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W Nicholas

Publications and source records attributed to W Nicholas.

8 recordsLinked to original sources
PubMed2004

A comparative study of envelope mastectomy and immediate reconstruction (EMIR) with standard latissimus dorsi immediate breast reconstruction.

BACKGROUND: Latissimus dorsi breast reconstruction has problems with scars at the donor site and on the reconstructed breast. We report the feasibility and aesthetic results of Envelope Mastectomy and Immediate Reconstruction (EMIR), which utilises a single lateral mammary fold incision. PATIENTS AND METHODS: Between 2001 and 2002, 20 EMIRs were performed in 19 patients, one as a staged bilateral procedure. Twenty consecutive patients, matched for body habitus, who had undergone standard latissimus dorsi breast reconstruction by the same surgeon from 1996 to 2000 were used as controls. Patient satisfaction was assessed using a validated Body Image Scale. Standard post-operative photographs were scored by three independent observers. RESULTS: Length of stay and complication rates were equivalent between both groups. Cosmetic self-assessment scores on the Body Image Scale and scores by the independent observers were satisfactory for both groups but no statistically significant difference was observed between groups. CONCLUSIONS: EMIR is a technically feasible and cosmetically acceptable method of immediate breast reconstruction.

Breast Neoplasms↗
PubMed2001

Evaluating an integrated approach to clinical quality improvement: clinical guidelines, quality measurement, and supportive system design.

BACKGROUND: Implementing clinical practice guidelines to change patient outcomes presents a challenge. Studies of single interventions focused on changing provider behavior demonstrate modest effects, suggesting that effective guideline implementation requires a multifaceted approach. Traditional biomedical research designs are not well suited to evaluating systems interventions. OBJECTIVES: RAND and the Army Medical Department collaborated to develop and evaluate a system for implementing guidelines and documenting their effects on patient care. RESEARCH DESIGN: The evaluation design blended quality improvement, case study, and epidemiologic methods. A formative evaluation of implementation process and an outcome evaluation of patient impact were combined. SUBJECTS: Guidelines were implemented in 3 successive demonstrations targeting low back pain, asthma, and diabetes. This paper reports on the first wave of 4 facilities implementing a low back pain guideline. METHODS: Organizational climate and culture, motivation, leadership commitment, and resources were assessed. Selected indicators of processes and outcomes of care were compared before, during, and after guideline implementation at the demonstration facilities and at comparison facilities. Logistic regression analysis was used to test for guideline effects on patient care. RESULTS: Process evaluation documented varied approaches to quality improvement across sites. Outcome evaluation revealed a significant downward trend in the percentage of acute low back pain patients referred to physical therapy or chiropractic care (10.7% to 7.2%) at demonstration sites and no such trend at control sites. CONCLUSIONS: Preliminary results suggest the power of this design to stimulate improvements in guideline implementation while retaining the power to evaluate rigorously effects on patient care.

Adolescent↗
PubMed1996

In vitro and in vivo characterisation of a recombinant carboxypeptidase G2::anti-CEA scFv fusion protein.

BACKGROUND: There is considerable interest in the specific targeting of therapeutic agents to cancer cells. Of particular promise is a technique known as Antibody-Directed Enzyme Prodrug Therapy (ADEPT). In this approach an enzyme is targeted to the tumour by its conjugation to a tumour specific-antibody tumour. After allowing sufficient time for the conjugate to localise at the tumour and clear from the circulatory system, a relatively non-toxic prodrug is administered. This prodrug is converted to a highly cytotoxic drug by the action of the targeted enzyme localised at the tumour site. OBJECTIVES: To construct gene fusions between the pseudomonad carboxypeptidase G2 (CPG2) gene and DNA encoding MFE-23 (an anti-carcinoembryonic antigen (CEA) single-chain Fv (scFv) molecule), derived from a phage display library. To overexpress the resultant gene fusions in Escherichia coli, and assess the in vitro and in vivo properties of the purified fusion proteins. STUDY DESIGN: To introduce unique cloning restriction sites into the 5'-end of the CPG2 gene by site-directed mutagenesis to facilitate fusion to the 3'-end of the gene encoding MFE-23 (constructs with or without a flexible (Gly4Ser)3 linker-encoding sequence were designed). To overexpress the resultant gene fusions under transcriptional control of the lac promoter and to direct the fusion proteins produced to the periplasmic space of E. coli through translational coupling to the pelB signal peptide. RESULTS: Biologically active recombinant CPG2::MFE-23 scFv fusion proteins were produced in E. coli and shown to possess enzyme and anti-CEA activity. Affinity chromatography followed by size exclusion gel filtration yielded approximately 0.7-1.4 mg/l from shake flask culture. The fusion protein in which the enzyme and antibody moieties were joined by a linker peptide was shown to be effectively localised in nude mice bearing human colon tumour xenografts, giving favourable tumour to blood ratios. CONCLUSION: MFE-23 scFv serves as an ideal candidate for the antibody arm of a bacterially expressed fusion protein with CPG2. The biological properties of this recombinant protein suggest that it may be employed for tumour specific prodrug activation. However, further assessment of its stability and pharmokinetics is required if genetic fusion is to be considered as an alternative to chemical conjugation.

Animals↗
PubMed1978

The borderline pituitary fossa in patients with amenorrhoea and/or galactorrhoea.

A retrospective clinicoradiological study of 80 patients with amenorrhoea and/or galactorrhoea showed: 1. Of 60 patients, in whom prolactin levels were estimated, 28 (47%) had hyperprolactinaemia (serum prolactin levels greater than 20 ng/ml). 2. Hyperprolactinaemia was present in 85% of patients with amenorrhoea and galactorrhoea, 35% of those with galactorrhoea only, and 12.5% of those with only amenorrhoea. 3. Pituitary adenomas were surgically removed from six patients; all but one had prolactin levels over 100 ng/ml. The level was 53 ng/ml in the sixth patient. 4. There is a considerable degree of observer variation in the interpretation of borderline sellar changes. 5. Minor abnormalities of the pituitary fossa were noted in 64% of patients with hyperprolactinaemia and 36% of those with normal prolactin levels. 6. The highest incidence of perfectly normal sellae was among patients with either amenorrhoea or galactorrhoea and normal serum prolactin.

Adenoma↗
PubMedDate not supplied

Mesothalamic discharge in a chronic pain, allergy and fluid retention syndrome (case report).

A 32-year-old woman was bedridden for a year because of chronic pain and headaches. She had insomnia, depression, suicidal thoughts and a severe chemical allergy. She had been on steroid therapy for two years and became Cushingoid with striae in the arm pits, groins and abdomen. However, she had no hypertension, nor the buffalo fat and hirsutism. She was very edematous, with a weight gain from 112 to 180 lbs. The fluid retention did not conform to the syndrome of inappropriate antidiuretic hormone. Studies revealed abnormal scalp EEG discharges and high-voltage seizure discharges in the posterior thalamus. Electrothalamic stimulation suppressed the thalamic discharges and relieved the patient's pelvic pain and headaches. After one month of several thalamic stimulations per day, she was able to get out of bed and ambulate. In addition, the patient no longer was edematous and was tolerating perfumes and floor detergents. Steroids were progressively reduced without complications of withdrawal. She went from a completely steroid dependent state to independent during the first 1-1/2 yrs of thalamic stimulation. With continued thalamic stimulation she has done well for 8-1/2 yrs, weighs 112 lbs, keeps house and drives a car. It's speculated the illness is a chronic pain multiple syndrome predominantly due to mesothalamic discharges and body infirmities. The mesothalamic discharge implicated neural networks, which represent biologic systems, i.e. pain, sleep, fluid retention, etc. Therapeutic stimulation attenuates the discharges and the neural networks return to their normal set points of homeostasis.

Adrenocorticotropic Hormone↗