Physiological correlates of seasonal growth patterns in lake trout Salvelinus namaycush.

Physiological correlates of seasonal growth patterns were measured in lake trout Salvelinus namaycush from two populations with contrasting diets (zooplankton-dominated diet in Louisa Lake; fish-dominated diet in Opeongo Lake). Fish in Opeongo Lake grew faster and were in better condition than fish in Louisa Lake. The most prominent biochemical difference between populations was higher citrate synthase (CS) and cytochrome c oxidase activity in the white muscle of fish from Opeongo Lake, indicating greater sustained swimming activity in this lake. In contrast, lactate dehydrogenase (LDH) activity in white muscle, an indicator of capacity for burst swimming, was similar between lakes. Nucleoside diphosphate kinase (NDPK) activity in white muscle, an indicator of protein synthesis, was higher in Opeongo Lake than in Louisa Lake but only in the autumn. In both lakes, protein concentration and therefore nutritional status increased as the growing season progressed from spring to summer to autumn. Biochemical indicators of growth and activity showed similar seasonal patterns in the two lakes with the spring characterized by high NDPK, high CS and high LDH activities (i.e. high levels of protein synthesis in association with high aerobic and anaerobic activities). These results suggest high foraging effort and allocation to growth early in the growing season in both lakes.

Prey life-history and bioenergetic responses across a predation gradient.

To evaluate the importance of non-consumptive effects of predators on prey life histories under natural conditions, an index of predator abundance was developed for naturally occurring populations of a common prey fish, the yellow perch Perca flavescens, and compared to life-history variables and rates of prey energy acquisition and allocation as estimated from mass balance models. The predation index was positively related to maximum size and size at maturity in both male and female P. flavescens, but not with life span or reproductive investment. The predation index was positively related to size-adjusted specific growth rates and growth efficiencies but negatively related to model estimates of size-adjusted specific consumption and activity rates in both vulnerable (small) and invulnerable (large) size classes of P. flavescens. These observations suggest a trade-off between growth and activity rates, mediated by reduced activity in response to increasing predator densities. Lower growth rates and growth efficiencies in populations with fewer predators, despite increased consumption suggests either 1) a reduction in prey resources at lower predator densities or 2) an intrinsic cost of rapid prey growth that makes it unfavourable unless offset by a perceived threat of predation. This study provides evidence of trade-offs between growth and activity rates induced by predation risk in natural prey fish populations and illustrates how behavioural modification induced through predation can shape the life histories of prey fish species.

A biphasic parameter estimation method for quantitative analysis of dynamic renal scintigraphic data.

Dynamic renal scintigraphy is an established method in nuclear medicine, commonly used for the assessment of renal function. In this paper, a biphasic model fitting method is proposed for simultaneous estimation of both vascular and parenchymal parameters from renal scintigraphic data. These parameters include the renal plasma flow, vascular and parenchymal mean transit times, and the glomerular extraction rate. Monte Carlo simulation was used to evaluate the stability and confidence of the parameter estimates obtained by the proposed biphasic method, before applying the method on actual patient study cases to compare with the conventional fitting approach and other established renal indices. The various parameter estimates obtained using the proposed method were found to be consistent with the respective pathologies of the study cases. The renal plasma flow and extraction rate estimated by the proposed method were in good agreement with those previously obtained using dynamic computed tomography and magnetic resonance imaging.

Interpreting the von Bertalanffy model of somatic growth in fishes: the cost of reproduction.

We develop a model for somatic growth in fishes that explicitly allows for the energy demand imposed by reproduction. We show that the von Bertalanffy (VB) equation provides a good description of somatic growth after maturity, but not before. We show that the parameters of the VB equation are simple functions of age at maturity and reproductive investment. We use this model to show how the energy demands for both growth and reproduction trade off to determine optimal life-history traits. Assuming that both age at maturity and reproductive investment adapt to variations in adult mortality to maximize lifetime offspring production, our model predicts that: (i) the optimal age of maturity is inversely related to adult mortality rate; (ii) the optimal reproductive effort is approximately equal to adult mortality rate. These predictions are consistent with observed variations in the life-history traits of a large sample of iteroparous freshwater fishes.

Efficacy of cisapride therapy in functional dyspepsia.

AIM: To assess the efficacy of cisapride therapy in relieving symptoms of functional dyspepsia. METHODS: After a 2-week placebo run-in period, 61 out of 74 patients were eligible to enter a 4-week double-blind treatment phase, consisting of treatment with cisapride (10 mg) or placebo tablets t.d.s. Gastric emptying was assessed scintigraphically at entry to the study. Patients were stratified before treatment into those with or without active chronic (Helicobacter pylori) gastritis. Patients were also classified retrospectively into those with 'reflux-like' dyspepsia (n = 29) and those with 'motility-like' dyspepsia (n = 32). RESULTS: At the end of the active treatment phase, there was a similar significant (P < 0.001) reduction in total symptom score from baseline in both cisapride (8.9 +/- 0.5 to 5.8 +/- 0.6) and placebo (9.7 +/- 0.6 to 5.5 +/- 0.6) groups. Scores for heartburn and continual bloating were significantly reduced in the cisapride but not the placebo group; improvement was attributable to patients with normal, rather than delayed, rates of gastric emptying. For continual bloating, significant improvement also occurred in the cisapride subgroup without gastritis, but not in the subgroup with gastritis (mean symptom score reduction 0.48 +/- 0.18, P = 0.03). For global evaluation by the investigator and by the patient, the overall improvement rates were not statistically different between cisapride and placebo groups. In those with normal gastric emptying, however, there was a significant (P = 0.01) improvement in general well-being in the cisapride but not in the placebo group. CONCLUSIONS: We were unable to show major differences in the short-term efficacy of cisapride and placebo in functional dyspepsia. There were indications, however, of beneficial effects of cisapride over placebo in those with 'reflux-like' dyspepsia, and in those without gastroparesis.

The value of ultrasound, gonadotropin, and estradiol measurements for precise ovulation prediction.

The exact prediction of ovulation is becoming more important in the management of infertile women. Graafian follicle diameter, measured by ultrasound and plasma follicle-stimulating hormone, luteinizing hormone, and estradiol levels were compared retrospectively as predictors of ovulation in 14 normal women in whom ovulation was dated by conventional ultrasound techniques. Follicle diameter was found to be a better predictor of the anticipated time of ovulation than endocrine estimations for short-term as well as long-term predictions in normal women. The relationship between follicle diameter and plasma estradiol for each day before ovulation was linear but contained a great amount of scatter, suggesting that the assessment of normality of follicular development in infertile women may not be possible with the use of these parameters.

Measuring renal function in patients with diabetes mellitus.

We estimated the glomerular filtration rate in 33 patients from our diabetic clinic using three methods: the creatinine clearance measured from a timed urine sample and a serum creatinine; the creatinine clearance calculated from the serum creatinine according to the formula of Cockcroft and Gault; and, the plasma clearance of ethylenediaminetetra-acetic acid (EDTA) labeled with 51Cr ([51Cr]EDTA). We repeated the measurements in seven subjects. The measured creatinine clearance was not reproducible. The other two methods were correlated, but not according to the formula y = x. The calculated creatinine clearance significantly underestimated the [51Cr]EDTA clearance particularly at higher [51Cr]EDTA clearance rates. [51Cr]EDTA clearance has been shown by others to parallel, but underestimate, inulin clearance, the optimal method of estimating glomerular filtration rate but difficult to perform in routine practice. Accurately measuring renal function in routine clinical practice is difficult, and this must be borne in mind when making clinical decisions based on current measurements.

Estimation of renal scintigraphy parameters using a linear piecewise-continuous model.

Instead of performing a numerical deconvolution, we propose to use a linear piecewise-continuous model of the renal impulse response function for parametric fitting of renal scintigraphy data, to obtain clinically useful renal parameters. The strengths of the present model are its simplicity and speed of computation, while not compromising on accuracy. Preliminary patient case studies show that the estimated parameters are in good agreement with a more elaborate model.

Ni-DTPA doped agarose gel--a phantom material for Gd-DTPA enhancement measurements.

In order to study the relationship between the concentration of Gd-DTPA in tissue, and the resulting changes in relaxation times and signal intensity, a phantom material that has similar relaxation times to tissue and that can be doped with Gd-DTPA is required. The "tissue-equivalent" material should not contain Gd; nor should it alter the relaxivities of Gd-DTPA from their values in aqueous solution (R1 = 4.5 sec-1 mM-1; R2 = 5.5 sec-1 mM-1 at 1.5 T). Conventional materials, based on CuSO4-, MnCl2-, or GdCl3/LaCl3-agarose mixtures, are not suitable, since Gd is displaced from the Gd-DTPA chelate. The new material, consisting of Ni-DTPA dissolved in agarose, is easy to prepare and does not interact with Gd-DTPA. Its relaxation times are stable; relaxivity R1 was within 4% of its aqueous value over 109 days. T1s have low dependence on temperature (0.2-1.0%/degrees C at 21 degrees C) and on field strength, allowing the material to be used as a relaxation time standard for quality assurance. Equations giving the concentration of Ni-DTPA and agarose to produce a required T1 and T2 are provided.

The effect of sacrifice on image signal, T1, T2, and T*2 in liver, kidney, and brain of the Wistar rat.

Signal intensity in SE240/25 and GE240/25 images, T*2, T2, and T1 were measured prior to and after sacrifice at 1.5 T in liver, kidney, and brain of Wistar rats. Presacrifice, animals were maintained on 2-3% halothane, ensuring a high saturation of venous haemoglobin with oxygen, which emphasised blood oxygenation level dependent (BOLD) effects upon deoxygenation of haemoglobin postsacrifice. T*2 values (in ms) changed on sacrifice from 27.8 +/- 4.1 to 15.0 +/- 1.1 in liver (p << .001), from 57.4 +/- 6.5 to 52.8 +/- 5.7 in brain (p < .02), and from 52.3 +/- 10.3 to 37.6 +/- 11.9 in kidney cortex (p < .01). T*2 was also reduced in kidney medulla and papilla. T2 reduced on sacrifice (by a lesser amount than T*2), except in brain, which showed a small increase. T1 (ms) changed only in liver, showing a significant increase from 670 +/- 31 to 834 +/- 69 (p << .001). The ratio of signal postsacrifice to presacrifice was lowest in the SE240/25 and GE240/25 images of liver (0.73 +/- 0.03 and 0.52 +/- 0.05, respectively), but increased T1 may account for some of these changes. Expected signal ratios at sacrifice calculated from measured relaxation times agreed well with those observed experimentally. Relaxation changes observed on sacrifice were consistent with deoxygenation of haemoglobin. These results give an estimate of the maximum effects which changes of blood oxygen level might produce at 1.5 T and suggest that contrast due to variation of endogenous deoxyhaemoglobin may be exploitable in the liver.

The relaxivity of Gd-EOB-DTPA and Gd-DTPA in liver and kidney of the Wistar rat.

The NMR relaxivities of Gd-EOB-DTPA and Gd-DTPA were determined in the kidney and liver of intact male Wistar rats immediately following sacrifice and in vitro in solutions and gels, at 1.5 T using a clinical MR scanner, T1 and T2 values of tissue samples were derived from spin-echo image sequences. Tissue gadolinium concentrations were determined by radioassay of Gd153, Gd-EOB-DTPA T1 and T2 relaxivities, R1 and R2 (s-1 mmole-1 kg), were found to be 10.7 +/- 0.5 and 22.5 +/- 3.2 respectively, for liver, 2.4 +/- 0.2 and 12.1 +/- 1.7 for kidney cortex, 2.7 +/- 0.2 and 14.5 +/- 1.9 for kidney outer medulla, 2.0 +/- 0.2 and 11.4 +/- 2.1 for kidney inner medulla. Gd-DTPA R1 and R2 were found to be 4.8 +/- 0.4 and 14.5 +/- 3.7 for liver, 1.2 +/- 0.1 and 7.9 +/- 0.8 for kidney cortex, 1.6 +/- 0.1 and 10.2 +/- 1.4 for kidney outer medulla, 1.3 +/- 0.1 and 10.2 +/- 1.2 for kidney inner medulla. Gd-EOB-DTPA and Gd-DTPA R1 was increased in liver compared to agarose gets at 38 degrees C (4.49 +/- 0.03 and 3.47 +/- 0.06), but reduced in kidney tissues. All R2 were elevated compared to agarose gels at 38 degrees C (5.72 +/- 0.12 and 4.12 +/- 0.03). Elevated R2 and R1 (expressed in terms of the concentration of gadolinium per kg of tissue) can be accounted for in part by the lower water content of tissues compared with gels or solutions increased microviscosity and binding to macromolecules. In addition, susceptibility effects may give rise to further increases in R2. By contrast, the reduced R1 observed in kidney may be the result of compartmentalization of the magnetopharmaceuticals. Statistically improved fits were obtained for T1 recovery curves for liver in the presence of Gd-EOB-DTPA when a dual exponential model was used. Assuming in vitro values for the relaxivities of these artificial contrast agents will lead to inaccuracies when relating observed signal enhancement factors to tissue gadolinium concentration.

Comparative studies on two combination oral contraceptives, one containing synthetic estrogen, the other "natural" estrogens.

Two combined oral contraceptives, one containing ethinyl estradiol and the other micronized estradiol and estriol, were compared by measuring a variety of endocrine and renal parameters over nine months. Significant changes were observed in plasma renin activity (P.R.A.) on the synthetic estrogen. Much larger changes were observed in the total urinary estrogens on patients taking the "natural" estrogens reflecting the amount of estrogens required to be excreted in the urine.

Computer generation of random deviates.

The need for random deviates arises in many scientific applications, such as the simulation of physical processes, numerical evaluation of complex mathematical formulae and the modeling of decision processes. In medical physics, Monte Carlo simulations have been used in radiology, radiation therapy and nuclear medicine. Specific instances include the modelling of x-ray scattering processes and the addition of random noise to images or curves in order to assess the effects of various processing procedures. Reliable sources of random deviates with statistical properties indistinguishable from true random deviates are a fundamental necessity for such tasks. This paper provides a review of computer algorithms which can be used to generate uniform random deviates and other distributions of interest to medical physicists, along with a few caveats relating to various problems and pitfalls which can occur. Source code listings for the generators discussed (in FORTRAN, Turbo-PASCAL and Data General ASSEMBLER) are available on request from the authors.

Body surface area: Du Bois and Du Bois revisited.

The Du Bois and Du Bois body surface area (BSA) equation is used widely to normalise physiological parameters. However, that only nine subjects were used in its derivation does not appear to be well known and does not justify its ubiquitous application. Furthermore, the derivation appears to be hampered by a lack of modern statistical methods and the omission of a large amount of available data. We have shown that the omitted data, obtained by measurement of the length of body parts, were identical to the data obtained by encasing subjects in moulds ¿BSA (moulds; cm2) = [1.00 (0.02)] x BSA (linear measurements) + [123 (347)]¿. Non-linear regression analysis of the BSA of all 42 subjects reported by Du Bois and Du Bois gave new values for the constants of the model ¿BSA (cm2) = 94.9 x [weight (kg)0.441] x [height (cm)0.655]¿. Although the original equation obtained by Du Bois and Du Bois was found to be adequate in adults, we recommend that it should not be used in daily practice, owing to the low number of subjects used in its derivation. The work presented here has placed the original results of Du Bois and Du Bois on a more robust statistical footing, yielding values for the model constants that would have been obtained if Du Bois and Du Bois had had access to modern statistical methods.

Cell kinetics methods for clinical use: assessment of autoradiography and 125I-iodo-deoxyuridine with mouse Ehrlich tumour.

Superficial Ehrlich tumours in mice were used to assess how much information on cell kinetics could be obtained from only the simplest techniques of autoradiography, and in situ monitoring of 125I-iodo-deozyuridine. These techniques were selected as being readily applicable to clinical situations. Intradermal tumours were studied from the earliest stages of rapid growth to large slow growing tumours with necrotic cores, as well as tumours undergoing regression. For comparison, intramuscular tumours were studied with systemic injections of radioactive DNA precursors. It was found that extensive information on cell production and loss rates was obtained from a single injection of tritiated thymidine followed by a single biopsy, or alternatively in vitro labelling of one minute biopsy specimen, and measurements of only the labelling index, together with a knowledge of the tumour's growth characteristics. Following a single localized injection of 125I-iodo-deoxyuridine, the loss rate of radioactivity measured in situ for a period of about 1 week provided an index of cell loss rate from the tumours.

Lack of association between gastric emptying of solids and symptoms in nonulcer dyspepsia.

Gastric motor dysfunction and concomitant gastric stasis have been implicated in the pathogenesis of nonulcer dyspepsia, but a cause-and-effect relationship is not established. Essential dyspepsia refers to a subgroup of nonulcer dyspepsia patients who have no evidence of irritable bowel syndrome, gastroesophageal reflux, or pancreaticobiliary disease. In 32 patients with essential dyspepsia, and 32 randomly selected dyspepsia-free community controls of similar age and sex, we measured gastric emptying of solids using Tc99m-Sulphur Colloid in a fried egg sandwich. Subjects with neuromuscular or other diseases that may alter gastric emptying were excluded. Symptoms were assessed by a standard questionnaire. Data processing was carried out "blinded" to the subjects' clinical status. Female patients took significantly longer to empty half the initial stomach activity (mean 90 min) than female controls (mean, 73 min; p = 0.02). The rate of emptying at 25 min was also significantly less in female patients than in controls. Female and male controls, and male patients, had similar emptying times. Delayed emptying was not associated with the occurrence of postprandial pain, belching, or nausea; there was a trend for the half-time rate of emptying to be greater in patients with abdominal distention. While gastric emptying of solids is slightly delayed in females with essential dyspepsia as a group, this may not explain their symptoms.

Reduced pregnancy rates in AID women with unsuspected ovulatory failure.

A review over five years of 232 patients attending an artificial insemination by donor (AID) clinic was undertaken in order to detect abnormalities in ovulation patterns. Ovulation was determined by luteal phase progesterone estimations. Unexpected anovulation was found in 36% of the patients attending despite an apparently normal previous menstrual history and investigations. This group consisted of 22% who were anovulatory from commencement in the programme and 14% who became anovulatory during treatment. The cumulative pregnancy rates at 15 months for these two groups were lower (73% and 55%) than that for the remaining patients who ovulated normally (90%). A proportion (16%) of the latter group were receiving clomiphene therapy for anovulation recognized before entering the programme. The lower pregnancy rate could not be related to other factors influencing conception and occurred in spite of clomiphene therapy. These results should assist in advising patients on their chances of conception, preventing early discouragement but not encouraging long term insemination which may not improve the pregnancy rate.

Relaxivity of Gd-EOB-DTPA in the normal and biliary obstructed guinea pig.

After injection of Gd-EOB-DTPA, T1 and T2 were determined on a clinical MR scanner (1.5 T) in the liver and kidneys of sacrificed but intact guinea pigs with normal and obstructed biliary systems and in bile, urine, and blood collected postmortem. Tissue [Gd] was determined by radioassay of 153Gd and relaxivities (R1 and R2; units of s(-1) x mmol(-1) x kg) of Gd-EOB-DTPA calculated. Compared with R1 in 2% agarose gel (4.49 +/- 0.03), in normal animals R1 was increased in liver (9.3 +/- 0.5), similar in kidney cortex (4.1 +/- 0.5), but reduced in kidney medulla (2.5 +/- 0.4) and papilla (2.7 +/- 0.4). Chronic biliary obstruction did not change R1 in liver (9.7 +/- 4.3) but reduced R1 further in kidney tissues (1.0-0.4). In normal animals, R2 values of all tissues (9.5-18.4) were greater than R2 in gel (5.72 +/- 0.12). Biliary obstruction possibly elevated R2 in liver (40.1 +/- 63.5), severely depressed R2 in kidney cortex (-4.2 +/- 6.2) and medulla (-2.3 +/- 5.4), and reduced R2 in papilla (5.4 +/- 4.6). Obstruction had little effect on R1 and R2 in bile and urine. Water content, macromolecular binding, microviscosity, compartmentalization, and susceptibility effects can readily account for the R1 and R2 observed in liver and kidney. Negative R2 could be a result of several factors, including reduced endogenous magnetic field gradients due to "susceptibility matching" as [Gd] increased, changes in tissue T2 with period of ligation, or a physiological effect of EOB-DTPA. These results show that disease can alter both R1 and R2 from their values in normal tissues.

Gastroparesis and small bowel dysmotility in irritable bowel syndrome.

Alterations in both gastric emptying (GE) and small bowel motility have been reported in irritable bowel syndrome (IBS); the relationship, however, between these different measures of upper gut motor function in IBS has not been assessed. The aims of this study were therefore: (1) to compare the prevalence and characteristics of altered small bowel motility in IBS patients with and without delayed GE; and (2) to assess the interrelationships between fasting and postprandial small bowel motility in IBS, accounting for delayed GE. Forty-four IBS patients and 25 healthy controls underwent 24 hr ambulant recording of interdigestive and digestive small bowel motility. On a separate occasion the IBS patients had GE of both solids and liquids measured by a dual-isotope scintigraphic technique. Thirty-nine percent of IBS patients had delayed GE. Patients with normal GE had no interdigestive small bowel abnormalities. However, in patients with delayed GE fasting phase II burst frequency was higher than in controls [median 0.21/hr (IQR 0.15-0.34) vs 0.06/hr (0-0,16), P = 0.004]. Postprandially, abnormal phase III-like activity was higher in diarrhea-predominant IBS patients (0-0.08/hr vs 0/hr, P = 0.01), than in patients with normal GE or controls. Furthermore, IBS patients with delayed GE did not have the normal correlation between fasting and postprandial motor parameters (percentage occurrence of clustered contractions, postprandial pattern duration vs preceding MMC cycle length). In conclusion, small bowel motor dysfunction occurs more frequently in IBS patients with concomitant gastroparesis than in patients with normal GE. These findings provide further evidence that a neuropathic process may contribute to the pathogenesis of IBS in a subgroup of IBS patients.

Effects of cigarette smoking on solid and liquid intragastric distribution and gastric emptying.

BACKGROUND: The acute effects of cigarette smoking on gastric emptying are controversial, whereas its effects on the intragastric distribution of solids and liquids are not established. METHODS: Dual isotope gastric scintigraphy was performed in 15 habitual smokers (studied twice, either sham smoking or actively smoking) and in 15 age- and sex-matched nonsmokers. RESULTS: Acute smoking was associated with an increased prevalence of episodes of retrograde intragastric movement of solids (3 of 15 sham subjects vs. 12 of 15 actively smoking subjects; P < 0.01) and of liquids (0 of 15 vs. 7 of 15; P < 0.01) from distal to proximal stomach. Fundal half-emptying time (T1/2) for liquids was also prolonged by smoking (43 +/- 19 minutes sham vs. 125 +/- 216 minutes active; P < 0.05). Acute smoking delayed solid lag time (13 +/- 6 minutes sham vs. 32 +/- 18 active; P < 0.05) and liquid T1/2 (46 +/- 21 vs. 90 +/- 50 minutes; P < 0.05). In the nonsmokers, such episodes of proximal intragastric redistribution did not occur, and intragastric and overall emptying parameters did not differ significantly from those of habitual sham smokers. CONCLUSIONS: Acute cigarette smoking produces excessive antrofundal redistribution of both solid and liquid contents and delays solid and liquid gastric emptying.