PubMed Health⌕ Search

Biomedical subjects

J Cobb

Publications and source records attributed to J Cobb.

At least 19 recordsLinked to original sources
PubMed2006

Hands-on robotic unicompartmental knee replacement: a prospective, randomised controlled study of the acrobot system.

We performed a prospective, randomised controlled trial of unicompartmental knee arthroplasty comparing the performance of the Acrobot system with conventional surgery. A total of 27 patients (28 knees) awaiting unicompartmental knee arthroplasty were randomly allocated to have the operation performed conventionally or with the assistance of the Acrobot. The primary outcome measurement was the angle of tibiofemoral alignment in the coronal plane, measured by CT. Other secondary parameters were evaluated and are reported. All of the Acrobot group had tibiofemoral alignment in the coronal plane within 2 degrees of the planned position, while only 40% of the conventional group achieved this level of accuracy. While the operations took longer, no adverse effects were noted, and there was a trend towards improvement in performance with increasing accuracy based on the Western Ontario and McMaster Universities Osteoarthritis Index and American Knee Society scores at six weeks and three months. The Acrobot device allows the surgeon to reproduce a pre-operative plan more reliably than is possible using conventional techniques which may have clinical advantages.

Aged↗
PubMed2004

Pain in the well-fixed, aseptic titanium hip replacement. The role of corrosion.

We have investigated nine patients with cemented Furlong (JRI, London, UK) titanium hip replacements who presented with early pain despite a well-fixed, aseptic prosthesis. All were followed up clinically and radiologically at regular intervals. Pain was located in the thigh and was worse at night. Radiographs showed cortical hypertrophy of the femur around the tip of the stem. Eight of the nine patients subsequently required single-stage revision using an uncemented prosthesis, which relieved the pain. At revision, the pH of the tip of the stem was found to be highly acidic with macroscopic evidence of corrosion consisting of multiple layers of titanium oxides when studied by X-ray dispersive analysis. Cemented titanium implants have a potential for crevice corrosion leading to cortical hypertrophy and intractable pain.

Aged↗
PubMed2003

Single center experience of a new intensive induction therapy for ewing's family of tumors: feasibility, toxicity, and stem cell mobilization properties.

PURPOSE: To examine the feasibility, tolerability, and toxicity of an intensified induction regimen (vincristine, ifosfamide, doxorubicin, and etoposide [VIDE]) in patients with newly diagnosed Ewing's family of tumors (EFT); to assess ability to maintain dose-intensity, and predictability of peripheral-blood stem cell mobilization. PATIENTS AND METHODS: Thirty patients were treated with vincristine 1.4 mg/m2 (maximum 2 mg) on day 1, doxorubicin 20 mg/m2, ifosfamide 3 g/m2 plus mesna and etoposide 150 mg/m2 on days 1 to 3. Cycles were given every 21 days for up to six cycles. RESULTS: One-hundred and seventy cycles of VIDE were given. The median treatment interval was 21 days (21 to 42) and nadir count: hemoglobin 8.3 (6.3 to 11.9), neutrophils 0.045 (0.0 to 2.1), and platelets 45 (3 to 343). There were 96 episodes of infection requiring hospitalization (56%). Growth factor support reduced infectious complications by 34%. Etoposide dose was reduced, or omitted, in 24% of cycles. Four patients did not complete six cycles due to unacceptable toxicity and one patient progressed on treatment. Twenty patients underwent peripheral-blood stem cell harvesting, 15 after cycle 3, and five after cycle 4. Median CD34+ yield was 4.6 x 106/kg per patient (1.8 to 14.5). Overall response to treatment, measured in 24 patients, was 88%. Seven of 11 patients undergoing surgery achieved greater than 90% necrosis of tumor (64%). CONCLUSION: VIDE is an effective induction regimen with substantial but acceptable toxicity that allows predictable mobilization of stem cells. Maintenance of dose-intensity is feasible in the majority of patients. Growth factors play a role in maintaining dose-intensity and reduce infectious complications.

Adolescent↗
PubMed2002

Noninvasive measurement techniques for monitoring of microvascular function in the diabetic foot.

There are, currently, 3 established clinical techniques routinely employed to determine the risk of ulceration in the diabetic foot. These are assessment of the circulation, the nervous control of sensation, and foot sensitivity to loading. Macrovascular measurements are used to assess sufficiency of the arterial supply to the foot. Evaluation of somatic neuropathy provides an indication of loss of plantar sensation. Skin pressure measurements indicate abnormalities in plantar loading. This combined approach is effective in allowing preventative measures to be applied prior to the onset of ulceration. In contrast, clinical measurement of microvascular function in the diabetic foot is uncommon. Indeed, there remains uncertainty regarding the importance of micro-vascular complications in the development of foot ulcers. This is in part due to the difficulty of making in vivo measurements of microvascular function. This article evaluates 3 noninvasive measurement techniques for routine microvascular assessment of the diabetic foot: transcutaneous oxygen tension, laser Doppler flowmetry, and near-infrared spectroscopy. These techniques can be used to obtain useful parameters of microvascular function including surface oxygen,blood flow, intracellular oxygenation, and cellular respiration. In principle, such measurements can be related to underlying pathophysiology, for example, microangiopathy or autonomic neuropathy. This article considers how these general techniques can be adapted to support routine clinical measurement of microvascular function, particularly in the neuropathic diabetic foot.

Journal Article↗
PubMed2001

Cranial neural crest cells contribute to connective tissue in cranial muscles in the anuran amphibian, Bombina orientalis.

The contribution of cranial neural crest cells to the development and patterning of cranial muscles in amphibians was investigated in the phylogenetically basal and morphologically generalized frog, Bombina orientalis. Experimental methods included fluorescent marking of premigratory cranial neural crest and extirpation of individual migratory streams. Neural crest cells contributed to the connective tissue component, but not the myofibers, of many larval muscles within the first two branchial arches (mandibular and hyoid), and complex changes in muscle patterning followed neural crest extirpation. Connective tissue components of individual muscles of either arch originate from the particular crest migratory stream that is associated with that arch, and this relationship is maintained regardless of the segmental identity-or embryonic derivation-of associated skeletal components. These developmental relations define a pattern of segmentation in the head of larval anurans that is similar to that previously described in the domestic chicken, the only vertebrate that has been thoroughly investigated in this respect. The fundamental role of the neural crest in patterning skeleton and musculature may represent a primitive feature of cranial development in vertebrates. Moreover, the corresponding developmental processes and cell fates appear to be conserved even when major evolutionary innovations-such as the novel cartilages and muscles of anuran larvae-result in major differences in cranial form.

Animals↗
PubMed2001

The first clinical application of a "hands-on" robotic knee surgery system.

The performance of a novel "hands-on" robotic system for total knee replacement (TKR) surgery is evaluated. An integrated robotic system for accurately machining the bone surfaces in TKR surgery is described. Details of the system, comprising an "active constraint" robot, called Acrobot, a "gross positioning" robot, and patient clamps, are provided. The intraoperative protocol and the preoperative, CT-based, planning system are also described. A number of anatomical registration and cutting trials, using plastic bones, are described, followed by results from two preliminary clinical trials, which demonstrate the accuracy achieved in the anatomical registration. Finally, the first clinical trial is described, in which the results of the anatomical registration and bone cutting are seen to be of high quality. The Acrobot system has been successfully used to accurately register and cut the knee bones in TKR surgery. This demonstrates the great potential of a "hands-on" robot for improving accuracy and increasing safety in surgery.

Arthroplasty, Replacement, Knee↗
PubMed2001

Malignant transformation in synovial chondromatosis of the knee?

Although it has been reported, malignant transformation of synovial chondromatosis is rare. We report a case of malignant transformation of synovial chondromatosis in a knee to a low-grade chondrosarcoma, which was treated with synovial excision and total knee replacement. We also present a literature review of the subject. The case illustrates that malignant transformation should be suspected in chronic cases with a sudden exacerbation of symptoms and that interpretation of histology in cartilage lesions is difficult. It also demonstrates that even when guided biopsy techniques are used, the sampling error of a needle biopsy in any large lesion is unavoidable.

Bone Neoplasms↗
PubMed2001

An in-shoe laser Doppler sensor for assessing plantar blood flow in the diabetic foot.

Increased pressure due, to sensory neuropathy, is important in the development of plantar ulceration in type II diabetes. However, additional factors are thought to pre-dispose the skin tissue to ulceration. Autonomic neuropathy and microangiopathy are the basis for the capillary steal theory and the haemodynamic hypothesis, developed to explain the aetiology of this type of ulcer, in terms of microvascular complications. The aim of the present study was to develop a system to allow assessment of blood flow at prevalent sites of ulceration. Previous studies have been limited to assessment of the bare foot under rest conditions. The new system allows measurements to be made in-shoe, during static and dynamic loading. The system comprises a laser Doppler sensor, a load sensor, measurement shoe, instrumentation and analysis software. The measurement shoe was designed to minimise movement artefact and provide thermal insulation for the foot. A simple flow rig was used to characterise the sensor. The blood flux response was linear (<5% deviation from ideal) for particle concentrations up to 0.25% and for mean particle velocities up to 8mm s(-1). The worst case drift in the response over a six-month period was 3.7%. Device to device repeatability varied by 12.5% over five devices.

Artifacts↗
PubMed2001

Evidence for meiotic spindle checkpoint from analysis of spermatocytes from Robertsonian-chromosome heterozygous mice.

Mice heterozygous for Robertsonian centric fusion chromosomal translocations frequently produce aneuploid sperm. In this study RBJ/Dn x C57BL/6J F1 males, heterozygous for four Robertsonian translocations (2N=36), were analyzed to determine effects on germ cells of error during meiosis. Analysis of sperm by three color fluorescence in situ hybridization revealed significantly elevated aneuploidy, thus validating Robertsonian heterozygous mice as a model for production of chromosomally abnormal gametes. Primary spermatocytes from heterozygous males exhibited abnormalities of chromosome pairing in meiotic prophase and metaphase. In spite of prophase abnormalities, the prophase/metaphase transition occurred. However, an increased frequency of cells with misaligned condensed chromosomes was observed. Cytological analysis of both young and adult heterozygous mice revealed increased apoptosis in spermatocytes during meiotic metaphase I. Metaphase spermatocytes with misaligned chromosomes accounted for a significant proportion of the apoptotic spermatocytes, suggesting that a checkpoint process identifies aberrant meioses. Immunofluorescence staining revealed that kinetochores of chromosomes that failed to align on the spindle stained more intensely for kinetochore antigens CENP-E and CENP-F than did aligned chromosomes. Taken together, these observations are consistent with detection of malattached chromosomes by a meiotic spindle checkpoint mechanism that monitors attachment and/or congression of homologous chromosome pairs. However, the relatively high frequency of gametic aneuploidy suggests that the checkpoint mechanism does not efficiently eliminate all germ cells with chromosomal abnormalities.

Aneuploidy↗
PubMed2001

Development of an odorant emission model for sewage treatment works.

In the field of odour assessment, much attention has been paid to the measurement of odour concentration. Whilst the concentration of an odour at a receptor is a useful indicator of annoyance, the concentration at the source tells only half the story. The emission rate - the product of odour concentration and air flow rate - is required to appreciate the significance of odour sources. Knowledge of emission rates allows odour sources to be ranked in terms of significance and facilitates appropriate selection and design of odour control units. The emission rate is also a key input for atmospheric dispersion models. Given the increasing importance of odour to sewage treatment works operators, there is a clear need for predictive methods for odour emission rates. Theory suggests that the emission of odorants from sewage to air is controlled by mass transfer resistances in both the gas and liquid phase. These are in turn controlled by odorant and emission source characteristics. The required odorant characteristics are largely known, and mass transfer from many different types of emission sources have been studied. Sewage treatment processes can be described by one or more of six characteristic emission sources, these being quiescent surfaces, channels, weirs and drop structures, diffused aeration, surface aeration and flow over media. This paper describes the development of odorant mass transfer models for these characteristic emission types. The models have been applied in the form of spreadsheet models to the prediction of H2S emissions and the results compared with commercial VOC emission models.

Air Movements↗
PubMed2000

RADARx: Recognizing, Assessing, and Documenting Adverse Rx events.

BACKGROUND: Adverse events are a leading cause of morbidity and mortality. Adverse Drug Events (ADEs) are frequent, under-reported, costly, and largely preventable. Computerized tools expose effectively ADEs and can reduce their impact. METHODS: RADARx is a Veterans Administration (VA) VistA-compatible M software program that integrates computerized ADE screening, probability assessment, documentation, and reporting capabilities. Data dictionary mapping tools have enabled RADARx implementation at 3 sites. All RADARx alerts generated at VA Medical Center (VAMC) Nashville from 7/1/99 to 9/30/99 were evaluated. RESULTS: Total ADEs documented using RADARx numbered 57. RADARx discovered 34 ADEs and 48 'potential' ADEs; 23 ADEs were found using traditional means. Overall, 11% of RADARx alerts were true positives. Pharmacist review of the 8-20 alerts generated daily costs between 10 and 30 minutes.

Adverse Drug Reaction Reporting Systems↗
PubMed1999

What are the spermatocyte's requirements for successful meiotic division?

The consequences of error during meiotic division in spermatogenesis can be serious: aneuploid spermatozoa, embryonic lethality, and developmental abnormalities. Recombination between homologs is essential to ensure normal segregation; thus the spermatocyte must time division precisely so that it occurs after recombination between chromosomes and accumulation of the cell-cycle machinery necessary to ensure an accurate segregation of chromosomes. We use two systems to investigate meiotic division during spermatogenesis in the mouse: pharmacological induction of meiotic metaphase in cultured spermatocytes and transillumination-mediated dissection of stage XII seminiferous tubule segments to monitor progress through the division phase. By these approaches we can assess timing of acquisition of competence for the meiotic division phase and the temporal order of events as division proceeds. Competence for the meiotic division arises in the mid-pachytene stage of meiotic prophase, after chromosomes have synapsed and coincident with the accumulation of the cell-cycle regulatory protein CDC25C. The activity of both MPF and topoisomerase II are required. The earliest hallmarks of the division phase are nuclear envelope breakdown, followed by phosphorylation of histone H3 and chromosome condensation. These events are likely to be monitored by checkpoint mechanisms since checkpoint proteins can be localized in nuclei and DNA-damaging agents delay entry into the meiotic division phase. Understanding how the spermatocyte regulates its entry into the meiotic division phase can help clarify the natural mechanisms ensuring accurate chromosome segregation and preventing aneuploidy. J. Exp. Zool. (Mol. Dev. Evol.) 285:243-250, 1999.

Animals↗
PubMed1999

Acquisition of competence to condense metaphase I chromosomes during spermatogenesis.

Little is known about the timing of meiotic prophase events during spermatogenesis in the mouse or how these events are related to cell-cycle progression. This work was designed to test hypotheses about the timing and biochemical correlates of developmental acquisition of competence to condense bivalent pairs of homologous chromosomes held together by chiasmata. The experimental approach takes advantage of the fact that okadaic acid (OA) treatment of pachytene spermatocytes causes precocious entry into metaphase I (MI) of meiosis. Leptotene and zygotene (L/Z) spermatocytes are not competent to respond to OA with condensation of chiasmate bivalent chromosomes. Competence for MI condensation of chiasmate bivalents is acquired by the middle of the pachytene stage of meiotic prophase, several days after homologous chromosomes become fully synapsed. The acquisition of MI competence is paralleled by the accumulation of histone H1t in the nuclei of mid-pachytene spermatocytes. Biochemical differences also exist between the incompetent L/Z spermatocytes and the competent pachytene spermatocytes. Both have the molecular components of metaphase promoting factor, CDC2 and CYCLIN B1; however, the histone H1 kinase activity of metaphase promoting factor of incompetent L/Z spermatocytes is not activated by OA, as it is in competent pachytene spermatocytes. Additionally, the CDC25C protein phosphatase is present in competent pachytene spermatocytes, but not in incompetent L/Z or early pachytene spermatocytes. Both incompetent and competent spermatocytes accumulate MPM-2 phosphoepitopes and phosphorylated histone H3 in response to OA treatment, indicating that presence of these antigens is not sufficient to promote condensation of meiotic chromosomes. These data demonstrate that meiotic competence of spermatocytes is acquired after homologous chromosome pairing is established and is coincident with first appearance of histone H1t and CDC25C protein phosphatase in spermatocytes.

Animals↗
PubMed1999

Meiotic events at the centromeric heterochromatin: histone H3 phosphorylation, topoisomerase II alpha localization and chromosome condensation.

Mechanisms of chromosome condensation and segregation during the first meiotic division are not well understood. Resolution of recombination events to form chiasmata is important, for it is chiasmata that hold homologous chromosomes together for their oppositional orientation on the meiotic metaphase spindle, thus ensuring their accurate segregation during anaphase I. Events at the centromere are also important in bringing about proper attachment to the spindle apparatus. This study was designed to correlate the presence and activity of two proteins at the centromeric heterochromatin, topoisomerase II alpha (TOP2A) and histone H3, with the processes of chromosome condensation and individualization of chiasmate bivalents in murine spermatocytes. We tested the hypothesis that phosphorylation of histone H3 is a key event instigating localization of TOP2A to the centromeric heterochromatin and condensation of chromosomes as spermatocytes exit prophase and progress to metaphase. Activity of topoisomerase II is required for condensation of chromatin at the end of meiotic prophase. Histone H3 becomes phosphorylated at the end of prophase, beginning with its phosphorylation at the centromeric heterochromatin in the diplotene stage. However, it cannot be involved in localization of TOP2A, since TOP2A is localized to the centromeric heterochromatin throughout most of meiotic prophase. This observation suggests a meiotic function for TOP2A in addition to its role in chromatin condensation. The use of kinase inhibitors demonstrates that phosphorylation of histone H3 can be uncoupled from meiotic chromosome condensation; therefore other proteins, such as those constituting metaphase-promoting factor, must be involved. These results define the timing of important meiotic events at the centromeric heterochromatin and provide insight into mechanisms of chromosome condensation for meiotic metaphase.

Animals↗
PubMed1999

Non-alcoholic steatohepatitis and iron: increased prevalence of mutations of the HFE gene in non-alcoholic steatohepatitis.

BACKGROUND/AIMS: Non-alcoholic steatohepatitis (NASH) is increasingly recognized, and its pathogenesis is believed to involve increased oxidative stress. Elevated levels of serum ferritin and positive liver iron stains are often observed in patients with NASH, and the pathogenesis of liver injury due to iron is also thought to involve oxidative stress. The aim of this study was to determine whether there is an association of NASH and mutations in the HFE gene associated with hereditary hemochromatosis (HHC). METHODS: Clinical, laboratory, and histopathological data on all 57 subjects with a final diagnosis of NASH seen between August 1990 and August 1997 at our Liver Center were analyzed. Thirty-six Caucasian subjects (23 men) with NASH underwent mutational analyses of HFE gene mutations performed. The prevalence of HFE gene mutations was compared to that in 348 Caucasian normal controls. Data were analyzed by both parameteric and non-parametric methods with similar results. RESULTS: One subject (2.8%) with NASH was homozygous for the C282Y mutation and six (16.7%) were heterozygous, compared with 0%, and 11.2%, respectively, of controls. Two (5.6%) subjects with NASH were homozygous for the H63D mutation and 16 (44.4%) were heterozygous, whereas 2.9% and 26.4%, respectively, of controls had these genotypes. The prevalence of heterozygosity (61.1%) for either mutation was significantly higher in subjects with NASH than in controls (38%) (p = 0.008), and the prevalence of homozygosity or heterozygosity combined in NASH subjects (69.4%) was significantly higher than for controls (40.5%, p = 0.001). Sex (63-67% male) and age at diagnosis of NASH did not differ between those with or without HFE mutations, but men with NASH were significantly more likely than women to have the H63D mutation (15/23 vs. 3/13, p<0.05) Levels of serum ferritin, iron, transferrin saturation levels, and the degree of hepatic iron staining were significantly higher (p<0.05) in subjects with NASH who carried an HFE mutation than in those without. Differences in hepatic iron concentrations or hepatic iron indices between NASH subjects with and without HFE mutations were not significant. Those with C282Y mutations had significantly more hepatic fibrosis than those without (p<0.05). Those with HFE mutations had significantly higher levels of serum ALT (90+/-11 [mean +/- SE]) than those without (55+/-6; p = 0.02). CONCLUSION: The prevalences of the HFE gene mutations associated with hereditary hemochromatosis are increased among North American subjects with NASH.

Adult↗
PubMed1999

TP53 overexpression in radiation-induced osteosarcoma of the rabbit mandible.

The objective of this study was to investigate the incidence of overexpression of TP53 (formerly known as p53) in osteosarcomas occurring after treatment of rabbit mandibles with high-dose external-beam radiation. As part of a protocol investigating hyperbaric oxygen treatment for osteoradionecrosis, 102 female New Zealand-White rabbits underwent mandibular radiation treatments with a total dose of 64 Gy in 20 treatment fractions. Twelve animals died during irradiation, leaving 90 animals at risk for tumor development. These animals were divided into one control group and 12 other groups each treated with different schedules of postirradiation hyperbaric oxygen. All animals were sacrificed after the hyperbaric oxygen treatment, approximately 8 months after completion of irradiation. Seventeen of the 90 animals that survived after irradiation developed high-grade osteosarcomas, for a 19% incidence of malignancy. Tumor sizes ranged from 1-4 cm. Immunohistochemistry staining of the 17 tumors detected a 59% overall incidence of TP53 overexpression. There was no correlation between the intensity of hyperbaric oxygen treatment and development of osteosarcoma. The high incidence and short interval of development of osteosarcoma suggest that the study animals may have had a genetic predisposition to radiation-induced osteosarcoma. Additionally, our data provide further evidence that TP53 mutations may play an important role in radiation-induced osteosarcoma.

Animals↗
PubMed1998

Identification of morc (microrchidia), a mutation that results in arrest of spermatogenesis at an early meiotic stage in the mouse.

The microrchidia, or morc, autosomal recessive mutation results in the arrest of spermatogenesis early in prophase I of meiosis. The morc mutation arose spontaneously during the development of a mouse strain transgenic for a tyrosinase cDNA construct. Morc -/- males are infertile and have grossly reduced testicular mass, whereas -/- females are normal, indicating that the Morc gene acts specifically during male gametogenesis. Immunofluorescence to synaptonemal complex antigens demonstrated that -/- male germ cells enter meiosis but fail to progress beyond zygotene or leptotene stage. An apoptosis assay revealed massive numbers of cells undergoing apoptosis in testes of -/- mice. No other abnormal phenotype was observed in mutant animals, with the exception of eye pigmentation caused by transgene expression in the retina. Spermatogenesis is normal in +/- males, despite significant transgene expression in germ cells. Genomic analysis of -/- animals indicates the presence of a deletion adjacent to the transgene. Identification of the gene inactivated by the transgene insertion may define a novel biochemical pathway involved in mammalian germ cell development and meiosis.

Animals↗