Treatment of severe acute respiratory distress syndrome: a final report on a phase I study.

Adult respiratory distress syndrome (ARDS) has a high mortality. Its only effective treatment is respiratory therapy. If this fails mortality is probably 100 per cent. No other treatment for ARDS has proved effective including "magic bullets." Twenty patients suffering from ARDS secondary to trauma and/or sepsis failed to respond to treatment with mechanical ventilation and positive end-expiratory pressure. On the assumption that disseminated intravascular coagulation initiates ARDS by occluding the pulmonary microcirculation with microclots, the patients were treated with plasminogen activators. The patients responded with significant improvement in partial pressure of oxygen in arterial blood. No bleeding occurred and clotting parameters remained normal. We conclude that ARDS can be safely treated with plasminogen activator.

Effects of individual vs group penning on the performance of weanling pigs.

Two experiments (five trials) were conducted to determine the effects of individual vs group penning on the performance of 4-wk-old crossbred barrows and gilts. In each experiment, half the pigs were tested in a group pen (four pigs) for two 7-d periods and individually for one 7-d period and the other pigs were fed individually for two periods and as a group for one period. In Exp. 1 (two trials, each with five replicates of eight pigs), individually penned pigs had physical and visual contact with pigs in the adjoining pens; in Exp. 2 (three trials, each with five replicates of eight pigs), such contact was denied. Growth rate, feed intake, and feed efficiency were determined at the end of each period. In addition, during Trial 3 of Exp. 2 blood samples were collected at the end of each period and plasma was assayed for cortisol and triiodothyronine (T3) concentrations. Penning sequences produced inconsistent weight gains and feed intake. Differences in gain favored (P < .04) the individually penned pigs during Trial 3 of Exp. 2 and differences in feed intake favored the individually penned pigs during Trial 2 of Exp. 1 (P < .009) and during Trials 2 and 3 of Exp. 2 (P < .02 and P < .009, respectively). Penning treatment had no effect on feed efficiency, plasma cortisol, or T3 concentrations. These data suggest that pigs perform equally well whether fed and housed individually or in groups, with no indications of stress associated with individual pens and isolation.

Changes in bone mineral density and markers of bone remodeling during lactation and postweaning in women consuming high amounts of calcium.

A randomized clinical intervention trial to determine effects of lactation and 1 g of calcium (Ca) on bone remodeling was conducted in 15 women (calcium = 7, placebo [P] = 8) consuming 1.3-2.4 g of Ca/day from diet + prenatal supplement. Study periods were baseline, < or = 2 weeks postpartum; lactation, 3 months lactation; and postweaning, 3 months postweaning. Bone mineral density (BMD) corrected for body weight was determined by dual-energy X-ray absorptiometry (DXA). Indicators of calcium metabolism, bone turnover, and lactation were measured: calcium metabolism, parathyroid hormone (PTH), 25-hydroxyvitamin D (25[OH]D), 1,25-dihydroxyvitamin D (1,25[OH]2D); bone turnover, formation, procollagen I carboxypeptides (PICP), osteocalcin, and bone alkaline phosphatase (B-ALP), resorption, tartrate resistant acid phosphatase (TRAP); and lactation, prolactin (PRL). Mean BMD changes differed by site: baseline to lactation -4.3% (P) (p < 0.04) and -6.3% (Ca) (p < 0.01) at the lumbar spine (L2-L4) and 5.7% gains of the ultradistal (UD) radius (Ca) (p < 0.04); lactation to postweaning, -6% to -11% at all sites of the radius and ulna (Ca, P) (p < 0.04) +3% at L2-L4 (Ca) (p < 0.03); baseline to postweaning, (UD) radius -5.2% (P) (p < 0.03), UD radius + ulna -6% to -8% (Ca, P) (p < 0.04) but no significant loss of L2-L4 or total body. Bone turnover markers were higher at lactation than postweaning: PICP (+34%, p < 0.001), osteocalcin (+25%, p < 0.01), TRAP (+11%, p < 0.005) as well as PRL (+81%, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Retrospective evaluation of production characteristics in Sinclair miniature swine--44 years later.

Three hundred seventy-one litter records collected between 1985 and 1993 from 156 Sinclair S-1 miniature sows, a Hormel-derived strain of miniature swine, were retrospectively analyzed and compared with published records for 1950 to 1952 and 1963 to 1965. The effect of several variables such as season and month of parturition, age of sow, parity, and litter size on reproductive parameters of the Sinclair miniature swine were evaluated. The mean and standard error of the mean for litter size, number of liveborn, number of stillborn, and litter size at weaning of the Sinclair S-1 miniature swine were 7.20 +/- 0.12, 6.57 +/- 0.12, 0.63 +/- 0.06, and 5.75 +/- 0.12 piglets respectively. From a total of 2,436 liveborn piglets, 2,133 (87.56%) were weaned. The litter size at birth was similar to that previously reported for this strain of swine, whereas the litter size at weaning increased (P < 0.001) from 4.7 piglets during 1963 to 1965 to 5.8 piglets in our study. The average birth weight decreased (P < 0.001) from 0.90 kg in 1950 to 1952 and 0.72 kg in 1963 to 1965 to 0.59 kg in our study. Reproductive variables that had a considerable effect on the miniswine reproduction included month of parturition, age of sow, parity, and litter size. Primiparous sows had the smallest litter size and lowest number of weaned piglets. Sows during their second and third parity or sows between 2 and 4 years old had the best reproductive performances. Litter size and number of stillborn increased with parity and age of sow, resulting in fewer piglets weaned in older sows.(ABSTRACT TRUNCATED AT 250 WORDS)

Estimation of acute toxicity by fitting a dose-time-response surface.

In acute toxicity testing, organisms are continuously exposed to progressively increasing concentrations of a chemical and deaths of test organisms are recorded at several selected times. The results of the test are traditionally summarized by a dose-response curve, and the time course of effect is usually ignored for lack of a suitable model. A model which integrates the combined effects of dose and exposure duration on response is derived from the biological mechanisms of aquatic toxicity, and a statistically efficient approach for estimating acute toxicity by fitting the proposed model is developed in this paper. The proposed procedure has been computerized as software and a typical data set is used to illustrate the theory and procedure. The new statistical technique is also tested by a data base of a variety of chemical and fish species.

Calcium homeostasis and bone metabolism during pregnancy, lactation, and postweaning: a longitudinal study.

Ten women were followed serially to determine the effect of stages of reproduction on calcium and bone metabolism. The study periods were nonpregnant nonlactating, the end of each trimester of gestation, 3 mo lactation, and postweaning. Comparisons were with nonpregnant nonlactating status for each individual. Fractional calcium absorption (P < 0.0001) and concentrations of 1,25-dihydroxyvitamin D (P < 0.01) were higher in the second and third trimesters. Total urinary calcium was higher during pregnancy and lower postweaning. Parathyroid hormone (PTH) concentrations were higher only postweaning (P < 0.01). Markers of bone turnover increased at the third trimester and during lactation: serum tartrate resistant acid phosphatase and bone specific alkaline phosphatase, and urinary deoxypyridinoline (P < 0.01). Serum procollagen I carboxypeptides increased only in the third trimester (P < 0.01). Bone mineral density by single-photon absorptiometry did not differ by period. We conclude that absorption and urinary excretion of calcium increase during pregnancy whereas bone turnover increases during late pregnancy and lactation; only renal changes consistent with an increase in PTH were seen postweaning.

Effect of food deprivation on baseline iodothyronine and cortisol concentrations in healthy, adult horses.

Six healthy, adult horses, with normal (mean +/- SEM) baseline serum concentrations of total triiodothyronine (T3, 1.02 +/- 0.16 nmol/L), free T3 (FT3, 2.05 +/- 0.33 pmol/L), total thyroxine (T4, 19.87 +/- 1.74 nmol/L), free T4 (FT4, 11.55 +/- 0.70 pmol/L), total reverse T3 (rT3, 0.68 +/- 0.06 nmol/L), and cortisol (152.75 +/- 17.50 nmol/L), were judged to be euthyroid on the basis of response to a standardized thyroid-stimulating hormone response test. Serum concentrations of T3, FT3, T4, FT4, rT3, and cortisol were determined immediately before and every 24 hours during a 4-day period of food deprivation, when water was available ad libitum. Similar variables were measured 72 hours after refeeding. Decreases (to percentage of baseline, prefood deprivation value) in circulating T3 (42%), T4 (38%), FT3 (30%), and FT4 (24%) concentrations were maximal after 2, 4, 2, and 4 days of food deprivation, respectively (P < 0.05). Increases (compared with baseline, prefood deprivation value) in rT3 (31%) and cortisol (41%) concentrations were maximal after 1 and 2 days of food deprivation, respectively (P < 0.05). Refeeding resulted in increase in serum T4 and FT4, and decrease in rT3 and cortisol concentrations toward baseline values, after 72 hours (P < 0.05). Refeeding did not effect a return of T3 or FT3 concentration to baseline values after 72 hours (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of dexamethasone administration on serum thyroid hormone concentrations in clinically normal horses.

The effect that 5 consecutive days of treatment with dexamethasone (0.04 mg/kg of body weight, IM, q 24 h) would have on baseline concentrations of triiodothyronine (T3), thyroxine (T4), reverse T3 (rT3), free T3 (FT3), and free T4 (FT4), and on response to thyroid-stimulating hormone (TSH) administration was determined in 12 clinically normal horses. Results of TSH response tests indicated that the horses could be placed into 2 groups: in 6 horses (group A), T4 concentration after administration of TSH was more than twice the baseline concentration; in the other 6 horses (group B), T4 concentration 6 hours after administration of TSH was less than twice the baseline concentration. Baseline serum concentrations of T3, T4, rT3, FT3, and FT4 were not significantly different between group-A and group-B horses. In both groups of horses, serum T3, T4, rT3, and FT4 concentrations were significantly increased 6 hours following TSH administration, compared with baseline concentrations. Treatment with dexamethasone resulted in significant (P < 0.05) increases in baseline concentrations of rT3 and FT3 in group-A horses and baseline concentrations of rT3 in group-B horses. The response to TSH administration following dexamethasone treatment appeared to be blunted with significant (P < 0.05) increases only in T3, T4, and FT4 concentrations in group-A horses and FT4 concentration in group-B horses. The magnitude of change in serum FT3 concentration in response to TSH administration was significantly less (P = 0.05) following dexamethasone treatment, compared with magnitude of change prior to dexamethasone treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Development toxicity of fumonisin in Syrian hamsters.

The effects of fumonisin on development of Syrian hamster fetuses were studied using fumonisin B1 and B2 extracted from Fusarium moniliforme corn-culture and purified fumonisin B1. A significant increase in litters with fetal deaths occurred with the high doses of purified (18 mg FB1/kg) and culture-extracted (18 mg FB1 plus 4.5 mg FB2) fumonisin. It is concluded that prenatal exposure to fumonisin on days 8 and 9 of gestation is detrimental to fetal hamster survivability but does not induce clinical maternal intoxication at these doses. Equivalent doses of fumonisin B1, whether from culture-extract or pure solution produced similar results.

Differences in blood flow to uterine segments and placentae in relation to sex, intrauterine location and side in pregnant rats.

The effects of location within the left or right uterine horn, position within each uterine horn, and fetal sex on fetal bodymass, blood flow to individual uterine segments associated with fetuses, and blood flow to the maternal portion of the placenta were investigated in rats. Sprague-Dawley rats were anaesthetized on day 5, 10, 15, 20, 21 or 22 of pregnancy, and radioactive microspheres with diameters of 15 mm were injected via a left ventricular cannula to measure blood flow to tissues. Tissues were weighed wet, and the rate of blood flow, corrected for wet mass (ml min-1 g-1 tissue), was calculated. Microspheres were not detected in fetuses, suggesting that they did not pass from maternal into fetal blood. Uterine blood flow was greater at the cervical and ovarian ends than in the middle of the uterus; on day 15 the rate of blood flow at the cervical and ovarian ends of each uterine horn was over twice that in the middle. The blood flow to the right uterine horn was greater than to the left horn. Blood flow to placentae increased dramatically between day 15 and day 20. There were marked differences in architecture between the uterine artery feeding the ovarian end of the right and left uterine horn, and blood flow to placentae located at the ovarian end of the right uterine horn was greater than to placentae in the same location in the left uterine horn. The blood flow to placentae and fetal bodymass were greater for female than for male fetuses on day 20, but on day 22 the reverse was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of Re-17 mutant Salmonella typhimurium bacterin toxoid on clinical coliform mastitis.

The objective of this study was to test the hypothesis that the incidence and severity of clinical coliform mastitis could be decreased by Re-17 mutant Salmonella typhimurium bacterin toxoid. Holstein-Friesian cows from two Arizona dairies were selected for this study based on July through November projected calving dates; peak lactation occurred during the period of highest rainfall and peak environmental stress. The cows were randomly assigned to either a vaccinate or a control group, and 1292 cows were paired by herd, parity, calving date, and milk yield. The 646 vaccinates were injected twice during the third trimester of pregnancy with an Re-17 mutant S. typhimurium bacterin toxoid, and the 646 controls were not vaccinated. Vaccinated cows had significantly fewer clinical cases of coliform mastitis with positive coliform cultures and had lower culling rate from coliform mastitis than control cows during the first 5 mo of lactation. During the same period, the mortality rate from clinical coliform mastitis was 75% less in the vaccinated clinical coliform mastitic group than in the control group. Incidence of mastitis increased with advancing parity. The Re-17 mutant Salmonella typhimurium bacterin toxoid provided cross-protection against coliform mastitis; incidence and severity of clinical coliform mastitis were significantly lowered during the first 5 mo of lactation.

Developmental toxicity in hamsters of an aqueous extract of Fusarium moniliforme culture material containing known quantities of fumonisin B1.

The purpose of this study was to investigate potential detrimental effects of fumonisin B1 on the developing hamster. In experiments 1 and 2, timed-bred hamsters were dosed with 0.0 to 12.0 mg fumonisin B1/kg from day 8 to day 10 or day 12 of gestation. Clinical signs of material toxicity were not observed. Pregnant animals had reduced weight gains and lower total bilirubin levels than nonpregnant females. Hamsters were euthanized on day 15 of gestation. Histologic evaluation revealed autolytic placental changes expected in terminal gestation, as well as more advanced placental necrosis in association with fetal resorptions. Mean fetal weights and crown-rump lengths of living term fetuses on a per-litter basis did not differ between untreated controls and treated animals given 6.0 mg fumonisin B1/kg or less. However, at higher doses of fumonisin B1, there was an increased incidence of prenatal losses (deaths and resorptions). A greater percentage of litters had 1 or more fetuses affected, and a greater percentage of total fetuses were lost/litter as the fumonisin dosage increased. At 12.0 mg/kg, all litters were affected and 100% of the fetuses were dead and resorbing. Fumonisin B1 appears a developmental toxicant in hamsters. Toxicity is manifest by increased numbers of prenatal deaths and resorptions at doses that do not induce clinicopathologic evidence of maternal toxicity.

Absorption of an alternate source of immunoglobulin in pups.

Newborn pups from 4 large litters were alloted to 6 groups to determine effect of time and route of administration on absorption of an alternate source of immunoglobulin. Selective absorption of specific classes of immunoglobulins was also investigated. The alternate source of immunoglobulin consisted of pooled serum that was administered either PO or SC. Control groups were either left with the dam (group C1) or fed milk replacer (group C2). Blood samples were collected from pups at birth and 24 hours. Immunoglobulin (IgA, IgG, IgM) concentrations were determined by use of radial immunodiffusion on samples of pooled serum, colostrum, and pups' serum (birth and 24 hours). Serum IgA concentration was less than the sensitivity of the procedure and was not included in the statistical analysis. Pups fed 8 ml of pooled serum at birth and 12 hours later (group T1) absorbed more (P less than 0.05) IgG and IgM than did group-C2 pups, but less (P less than 0.05) than did group-C1 pups. Pups fed 8 ml of pooled serum at 12 hours only had significant (P less than 0.05) increase of IgG concentration, but no absorption of IgM (P greater than 0.05) at 24 hours, compared with control pups (group C2). Pups administered 8 ml of pooled serum SC at birth (group SC1) had similar (P greater than 0.05) absorption of IgG and higher (P less than 0.05) absorption of IgM than did pups of group T1.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of coronary occlusion duration on reactive hyperemia in conscious dogs and ponies.

Coronary reactive hyperemia duration (RHD) and coronary blood flow debt repayment (BFDR) were compared in conscious dogs and ponies instrumented with coronary artery Doppler flow probes and pneumatic occluders. Additional ponies were instrumented with pacing electrodes. With the use of a Latin square design, eight animals of each species were subjected to a randomized series of nine coronary occlusions ranging from 5 s to 2 min in duration. In both species, postocclusion blood flow velocity rose rapidly and plateaued at similar peak levels relative to control, but in ponies this plateau lasted significantly longer. The interspecies difference in plateau duration increased as a function of coronary occlusion duration (COD). RHD ranged from 19.5 +/- 5.9 to 139.7 +/- 5.9 s in dogs and from 26.6 +/- 9.0 to 395.0 +/- 9.0 s in ponies. The slope of the RHD vs. COD curve was steeper in ponies. BFDR was similar in dogs and ponies at the shortest COD (418.1 +/- 26 vs. 451.4 +/- 58%) but declined in dogs as a function of COD to 232.3 +/- 26%. In ponies, BFDR increased as a function of COD to a maximum of 945.4 +/- 58% with a 60-s occlusion and then declined to 614.3 +/- 58%. RHD was not significantly altered in ponies when heart rate was changed to match that in dogs. Although the underlying basis for these interspecies differences in RHD and BFDR was not determined, the differences were considered to be too large to be explained by animal model differences in coronary conductance, collateral blood flow, or myocardial oxygen consumption.(ABSTRACT TRUNCATED AT 250 WORDS)

Seasonality and variability of the interestrous interval in the bitch.

Records from two breeding colonies (A and B) located near each other were analyzed for this experiment. Colony A consisted of 19 bitches (8 Maltese, 5 Yorkshire, 3 Lhasa Apso, and 3 Bouvier des Flandres), while Colony B consisted of 48 Beagle bitches. A total of 126 interestrous intervals (141 estrous cycles) from Colony A were reviewed to quantitate the variability of the interestrous interval. Analysis of variance showed that the degree of variation of the estrous cycle length within bitches (65%) was about twice the degree of variation of means of the estrous cycle length among bitches (35%). It was found that the estrous cycle length is extremely variable, and it cannot be used to predict the next estrus in a single bitch, although some bitches were very consistent. The seasonal and monthly distribution of estrous cycles throughout the year was also analyzed from bitches kept in Colonies A and B for a total of 210 estrous cycles. The data were collected over a four-year period. A seasonal pattern was observed when the cumulative distributions over years were analyzed. A higher frequency of estrous cycles was observed during winter and summer. This seasonality pattern was not observed when individual years were analyzed separately. However, the overall probability that an estrus would occur at any month of the year was the same for each month (1/12) when cumulative distribution over years were analyzed.

Cardiovascular effects of detomidine, a new alpha 2-adrenoceptor agonist, in the conscious pony.

The cardiovascular effects of detomidine and xylazine were compared in six chronically instrumented, conscious ponies. Ponies were instrumented with a micromanometer in the left ventricular chamber, a Doppler flow probe on a coronary artery and sonomicrometer crystals in the left ventricular free wall. Heart rate, ventricular systolic pressure, stroke work, dP/dtmax, minute work and coronary blood flow were measured for 4 h following intravenous injection of detomidine at several doses or xylazine at 1.1 mg/kg. Both drugs caused a profound hypertensive response at 15 s post-injection. The magnitude of the pressure change did not increase with detomidine doses greater than 20 micrograms/kg. There was a dose-dependent effect on the duration of the hypertension. Bradycardia and A-V blockade of similar magnitude followed the hypertension at all drug doses. Both drugs caused a negative inotropic effect on the heart at all doses. Minute work, a mechanical index of myocardial O2 demand, and coronary flow decreased to a similar extent following all drug treatments. With the exception of a greater hypertensive response, detomidine at the dosages studied, produced cardiovascular effects that were very similar to those of the recommended dosage of xylazine.

Isoleucine requirement of young growing male guinea pigs.

The isoleucine requirement of young, growing male guinea pigs was investigated by use of crystalline amino acid diets containing 3.65% nitrogen. Three-week-old guinea pigs were fed one of eight crystalline amino acid diets ranging from 0.2 to 1.2% isoleucine for 22 d. Diets were evaluated on the basis of body weight changes, nitrogen retention, carcass weight, liver weight, hematocrit, hemoglobin and carcass and liver weights expressed as percentages of live body weight. A 0.5% level of dietary isoleucine (2.2% of total nitrogen X 6.25) was the lowest level fed that did not have a response significantly lower than the higher levels fed, and that generally promoted a thrifty and well-groomed appearance of the animals.

Ovarian follicular populations and in vitro steroidogenesis on three different days of the bovine estrous cycle.

This study was undertaken to determine changes in follicular populations on ovaries of dairy cows during three stages of the estrous cycle and their steroidogenic capacity in vitro. Numbers of small (2.0 to 5.0 mm), intermediate (5.1 to 10 mm) and large (greater than 10 mm) antral follicles on ovaries of multiparous cows and heifers (n = 31) in the early luteal (d 4), mid-luteal (d 12) and follicular phase (d 19) of the estrous cycle were determined (d 0 = estrus), and steroidogenic capacity of intermediate and large follicles was measured in vitro. Total number of follicles and number of small follicles were greatest (P less than .05) on d 19 compared with d 12, with numbers on d 4 not different from either d 12 or 19. Intermediate follicles were fewer (P less than .05) on d 19 compared with d 4 or 12. Numbers of large follicles did not change. The proportion of estrogen active (EA) follicles was greater (P less than .05) on d 19 compared with d 4 or 12. Accumulation of estradiol-17 beta (E) into culture medium by intermediate follicles decreased (P less than .05) with increasing days of the estrous cycle, while accumulation of progesterone (P) was greater on d 19. In large follicles, accumulation of E into culture medium was greatest (P less than .05) on d 19 and the lowest on d 12 (P less than .05). In summary, the proportion of EA follicles increases during the preovulatory period, and E production increases in large EA follicles.(ABSTRACT TRUNCATED AT 250 WORDS)