Biomedical subjects
M Holden
Publications and source records attributed to M Holden.
Back in the limelight.
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Microbial genomics. Dynamic duos.
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Medical image registration.
Radiological images are increasingly being used in healthcare and medical research. There is, consequently, widespread interest in accurately relating information in the different images for diagnosis, treatment and basic science. This article reviews registration techniques used to solve this problem, and describes the wide variety of applications to which these techniques are applied. Applications of image registration include combining images of the same subject from different modalities, aligning temporal sequences of images to compensate for motion of the subject between scans, image guidance during interventions and aligning images from multiple subjects in cohort studies. Current registration algorithms can, in many cases, automatically register images that are related by a rigid body transformation (i.e. where tissue deformation can be ignored). There has also been substantial progress in non-rigid registration algorithms that can compensate for tissue deformation, or align images from different subjects. Nevertheless many registration problems remain unsolved, and this is likely to continue to be an active field of research in the future.
Arterial reconstruction for radial artery occlusion.
This study was designed to detail the history and symptoms of symptomatic radial artery vaso-occlusive disease and to evaluate the results of radial artery reconstruction. Thirteen patients with symptomatic vaso-occlusive disease of the radial artery unresponsive to management by nonoperative modalities were managed with arterial reconstruction. All cases were treated with reversed interpositional vein grafting from the radial artery in the forearm (end-to-side) to the deep arch distally (end-to-end). Patients completed preoperative and postoperative assessments of symptoms and function, cold sensitivity (cold intolerance), and digital microvascular perfusion (isolated cold stress test evaluation with laser Doppler fluxmetry). At the follow-up examination all vascular grafts were patent, as determined by Allen's testing and Doppler ultrasound. The patients reported symptoms and functional status that demonstrated significant improvement following reconstruction. Microvascular evaluations demonstrated a significant improvement in digital microvascular perfusion as assessed by laser Doppler fluxmetry and digital temperature recordings with a resultant resolution of ischemic pain, numbness, and ulceration.
Voxel similarity measures for 3-D serial MR brain image registration.
We have evaluated eight different similarity measures used for rigid body registration of serial magnetic resonance (MR) brain scans. To assess their accuracy we used 33 clinical three-dimensional (3-D) serial MR images, with deformable extradural tissue excluded by manual segmentation and simulated 3-D MR images with added intensity distortion. For each measure we determined the consistency of registration transformations for both sets of segmented and unsegmented data. We have shown that of the eight measures tested, the ones based on joint entropy produced the best consistency. In particular, these measures seemed to be least sensitive to the presence of extradural tissue. For these data the difference in accuracy of these joint entropy measures, with or without brain segmentation, was within the threshold of visually detectable change in the difference images.
Anatomic and physiologic evaluation of upper extremity ischemia.
This study assessed the accuracy of arteriography and laser Doppler perfusion imaging (LDPI) as predictors of digital ischemia and correlated upper extremity symptoms, function, and nutritional flow with arteriographic and laser Doppler assessments. Multiple-level occlusive disease was documented in 25 hands (23 patients) by arteriography. LDPI demonstrated one or more hypoperfused digits in 17 hands. Patient questionnaires were used to assess upper extremity symptoms, pain, cold sensitivity, and function. Spearman correlation coefficients indicated that arteriography is a poor indicator of nutritional perfusion as measured by LDPI. Neither arteriography or laser Doppler perfusion imaging served as an indicator of the severity of cold intolerance. However, upper extremity symptoms and functional status correlated with both laser Doppler measurements and the level of cold sensitivity. Laser Doppler perfusion imaging and arteriographic analysis provide complimentary data in the evaluation of upper extremity ischemia.
Innervation density of the base of the palm.
Cutaneous nerves of the palm were localized and quantitated by longitudinal axis, proximity to the distal palmar crease, and tissue layer to identify an incision that would avoid injury to the palmar branches of cutaneous nerves. Cadaveric palms (n = 10) harvested en bloc were fixed at physiologic tension and prepared using the celloidin method and hematoxylin-eosin staining. The cutaneous nerves of the palm were counted and classified by their size and location within each tissue layer and longitudinal axis as well as by proximal, middle, and distal locations within each axis. The mean number of large nerves identified within regions of the palm differed by tissue layer and longitudinal axis but not by longitudinal location within axes. The long/ring finger web space was characterized by the lowest innervation density; the index/long finger web space and ring finger axis were characterized by the greatest innervation density. An incision in the long/ring finger web space 2 cm proximal to Kaplan's cardinal line should result in injury to fewer nerves and reduce the incidence of painful neuromas during open carpal tunnel release.
Cloning and expression of the ApaLI, NspI, NspHI, SacI, ScaI, and SapI restriction-modification systems in Escherichia coli.
The genes encoding the ApaLI (5'-GTGCAC-3'), NspI (5'-RCATGY-3'), NspHI (5'-RCATGY-3'), SacI (5'-GAGCTC-3'), SapI (5'-GCTCTTCN1-3', 5'-N4GAAGAGC-3') and ScaI (5'-AGTACT-3') restriction-modification systems have been cloned in E. coli. Amino acid sequence comparison of M.ApaLI, M.NspI, M.NspHI, and M.SacI with known methylases indicated that they contain the ten conserved motifs characteristic of C5 cytosine methylases. NspI and NspHI restriction-modification systems are highly homologous in amino acid sequence. The C-termini of the NspI and NlaIII (5'-CATG-3') restriction endonucleases share significant similarity. 5mC modification of the internal C in a SacI site renders it resistant to SacI digestion. External 5mC modification of a SacI site has no effect on SacI digestion. N4mC modification of the second base in the sequence 5'-GCTCTTC-3' blocks SapI digestion. N4mC modification of the other cytosines in the SapI site does not affect SapI digestion. N4mC modification of ScaI site blocks ScaI digetion. A DNA invertase homolog was found adjacent to the ApaLI restriction-modification system. A DNA transposase subunit homolog was found upstream of the SapI restriction endonuclease gene.
The effect of transdermal nicotine on digital perfusion in reformed habitual smokers.
The effects of transdermal nicotine-assisted smoking cessation on digital perfusion and health-related quality of life were assessed in 10 chronic smokers. Components of digital blood flow were evaluated by digital temperature and laser Doppler fluxmetry before, during, and after a standardized cold challenge. Nutritional flow was measured by vital capillaroscopy; a quantitative perfusion profile was obtained by laser Doppler perfusion imaging. A battery of validated measures were used to evaluate health-related quality of life. The microvascular response of smokers was evaluated before smoking cessation and at 2 and 7 days after smoking cessation and was compared with the response of nonsmoking controls. Results demonstrated that a (1) cutaneous microvascular perfusion was lower in smokers than nonsmokers, (2) the acute administration of transdermal nicotine did not decrease cutaneous perfusion, (3) smoking cessation and transdermal nicotine normalized digital microvascular perfusion by 7 days, and (4) transdermal nicotine and smoking cessation did not negatively impact health-related quality of life.
A method for the confirmation and identification of drugs of misuse in urine using solid phase extraction and gas-liquid chromatography with mass spectrometry.
A method is described for the confirmation/identification of a range of commonly misused drugs in urine samples. The method has been used for two years without problems for a range of purposes including hospital/clinic drugs of misuse screening and for toxicology in coroner's cases. Urine samples which have given a positive result on immunochemical screening for a particular drug group or groups (for example, opiates) can be processed with identification of the drugs present using a single procedure. Bond ElutCertify columns are used for the extraction of drugs from the samples followed by propionylation and gas chromatography with mass selective detection.
Twelve-year experience with Carpentier-Edwards PERIMOUNT pericardial valve in the mitral position: a multicenter study.
BACKGROUND AND AIMS OF THE STUDY: The study aim was to assess the durability of the Carpentier-Edwards PERIMOUNT pericardial bioprosthesis in the mitral position. METHODS: This seven-center retrospective clinical study involved the follow up of 333 patients who underwent isolated mitral valve replacement and 102 patients who underwent double (mitral and aortic) valve replacement with the PERIMOUNT pericardial valve between 1984 and 1989. Mean patient age at implant was 60.7 +/- 11.6 years; 41.1% were males. The most common etiology was rheumatic heart disease (53.9%) and the most common mechanism mitral insufficiency. All patients but six were followed for an average of 7.2 +/- 3.6 years after surgery; total follow up was 3071.7 patient-years (pt-yr). RESULTS: The total operative mortality rate was 7.6%; this included a valve-related mortality rate of 0.2%. The late mortality rate was 5.2% per pt-yr, of which 1.4% per pt-yr was considered valve-related. At 11 years, the overall actuarial survival rate was 53.3 +/- 2.8%, and actuarial freedom from valve-related death 83.9 +/- 2.6%. At follow up, 80% of patients were in NYHA class I or II, and 74% showed improvement. Twenty-eight incidences of deterioration requiring explant were observed. At 11 years the actuarial freedom from explant due to structural failure was 84.9 +/- 3.1%. Rates of structural failure decreased with age: the actuarial freedom from explant due to structural failure was 78.1 +/- 4.8% for patients aged < or = 60 years, 89.4 +/- 4.4% for those aged 61-70 years, and 100% for those aged over 71 years. CONCLUSION: The Carpentier-Edwards PERIMOUNT pericardial bioprosthesis is a reliable choice when a tissue valve is required, especially in patients over 60 years of age.
The Tsp45I restriction-modification system is plasmid-borne within its thermophilic host.
Thermus species YS45 harbors two small cryptic plasmids of 5.8 (pTsp45s) and approximately 12 kb (pTsp45I). Plasmid pTsp45s has been entirely sequenced, revealing three significant ORFs. In addition to a previously reported thermophilic plasmid-encoded replication protein (Rep), pTsp45s contains two genes for the Tsp45I methyltransferase (M.Tsp45I) and restriction endonuclease (Tsp45I). These two converging genes (tsp45IM and tsp45IR) overlap by 4 bp at their stop codons within an XbaI site. M.Tsp45I (413 aa, 47.0 kDa, recognizing 5'-GTSAC-3') is highly homologous to other m6A-methyltransferases, especially M.EcaI (recognizing 5'-GGTNACC-3'). Tsp45I (332 aa, 37.4 kDa, cleaving 5'-/GTSAC-3') is not homologous to M.Tsp45I, or to other restriction endonucleases. Recombinant Tsp45I is stably produced in E. coli, and cleaves DNA at 65 degrees C with the same specificity as the native enzyme. Therefore, the thermophilic Tsp45I restriction-modification system is plasmid-borne within its native host.
Probing the interactions of putidaredoxin with redox partners in camphor P450 5-monooxygenase by mutagenesis of surface residues.
The role of surface amino acid residues in the interaction of putidaredoxin (Pdx) with its redox partners in the cytochrome P450cam (CYP101) system was investigated by site-directed mutagenesis. The mutated Pdx genes were expressed in Escherichia coli, and the proteins were purified and studied in vitro. Activity of the complete reconstituted P450cam system was measured, and kinetic parameters were determined. Partial assays were also conducted to determine the effect of the mutations on interactions with each redox partner. Some mutations altered interactions of Pdx with one redox partner but not the other. Other mutations affected interactions with both redox partners, suggesting some overlap in the binding sites on Pdx for putidaredoxin reductase and CYP101. Cysteine 73 of Pdx was identified as important in the interaction of Pdx with putidaredoxin reductase, whereas aspartate 38 serves a critical role in the subunit binding and electron transfer to CYP101.
Development and validation of a computerized screening test for personality disorders in DSM-III-R.
The available self-report instruments designed to measure personality disorder (PD) are time-consuming to administer and/or score and can be impractical for routine clinical use. There is a need for a computerized method of personality assessment based on contemporary systems of classification. A computerized DSM-III-R-based questionnaire was developed and validated against the structured clinical interview for DSM-III-R Axis-II disorders on a sample of 60 subjects. The computerized test showed moderate validity as a diagnostic instrument (mean kappa coefficient = 0.47). With adjusted cut-off scores it was valid as a screening instrument (mean sensitivity = 0.87). Antisocial, borderline and avoidant PD scores were strongly correlated across measures and not subject to significant observer bias.
The effect of contusion and cryotherapy on skeletal muscle microcirculation.
OBJECTIVE: The most common treatment of soft tissue contusions is ice application (cryotherapy). The physiological basis for this therapy is assumed to be cold-mediated vasoconstriction resulting in decreased edema formation and a reduction in overall morbidity. This proposed mechanism has not been tested. The present research examined the hypothesis that cryotherapy following contusion is effective because it reduces microvascular perfusion and subsequent edema formation. EXPERIMENTAL DESIGN: The microcirculatory responses to contusion were studied with and without cryotherapy in a chronically instrumented rat model. Initial studies evaluated the immediate effects of cryotherapy on arteriolar and venular diameters and microvascular perfusion (using laser Doppler floxmetry). Variables were measured before and immediately after 20 minutes of cryotherapy. Two additional studies monitored the same microvascular parameters longitudinally in four sets of chronically instrumented animals. Groups of rats studied had contusion or sham contusion with ice treatment or no ice treatment. Measurements were performed repeatedly before and after treatment for 24 hours or 96 hours after contusion/sham contusion. RESULTS: The acute microvascular effects of cryotherapy were vasoconstriction and decreased perfusion. However, when cryotherapy was used as a treatment following contusion/sham contusion, there were no long-lasting microvascular effects of cryotherapy either in the presence or absence of contusion. CONCLUSIONS: These results indicate that cryotherapy of striated muscle following contusion does not reduce microvascular diameters or decrease microvascular perfusion. Alternate mechanisms of action for cryotherapy treatment need to be investigated.