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Biomedical subjects

M J Gardner

Publications and source records attributed to M J Gardner.

At least 19 recordsLinked to original sources
PubMed2006

Vertebral height restoration in osteoporotic compression fractures: kyphoplasty balloon tamp is superior to postural correction alone.

INTRODUCTION: Kyphoplasty has been shown to restore vertebral height and sagittal alignment. Proponents of vertebroplasty have recently demonstrated that many vertebral compression fractures (VCFs) are mobile and positional correction can lead to clinically significant height restoration. The current investigation tested the hypothesis that positional maneuvers do not achieve the same degree of vertebral height correction as kyphoplasty balloon tamps for the reduction of low-energy VCFs. METHODS: Twenty-five consecutive patients with a total of 43 osteoporotic VCFs were entered into a prospective analysis. Each patient was sequentially evaluated for postural and balloon vertebral fracture reduction. Preoperative standing and lateral radiographs of the fractured vertebrae were compared with prone cross-table lateral radiographs with the patient in a hyper-extension position and on pelvic and sternal rolls. Following positional manipulation, patients underwent a unilateral balloon kyphoplasty. Postoperative standing radiographs were evaluated for the percentage of height restoration related to positioning and balloon kyphoplasty. RESULTS: In the middle portion of the vertebrae, the percentage available for restoration restored with extension positioning was 10.4% (median 11.1%) and after balloon kyphoplasty was 57.0% (median 62.2%). This difference was statistically significant (p<0.001). Thus, kyphoplasty provided an additional 46.6% of the height available for restoration from the positioning alone. With operative positioning, 51.2% of VCFs had >10% restoration of the central portion of the vertebral body, whereas 90.7% of fractures improved at least 10% following balloon kyphoplasty (p<0.002). CONCLUSION: Although this study supports the concept that many VCFs can be moved with positioning, balloon kyphoplasty enhanced the height reduction >4.5-fold over the positioning maneuver alone and accounted for over 80% of the ultimate reduction. If height restoration is the goal, kyphoplasty is clearly superior in most cases to the positioning maneuver alone.

Aged↗
PubMed2006

Phase-specific gene expression underlying morphological adaptations of the dimorphic human pathogenic fungus, Coccidioides posadasii.

Coccidioides posadasii is a dimorphic fungal pathogen that grows as a filamentous saprobe in the soil and as endosporulating spherules within the host. To identify genes specific to the pathogenic phase of Co. posadasii, we carried out a large-scale study of gene expression in two isolates of the species. From the sequenced Co. posadasii genome, we chose 1,000 open reading frames to construct a 70-mer microarray. RNA was recovered from both isolates at three life-cycle phases: hyphae, presegmented spherules, and spherules releasing endospores. Comparative hybridizations were conducted in a circuit design, permitting comparison between both isolates at all three life-cycle phases, and among all life-cycle phases for each isolate. By using this approach, we identified 92 genes that were differentially expressed between pathogenic and saprobic phases in both fungal isolates, and 43 genes with consistent differential expression between the two parasitic developmental phases. Genes with elevated expression in the pathogenic phases of both isolates included a number of genes that were involved in the response to environmental stress as well as in the metabolism of lipids. The latter observation is in agreement with previous studies demonstrating that spherules contain a higher proportion of lipids than saprobic phase tissue. Intriguingly, we discovered statistically significant and divergent levels of gene expression between the two isolates profiled for 64 genes. The results suggest that incorporating more than one isolate in the experimental design offers a means of categorizing the large collection of candidate genes that transcriptional profiling typically identifies into those that are strain-specific and those that characterize the entire species.

Adaptation, Biological↗
PubMed2005

Prevention and treatment of osteoporotic fractures.

With the aging international population, osteoporosis has become an epidemic. This painless disease is characterized by a decreased bone mass, resulting in decreased structural integrity of bone, and often goes undiagnosed. Typical osteoporotic fractures include vertebrae, hip, and wrist fractures, and these may have a dramatic impact on quality of life, even if the fracture is successfully treated. Many antiresorptive agents have demonstrated the ability to reduce the risk of osteoporotic fractures, and newer anabolic agents may further reduce risk. Non-medical treatments, such as external hip protectors and balance and low-impact strength training, are also very effective in preventing fractures. Before specific treatments can be addressed, however, osteoporosis must first be considered as a diagnosis in any patient with a low-energy fracture. This requires continued public health initiatives involving patient and physician education regarding the necessity for bone mass measurement and the merits of antiresorptive therapy.

Bone Density Conservation Agents↗
PubMed2004

Profiling gene expression in Coccidioides posadasii.

Coccidioides posadasii is a dimorphic fungal pathogen which grows as a filamentous saprobe in the soil and multicellular parasitic form in host lung tissue. Studies of gene expression profiles during saprobic and parasitic phase development can provide clues about morphogenetic regulation and may lead to the discovery of molecular targets for novel antifungal drugs. Suppression-subtractive hybridization (SSH) and quantitative real-time polymerase chain reaction (QRT-PCR) were used to identify and quantify differential gene expression during in vitro growth of Coccidioides. DNA fragments obtained from the subtraction of cDNA pools derived from the saprobic and parasitic phase RNA preparations were each cloned into an appropriate vector and subjected to sequence analysis. Semi-quantitative, reverse transcription polymerase chain reaction (RT-PCR) experiments were first conducted to assess whether these inserts represented differentially expressed genes. Nucleotide sequences of the partial and full-length genes selected by RT-PCR were obtained by genome walking and rapid amplification of cDNA ends (RACE) methods. QRT-PCR analysis of the expression of these genes during saprobic and parasitic cell growth was then conducted using DNA standard curves normalized to a constitutively expressed control gene. Four C. posadasii genes whose expression is essentially restricted to the parasitic cycle were discovered using this approach. These genes include homologues of OPS1 (encodes opsin-related protein), MDR1 (multidrug resistance protein), ALDR1 (aldehyde reductase), and PSP1 (hypothetical lipid transporter/flippase protein). The combined applications of SSH and QRT-PCR permit global analysis of gene expression patterns in C. posadasii.

Coccidioides↗
PubMed2003

Construction of a BAC library and generation of BAC end sequence-tagged connectors for genome sequencing of the African malaria mosquito Anopheles gambiae.

A Bacterial Artificial Chromosome (BAC) genomic DNA library of Anopheles gambiae, the major human malaria vector in sub-Saharan Africa, was constructed and characterized. This library (ND-TAM) is composed of 30,720 BAC clones in eighty 384-well plates. The estimated average insert size of the library is 133 kb, with an overall genome coverage of approximately 14-fold. The ends of approximately two-thirds of the clones in the library were sequenced, yielding 32,340 pair-mate ends. A statistical analysis (G-test) of the results of PCR screening of the library indicated a random distribution of BACs in the genome, although one gap encompassing the white locus on the X-chromosome was identified. Furthermore, combined with another previously constructed BAC library (ND-1), ~2,000 BACs have been physically mapped by polytene chromosomal in situ hybridization. These BAC end pair mates and physically mapped BACs have been useful for both the assembly of a fully sequenced A. gambiae genome and for linking the assembled sequence to the three polytene chromosomes. This ND-TAM library is now publicly available at both http://www.malaria.mr4.org/mr4pages/index.html/ and http://hbz.tamu.edu/, providing a valuable resource to the mosquito research community.

Animals↗
PubMed2003

Aluminium speciation in effluents and receiving waters.

The respective speciation of aluminium in sewage effluent and in river water receiving effluent, has been examined. Results showed that concentrations of reactive aluminium changed over a timescale of hours and were controlled predominantly by pH. A minimum concentration of reactive aluminium occurred at a pH of approximately 6.8, coinciding with the prevalence of non-reactive, insoluble Al(OH)3 species. For receiving waters of low pH value, typically < pH 5, a large proportion of the 'naturally present' aluminium can be present in a reactive form at concentrations higher than the proposed Environmental Quality Standard (EQS). Mixing of waters of this type with effluent of a higher pH value leads to the precipitation of aluminium hydroxide. Mixing of effluent of pH value in the range 7.5-8.0 with river water in the same (or slightly higher) pH range appears to result in no appreciable change in the proportion of reactive aluminium; the change in concentration tends to be related simply to dilution. On the basis of a theoretical knowledge of aluminium speciation, results obtained in this work indicate that it is possible to make predictions about the proportion of reactive aluminium present in a receiving water, based on the pH values of the effluent water mixture and the concentration in the effluent. Reasonable comparisons between measured and predicted values were obtained at higher pH values, but the relationship was less certain at pH values less than 6.5 for which levels of reactive metal tended to be higher than the quality standard value.

Aluminum↗
PubMed2002

Partitioning of marine antifoulants in the marine environment.

The partitioning behaviour of the organic biocides, Irgarol 1051 and diuron and two inorganic biocides (copper and zinc) was investigated using six sediments of differing physico-chemical properties collected from unimpacted sites along the south coast of England. The kinetics of sorption and equilibrium partitioning between the sediments and seawater were investigated over a period of 20 days. Resulting organic carbon/water partition coefficients (log Koc) were related to suspended sediment concentration and ranged from 2.28 to 5.20 for diuron; and from 2.41 to 4.89 for Irgarol 1051. Sediment/water partition coefficients (log Kp) for copper and zinc varied from 2.46 to 5.08 l/kg and from 2.49 to 4.97 l/kg, respectively. Kinetic data indicated that there were significant interactions between the dissolved and particulate phases at the start of the experiments, just after mixing. This is thought to be a result of redistribution of organic carbon between the two phases.

Journal Article↗
PubMed2002

Survey of four marine antifoulant constituents (copper, zinc, diuron and Irgarol 1051) in two UK estuaries.

A field survey of antifoulant concentrations was undertaken in two UK estuaries (Hamble and Orwell) in 1998 and 1999. The two locations offered variations in physical aspects (Orwell estuary being significantly larger than the Hamble) as well as differences in boat densities (Hamble having almost twice as many vessels moored in the estuary and marinas). Samples were analysed for copper, zinc, diuron and Irgarol 1051, and were collected in summer and winter in order to identify potential seasonal variations in concentrations. The effect that different marina types (e.g. locked marina, one located in a natural inlet and pontooned ones in the open estuary) had on antifoulant concentrations were also investigated. Concentrations of the organic booster biocides, diuron and Irgarol 1051 in the marinas and estuaries were mainly influenced by leaching from antifoulant paints applied to the hulls of leisure craft, and so levels reflected the number of vessels present in the water. As a consequence significantly higher concentrations were found in marinas (up to ca. 900 ng l(-1) for diuron and 240 ng l(-1) for Irgarol 1051) compared with estuaries (up to ca. 400 ng l(-1) for diuron and 100 ng l(-1) for Irgarol 1051) and in summer compared with winter. Sediment concentrations of Irgarol 1051 and diuron were rarely detectable other than in the marinas where high concentrations were detected near slipways assumed to be derived from washed off paint chips. Dissolved concentration profiles for copper and zinc in the estuaries and marinas were different from those for the organic booster biocides partly because other sources of these metals contributed to estuarine and marina loads. In particular, riverine loads and inputs from sacrificial anodes attached to leisure craft, exhibited a major influence of estuarine levels of zinc. Consequently, only in the Hamble estuary for copper was there a clear distinction between summer (typically 3-4 microg l(-1)) and winter dissolved values (typically 1-2 microg l(-1)) that could be largely attributable to the leaching of antifoulant paints. Sediment concentrations for both metals were similar for both estuaries, with little variation between winter and summer values (Zn ranging from 28 to 614 mg kg(-1) and Cu from 6 to 1016 mg kg(-1)) as with the organic booster biocides highest levels were measured at the base of slipways in marinas.

Copper↗
PubMed2001

Differences between perspectives of physicians and patients on anticoagulation in patients with atrial fibrillation: observational study.

OBJECTIVE: To determine and compare physicians' and patients' thresholds for how much reduction in risk of stroke is necessary and how much risk of excess bleeding is acceptable with antithrombotic treatment in people with atrial fibrillation. DESIGN: Prospective observational study. SETTING: Tertiary and peripheral referral centres in Nova Scotia, Canada. PARTICIPANTS: 63 physicians who were treating patients with atrial fibrillation and 61 patients at high risk for atrial fibrillation. MAIN OUTCOME MEASURES: Participants underwent a face to face interview with a probability trade-off tool. Thresholds were determined for the minimum reduction in risk of stroke necessary and the maximum increase in risk of excess bleeding acceptable for treatment with aspirin and warfarin in people with atrial fibrillation. RESULTS: The minimum number of strokes that needed to be prevented in 100 patients over two years for warfarin to be justified was significantly lower for patients than for physicians (1.8 (SD 1.9) v 2.5 (1.6), P=0.009), whereas for aspirin there was no difference between patients and physicians (1.3 (1.3) v 1.6 (1.5), P=0.29). The maximum number of excess bleeds acceptable in 100 patients over two years for use of warfarin and aspirin was significantly higher for patients than for physicians (warfarin 17.4 (7.1) v 10.3 (6.1); aspirin 14.7 (8.5) v 6.7 (6.2); P<0.001 for both comparisons). CONCLUSIONS: Patients at high risk for atrial fibrillation placed more value on the avoidance of stroke and less value on the avoidance of bleeding than did physicians who treat patients with atrial fibrillation. The views of the individual patient should be considered when decisions are being made about antithrombotic treatment for people with atrial fibrillation.

Adult↗
PubMed2001

Exploring the transcriptome of the malaria sporozoite stage.

Most studies of gene expression in Plasmodium have been concerned with asexual and/or sexual erythrocytic stages. Identification and cloning of genes expressed in the preerythrocytic stages lag far behind. We have constructed a high quality cDNA library of the Plasmodium sporozoite stage by using the rodent malaria parasite P. yoelii, an important model for malaria vaccine development. The technical obstacles associated with limited amounts of RNA material were overcome by PCR-amplifying the transcriptome before cloning. Contamination with mosquito RNA was negligible. Generation of 1,972 expressed sequence tags (EST) resulted in a total of 1,547 unique sequences, allowing insight into sporozoite gene expression. The circumsporozoite protein (CS) and the sporozoite surface protein 2 (SSP2) are well represented in the data set. A BLASTX search with all tags of the nonredundant protein database gave only 161 unique significant matches (P(N) < or = 10(-4)), whereas 1,386 of the unique sequences represented novel sporozoite-expressed genes. We identified ESTs for three proteins that may be involved in host cell invasion and documented their expression in sporozoites. These data should facilitate our understanding of the preerythrocytic Plasmodium life cycle stages and the development of preerythrocytic vaccines.

Amino Acid Motifs↗
PubMed2001

Circadian variation of paroxysmal atrial fibrillation. PA3 Investigators. Atrial Pacing Peri-ablation for Prevention of Atrial Fibrillation Trial.

The circadian variation of paroxysmal atrial fibrillation (AF) was studied in 67 patients who received a dual-chamber pacemaker 3 months before a planned atrioventricular node ablation. A distinct circadian variation of AF was observed with 2 time peaks in initiation (1 in the early morning and 1 in the early evening hours), which was modulated by atrial pacing, the duration of AF, and the use of beta-adrenergic blocking agents.

Amiodarone↗
PubMed2001

A status report on the sequencing and annotation of the P. falciparum genome.

Almost 5 years ago, an international consortium of sequencing centers and funding agencies was formed to sequence the genome of the human malaria parasite Plasmodium falciparum. A novel chromosome by chromosome shotgun strategy was devised to sequence this very AT-rich genome. Two of the 14 chromosomes have been completed and the remaining chromosomes are in the final stages of gap closure. The consortium recently developed plans for the annotation and analysis of the complete genome sequence and its publication in 2002.

Animals↗
PubMed2001

Optimal electrocardiographic leads for detecting acute myocardial ischemia.

This study identifies the most sensitive electrocardiographic leads for monitoring ST-segment changes caused by acute coronary ischemia. The data set consisted of 120-lead electrocardiograms (ECGs) digitally recorded during balloon-inflation angioplasty in 3 groups of patients with single-vessel disease (left anterior descending [LAD], 32; right coronary artery [RCA], 36; left circumflex [LCx], 23). The ST deviation was measured in all recorded leads during baseline and ischemic states, and its difference between these 2 states (DeltaST) was calculated at 352 sites and plotted as DeltaST maps. The patients in each group were divided, by means of DeltaST criteria, into subgroups of "responders" and "nonresponders." Mean DeltaSTs for each group/subgroup were calculated and standardized by the corresponding standard deviation (SD); these values were plotted as mean DeltaST and t maps. Sites where extrema of DeltaST occurred most frequently were sought in bootstrap trials, performed in each group/subgroup. The results suggest that the optimal sites for the ischemia-sensitive leads are: V(3) (+) and just below V(8) (-) for LAD-related ischemia; the left iliac crest (+) and above V(3) at the third intercostal space (-) for RCA-related ischemia; and just below V(8) (+) and above V(2) at the third intercostal space (-) for LCx-related ischemia. Three "optimal" bipolar leads using these sites registered, in the responders from the LAD, RCA, and LCx groups, mean DeltaST (+/-SD) of 232 +/- 59, 245 +/- 96 and 158 +/- 91 microV, respectively; the corresponding t values were 15.14, 9.90, and 6.75. In the 12-lead ECG, only lead V(3) approached optimal DeltaST and t values for the LAD responders (187 +/- 61 microV; t = 11.75) and lead III for the RCA responders (191 +/- 76 microV; t = 9.73), but even these values were significantly suboptimal (P = 0.0011 and P = 0.0120, respectively). We found that the "optimal" bipolar leads can be derived, to an excellent approximation, from the 12 standard leads or from 3 EASI leads (with 3 electrodes at Frank's transverse level and 1 on the manubrium), by using precalculated regression coefficients. By means of bootstrap trials, we estimated the mean sensitivity (SE) and the mean positive predictive value (PPV) with which 3 "optimal" vessel-specific leads could identify ischemia related to the LAD, RCA, and LCx arteries, in the test set, as (SE/PPV) 94.7/92.8%, 78.7/80.9%, and 81.5/80.9%. A similar diagnostic performance can be achieved by vessel-specific leads derived from the 12-lead ECG (93.0/93.4%, 76.6/82.0%, and 82.7/77.1%) and, interestingly, from the EASI lead system (97.8/88.4%, 78.0/80.2%, and 76.8/83.2%). Thus, although the "optimal" bipolar leads for detecting ischemia related to each of the 3 coronary arteries were found to require sampling outside the 12-lead ECG, these leads can be derived from the full set of 12 standard leads or--for clinical monitoring applications--from the EASI lead system by using fewer electrodes at convenient locations.

Acute Disease↗
PubMed2001

Evaluation and treatment of dural tears in lumbar spine surgery: a review.

Incidental durotomy is a frequent complication of lumbar spinal surgery. The number and complexity of spinal procedures is increasing, leading to a greater prevalence of dural tears; therefore, it is imperative that spine surgeons be familiar with safe and effective closure techniques. Occasionally, a tear may not be recognized during the procedure, so that one must recognize the signs and symptoms of a cerebrospinal fluid leak postoperatively. Several newer treatment concepts show promise. The current study represents an extensive review of the recent literature on the prevalence, mechanism, diagnosis, treatment, and outcomes of dural tears. The authors provide an overview of the problem, an update on current treatment strategies, and describe the senior author's technique of repair, which is easy to do and is effective in stopping additional leakage of cerebrospinal fluid.

Dura Mater↗
PubMed2001

The effects of core and peripheral warming methods on temperature and physiologic variables in injured children.

INTRODUCTION: Injured children are at risk for thermoregulatory compromise, where temperature maintenance mechanisms are overwhelmed by severe injury, environmental exposure, and resuscitation measures. Adequate thermoregulation can be maintained, and heat loss can be prevented, by core (administration of warmed intravenous fluid) and peripheral (application of convective air warming) methods. It is not known which warming method is better to maintain thermoregulation and prevent heat loss in injured children during their trauma resuscitations. The purpose of this feasibility study was to compare the effects of core and peripheral warming measures on body temperature and physiologic changes in a small sample of injured children during their initial emergency department (ED) treatment. METHODS: A prospective, randomized experimental design was used. Eight injured children aged 3 to 14 years (mean = 6.87, SD = 3.44 ) treated in the ED of Children's Hospital of Pittsburgh were enrolled. Physiologic responses (eg, heart rate, blood pressure, respiratory rate, arterial oxygen saturation, core, peripheral temperatures) and level of consciousness were continuously measured and recorded every 5 minutes to detect early thermoregulatory compromise and to determine the child's response to warming. Data were collected throughout the resuscitation period, including transport to CT scan, the inpatient nursing unit, intensive care unit, operating room or discharge to home. Core warming was accomplished with the Hotline Fluid Warmer (Sims Level 1, Inc., Rockland, MA), and peripheral warming was accomplished with the Snuggle Warm Convective Warming System (Sins Level 1, Inc., Rockland, MA). Data were analyzed using descriptive and inferential statistics. RESULTS: There were no statistically significant differences between the two groups on age (t = -0.485, P = 0.645); weight (t = -0.005, P = 0.996); amount of prehospital intravenous (IV) fluid (t = 0314, P = 0.766); temperature on ED arrival (t = 0.287, P = 0.784); total amount of infused IV fluid (t = -0.21, P = 0.8); and length of time from ED admission to hospital admission (t = -0.613, P = 0.56). There were no statistically significant differences between the two groups on RTS (t = -0.516, P = 0.633). When comparing the mean differences in temperature upon hospital admission, no statistically significant differences were found (t = -1.572, P = 0.167). There were no statistically significant differences between the two groups in tympanic [F(15) = 0.71, P = 0.44] and skin [F(15) = 0.06, P = 0.81] temperature measurements over time. CONCLUSION: Core and peripheral warming methods appeared to e effective in preventing heat loss in this stable patient population. A reasonable next step would be to continue this trial in a larger sample of patients who are at greater risk for heat loss and subsequent hypothermia and to use a control group.

Adolescent↗