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Biomedical subjects

L Finn

Publications and source records attributed to L Finn.

51 records · Page 3Linked to original sources

Alternative splicing of CD44 pre-mRNA in human colorectal tumors.

Expression of the CD44 molecule has been linked to tumor growth and metastases in both human and rodent cancers. Alternatively spliced variants expressed in rat and mouse tumors have been shown to confer metastatic potential to non-metastatic carcinoma cell lines, and human homologues of rat variant mRNA sequences are expressed in human tumors. In the present study matched sets of RNA from adenocarcinomas of the colon and distant normal mucosa were assayed for CD44 expression by quantitative RT-PCR. Retrospective analysis revealed that colonic tumor cells had both quantitative and qualitative differences in CD44 expression when compared to normal mucosa. These were: 1) an increase in levels of CD44 transcripts, 2) an increase in levels of alternatively spliced transcripts, 3) the presence of larger alternatively spliced transcripts with inserts > 400 bases and 4) the primary alternatively spliced CD44 isoform in colonic adenocarcinomas in all cases is CD44R. Interestingly, two patterns of CD44 isoform expression termed "variant dominant" or "balanced" patterns of expression, based on the ratio of variant to standard CD44 transcripts (R+V's/H), could be differentiated. An unfavorable prognosis was suggested for tumors expressing increased levels of CD44 variant exons previously associated with tumor metastasis. Specifically, patients with tumors expressing the "variant dominant" pattern of expression irregardless of Dukes classification and Dukes C and D staged tumors of both patterns exhibited a poorer prognosis.

Adenocarcinoma↗

Pattern of failure and survival of patients with metastatic urothelial tumors relapsing after cis-platinum-based chemotherapy.

Cis-platinum-based chemotherapy combinations have improved the outcome of patients with metastatic urothelial tumors, since two-thirds of these patients respond to treatment. Nevertheless, the majority of such patients have relapse within a median of 12 months. To define the pattern of failure and subsequent outcome, we retrospectively assessed 58 consecutive patients with relapse after prior response to cis-platinum-based combination chemotherapy. Of the patients who presented initially with local-regional metastases, 74% had relapse with involvement of a similar site, while only 26% of these patients had visceral metastases at relapse. The median survival after relapse was 9 months, and parameters associated with longer survival were local-regional relapse (10.7 months) and response to salvage chemotherapy (12.6 months). These data suggest that select patients with urothelial tumors and local-regional metastases may benefit from consolidation therapy with surgery or radiotherapy after maximum response to chemotherapy.

Adult↗

Phase I study of interleukin-2 combined with interferon-alpha and 5-fluorouracil in patients with metastatic renal cell cancer.

Interferon-alpha (IFN-alpha) and interleukin-2 (IL-2) each has produced a 15%-20% response in metastatic renal cell cancer. Combining IFN-alpha with either IL-2 or 5-fluorouracil (5-FU) enhanced IFN-alpha activity. We have therefore conducted a Phase I Study combining IL-2, IFN-alpha, and 5-FU. The patients were continuously infused with IL-2 (1-3 x 10(6) u/m2) and 5-FU (600-750 mg/m2) for a 5-day period every 28 days, and IFN-alpha (4-5 x 10(6) u/m2) was injected subcutaneously daily. Lymphokine-activated killer (LAK) and natural killer (NK) cell activity was measured on days 0 and 8. Twenty-one patients received 76 courses. All primary tumors were controlled by surgery (81%) or angioinfarction. Hematologic toxicity was mild; median nadir of platelets was 117 K/microL and of granulocytes was 1.2 K/microL. Dose-limiting toxicity included mucositis, liver damage, and hypotension. No treatment-related death occurred, and only one patient required intensive-care-unit support. Two patients had an objective response, one of which was a complete response. Increased LAK cell and NK cell activity occurred at all IL-2 dose levels. Simultaneous delivery of IL-2, IFN-alpha, and 5-FU is safe and shows antitumor and biologic activity. 5-FU did not appear to suppress IL-2-induced LAK and NK cell activation. Maximum tolerated dose of the three-drug combination is IL-2, 2 x 10(6) u/m2, 5-FU 600 mg/m2, and IFN-alpha, 4 x 10(6) u/m2.

Adult↗

Evidence of malignant features in histologically mature teratoma.

A total of 33 specimens from 29 patients with residual stable teratoma and mature growing teratoma after chemotherapy was analyzed for clinicopathological and deoxyribonucleic acid (DNA) flow cytometric variables, as well as the presence of proliferative antigen and tumor marker levels in an attempt to explain their clinical behavior. We compared the flow cytometric and histological data of these stable and growing teratomas, and of nonseminomatous germ cell tumors before chemotherapy. The DNA content of residual teratoma did not differ significantly from that of the primary testicular tumors (1.38 versus 1.48). Histological analysis of stable and growing teratomas revealed no significant difference but proliferative cellular nuclear antigen was expressed mainly in the epithelial component of the growing teratoma. alpha-Fetoprotein, beta-human chorionic gonadotropin and carcinoembryonic antigen were elevated in the fluid of 6 excised teratomas, while concomitant serum levels were normal. The aneuploidy and elevated cystic fluid tumor markers confirm the malignant phenotype of post-chemotherapy residual teratomas. Therefore, complete surgical removal is essential despite the benign histological appearance.

Antigens, Neoplasm↗

Cisplatin combination chemotherapy for elderly patients with urothelial tumours.

The proportion of cancer patients who receive potentially curative therapy declines with increasing chronological age. Between January 1979 and January 1988, 36 patients aged from 76 to 84 years (median 78) consented to cisplatin combination chemotherapy. Eighteen patients received 1 to 7 cycles of adjuvant chemotherapy (median 5). This resulted in a drop in creatinine clearance rate from 70 +/- 28.5 ml/min to 49 +/- 20 ml/min. Eight patients (44%) are alive without evidence of disease, with a whole group median survival of 23 months. The dose intensity of cisplatin was found to predict recurrence. Eighteen other patients were treated for metastatic disease; 39% had an objective response after receiving 2 to 9 cycles (median 7). Only 2 patients (11%) are alive and free of disease. In this group no significant kidney damage occurred and the dose intensity of cisplatin did not predict response. Treatment resulted in a significant sepsis rate (39%) and 6 patients (17%) withdrew from treatment because of toxicity. It was concluded that cisplatin combination chemotherapy can be administered without treatment-related death and its efficacy is similar to that in younger patients. Age should not exclude patients from the potential benefit of such therapy. An important cause of reduced benefit from chemotherapy among elderly patients may be the reduced dosage of cisplatin.

Aged↗

Escalated therapy for refractory urothelial tumors: methotrexate-vinblastine-doxorubicin-cisplatin plus unglycosylated recombinant human granulocyte-macrophage colony-stimulating factor.

Thirty-two assessable patients with metastatic urothelial tumors refractory to standard chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) were treated with escalated doses of MVAC plus unglycosylated recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). Results of this phase I trial revealed that escalated MVAC (30 mg of methotrexate/m2, 4 mg of vinblastine/m2, 60 mg of doxorubicin/m2, and 100 mg of cisplatin/m2) can be tolerated by heavily pretreated patients. The side effects of rhGM-CSF are dose- and schedule-dependent. The maximum tolerated dose is 250 micrograms/m2 per day as a single dose administered subcutaneously (SC) for 10 consecutive days. This dose is well tolerated in outpatients, resulting in only modest fever and few side effects. The same dose delivered as a continuous infusion or a higher dose delivered either as a continuous infusion or SC caused significant side effects. For phase II trials, the starting dose of rhGM-CSF when combined with escalated MVAC is 120 micrograms/m2 per day SC for 10 consecutive days. forty percent of the treated patients responded, seven (23%) with complete remission and five (17%) with partial remission. This response rate is higher than anticipated from such a modest dosage escalation in chemotherapy-refractory patients.

Agranulocytosis↗

A prospective randomized trial comparing MVAC and CISCA chemotherapy for patients with metastatic urothelial tumors.

To evaluate the relative efficacy of cisplatin, cyclophosphamide, and Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) (CISCA) versus methotrexate, vinblastine, Adriamycin, and cisplatin (MVAC), a prospective randomized trial was performed in patients with advanced metastatic urothelial tumors. Patients were stratified by histologic disease type and degree of tumor dissemination. Equal distribution of the clinical characteristics was achieved. One hundred ten patients with metastatic disease of the urinary tract (86 bladder, 16 renal pelvis, seven ureter, one prostatic urethra) met eligibility criteria and were enrolled on study. These represented 82% of the total patients seen during the study period in the Section of Genitourinary Oncology who met the eligibility criteria. The combined complete and partial response rate was significantly higher for patients treated with MVAC than for those treated with CISCA (65% v 46%; P less than .05). The survival duration of MVAC-treated patients was significantly longer than that of CISCA-treated patients (mean, 62.6 weeks; median, 48.3; range, 5.0+ to 162.3+ v mean, 40.4 weeks; median, 36.1; range, 7+ to 147.1+). We conclude that MVAC chemotherapy is superior to CISCA chemotherapy, achieving a higher response rate and a longer survival for equivalent patients with metastatic urothelial tumors.

Adult↗

Interferon alternating with chemotherapy for patients with metastatic renal cell carcinoma.

A prospective randomized trial tested the hypothesis that interferon and cytotoxic chemotherapy delivered sequentially would be synergistic and would increase the response rate in metastatic renal cell carcinoma. Thirty-six patients were entered and randomized to chemotherapy only (5-fluorouracil, doxorubicin, mitomycin, and cis-platin) vs. interferon alternating with the same chemotherapy. Only 4 of 32 evaluable patients (13%), 2 in each arm, had a major response. Three patients in the alternating arm had minor responses. Complete, partial, and minor responses totaled 7 (22%). All four patients whose only disease was lung metastasis had some evidence of response (p = 0.001). Interferon alternating with chemotherapy did not appear to improve the major response rate over chemotherapy alone. Responses in metastatic renal cell carcinoma appear confined to a favorable subset of patients.

Antineoplastic Combined Chemotherapy Protocols↗

Elongation of peripheral nerve and viscera containing smooth muscle.

Peripheral nerve, ureter, and small bowel will all elongate over a soft-tissue expander. Elongation of peripheral nerve serves as an effective alternative to nerve grafting both in selected clinical cases and in experimental settings. While canine ureter functions well with little morphologic change following elongation, the rabbit small bowel morphology and function are significantly altered after elongation through expansion.

Animals↗

Infection control in GP surgeries: safe practices?

Any increase in the use of invasive procedures carries with it an increased risk of cross-infection. The spread of the human immunodeficiency virus, together with increasing awareness of hepatitis B virus, cytomegalovirus and human papillomavirus have focused attention on the nature and adequacy of procedures to prevent cross-infection in general practice.

Ambulatory Surgical Procedures↗

Nurses' documentation of infection control precautions: 1.

Inadequate nursing records may contribute to untoward incidents and yet advised precautions for the control of infection can be poorly documented. The infection control nurse must promote a safe environment for the patient and ensure that an effective control policy is carried out. The literature suggests that nurses may lack the necessary knowledge and skills with which to assess, plan and evaluate appropriate care for safe infection control. This article, the first of two parts, discusses these issues together with various strategies at the infection control nurse's disposal that may influence nursing practice and the documentation of care.

Clinical Competence↗

Nurses' documentation of infection control precautions: 2.

A small action research study was undertaken, using a quasi-experimental approach, to establish to what extent infection control advice was documented and to assess the effectiveness of the provision of an example care plan for control of infection. The study population comprised two groups of patients colonized or infected with ALERT organisms and involved 28 wards in six hospitals. Baseline data confirmed that infection control precautions were documented for less than 25% of patients overall. Provision of an 'example' care plan, together with guidance in its use, was followed by an increase in documentation for all items audited, while identification of the infection in the care plan showed a statistically significant increase (P < 0.05). However, in spite of this apparent improvement the documentation of appropriate care for control of infection remained inadequate. It is concluded that, while various strategies to effect change are at the infection control nurse's disposal, the need to integrate infection control with practice must be addressed at every level to include managers, educators and practitioners.

Education, Nursing, Continuing↗

Population-based study of sleep-disordered breathing as a risk factor for hypertension.

BACKGROUND: Clinical observations have linked sleep-disordered breathing, a condition of repeated apneas and hypopneas during sleep, with hypertension but evidence for an independent association has been lacking. Understanding this relationship is important because the prevalence of sleep-disordered breathing is high in adults. OBJECTIVE: To test the hypothesis that sleep-disordered breathing is related to elevated blood pressure independent of confounding factors. METHODS: The sample included 1060 employed women and men aged 30 through 60 years who had completed an overnight protocol as part of the Wisconsin Sleep Cohort Study. In-laboratory polysomnography was used to determine sleep-disordered breathing status, quantified as the number of apneas and hypopneas per hour of sleep (apnea-hypopnea index). Blood pressure was measured on the night polysomnography was performed. RESULTS: Blood pressure increased linearly with increasing apnea-hypopnea index (P = .003 for systolic, P = .01 for diastolic, adjusted for confounding factors). The magnitude of the linear association increased with decreasing obesity. At a body mass index (weight in kilograms divided by the square of the height in meters) of 30 kg/m2, an apnea-hypopnea index of 15 (vs 0) was associated with blood pressure increases of 3.6 mm Hg for systolic (95% confidence interval, 1.3-6.0) and 1.8 mm Hg for diastolic (95% confidence interval, 0.3-3.3). The odds ratio for hypertension associated with an apnea-hypopnea index of 15 (vs 0) was 1.8 (95% confidence interval, 1.3-2.4). CONCLUSIONS: There is a dose-response relationship between sleep-disordered breathing and blood pressure, independent of known confounding factors. If causal, the high prevalence of sleep-disordered breathing could account for hypertension in a substantial number of adults in the United States.

Adult↗