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Biomedical subjects

K Coleman

Publications and source records attributed to K Coleman.

At least 37 records · Page 2Linked to original sources

Ethnicity and use of acute psychiatric beds: one-day survey in north and south Thames regions.

BACKGROUND: Previous studies have shown higher rates of psychiatric admissions, compulsory admissions, and diagnosed schizophrenia in Black ethnic groups compared with other population groups. METHOD: In a point-prevalence study, demographic and clinical data were collected for adult acute and low-level secure psychiatric in-patients in all National Health Service and seven private psychiatric units in North and South Thames regions on 15 June 1994. RESULTS: A total of 3710 adult acute and 268 low-level secure psychiatric patients were surveyed; 75% of the patients were White, 16% were Black, and 4% were Asian. Analysis reveals that a high proportion of the Black population were admitted to a psychiatric unit; that Black patients are more likely to be admitted under Section; to be located in locked wards; have an inpatient diagnosis of schizophrenia; and not be registered with a general practitioner. CONCLUSIONS: These findings demonstrate the over-representation of Black ethnic groups within current psychiatric provision. The complement of services to all minority ethnic groups should be examined in terms of access, appropriateness and quality of care. Racism awareness and staff training need to be incorporated into mental health service provision as a matter of priority.

Acute Disease↗

Prognostic value of morphometric features and the callender classification in uveal melanomas.

PURPOSE: Cytomorphometric analysis of uveal melanoma has focused on nucleolar characteristics, although nuclear measurements are easier and more reproducible. In this study, we examine a restricted set of nuclear and nucleolar cytomorphometric variables in the search for the most quantifiable and reproducible prognostic parameter among these and discover a means of assessing the malignancy of tumors within the different Callender subgroups. METHODS: Uveal melanomas from 94 patients with a minimum follow-up of 5 years underwent nuclear and nucleolar morphometric analysis using a digitized interactive video overlay system. Statistical analysis included univariate and multivariate survival analysis on morphometric variables and classic prognostic parameters (such as Callender cell type, size, etc.). RESULTS: Univariate analysis of cytomorphometric parameters showed the standard deviation of nuclear area (NASD) to be the most significant variable (P < 0.0001: Mantel-Cox, 15.2). This was followed by the difference between nuclear and nucleolar areas (P < 0.002; Mantel-Cox, 9.5), the standard deviation of nucleolar area (SDNA) (P < 0.01; Mantel-Cox, 6.4), and the standard deviation of the shortest nuclear axis (P < 0.02; Mantel-Cox, 6.4). There was a trend for significance with the mean of the ten largest nucleoli (P < 0.07). Multivariate analysis of clinical and cytomorphometric variables showed improvement of prognostic prediction with a combination of the NASD, largest tumor dimension, and glaucoma (P < 0.0001; Mantel-Cox, 26.3). Callender cell type was strongly correlated with the NASD (P < 0.0002), the mean axis ratio of the nuclear area (P < 0.0007), and the mean of the ten largest nucleoli (P < 0.0007). CONCLUSION: Cytomorphometric analysis of uveal melanoma should include nuclear area and may identify tumors of differing malignancy within the same Callender class.

Adolescent↗

No way out: the delayed discharge of elderly mentally ill acute and assessment patients in north and south Thames regions.

We examined the characteristics of patients occupying elderly-mentally-ill acute and assessment beds in all mental health units within North and South Thames Regions; the proportion of patients defined as no longer requiring acute care (inappropriately located); and the unmet need for alternative service provision these patients required. Of the 1510 patients surveyed, 24.4% (n = 368) were defined as inappropriately located. For inappropriately located patients unable to be discharged home most (52.8%, n = 154) required residential care or nursing-home provision. A large proportion of these patients were very elderly (aged 85+ years), had dementia, and required high levels of supervision. This study indicates that purchasers, mental health service managers and social services departments should devise a more appropriate mix of inpatient and community provision. Particular emphasis needs to be placed on the greater provision of residential care and nursing homes with an appropriate skill-mix to care for this complex care group.

Acute Disease↗

Use of acute psychiatric beds: a point prevalence survey in North and South Thames regions.

BACKGROUND: Concerns have been expressed, particularly in inner cities, about the growing pressure on acute psychiatric beds, evidenced by increased occupancy rates, difficulties in accessing beds, and increasing use of private beds by health authorities. This study investigated these concerns by conducting a census of psychiatric patients occupying acute beds. The proportion of patients who no longer required acute care and their needs for alternative provision were determined, together with bed occupancy rates. METHODS: A point prevalence survey of acute psychiatric patients in all National Health Service acute psychiatric units and seven private psychiatric units in North and South Thames regions was conducted on 15 June 1994. Sociodemographic, diagnosis and admission characteristics data were collected. Patients who no longer required acute care were identified and the alternative service provision required for these patients was determined. Bed occupancy rates were calculated. RESULTS: A total of 3710 psychiatric patients (including those on leave) were ennumerated. More than one in five (23.2 per cent) were defined as inappropriately located. The main alternative services required for inappropriately located patients who could be discharged to the community were professional support in patient's home (71.5 per cent), and housing or more appropriate housing (61 per cent). For inappropriately located patients who could not be discharged into the community, the main alternative services required were group home (29.3 per cent) and in-patient rehabilitation (20.8 per cent). Bed occupancy rates were high on the day of the survey (95 per cent). CONCLUSION: Best use is not being made of acute psychiatric beds in the Thames regions. A high proportion of patients occupying beds are those who no longer require acute care, but for whom alternative services are unavailable.

Acute Disease↗

Clinical-based vs insurance-based recommendations for substance abuse treatment level.

An exploratory study of 250 patients was conducted at three treatment facilities in Western Pennsylvania, USA, to determine: 1) the extent of disagreement between clinical-based [using American Society of Addiction Medicine (ASAM) criteria] and insurance-based [using Managed Care Organization (MCO) criteria] recommendations for treatment levels, and 2) the extend of ASAM recommendations that become the actual treatment. Cross-tabulations showed: 1) ASAM and MCO recommendations were the same for 85% of the cases, and 2) ASAM recommendations became the actual treatment in 93% of the cases. The exceptionally high level of ASAM-MCO agreement suggests a convergence in ASAM and MCO criteria and a deference to ASAM criteria in practice.

Adolescent↗

Risk-adjusted Medicare capitation rates using ambulatory and inpatient diagnoses.

Researchers at The Johns Hopkins University (JHU) developed two new diagnosis-oriented methodologies for setting risk adjusted capitation rates for managed care plans contracting with Medicare. These adjusters predict the future medical expenditures of aged Medicare enrollees based on demographic factors and diagnostic information. The models use the Ambulatory Care Group (ACG) algorithm to categorize ambulatory diagnoses. Two alternative approaches for categorizing inpatient diagnoses were used. Lewin-VHI, Inc. evaluated the models using data from 624,000 randomly selected aged Medicare beneficiaries. The models predict expenditures far better than the Adjusted Average per Capita Cost (AAPCC) payment method. It is possible that risk adjusted capitation payments could encourage health plans to compete on the basis of efficiency and quality and not risk selection.

Aged↗

Rapid detection of antimicrobial activity using flow cytometry.

Different antibiotic classes vary considerably in their modes of action and hence in their effects on the bacterial cell. Flow cytometry was used to analyse E. coli cells treated with five antibiotics differing in their modes of action. The ratio of protein content, as measured by fluorescence, to forward light scatter (i.e., FL1:FSC) provided a simple and reliable way of detecting within 2 h of treatment antimicrobial activity at a 0.5 minimum inhibitory concentration. This ability to detect antimicrobial activity rapidly offers considerable advantages in drug research for the rapid detection of novel antimicrobials and may, with further development, find a use in the clinic for rapid susceptibility testing as an aid to the selection of therapy.

Amdinocillin↗

Construction and characterization of a humanized anti-gamma-Ig receptor type I (Fc gamma RI) monoclonal antibody.

The murine mAb 22 (M22) binds to the human high affinity receptor for the Fc portion of IgG (Fc gamma RI). This mAb recognizes an epitope on Fc gamma RI that is distinct from the natural ligand (Fc) binding site, and, therefore, can bind to Fc gamma RI in the presence of saturating levels of IgG found in vivo. Fc gamma RI is expressed only on cytotoxic effector cells and it acts as an efficient mediator (trigger molecule) of effector functions. Directing tumor cells or other pathogens to Fc gamma RI utilizing M22 conjugated to an anti-tumor- or to an anti-pathogen-specific mAb may represent an effective method to enhance their removal and destruction under physiologic conditions. Humanization of M22 may improve the therapeutic potential of the mAb since murine mAbs normally elicit a human anti-mouse Ab response. In this report we describe the humanization of M22 by CDR-grafting onto human V region frameworks based on KOL VH and REI V kappa attached to human IgG1 and kappa constant domains. This humanized mAb, H22, displays equivalent binding specificity and affinity as its murine counterpart. In addition, H22 is able to trigger superoxide release from Fc gamma RI-bearing cells, a finding that demonstrates that H22 triggers Fc gamma RI functions. The successful humanization of mAb 22 is an important step in the development of Fc gamma RI-directed immunotherapy.

Amino Acid Sequence↗

DNA ploidy status in 84 ocular melanomas: a study of DNA quantitation in ocular melanomas by flow cytometry and automatic and interactive static image analysis.

Deoxyribonucleic acid (DNA) ploidy was quantified in 84 ocular melanomas (median follow-up, 11-years) by flow cytometry, CAS 200 interactive image analysis, and Pathology Image Processing Environment (PIPE; Department of Quantitative Pathology, Free University, Amsterdam, The Netherlands) automatic image analysis (75). Overall, 32.1% of the melanomas were aneuploid, 2.3% were tetraploid, and 66.6% were diploid. Pathology Image Processing Environment analysis estimated DNA ploidy in 12 tumors that were unprocessable by flow cytometry. Of 10 tumors that were diploid by flow cytometry, PIPE detected stemline aneuploidy in five and some aneuploid cells in five more. Seven tumors were aneuploid by PIPE but diploid by CAS 200, five of which contained occasional DNA aneuploid cells on the CAS 200 histograms. Pathology Image Processing Environment analysis quantified tumor samples with an average of 500 (250 to 1,050) cells in less than 10 minutes. All cells classified as spindle A according to the Callender system (more than 10,000) were diploid. Spindle B and epithelioid cells occupied both diploid and aneuploid peaks on the DNA histograms. Dioxyribonucleic acid variables did not correlate with established prognosticators, such as Callender cell type, largest tumor dimension, or glaucoma, nor did they reach significance by univariate and multivariate analyses. The value of these findings as a diagnostic support in uveal melanoma, particularly in combination with fine needle aspiration biopsy, is discussed.

DNA, Neoplasm↗

Oocyte storage affects the kinetics of insulin-induced GVBD in Xenopus laevis oocytes.

Xenopus laevis oocytes underwent meiotic maturation in response to progesterone or insulin stimulation. However, the kinetics of the oocytes' response to the steroid was much faster than the response induced by insulin even under saturating hormone concentrations. This time differential was seen in oocytes that were stimulated with either hormone shortly after they were isolated from the animal. On the contrary, if oocytes were first cultured in MBS medium for 12-14 hours and then treated with either hormone, the oocytes responded to insulin and progesterone with similar kinetics. This result was not due to the ionic strength, potassium concentration or pH of the medium. The effect of storage in MBS was ligand specific for insulin. The extra 12-14 hours in MBS medium had no effect on the oocytes' response to progesterone.

Animals↗

Autocrine transforming growth factor-beta 1 and beta 2 expression is increased by cell crowding and quiescence in colon carcinoma cells.

Although a great deal is known about the cellular effects of exogenous transforming growth factor-beta (TGF-beta) treatment and the effects of various exogenous agents (including TGF-beta's themselves) on TGF-beta expression, studies of cellular controls for autocrine TGF-beta expression and function have been rare. Since exogenous TGF-beta treatment blocks progression through the cell cycle, it seemed likely that autocrine TGF-beta activity would be induced by growth states in which there was little or no cell division such as confluency or quiescence. Specific TGF-beta 1 or beta 2 neutralizing antibody treatment of a colon carcinoma cell line designated CBS showed that autocrine TGF-beta activity could be demonstrated in quiescent cells but not in preconfluent cells. Studies of kinetics of TGF-beta 1 and beta 2 mRNA levels during the establishment of quiescence revealed a significant increase of both isoforms in quiescent cells. The quiescent cells also secreted three- to fourfold and four-to fivefold higher levels of total (latent plus active) TGF-beta 1 and beta 2 protein in the conditioned media than the confluent cells and preconfluent cells, respectively. There was no detectable active form of either TGF-beta isoform in the conditioned media of preconfluent cells, whereas a significant amount of active TGF-beta 1 and beta 2 was detected in the conditioned media of quiescent cells. Quantitative RNase protection assays were developed to compare the effects of cell crowding vs quiescence on TGF-beta expression. TGF-beta 1 was primarily induced by quiescence. TGF-beta 2 was induced by both quiescence and cell crowding. Increased TGF-beta 1 mRNA levels appeared to be exclusively due to an increase in stability, while increased TGF-beta 2 mRNA levels were due to increased transcription. This growth state-related induction of TGF-beta's was also observed in two other colon carcinoma cell lines. These studies show that TGF-beta 1 and beta 2 are autocrine-negative factors which can be situationally expressed by cells as a function of their growth state. Autocrine expression of the TGF-beta's in this model system appears not to affect exponentially growing cells, but rather to function by maintaining a quiescent state and/or by blocking progression through the cell cycle.

Carcinoma↗

Bacterial resistance mechanisms as therapeutic targets.

In the 50 years since antimicrobial agents were first introduced, bacteria have acquired a wide variety of mechanisms which have enabled them to resist the effects of these drugs. One way of overcoming this problem is to administer an antibiotic with an agent which counteracts the mechanism of resistance to that antibiotic; an example of such an approach which has already been successfully implemented is the combination of a beta-lactam antibiotic with a beta-lactamase inhibitor. This review describes antibiotic resistance mechanisms which might lend themselves to an inhibitor approach and the potential therapeutic applications of such a strategy.

Bacteria↗

Continuous passive motion in seating: a new strategy against low back pain.

Low back pain commonly reduces tolerance for the prolonged sitting required by many occupations and routine daily activities. In order to provide lumbar lordotic continuous passive motion (CPM), a pneumatic device was developed. This device includes a lumbar support bladder, which is cyclically inflated and deflated by a pump and valve system. This system is controlled by a timer and by pressure feedback from the bladder. The user selects cycle duration and support pressure. Using a simulated automobile setting, the first part of this study demonstrated that CPM produces lumbar lordotic motion and improved comfort for subjects without histories of low back pain. In the second part of the study, 28 people with chronic low back pain reported greater comfort using CPM during their routine motor vehicle operation. Further research is needed to determine whether this promising new strategy against low back pain can reduce occupational disability due to sitting intolerance.

Adult↗

Syntactic structure analysis in uveal melanomas.

Syntactic structure analysis was carried out successfully on 92 paraffin embedded uveal melanomas, taken from patients with a minimum follow up of 5 years. This simple, fast, and reproducible method of describing the tumour architecture has been significantly correlated with malignancy in tumours from several sites. Paraffin sections 5 microns thick, were cut and stained with haematoxylin and eosin. Tumours were classified according to a modification of the Callender classification. A minimum spanning tree (MST), using the centre points of tumour nuclei, was constructed in five randomly chosen fields with an interactive digitising video overlay system. Ten syntactic structure features were derived from each MST; subsequently, the mean and standard deviation of the five fields analysed were calculated for further statistical analysis. Reproducibility was acceptable with a mean correlation coefficient of 0.70. In univariate survival analysis, the percentage of points with three neighbours yielded prognostic significance (p < 0.05). Minimum spanning tree variables were compared (chi 2 test) with classic tumour prognosticators and there was a significant correlation between Callender cell type and the following MST parameters: mean number of points (p < 0.003); MST length (p < 0.003); mean line length (p < 0.01); number of nuclei with one neighbour (p < 0.004); number of nuclei with two neighbours (p < 0.02), and number of nuclei with three neighbours (p < 0.005). Syntactic structure analysis is an evolving technique, but may be able to mathematically (and reproducibly) describe melanoma architecture across the spectrum of the Callender classes. This would also allow architectural grading of tumours within the specific Callender groups, providing more precise prognostic information. Further modifications of this technique are necessary to optimise prognostic potential when applied to uveal melanomas.

Algorithms↗

Transforming growth factor-beta 1 induces transforming growth factor-alpha promoter activity and transforming growth factor-alpha secretion in the human colon adenocarcinoma cell line FET.

FET cells are well differentiated human adenocarcinoma cells whose growth is partially inhibited (50-60%) by transforming growth factor-beta 1 (TGF-beta 1). In exponentially growing cultures, TGF-beta 1 induces the expression of transforming growth factor-alpha (TGF-alpha) by 3-fold. To determine whether this induction is the result of increased TGF-alpha promoter activity, FET cells were transiently transfected with a plasmid containing 2816 base pairs of the 5'-flanking region of the TGF-alpha gene linked to luciferase. Transfected FET cells treated with growth-inhibitory concentrations of TGF-beta 1 (10 ng/ml) showed up to a 10-fold increase in luciferase activity. The increase in luciferase activity was dose dependent through the normal physiological range of TGF-beta 1 (0.5-20 ng/ml), saturating at 10 ng/ml. This effect was also TGF-alpha promoter specific, inasmuch as the Rous sarcoma virus long terminal repeat used as a control remained relatively insensitive to the effects of TGF-beta 1. By using progressively smaller portions of the TGF-alpha promoter region, the TGF-beta 1-responsive element was mapped between base pairs -77 and -201 of the 5'-flanking region. TGF-beta 1 treatment also affected epidermal growth factor receptor levels. FET cells treated with TGF-beta 1 (10 ng/ml) for 48 h showed a 20% decrease in the number of epidermal growth factor receptors and a 2-fold increase in the number of high affinity epidermal growth factor receptors on their surface. These results indicate that TGF-beta 1 acts as a positive regulator of TGF-alpha transcription, and they suggest a possible mechanism by which these cells circumvent the growth-inhibitory effects of TGF-beta 1.

Adenocarcinoma↗