PURPOSE: The chronic and acute toxicities associated with conventional radiotherapy of localized prostate cancer are well documented. However, the degree and incidence of toxicities with conformal techniques are not known. Studying side effects associated with modern radiotherapeutic techniques is more important now since there has been a general trend to use computerized tomography-based techniques in recent years; beam's eye view-based conformal techniques are also becoming more commonplace. It is possible that the local disease control can be improved with the delivery of higher doses than currently used. Conformation of the treatment volume to the target volume may facilitate such dose-escalation. However, prior to such dose-escalation, it is important to know the toxicities associated with such techniques with conventional doses. METHODS AND MATERIALS: We have compared week-by-week acute toxicities associated with conventional (Group A, 16 patients), computerized tomography-based, manual (Group B, 57 patients) and beam's eye view-based (Group C, 43 patients) techniques during 7 weeks of radiotherapy. Group B and C patients were treated contemporaneously (1988-1990). RESULTS: Acute side effects gradually increased from week 1 through weeks 4-5 and generally declined or plateaued after that. The incidence of acute toxicities was significantly less with the beam's eye view/based technique than with the other two methods. For instance, the percentages of Grade 2 acute genitourinary toxicities for Groups A, B, and C were as follows: Week 1-0, 0, 0; Week 2-6, 0, 0; Week 3-6, 9, 2; Week 4-12, 14, 9; Week 5-35, 14, 9; Week 6-31, 16, 7; Week 7-33, 8, 8, respectively. The p values associated with differences in acute genitourinary toxicities for Weeks 1-7 using chi-square test were 0.072, 0.627, 0.389, 0.538, 0.123, 0.06, and 0.012; the p values for acute gastrointestinal toxicities were 0.512, 0.09, 0.031, 0.031, 0.003, < 0.0001, and 0.004, respectively. Pairwise comparison (Wilcoxon rank-sum test) showed statistically significant lower acute toxicity in Group C than Group B (e.g., p values, Weeks 1-7 for gastrointestinal toxicity: 0.633, 0.056, 0.010, 0.014, < 0.0001, < 0.0001, and < 0.0001, respectively) in the latter part of the treatment course. No correlation was found between the extent of toxicity and the patient age or the overall treatment time. Also, no correlation was found between the degree of toxicity and the radiation dose and fraction size, within the narrow ranges used (65-70 Gy and 180-200 cGy, respectively). A trend suggesting increased severity of toxicity with increase in the volume of treatment was seen. CONCLUSION: The findings in this retrospective study need to be confirmed by other prospective studies.

Acute Disease↗

PubMed1993

Environmental modulation of the autonomy of cytotoxic T lymphocytes.

The extent to which one compartment of the immune system depends on another for efficient function is important to establish to fully comprehend disease phenotypes arising from selective immunodeficiency. Just how much the major histocompatibility complex class I-restricted cytotoxic T cell responses depend on class II-restricted T cell help has been controversial. Using the influenza A virus system, we show that mice unable to make class II-restricted T cell responses due to an engineered defect in class II molecule expression are able to mount virtually normal cytotoxic responses when bred under specific-pathogen-free conditions. However, when exposed to the more diverse environmental challenges of a conventional breeding facility, a situation that more closely parallels immunodeficient states in man, they show impaired cytotoxic responses.

Amino Acid Sequence↗

PubMed1993

Computed tomography and neurological soft signs in obsessive-compulsive disorder.

Computed tomography was used to compare the following three groups: obsessive-compulsive disorder (OCD) patients with high scores on a soft neurological sign examination, OCD patients with low soft neurological sign scores, and control subjects. Neuranatomical structures were measured using quantitative volumetric analysis. OCD patients with high soft sign scores had significantly increased ventricular volumes compared with OCD patients with low soft sign scores and control subjects. Caudate and lenticular nucleus volumes did not differ between groups.

Adult↗

PubMed1993

A potential imaging agent for the GABAA receptor: 4-t-butyl-1-(4-[123I]iodophenyl)-2,6,7-trioxabicyclo-[2.2.2]octane.

Based upon the known high toxicity and high antagonist activity of t-butylorthobenzoates towards the GABA receptor complex, 4-t-butyl-1-(4-iodophenyl)-2,6,7-trioxabicyclo[2.2.2]octane 5 and its radioiodo analogues ([123I]-5 and [131I]-5 were prepared as potential markers for the gated chloride channel of GABAA receptors. Mice showed rapid clearance of [131I]-5 from all organs including the brain. The radioactivity was found to proceed into the urine in spite of the high lipophilicity of 5, the high binding affinity of 5 for plasma protein and the apparent chemical stability of 5 in plasma.

Animals↗

PubMed1993

CD4-positive helper T lymphocytes mediate mouse cardiac allograft rejection independent of donor alloantigen specific cytotoxic T lymphocytes.

Mouse heterotopic cardiac allograft recipients were depleted of CD4+ or CD8+ T lymphocytes in vivo to assess cellular requirements for graft infiltration, tissue damage, and acute allograft rejection. Modified limiting dilution analysis was employed to quantitate IL-2-producing Th lymphocytes (HTL) and CTL infiltrating the graft. Results were correlated with graft function and histologic evidence of tissue damage. In unmodified recipients, large numbers of donor alloantigen-specific CTL infiltrated the graft, overshadowing a modest number of HTL. CTL infiltration coincided with tissue damage and loss of graft function, suggesting a key role for CTL in rejection. In vivo treatment with anti-CD4 mAb inhibited both HTL and CTL infiltration, and no histologic evidence of tissue damage was observed. This observation suggested that HTL, although few in number, regulated the development of effector CTL and/or entry of these CTL into the graft. Reconstitution of HTL-depleted recipients with IL-2 resulted in graft infiltration by stimulated CTL, as assessed by modified limiting dilution analysis. However, these stimulated CTL failed to mediate tissue damage, and graft survival was prolonged. Unlike CTL obtained from unmodified recipients, graft-infiltrating CTL of IL-2-reconstituted mice were incapable of directly lysing donor cells in a 51Cr release assay. Hence, while IL-2 facilitated partial CTL differentiation and mobilization to the graft, additional signals appear necessary for maturation into lytic CTL. Furthermore, in recipients depleted of CTL by treatment with anti-CD8 mAb, HTL infiltrating the allograft, though few in number, were associated with extensive tissue damage and loss of graft function. These data suggest a less important role for CTL in the rejection process, and indicate that graft-infiltrating CTL are insufficient as sole mediators of cardiac allograft rejection. Potential mechanisms by which CD4+ HTL mediate cardiac allograft rejection independent of CTL are discussed.

Animals↗

PubMed1993

Influence of age and hemodynamics on myocardial blood flow and flow reserve.

BACKGROUND: Aging is associated with changes of the systolic blood pressure that may increase cardiac work and myocardial blood flow at rest and reduce the myocardial flow reserve. This might be misinterpreted as age-related impairment of the coronary vasodilator capacity. METHODS AND RESULTS: Myocardial blood flow was quantified at rest and after administration of intravenous dipyridamole in 40 healthy volunteers (12 women and 28 men) with 13N-ammonia and positron emission tomography. Eighteen of the normal subjects were less than and 22 were older than 50 years (31 +/- 9 versus 64 +/- 9 years). The resting rate-pressure product was lower in the younger than in the older subjects (6895 +/- 1070 versus 8634 +/- 1890; P < 0.01). Myocardial blood flow at rest averaged 0.76 +/- 0.17 mL.min-1.g-1 in the younger volunteers and 0.92 +/- 0.25 mL.min-1.g-1 in the older volunteers (P < 0.05). Hyperemic blood flows did not differ between younger and older subjects (3.0 +/- 0.8 versus 2.7 +/- 0.6 mL.min-1.g-1; P = NS); however, minimal coronary resistance was higher in the older subjects. Corrected for indexes of coronary driving pressure, hyperemic flow was lower in older than in younger normal subjects. The higher resting blood flows combined with similar hyperemic flows resulted in a lower myocardial flow reserve in the older than in the younger normal subjects (4.1 +/- 0.9 versus 3.0 +/- 0.70; P < 0.0001). The flow reserve was more closely correlated with resting than with hyperemic blood flows. CONCLUSIONS: Aging does not alter significantly dipyridamole-induced hyperemic flows; although coronary vascular resistance after dipyridamole was somewhat increased in older subjects. The gradual decline of the myocardial blood flow reserve correlates with an age-related increase of baseline myocardial work and blood flow. These findings suggest that the reduced flow reserve with age is primarily due to increased cardiac work and blood flow at rest rather than to an abnormal vasodilator capacity.

Adult↗

PubMed1993

Noninvasive detection of vertebral artery dissection.

BACKGROUND AND PURPOSE: We sought to identify the use of duplex and transcranial Doppler sonography in the noninvasive diagnosis of vertebral dissection. METHODS: Ten patients with a diagnosis of symptomatic vertebral artery dissection confirmed by cerebral angiography were retrospectively analyzed. RESULTS: Computed tomographic scanning and magnetic resonance imaging together delineated lateral medullary or cerebellar infarcts in 7 patients. Angiography documented a total of 21 vertebral artery lesions (16 stenoses and 5 occlusions), with 7 of 10 patients having multiple sites of vertebral artery dissection. Vertebral Doppler was abnormal in 8 of the 10 patients. A high resistance signal in the relevant vertebral artery was found in 6 patients, no flow in a well-imaged vertebral artery in 1, and bilateral retrograde vertebral artery flow in 1 patient. Transcranial Doppler was abnormal in only 2 patients, with reduced pulsatility index in 1 and high resistance vertebral signal in another. A hyperintense intramural signal of the affected vertebral artery by magnetic resonance imaging was documented in 1 patient in whom Doppler sonography was nondiagnostic. CONCLUSIONS: Vertebral artery dissection can be detected and monitored by noninvasive vertebral Doppler and magnetic resonance imaging in the setting of a clinically suggestive presentation.

Adult↗

PubMed1993

Correction of erythrocyte deformability defect in ALX-induced diabetic rabbits after treatment with aminoguanidine.

To test whether treatment with aminoguanidine, a drug known to prevent cross-linking between glycated proteins, is effective in improving reduced erythrocyte deformability in diabetes, we studied a group (n = 6) of ALX-induced long-term (12.7 +/- 2.2 mo of hyperglycemia) diabetic New Zealand white rabbits before and after 20 wk of treatment with aminoguanidine (100 mg.kg-1 x day-1). The key findings were as follows: 1) at 12 wk of treatment with aminoguanidine, mean erythrocyte deformability normalized and remained within the normal reference range throughout the period of aminoguanidine administration; 2) 10 wk after discontinuing aminoguanidine in a subset of diabetic rabbits, mean erythrocyte deformability deteriorated by approximately 50%; 3) blood glucose and total GHb did not vary significantly during treatment with aminoguanidine nor after its discontinuation.

Animals↗

PubMed1992

Ultrasonic "hole sign": a reliable sign of perforation of the gallbladder?

Explore the source record for details and available documents.

Aged↗

PubMed1992

A randomised trial of second-line hormone vs single agent chemotherapy in tamoxifen resistant advanced breast cancer.

Sixty patients with advanced breast cancer unresponsive to tamoxifen have been randomised to receive four course of mitozantrone, 14 mg m-2 (n = 30) intravenously every 3 weeks (9 weeks total) or megesterol acetate, 160 mg bd (n = 30). One in three patients (11 from each group) had substantial disease control for a minimum period of 6 months i.e., lack of progression; seven patients (23%) showed objective response to mitozantrone compared to four (13%) receiving megesterol. Non-progressive disease occurred in all sites, including visceral metastases and receptor negative patients. There were no significant differences between treatment groups in the median time (5 months each) to disease progression response duration or survival (13 months megesterol, 11 months mitozantrone) from commencing second-line therapy. Toxicity was considerably higher in the mitozantrone group. Second-line hormonal therapies can produce similar therapeutic results as those achieved from a short course of a 'short option' single agent cytotoxic in patients who were previously thought hormone insensitive. Provided that the patient does not have life threatening disease a trial of megesterol acetate is worth consideration in that it does not prejudice subsequent response to combination cytotoxic chemotherapy.

Breast Neoplasms↗

PubMed1992

Effects of alloxan-induced diabetes on hemorheology in rabbits.

Plasma viscosity (PV), apparent whole blood viscosity (WBV), relative blood viscosity (RV) and erythrocyte deformability (filterability) (EDF) were determined in 13 New Zealand White (NZW) rabbits with alloxan induced-diabetes (AID) and 8 normal NZW rabbits, matched for age, sex and weight. AID rabbits were divided into two groups depending on the duration of hyperglycemia (long-term, greater than 6.0 months (n = 7), and short-term, less than or equal to 3.0 months of hyperglycemia, n = 6). Comparing long-term AID rabbits to normal animals, we found significant increases in WBV (P less than 0.001, 0.005 for high and low rates of shear, respectively), and a marked reduction in EDF (P less than 0.001). There was no significant difference in PV between long-term AID and normal rabbits. Conversely, PV was significantly increased in rabbits with short-term diabetes (P less than 0.01) while there was a concurrent significant increase in WBV measured at high and low rates of shear (P less than 0.001, 0.001, respectively). No difference was detected in EDF between normal and short-term AID rabbits. Furthermore, in long-term AID rabbits there was a strongly positive correlation between RV and reduced erythrocyte deformability (r = 0.94, P = 0.006) while WBV strongly correlated with PV (r = 0.92, P = 0.004) in the short-term AID subgroup. We conclude from these data: (1) elevated blood viscosity in long term AID rabbits is associated with reduced erythrocyte filterability; and (2) elevated WBV in short-term AID rabbits is associated with increased PV.

Animals↗

PubMed1991

Colonic motility and transit in health and ulcerative colitis.

Preprandial and postprandial colonic motility and transit (scintigraphy), with respect to the splenic flexure, were studied in 10 patients with ulcerative colitis and in 9 healthy subjects. The healthy subjects had a postprandial increase in intraluminal pressure that was significantly (P less than 0.03) greater in the descending colon than in other regions of the colon. In ulcerative colitis, the pressure was decreased in all regions compared with healthy subjects, with no significant pressure gradient among different regions. In normal subjects, transit was quiescent during fasting; eating stimulated both antegrade and retrograde transit. In ulcerative colitis, transit was variable before as well as after the meal. Both healthy subjects and patients with ulcerative colitis had more rapid emptying from the splenic flexure into the sigmoid than into the transverse colon. More frequent, low-amplitude, postprandial propagating contractions occurred in ulcerative colitis (P less than 0.05) than in healthy subjects. Propagating contractions were always antegrade and caused a rapid movement of the tracer into the sigmoid. In conclusion, ulcerative colitis is characterized by (a) decreased contractility, (b) increased low-amplitude propagating contractions, and (c) variable transit. These disturbances may accentuate the diarrhea in ulcerative colitis.

Adult↗

PubMed1991

APACHE II: prediction of outcome of 451 ICU oncology admissions in a community hospital.

The APACHE II system has been shown to be a reliable and useful means of evaluating patient outcome from the intensive care unit when applied to a broad spectrum of diagnoses. The major purpose of this study was to determine the use of APACHE II as a means of predicting outcome of ICU oncology patients. Data were retrospectively collected for 451 ICU oncology admissions. A direct relationship between severity of physiologic derangement and patient risk of death was demonstrated. Patients with scores of 30 or greater had hospital mortality rates of 100% for postoperative and 92.6% for nonoperative patients. The APACHE II was a useful means of predicting the outcome of ICU oncology patients. This potentially provides the patient, family, and physician an objective dimension in making decisions whether to transfer the oncology patient.

Adolescent↗