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Biomedical subjects

N Daly

Publications and source records attributed to N Daly.

At least 19 recordsLinked to original sources
PubMed1999

Bromodeoxyuridine induces keratin protein synthesis at a posttranscriptional level in human lung tumour cell lines.

Keratin intermediate filaments are formed in epithelial cells in a cell- and tissue-specific manner, but much remains unknown regarding the mechanisms which control the synthesis of these proteins. We examined the effect of the differentiation modulation agent, bromodeoxyuridine (BrdU), on two human keratin-negative (by immunocytochemistry) lung cell lines, DLKP and H82, and showed immunohistochemically that treatment with 10 microM BrdU over 7 days induced K8 and K18 protein synthesis in both lines. Immunoprecipitation and Western blot analyses revealed low levels of K8 and K18 proteins in untreated cell homogenates. These levels increased following treatment with BrdU for 7 days. K8 and K18 mRNAs were detected by Northern blot and reverse transcriptase polymerase chain reaction analyses in both lines before BrdU treatment, but no increase in mRNA levels was observed in either cell line over 21 days of treatment. This suggests, firstly, that keratin synthesis is normally blocked at a posttranscriptional level in DLKP and H82 cells, and secondly, that BrdU can reverse this block. A549 is a human lung cell line which contains K8 and K18 proteins. Treatment with BrdU increased K8 and K18 protein levels in these cells. No corresponding increase in K8 mRNA levels occurred, while an apparent increase in K18 mRNA levels was detected. HL-60 is a leukaemic cell-line of haematopoietic rather than epithelial lineage which contains K8 and K18 mRNA transcripts prior to BrdU treatment, but does not contain keratin proteins. Again, K8 and K18 mRNA levels remained unchanged during BrdU treatment. However, neither K8 nor K18 proteins were detected following treatment, although BrdU is known to alter expression of other genes in HL-60 cells. BrdU thus appears to act at a posttranscriptional level and in an epithelial-specific manner to reverse a block in keratin synthesis in keratin-negative lung cancer cells and increase synthesis in keratin-positive lung cancer cells. This may represent a regulatory step in early lung development or a mechanism whereby tumour cells downregulate expression of a differentiated phenotype.

Antimetabolites, Antineoplastic↗
PubMed1997

Carcinoma of the intact uterine cervix treated with radiotherapy alone: a French cooperative study: update and multivariate analysis of prognostics factors.

PURPOSE: To determine independent prognostic factors in a group of 1875 patients with invasive carcinoma of the intact uterine cervix treated with radiotherapy alone in a French cooperative study from 1970 to 1993. MATERIALS AND METHODS: Patients were staged according to the UICC-FIGO and MDAH substaging. The distribution per FIGO stage was Ia-Ib: 25.5%; IIa: 12%; IIb: 29%; IIIa: 5%; IIIb: 25%, and IV: 3.5%. Ninety-two percent had squamous cell carcinoma. The maximum diameter of the clinically detectable cervical disease was less than 3 cm in 24.5% of Stages I-II and in 10% of Stages III-IV, more than 5 cm in 13.5% of Stages I-II, and in 16% of Stages III-IV. Nodal involvement was shown on lymphangiogram in 16% of Stages I-II and in 32.5% of Stages III-IV. RESULTS: 1) Univariate analysis of Stages I and II: stage, cervical disease diameter, and nodal involvement are significant prognostic factors. Five-year specific survival rate (5ySS) is 83.5% in Stage Ib, 81% in IIa and 71% in IIb. Five-year disease-free survival rate (5yDFS) is 86% in tumors less of 3 cm, 76% in tumors of 3 to 5 cm, and 61.5% in tumor larger than 5 cm. Lymphangiogram strongly influences the 5-year pelvic disease-free survival rate (5yPDFS): respectively, 90% in nonpositive lymphangiogram vs. 65% when positive. A significant drop in specific and disease-free survival is observed (10 and 14%, respectively (p = 0.04) when comparing adenocarcinoma and squamous cell carcinoma. Age is a significant prognostic factor for specific survival because patients aged less than 30 years old have 91% vs. about 75% for patients over 30 years (p = 0.03). 2) Univariate analysis of Stages III-IV: Stage and positive lymphangiogram are predictive factors for relapse and death. The MDAH substaging is more reliable to predict the probability of pelvic disease-free survival in Stage III. At 5 years, the FIGO Stages IIIa and IIIb have a rather similar PDFS (65% vs. 59%). Conversely, the difference of survival rates between MDAH Stage IIIA and Stage IIIB is more demonstrative (69% vs. 47.5%). 3) Multivariate analysis (Cox P. H. R. model). Nodal involvement and stage remain significant for all three models in all stages (p < 0.0001). Age above 70 years influences specific survival for Stage I-II (p = 0.01). Tumors larger than 5 cm and adenocarcinoma also appear to be independent prognostic factors for specific and disease-free survival in Stage I-II (p = 0.05 and p = 0.005, respectively). CONCLUSIONS: The relevance of tumor size (less or greater than 4 cm) is now recognized in the 1995 revised FIGO staging in Stage Ib but unfortunately not in other stages. Tumor size per stage and nodal status should be systematically recorded to allow a better prediction of failure rates and to compare literature reports.

Adenocarcinoma↗
PubMed1996

mdr1 ribozyme mediated reversal of the multi-drug resistant phenotype in human lung cell lines.

An mdr1 hammerhead was introduced into two adriamycin-selected multi-drug resistant human lung cell lines both of which over-express p-glycoprotein. Expression of the ribozyme resulted in a decrease in mdr1 mRNA expression and an increase in drug sensitivity in both cell lines. This would suggest that the use of specific ribozymes may represent an effective and specific approach in order to restore cellular sensitivity towards anti-cancer drugs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

ENT surgery in children with inherited bleeding disorders.

Inherited bleeding disorders are frequently considered an absolute contraindication to tonsillectomy and other ENT procedures. Over a 15-year period we have performed ten elective tonsillectomies and five bilateral myringotomies on children with inherited bleeding disorders. All procedures were carried out with the close co-operation of the Haematology Department in the hospital. All patients underwent uneventful surgery. One patient returned after tonsillectomy with a secondary haemorrhage which did not require surgical intervention. We present our team approach to the management of these children and demonstrate that necessary surgical intervention can be undertaken safely in this select group of patients.

Child↗
PubMed1996

Fractures and dislocations of the digits.

Digital trauma is a common, but often underappreciated, entity in podiatric practice. This article outlines the pathomechanics, diagnosis, and treatment of digital fractures and dislocations as well as injuries to the toenail and nailbed.

Fracture Fixation↗
PubMed1995

Observation of the mechanism of snoring using sleep nasendoscopy.

We have performed sleep nasendoscopy on 54 adult snorers in whom obstructive sleep apnoea had been excluded by an overnight sleep study. The purpose of the study was to identify the site or sites of noise production in each case. This was successfully achieved in 50 of the 54 and 70% showed palatal flutter snoring only. In a further 20%, palatal flutter snoring was combined with evidence of noise generation at another site. The second site was supraglottic in 10%, tonsillar in 8% and tongue base in 2%. The tongue base was also the sole site of noise generation in 8% and the epiglottis was the sole site in 2%. This study suggests that sleep nasendoscopy can identify different mechanisms of snoring in individual patients. This information is likely to be of use in formulating a logical surgical treatment plan.

Adult↗
PubMed1995

Choosing talkers for the BKB/A Speechreading Test: a procedure with observations on talker age and gender.

A procedure is described for choosing talkers for the BKB/A (BKB/Australian version) Speechreading Test. The main aims were: to select several talkers from a pool of potential talkers, to avoid adventitiously choosing a markedly atypical single talker; to assess speechreading as a general skill rather than as talker-specific; and to select talkers who were acceptable to speechreaders, relatively easy to speechread, and comparable in their speechreadability. Because of the number of variables involved and the demanding nature of the task for speechreaders, a three-stage selection procedure was adopted. In the resulting BKB/A 21-sentence list Speechreading Test, four of the 16 sentences in a list are each spoken by four talkers, chosen as follows. In Stage 1, 16 talkers (four of each age/gender set: older men, older women, younger men, younger women) were selected from an original pool of 40 (10 of each set), via rankings made by eight hearing-impaired judges with speechreading experience. In Stage 2, the final four talkers (one of each set) were selected from the 16 via the speechreading scores of further hearing-impaired subjects with speechreading experience. In Stage 3, the order of talker appearance within lists (in random order versus over blocks of four consecutive sentences) was determined. This three-stage approach to talker selection identified differences between talker candidates within sets, except for younger men, and suggested that, overall, younger women were the easiest to speechread. The discussion addresses the merits and disadvantages of this approach to talker selection, and suggests some reasons for the documented differences in speechreadability among talkers of different age and gender.

Cross-Over Studies↗
PubMed1993

Carcinoma of the cervical stump: a review of 213 cases.

From 1970 to 1987, 213 cases of carcinoma of the cervical stump were accrued in a multi-institutional prospective cooperative study. This group accounted for 5.5% of cervical carcinoma diagnosed during the same period. 13 had in situ carcinoma and 200 had invasive carcinoma (96% squamous cell carcinoma, 4% adenocarcinoma). Radiotherapy alone (external and brachytherapy) was given to 77%, brachytherapy and surgery to 15% and surgery alone to 8%). FIGO stage distribution was: I (31%), IIa (15%), IIb (27%), IIIa (5%), IIIb (17%) and IV (5%). Five-year locoregional control per stage was 100% in Ia, 85% in Ib, 82% in IIa, 71% in IIb, 45% in IIIa, 54% in IIIb and 30% in IV. Corrected 5-year survival per stage was 82% in Ib, 78% in IIa, 73% in IIb, 69% in IIIa, 38% in IIIb and 0% in IV. The diameter of disease in stage II strongly influenced the 5-year locoregional control (81% for tumours of less than 3 cm vs. 68% for tumours more than 3 cm). Lymphangiogram was associated with a 44.5% 5-year locoregional control when positive vs. 74% when non-positive. Brachytherapy was advantageous in obtaining locoregional control in patients receiving external irradiation and brachytherapy: 81.5% vs. 38.5% in patients treated with external radiotherapy alone. Surgery was performed only for in situ carcinoma and for part of stages Ia, Ib and IIa. There is no significant difference in locoregional control at equal stage between radiotherapy alone and treatment schemes including surgery. However, lethal complications were observed in 6% of the patients of the surgical group as compared to 0.6% of the patients treated with radiotherapy alone. Radical radiotherapy seems to provide similar results of locoregional control and survival at equal stages in carcinoma of the cervical stump compared to carcinoma developed on an intact uterus. The rate of severe complications reported with the French-Italian glossary is 13% for G3 and 3% for G4, which is close to the observed rate during the same period in our series of radical radiotherapy to the intact uterus.

Adult↗
PubMed1992

Topical application of WR-2721 to prevent radiation-induced proctosigmoiditis. A phase I/II trial.

Patients undergoing x-ray therapy to the pelvis have intestinal symptoms proportional to the volume treated and the dose delivered. WR-2721, S-2 (3-aminopropylaminoethyl) phosphorothioic acid, is an organic thiophosphate compound that selectively protects normal tissues against radiation effects. A Phase I/II study was done to test the ability of topical application of WR-2721 to protect the mucosa of the rectosigmoid from radiation damage. Thirty-one patients were enrolled in this study, of which, seven were control subjects. Twenty-four patients received WR-2721 daily, in enema form, 45 minutes before treatment. The patients were assigned by groups of three to receive increasing doses of WR-2721 beginning with 100 mg/enema to 450 mg/enema. Rectal mucosal biopsies were obtained within the treated field before, during, and at the end of therapy. The degree of damage to the rectal mucosa was scored on the basis of a 0 to 4 scale (with 0, least damage to 4, most damage) as determined by the percentage of damaged mucosal crypt glands. The patients' symptoms were recorded once a week during the entire course of therapy. The biopsy scores of the control group were slightly higher than those of the treatment groups; however, this difference did not appear to be significant. In the treated groups, there was a slight decrease in the biopsy scores with increasing doses of WR-2721, but this trend was not sustained. There were no differences among any of the groups in the symptoms experienced during the course of therapy. This study showed that WR-2721 could be administered safely in enema form in doses ranging from 100 to 450 mg/enema, but this drug did not protect the rectosigmoid mucosa from radiation damage at the doses administered.

Administration, Topical↗
PubMed1992

Cervical and vaginal cancer associated with pessary use.

From 1967 to 1990, 96 previously untreated patients with cervicovaginal cancer associated with a history of vaginal pessary use to control uterovaginal prolapse were referred to eight radiation therapy departments in France. Sixty-eight patients had cervical cancer, and 28 had vaginal cancer. The mean interval between pessary insertion and cancer diagnosis was 18 years, with a range of 1 to 41 years. Most patients received radiation therapy and brachytherapy. Few (5%) had Grade 3 treatment side effects. The overall 5-year relative survival rate was 54%; nonsurvival was related to locoregional recurrence. Because almost all tumors occurred at the site of pessary insertion, foreign body chronic inflammation in association with viral infection may be the cause of the tumors.

Aged↗
PubMed1992

Lateral subtalar dislocation. A literature review and unusual case report.

An unusual case of suspected lateral subtalar joint dislocation was reported. A review of the literature found that medial dislocations were reported four times more frequently than lateral dislocations. Half of the cases of subtalar dislocation reviewed here described associated fractures, the incidence of which was higher in lateral dislocations. In both types of dislocations examined, almost half were reduced nonoperatively. In most cases, long-term results of repair of these injuries were considered favorable.

Adult↗
PubMed1992

Modification of the crescentic osteotomy for hallux valgus correction. A preliminary report.

A new proximal osteotomy for hallux valgus correction, which has several advantages, is presented. These advantages include good stability; ease of rigid, two-point internal fixation; accurate, reproducible correction of the intermetatarsal angle; minimal shortening or elevation of the metatarsal; and early weightbearing. Preliminary results on 12 feet of 12 patients over a 3-year period have been encouraging and may indicate that this osteotomy is a viable alternative when considering proximal osteotomy for correction of hallux valgus.

Hallux Valgus↗
PubMed1991

Combined postoperative radiotherapy and weekly cisplatin infusion for locally advanced squamous cell carcinoma of the head and neck: preliminary report of a randomized trial.

A prospective clinical trial was designed to evaluate efficacy, toxicity, and patient compliance of concomitant postoperative radiotherapy and Cisplatin infusion in patients with Stage III or IV S.C.C. of the head and neck and histological evidence of extra-capsular spread of tumor in lymph node metastase(s). Cisplatin 50 mg IV with forced hydration was given or not every week (i.e., 7 to 9 cycles) concurrently with radiotherapy. Between 1984 and 1988, 83 patients were randomized: 44 were treated by irradiation without chemotherapy (RT group) and 39 by the combined modality (CM group). There was no significant difference between the two groups in terms of patient characteristics, primary sites, tumor differentiation, T.N. stages, or postoperative prognostic factors. All patients completed the planned radiotherapy. There were seven severe toxicities (greater than grade 3) in the RT group. In the CM group, 30 severe toxicities occurred in 16/39 (41%) patients but none was life-threatening. Seven of 39 (18%) patients received less than two-thirds of the scheduled Cisplatin courses because of intolerance, mainly nausea and vomiting. Preliminary results show a better disease-free survival for the CM group (65% at 24 months) than for the RT group (41% at 24 months). This significant difference is largely due to increased loco-regional control in the CM group (79% vs 59%), the actuarial distant metastasis rates in patients controlled above the clavicles not being statistically different in the two groups.

Carcinoma, Squamous Cell↗
PubMed1991

Lisfranc's fracture-dislocation. A review of the literature and case reports.

The authors present an in-depth discussion of Lisfranc's fracture-dislocations, including classifications, mechanisms of injury, radiographic evaluation, and a literature review. Four cases are presented for review. Lisfranc's fracture-dislocation is a rare injury that can lead to prolonged disability if undiagnosed or if there is a delay in treatment.

Adult↗