Search PubMedSearch

Biomedical subjects

M Harrington

Publications and source records attributed to M Harrington.

At least 19 recordsLinked to original sources

A review of recent findings on substance abuse treatment for pregnant women.

Recent years have brought an increased interest in the treatment needs of pregnant substance abusers. This article reviews the literature on this subject, providing an overview of what is known about the prevalence of substance abuse during pregnancy; the factors in women's lives, especially pregnant women, that lead to substance abuse and that facilitate and impede treatment success; and the components of successful treatment programs. The prevalence of prenatal illicit drug use is known to be about 5% of all pregnant women nationwide, with higher rates for selected subgroups. Local studies have shown much higher rates. Substance abuse is associated with poverty, with the substance abuse of significant others, and with family violence. Perinatal substance abusers experience poorer birth outcomes. The negative consequences for babies do not stop at birth; home environments may be chaotic and often children are removed from their mother's care if substance abuse continues after birth. While the literature on prevalence, correlates, and outcomes of perinatal substance abuse is plentiful, there continues to be sparse information on successful treatment approaches. Sample sizes are small and there are few studies with adequate comparison groups. The small number of outcome studies we review suggest that, as with the broader treatment literature for other populations, success (as measured by abstinence) is associated with retention. Retention is facilitated by the provision of support services, such as child care, parenting classes, and vocational training. There is no clear empirical basis for concluding that one type of treatment (for example, residential treatment) is more effective than another.

Adolescent

Transcriptional regulation of the mouse CSF-1 gene.

Research in our laboratory is aimed at understanding the cellular and molecular mechanisms that govern colony stimulating factor-1 (CSF-1) gene expression. Our hypothesis is that a basal set of trans-acting factors is bound to the CSF-1 gene during fibroblast proliferation, resulting in constitutive CSF-1 gene expression. Modulation of CSF-1 gene transcription by growth-arrest (decrease) or stimulation of growth-arrested fibroblasts (re-initiate) is mediated by changes in the basal set of factors bound and/or by the addition of stimulus-specific factors. We have extended our hypothesis to include other cell types (monocytes) to determine if mechanisms used to control CSF-1 gene expression in fibroblasts are unique or represent common nontissue-specific regulatory mechanisms. Analysis of CSF-1-CAT reporter constructs in transiently transfected fibroblasts and monocytes was used to identify CSF-1 genomic sequences that affect transcriptional activity. DNase I protection, electrophoretic mobility shift, and methylation interference assays were used to identify the putative cis-acting elements. Results of our study suggest multiple trans-acting factors may regulate CSF-1 gene expression; some may be tissue specific, while others, such as AP1, CTF/NF1, Sp1, and Sp3, are shared in common.

Animals

A community/hospital leg ulcer service.

This paper outlines the implementation of a multidisciplinary integrated community and hospital leg ulcer service in 1993 and its effect on the health outcomes and quality of life of patients living in the area of the Hounslow and Spelthorne Community and Mental Health Trust prior to and following the establishment of the service.

Aged

Effects of gamma-irradiation on the M-CSF-promoter linked to a chloramphenicol aminoacyl transferase reporter gene expressed in a clonal murine bone marrow stromal cell line.

The effects of cytokines produced by bone marrow stromal cells on closely associated hematopoietic cells constitute a major component of the physiology of the hematopoietic microenvironment. A major cytokine produced by marrow stromal cells is macrophage colony-stimulating factor (M-CSF). To determine the effect of gamma-irradiation on the M-CSF promoter in bone marrow stromal cells, we selected a clonal cell line from the C3H/HeJ mouse marrow stromal cell line D2XRII and stably transfected a reporter construct containing the murine M-CSF-promoter linked to a chloramphenicol aminoacyl transferase (CAT) gene. CAT activity was measured at serial time points after gamma-irradiation in vitro to doses between 500 and 10,000 cGy at a dose rate of 116 cGy/min. D2XRII marrow stromal cells treated with phorbol myristate acetate (40 micrograms/ml, four h), demonstrated a significant two-fold increase in CAT activity. In contrast, CAT activity measured immediately, 24 h, 72 h or 1 week after gamma-irradiation, showed no significant increase or decrease in CAT activity. An increase in CAT activity was detected 48 h after irradiation with cells that received 5,000 cGy. Thus, single fraction gamma-irradiation of plateau phase bone marrow stromal cells did not decrease M-CSF-promoter activity. These results are consistent with prior experimental data demonstrating stable levels of release of M-CSF protein following gamma-irradiation of bone marrow stromal cells and imply that the stability of transcription of the gene for this important cytokine is protected from irradiation.

Animals

Polyhydroxy and polyethyleneglycol (meth)acrylate polymers: physical properties and general studies for their use as electrophoresis matrices.

A new series of materials have been tested for their suitability as electrophoresis matrices. The mechanical and optical properties of gels composed of polyethyleneglycol (meth)acrylate esters or polyhydroxy (meth)acrylate esters in water and in various concentrations of organic solvents are described. Several crosslinkers including polyethyleneglycol and polyhydroxy di(meth)acrylates, piperazine diacrylate, and bisacrylamide were used in these studies. Electrophoretic migration and separation of a series of protein standards through polyethyleneglycol methacrylate (PEGM) 200, PEGM 400, and glyceryl methacrylate is demonstrated. Further, copolymerization of all of the monomers with acrylamide was performed and the distribution of monomer incorporation into the polymer network calculated. All monomers and copolymers that were examined by IR spectroscopy showed greater than 99% polymerization. These results justify their further study for biomolecule separations.

Cross-Linking Reagents

Polyethyleneglycol methacrylate 200 as an electrophoresis matrix in hydroorganic solvents.

The properties of gels composed of poly(polyethyleneglycol methacrylate) and copolymers of polyethyleneglycol methacrylate and acrylamide were studied. These novel electrophoresis matrices are amphigels (swellable in water and organic solvents) that have unprecedented organic solvent compatibility. Hydrophobic proteins which are poorly solubilized in aqueous detergent systems (e.g., zein) are well-resolved in these gels with hydro-organic solvents. This is especially relevant for isoelectric focusing, to avoid using either ionic detergents that may interfere with the focusing, or urea that may cause carbamylation of proteins. Variations of crosslinker, buffer, and solvent systems in these gels were explored.

Electrophoresis

Human cerebrospinal fluid protein database: edition 1992.

Two-dimensional electrophoresis maps of human cerebrospinal fluid proteins are presented in the form of labeled images. 931 protein spots are identified in spinal fluid from a normal volunteer. Distinct spots that represent variants of the same protein, especially posttranslational modifications, are estimated to reduce the 931 different spots to < 200 different proteins. 248 spots of 29 protein groups have been identified and are indicated on enlargements of specific gel regions. The distribution of protein abundance, mass, charge and shape characteristics of these normal 931 spinal fluid spots are graphically profiled. Analysis of the shape parameter "vertical height: width ratio" reveals that a ratio > 3.5 correlates with glycoproteins, enabling their identification simply by image analysis. Proteins that are not present on the normal map, but appear in spinal fluid in patients with schizophrenia and Creutzfeldt-Jakob disease are illustrated on additional maps.

Cerebrospinal Fluid Proteins

The role of 99Tcm-HMPAO white cell imaging in suspected orthopaedic infection.

Accurate diagnosis is essential for the effective management of suspected bone infection. Current imaging techniques have had limited success and further work is required. Although white cell labelling techniques have been available for many years the radiopharmaceuticals employed have disadvantages, particularly in their availability and suitability for imaging. These problems have been overcome by the use of 99Tcm-HMPAO as an in vitro leukocyte labelling agent. The aims of this study were to assess retrospectively its role and accuracy in imaging orthopaedic infection and to compare the results with three-phase bone imaging. 30 patients with suspected bone infection underwent three-phase methylene diphosphonate (MDP) bone imaging and labelled leukocyte imaging on separate occasions. 16 bone scans were positive for infection, of which 14 were subsequently confirmed, and there were no false negatives. There were no false positive white cell studies and only one infection was not identified. 99Tcm-HMPAO white cell imaging has been shown to be an accurate technique for the diagnosis of bone infection but should be performed only following a positive finding on three-phase bone scanning, since the latter is highly sensitive but significantly less expensive, making it a more appropriate screening procedure.

Adolescent

Leukocyte scanning with 111In is superior to magnetic resonance imaging in diagnosis of clinically unsuspected osteomyelitis in diabetic foot ulcers.

OBJECTIVE: To compare the accuracies of MRI and leukocyte scanning in diagnosing clinically unsuspected osteomyelitis in diabetic foot ulcers. RESEARCH DESIGN AND METHODS: A prospective study of 16 diabetic foot ulcers in 12 patients, including both ambulatory and hospitalized patients, was performed at a university medical center. Pedal images were obtained by leukocyte scanning with [111In]oxyquinoline and MRI. Definitive diagnosis of osteomyelitis then was determined by bone biopsy for culture and histology. RESULTS: Biopsy-proven osteomyelitis was present in 7 (44%) of the 16 foot ulcers. The diagnosis was suspected clinically in 0%. Leukocyte scanning was 100% sensitive, whereas MRI was only 29% sensitive in diagnosing osteomyelitis in diabetic foot ulcers. Specificities were 67 and 78%, respectively. The positive and negative predictive values (70 and 100%, respectively) for the leukocyte scan also were greater than those of MRI (50 and 58%, respectively). CONCLUSIONS: Leukocyte scanning is superior to MRI in detecting clinically unsuspected osteomyelitis in diabetic foot ulcers.

Biopsy

Unsuspected osteomyelitis in diabetic foot ulcers. Diagnosis and monitoring by leukocyte scanning with indium in 111 oxyquinoline.

OBJECTIVE: The prevalence of osteomyelitis in diabetic foot ulcers is unknown. Early diagnosis of this infection is critical, as prompt antibiotic treatment decreases the rate of amputation. We therefore assessed the prevalence of osteomyelitis in 35 diabetic patients with 41 foot ulcers. We compared results of roentgenograms, leukocyte scans with indium In 111 oxyquinoline, and bone scans with the diagnostic criterion standards of bone histologic and culture findings. Leukocyte scans were repeated at 2- to 3-week intervals during antibiotic treatment. DESIGN: Cohort study. SETTING: Institutional and private, ambulatory and hospitalized patients. PATIENTS: Consecutive sample of 54 diabetic patients. Thirty-five patients with 41 foot ulcers were included. RESULTS: As determined by bone biopsy and culture, osteomyelitis was found to underlie 28 (68%) of 41 diabetic foot ulcers. Only nine (32%) of the 28 cases were diagnosed clinically by the referring physician. Underscoring the clinically silent nature of osteomyelitis in these ulcers, 19 (68%) of 28 occurred in outpatients, 19 (68%) of 28 occurred in ulcers not exposing bone, and 18 (64%) of 28 had no evidence of inflammation on physical examination. All patients with ulcers that exposed bone had osteomyelitis. Of the imaging tests, the leukocyte scan had the highest sensitivity, 89%. In patients with osteomyelitis, the leukocyte scan image intensity decreased by 16 to 34 days of antibiotic treatment and normalized by 36 to 54 days. CONCLUSION: The majority of diabetic foot ulcers have an underlying osteomyelitis that is clinically unsuspected. Leukocyte scans are highly sensitive for diagnosing osteomyelitis in diabetic foot ulcers and may be useful for monitoring the efficacy of antibiotic treatment. We recommend that diabetic patients with foot ulcers that expose bone should be treated for osteomyelitis. Diabetic patients with foot ulcers that do not expose bone should undergo leukocyte scanning, which eliminates the risk of bone biopsy in diagnosing osteomyelitis and allows for the diagnosis and treatment of this well-known but often silent precursor of lower extremity amputation.

Diabetes Mellitus, Type 2

Synergistic effect of human lactoferrin and recombinant murine interferon-gamma on disease progression in mice infected with the polycythemia-inducing strain of the Friend virus complex.

Mice infected with the polycythemia-inducing strain of the Friend virus complex (FVC-P) have been used as a leukemic mouse model. In the present study, purified iron-saturated human lactoferrin (LF) and recombinant murine (rmu) interferon-gamma (IFN-gamma), alone or in combination, were used to influence disease progression in virally infected mice. DBA/2 mice were injected i.v. with FVC-P, and were treated s.c. with 100 micrograms LF at day 7, and/or rmuIFN-gamma at 5 x 10(4) units/day for 3 days beginning at day 6 after viral infection. Mice were assessed for survival, and also 14 days after virus inoculation, the mice were killed and spleen extracts were assessed for spleen focus forming virus (SFFV) titers by spleen focus forming unit (SFFU) assay, SFFV mRNA and genomic DNA expression, and natural killer (NK) cell activity. Treatment with LF or rmuIFN-gamma alone had little or no effect on SFFU numbers or SFFV mRNA or genomic DNA expression. However, dramatically decreased SFFV titers and levels of SFFV mRNA and genomic DNA were observed in mice treated with the combination of LF and rmuIFN-gamma. NK cell activity decreased by FVC-P was returned to normal levels by LF and rmuIFN-gamma. The combined treatment also enhanced the survival rates of FVC-P-infected mice. The results suggest synergistic suppressive effects of LF with rmuIFN-gamma on disease progression in FVC-P-infected mice. This information might be of significance as a potential therapy for patients with leukemia and those infected with retroviruses.

Animals