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Biomedical subjects

M Kaufman

Publications and source records attributed to M Kaufman.

At least 19 recordsLinked to original sources
PubMed2006

Post-Peninsular War activities of Sir James McGrigor (1771-1858), Wellington's Director-General of the Army Medical Department.

James McGrigor (1771-1858) entered the Army Medical Department in September 1793, when he purchased a Surgeoncy in De Burgh's regiment. He transferred to the Blues (the Royal Horse Guards) in 1804 and shortly afterwards his organizational skills were recognized by the Duke of York. In 1811, he recommended McGrigor to Wellington, who commanded the British Forces in the Peninsula, and McGrigor joined Wellington in January 1812. As a result of his outstanding achievements during the Peninsular War, McGrigor was knighted in 1814. He later played a critical role in the post-Peninsular War Army by elevating the academic standard of the intake of medical officers as well as improving the standard of those who wished to gain promotion in the service. He established an extensive Anatomy, Pathology and Natural History Museum and the reference library at Fort Pitt at Chatham in Kent. He retired at the beginning of 1851, and died in London in April 1858, aged 87. In 1863, the museum collections were moved initially to the Army Medical School at Netley. At a later date these collections were dispersed and their present whereabouts are unknown. A significant proportion of his library is presently located in the Contemporary Medical Archives Centre on permanent loan in the library of the Wellcome Institute for the History of Medicine.

Education, Medical↗
PubMed2005

Genealogy of John and Charles Bell: their relationship with the children of Charles Shaw of Ayr.

The Reverend William Bell had six children who survived infancy. Two of his sons entered the legal profession and two other sons became distinguished anatomists and surgeons--John Bell, said for 20 years to have been the leading operating surgeon in Britain and throughout the world--and Sir Charles Bell, possibly the most distinguished anatomist and physiologist of his day. Information is not known about the fifth son or their sister. Charles Shaw, a lawyer of Ayr, had four sons and two daughters who survived infancy. Two of his sons, John and Alexander, became anatomists and later surgeons at the Middlesex Hospital, and both worked closely with Charles Bell at the Great Windmill Street School of Anatomy. His third son entered the law and his fourth son became a distinguished soldier. The two daughters of Charles Shaw married into the Bell family: Barbara married George Joseph Bell and Marion married Mr (later Sir) Charles Bell.

Anatomy↗
PubMed2004

Validating the subcutaneous model of injectable autologous cartilage using a fibrin glue scaffold.

PURPOSE: To create and validate an injectable model for autologous in vivo cartilage engineering with ultimate clinical applicability in human subjects. HYPOTHESIS: Cartilage can be generated subcutaneously using fibrin glue and autologous chondrocyte components. BACKGROUND: To date, cartilage engineering studies have been limited by several factors. Immunocompromised animals and nonautologous chondrocytes have been successfully used to create cartilage, but results using identical designs failed in immunocompetent subjects. Recent studies using more biocompatible tissues and matrices have been performed with both in vitro and in vivo steps. Although successful, several problems are notable. In vitro cartilage displays a poor modulus of elasticity, even after in vivo implantation. Variable deformation and volume loss occurs when in vitro specimens are matured in vivo. These concerns limit the clinical utility of these methods. We therefore set out to create autologous cartilage using a model that was clinically feasible, easy to create, and could be performed with very low patient harvest morbidity. MATERIALS AND METHODS: Eight New Zealand white rabbits underwent a unilateral harvest of ear cartilage. Samples were then digested using standard methods. Cell counts and survival assays were performed before implantation. One sample of fibrin glue (Tisseel) and chondrocytes was injected subcutaneously into each donor rabbit and then left in situ for 3 months. A second sample with both basic fibroblast growth factor (b-FGF) and insulin-like growth factor (IGF)-1 in the injection suspension was also assessed (for a total of 16 samples). After harvest, analysis of overall volume, histology, and chondrocyte drop out counts was performed. RESULTS: Cartilage formation occurred in 8 of 14 (57%) specimens that were obtained at the time of sacrifice. Of note, 6 of 7 (85%) non-growth-factor containing samples yielded positive results. Comparison with the success rate using concomitant growth factors (2/7) showed a negative effect on cartilage yield (P = .015). Chondrocyte survival, based on chondrocyte dropout counts, was not effected. Angiogenesis appeared to correlate with cartilage formation in the central regions of the implant. Alcian blue demonstrated the presence of active matrix deposition, and elastin Verhoff-van Geison (EVG) stains were positive, showing an elastic cartilage phenotype. Very limited osteoid formation was seen in successful implants. Failed implants demonstrated avascular necrosis, giant cell reactions, and inflammatory infiltrates. CONCLUSIONS: This study validates the subcutaneous site as a recipient bed for the engineering of autologous cartilage in vivo. It also represents the first subcutaneous implantation of fibrin glue and chondrocytes in an immunocompetent host as well as the first published report of elastic cartilage generation in vivo. Although the model needs to be further streamlined to increase yields and overall volume, this study clearly demonstrates the feasibility of in vivo chondrogenesis (85% success). The addition of FGF and IGF-1 at the concentrations used negatively influenced cartilage yield. However, extrapolation of these results to other combinations or concentrations can not be done, and this issue deserves further investigation.

Animals↗
PubMed2002

Vitamin D receptor gene allelic variants, bone density, and bone turnover in community-dwelling men.

The role of vitamin D receptor (VDR) gene polymorphisms in the determination of bone mass and bone turnover is controversial in women. The aim of the study was to determine whether VDR polymorphisms are associated with indices of bone mineral density (BMD) (by dual-energy X-ray absorptiometry and by ultrasound) and/or with bone turnover and muscle strength, factors related to both BMD and fracture risk. For this purpose, we investigated a cohort of community-dwelling men >70 years (n = 271) and a group of healthy control subjects between the ages of 20 and 50 years (n = 137). VDR TaqI, ApaI, and FokI genotypes were determined using enzymatic restriction digestion of polymerase chain reaction (PCR) fragments. In the elderly group, the lowest BMD value at the femoral neck and at the calcaneus was observed in subjects with the "At-At" haplotype genotype, with differences between extreme haplotype groups ("At-At" vs. noncarriers of the "At" allele) ranging from 5.8% to 34.3% (p < or = 0.05). Moreover, at the different subregions of the distal forearm and the tibia, the lowest BMD estimates were consistently associated in both elderly and younger men with the "At" haplotype allele, although this did not approach statistical significance. Elderly subjects with the "At-At" genotype had a significantly higher serum osteocalcin level. BMD was not significantly related to the FokI VDR polymorphism at any of the assessed skeletal sites, nor were any of the biochemical markers associated with the FokI VDR genotype. There were no differences between genotype groups for any of the indices of muscle strength. The present study indicates that the VDR genotype is associated with BMD in healthy community-dwelling elderly men and tends to be associated with biochemical markers, particularly of bone formation, in elderly men.

Adult↗
PubMed2002

Is Chlamydia pneumoniae found in spinal fluid samples from multiple sclerosis patients? Conflicting results.

Cerebrospinal fluid samples from controls and patients with multiple sclerosis (MS) were split and sent to laboratories with different experiences for the detection of Chlamydia pneumoniae by polymerase chain reaction. Vanderbilt investigators identified C. pneumoniae in the majority of patients with MS and uncommonly in controls. Laboratories at Johns Hopkins University, University of Umeå, and the Centers for Disease Control and Prevention did not identify C. pneumoniae in any of the samples. Conflicting reports of C. pneumoniae detection in the some samples from patents with MS highlight the need to exchange detection techniques among laboratories involved in this controversy.

Adolescent↗
PubMed2001

Increased serum S100beta protein concentrations following severe head injury in humans: a biochemical marker of brain death?

This study investigated S100beta protein as a biochemical serum marker of brain damage in severe head injury and brain death victims. Blood samples obtained from 15 patients with severe head injury admitted to the trauma intensive care unit (ICU), five patients with a diagnosis of brain death due to hemorrhage following cerebral aneurysm rupture, and five healthy individuals were investigated. The S100beta protein serum concentrations were analyzed with a immunoradiometric assay kit. The 15 patients with severe head injury were followed up for 6 months. Outcome was considered either death or recovery with ICU discharge. S100beta concentrations were closely related to brain damage. Among the severe head injury victims, higher S100beta concentrations were detected in those patients that progressed to death. The individuals with brain death had similar mean S100beta concentrations, irrespective of its cause (either trauma or vascular rupture). S100beta protein is a promising serum outcome predictor for severe head injury victims and may contribute to the early diagnosis of brain death.

Adolescent↗
PubMed2001

Positive feedback circuits and adaptive regulations in bacteria.

The mechanisms by which bacteria adapt to changes in their environment involve transcriptional regulation in which a transcriptional regulator responds to signal(s) from the environment and regulates (positively or negatively) the expression of several genes or operons. Some of these regulators exert a positive feedback on their own expression. This is a necessary (although not sufficient) condition for the occurrence of multistationarity. One biological consequence of multistationarity may be epigenetic modifications, a hypothesis unusual to microbiologists, in spite of some well-known epigenetic modifications in bacteria. We propose here that the occurrence of mucoidy in the opportunistic pathogen Pseudomonas aeruginosa, which is currently attributed to mutations only, may also be an epigenetic modification. A theoretical approach using a generalised logical analysis lends credit to this hypothesis and suggests experiments to ascertain it.

Alginates↗
PubMed2001

The Edinburgh Mouse Atlas: using the CD.

This paper provides a simple introduction to the reconstructions and data-handling tools stored on the Edinburgh Mouse Atlas CD, together with some of the ways in which the viewers and software can be used to understand mouse development and analyse data. The key aspect of the Mouse Atlas is that the underlying models are a complete representation of the histology, which has not been constrained to a particular interpretation. This means, for example, that the current anatomy domains can be further subdivided as required to any resolution up to the resolution of the models (2-7 microm). In the CD of the early embryos described here, virtually all tissues that can be usefully distinguished either by the histology or morphologically have been delineated.

Animals↗
PubMed2001

Using computer graphics to preserve function in resection of malignant melanoma of the foot.

The increasing incidence of malignant melanoma challenges physicians to find innovative ways to preserve function and appearance in affected areas that require partial resection. We carefully planned the resection of a malignant lesion between the third and fourth toes of a 77-year-old man with the aid of computer technology. The subsequent excision of the third, fourth, and fifth digits was executed such that the new metatarsal arc formed would approximate the dimensions of the optimal hyperbola, thereby minimizing gait disturbance.

Aged↗
PubMed2000

Stimulus novelty differentially affects attentional allocation in PTSD.

BACKGROUND: This study investigated attentional allocation in 39 Vietnam combat veterans, 25 with and 14 without posttraumatic stress disorder, assessing P300 amplitudes and latencies during both three-tone and novelty "oddball" tasks. METHODS: The three-tone oddball task consisted of three stimuli: frequent tones (85%), rare target tones (7.5%), and rare distractor tones (7.5%). The novelty oddball task was identical to the three-tone task except that the rare distractor tones were replaced with nonrepeating novel sounds (7.5%). RESULTS: Combat veterans with posttraumatic stress disorder showed significant P300 amplitude enhancements at frontal sites in response to distracting stimuli during the novelty but not during the three-tone oddball tasks. There were no amplitude differences in target tones during either task. CONCLUSIONS: The data suggest that combat veterans with posttraumatic stress disorder demonstrate P300 responses consistent with a heightened orientation response to novel, distracting stimuli. This finding is consistent both with the clinical presentation of the disorder and with theoretical notions that individuals with posttraumatic stress disorder demonstrate information-processing biases towards vague or potentially threatening stimuli.

Anxiety↗
PubMed2000

Fluorescein fluorescence hyperpolarization as an early kinetic measure of the apoptotic process.

The ability to identify apoptotic cells within a complex population is crucial in the research and diagnosis of normal physiology and disease states. The Cellscan mark S (CS-S) cytometer was used in this study to detect intracellular fluorescence intensity and polarization (FI and FP) in several well-established models of apoptosis: Following spontaneous apoptosis, as well as glucocorticoid or anti Fas-induced apoptosis, CS-S individual cell-based analysis revealed the appearance of a cell cluster characterized by low FI and high FP. Temporal analysis of annexine V binding and FP measurements following DXM treatment showed that hyperpolarization preceded phosphatidylserine appearance on the outer plasma membrane. The early increase in FP was found to be dose dependent and inversely related to cell diameter. Cell dehydration and alteration of plasma membrane transport properties, both occurring during early stages of apoptosis, may be involved in the phenomena of intracellular fluorescein hyper-polarization in apoptosis.

Animals↗
PubMed2000

Analysis of enzyme kinetics in individual living cells utilizing fluorescence intensity and polarization measurements.

BACKGROUND: The Cellscan mark-S (CS-S) scanning cytometer was used for tracing enzymatic reactions in the same individual cells under various physiological conditions over periods of minutes. On-line reagent addition and changes in the experimental conditions (buffers, ions, substrates and inhibitors) were performed. METHODS: Kinetic events were monitored by fluorescence intensity (FI) and fluorescence polarization (FP) measurements of fluorescein diacetate (FDA) and chloromethyl fluorescein diacetate (CMFDA) intracellular hydrolysis. FP measurements have been used to assess the intracellular marker's mobility restrictions. RESULTS: Kinetic measurement along 1000 s of FDA labeled individual Jurkat T cells, indicated variation of 65% for FI(t) and approximately 10% for FP(t). While FI increased linearly with time, FP(t) decreased nonlinearly and asymptotically, reaching a constant value. The FP(t) of CMFDA-labeled cells was different from that of FDA-labeled cells. Average cellular Km of 3.9 microM was calculated from individual cell FDA hydrolysis curves. CONCLUSIONS: (1) Analysis of the reaction kinetics of intracellular enzymes can be refined by using FP measurements of the products of fluorogenic substrates in addition to the FI measurements. (2) Subpopulations or individual cells could be classified according to their reaction rates. (3) A specific dependence of FP(t) on type of enzyme substrate is suggested.

Binding, Competitive↗
PubMed2000

Atypical features prompting neuroimaging in acute optic neuropathy in adults.

BACKGROUND: Acute optic neuropathy due to an intracranial lesion may masquerade as optic neuritis or nonarteritic anterior ischemic optic neuropathy (NAION). We reviewed the records of patients who presented with acute unilateral optic neuropathy that was initially diagnosed as optic neuritis or NAION but who ultimately proved to have an underlying structural lesion. METHODS: Retrospective observational case series. We reviewed the records of patients with the initial diagnosis of optic neuritis or NAION in whom the diagnosis was changed to an intracranial etiology at four tertiary care neuro-ophthalmology centres between 1995 and 1998. RESULTS: Eight cases were identified in which atypical features prompted further investigation, including neuroimaging, leading to the diagnosis of an intracranial etiology for the optic neuropathy. Five patients were discovered to have neoplasms (a tuberculum sellae meningioma in two cases, an optic nerve sheath meningioma in two cases and a metastatic lesion in one case), and three patients had intracranial sarcoidosis. Atypical features for optic neuritis included a progressive course, absence of pain, optic atrophy at presentation, lack of significant visual improvement and age over 40 years. For NAION, the atypical features included progressive course, optic atrophy on presentation, absence of vasculopathic risk factors and preceding transient visual loss. INTERPRETATION: Clinicians should be aware that patients with intracranial lesions may present with acute optic neuropathy mimicking optic neuritis or NAION and that certain atypical features should warrant consideration for neuroimaging.

Acute Disease↗
PubMed2000

Positive feedback circuits and memory.

The concept of regulatory feedback circuit refers to oriented cyclic interactions between elements of a system. There are two classes of circuits, positive and negative, whose properties are in striking contrast. Positive circuits are a prerequisite for the occurrence of multiple steady states (multistationarity), and hence, they are involved in all processes showing hysteresis or memory. Endogenous or exogenous perturbations can lead the system to exhibit or to evoke one particular stable regime. The role of positive circuits in cell differentiation and in immunology is well documented. Negative circuits are involved in homeostatic regulation, with or without oscillations. The aim of this paper is to show: a) that positive circuits account for many features of memory stricto sensu (i.e., neural memory and mnesic evocation) as well as largo sensu (e.g. differentiation or immunological memory); and b) that simple combinations of positive and negative circuits provide powerful regulatory modules, which can also be associated in batteries. These entities have vast dynamical possibilities in the field of neurobiology, as well as in the fields of differentiation and immunology. Here we consider a universal minimal regulatory module, for which we suggest to adopt the term 'logical regulon', which can be considered as an atom of Jacob's integron. It comprises a positive and a negative circuit in its interaction matrix, and we recall the main results related to the simultaneous presence of these circuits. Finally, we give three applications of this type of interaction matrix. The first two deal with the coexistence of multiple stable steady states and periodicity in differentiation and in an immunological system showing hysteretic properties. The third deals with the dual problems of synchronization and desynchronization of a neural model for hippocampus memory evocation processes.

Cell Differentiation↗
PubMed2000

The significant change for the Timed 25-foot Walk in the multiple sclerosis functional composite.

The Timed 25-Foot Walk is under evaluation as a clinical tool to follow patients with MS. Several approaches have been taken to define a clinically significant change in this measurement. This study was undertaken to define the range of values expected for the Timed 25-Foot Walk and to correlate prospectively the change in walk-time that occurs during an exacerbation of MS associated with subjective difficulty walking. Five results from this study are emphasized. (1) Patients who were minimally affected by MS frequently walked 25 feet between three and five seconds. (2) the walk-time variability, defined as the ratio of the longest to the shortest walk-time, minus 1, times 100%, for three consecutive trials was generally 20% or less; (3) if the two fastest walk-times obtained in three trials were compared, the walk-time variability was almost always 10% or less; (4) for clinically stable individuals, the walk-times of single trials separated by 12 months or less generally varied less than 20%; and (5) patients who complained of difficulty walking, but who did not have changes otherwise detectable by examination, generally had a prolongation of walk-time. These results suggest that an increase of more than 20% in the Timed 25-Foot Walk may indicate a significant change in gait. Multiple Sclerosis (2000) 6 286 - 290

Disability Evaluation↗
PubMed2000

The Toronto Lesbian Family Study.

Twenty-seven lesbian mothers completed standardized tools chosen to assess current functioning, followed by a video-taped interview. Verbal children were also interviewed. Questions involved perceptions of the mothers' and children's experiences of being homosexual or being raised by homosexual parents, knowledge and fantasies about the donor/father, feelings regarding the role of fathers, parents' experiences of being fathered, legal issues, and development. All mothers were strongly lesbian identified and most were completely "out." All but one mother planned to or had told their children. All mothers planned to reveal donor information at an appropriate age. Many, especially parents of boys, had concerns about lack of a male role model, but none felt this would negatively affect the child's development. Mothers were open to having their child ask questions and even seek out the donor when older. Thirty-one percent of mothers reported a positive relationship with their own father, 42% a father who was present but unavailable or punitive and 27% a completely absent father for large parts of their childhood. Couples divided parenting work based on individual strengths and interests, work schedules and demands. Only two of the couples felt that one of them played a role typical of a father. An aggregate score was compiled for each mother based on the number of negative outcomes in the standardized tools. The mean number of negative outcomes for the mothers was 3.15 (SD = 1.85). Of the six women with 5 or more negative outcomes on the scales, three were single parents and one had lost her partner when her child was two months old. On the CESD, three mothers showed depression levels that were high. The Internal External scale showed 42% of mothers to have an external locus of control. Three mothers scored negatively on the Family Assessment Device. Ninety-two percent of women showed moderate to high self-esteem on the Rosenberg Self-Esteem scale, and the Parenting Stress Index found only 4 women showing enough stress to warrant follow-up. Mothers who reported very negative early experiences of coming out were more likely to report current depressive symptoms (p = .03). All but one child living in two-mother homes identified both mothers as part of their family. Our initial impression is that these are primarily strong families with a variety of parenting skills, stressors and philosophies.

Adult↗