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Biomedical subjects

K Potter

Publications and source records attributed to K Potter.

At least 19 recordsLinked to original sources

Design and assessment of a tissue-engineered model of human phalanges and a small joint.

OBJECTIVES: To develop models of human phalanges and small joints by suturing different cell-polymer constructs that are then implanted in athymic (nude) mice. DESIGN: Models consisted of bovine periosteum, cartilage, and/or tendon cells seeded onto biodegradable polymer scaffolds of either polyglycolic acid (PGA) or copolymers of PGA and poly-L-lactic acid (PLLA) or poly-epsilon-caprolactone (PCL) and PLLA. Constructs were fabricated to produce a distal phalanx, middle phalanx, or distal interphalangeal joint. SETTING AND SAMPLE POPULATION: Studies of more than 250 harvested implants were conducted at the Northeastern Ohio Universities College of Medicine. EXPERIMENTAL VARIABLE: Polymer scaffold, cell type, and implantation time were examined. OUTCOME MEASURE: Tissue-engineered specimens were characterized by histology, transmission electron microscopy, in situ hybridization, laser capture microdissection and qualitative and quantitative polymerase chain reaction analysis, magnetic resonance microscopy, and X-ray microtomography. RESULTS: Over periods to 60 weeks of implantation, constructs developed through vascularity from host mice; formed new cartilage, bone, and/or tendon; expressed characteristic genes of bovine origin, including type I, II and X collagen, osteopontin, aggrecan, biglycan, and bone sialoprotein; secreted corresponding proteins; responded to applied mechanical stimuli; and maintained shapes of human phalanges with small joints. CONCLUSION: Results give insight into construct processes of tissue regeneration and development and suggest more complete tissue-engineered cartilage, bone, and tendon models. These should have significant future scientific and clinical applications in medicine, including their use in plastic surgery, orthopaedics, craniofacial reconstruction, and teratology.

Animals↗

Radiosurgery planning supported by the GEMSS grid.

GEMSS (Grid Enabled Medical Simulation Services IST-2001-37153) is an EU project funded to provide a test bed for Grid-enabled health applications. Its purpose is evaluation of Grid computing in the health sector. The health context imposes particular constraints on Grid infrastructure design, and it is this that has driven the feature set of the middleware. In addition to security, the time critical nature of health applications is accommodated by a Quality of Service component, and support for a well defined business model is also included. This paper documents experience of a GEMSS compliant radiosurgery application running within the Medical Physics department at the Royal Hallamshire Hospital in the UK. An outline of the Grid-enabled RAPT radiosurgery application is presented and preliminary experience of its use in the hospital environment is reported. The performance of the software is compared against GammaPlan (an industry standard) and advantages/disadvantages are highlighted. The RAPT software relies on features of the GEMSS middleware that are integral to the success of this application, and together they provide a glimpse of an enabling technology that can impact upon patient management in the 21st century.

Decision Support Systems, Clinical↗

Is 'virtual histology' the next step after the 'virtual autopsy'? Magnetic resonance microscopy in forensic medicine.

AIM: The study aimed to validate magnetic resonance microscopy (MRM) studies of forensic tissue specimens (skin samples with electric injury patterns) against the results from routine histology. METHODS AND RESULTS: Computed tomography and magnetic resonance imaging are fast becoming important tools in clinical and forensic pathology. This study is the first forensic application of MRM to the analysis of electric injury patterns in human skin. Three-dimensional high-resolution MRM images of fixed skin specimens provided a complete 3D view of the damaged tissues at the site of an electric injury as well as in neighboring tissues, consistent with histologic findings. The image intensity of the dermal layer in T2-weighted MRM images was reduced in the central zone due to carbonization or coagulation necrosis and increased in the intermediate zone because of dermal edema. A subjacent blood vessel with an intravascular occlusion supports the hypothesis that current traveled through the vascular system before arcing to ground. CONCLUSION: High-resolution imaging offers a noninvasive alternative to conventional histology in forensic wound analysis and can be used to perform 3D virtual histology.

Adult↗

Pictorial review: MRI of chronic spinal cord injury.

Patients who have suffered a spinal cord injury and who demonstrate new or changing clinical features such as increasing myelopathy, ascending neurological level, pain or increasing muscle spasms may have developed a late complication such as post-traumatic syrinx. MRI is the investigation of choice for assessment of chronic spinal cord injury. The aim of this pictorial review is to illustrate the various late appearances of the injured spinal cord.

Atrophy↗

Cartilage calcification studied by proton nuclear magnetic resonance microscopy.

A three-dimensional (3D) mineralizing culture system using hollow fiber bioreactors has been developed to study the early stages of endochondral ossification by proton nuclear magnetic resonance (NMR) microscopy. Chondrocytes harvested from the cephalic half of the sterna from 17-day-old chick embryos were terminally differentiated with 33 nM of retinoic acid for 1 week and mineralization was initiated by the addition of 1% beta-glycerophosphate to the culture medium. Histological sections taken after 6 weeks of development in culture confirmed calcification of the cartilage matrix formed in bioreactors. Calcium to phosphorus ratios (1.62-1.68) from X-ray microanalysis supported electron diffraction of thin tissue sections showing the presence of a poorly crystalline hydroxyapatite mineral phase in the cultures. After 4 weeks of culture, quantitative proton NMR images showed water proton magnetization transfer rate constants (km) were higher in premineralized cartilage compared with uncalcified cartilage, a result suggesting collagen enrichment of the matrix. Notably after 5 weeks mineral deposits formed in bioreactors principally in the collagen-enriched zones of the cartilage with increased km values. This caused marked reductions in water proton longitudinal (T1) and transverse (T2) relaxation times and water diffusion coefficients (D). These results support the hypothesis that mineralization proceeds in association with a collagen template. After 6 weeks of culture development, the water proton T2 values decreased by 13% and D increased by 7% in uncalcified areas, compared with the same regions of tissue examined 1 week earlier. These changes could be attributed to the formation of small mineral inclusions in the cartilage, possibly mediated by matrix vesicles, which may play an important role in cartilage calcification. In summary, NMR images acquired before and after the onset of mineralization of the same tissue provide unique insights into the matrix events leading to endochondral mineral formation.

Animals↗

Imaging of collagen and proteoglycan in cartilage sections using Fourier transform infrared spectral imaging.

OBJECTIVE: To test the hypothesis that Fourier transform infrared (FTIR) spectral imaging, coupled with multivariate data processing techniques, can image the spatial distribution of matrix constituents in native and engineered cartilage samples. METHODS: Tissue sections from native and trypsin-digested bovine nasal cartilage (BNC) and from engineered cartilage, generated by chick sternal chondrocytes grown in a hollow fiber bioreactor, were placed either on calcium fluoride windows for FTIR analysis or gelatinized microscope slides for histologic analysis. Based on the assumption that cartilage is predominantly chondroitin sulfate (CS) and type II collagen, chemical images were extracted from FTIR spectral imaging data sets using 2 multivariate methods: the Euclidean distance algorithm and a least-squares approach. RESULTS: Least-squares analysis of the FTIR data of native BNC yielded a collagen content of 54 +/- 13% and a CS content of 37 +/- 16% (mean +/- SD). Euclidean distance analysis of measurements made on trypsin-digested BNC demonstrated only trace amounts of CS. For engineered cartilage, the CS content was significantly lower (15 +/- 5%), while the collagen content (73 +/- 6%) was significantly higher than biochemically determined values (CS 34%, collagen 5%, protein 61%). These differences are due to the fact that the dimethylmethylene blue assay overestimated the CS content of the tissue because it is not specific for CS, while the FTIR spectral imaging technique overestimated the collagen content because it lacks specificity for different proteins. CONCLUSION: FTIR spectral imaging combines histology-like spatial localization with the quantitative capability of bulk chemical analysis. For molecules with a unique spectral signature, such as CS, the FTIR technique coupled with multivariate analysis can define a unique spatial distribution. However, for some applications, the lack of specificity of this technique for different types of proteins may be a limitation.

Animals↗

The mental and physical health of female sex workers: a comparative study.

OBJECTIVES: The objective of this study was to compare the mental and physical health, adult abuse experiences and social networks of female sex workers with data previously collected from two large community samples of age-matched women. METHOD: A convenience sample of sex workers were interviewed and completed two well-established questionnaires, the General Health Questionnaire (GHQ-28) and the Intimate Bond Measure (IBM). Sex workers were invited to reflect on their experiences of their work. RESULTS: There were no differences in mental health on the GHQ-28 or in self-esteem (measured by an item on the Present State Examination) between the two groups. Neither were there any differences in their assessment of their physical health or the quality of their social networks. Sex workers were less likely to be married and had been exposed to more adult physical and sexual abuse than the comparison group. They were more likely to smoke and to drink heavily when they drank. One-third said that their general practitioner was not aware of their work. A subgroup not working with regular clients or in a massage parlour had higher GHQ-28 scores and may be an at-risk group. Narrative information about the work, particularly its intermittent nature, is presented. CONCLUSIONS: No evidence was found that sex work and increased adult psychiatric morbidity are inevitably associated, although there may be subgroups of workers with particular problems. The illegal and stigmatized nature of sex work are likely to make usual public health strategies more difficult to apply, considerations which should give concern from a preventive health standpoint.

Adolescent↗

Histomorphometry of the embryonic avian growth plate by proton nuclear magnetic resonance microscopy.

Quantitative nuclear magnetic resonance (NMR) microscopy was used to characterize the biochemical and morphological properties of the different zones within the growth plate of an embryonic chick femur. For precalcified tissue, water proton transverse relaxation times (T2) and magnetization transfer values (MT) were directly and inversely dependent, respectively, on tissue cellularity, defined as the intracellular area per unit area on histological sections. T2 values extrapolated for intra- and extracellular water were 96 ms and 46 ms, respectively. The extracellular T2 was comparable with that measured for mature cartilage. The MT values extrapolated for intra- and extracellular compartments were 0.32 and 0.85, respectively. These values were comparable with those values reported in the literature for cell pellets and for mature cartilage tissue. Thus, cellularity dominated the NMR properties of this immature cartilage tissue. Mineral deposits within calcified cartilage and periosteal bone invoked NMR relaxation processes that were dependent on the inorganic mineral phase. Additionally, collagen molecules present in mineralized zones gave rise to a significant MT effect. These results show the utility of water proton NMR microscopy for assessing both the organic and inorganic phases within mineralized tissues.

Animals↗

Response of engineered cartilage tissue to biochemical agents as studied by proton magnetic resonance microscopy.

OBJECTIVE: To test the hypothesis that magnetic resonance imaging (MRI) results correlate with the biochemical composition of cartilage matrix and can therefore be used to evaluate natural tissue development and the effects of biologic interventions. METHODS: Chondrocytes harvested from day-16 chick embryo sterna were inoculated into an MRI-compatible hollow-fiber bioreactor. The tissue that formed over a period of 2-4 weeks was studied biochemically, histologically, and with MRI. Besides natural development, the response of the tissue to administration of retinoic acid, interleukin-1beta (IL-1beta), and daily dosing with ascorbic acid was studied. RESULTS: Tissue wet and dry weight, glycosaminoglycan (GAG) content, and collagen content all increased with development time, while tissue hydration decreased. The administration of retinoic acid resulted in a significant reduction in tissue wet weight, proteoglycan content, and cell number and an increase in hydration as compared with controls. Daily dosing with ascorbic acid increased tissue collagen content significantly compared with controls, while the administration of IL-1beta resulted in increased proteoglycan content. The water proton longitudinal and transverse relaxation rates correlated well with GAG and collagen concentrations of the matrix as well as with tissue hydration. In contrast, the magnetization transfer value for the tissue correlated only with total collagen. Finally, the self-diffusion coefficient of water correlated with tissue hydration. CONCLUSION: Parameters derived from MR images obtained noninvasively can be used to quantitatively assess the composition of cartilage tissue generated in a bioreactor. We conclude that MRI is a promising modality for the assessment of certain biochemical properties of cartilage in a wide variety of settings.

Animals↗

Vascular surgical society of great britain and ireland: review of out-of-hours vascular procedures in a tertiary vascular unit

BACKGROUND: The aim of this study was to review out-of-hours vascular procedures in a tertiary vascular unit. METHODS: The vascular emergencies that presented outside normal working hours (17. 00 to 08.00 hours) in a vascular unit between January and June 1998 were reviewed. Only cases considered to be life or limb threatening and requiring urgent surgical or radiological intervention were assessed. RESULTS: The Table shows that a significant number of vascular emergencies was performed out of hours in one unit. This was, in part, due to an increase in the number of tertiary referrals, which represented 57 per cent of all emergency procedures. Reasons for the tertiary referrals were: no consultant vascular surgeon on call (33 per cent), no consultant interventional radiologist on call (26 per cent), lack of intensive care beds (30 per cent) and complex procedure (11 per cent). The overall mortality rate of patients referred in this period was 15 per cent. The unit has three consultant vascular surgeons, two consultant interventional radio- logists and one vascular specialist registrar. CONCLUSION: The significant increase in out-of-hours vascular emergencies, both surgical and radiological, has placed an enormous demand on senior members of the team. In addition, it has had a significant impact on the unit's elective admissions and waiting lists, in particular those for routine general surgery. To support the growth in complex emergency referrals, senior vascular fellows in both vascular surgery and radiology have been appointed and proposals are underway to restructure local vascular services.

Journal Article↗

Early developmental experiences of female sex workers: a comparative study.

OBJECTIVE: The aim of this paper is to explore the early family environment of a sample of female sex workers and compare the findings with a large community data set of similarly aged women. METHOD: Sex workers recruited by a snowball method were given a semi-structured interview, which included the Parental Bonding Instrument. These results were compared to those from the Otago Women's Child Sexual Abuse (OWCSA) study. RESULTS: The sex workers' families were of lower socioeconomic status and had experienced more parental separation than had the OWCSA families. The mothers of sex workers were more frequently the family's main wage earner. Sex workers described both parents as less caring than did the OWCSA women. They were significantly more likely than the OWCSA women to report childhood sexual abuse. The sex workers were more likely to have left home early, to have become pregnant before the age of 19 years and to not have completed tertiary study. CONCLUSIONS: The sex workers studied came from families with more interpersonal difficulties during childhood and adolescence than did a control community sample of similarly aged women. The relevance and generalisability of this conclusion to the wider sex worker population is difficult to determine, given the non-random selection of this sex worker sample.

Adolescent↗

Mycosis fungoides in a horse.

A 17-year-old Quarter Horse mare was examined to determine the cause of a vulvar mass. Differential diagnoses for the swollen, ulcerated tissue included hypersensitivity reaction to insect stings or bites and cutaneous neoplasia. During the next 4 months, the mass enlarged involving the skin of the perineum and ventral aspect of the abdomen with secondary dependent edema of both hind limbs. Histologic examination of biopsy and necropsy specimens revealed changes consistent with a diagnosis of mycosis fungoides (cutaneous T-cell lymphoma). Diagnostic features included invasion of neoplastic lymphocytes into the epidermis and detection of T-cell lineage of neoplastic cells. Location of lesions at a mucocutaneous junction, association with epidermal ulcers, and progressive skin involvement mimic the condition in human beings and other species. Prognosis is poor when the condition is at the tumor stage (invasion of deep tissues).

Abdomen↗

Somatic hypermutation introduces insertions and deletions into immunoglobulin V genes.

During a germinal center reaction, random mutations are introduced into immunoglobulin V genes to increase the affinity of antibody molecules and to further diversify the B cell repertoire. Antigen-directed selection of B cell clones that generate high affinity surface Ig results in the affinity maturation of the antibody response. The mutations of Ig genes are typically basepair substitutions, although DNA insertions and deletions have been reported to occur at a low frequency. In this study, we describe five insertion and four deletion events in otherwise somatically mutated VH gene cDNA molecules. Two of these insertions and all four deletions were obtained through the sequencing of 395 cDNA clones (approximately 110,000 nucleotides) from CD38+IgD- germinal center, and CD38-IgD- memory B cell populations from a single human tonsil. No germline genes that could have encoded these six cDNA clones were found after an extensive characterization of the genomic VH4 repertoire of the tonsil donor. These six insertions or deletions and three additional insertion events isolated from other sources occurred as triplets or multiples thereof, leaving the transcripts in frame. Additionally, 8 of 9 of these events occurred in the CDR1 or CDR2, following a pattern consistent with selection, and making it unlikely that these events were artifacts of the experimental system. The lack of similar instances in unmutated IgD+CD38- follicular mantle cDNA clones statistically associates these events to the somatic hypermutation process (P = 0.014). Close scrutiny of the 9 insertion/deletion events reported here, and of 25 additional insertions or deletions collected from the literature, suggest that secondary structural elements in the DNA sequences capable of producing loop intermediates may be a prerequisite in most instances. Furthermore, these events most frequently involve sequence motifs resembling known intrinsic hotspots of somatic hypermutation. These insertion/deletion events are consistent with models of somatic hypermutation involving an unstable polymerase enzyme complex lacking proofreading capabilities, and suggest a downregulation or alteration of DNA repair at the V locus during the hypermutation process.

Amino Acid Sequence↗

Cartilage formation in a hollow fiber bioreactor studied by proton magnetic resonance microscopy.

The ideal in vitro system for investigating the regulation of cartilage formation and maintenance would allow for three-dimensional tissue growth, a wide range of biochemical interventions, and non-destructive evaluation. We have developed a hollow fiber bioreactor (HFBR) system which meets these criteria. After injection with embryonic chick sternal chondrocytes, neocartilage is elaborated around the hollow fibers, reaching a thickness of up to a millimeter after four weeks of growth. This process was monitored over time with nuclear magnetic resonance (NMR) microimaging and correlative biochemical and histologic analyses. Tissue volume and cellularity increased greatly during development. This was accompanied by changes in magnetic resonance properties consistent with increased macromolecular content. Further, tissue heterogeneity, observed as regional variations in cell size in histologic sections, was also observed in quantitative NMR images.

Animals↗

Magnetic resonance microscopy studies of cation diffusion in cartilage.

The diffusion of copper ions in bovine nasal cartilage (BNC), a dense connective tissue, was investigated to further the understanding of ion transport in charged biopolymer systems. Using an inversion-recovery null-point imaging technique, it was found that the diffusion rate of divalent copper ions into cartilage was significantly lower in normal BNC than in BNC in which the matrix fixed charges had been reduced by enzymatic digestion or acid neutralization. In normal cartilage, counterion diffusion was not well described by a simple Fickian process, likely owing to the high charge density of the constituent molecules. In contrast, in both digested and acid neutralized BNC, counterion diffusion appeared Fickian. Features of the ion transport process were modeled using a diffusion equation which included a linear sorption term to account for cation binding. The diffusion coefficient of copper in cartilage increased with decreasing matrix fixed charge and was constant for reservoir concentrations up to 30 mM. The activation energy for the diffusion of copper into BNC was determined to be 34.5 kJ/mol.

Animals↗

Evaluation of potential sources of bias in a genetic epidemiologic study of breast cancer.

Systematic errors, or bias, can arise at several stages of a study, including selection of subjects, measurement of exposure and disease, and data analysis. Little attention appears to have been paid to potential sources of bias in genetic epidemiologic studies, despite the fact that the study of units (families) and members (relatives) within those units produces unique opportunities for bias to be introduced. The ability to evaluate whether selection bias has occurred is rare. In 1944, a case-control family study of breast cancer was initiated at the Dight Institute for Human Genetics at the University of Minnesota. A follow-up study of these 544 families is currently being conducted on sisters, daughters, nieces, and granddaughters of the probands, and a control group of women who are spouses of male first- and second-degree relatives. Updated data are collected on females who are 18 years or older through telephone interviews and questionnaires. The availability of detailed family history information on these families at baseline provided an opportunity to evaluate several potential sources of bias. Analyses were performed to determine if families lost to follow-up differed from those who were successfully located or excluded (ineligible), and whether participation rates within a family differed by relationship to proband, age, and family history of cancer. The latter participation rates for individuals were examined with respect to a telephone interview, a mailed questionnaire, and screening mammography. There were no statistically significant differences in the cancer histories of families that were excluded, those that were lost to follow-up, and those that participated. Within families, degree of relationship to the breast cancer proband was significantly associated with age-adjusted participation rates on mailed questionnaires (P < 0.005) and mammography (P < 0.005), but not telephone interviews (P = 0.29). After adjustment for age, marry-ins with a family history of breast cancer were not significantly more likely than marry-ins without a family history to undergo mammography (P = 0.11) or return mailed questionnaires (P = 0.74). Although non-participation is a potentially serious source of bias to a genetic epidemiologic study and the effect of variable participation rates should be explored when investigating the genetic component of a disease, it does not appear to be a problem for this particular study.

Adolescent↗