Biomedical subjects

M E Randall

Publications and source records attributed to M E Randall.

At least 37 records · Page 2Linked to original sources

PubMed1994

Increased chronic bowel complications with split-course pelvic irradiation.

PURPOSE: To assess the possible impact of various treatment factors including split-course versus continuous course treatment on the incidence of chronic bowel complications in patients receiving adjuvant pelvic radiotherapy. METHODS AND MATERIALS: A retrospective review was performed of records of 153 patients treated with adjuvant external beam pelvic radiation therapy without brachytherapy for endometrial and colorectal carcinomas. Continuous course radiotherapy was administered in 91 patients (59%) and 62 patients (41%) received split course treatment with a planned 2 week mid-treatment break. Mean pelvic dose and daily fraction size were 51.4 and 1.71 Gray, respectively. Multiple patient and treatment variables were assessed for their possible relationship to chronic bowel complications. Univariate and multivariate statistical analyses were carried out. RESULTS: Twenty-seven patients (18%) developed chronic bowel complications at a median interval of 12 months after radiotherapy. Of all factors analyzed, only the use of split course technique was associated with a significantly higher rate of chronic bowel injury and decreased complication-free survival (p = 0.009). CONCLUSION: This study supports earlier suggestions that the use of split course rather than continuous course pelvic radiotherapy can increase late intestinal complication rates. Possible pathophysiologic mechanisms are discussed.

Adult↗

PubMed1994

Blockade of GABA uptake with tiagabine inhibits audiogenic seizures and reduces neuronal firing in the inferior colliculus of the genetically epilepsy-prone rat.

Tiagabine is a new anticonvulsant drug that blocks the uptake of GABA, prolonging the action of this inhibitory transmitter. In the present study the effects of systemically administered tiagabine [30 mg/kg, ip (ED50)] were examined on audiogenic seizure (AGS) severity and neuronal firing in the inferior colliculus (IC) in the freely moving genetically epilepsy-prone rat (GEPR-9). The IC is known to be critical to AGS initiation. The effects of focal microinjection of tiagabine into the IC were also examined. Bilateral focal microinjection of tiagabine into the IC significantly reduced seizure severity in the GEPR-9. Systemically administered tiagabine also produced a significant reduction in seizure severity in the GEPR-9. Tiagabine produced a reduction in IC (central nucleus) neuronal firing, which was significant only at high acoustic intensities (90-105 dB), concomitant with the considerable reduction in seizure severity. These data are consistent with enhancement by tiagabine of gamma-aminobutyric acid (GABA)-mediated inhibition in IC, which is most prominent at high acoustic intensities. The time course of the reduction in neuronal firing of IC neurons paralleled the reduction in seizure severity. Previous studies have shown that two forms of GABA-mediated inhibition (intensity-induced and offset inhibition) in IC neurons are most prominent at high stimulus intensities, which are required to induce AGS. The blockade of GABA uptake by tiagabine may act to inhibit audiogenic seizures, in part, by intensifying these naturally occurring forms of acoustically evoked inhibition in inferior colliculus neurons.

Acoustic Stimulation↗

PubMed1994

Radiation therapy and combined chemo-irradiation in advanced and recurrent endometrial carcinoma.

The advent of surgical staging for endometrial carcinoma has identified multiple combinations and degrees of various risk factors. Therefore, it is obvious that questions regarding adjuvant treatment in advanced disease must be generally stated and the answers, when available, may not be specifically applicable to individual patients. Hopefully ongoing and future prospective trials will help to resolve questions about the proper role of RT and/or chemo-irradiation and the proper technique and treatment volume when RT is used.

Carcinoma↗

PubMed1993

Pathologic stage III endometrial carcinoma. Prognostic factors and patterns of recurrence.

BACKGROUND: This review was done to assess the outcomes and patterns of recurrence in a group of patients with Stage III endometrial carcinoma that might help guide adjuvant therapy. METHODS: A retrospective review was performed of 105 patients treated from 1970-1990 at three institutions. All patients underwent abdominal hysterectomy, with 60 having pathologic node assessment and 45 having cytologic examination of peritoneal washings. A single extrauterine site was involved in 75% of patients; 20% and 5% had two and three sites involved, respectively. All patients received postoperative external beam irradiation to the pelvis or pelvis and paraaortic regions for pathologically positive paraaortic nodes. Actuarial techniques were used to estimate the survival and recurrence rates. RESULTS: The 5-year disease-free survival rate for all patients was 64%. Univariate analysis revealed that the depth of myometrial penetration, the clear cell or papillary serous pathologic type, the histologic grade, and the number of extrauterine sites predicted disease-free survival. Cox regression revealed the grade and pathologic findings to be independent predictors of disease-free survival. The overall 5-year pelvic recurrence rate was 21%, with multivariate analysis revealing the grade to be the strongest prognostic factor. Pathologic findings and the number of involved extrauterine sites were the most important prognostic factors for abdominal recurrence and other sites of distant relapse. CONCLUSIONS: The subgroup of patients with low-grade endometrial tumors or superficial myometrial penetration has a low distant relapse rate. Local control remains the goal of therapy in these patients. Patients with high-grade tumors, deep myometrial penetration, clear cell or papillary serous histologic types, or two or more involved extrauterine sites are at high risk for distant recurrence that may include the abdomen. Investigative strategies delivering aggressive adjuvant therapy are appropriate.

Adenocarcinoma↗

PubMed1993

A call to WAR.

Explore the source record for details and available documents.

Abdomen↗

PubMed1993

Noncompetitive and competitive NMDA antagonists exert anticonvulsant effects by actions on different sites within the neuronal network for audiogenic seizures.

Excitant amino acids are implicated in audiogenic seizure (AGS) susceptibility in the genetically epilepsy-prone rat (GEPR). In the present study systemic administration of NMDA receptor antagonists significantly decreased AGS severity in the GEPR. Systemic administration of the competitive NMDA antagonists 3-((+-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonate (CPP) and 2-amino-7-phosphonoheptanoic acid and the non-competitive antagonist dizocilpine (MK-801) were effectively anticonvulsant in the GEPR. The inferior colliculus is the most critical nucleus for AGS initiation in the GEPR and an excitant amino acid is implicated as an important excitatory transmitter in inferior colliculus neurons. Systemically administered CPP significantly reduced inferior colliculus neuronal firing in the normal behaving rat and the GEPR concurrently with blockade of AGS and this effect occurred at nearly all sound intensities tested. Systemic administration of MK-801, while effective in blocking AGS, produced no consistent change in inferior colliculus neuronal firing, which is consistent with its very low potency in blocking AGS with bilateral microinjection into the inferior colliculus. These findings suggest that an important action of competitive, but not noncompetitive, NMDA antagonists is on brain stem auditory nuclei, especially the inferior colliculus, that are critical to AGS. MK-801 appears to exert its anticonvulsant effects in AGS network sites beyond the inferior colliculus. These findings and recent inferior colliculus slice studies suggest that NMDA receptors in inferior colliculus may have quantitatively different properties from those in other brain regions. These differences in NMDA receptor function in inferior colliculus may reflect NMDA receptor heterogeneity observed in binding studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗

PubMed1993

Interstitial reirradiation for recurrent gynecologic malignancies: results and analysis of prognostic factors.

Thirteen patients with recurrent or new primary gynecologic malignancies after previous radiation therapy (RT) underwent interstitial reirradiation (IRI) from July 1986 through December 1990. Mean and median ages were 63 and 70 years, respectively. Mean and median implanted volumes were 14.3 and 12 cc, respectively. Overall, 9/13 (69%) had complete responses to IRI and 6 (46%) continue to have no evidence of disease (NED) 24-71 months later (median follow-up, 59 months). Of 7 patients with recurrent cervical or new primary vaginal carcinoma, 5 (71%) remain free of disease 27-71 months (median, 58 months) after IRI. Of 6 patients with recurrent endometrial carcinomas, only 1 (16%) continues with NED 24 months after IRI. Patients with NED after IRI had a median disease-free interval prior to IRI of 100 months compared to 6 months in patients failing IRI. Trends toward improved outcomes were observed in squamous vs adenocarcinoma, smaller tumor volumes, higher implant doses, and vaginal wall/suburethra vs vaginal cuff location. One possible complication, a rectovaginal fistula, developed in the presence of recurrent cervical cancer 22 months after IRI. Interstitial reirradiation is an effective treatment for selected patients with recurrent gynecologic malignancies after previous RT. Advantages of IRI over radical surgery include its potential to preserve organ structure and function and its applicability to patients with medical contraindications to salvage surgery. Furthermore, since subsequent exenterative surgery should not be compromised in patients failing IRI, a policy of IRI as initial treatment may be justified for patients in whom the potential for morbidity is limited.

Adult↗

PubMed1993

Stimulation or blockade of the dorsal nucleus of the lateral lemniscus alters binaural and tonic inhibition in contralateral inferior colliculus neurons.

Recent studies have demonstrated that several specific types of acoustically-evoked GABA-mediated inhibition occur in neurons of the central nucleus of inferior colliculus (ICc). The dorsal nucleus of the lateral lemniscus (DNLL) provides a major GABAergic projection to ICc. The present study examined the effects of electrical or chemical stimulation or reversible blockade within the DNLL on the discharge characteristics of ICc neurons in anesthetized rats. Microinjection of a local anesthetic (lidocaine) or a GABA-A agonist (THIP) via a cannula placed into DNLL reversibly blocked acoustically-evoked binaural inhibition and increased spontaneous firing in most contralateral ICc neurons. Trains of electrical pulses or microinjection of the excitant amino acid, kainate, into DNLL resulted in reduced acoustically-evoked firing, which was similar to binaural inhibition, in most contralateral ICc neurons examined. The effects of DNLL electrical stimulation were reversibly blocked by microinjection of THIP into the stimulation site, suggesting that the effect of the electrical stimulation is mediated by direct effects on cell bodies of DNLL neurons. These data support the idea that contralateral GABAergic input from the DNLL is inhibitory to ICc neurons. Thus, binaural inhibition and tonic inhibition in ICc neurons may be mediated, in part, by the GABAergic projection from the contralateral DNLL.

Acoustic Stimulation↗

PubMed1993

Impact of bone density corrections on target dose delivered to the prostate with 4 MV, 6 MV, 10 MV, and 18 MV photons.

Doses for definitive prostate irradiation have been derived empirically using low-energy megavoltage equipment without availability of bone density corrections. With their increased availability, higher energy photons are being used more frequently because of their improved depth of penetration. Although inhomogeneity corrections lead to greater accuracy of dose delivery, the clinical utility of corrections in the pelvis is unclear. This study evaluates the effect of bone density on the dose delivered with respect to the photon energy employed. Contours and volumes for 10 patients were taken from computed tomography scans at the center of the prostate gland. Treatment plans for bilateral prostate arc fields were run on the Capintec Treatment Planning System for 4, 6, 10, and 18 MV photon energies. The monitor units needed to deliver 6500 cGy to isocenter without bone correction were used for calculations, both with and without bone correction using the equivalent path length algorithm. The median dose to the isocenter was 6500 cGy for all energies without bone correction. The median doses using the uncorrected monitor units for the 4 MV, 6 MV, 10 MV, and 18 MV photon beams corrected for bone density were 6033, 6062, 6166, and 6228 cGy, respectively. The variance in target doses observed in our patient sample was +/- 2.3%, +/- 2.2%, +/- 1.7%, and +/- 1.4%, respectively, for the 4 MV, 6 MV, 10 MV, and 18 MV beams with bone correction. The increased density of bone in the pelvis does alter the actual dose to the prostate from external beam treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Density↗

PubMed1992

An immunohistochemical study of perianal Paget's disease. Possible origins and clinical implications.

The histogenesis of perianal Paget's disease is controversial. A clinical and pathologic study was done of a patient with a history of adenocarcinoma of the rectum for whom a subsequent diagnosis of perianal Paget's disease was the sole manifestation of recurrent rectal cancer. Immunohistochemical techniques were used to compare and contrast the original rectal adenocarcinoma with the subsequent perianal skin recurrence confined to the epidermis. Both the rectal adenocarcinoma and the Paget's cells were positive for cytokeratin, epithelial membrane antigen, B72.3, and carcinoembryonic antigen and negative for gross cystic disease fluid protein-15, Leu-M1, CA 125, and S-100 protein. These findings, their relevance to the histogenesis of perianal Paget's disease, and the possible clinical implications are discussed.

Adenocarcinoma↗

PubMed1992

Glutamate in the inferior colliculus plays a critical role in audiogenic seizure initiation.

Alterations of excitant amino acid (EAA) action are implicated in seizure susceptibility in the genetically epilepsy-prone rat (GEPR). The inferior colliculus (IC) is critical for audiogenic seizure (AGS) initiation in the GEPR. The present study observed that bilateral microinjection into the IC of L-canaline, a glutamate synthesis inhibitor, decreased AGS severity in the GEPR and also decreased potassium-evoked release of glutamate from IC slices. Bilateral microinjection of NMDA receptor antagonists, 2-amino-7-phosphonoheptanoate (AP7) or 3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonate (CPP) into IC blocked AGS, and an antagonist at non-NMDA EAA receptors, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), also blocked AGS. NMDA receptor antagonists were 5-200 times more effective than CNQX. Microinjection of a non-competitive NMDA receptor antagonist, dizocilpine (MK-801), into IC had little effect except with very high doses. Microinjection of CPP or AP7 into the IC blocked AGS at considerably lower doses as compared to pontine reticular formation (PRF). However, MK-801 attenuated AGS when microinjected into PRF at doses that were ineffective in IC. Systemically administered CPP blocked AGS and significantly reduced IC neuronal firing in the behaving GEPR, suggesting an important action of systemically administered NMDA receptor antagonists on brainstem auditory nuclei critical to AGS. The present results support a critical role for glutamate acting, in part, through NMDA receptors in IC in initiation of AGS.

Acoustic Stimulation↗

PubMed1991

Issues in gynecologic radiation oncology.

Radiation therapy has a number of established roles in the curative, adjuvant, and palliative management of gynecologic malignancies. Specific indications for use of radiation therapy, concepts of integration of radiation therapy with other modalities, and techniques of radiation therapy, however, continue to evolve. Rather than discuss the use of radiation therapy in specific diseases, this paper reviews recent studies dealing with current issues in gynecologic radiation oncology.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1991

Curative potential of primary whole-abdomen irradiation in ovarian carcinoma.

Ovarian carcinoma remains a leading cause of cancer mortality in American women. The identification of active chemotherapy drugs and regimens has resulted in much less frequent use of radiation therapy at a time when technical and conceptual advances have been made. Unfortunately, the shift from radiotherapy to chemotherapy has not produced a discernible improvement in patient survival. Retrospective and prospective data suggest that whole-abdomen irradiation offers curative potential in patients with nonbulky residual disease after surgical cytoreduction. Its use should therefore be reconsidered as a primary adjuvant therapy in properly selected patients.

Abdomen↗

PubMed1991

T1-T2 carcinoma of the glottis: relative hypofractionation.

Radiation therapy, the preferred primary treatment for early squamous cell carcinoma of the glottis, offers high local control rates with voice preservation; however, the optimal treatment schedule is subject to debate. Local control, with and without surgical salvage, and associated long-term effects and complications were retrospectively analyzed in 90 patients treated with definitive radiation therapy for T1-T2 squamous cell carcinoma of the glottis. Patients received three weekly fractions of 333 cGy to a total dose of 60 Gy in 6 weeks. Median follow-up was 51.5 months. With radiation therapy alone, local control was 92% for T1 disease and 88% for T2; with surgical salvage, the control rate was 99%. Long-term effects included moderate hoarseness (16% of patients) and moderate or severe laryngeal edema (10% of patients). In seven patients who underwent salvage surgery, the complication rate was 29%. Despite excellent local control, this regimen may produce more long-term effects and complications than conventional fractionation.

Carcinoma, Squamous Cell↗

PubMed1990

Audiogenic seizure severity and hearing deficits in the genetically epilepsy-prone rat.

Hearing deficits have been observed in rodents that are susceptible to audiogenic seizures (AGS), including the genetically epilepsy-prone rat (GEPR). AGS susceptibility can be induced in normal animals by treatments that damage the cochlea. In this study, we measured the relative degree of hearing loss in animals from the GEPR substrains that exhibit different degrees of AGS severity and examined the relationship between the deficit and the AGS severity. Auditory brain stem response (ABR) thresholds to clicks in the GEPR substrain that exhibits exclusively maximal AGS severity (GEPR-9) were significantly elevated, and latencies for ABR peaks I, III, and IV were significantly increased as compared to normal Sprague-Dawley rats. ABR thresholds for the substrain of GEPRs were even higher than those in the GEPR-9, and ABR waveforms were distorted. ABR peak IV was significantly longer than normal in the GEPR-3 substrain, as were mean interpeak intervals and central conduction times. These data indicate that significant hearing deficits occur in the GEPR-3 substrain. In non-AGS-susceptible progeny of the GEPR-9 [GEPR-0(9)], ABR thresholds were not significantly different from normal. These data along with studies of ABR thresholds in thyroid-deficient rats suggest that an inverted U-shaped relationship exists between hearing deficit and AGS severity. That is, moderate threshold elevations are associated with increasing AGS severity, but when the hearing deficit exceeds a certain level, a decrement in AGS severity occurs.

Acoustic Stimulation↗

PubMed1990

Influence of grade, histologic subtype, and timing of radiotherapy on outcome among patients with stage II carcinoma of the endometrium.

In 1988, the Federation of International Gynecologic Oncologists (FIGO) adopted a new staging system mandating preradiotherapy surgical staging in endometrial cancer. To evaluate the potential impact of this recommendation on patients with cervical involvement (stage II), an analysis of 184 consecutive patients with clinical or pathologic stage II carcinoma of the endometrium treated with definitive intent at three institutions was performed. Median follow-up time was 5.7 years. Treatment consisted of total abdominal hysterectomy and bilateral salpingo-oophorectomy with preoperative radiation therapy (RT) (54%), postoperative RT (37%), or both (1%); definitive RT (7%); or radical hysterectomy (1%). The median total RT dose for combined intracavitary and external beam or either alone was 70.6 Gy with a range of 32.4-105.0 Gy. The overall 5-year survival rate and disease-free survival (DFS) rate at 5 years were 70 and 79%, respectively. Of patients treated with surgery and adjuvant radiation, 13% (22/168) had infield pelvic failure (PF) and 18% (31/168) had distant metastases (DM). Patterns of failure in patients receiving preoperative and postoperative radiotherapy are presented. Univariate analysis of pretreatment and treatment factors, including histology, grade, clinical stage, extent of cervical involvement, and timing of adjuvant radiation, revealed histology and grade to be significant predictors of DFS, PF, and DM. Clinical stage was a significant predictor of DFS only in univariate analysis. Multivariate analysis found only histology (P less than 0.001) and grade (P = 0.002) to be predictors of DFS. From this review, we conclude that histology and grade are independent predictors of DFS, and more aggressive treatment should be directed at patients with stage II endometrial cancer found to have high grade adenocarcinoma or papillary serous/clear cell histologic variants. The timing of radiotherapy was not an independent predictor of outcome; therefore, preradiotherapy surgical staging should not impact on DFS and should provide surgicopathologic information to tailor treatment and predict prognosis. The FIGO clinical staging system used in this analysis was not an independent predictor of outcome, and future multivariate analyses will be necessary to test the predictive value on outcome of the new 1988 FIGO surgical staging.

Female↗

PubMed1990

Role of intracavitary cuff boost after adjuvant external irradiation in early endometrial carcinoma.

Management of early endometrial carcinoma often consists of surgicopathologic staging followed by adjuvant radiation therapy (RT) for patients at risk of local recurrence. While an intracavitary vaginal cuff boost (VCB) is commonly given after external beam radiation therapy, its effects on local control and complication rates are unknown. To assess these effects, we reviewed 157 patients with FIGO Stage I (n = 134) or incidentally diagnosed (n = 23) endometrial adenocarcinomas. After surgery and external radiation therapy, 103 patients (65.6%) received a vaginal cuff boost of 3000-5000 cGy surface dose (Group I) and 54 (34.4%) did not (Group II). One hundred and two Group I and 52 Group II patients were evaluable for analysis. Median follow-up was 78.0 months for Group I and 60.0 months for Group II. Despite a preponderance of poor prognostic factors in Group II, no significant difference in local failure was seen. A component of local failure was seen in 6 Group I patients (6.0%) and 4 Group II patients (7.7%), p = 0.74. Distant failure, reflecting more advanced disease, was higher in Group II (19.2%) than in Group I (9.0%). Late complications included rectal bleeding/proctitis in 18.6% of Group I patients and 3.8% of Group II patients (p = 0.01). Overall, grade 2 complications occurred in 27.5% and 15.4% of Group I and II patients, respectively (p = 0.09). No difference in frequency of grade 3 complications was evident. Based on this retrospective study, intracavitary vaginal cuff boost after surgery and postoperative external beam radiation therapy does not appear to improve local control in early endometrial adenocarcinoma. Its possible effect on complication rates is uncertain.

Adult↗

PubMed1989

Analysis of failure patterns in stage III endometrial carcinoma and therapeutic implications.

The poor outcome of certain patients with Stage III endometrial carcinoma has led some investigators to direct adjuvant therapy to the abdominal cavity. To better define failure patterns, a review of 126 patients with Stage III endometrial carcinoma treated at four institutions was performed. Seventy-four patients were diagnosed at surgery with pathologic Stage III disease, whereas 52 patients presented with clinical Stage III disease. Most patients received external beam irradiation to the pelvis with a variety of boost techniques. Site of disease, grade, depth of invasion, and pathology were examined for prognostic significance. Actuarial techniques were used to analyze survival and recurrences. For the 52 clinical Stage III patients, 5-year survival was 36%. The median survival of 20 patients who were treated with radiation therapy (RT) following biopsy was 9 months. Pelvic control was poor in these patients, with 16/18 evaluable patients failing locally. Thirty-two patients who underwent resection with adjunctive RT had a 5-year survival of 48%. Local failure occurred in 40% of patients, whereas 38% of patients had abdominal failure. Isolated abdominal failure was infrequent with 6% failing as isolated recurrence, and 16% failing as the only site of distant disease. For 74 pathologic Stage III patients, 5-year survival was 54%. Local failure resulted in 20% of patients, and isolated abdominal failure occurred in 7% of patients. The subset of patients with ovarian or tubal involvement included 42 patients, with a 5-year survival of 60%. Further analysis of this subset by grade and depth of myometrial penetration was found to be prognostically significant. Twenty-four patients who were Stage III because of parametrial or pelvic peritoneal involvement had a 5-year survival of 44%. Local control and survival is improved in Stage III patients treated with surgical resection. The high rate of distant metastases in both abdominal and extra-abdominal sites has significant therapeutic implications.

Adult↗