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Biomedical subjects

R L Stephens

Publications and source records attributed to R L Stephens.

At least 37 records · Page 2Linked to original sources

Mutant p53 expression in prostate carcinoma.

The expression of the mutant p53 tumor suppressor gene was evaluated in 33 human prostate carcinomas. Using an immunohistochemical method with monoclonal antibodies PAb 1801 and PAb 240, 26 (79%) tumors demonstrated positive immunostaining for mutant p53. Only areas of glandular tumor were positive, with adjacent stromal elements and areas of glandular hyperplasia being negative. The predominant staining pattern was cytoplasmic. This pattern may be related to p53 binding to certain heat shock proteins (HSP 72/73), as a monoclonal antibody to these proteins demonstrated a cytoplasmic location as well. These results demonstrate that abnormal p53 expression is a frequent event in prostate cancer.

Adenocarcinoma↗

Doxorubicin, mitomycin C and 5-fluorouracil in the treatment of hormone refractory adenocarcinoma of the prostate: a Southwest Oncology Group study.

In a Southwest Oncology Group phase II clinical trial, 68 patients with hormone refractory carcinoma of the prostate were treated with a combination of doxorubicin, mitomycin C and 5-fluorouracil. Of the patients 11 were classified as good risk and 57 as poor risk. There were 1 complete and 10 partial remissions for a response rate of 16.2% (exact 95% confidence interval 8.4 to 27.1%). Median survival was 9 months (maximum 14) for good risk patients and 10 months (maximum 42) for poor risk patients. Toxicity was significant with leukopenia identified as dose limiting. Because of the low rate of response and significant toxicity, this regimen cannot be recommended as standard therapy for metastatic hormone refractory prostate cancer.

Adenocarcinoma↗

p53 expression in incidental prostatic cancer.

Incidental prostate cancer is an indolent disease typically characterized by a benign clinical course. This is not clearly established, however, as recent reports suggest that up to 27% of cases progress with long-term follow-up. The indolent history of this disease led initially to the hypothesis that mutations of the p53 gene would be an infrequent event in this patient population. Archival specimens from 24 patients with Stage A1 carcinomas were evaluated for abnormal p53 expression. In 23 patients the disease was diagnosed after transurethral resection for bladder outlet obstructive symptoms, and in one patient after a radical prostatectomy. Using a monoclonal antibody (PAb 240) and an immunohistochemical technique, a total of 36 microfoci of tumor were evaluated. Thirteen (36%) microfoci were positive with an intense nuclear staining pattern (2+), and eight (22%) microfoci had an intermediate staining pattern. Four areas of prostatic intraepithelial neoplasia also stained positively with a 2+ staining pattern. These results suggest that abnormal p53 expression is a feature of a significant number of incidental prostatic carcinomas and that this occurrence is an early event in the development of the malignant phenotype.

Aged↗

Phase II trial of mitotane and cisplatin in patients with adrenal carcinoma: a Southwest Oncology Group study.

PURPOSE: Previous reports of chemotherapy in patients with adrenal cancer have described responses to cisplatin (CDDP). Because of these reports of good results, a phase II trial that used CDDP with and without mitotane (o,p'DDD) was initiated. PATIENTS AND METHODS: Patients with metastatic or residual adrenocortical carcinoma with objectively measurable disease or biochemical abnormalities were divided into good-risk and poor-risk categories. The latter received CDDP 100 mg/m2 intravenously, and the former received 75 mg/m2. o,p'DDD was administered at a 1,000-mg dose orally four times a day along with cortisone acetate and Florinef (fludrocortisone acetate; Bristol-Myers Squibb Co, Princeton, NJ). RESULTS: Of a total of 42 patients entered onto the study, 37 were eligible. Twenty-nine patients received good-risk and eight received poor-risk doses of CDDP. Functioning tumors were present in 45% of patients. Objective responses were noted in 30% (11 of 37) patients (95% confidence interval, 16% to 50%). Response duration was 7.9 months, and the median time to response was 76 days. The median survival of the 37 eligible patients was 11.8 months, and a significant survival advantage was found for patients who underwent prior surgical removal of their primary tumor or bulky disease, who had a performance status of 0 or 1, or who had synchronous metastatic disease. Toxicity of the CDDP and o,p'DDD combination was moderate to severe, and the most common side effects were gastrointestinal, renal, and neurologic. CONCLUSION: The regimen of CDDP and o,p'DDD has activity in patients with adrenocortical carcinoma; however, the toxicity of this treatment was moderate to severe.

Adolescent↗

Phase II trial of ifosfamide and cisplatin in the treatment of metastatic sarcomas: a Southwest Oncology Group study.

The Southwest Oncology Group (SWOG) performed a phase II trial of a combination of ifosfamide/mesna/cisplatin in patients with metastatic soft-tissue sarcoma who had previously received one chemotherapeutic regimen. A total of 39 patients were registered in the study, including 7 treated during a limited-institution pilot phase; 38 patients were fully eligible and evaluable. During the pilot phase, patients were treated with 2.5 g/m2 ifosfamide daily on days 1-3, 2.5 g/m2 mesna daily on days 1-4, and 100 mg/m2 cisplatin on days 2 and 9. Due to excessive myelosuppression, the day-9 cisplatin dose was dropped when the study was opened groupwide, and the subsequent 32 patients were treated at 3- to 4-week intervals with 2.5 g/m2 ifosfamide daily on days 1-3, 2.5 g/m2 mesna daily on days 1-4, and 100 mg/m2 cisplatin on day 2. Myelosuppression was severe, with granulocytopenia (< 0.5 x 10(9)/l) being observed in 26 of 38 patients. Three cases of National Cancer Institute grade 3 or 4 nephrotoxicity (serum creatinine, > 3 times the normal value) and three cases of grade 3 or 4 central nervous system toxicity were reported. Overall, three complete and five partial responses were achieved, for a major response rate of 21%. The median survival of all patients was 11 months. We conclude that ifosfamide-based chemotherapy can produce objective responses in previously treated patients with metastatic soft-tissue sarcoma but that cisplatin increases the toxicity of therapy. Phase II trials of new agents are needed to identify drugs with clinical activity in the treatment of soft-tissue sarcomas.

Adolescent↗

Thyrotropin-releasing hormone analogue and serotonin interact within the dorsal vagal complex to augment gastric acid secretion.

The effects of serotonin (5HT) and a thyrotropin-releasing hormone (TRH) analogue, RX77368, on vagal control of gastric acid secretion were studied. Microinjection of RX77368 (0.66 pmol in 10 nl), but not 5HT (8 pmol in 10 nl), into the dorsal vagal complex (DVC) evoked a significant increase in acid output. When the same doses of RX77368 and 5HT were co-injected, the amount of acid secreted was significantly greater than that due to RX77368 alone. Thus, 5HT and the TRH analogue interact within the DVC to enhance vagal stimulation of acid secretion. The study suggests a possible functional significance of raphe TRH/serotonergic tracts projecting to the DVC.

Animals↗

Fluoxetine pretreatment potentiates intracisternal TRH analogue-stimulated gastric acid secretion in rats.

Central injection of TRH or its metabolically stable analogue RX 77368 has been demonstrated to produce a vagal-dependent stimulation in gastric acid secretion. Accumulating evidence exists regarding the interaction of serotonin (5HT) with TRH containing neuronal systems. This study was performed to assess the effect of pretreatment with the 5HT uptake inhibitor fluoxetine on the TRH analogue-induced gastric acid secretory response. Systemic fluoxetine (30 mumol/kg, i.v.) produced a 43-85% increase in the intracisternal RX 77368 (78-780 pmol)-induced gastric acid output, while not affecting the basal acid response. The acid response to a lower dose of RX 77368 (26 pmol) was not altered. In addition, intracisternal fluoxetine (180 nmol) produced a 71% augmentation of the acid secretory response of i.c. RX 77368 (260 pmol). Intracisternal injection of lower doses (60, 120 nmol), or intravenous injection of 180 nmol of fluoxetine was ineffective in altering the intracisternal RX 77368-induced acid response. Pretreatment with the noradrenergic or dopaminergic uptake inhibitor desipramine or GBR 12909 did not alter the RX 77368-stimulated gastric acid secretory response. The results show that fluoxetine pretreatment potentiates the effect of intracisternal RX 77368 on acid secretion. The effect appears to be impulse dependent, and central sites of action are involved. The data suggest an interaction of synaptic serotonin with a RX 77368-elicited event (activation of TRH receptors, second messenger systems and/or firing of the motor vagus) results in potentiation of the RX 77368-induced gastric response.

Animals↗

Phase II evaluation of didemnin B in advanced adenocarcinoma of the kidney. A Southwest Oncology Group study.

The Southwest Oncology Group studied the response rate and toxicity of didemnin B (3.47 mg/m2 i.v. q 28 days) in patients with advanced renal cell carcinoma. There were no responses in 22 response evaluable patients. Toxicity was significant with 10 patients having grade 3 or 4 toxicity. Toxicity seen included nausea and vomiting, exacerbation of coronary artery disease, hyperglycemia, anorexia, diarrhea and hepatitis. Didemnin B was toxic but inactive in patients with renal cell treated at this dose.

Adenocarcinoma↗

Treatment of stages B3 and C seminoma with chemotherapy followed by irradiation therapy. Southwest Oncology Group Study.

Beginning in 1981, 28 patients with advanced seminoma were treated with combination chemotherapy followed by irradiation to evaluate the possibility of improved survival using both modalities. The treatment protocol consisted of two courses of vincristine, actinomycin-D, and cyclophosphamide followed by reassessment. Those initially presenting with Stage B3 disease who achieved a complete response to two cycles of chemotherapy then underwent irradiation. All others were given a third course of chemotherapy before undergoing irradiation. The pre-radiation portion of this protocol produced a complete response rate of only 25 percent, substantially less than other, more recent, protocols. Radiation therapy produced a complete response in 69 percent of those who did not achieve a complete response from chemotherapy, increasing the complete response rate from 25 percent to 64 percent. Given this response rate to radiation therapy and the difficulty of dissection and associated morbidity with the surgical excision of postchemotherapy residual masses, the best option at this time may be observation with salvage chemotherapy and/or radiation reserved for those with disease progression.

Antineoplastic Combined Chemotherapy Protocols↗

Antiulcer activity of the calcium antagonist propyl-methylenedioxyindene--V. Localization of site of action.

1. Propyl-methylenedioxyindene (pr-MDI) is an intracellular calcium antagonist which inhibits cold-restraint stress ulceration at subcardiovascular doses (less than or equal to 30 mg/kg). It also inhibits gastric acid secretion evoked by RX77368 (a stable analog of thyrotropin-releasing hormone, the putative mediator of cold-restraint stress ulcers). 2. The objective of this investigation was to localize the site of the inhibitory effect of pr-MDI on gastric acid secretion stimulated by intracisternal (i.c.) administration of RX77368 (100 ng) in rats. 3. Peripheral administration of pr-MDI (30 mg/kg i.p. or i.v.) inhibited the elevated basal and the RX 77368-induced acid secretion in conscious 2-hr pylorus-ligated rats. This effect was completely blocked in anesthetized (urethane or pentobarbital) acute gastric fistula rats. 4. Intracisternal administration of pr-MDI (0.1-1 mumol) produced a dose-related inhibition of acid secretion in conscious pylorus-ligated rats. However, urethane anesthesia completely blocked the inhibitory effect of i.c.-administered pr-MDI (1 mumol) on RX77368-induced acid secretion. 5. Since previous studies indicate that anesthesia does not inhibit peripheral actions of pr-MDI (e.g. the antiarrhythmic effect), the convergent evidence suggests that the inhibitory effect of pr-MDI on gastric acid secretion is mediated primarily via the central nervous system.

Animals↗

Case report: breast cancer in males--a genetic consideration.

For many years, it has been recognized that a portion of female breast cancer is inherited. More recently, the probable contribution of heredity to at least a subset of male breast cancer also has surfaced. This report, which describes affected brothers, a half sister, and the common paternal grandmother, provides further support for the role of genetic factors in male breast cancer. Also noteworthy was the presence of prostate carcinoma in the sibling with bilateral disease and in the unaffected father.

Adult↗

TRH analogue microinjected into specific medullary nuclei stimulates gastric serotonin secretion in rats.

Brain nuclei involved in vagal release of gastric serotonin (5-HT) were investigated in urethan-anesthetized rats acutely implanted with gastric cannula. Gastric secretions were collected every 10-15 min for 2 h, and measurement of serotonin 5-HT was performed by high-performance liquid chromatography (HPLC) with electrochemical detection and that of acid by titration. The stable thyrotropin-releasing hormone (TRH) analogue, RX 77368, microinjected into the dorsal vagal complex (DVC) (1.5-77 pmol/50 nl) induced a dose-related and long-lasting increase in gastric 5-HT and acid output. TRH (276 pmol) microinjected into the DVC also stimulated gastric 5-HT secretion. TRH action was abolished by vagotomy. RX 77368 (77 pmol) increased 5-HT release after microinjection into the raphe obscurus, raphe pallidus, and nucleus ambiguus, although the responses were significantly lower compared with that induced by DVC microinjection. No changes in gastric 5-HT release were observed when the peptide was microinjected into the lateral hypothalamus, hypoglossal, paramedian reticular, inferior olive, lateral paragigantocellular or spinal trigeminal nucleus. The potent gastric 5-HT release induced by TRH or TRH analogue into the DVC added to the presence of TRH receptors and TRH-LI nerve terminals in the DVC suggest a role of medullary TRH in the vagal regulation of gastric 5-HT release.

Animals↗

Imagery: a treatment for nursing student anxiety.

This study examined the effectiveness of audiotaped imagery in reducing anxiety and improving test performance among first-year nursing students. Volunteer subjects were randomly assigned to three groups, imagery-only, imagery/relaxation, and a no-treatment control group. Pottest state anxiety scores in these groups were significantly lower (p = .001) than in the no-treatment control group. Test performance did not differ significantly (p = .067). Subjects using the audiotaped imagery reported an increased sense of well-being, improved ability to sleep, greater energy, and improved self-confidence.

Adolescent↗

Effects of 2 mg and 4 mg atropine sulfate on the performance of U.S. Army helicopter pilots.

Atropine autoinjectors are issued to aviators for use in the event of organophosphate poisoning on the battlefield. This investigation assessed the effects of unchallenged 2 mg and 4 mg doses on flight performance, vision, tracking, cognitive performance, and electroencephalograms of 12 Army aviators. Effects were seen most often with the 4 mg dose in terms of aircraft control problems, vision disturbances, impaired tracking, reduced cortical activation, and decreased cognitive skill. These problems indicate helicopter tactical flight is dangerous after an unchallenged 4 mg dose. Other types of flight should also be avoided for at least 12 h after atropine.

Adult↗

Oncology patients and the living will.

The Patient Self-Determination Act now requires hospitals, nursing homes, and health maintenance organizations to ask patients if they have executed and are in possession of a living will. This article provides a brief historical perspective of what living wills are, how patient autonomy has contributed to their existence, and what distinguishes a living will from a durable power of attorney for health care. Included are working examples of these advance directives and a description of the University of Kansas Cancer Unit's positive experience with living wills. The final section discusses the meaning of certain pivotal terms, looks at the current under-utilization of living wills, and closes with an examination of the Blackhall thesis of futility.

Attitude to Death↗