Biomedical subjects

P Houghton

Publications and source records attributed to P Houghton.

At least 19 recordsLinked to original sources

PubMed2006

Antidermatophyte activity of medicago extracts and contained saponins and their structure-activity relationships.

Saponin-rich extracts of Medicago sativa L. have been shown to display antifungal activity against a range of common fungibut only a few individual saponins have been tested against dermatophytes. Total saponins were separately obtained from roots and aerial parts of Medicago sativa, M. murex, M. arabica and M. hybrida. Nineteen saponins and three parent triterpenoids, were tested against three dermatophytic fungi Microsporum gypseum, Trichophyton interdigitale and T. tonsurans using mircowell plate serial dilution assay to determine the Minimum Inhibitory Concentration (MIC). Miconazole was used as a positive control. T. tonsurans appeared to be the most sensitive of the dermatophytes to the active compounds. Aglycones showed less antifungal effect than the glycosides, which displayed a range of activities. Monodesmosidic glycosides of medicagenic acid were the most active compounds, especially the 3-O-beta-D-glucopyranoside, which displayed MIC less than 0.09mm against all three fungi, although those of hederagenin and zanhic acid also showed weak activity (MIC 3.3mm against two fungal species). Bidesmosidic saponins had weaker activity than monodesmosidic ones. This corresponds to activity of these and similar compounds against other fungal species but this is the first comprehensive report of activity of Medicago saponins against dermatophytes.

Antifungal Agents↗

PubMed2004

Educational intervention in the management of acute procedure-related wound pain: a pilot study.

OBJECTIVE: This report describes the pilot testing of an educational intervention to manage acute pain associated with wound care in an outpatient clinic. The intervention included essential elements of pain education identified in the acute pain literature: provision of information; pain measurement; establishing expectations; treatment planning; teaching environment. METHOD: The intervention was tested on five patients attending a wound clinic for scheduled treatment. Patients were aged 65 years or older and had a history of experiencing pain during treatment procedures such as dressing changes and debridement. Before the intervention, the study nurse gave the patients information about the procedure, discussed strategies they could use to make it as comfortable as possible, and explained how they could use a rating scale to denote any physical and emotional distress. RESULTS: All patients used the intervention strategies. Three out of five reported reduced pain and/or distress following the intervention. CONCLUSION: The pilot study supported the use of education as a pain control strategy in wound care and illuminated key methodological issues for further research on this topic.

Aged↗

PubMed2001

Protection and in vivo selection of hematopoietic stem cells using temozolomide, O6-benzylguanine, and an alkyltransferase-expressing retroviral vector.

Transfer of drug resistance genes to hematopoietic stem cells offers the potential to protect cancer patients from drug-induced myelosuppression and to increase the number of gene-modified cells by in vivo selection. In this study, a retroviral vector expressing both a P140K variant of human O6-methylguanine-DNA methyltransferase (MGMT) and an EGFP reporter gene was evaluated for stem cell protection in a murine transplant model. Mice transplanted with vector-transduced cells showed significant resistance to the myelosuppressive effects of temozolomide (TMZ), an orally administered DNA-methylating drug, and O6-benzylguanine (BG), a drug that depletes cells of wild-type MGMT activity. Following drug treatment, increases in EGFP(+) peripheral blood cells were seen in all peripheral blood lineages, and secondary transplant experiments proved that selection had occurred at the stem cell level. In a second set of experiments in which transduced cells were diluted with unmarked cells, efficient stem cell selection was noted together with progressive marrow protection with repeated treatment courses. Altogether, these results show that P140K MGMT gene transfer can protect stem cells against the toxic effects of TMZ and BG and that this vector/drug system may be useful for clinical myeloprotection and for in vivo selection of transduced stem cells.

Alkyl and Aryl Transferases↗

PubMed2001

Best practices for the prevention and treatment of venous leg ulcers.

Chronic venous insufficiency is the most common cause of leg ulcers. Its incidence increases as the population ages. Managing venous leg ulcers involves treating the cause, optimizing local wound care, and addressing patient-centered concerns. The cornerstone of the diagnosis of chronic venous insufficiency includes demonstrating venous disease. The clinician must rule out significant coexisting arterial disease by performing a thorough clinical assessment and obtaining an ankle brachial pressure index. The most important aspect of treatment is resolving edema through high compression therapy for those individuals with an ankle brachial pressure index greater than or equal to 0.8. Other components of successful chronic venous insufficiency management include increasing mobility and medical management. Selected patients may respond to surgery, biologicals, adjunctive therapies, and lifestyle enhancements. Twelve recommendations are made incorporating current best clinical practices and expert opinion with available research. The approach to venous disease is best accomplished through a multidisciplinary team that revolves around the active participation of patients and their families. The authors' intent is to provide a practical, easy-to-follow guide to allow healthcare professionals to provide best clinical practices.

Humans↗

PubMed2001

Standard cardiac rehabilitation is less effective for diabetics.

To assess clinical outcomes and lifestyle modifications in diabetic patients attending a standard cardiac rehabilitation programme following myocardial infarction (MI), a retrospective longitudinal study was undertaken in a district general hospital in the north west of England. A total of 1804 patients attended the cardiac rehabilitation programme over 10 years, of whom 223 (12.4%) had diabetes mellitus. Drugs were underprescribed in all patients, aspirin and beta-blockers especially in diabetics (75.3% vs 90.3%, p < 0.0001; 38.6% vs 60.8%, p < 0.0001). Smoking cessation was poor in diabetics (54.2% vs 69.1%, p < 0.003) and diabetics were less likely to attend at least one session of physiotherapy (26.9% vs 58.6%, p < 0.0001). Diabetics had higher mortality at one year (15.7% vs 5.6%; p < 0.0001), mostly associated with cardiovascular disease (13.4% vs 5.4%, p < 0.0001). Standard cardiac rehabilitation programmes appear to be less effective for patients with diabetes mellitus. We suggest that patients presenting with an existing chronic condition need specialised programmes of rehabilitation to integrate the care of that condition with their recent MI. Aggressive drug therapy following acute MI should also be prescribed in all patients when not contraindicated by other evidence.

Adult↗

PubMed2000

Strong immunostaining for myogenin in rhabdomyosarcoma is significantly associated with tumors of the alveolar subclass.

Rhabdomyosarcomas are a heterogeneous group of tumors with respect to their molecular basis, degree of differentiation, histology, and clinical behavior. Because of the wide variation of tumor morphology, it is often difficult to distinguish between the distinct subtypes of rhabdomyosarcomas. By using cryosections of tumor specimens and immunohistochemistry, in the present study we show that strong expression of myogenin in rhabdomyosarcoma is associated with alveolar histology (P = <0.0001, Fisher's exact test). Although staining for myogenin was observed in 22 of 26 rhabdomyosarcomas, all alveolar rhabdomyosarcomas (nine of nine) showed high levels of staining for myogenin, as defined by the frequency and intensity of staining of the tumor cells. The staining pattern suggests that the tumor cells are clonally derived from myogenin-positive progenitor cells. In contrast, most embryonal rhabdomyosarcomas (13 of 15) were either negative or showed a low level of staining for myogenin. In these tumors a larger proportion of tumor cells were distinctly negative for myogenin. Six of seven alveolar rhabdomyosarcomas that strongly stained for myogenin were also positive for Pax3-7/Forkhead (FKHR) by polymerase chain reaction/reverse transcriptase-polymerase chain reaction. One of two embryonal rhabdomyosarcomas that strongly stained for myogenin was retrospectively found to be positive for Pax3/FKHR transcripts. Quantitative analysis for myogenin by Western blotting using a smaller subset of rhabdomyosarcomas revealed that in general there was a good correlation between immunohistochemical staining and Western blotting (P = 0.01, Pearson Correlation), although the former technique was more sensitive for detecting tumors with low levels of the protein. On average, alveolar rhabdomyosarcomas expressed at least threefold more myogenin than embryonal rhabdomyosarcomas. Our data show that staining for myogenin will be a simple, rapid, and accurate adjunct for distinguishing between alveolar and embryonal rhabdomyosarcomas. We propose that embryonal rhabdomyosarcomas result from an early block in myogenesis, before the expression of myogenin. In contrast, we propose that alveolar rhabdomyosarcomas either originate from a late block in myogenesis (after expression of myogenin) or that the pathological mechanisms involved in these neoplasms also induce strong expression of this protein.

Antibodies, Monoclonal↗

PubMed2000

Best practices for the prevention and treatment of pressure ulcers.

In this article, the Canadian Association of Wound Care puts forward 12 recommendations for best practices in the prevention and treatment of pressure ulcers that focus on an interdisciplinary patient-centered approach. These recommendations are a synthesis of the Agency for Health Care Policy and Research guidelines, European guidelines, and current literature as interpreted by the Canadian experience and achieved through a national consensus panel. The article concludes that best practice guidelines must be fluid documents that respond to new evidence and experience.

Bacterial Infections↗

PubMed1998

Medicinal plants and Alzheimer's disease: Integrating ethnobotanical and contemporary scientific evidence.

The use of complementary medicines such as plant extracts in dementia therapy, varies according to the different cultural traditions. In orthodox Western medicine, contrasting with that in China and the Far East for example, pharmacological properties of traditional cognitive or memory enhancing plants have not been widely investigated in the context of current models of Alzheimer's disease. An exception is Ginkgo biloba in which the ginkgolides have antioxidant, neuroprotective, and cholinergic activities relevant to Alzheimer's disease mechanisms. The therapeutic efficacy of Ginkgo biloba extracts in Alzheimer's disease in placebo-controlled clinical trials is reportedly similar to currently prescribed drugs such as tacrine or donepezil and, importantly, undesirable side effects of Ginkgo biloba are minimal. Old European reference books (eg, medical herbals) document a variety of other plants such as Salvia officinalis (sage) and Melissa officinalis (balm) with memory improving properties, and cholinergic activities have recently been identified in extracts of these plants. Precedents for modern discovery of clinically relevant pharmacological activities in plants with long-established medicinal use include, for example, the interaction of alkaloid opioids in Papaver somniferum (Opium poppy) with endogenous opiate receptors in the brain. With recent major advances in understanding the neurobiology of Alzheimer's disease, and as yet limited efficacy of so-called rationally designed therapies, it may be timely to re-explore historical archives for new directions in drug development. This article considers not only the value of an integrative traditional and modern scientific approach to developing new treatments for dementia, but also in the understanding of disease mechanisms. Long before the current biologically based hypothesis of cholinergic derangement in Alzheimer's disease emerged, plants now known to contain cholinergic antagonists were recorded for their amnesic and dementia-inducing properties.

Alzheimer Disease↗

PubMed1997

Methylator resistance mediated by mismatch repair deficiency in a glioblastoma multiforme xenograft.

A methylator-resistant human glioblastoma multiforme xenograft, D-245 MG (PR), in athymic nude mice was established by serially treating the parent xenograft D-245 MG with procarbazine. D-245 MG xenografts were sensitive to procarbazine, temozolomide, N-methyl-N-nitrosourea, 1,3-bis(2-chloroethyl)-1-nitrosourea, 9-aminocamptothecin, topotecan, CPT-11, cyclophosphamide, and busulfan. D-245 MG (PR) xenografts were resistant to procarbazine, temozolomide, N-methyl-N-nitrosourea, and busulfan, but they were sensitive to the other agents. Both D-245 MG and D-245 MG (PR) xenografts displayed no O6-alkylguanine-DNA alkyltransferase activity, and their levels of glutathione and glutathione-S-transferase were similar. D-245 MG xenografts expressed the human mismatch repair proteins hMSH2 and hMLH1, whereas D-245 MG (PR) expressed hMLH1 but not hMSH2.

Animals↗

PubMed1996

Associations between atlantoaxial and craniomandibular anatomy.

Roentgen-cephalometric studies have shown that anatomical features of the craniocervical junction are associated with head posture, cranial base angulation, and mandibular shape and growth. The aim of the present work was to study relationships between atlantoaxial and craniofacial morphology based on macroscopical observations of skeletal material derived from 38 prehistoric Polynesian and 53 prehistoric Thai people. The two uppermost cervical vertebrae and the mandible of each individual were studied macroscopically and each skull base was analyzed on cephalometric X-rays in lateral projection. The height of the atlantal anterior and posterior arches displayed a significant negative correlation with the cranial base angulation, in that the higher the arches the steeper the flexure between the sphenoidal/clival and clival/foraminal planes. None of the axial variables were associated with the cranial base angulation. The height of the atlantal posterior arch was also associated with the mandibular length, ramal height and gonial angle. Thus, in general, a high arch was seen in conjunction with a long, high and square shaped mandible, whereas a low arch was usually found together with a short and low mandible characterized by an obtuse jaw angle. The anterior height of the axis (vertebral mass + dens) was significantly associated with mandibular length and ramal height. It is suggested that these results are evidence of the intimate ontogenetic development of the atlas and the cranial base, and a reflection of the functional relationship between atlas and cranium.

Anthropology↗

PubMed1995

Asymmetry in the human skeleton. A study on prehistoric Polynesians and Thais.

Atlantal, long bone, and craniofacial measurements of prehistoric Polynesian and Thai skeletons were analysed to ascertain the extent and direction of bilateral asymmetry. The atlantal articular mass was constantly and significantly higher on the right side than on the left. In Thais, the midlongitudinal axis of the atlanto-occipital facet on the right side had a steeper inclination than that on the left. In both groups the dental occlusion was less mesial on the right side and the mandible was shorter, significantly so in the Thais. The long bones were more asymmetric in the Polynesians than in the Thais. Height asymmetry of atlas lateral tuberculum correlated inversely with mandibular ramal width asymmetry. Atlanto-occipital facet length asymmetry correlated with asymmetry of the gonial angle and facet angulation asymmetry correlated inversely with radial length asymmetry. Our results suggest a pervading asymmetry of skeletal structures which we ascribe as local adaptations to functional demands rather than as due to a uniform asymmetric growth pattern.

Animals↗

PubMed1994

Immunohistochemical analysis of the distribution of MyoD1 in muscle biopsies of primary myopathies and neurogenic atrophy.

The expression of the myogenic determination gene MyoD1 plays a primary role in the commitment of primitive mesenchymal cells to a striated muscle lineage and is down-regulated during later stages of differentiation. To determine the potential role of this gene in myopathic conditions, we examined its expression by means of immunohistochemical analysis, using a series of muscle biopsies from 14 patients with a variety of primary myopathies and neurogenic disorders. Utilizing the avidin-biotin-complex technique, cryostat sections were stained with monoclonal antibody 5.8 A, which we have previously described as having a high level of specificity for tumors with rhabdomyoblastic differentiation. Of special interest was the observation in 4 of 8 cases of neurogenic atrophy of varying levels of cytoplasmic positivity of muscle fibers, appearing to correlate with their degree of atrophy, in addition to weak nuclear staining. Muscle biopsies from 2 patients with Duchenne's muscular dystrophy and 2 patients with autoimmune inflammatory myopathies demonstrated various levels of nuclear positivity in scattered foci that appeared to correlate with areas of regeneration. A biopsy from a single case of neurogenic atrophy secondary to infantile spinal muscular atrophy (Werdnig-Hoffmann's disease) demonstrated diffuse but relatively weak staining of myofiber nuclei, in contrast to sections of normal striated muscle and muscle biopsies from patients with unexplained myoglobinuria, which exhibited only minimal amounts of staining. These data are compatible with observations that MyoD1 expression is related to electrical activity and muscle regeneration.

Adult↗

PubMed1994

The molecular basis of skeletal muscle differentiation.

In recent years, significant advances have been made in understanding the molecular mechanisms involved in the regulation of skeletal-muscle differentiation. This review focuses on the role of the MyoD family of myogenic transcription factors that includes MyoD, myf-5, myogenin, and MRF4 (herculin or myf-6) in myogenesis. Members of this family share sequence homology for the basic-helix-loop-helix (bHLH) regulatory motif. The basic domain is required for DNA binding, whereas the HLH domain is required for dimerization. The bHLH motif confers both properties of transcriptional activation of muscle specific genes and inhibition of cell growth through collaboration with the E2A gene products (E12 and E47) and the retinoblastoma gene product (pRB). The functions of the MyoD family can be suppressed through inhibition of their expression or activity by various factors. These include peptide growth factors (FGF and TGF-beta), immediate early gene products (Fos, Jun and Myc), other oncogene products (Ras, Src), the Id protein, and innervation. The use of gene-knockout animal models has shown that there is some degree of functional redundancy in that inactivation of either MyoD or myf-5 has no effect on muscle development, whereas inactivation of both genes results in an absolute lack of muscle cells. In contrast, the inactivation of myogenin alone results in mice with gross deficiency of mature muscle.

Animals↗

PubMed1993

Neandertal supralaryngeal vocal tract.

Interpretations of skeletal anatomy claiming to show that Neandertals could not have had a similar supralaryngeal vocal apparatus to that of humans are demonstrated to be flawed. Correction of the errors suggests that the Neandertal vocal apparatus need not have differed from that of recent humans.

Animals↗

PubMed1992

Desmin positivity in primitive neuroectodermal tumors of childhood.

In this report, we describe two rosette-forming primitive neuroectodermal tumors that were found to contain desmin by both immunohistochemistry and Western blotting. Electron microscopy on both cases was consistent with primitive neuroectodermal tumors and revealed that the tumor cells contained cytoplasmic bundles of intermediate filaments. In both cases, studies for MyoD1 protein using immunohistochemistry and Western blotting were negative. Thus, the detection of desmin in a pediatric neoplasm does not absolutely exclude the diagnosis of primitive neuroectodermal tumor and should not be considered as prima facie evidence that a small-cell tumor is a rhabdomyosarcoma.

Abdominal Neoplasms↗

PubMed1991

MyoD1 protein expression in alveolar soft part sarcoma as confirmatory evidence of its skeletal muscle nature.

A typical case of alveolar soft part sarcoma was found to express in a strong and widespread fashion the marker MyoD1 protein. This nuclear phosphoprotein is the product of a regulatory gene that controls the commitment of a cell to myogenic lineage; it therefore provides strong and perhaps definitive evidence in support of the skeletal muscle nature of this enigmatic neoplasm.

Cell Transformation, Neoplastic↗

PubMed1990

Polynesian face and dentition: functional perspective.

Widely dispersed throughout the Pacific, Polynesians are a biologically distinctive people in form and size of both body and head. Large-bodied and well-muscled, their body phenotype is suited to life in a thermolabile oceanic environment. Their craniofacial skeleton is large and robust, with mandibular size and form (the "rocker" mandible) being especially characteristic. In this paper the Polynesian variants of body form, and of facial size (including dentition) and form, are interpreted from a functional perspective.

Anthropometry↗

PubMed1990

An annual event.

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Health Education↗