Antenatal sonographic diagnosis of a dacryocystocele.
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Adolescent↗
Biomedical subjects
G Walsh
Publications and source records attributed to G Walsh.
The industrial production of enzymes.
The production of enzymes is a pursuit central to the modern biotechnology industry. Markets for traditional industrial enzymes continue to grow while the continued emphasis on biotechnological endeavours has generated demand for an ever increasing number of additional biocatalysts. The advent of genetic engineering has now facilitated the large-scale production of enzymes and other proteins which are produced naturally only in minute quantities. This development is particularly significant with regard to the production of enzymes and other proteins of therapeutic significance, which are now available in clinically useful quantities.The level of downstream processing to which any enzyme is subjected is dependent upon its intended application. Industrial enzymes produced in bulk generally require little downstream processing, and hence are relatively crude preparations. Enzymes destined for therapeutic applications are subject to a far higher degree of downstream processing, often incorporating 3-4 chromatographic steps. While enzymology is one of the longest established branches of the biochemical sciences, it continues to be an area of ongoing, active research. The continual discovery of new enzymes and a greater understanding of previously discovered enzymes and their functional significance suggests many novel applications for these catalytic activities. The intestinal production and utilization of enzymes will continue to be of central importance in the biotechnology industry.
Journal Article↗
GM-CSF activates regenerative epidermal growth and stimulates keratinocyte proliferation in human skin in vivo.
Granulocyte/macrophage-colony-stimulating factor (GM-CSF), an immunomodulator of hematopoietic cells, has also been shown to stimulate human keratinocyte proliferation in vitro and speed healing of wounds in the skin of lepromatous leprosy patients. In this study we have examined the in vivo effects of recombinant human GM-CSF on epidermal keratinocyte proliferation and on expression of proteins marking regenerative epidermal growth. Skin biopsies from GM-CSF injected cutaneous sites were obtained between 1 and 6 d following administration of 7.5 or 15 micrograms of the growth factor. Activation of keratinocyte proliferation, quantified as the expression of the Ki67+ nuclear antigen, was noted 1 d following GM-CSF administration. A regenerative epidermal phenotype, demonstrated by immunohistochemical staining of cellular proteins involucrin, filaggrin, and keratin 16, was similarly noted as early as 1 d following GM-CSF injection. This phenotype persisted as late as 6 d post-injection. These results suggest that GM-CSF injection into human skin induces keratinocyte proliferation as well as regenerative differentiation of the epidermis. To date no other cytokine has been shown to be mitogenic for human keratinocytes both in vivo and in vitro or to alter keratinocyte differentiation along the "alternate" or regenerative pathway.
Cell Differentiation↗
Use of a slit lamp to measure back vertex distance.
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Eyeglasses↗
Phase II study of continuous infusion fluorouracil with epirubicin and cisplatin in patients with metastatic and locally advanced breast cancer: an active new regimen.
PURPOSE: To investigate the efficacy and toxicity of continuous infusion fluorouracil (5-FU) with every-3-weeks epirubicin and cisplatin (ECF) in advanced breast cancer in a phase II study. PATIENTS AND METHODS: Forty-three patients with metastatic (n = 29) or locally advanced/inflammatory (n = 14) breast cancer were treated with 5-FU 200 mg/m2/d via a Hickman line using an ambulatory pump for 6 months with epirubicin 50 mg/m2 intravenously (IV) and cisplatin 60 mg/m2 IV every 3 weeks, for eight courses. RESULTS: The overall response rate (complete plus partial) was 84% (95% confidence interval [Cl], 76% to 96%), with a complete response rate of 24% (95% Cl, 9% to 40%) in patients with metastatic disease and 36% (95% Cl, 11% to 61%) in patients with locally advanced disease. The main World Health Organization [WHO] grade 3 or 4 toxicities included leukopenia, emesis, and alopecia. CONCLUSION: Infusional ECF is a highly active regimen in advanced breast cancer and warrants evaluation in high-risk early breast cancer.
Adult↗
Intra-articular morphine for pain relief after anterior cruciate ligament repair.
We have performed a randomized, double-blind controlled study in patients undergoing elective anterior cruciate ligament repair, to assess the effect of intra-articular morphine on postoperative pain. The morphine group (n = 11) received morphine 5 mg in saline 25 ml and the control group (n = 9), saline 25 ml intra-articularly. Patients in the morphine group had significantly smaller pain scores throughout the 24-h postoperative period compared with those in the control group (P < 0.05). There was less requirement for supplementary analgesics in the morphine group.
Anterior Cruciate Ligament↗
Risks and benefits of using Marlex mesh in chest wall reconstruction.
The records of 101 patients who had undergone chest wall reconstruction both with and without stabilization of the chest wall by Marlex mesh were reviewed to see if Marlex reduced ventilator dependence and hospital stay, and to determine whether the use of Marlex was associated with any increased risk of infection. In 40 patients in whom Marlex was used, the mean number of days on postoperative ventilator support was 0.8, and mean hospital stay was 9.7 days. In 61 patients in whom Marlex was not used, the mean number of days on ventilator support was 4.9, and mean hospital stay was 17.5 days. These differences were statistically significant (p = 0.03, p = 0.006). Two patients in the Marlex-stabilized group (5%) developed wound infections, but these were preceded by ischemic necrosis of overlying flaps. None of the patients without Marlex developed wound infections. That difference was not statistically significant. We conclude that the use of Marlex in chest wall reconstruction does not significantly increase the risk of wound infection, provided that overlying tissues are properly vascularized and remain viable, and that synthetic mesh does improve chest wall stability and reduce ventilator dependence and overall hospital stay.
Adult↗
Staff perspectives on sexual behavior of patients in a state psychiatric hospital.
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Adult↗
Novel responses of human skin to intradermal recombinant granulocyte/macrophage-colony-stimulating factor: Langerhans cell recruitment, keratinocyte growth, and enhanced wound healing.
Recombinant granulocyte/macrophage-colony-stimulating factor (rGM-CSF), prepared from Chinese hamster ovary (CHO) cells and Escherichia coli, was administered to 35 patients with the borderline and polar lepromatous forms of leprosy by the intradermal and subcutaneous routes at doses of 7.5-45.0 micrograms/d for 10 d. With each of these doses and routes, increases in the number of circulating eosinophils were noted. After the intradermal injection, the local skin sites demonstrated zones of roughening and micronodularity that appeared within 24-48 h and persisted for more than 6 d. Reinjection of sites led to enhanced areas of epidermal reaction. GM-CSF prepared from CHO cells was a more potent inducer of this effect. GM-CSF given by the subcutaneous route, at higher doses, failed to initiate these changes. At the microscopic level, the epidermis became thickened (+75%) with increased numbers and layers of enlarged keratinocytes. These contained increased numbers of ribosomes and prominent nucleoli, and were imbedded in a looser meshwork of the zona Pellucida. The modified keratinocytes remained MHC class II antigen negative throughout the course of the response. A major change in the dermis was the progressive accumulation of CD1+, Birbeck granule-positive cells. These Langerhans were recognizable at 48 h after intradermal injection and reached maximum numbers by 4 d. During this period the number of epidermal Langerhans cells remained relatively constant. No increment in dermal Langerhans cells occurred when GLM-CSF was injected by the subcutaneous route. No appreciable increase in the numbers of T cells and monocytes was noted, and granulocytes and eosinophils were largely present within the dermal microvasculature. 4-mm punch biopsies taken from injected sites and adjacent controls were compared in terms of the rapidity of wound healing. 22 of 26 sites demonstrated more rapid filling and hemostasis, whereas four were equivalent to controls. We conclude that rGM-CSF, when introduced into the skin, leads to enhanced keratinocyte growth, the selective recruitment of Langerhans cells into the dermis, and enhanced wound healing of the prepared site. There was no evidence of an enhanced cell-mediated response to Mycobacterium leprae, and bacillary numbers remained unchanged.
Adolescent↗
Time-averaged accommodation response to flickering stimuli.
Experiments are described in which the steady-state accommodation response versus stimulus curve was measured with an infrared autorefractor for high-contrast stimuli having a 100% square-wave temporal modulation of luminance in the frequency band 1-200 Hz. Slightly more accurate responses were found at frequencies approximately 50-100 Hz, i.e. above flicker fusion. The relevance of the results to practical situations in which flicker may be experienced is discussed.
Accommodation, Ocular↗
Variation in ocular modulation and phase transfer functions with grating orientation.
For circular pupils of diameters < or = 2 mm the optical performance of the eye in monochromatic light is effectively diffraction-limited, so that its modulation transfer function (MTF) is essentially independent of grating orientation and its phase transfer function (PTF) is close to zero. For larger pupils, however, the wave aberration of the eye usually exceeds the Rayleigh quarter-wavelength limit. It is shown that the monochromatic MTF may then display marked variation with orientation and the associated PTFs can be non-zero. The exact effects vary markedly with the individual subject. In white light additional asymmetries may occur due to transverse chromatic aberration.
Contrast Sensitivity↗
A randomised comparative trial of mitozantrone/methotrexate/mitomycin C (MMM) and cyclophosphamide/methotrexate/5 FU (CMF) in the treatment of advanced breast cancer.
Mitozantrone (Novantrone) has recently been incorporated into a new combination chemotherapy regimen with mitomycin-C and methotrexate (MMM) against advanced breast cancer. We have compared MMM (mitozantrone 8 mg m-2 i.v. q 3 weekly, methotrexate 35 mg m-2 i.v. q 3 weekly, mitomycin-C 8 mg m-2 i.v. q 6 weekly) with CMF (cyclophosphamide 100 mg orally, days 1-14, methotrexate 35 mg m-2 i.v., days 1 and 8, 5-FU 1,000 mg i.v., days 1 and 8, q 4 weekly), each regimen with folinic acid rescue, in a randomised trial, 29/57 evaluable patients treatment with MMM achieved an objective response (51%) compared with 33/55 treated with CMF (60%). Overall median survival was 16 months for MMM and 12 months for CMF. Subjective toxicity was low for both regimens and the only significant difference was in incidence of diarrhoea (50% for CMF vs 21% for MMM). Haematological toxicity was similar, leading to treatment delays and/or dose reductions in 35% patients with CMF vs 43% with MMM. Thrombocytopenia was significantly increased in MMM (34% vs 14%). No clinical cardiotoxicity was seen, but a significant reduction in left ventricular ejection fraction occurred in four patients on CMF vs 2 on MMM. MMM is an active, well tolerated new chemotherapy regimen for advanced/metastatic breast carcinoma with an efficacy and toxicity spectrum very similar to CMF.
Adult↗
The subjective sensitivity to small changes in the contrast of a suprathreshold grating.
Small periodic (0.25-40 Hz) changes in the contrast of suprathreshold, spatially sinusoidal (0.8-10.5 c/deg) grating test objects were generated on an oscilloscope screen. It was found that the minimum temporal modulation in spatial contrast which could be detected subjectively was approximately proportional to the mean contrast of the grating during the change, provided that the minimal spatial modulation of the grating was above threshold. The contrast increment threshold was dependent on both the grating spatial frequency and the temporal frequency of the modulation: for any fixed temporal frequency in the range 2-8 Hz it increased approximately linearly with spatial frequency; for fixed spatial frequency the threshold was minimal at temporal frequencies of a few Hz. The relevance of these results to the possible role of fast fluctuations in the control of accommodation response is considered.
Accommodation, Ocular↗
Duct carcinoma in situ: predictors of local recurrence and progression in patients treated by surgery alone.
Between 1972 and 1982, 60 patients with histologically proven duct carcinoma in situ (DCIS) without evidence of invasive disease were treated by surgery alone. Treatment was not randomised and was total mastectomy (19), subcutaneous mastectomy (6) or local excision (35). Follow-up was by clinical examination and mammography with a median follow-up of 9 years (range 4-16 years). Twenty-six patients (43%) have recurred locally. The estimated proportion recurrence free at 7 years is 59% (95% CI 46-72%). Local recurrence on the chest wall occurred in one patient having total mastectomy and in the chest wall or nipple in three patients having subcutaneous mastectomy. Twenty-two patients recurred locally in the breast after conservative surgery. The 7-year recurrence-free rates were 94%, 44% and 45% respectively in the three groups. Of those patients who recurred locally 14/26 (54%) did so with invasive disease. Of the 34 who did not develop local recurrence, two developed metastases. The only factor which correlated with local recurrence and invasive local recurrence on multivariate analysis was conservative surgery (hazard ratio 4.71 (1.59-14.0), P = 0.001, and 4.05 (1.00-18.7), P = 0.03, respectively). DCIS can be an aggressive local disease and local excision may be inadequate treatment.
Breast Neoplasms↗
Endoscopic guided percutaneous tracheostomy: early results of a consecutive trial.
Percutaneous tracheostomy is increasingly being used for patients needing prolonged ventilatory support. The purpose of this study was to assess the feasibility of widespread application of endoscopic guided percutaneous tracheostomy. Sixty-one consecutive ICU patients requiring prolonged mechanical ventilation underwent bedside endoscopic guided percutaneous tracheostomy. Using a modified Ciaglia technique, a #6-10 tracheostomy tube was introduced between the second and third tracheal rings. Bronchoscopic transillumination facilitated identification of the appropriate tracheostomy site, and verified satisfactory placement of dilators and tracheostomy tube. There was one procedure-related death due to arrhythmia. Procedure-related complications included (n = 7): bleeding (controlled with local pressure), two infections, two cuff tears, and two obstructions of the tracheal tube. The tracheostomy was eventually removed in 13 patients. Bronchoscopic evaluation of three patients at 4 months post-tracheostomy removal was normal and there has been no clinical evidence suggestive of tracheal stenosis in the remaining ten extubated patients. There was a 50% reduction in cost when compared to operative tracheostomy. Percutaneous tracheostomy is a simple, safe, cost-effective bedside procedure for critically ill ventilator-dependent patients. Endoscopic guidance appears to increase the safety of this procedure and may prevent complications of pneumothorax, subcutaneous emphysema, and paratracheal false passage previously reported with blinded percutaneous methods.
Adult↗
Duct carcinoma-in-situ: can we predict recurrence after surgery?
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Breast Neoplasms↗
Primary medical therapy for operable breast cancer.
Fifty-seven patients with large but potentially operable primary breast cancer were treated with primary medical therapy rather than initial mastectomy, using chemotherapy (15) or endocrine therapy (42) with the tumour remaining in situ. Of patients treated with chemotherapy, one (7%) achieved a complete remission, and eight (53%) a partial response (overall response rate 60%). Only one patient had progressive disease while on chemotherapy. Of patients who received endocrine therapy, one (2%) achieved a complete response, and 19 (45%) a partial response (overall response rate 47%). Two patients progressed on endocrine therapy. Only 10 patients have so far had a subsequent mastectomy (18%), and 17 (30%) have had radiotherapy and/or conservative surgery. The rest are still on medical therapy. With a median follow-up of 19 months (range 6-42 months) only two patients have had a local recurrence after being disease-free and none have developed uncontrollable local recurrence. Eight (14%) have developed distant metastases and four (7%) have died of metastatic disease. Primary medical therapy may offer an effective alternative to mastectomy for patients with operable breast carcinomas too large for conservative surgery and merits further study.
Adult↗
Variations in the local refractive correction of the eye across its entrance pupil.
We show that normally a spherocylindrical lens will correct the local refractive error of any small area of the pupil. In general, however, the correction varies with position across the pupil. Plots are given to illustrate this variation for 2 typical individual eyes and for the average of 11 eyes, as calculated from the corresponding wavefront aberrations. The implications of these results for the design and use of objective optometers are briefly considered.
Astigmatism↗