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Biomedical subjects

P Hahn

Publications and source records attributed to P Hahn.

At least 19 recordsLinked to original sources
PubMed1992

The objective evaluation of alternative treatment plans. III: The quantitative analysis of dose volume histograms.

The computer program OSCAR evaluates dose-volume histograms in a consistent way for use in 3-dimensional treatment planning. Based on a dose prescription specified by a radiation oncologist, the technique provides a quantitative and easily understood visual analysis of a proposed dose distribution. Rapid, reliable, and consistent choices can be made between alternative treatment plans, and if necessary the results of OSCAR calculations can be used to guide the design of a plan that will be closer to the required prescription. The method is well suited to use in the definition of treatment protocols. The use of OSCAR is demonstrated by applying it to the evaluation of alternative volumetric treatment plans for ca lung. The results demonstrate the importance of using corrections for inhomogeneous tissue density in the calculation of 3-dimensional dose distributions.

Computer Graphics↗
PubMed1992

Ontogeny of acyl-CoA: cholesterol acyltransferase in rat liver, intestine, and adipose tissue.

The development of acyl-coenzyme A: cholesterol acyltransferase (ACAT), was determined in the rat liver, intestine, and white (WAT) and brown adipose tissue (BAT). Animal studies have shown that dietary manipulation of cholesterol metabolism during an animal's early development can have persistent and permanent effects. Therefore it is important that the ontogeny of ACAT, one of the key enzymes in cholesterol metabolism, be clearly established. White Wistar rats were killed on day 21 of gestation, at birth, and on postnatal days 10, 14, 18, 21, 22, 25, 30, and 60. The tissues were rapidly excised, microsomes were prepared, and the activity of ACAT was measured as the rate of incorporation of [1-14C]oleoyl coenzyme A into cholesterol esters. Age-specific changes were observed in three of the four tissues investigated. Rat liver and intestine possess significant amounts of ACAT activity throughout development with marked variations in activity during this time. ACAT activity in BAT is low and variable throughout development with the exception of high activity noted in the adult animal. WAT contained little or no ACAT activity during development.

Acetyl Coenzyme A↗
PubMed1992

The control of cholesterol metabolism and plasma lipid levels in infant rats.

Infant rats received an i.p. injection of insulin, anti-insulin serum, streptozotocin, antiglucagon serum or dexamethasone. All substances except the antiinsulin serum, raised the plasma triglyceride level. Both antisera decreased plasma cholesterol levels, while streptozotocin, insulin and dexamethasone caused an increase. The activity of 3-hydroxy-3-glutaryl CoA reductase in liver and brown adipose tissue changed inversely to the cholesterol level. However, small intestinal enzyme activity was increased by insulin administration inspite of the rise in plasma cholesterol.

Adipose Tissue↗
PubMed1991

Carcinoma of female urethra. Manitoba experience: 1958-1987.

Fourteen female patients with primary urethral carcinoma were treated at the Manitoba Cancer Foundation in the last twenty-nine years. The relationship of natural history to the stage, location, and therapeutic modality has been reviewed. A higher stage and length of urethral involvement affected prognosis negatively, whereas lower stage had a positive prognostic effect and location of tumor had no prognostic influence. Two patients with Stage C, who failed to received inguinal node radiotherapy, died of disease recurring in the inguinal area. Patients who received inguinal radiation (3 patients Stages B, C, and D1) had no regional recurrence. It is suggested that, for all female urethral carcinoma, bilateral ilioinguinal nodes be included in the radiation field. For radical treatment, iridium 192 insertion in combination with external beam treatment is recommended.

Adenocarcinoma↗
PubMed1991

The objective evaluation of alternative treatment plans: II. Score functions.

A series of six patients with adenocarcinoma of the prostate, Stages A2, B1, or B2, were planned for treatment using a four-field box technique at 25 MV. Plans were prepared by three techniques: composite, mid-plane, and conformal. The dose distributions at the central plane and at two planes offset by +/- 2 cm were evaluated by means of score functions which quantify the magnitude of regret for target dose gradient, target over- and under-dose, non-target tissue overdose, and for overdose to the rectum, bladder, and femoral heads. The score functions are normalized to give values in the range from 10 (ideal) to zero (limit of acceptability), with negative values indicating unacceptable deviations from the prescribed dose limits. The scores for off-axis conformal plans were found to be essentially the same as for mid-plane plans on the central plane. However, mid-plane planning was shown to be totally inadequate for off-axis planes, where the average target gradient and underdose scores were reduced by 10 units. Composite planning resulted in adequate target coverage on all planes, but at the expense of unacceptable overdose to non-target tissue. The effect of reducing the posterior beam weight to half that of the other three beams was to reduce the target gradient score by 1.6 +/- 0.5 units and to increase the rectal score by 0.9 +/- 0.3 units.

Adenocarcinoma↗
PubMed1991

Regulation of ketone formation and phosphoenolpyruvate carboxykinase activity in the small intestinal mucosa of infant rats.

We studied the effect of different hormones added in vivo or in vitro on ketogenesis and phosphoenolpyruvate carboxykinase (PEPCK) activity in the small intestinal mucosa of suckling rats. Injection of insulin or dexamethasone in vivo or of an antiglucagon antiserum decreased the rate of ketone formation in the mucosa whereas injection of anti-insulin antiserum led to increased mucosal ketogenesis. PEPCK activity in the mucosa was decreased by the antiglucagon serum but was not affected by insulin or anti-insulin serum injections. Both liver and brown fat PEPCK responded as expected with the activity being elevated by anti-insulin serum and depressed by both insulin and antiglucagon serum. In the in vitro experiments, no effect of any of the agents on PEPCK was found. Ketone formation was suppressed in vitro by insulin or dexamethasone addition to the medium.

Animals↗
PubMed1990

X-ray induction of methotrexate resistance due to dhfr gene amplification.

The effect of ionizing radiation on methotrexate (MTX) resistance and gene amplification in cultured mammalian cells was investigated. X-irradiation of mouse EMT-6 cells induced cell killing and MTX resistance due to amplification of dihydrofolate reductase (dhfr) gene in a dose-dependent manner. The highest yields of mutant cells were obtained at approximately D37 (the dose at which 37% of the cells survive), where the frequency of MTX-resistant cells was four- to eightfold over that of the unirradiated population. The proportion of MTX-resistant cells among the survivors increased logarithmically with dose, up to a 1000-fold increase over unirradiated cells at 1000 cGy, the highest dose tested. The induced frequency of MTX resistance after X-irradiation was greater than the induced frequency of 8-azaguanine resistance, which indicates deletion of the hypoxanthine phosphoribosyltransferase gene. Inhibition of poly(ADP-ribose) polymerase by the addition of 3-aminobenzamide before irradiation increased both cell killing and MTX resistance. Metaphase spreads of chromosomes from EMT-6 cells that had been irradiated and subjected to stepwise increases in MTX concentration showed numerous double minutes. Pulsed-field gel electrophoresis of the DNA from cells containing radiation-induced double minutes showed that many copies of the dhfr gene were present on circular DNA molecules of 10(6), 2 x 10(6), and 3 x 10(6) base pairs. These results suggest a relationship between the induction of chromosome aberrations and the induction of gene amplification.

Animals↗
PubMed1990

Treatment planning for protocol-based radiation therapy.

Many protocol studies are conducted in which patients are assigned to alternative treatment regimens. Typically the dosimetric specifications will define the maximal and minimal target doses and maximal doses to specified critical normal structures, and the success of the study will depend upon the consistency and reliability with which these dose specifications are applied. We have investigated the use of dose-area histograms to ensure complete adherence to protocol dose specifications. A dose prescription is prepared that defines upper and lower target doses as well as normal tissue dose tolerance levels for all organs of interest. In addition, dose-volume histograms are derived which provide quantitative measures of the extent to which each dose limit has been met. This technique can be used during treatment planning to prevent protocol violations of pre-defined severity, or for retroactive correlation of local tumor recurrence and treatment-related morbidity with dose levels in the target and normal tissues. An example is presented for a protocol study of ca prostate, stages A and B, in which seven treatments were evaluated at the mid-plane for protocol violations.

Clinical Trials as Topic↗
PubMed1990

Studies on prostaglandin and luteolysis in the pseudopregnant rabbit.

The ability of pulsatile infusion of prostaglandin F2 alpha (PGF2 alpha) or 13, 14-dihydro prostaglandin F2 alpha to induce corpus luteum regression was examined in the pseudopregnant rabbit. Each prostaglandin was infused in 5, 1-hour pulses (1 per 6 hours) during a 25-hour period starting day 9 or 10 of pseudopregnancy. Although both prostaglandins were capable of inhibiting progesterone secretion, pulse administration was no more effective than continuous infusion. To determine if PGF2 alpha was released into the systemic circulation during spontaneous luteolysis, starting day 12 of pseudopregnancy serial blood samples were collected every 90 minutes from the jugular vein. Prostaglandin F levels remained steady (1-2 ng/ml over the collection period with no apparent increase associated with functional luteolysis. Although prostaglandins may be involved in luteolysis in the rabbit, the present results suggest that it is unlikely that PGF2 alpha by itself is responsible for the sustained fall in progesterone secretion at the end of the pseudopregnancy.

Animals↗
PubMed1990

Comparison of breast-feeding and formula feeding on intestinal and hepatic cholesterol metabolism in neonatal pigs.

Infant formulas (IFs) contain reduced cholesterol concentrations compared with breast milk (SM); how neonatal cholesterol metabolism responds to this difference is largely unknown. The effect of exclusive feeding of SM vs low-cholesterol IF on intestinal and hepatic cholesterol concentrations and synthesis during early postnatal development were compared in piglets. Animals were killed at birth or on days 5, 10, 15, or 25 postpartum. Plasma cholesterol concentrations were higher in SM-fed than in IF-fed piglets on days 15 and 25. In intestine both HMG-CoA reductase activity and 3H2O incorporation rates into cholesterol were similar for both groups or reduced in the IF-fed group at days 15 and 25. In liver, HMG-CoA reductase activity was higher in IF-fed than in SM-fed piglets on days 5, 10, and 15. Results indicate that during the early postpartum period, response to lower cholesterol intakes with IF occurs by increasing hepatic sterol synthesis whereas intestinal synthesis is largely unaffected.

Animals↗
PubMed1990

Diet and metabolic development.

For many years, investigators have been concerned with mechanisms that control and alter genetically regulated development. An intriguing aspect of these mechanisms is the ability of environmental factors to induce certain metabolic processes. Animal studies have shown that dietary manipulation of cholesterol and fatty acid metabolism during development can have persistent and permanent effects. In addition, there appears to be a critical period when changes in the diet can have lasting consequences. The changes in the control exerted by nutritional factors on metabolic development coincide with three phases of development: prenatal, suckling, and weaning. The effects of diet on cholesterol and fatty acid metabolism throughout these three phases of development will be addressed in this review.

Animals↗
PubMed1990

Development of cholesterol metabolism: the effect of diet composition at weaning.

Wistar rats were weaned on day 18 to a high fat (HF), high carbohydrate (HG) or high cholesterol (HCO 2%) diet. The activities of 3-hydroxy-3-methylglutaryl-CoA-reductase (HMGR), 7 alpha-hydroxylase (7-OHase) and acyl-CoA-cholesterol-acyltransferase (ACAT) were assayed in the liver and small intestinal mucosa on days 21, 25 and 30 and in adult animals. An HF diet raises hepatic ACAT and HMGR activities in young rats but has the opposite effect in the gut. The cholesterol diet also raises hepatic ACAT activity, but less so than the HF diet. In the gut, however, the HCO diet invokes the greatest rise in ACAT of all the diets tested. Except in adult rats, the HG diet always raises hepatic ACAT activity more than the HCO diet or the Purina Chow. In the gut, however, activity is very low for the HG diet, much lower than for the HCO diet. Early feeding of the HCO diet for 12 days (from day 18 to 30) and refeeding the same diet from day 48 to 50 resulted in a subsequent response to the HCO diet. It is concluded that early weaning results in changes in enzyme activities that depend on the composition of the diet fed at weaning and that this may also effect the later response to the same and perhaps other diets.

Acetyl-CoA C-Acyltransferase↗
PubMed1989

Cholesterol metabolism in infant rats, effect of 6-hydroxydopamine and guanfacine.

Infant rats (10-16 days) and weaned animals (older than 18 days) were treated with drugs inhibiting beta-adrenergic activity and were sacrificed 4 days later. 6-Hydroxydopamine acts on postsympathetic nerve fibres, and guanfacine stimulates alpha 2-receptors. Both drugs caused a rise in plasma cholesterol and a decrease in hepatic 3-hydroxy-3-methylglutaryl CoA reductase activity in infant but not in weaned animals. The activity of acylcholesterol acyl CoA transferase, on the other hand, was decreased after drug administration. Thus, both antihypertensive drugs may cause changes in cholesterol metabolism, especially in infant animals.

Adipose Tissue, Brown↗
PubMed1988

The objective evaluation of alternative treatment plans: I. Images of regret.

An innovative approach to treatment planning is described in which a planned dose distribution is evaluated in terms of prescribed limits of acceptability, and any discrepancies (referred to as "regions of regret") are displayed in the form of a contour diagram in which colors are used to represent different types and degrees of regret. A commercial treatment planning system has been modified to display images of regret in addition to conventional isodose plots, and is used for the comparison of alternative plans in terms of adequate target coverage and minimal irradiation of sensitive organs. Required tumor dose levels and organ-specific tolerance doses are prepared in advance by the clinician for each site and stored in a prescription file for use in the planning process. The method is found to expedite the optimization procedure, is objective and reproducible, and provides clear documentation of the selection process.

Computer Graphics↗