increased to $7556 per life-year gained. RESULTS OF SENSITIVITY ANALYSIS: The model was most sensitive to the estimated survival gain from screening siblings and children, to the prevalence of HNPCC mutations among patients with newly diagnosed cancer, and to the discount rate. In probabilistic analysis, the 90% CI for the cost-effectiveness of screening patients with cancer plus their relatives was $4874 to $21 576 per life-year gained. CONCLUSION: Screening patients with newly diagnosed colorectal cancer for HNPCC is cost-effective, especially if the benefits to their immediate relatives are considered.

Age Distribution↗

Complete genome sequence of Caulobacter crescentus.

The complete genome sequence of Caulobacter crescentus was determined to be 4,016,942 base pairs in a single circular chromosome encoding 3,767 genes. This organism, which grows in a dilute aquatic environment, coordinates the cell division cycle and multiple cell differentiation events. With the annotated genome sequence, a full description of the genetic network that controls bacterial differentiation, cell growth, and cell cycle progression is within reach. Two-component signal transduction proteins are known to play a significant role in cell cycle progression. Genome analysis revealed that the C. crescentus genome encodes a significantly higher number of these signaling proteins (105) than any bacterial genome sequenced thus far. Another regulatory mechanism involved in cell cycle progression is DNA methylation. The occurrence of the recognition sequence for an essential DNA methylating enzyme that is required for cell cycle regulation is severely limited and shows a bias to intergenic regions. The genome contains multiple clusters of genes encoding proteins essential for survival in a nutrient poor habitat. Included are those involved in chemotaxis, outer membrane channel function, degradation of aromatic ring compounds, and the breakdown of plant-derived carbon sources, in addition to many extracytoplasmic function sigma factors, providing the organism with the ability to respond to a wide range of environmental fluctuations. C. crescentus is, to our knowledge, the first free-living alpha-class proteobacterium to be sequenced and will serve as a foundation for exploring the biology of this group of bacteria, which includes the obligate endosymbiont and human pathogen Rickettsia prowazekii, the plant pathogen Agrobacterium tumefaciens, and the bovine and human pathogen Brucella abortus.

Adaptation, Biological↗

Parameter solicitation for planning cost effectiveness studies with dichotomous outcomes.

When economic endpoints are included alongside clinical effectiveness measures in randomized clinical trials (RCT), they are summarized together by the incremental cost effectiveness ratio (ICER). Adding economic endpoints to an RCT complicates the planning of experiments because investigators must now solicit their beliefs about costs, but even more challenging, they must also specify their association with effectiveness. Solicitation of correlations between costs and effects can be unintuitive, and so potentially highly inaccurate. This is unfortunate because power is highly sensitive to the association between costs and effects. Mis-specification in this association may lead to substantially underpowered or overpowered studies. We show that when clinical effectiveness measures are dichotomous, specification of the correlation between costs and effects can be avoided by instead describing their association with a mixture model. This representation leads to simple and highly intuitive parameter specifications. It may also be used to generate realistic raw data that can be used to evaluate experiment power with simulation. We give particular attention to evaluating and interpreting power when Fieller's theorem method (FTM) is used to calculate confidence for, and test hypotheses about, the ICER. Data from a previously published clinical trial are used to demonstrate the use of this new method to calculate sample size for a cost effectiveness study.

Cost-Benefit Analysis↗

The impact of including future medical care costs when estimating the costs attributable to a disease: a colorectal cancer case study.

A source of controversy in the economic literature concerns whether to include or exclude future medical care costs when computing attributable costs for lifesaving interventions. Although it is hypothesized that including future medical care costs will offset the cost savings achieved through prevention, the magnitude of the effect is not known. The objectives of the present study are to develop a methodology for estimating the excess costs of care among colorectal cancer patients, including and excluding future costs of care, and comparing these results with previous studies that do not include costs in added years of life. Subjects in the study included those identified with colorectal cancer drawn from the Surveillance, Epidemiology and End Results (SEER)-Medicare database and an age- and gender-matched control group drawn from the general Medicare population. Using the Kaplan-Meier Sample Average estimator, we directly estimate expected 11-year costs, and then, with the addition of some simple extrapolating assumptions, determine expected 25-year costs. The latter time horizon captures lifetime costs for over 90% of the cohort. Males results for discounted, stage-specific 11- versus 25-year excess costs: in situ, 22411 dollars versus 23494 dollars; Stage 1, 29365 dollars versus 32510 dollars; Stage 2, 28114 dollars versus 25263 dollars; Stage 3, 27397 dollars versus 19647 dollars; Stage 4, 3006 dollars versus 7837 dollars. Trends were similar for females. It can be concluded that adding costs of care in future years for those whose colorectal cancer is prevented owing to screening greatly alters the estimate of lifetime excess costs for colorectal cancer patients, and can produce negative results for advanced stage disease. The results emphasize the need to adopt a standard approach for dealing with future costs when evaluating lifesaving interventions for cost-effectiveness analyses.

Cohort Studies↗

Baló's concentric sclerosis: surviving normal myelin in a patient with a relapsing-remitting dinical course.

Baló's concentric sclerosis is a demyelinating disorder in which bands of demyelination alternate with concentric bands of myelin preservation. The pathogenesis of the lesion is unknown. Previous reports using modern histopathologic techniques have shown the bands of myelin preservation to be comprised of remyelinated or partially demyelinated myelin. Here we report a case of Baló's concentric sclerosis in a 24-year-old East Indian patient with a previous history of relapsing-remitting multiple sclerosis (MS). Pathologically, the bands of myelin preservation showed myelin sheaths of normal thickness, with focal areas of demyelination. The findings, taken together with those of previously reported cases, suggest that Baló's concentric sclerosis is a variant of MS, and the concentric lesion may be an intermediary form in evolution of a chronic active MS plaque. The pathogenesis of this concentric lesion may be explained by periodic suppression of demyelination in the rapidly expanding border, allowing remyelination or only transient incomplete demyelination to occur.

Adult↗

Genome sequences of Chlamydia trachomatis MoPn and Chlamydia pneumoniae AR39.

The genome sequences of Chlamydia trachomatis mouse pneumonitis (MoPn) strain Nigg (1 069 412 nt) and Chlamydia pneumoniae strain AR39 (1 229 853 nt) were determined using a random shotgun strategy. The MoPn genome exhibited a general conservation of gene order and content with the previously sequenced C.trachomatis serovar D. Differences between C.trachomatis strains were focused on an approximately 50 kb 'plasticity zone' near the termination origins. In this region MoPn contained three copies of a novel gene encoding a >3000 amino acid toxin homologous to a predicted toxin from Escherichia coli O157:H7 but had apparently lost the tryptophan biosyntheis genes found in serovar D in this region. The C. pneumoniae AR39 chromosome was >99.9% identical to the previously sequenced C.pneumoniae CWL029 genome, however, comparative analysis identified an invertible DNA segment upstream of the uridine kinase gene which was in different orientations in the two genomes. AR39 also contained a novel 4524 nt circular single-stranded (ss)DNA bacteriophage, the first time a virus has been reported infecting C. pneumoniae. Although the chlamydial genomes were highly conserved, there were intriguing differences in key nucleotide salvage pathways: C.pneumoniae has a uridine kinase gene for dUTP production, MoPn has a uracil phosphororibosyl transferase, while C.trachomatis serovar D contains neither gene. Chromosomal comparison revealed that there had been multiple large inversion events since the species divergence of C.trachomatis and C.pneumoniae, apparently oriented around the axis of the origin of replication and the termination region. The striking synteny of the Chlamydia genomes and prevalence of tandemly duplicated genes are evidence of minimal chromosome rearrangement and foreign gene uptake, presumably owing to the ecological isolation of the obligate intracellular parasites. In the absence of genetic analysis, comparative genomics will continue to provide insight into the virulence mechanisms of these important human pathogens.

Animals↗