PubMed HealthSearch

Biomedical subjects

W M Rand

Publications and source records attributed to W M Rand.

At least 19 recordsLinked to original sources

Treatment of dogs with osteosarcoma by administration of cisplatin after amputation or limb-sparing surgery: 22 cases (1987-1990).

Twenty-two dogs with appendicular osteosarcoma were treated by amputation (n = 17) or limb-sparing surgery (n = 5). All dogs were given cisplatin (60 mg/m2 of body surface, IV) at 3-week intervals, beginning 1 week after surgery. Number of cisplatin treatments ranged from 1 to 6. Survival data for the 22 dogs were compared with survival data from a historical control group consisting of 162 dogs with appendicular osteosarcoma treated by amputation alone. Median survival time for the 22 dogs given cisplatin was estimated to be 46.4 weeks, and 1- and 2-year survival rates were estimated to be 45.5 and 20.9%, respectively. Survival time was significantly (P less than 0.0001) longer for treated dogs than for control dogs. Statistically significant relation was not found between survival time and number of cisplatin treatments. Three dogs were alive with no evidence of disease at the time of reporting. Of the remaining 19 dogs, 14 (73.4%) were euthanatized for problems documented to be related to metastases. Nine (47.4%) dogs were euthanatized because of bone metastases, and 5 (26.3%) were euthanatized because of pulmonary metastases. The proportion of dogs euthanatized because of bone metastases was significantly (P less than 0.0001) higher for treated than for control dogs. Median survival times for dogs developing bone and lung metastases were estimated to be 51.2 weeks and 21.2 weeks, respectively; however, this difference was not statistically significant. One local tumor recurrence was observed among dogs that had limb-sparing surgery. Significant difference in survival time was not observed between dogs that had limb-sparing surgery and dogs that underwent amputation.

Amputation, Surgical

Prognosis for dogs with appendicular osteosarcoma treated by amputation alone: 162 cases (1978-1988).

Long-term follow-up information pertaining to 162 dogs with appendicular osteosarcoma treated by amputation alone was collected from 17 veterinary institutions. The majority (72.5%) of dogs died or were euthanatized because of problems documented to be related to metastases. The first clinically apparent sites of metastasis were the lungs (60.8% of total), the skeleton (5.2%), or both (4.6%). A Kaplan-Meier survivorship distribution was plotted on the basis of available survival time data in all 162 dogs. The mean and median survival times were estimated to be 19.8 and 19.2 weeks, respectively, and the 1- and 2-year survival rates were estimated to be 11.5 and 2.0% respectively. Statistically significant relationships were not found between survival time and reporting institution, gender, site of primary tumor, whether the primary tumor was proximally or distally located, whether the primary tumor was located in the forelimb or hind limb, whether presurgical biopsy was performed, and whether death was tumor related. A significant (P less than 0.01) quadratic relationship was found between age and survival time. Survival time was longest in dogs 7 to 10 years old and was shorter in older and younger dogs.

Amputation, Surgical

Effect of aspiration of the preovulatory follicle on luteinization, corpus luteum function, and peripheral plasma gonadotropin concentrations in the mare.

Follicular fluid from small- to medium-sized follicles has been shown to have an inhibiting effect on luteinization of granulosa cells in vitro. This study was conducted to investigate the effect of in vivo removal of follicular fluid on luteinization, peripheral gonadotropin concentrations, and ovulation of secondary follicles in the mare. Follicular fluid was aspirated from the preovulatory follicles of mares when the diameter of the follicle was 30-34 mm (Group A), 35-39 mm (Group B), or 40-44 mm (Group C). Mares in Group D served as controls and the preovulatory follicle was not aspirated. Mares in Group A had a significantly earlier rise in peripheral progesterone concentrations than did controls. There was no difference in duration of progesterone secretion or peak progesterone production between groups. LH and FSH values were significantly higher for mares in Groups A and B than for control mares. Mares in Group A tended to have a higher incidence of secondary ovulations than did mares in other groups. These data support the in vitro findings that follicular fluid from small- to medium-sized follicles may contain a luteinization inhibitor, and indicate that presence of follicular fluid during the final days of follicular maturation is not essential for development of a normal CL.

Animals

Prognostic significance of ventricular blood in supratentorial hemorrhage: a volumetric study.

We reviewed CTs from 47 patients with 48 spontaneous, supratentorial brain hemorrhages to determine the effect of ventricular blood on outcome. We correlated volumetric analysis of the parenchymal (P) and ventricular (V) blood, as well as other clinical and CT features, with clinical outcome in a statistical analysis. Hemorrhages were located in putamen 20/48 (42%), thalamus 13/48 (27%), lobar 9/48 (19%), caudate 3/48 (6%), and miscellaneous locations 3/48 (6%). Outcome in putaminal hemorrhages was highly correlated with the total (P + V) and P blood volumes, whereas the V blood was less important. For thalamic hemorrhages, outcome correlated more highly with the V and P + V volumes than with the P portion. Outcome for all hemorrhages was significantly correlated, in descending order of importance, with the severity of the initial neurologic deficit, P + V blood, hydrocephalus, the number of ventricles containing blood, P, V, and blood in the 4th ventricle. In general patients with more than 20 cc of V blood did poorly. Although hydrocephalus was associated with poor outcome, ventricular drainage did not benefit 8 of 9 patients.

Aged

Lipogenesis from ketone bodies in the perfused rat liver: effects of acetate and ethanol.

The interactions between acetate or ethanol metabolism, lipogenesis, and ketone body utilization have been studied in isolated livers from fed rats perfused with 15 mM glucose and 10 mM acetate or ethanol. The contribution of acetate to ketogenesis is constant; on the other hand, the contribution of ethanol to ketogenesis increases with time, presumably because of the accumulation of acetate in the perfusate. Ketogenesis is decreased in the presence of ethanol (but not acetate), while ketone body utilization is not affected by ethanol or acetate. Acetate contributes one third and ethanol contributes one half of the carbon incorporated into fatty acids and 3-beta-hydroxysterols. Only a small fraction (less than 5%) of the incorporation of acetate or ethanol into fatty acids and sterols occurs via transient incorporation into ketone bodies.

Acetates

Leucine kinetics during three weeks at submaintenance-to-maintenance intakes of leucine in men: adaptation and accommodation.

Previous results of short-term diet studies of leucine kinetics have suggested that the currently accepted requirement value for the amino acid in adults is too low. In the present study the effects of a more prolonged diet period at low leucine intakes on leucine kinetics and nitrogen balance (NB) were explored in healthy young men. They (4 or 5 subjects per group) received an adequate leucine intake (80 mg/kg/d) for 1 or 2 weeks (Period 1) followed by either 7, 14 or 30 mg/kg/d for 3 weeks (Period 2) with a return to 80 mg/kg/d for 1 week (Period 3). Estimates of leucine fluxes (LF), oxidation (LO) and balance (LB) were based on a constant intravenous infusion of L-[1-13C]leucine, at end of Period 1, at 1 and 3 weeks of Period 2 and on days 1 and 3 of Period 3. At all three intakes LF and LO, during the fed state, fell between 1 and 3 weeks of Period 2. LB was negative at 1 week of Period 2 for all groups but had approached equilibrium by 3 weeks. N balance at 3 weeks was similar for all groups but during Period 3 was significantly higher (P less than 0.05) and markedly positive (+18 mgN/kg/d) for the 7 and 14 mg groups, compared with the 30 mg group (+4 mgN/kg/d), indicating that 'depletion' had occurred at the lower leucine intakes during Period 2. Our interpretation is that LB was approached by an adaptation in the 30 mg group whereas it was achieved in the 7 and 14 mg groups by an accommodation, associated with a reduced and low rate of leucine uptake into protein (LF minus LO). Thus, the leucine requirement was judged to be greater than 14 mg/kg/d, a level currently accepted as the upper range of the requirement for healthy adults. The significance of these findings for assessment of nutrient requirements is discussed, with emphasis on the limitation of NB measurements for evaluation of human amino acid requirements.

Adaptation, Biological

Retrospective analysis of data from five long-term, metabolic balance studies: implications for understanding dietary nitrogen and energy utilization.

Daily urinary nitrogen (N) excretion and body weight data of 42 healthy young adults, who received constant, adequate diets for up to 90 days, and maintained constant level of physical activity, were examined retrospectively. From the N excretion data, it was determined that, when corrected for long-term trends, daily variability was random and much larger than variability due to the long-term trends. Thus, N balance data based on commonly used diet periods of about 2 wk adequately estimates population variability. Body weight data for most subjects showed significant changes and many subjects experienced persistent linear changes throughout the entire experimental period. Thus, for most healthy young adults, neither dietary-induced thermogenesis nor changes in the efficiency of energy utilization appears to play a quantitatively important role in the maintenance of body weight (and body composition) in response to relatively modest discrepancies between the level of food intake and energy intake needed to balance initial total energy expenditure. The key importance of food intake regulation and/or physical activity in weight maintenance is emphasized by these findings.

Adolescent

Evaluation of the protein quality of an isolated soy protein in young men: relative nitrogen requirements and effect of methionine supplementation.

The protein nutritional value of an isolated soy protein (Supro-620) was evaluated in a series of nitrogen balance studies in healthy young male MIT students. Experiment 1 involved giving eight subjects graded intakes of the isolated soy protein while seven additional subjects received egg protein. Mean nitrogen intake required for N balance for the isolated soy protein and the egg protein were not significantly different (p greater than 0.1). In experiment 2, nine subjects received soy and the effects on N balance at various levels of L-methionine supplementation were studied. In experiment 3 eight subjects each were studied at two nitrogen intake levels of isolated soy protein/kg/day with methionine supplementation, and an unsupplemented egg protein period included. Results from experiment 2 and 3 at an 82 mg N/kg/day test level showed that N balance for 1.6% supplementation was significantly below that of unsupplemented egg while 1.1% and unsupplemented soy were indistinguishable from egg. No beneficial effects of methionine supplementation were observed when the test nitrogen intake level was 128 mg N/kg/day. These results indicate that for healthy adults, the isolated soy protein is of high nutritional quality, comparable to that of animal protein sources, and that the methionine content is not limiting for adult protein maintenance.

Adult

A long-term metabolic balance study in young men to assess the nutritional quality of an isolated soy protein and beef proteins.

To evaluate the capacity of an isolated soy protein to maintain long-term protein nutritional status in healthy young adult men, an 84-day metabolic balance experiment was conducted in eight subjects. The sole source of protein intake was provided by the isolated soy protein, given at a level of 0.8 g (N X 6.25) per kg per day. In a second and similar study, four young men received 0.8 g protein and three subjects 0.68 g protein per kg per day from beef proteins for 60 to 81 days. Body weight, nitrogen balance, blood chemistries, and body composition (whole body 40K) were monitored throughout each study. Body nitrogen balances were maintained within the range of N equilibrium in both diet groups. Body cell mass, as judged from 40K measurements, did not reveal any deterioration in protein nutritional status. These observations confirm the prediction, derived from previous short-term. N balance studies, that the nutritional quality of isolated soy protein is high and that this plant protein can serve as the sole source of essential amino acids and nitrogen for protein maintenance in adults.

Adolescent

Underestimation of metabolic rates owing to reincorporation of 14CO2 in the perfused rat liver.

(14)CO(2) production by perfused rat livers was simulated by infusing NaH(14)CO(3) into the perfusate. Recovery of label as (14)CO(2) gas + perfusate bicarbonate was 45-85%. Rates of (14)CO(2) exchange in the liver are 3-70 times greater than net rates of CO(2) production. Therefore (14)CO(2) reincorporation can lead to significant underestimations of rates of oxidation of (14)C-labelled substrates in liver.

Animals

An analysis of temporal patterns in urinary nitrogen excretion of young adults receiving constant diets at two nitrogen intakes for 8 to 11 weeks.

The temporal pattern of daily urinary nitrogen (UN) excretion was investigated in 21 young adult men and women who participated in two metabolic studies involving constant diets and lasting 8 to 11 weeks. For one group (16 subjects), nitrogen (N) intake was about 280 mg N/kg per day (mixed animal and plant protein sources) for 8 weeks; for the second group (five subjects), N intake was about 90 mg N/kg per day (egg protein) for 11 weeks. Two mathematical models were examined to determine how well they described the variations in UN. The first modeled only random variability while the second added a component of serial correlation (correlation between successive daily observations). After correcting the UN data for linear trend, to minimize effects of possible alterations in body composition, only two of the 21 subjects showed significant serial correlation of daily UN. Moreover, it is shown that any serial correlation undetectable in these data would not be of practical importance in estimating UN levels in short-term dietary experiments. It is concluded that the interpretation of metabolic N balance measurements involving constant N intakes over relatively short dietary periods in not complicated by cyclic, time-dependent variations in UN.

Adolescent

Diurnal variations in plasma concentrations of tryptophan, tryosine, and other neutral amino acids: effect of dietary protein intake.

The effect of dietary protein content on the diurnal variations in plasma neutral amino acid levels was studied in normal human subjects. For three consecutive 5-day periods, subjects consumed diets containing 0, 75, or 150 g of egg protein per day. Blood samples were drawn at 4-hr intervals on the 4th and 5th days of each period. Consumption of the protein-free diet caused plasma concentrations of all amino acids studied to fall in the late morning and afternoon, while the 150-g protein diet elicited increases in these levels during the daytime. Ingestion of the diet containing 75 g of egg protein tended to diminish the amplitudes of the daily rhythms in plasma amino acid levels, but most amino acids still exhibited small but significant elevations late in the evening. At all times of day, plasma concentrations of the large neutral amino acids studied (i.e., aromatic and branched-chain amino acids, and methionine) varied directly with the protein content of the diet. In contrast, the relationships between dietary protein content and the plasma concentrations of glycine and alanine, two small neutral amino acids, were inverse. The ratios of plasma tryptophan, tyrosine, and phenylalanine levels to the sum of the concentrations of other large neutral amino acids tended to fall as the protein content of the diet was increased. The corresponding ratio for valine increased as protein was added to the diet, while the leucine and isoleucine ratios were not correlated with dietary protein content. Since diet-induced changes in plasma trypotphan and tyrosine ratios in animals are known to cause parallel alterations in brain tryptophan and tyrosine levels, and thus in the rates of brain serotonin and catecholamine synthesis, our data suggest that ingestion of carbohydrates and protein may also normally affected brain monoamine synthesis in humans.

Adult

Diurnal variations in plasma neutral amino acid concentrations among patients with cirrhosis: effect of dietary protein.

The effect of varying dietary protein content on the daily rhythms in plasma neutral amino acid concentrations was studied in patients with chronic cirrhosis. For two consecutive 5-day periods, subjects consumed diets containing either 0 or 75 g of protein per day. Blood samples were drawn at 4-hr intervals on the 4th and 5th days of each dietary period. For most of the neutral amino acids, the changes in plasma concentration associated with time of day or with variations in dietary protein content were similar to those observed previously in normal subjects. Ingestion of the protein-free diet caused significant reductions in the daytime level of all amino acids studied, except for tryptophan, the concentration of which did not change during the 24-hr period. Ingestion of the 75-g protein diet caused plasma levels of most of theamino acids to increase slightly during the day; these increments were not statistically significant for tryptophan, tyrosine, leucine, and methionine. The absolute plasma concentrations of most of the neutral amino acids were also in the normal range; exceptions included methonine, tyrosine, and phenylalanine, whose plasma levels were significantly elevated above normal valves. The plasma ratios of tryptophan, tyrosine, and phenylalanine concentrations to the sum of the concentrations of other large neutral amino acids increased during the day uhen the protein-free diet was ingested; this effect was moderated by the addition of protein to the food. The plasma ratios for the branched-chain amino acids were depressed below normal; those for tyrosine, phenylalanine, and methionine were significantly increased. The plasma tryptophan ratio was within the normal range. These findings provide a basis for anticipating that the uptake from blood into brain of several of the large neutral amino acids may be modified in patients with chronic cirrhosis.

Adult

Nitrosamine carcinogenicity: a quantitative Hansch-Taft structure-activity relationship.

Statistically significant correlations have been demonstrated between carcinogenic activity, water-hexane partition coefficients and electronic factors for an extensive series of N-nitroso compounds. Electronic factors were expressed by the Taft sigma* values of substituents on the carbon atoms alpha to the N-nitroso group. Such correlations indicate that transport of the carcinogen to its active site has an important effect on its potency. The correlations also implicate reactivity at the alpha-carbon in the determination of carcinogenic activity and point out various structural types which do not follow the general rule.

Animals

Protein metabolism in human neonates: nitrogen-balance studies, estimated obligatory losses of nitrogen and whole-body turnover of nitrogen.

1. Aspects of nitrogen metabolism in the human neonate were assessed in one full-term infant and six premature infants by means of nitrogen-balance measurements, estimates of obligatory nitrogen losses and determinations of whole-body nitrogen turnover. 2. Our data indicate that the mean protein requirement for maintenance is 1-1 g of protein day-1 kg-1 and that 3-8 g of protein day-1 kg-1 should be sufficient for adequate growth in healthy premature babies. 3. The mean obligatory urinary, faecal and total nitrogen losses were estimated to be 24, 106, 145 mg day-1 kg-1 respectively. These figures are compared with published values for older infants, and the possible metabolic basis for changes in nitrogen losses during growth and development is discussed. 4. Mean values for whole-body protein synthesis and breakdown were 26-3 +/- 7-0 and 23-8 +/- 7-4 g of protein day-1 kg-1 respectively. Dietary nitrogen intake accounted for 6--18% of the nitrogen flux through the metabolic pool; urea excretion accounted for 2% of the nitrogen flux. 5. The net protein gain, estimated from nitrogen-balanced data, accounted for 9-6% of total daily protein synthesis. 6. These results are discussed in relation to published estimates of whole-body protein synthesis and breakdown at various ages. Their possible significance in the assessment of a "maintenance" requirement for protein and amino acids during the period of rapid growth and development is also considered.

Body Weight

Determination of protein allowances in human adults from nitrogen balance data.

The problem of predicting human protein requirements is examined in detail. Three methods from the literature are shown to represent a logical sequence wherin each takes into account more sources of variation than does the previous one. These are the single level method and two versions of the multiple level method, all of which assume a population response curve. A fourth method is proposed as the next step in this sequence. This method calculates a response curve for each individual and works with the individual requirements. Since each method makes fewer assumptions about the data and, therefore, about the biological situation of population protein needs, each method gives successively larger protein allowance values, while at the same time identifying the sources of variability and uncertainty in these estimates.

Adult