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Biomedical subjects

A Clarke

Publications and source records attributed to A Clarke.

At least 145 records · Page 8Linked to original sources
PubMed1995

Population screening for genetic susceptibility to disease.

Genetic screening for susceptibility to common diseases, such as the common cancers, cardiovascular disease, and diabetes, may soon be technically feasible. Commercial interests should not be allowed to introduce such screening before proper evaluation or without adequate counselling and support. The evaluation of such testing should include psychosocial and medical outcomes and outcomes for those given low risks as well as high risks. These tests may distract attention away from environmental factors contributing to disease, for which social and political measures may be more appropriate than individualised susceptibility screening and lifestyle modification.

Behavioral Research↗
PubMed1995

Guidelines, enthusiasms, uncertainty, and the limits to purchasing.

Recently government ministers have set out their vision of the future of purchasing. Ineffective treatments will be discarded and purchasing will be based on guidelines or protocols rather than activity. But have the advocates of this approach considered all the issues? This paper examines the challenges of balancing the desire for protocol based uniformity with the needs of individual patients, explores the extent to which existing purchasing structures can support this process, and questions whether such moves will actually lead to reduced costs. In each case it is concluded that oversimplistic analyses are likely to be misleading and that much of the current debate fails to recognise the complexity of health care.

Clinical Protocols↗
PubMed1995

Alpha-actinin in nemaline bodies in congenital nemaline myopathy: immunological confirmation by light and electron microscopy.

To elucidate the protein composition of the nemaline bodies present in the muscle fibres of patients with congenital nemaline myopathy (CNM), we studied muscle biopsies with monoclonal antibodies against alpha-actinin and desmin in combination with a modified Gomori trichrome method. Electron microscopy of immunolabelled resin embedded sections was used for cytochemical localisation of alpha-actinin and desmin. Light microscopy of sections immunolabelled for alpha-actinin showed a cross-striation of the muscle fibres corresponding to the Z band pattern, focal thickening of the Z bands and additional reactivity with a granular pattern corresponding to the presence of nemaline bodies. Labelling of desmin did not show a similar pattern. Electron microscopy confirmed the presence of alpha-actinin in the nemaline bodies and Z bands, whereas desmin was only found in intermediate filaments around the Z bands. Western blots showed single, sharp alpha-actinin bands indistinguishable from normal. Our results provide direct evidence for the presence of alpha-actinin in nemaline bodies and a lack of quantitative or qualitative differences between the alpha-actinin of normal and CNM muscle.

Actinin↗
PubMed1995

Indications for and outcome of total abdominal hysterectomy for benign disease: a prospective cohort study.

OBJECTIVE: To describe the indications for total abdominal hysterectomy for women with nonmalignant disease and to determine the immediate (initial ten days) and medium term outcome. DESIGN: A prospective cohort study. SETTING: Three district general hospitals in shire counties, two in outer London and one London teaching hospital. SUBJECTS: Three hundred and sixty-six women undergoing total abdominal hysterectomy (with or without other procedures) for nonmalignant disease. INTERVENTIONS: Self-completed patient questionnaires before and ten days, six weeks and three months after surgery. Data extracted from patients' hospital case notes. MAIN OUTCOME MEASURES: Complications plus change in symptoms, urinary and bowel function, general health status, sexual function, activities of daily living and quality of life. RESULTS: The principal indications were bleeding, pain or both. Symptoms were severe enough to be socially debilitating and have a major impact on lifestyle. Otherwise, the women were in good health. During the first ten post-operative days the women suffered more pain, urinary discomfort, constipation and a reduction in their ability to perform activities of daily living. Urinary (25%) and wound (25%) infections were the commonest complications. At the same time, significant improvements in psychological health occurred. By six weeks, the principal symptoms had resolved for 95% of the women and early adverse effects on urinary and bowel function had settled. This was reflected in improvements in health status and quality of life including sexual activity. Despite this, these changes did not meet the pre-operative expectations of some women. CONCLUSIONS: Most women reported substantial benefits from hysterectomy. However, women should be warned about early, transient adverse effects. These findings can serve as a benchmark for nonexperimental evaluations of the effectiveness of new treatment modalities.

Activities of Daily Living↗
PubMed1995

Aland island eye disease: clinical and electrophysiological studies of a Welsh family.

Clinical and molecular genetic studies were performed on a single, large, white family, in which congenital nystagmus and moderate to high refractive error segregated as a sex linked trait with manifestation in some female carriers. In this family, affected males demonstrate myopia, but a high proportion of female carriers, and some of the possibly affected males, show hypermetropia. Clinical ophthalmic examination and electrodiagnostic studies of retinal function were fully compatible with a diagnosis of either incomplete congenital stationary night blindness or of Aland island eye disease. Previous studies have mapped both disorders to the proximal short arm of the X chromosome: our molecular studies support this localisation. Incomplete congenital stationary nightblindness and Aland Island eye disease could be considered as a single entity.

Adult↗
PubMed1995

The myotubular myopathies: differential diagnosis of the X linked recessive, autosomal dominant, and autosomal recessive forms and present state of DNA studies.

Clinical differences exist between the three forms of myotubular myopathy. They differ regarding age at onset, severity of the disease, and prognosis, and also regarding some of the clinical characteristics. The autosomal dominant form mostly has a later onset and milder course than the X linked form, and the autosomal recessive form is intermediate in both respects. These differences are, however, quantitative rather than qualitative. Muscle biopsy studies of family members are useful in some cases, and immunohistochemical staining of desmin and vimentin may help distinguish between the X linked and autosomal forms. Determining the mode of inheritance and prognosis in individual families, especially those with a single male patient, still poses a problem. Current molecular genetic results indicate that the gene for the X linked form is located in the proximal Xq28 region. Further molecular genetic studies are needed to examine the existence of genetic heterogeneity in myotubular myopathy and to facilitate diagnosis.

DNA↗
PubMed1995

Twenty-four cases of the EEC syndrome: clinical presentation and management.

Twenty-four cases of EEC syndrome were identified as part of a nationwide study. Ectodermal dysplasia, by study definition, was present in all cases and hair and teeth were universally affected. Nail dysplasia was present in 19 subjects (79%) and the skin was affected in 21 (87%). The presence of hypohidrosis was not noted as a predominant feature in the syndrome and its occurrence appeared to depend on the presence of all other features. Distal limb defects from simple syndactyly to tetramelic cleft hand and foot were identified, including preaxial anomalies. Orofacial clefting was identified in 14 cases (58%) and lacrimal duct anomaly in 21 (87%). Significant clinical problems encountered were chiefly cosmetic or ophthalmological, but conductive deafness and genitourinary problems in some cases required surgical intervention. Altered self-image was also noted in some cases. Multidisciplinary management is necessary with the early involvement of the clinical geneticist. Developmentally, the EEC syndrome and related disorders represent disorders of ectodermal/mesodermal interaction. Candidate regions include 7q21.3, the "ectrodactyly" locus; other candidates include developmental genes implicated in the ectodermal/mesodermal interactive process.

Abnormalities, Multiple↗
PubMed1995

Response to demineralized bone matrix implantation in foals and adult horses.

Equine demineralized bone matrix, particle size 2 to 4 mm, was implanted SC and IM in 4 foals and 4 adult horses. The implants were removed between 5 and 8 weeks after implantation. Bone formation was induced by SC and IM implantations in all animals. The implantation site had a marked effect on the amount of bone that developed, bone being formed earlier and in greater amounts when the matrix was implanted IM. The amount of bone formed increased with increasing time after matrix implantation at both sites. Demineralized bone matrix implantation also led to formation of small amounts of chondroid tissue; this tissue was more common in IM than SC matrix implants, and increased in amount with increasing time after implantation. Formation of this chondroid tissue did not precede the formation of bone, and there was no evidence that implantation of demineralized bone matrix in horses induced endochondral ossification. Age of the host did not appear to affect the response.

Age Factors↗
PubMed1994

Source of catalysis in the lactate dehydrogenase system. Ground-state interactions in the enzyme-substrate complex.

The Raman spectra of both the NAD-pyruvate and the pyridine aldehyde adenine dinucleotide (PAAD)-pyruvate bound to pig heart, pig muscle, and Bacillus stearothermophilus lactate dehydrogenases were measured and are nearly the same, which is consistent with the conserved shell of residues surrounding the active-site cavity in these enzymes. The symmetrical stretching mode of the pyruvate carboxylate group, found at 1398 cm-1, is shifted only slightly when complexed to these enzymes, which shows that the group remains ionized in the ion pair complex with Arg-171 on the enzyme. The vibrational mode for the carbonyl stretch of the bound pyruvate moiety is shifted about 35 cm-1 to a lower frequency than observed for the carbonyl of unliganded pyruvate in the bacterial enzyme because of polarization of the carbonyl bond. Thus, the bacterial enzyme shows the same substrate activation because of the C(+)-O- charge separation that was seen previously with the mammalian enzymes. On the basis of an empirical Badger-Bauer relationship between frequency shift and interaction enthalpy, this shift in frequency is equivalent to an approximately -14 to -17 kcal/mol interaction between the enzyme and the adduct C = O coordinate, a substantial part of which is an electrostatic interaction (hydrogen bond) between the C V O and the protonated His-195. Thus, while the C = O bond is polarized on the enzyme (which requires energy), the overall ground-state enthalpy of the carbonyl imidazolium part of the reaction coordinate is stability substantially relative to its value in solution, and this is the dominant enthalpic effect on the entire reaction coordinate since the other internal coordinates for the hydride transfer are not much affected during formation of the ternary complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

What is a chronic disease? The effects of a re-definition in HIV and AIDS.

HIV disease has recently come to be defined as a chronic disease from both policy and clinical points of view. This paper investigates the meaning and some possible implications of the redefinition. The first section examines the features identifiable from medical texts used to define a disorder as either acute or chronic and explores some of the implications of the definition on patterns of care. In particular, different types of doctor-patient relationship are examined. The second section looks at the categorisation of HIV disease using these textbook definitions, finding that HIV is most appropriately labelled as chronic. The next section uses the clinical definitions to look at two conditions for comparison with HIV; testicular cancer and multiple sclerosis. In the fourth section the policy re-definition of HIV is investigated and one of the potential effects of a policy redefinition is discussed--a change in the extent to which services are centralised. The paper concludes that the policy and clinical communities confuse the picture of HIV disease as a chronic condition. There are strong parallels between care for people with HIV disease and care delivered for an acute condition. It therefore seems likely that the policy redefinition of the disease as chronic may not be entirely adequate to use as a current model for investigating or planning patterns of care in HIV disease.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Bipolar revisions with bone-grafting for cavitary and segmental acetabular defects. A minimum 5-year follow-up study.

Bipolar revisions used in massive uncontained acetabular defects often lead to high migration rates and early clinical failure. Reconstructions for less severe acetabular bone deficiencies were studied radiographically and clinically. Thirty-two bipolar revisions with bone-grafting were performed for cavitary and segmental acetabular defects. The average follow-up period was 6 years (range, 5-8.4 years). Medial migration averaged 2.3 mm (range, 0-7 mm), oblique migration averaged 2.9 mm (range, 0-8 mm), and superior migration averaged 5.9 mm (range, 0-15 mm). Continued migration at the final follow-up evaluation was noted in all but nine hips. Arrested migration was observed when cavitary defects were encountered. Segmental medial wall defects resulted in increased medial migration. Segmental superior rim defects resulted in large amounts of superior migration. Preoperative Harris hip scores averaged 47 before surgery and 86 at the final follow-up evaluation. Postoperative clinical scores did not deteriorate with radiographic evidence of progressive migration. Six reoperations for femoral complications of fracture or loosening were performed at an average of 4.7 years with concomitant conversion of the bipolar prosthesis to a fixed cementless cup. One re-revision was performed for acetabular disassembly at 6.6 years. When cavitary defects exist, allografting with a bipolar endoprosthesis can provide durable reconstructions with excellent clinical function. Bipolar revisions are also a relatively simple means of providing stability in recurrent dislocation cases.

Adult↗