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Biomedical subjects

J F Wilson

Publications and source records attributed to J F Wilson.

At least 19 recordsLinked to original sources

Is long-term survival possible with external beam irradiation for stage D1 adenocarcinoma of the prostate?

From 1972 to 1986, 354 patients with local and locoregional adenocarcinoma of the prostate were treated with curative intent at the Medical College of Wisconsin. Fifty-six of these patients were found to have Stage D1 disease (evidence of pelvic lymph node involvement). Using external beam irradiation alone, these patients were treated aggressively to the pelvis followed by a boost to the prostate. The median dose to the prostate was 6800 cGy, and to the pelvis, it was 5040 cGy. The median period of observation after treatment was 9 years. Actuarial survival was 76% at 5 years, and disease-free survival was 61% at 5 years. Twenty-three patients had biopsy-proved pelvic lymph node involvement; the other 33 were considered to have Stage D1 disease based on abnormal computed tomographic scans, lymphangiograms, or both. Actuarial survival and disease-free survival were calculated for both groups separately, and there was no statistical difference in the results. Major complications occurred in 3.6% (two patients) of this group with Stage D1 disease. These results support the continued use of aggressive external beam irradiation in patients with locoregional adenocarcinoma of the prostate.

Actuarial Analysis

Prognosis for breast cancer surgery and radiation therapy compared with mastectomy alone. A retrospective analysis of 759 patients with stage I/II breast cancer.

Seven hundred fifty-nine patients with Stage I/II breast cancer who were treated with mastectomy alone (558 patients) or breast-conserving surgery and tangential irradiation (201 patients) were evaluated. Median follow-up time was 34 months. Axillary node status showed differences between treatment groups. Seventy-two percent of patients undergoing lumpectomy and radiation therapy (Lx) versus 35% of patients in the mastectomy group were pathologically node-negative, 18% Lx versus 30% mastectomy alone had one to three nodes positive, and four or more positive axillary nodes were seen in 35% of mastectomy alone patients. Reflecting this trend, overall survival (P less than 0.007), time to locoregional failure (P less than 0.0005), and time to any failure (P less than 0.0001) favored Lx patients. Correcting for axillary node status, significant differences persisted only for node-negative patients. Median actuarial survival time was 73 months for the mastectomy alone group (196 patients) versus 120 months for the Lx group (144 patients) (P less than 0.02), with significant differences also noted in time to local failure (P less than 0.003) and time to any failure (P less than 0.001). Stratification according to primary tumor size in patients who were node-negative yielded marked differences in time to locoregional failure in T1 (less than 2 cm) (P less than 0.0006) presentations, with analysis approaching significance for T2 (2 to 5 cm) lesions (P less than 0.06). Disease-free interval was greater in node-negative Lx patients for both T1 (P less than 0.007) and T2 (P less than 0.05) presentations. Overall survival was not significantly different in node-negative Lx patients when primary tumor size was considered. Improved prognosis was identified in node-negative patients undergoing breast-conserving surgery and radiation therapy over mastectomy alone. Theoretical considerations included eradication of occult microscopic disease within the chest wall by tangential irradiation.

Adult

Hematoma-induced flap necrosis and free radical scavengers.

Skin flap necrosis due to underlying hematoma can be devastating in reconstructive surgery. The production of free radicals in ischemic tissue and cellular damage caused by them have been well established. Deferoxamine, which is both an iron chelator and a free radical scavenger may have a dual benefit in the pharmacologic manipulation of necrosis in a flap jeopardized by hematoma. Past studies showing the importance of free radical scavengers in improving flap survival in hematoma-induced flap necrosis have used the rat model. The porcine model was used for this study because it is the animal model that most closely resembles human skin. A statistically significant benefit of deferoxamine in reducing necrosis of a skin flap induced by hematoma formation was found. Deferoxamine appears to be promising but requires further investigation before it can be optimally used in human applications.

Animals

Endogenous glutamate stimulates release of alpha-melanocyte-stimulating hormone from the rat hypothalamus.

Release of alpha-melanocyte-stimulating hormone (alpha-MSH) and glutamic acid was quantified from superfused slices of rat hypothalamus. Application of L-glutamic acid 10(-4) M failed to evoke release of alpha-MSH but, in the presence of 10(-4) M dihydrokainic acid (DHK) an inhibitor of glutamate uptake systems, caused significant stimulation of release. DHK caused gradual and sustained increases in both alpha-MSH and glutamate release. That in alpha-MSH was blocked by 10(-4) M DL-2-amino-5-phosphopentanoic acid, a competitive N-methyl-D-aspartic acid (NMDA)-type glutamate receptor antagonist. We conclude that hypothalamic glutamate is subject to rapid uptake through mechanisms blocked by DHK and that alpha-MSH release is stimulated by endogenous and exogenous glutamate through NMDA-type receptors.

2-Amino-5-phosphonovalerate

Microdosimetric single event spectra of Ytterbium-169 compared with commonly used brachytherapy sources and teletherapy beams.

Ytterbium-169 has been developed as a possible replacement for Iridium-192 and Iodine-125. The Theory of Dual Radiation Action predicts that the initial slope of the cell survival curve and therefore the relative biological effect at low dose rate is proportional to dose average lineal energy, yd, which is the microscopic analog of the dose average linear energy transferred. The quality factor used in radiation protection has been shown to be a function of the frequency average lineal energy, yf. Single event microdosimetric spectra for 60Co, 137Cs, 192Ir, 125I and 169Yb were measured in air and at several depths in phantom with a Rossi proportional counter. These spectra show marked differences between sources. The microscopic analogs of the track average and dose average LET, (yd and yf, respectively) differ between isotopes by factors of two or even higher in comparison to megavoltage electron beams. These yd's and yf's for 169Yb are consistently higher when compared to 60Co or 137Cs but are approximately equal to those for 125I. Values of yf and yd for 192Ir are intermediate between 60Co and 169Yb. The Theory of Dual Radiation Action predicts a low dose rate RBE (assuming a 1 micron effective site diameter) compared to 60Co (in air) of: 1.00 for 137Cs, 1.29 for 192Ir, 1.60 for 169Yb and 1.77 for 125I.

Brachytherapy

Parasiticidal effect of chemotherapy in alveolar hydatid disease: review of experience with mebendazole and albendazole in Alaskan Eskimos.

Evidence that the larval stage of Echinococcus multilocularis in humans is killed by chemotherapy is presented in a review of our 17-year experience with treatment of alveolar hydatid disease in Alaska. The efficacy of chemotherapy was assessed with use of an in vivo assay of parasite viability by means of inoculation of voles, immunohistochemical tests, and histopathologic findings. Of 14 tests performed for nine patients, 12 in vivo assays (86%) were negative after chemotherapy, while only two (17%) of 12 vole tests for seven untreated patients were negative. Regression of arrest of growth of metastatic and primary hepatic lesions, together with their partial-to-complete calcification and prolonged survival times has been observed among patients treated with the benzimidazole compounds. For six who received appropriate chemotherapy, treatment has been discontinued for an average of 4.6 years (range, 3-7 years) without an increase lesion size or other evidence of reactivation.

Adult

Performance of techniques for measurement of therapeutic drugs in serum. A comparison based on external quality assessment data.

Ten assay techniques were compared using measurements of a range of 15 drugs spiked in freeze-dried samples of serum reported to the Heathcontrol External Quality Assessment Scheme between November 1988 and January 1991. Three measures of performance were studied: frequency of outliers greater than 3 standard deviations from the sample mean, the coefficient of variation (CV) of sample measurements, and the difference of the sample mean from the spike value. The most consistently precise technique was polarisation fluoroimmunoassay (PFIA). It was in the group of techniques producing significantly fewer outliers and lower CVs than other techniques for all its target analytes. However, a specific interaction with the animal serum used as sample matrix resulted in significant negative bias in PFIA measurements of carbamazepine. Other immunoassay techniques and high-performance liquid chromatography also performed well for a range of analytes, in most cases giving less than 6% of outliers with CVs of less than 13% and less than 5% bias. The least satisfactory techniques were nephelometry and gas-liquid chromatography with derivatisation, which for several analytes gave significantly more outliers and higher CV values than other techniques. In samples containing carbamazepine-10, 11-epoxide, immunoassay measurements of carbamazepine showed cross-reactivity with the epoxide metabolite of between 7 and 15%.

Carbamazepine

Aerobic fitness and opioidergic inhibition of cardiovascular stress reactivity.

The role of endogenous opioids in aerobic fitness-induced decrements in cardiovascular stress reactivity was examined by comparing the effects of opioid antagonism with naltrexone on responses to stress in young adults with high versus low levels of aerobic fitness. Two hundred forty subjects were given an activity questionnaire and males with the highest (Fit) and lowest (Nonfit) aerobic activity profiles were recruited for maximal oxygen consumption (VO2max) treadmill testing and psychological stress testing (final sample N = 28). Heart rate and blood pressures were measured during performance on a computer-controlled arithmetic task after pretreatment with either naltrexone (Trexan, DuPont) or a placebo. During placebo challenges, Fit subjects, compared with Nonfit, showed lower heart rate reactivity during stress and lower mean arterial blood pressures immediately before and during recovery from stress. Naltrexone eliminated these reactivity differences by increasing heart rate reactivity and raising mean arterial blood pressure in Fit subjects. These data suggest that aerobic fitness is associated with enhanced opioidergic inhibition of circulatory stress reactivity. Opioidergic modulatory effects on stress reactivity may comprise an important mechanism in fitness-associated risk reduction for cardiovascular disease.

Adult

Periocular lymphoproliferative diseases: natural history, prognostic factors, and treatment.

A study was undertaken to assess the natural history of periocular lymphoproliferative diseases, identify key prognostic factors, and clarify the role of orbital irradiation. Thirty-four patients with periocular lymphoproliferative disease were treated with orbital irradiation between 1975 and 1990. Eight patients had atypical lymphoid infiltrate, and 26 had malignant lymphoma. Forty-three eyes were irradiated with en-face electrons or 6-MV photons. Five-year disease-free survival for all stages was 65%; it was not significantly affected by bilaterality or site. Stage, distinction between atypical lymphoid infiltrate and malignant lymphoma, and working formulation grade were important prognostic indicators. A complete response during irradiation was achieved in 24 of 43 (56%) eyes at a median dose of 2,400 cGy, and a partial response was achieved in 19 (44%), with resolution at a median of 2.8 months. Patients with periocular reactive lymphoid hyperplasia or atypical lymphoid infiltrate may have or are at significant risk of developing lymphoma and dissemination. Local treatment remains important; orbital irradiation achieves prompt local control with acceptable morbidity.

Adult

Obesity stigma reduction in medical students.

The purpose of this study was to develop and evaluate an educational intervention designed to modify the stigma held by first-year medical students towards obese patients. The intervention, composed of video, audio and written components, was based on Petty and Cacioppo's elaboration likelihood model. Prior to the course, the medical students held largely accurate beliefs about the causes of obesity, but they still maintained negative stereotypes of the obese as lazy and lacking in self-control. Analysis of students' attitudes toward obese patients five weeks and one year after the course indicates that the intervention was effective. At the five-week assessment, students in the intervention group differed from students in the control group on six of eight measures of attitudes toward the obese. One year after the course, the intervention group was significantly more likely to rate genetic factors as important in obesity and less likely to blame the obese for their condition.

Adult

Malignant thyroid lymphoma presenting as acute airway obstruction.

Malignant thyroid lymphoma is an uncommon form of thyroid cancer which most commonly presents in elderly women. Most patients demonstrate a rapidly enlarging mass and may show tracheal deviation on chest roentgenogram. Radioisotopic scanning of the thyroid often demonstrates a "cold" or "cool" process of decreased uptake in the affected area. There is often an underlying lymphocytic thyroiditis process noted. Unfavorable prognosis is related to extracapsular extension, blood vessel wall infiltration, diffuse architectural pattern, and cervical lymph node involvement. We present two unusual cases of thyroid lymphoma presenting with acute airway obstruction and review the literature concerning this subject. One case presented a clinical and radiographic appearance similar to a prevertebral space abscess.

Abscess

A randomized comparison of patient-controlled versus standard analgesic requirements in patients undergoing cholecystectomy.

In the current study, 55 patients undergoing elective cholecystectomy were randomly allocated to receive postoperative analgesia (morphine sulfate) administered through either patient-controlled intravenous (PCA) or standard intramuscular (IM) routes. There were no significant differences in length of hospitalization or required dose of morphine sulfate. Patients randomized to PCA reported significantly improved subjective relief from pain and a smaller percentage of time in pain during each of the first two postoperative days. In addition, they reported less sedation and less interference with both postoperative breathing and pulmonary recovery than patients who received IM morphine. Theoretically, PCA regimens can deliver narcotic analgesia at a higher and more varied rate (with fewer side effects) compared with standard IM narcotic delivery, which is more limited by considerations of clinical doses. In PCA dosing, patients should experience less time in pain and sedation. The results of the current study support this premise.

Adult

Endogenous gamma-aminobutyric acid tonically inhibits release of alpha-melanocyte-stimulating hormone from rat hypothalamic slices.

Release of immunoreactive alpha-melanocyte-stimulating hormone (alpha-MSH) from superfused slices of rat hypothalamus was stimulated by the gamma-aminobutyric acid (GABA) receptor antagonist, bicuculline, and inhibited by the benzodiasepine, chlordiazepoxide, an allosteric GABA receptor modulator, demonstrating the presence of tonic inhibition of alpha-MSH release by endogenous GABA in hypothalamic tissue. Chlordiazepoxide increased the effect of exogenous GABA which by inhibiting basal release of alpha-MSH demonstrated that the tonic inhibition was not maximal in the resting state.

Animals

Anterior ischemic optic neuropathy causing blindness in the head and neck surgery patient.

Anterior ischemic optic neuropathy is an uncommon and devastating event that can result in unilateral or bilateral blindness. It has been reported as a complication of ophthalmologic or general surgical and cardiothoracic procedures as well as a spontaneous event in severe systemic disease. Aggravating intraoperative factors include anemia, hemorrhage, hypotension, preexisting small-vessel disease, and increased intraocular pressure. We present a case of anterior ischemic optic neuropathy as a complication in a 48-year-old man undergoing extensive resection of recurrent carcinoma of the head and neck. Possible contributing risk factors in our patient include preexisting hypertension, intraoperative blood loss, previous radical neck dissection with venous compromise, intraoperative head and neck edema, and the use of tightly adherent plastic bubble-type intraoperative eye protection. The possible pathogenesis of this devastating complication and recommendations for prevention and management of anterior ischemic optic neuropathy are described.

Blindness