[Primary revision with replasty of the anterior cruciate ligament]. / Die primäre Revision mit Replastik des vorderen Kreuzbandes.

OBJECTIVE: Restoration of knee stability after rerupture of an anterior cruciate ligament (ACL) graft. INDICATION: Acute and chronic functional instability with rerupture of an ACL graft with subjective instability with anatomical or non-anatomical bone tunnel without tunnel widening. CONTRAINDICATIONS: Partial anatomical bone tunnels of the previous operation, significant tunnel widening of anatomical bone tunnels, local infection of the knee joint, local soft tissue damage. SURGICAL TECHNIQUE: Graft choices are hamstring tendons (semitendinosus muscle, gracilis muscle), the quadriceps tendon, patellar tendon and a peroneus tendon split graft. In cases with anatomical tunnels, careful debridement is performed down to the tunnel wall. In non-anatomical tunnels, a new femoral tunnel is drilled over a deep anteromedial portal with the knee flexed more than 110° in the insertion area of the ACL. Using drills and dilators, a tunnel is prepared. At the tibia, the anterior horn of the lateral meniscus serves as a landmark in the absence of an ACL stump. The cortical tibial tunnel aperture is probed with a guide wire and the tunnel is drilled stepwise until the tunnel wall is reached, which is debrided with a spoon or synovial resector to remove graft residues and implants from the tunnel. The femoral fixation can either be done with a flip button, an interference screw or in the case of a bone block graft implant-free. At the tibial side, the graft is fixed with a resorbable interference screw and fixation button. POSTOPERATIVE MANAGEMENT: The rehabilitation program comprises 4-5 phases. Inflammatory phase (weeks 1-2): control of pain and swelling (cooling, isometric tension exercises, 20 kg partial load). Phase 2 (weeks 2-6): increasing load and range of motion with closed chain exercises (target: extension/flexion 0-0-120°). Phase 3 (from week 6): strength and coordination exercises. Phase 4: balance, strength and jump exercises. Return to competitive sport not before postoperative month 6-10. RESULTS: Included were 51 patients with recurrent instability after ACL surgery where primary ACL replacement was performed with ipsilateral bone quadriceps tendon graft or contralateral semitendinosus-gracilis graft. All patients had anatomical or non-anatomical tunnel locations without significant widening (>11 mm). After 2 years, the side-to-side difference for anterior tibial translation measured with the KT 1000 arthrometer was 2.0 ± 1.2 mm for the quadriceps group and 3.0 ± 2.9 mm for the semitendinosus-gracilis group (P = 0.461). No difference in the rate of positive pivot shift tests (P = 0.661); no significant difference in the individual Knee Injury and Osteoarthritis Outcome Score (KOOS) subscores or in the frequency of anterior knee pain.

The role of purinergic P2Y12 receptor blockers on the angiogenic properties of endothelial cells: an in vitro study.

Pharmacotherapy with agents that inhibit platelet function has proven to be effective in the treatment of acute coronary syndrome. Proper re-endothelization after angioplasty prevents adverse cardiovascular events. Therefore, in this in vitro study we examined how antiplatelet P2Y12 receptor blockers can affect endothelial cells' angiogenic properties. Endothelial cells were exposed to ticagrelor, prasugrel and clopidogrel in their highest concentrations obtained in serum after the treatment with loading and clinical doses. Further, the viability, apoptosis, and necrosis were tested and the following angiogenic properties such as proliferation, migration, invasiveness, tube formation, wound healing and the production of angiogenic mediators (bFGF, PDGF, MMP-2, Ang-2, TIMP-1). The results of this study showed that P2Y12 receptor blockers in the tested concentrations are safe for endothelial cells. They neither induced necrosis or apoptosis nor changed the endothelial cell viability, migration, invasiveness, tube formation, wound healing, the production of VEGF or its receptors. However, they reduced cell proliferation. It was shown that out of these three drugs, ticagrelor in its loading concentration had the most potent angiogenic property. It reduced cell proliferation and changed the production of angiogenic (bFGF, MMP-2) and angiostatic mediators (Ang-2). In conclusion, P2Y12 receptor blockers in the concentrations obtained in the serum during standard therapy reduced endothelial cell proliferation. Despite this slight antimitogenic effect, they did not change endothelial cell tube formation or wound healing. Out of the three tested drugs, ticagrelor had the most potent angiogenic effect in vitro, but not strong enough to disturb tube formation and wound healing.

Statistical considerations in the quantitation of serum immunoglobulin levels using the enzyme-linked immunosorbent assay (ELISA).

Several methods for analyzing ELISA data have been evaluated using optical density values derived by reacting serial two-fold dilutions of a rhesus monkey (Macaca mulatta) reference serum with dilutions of peroxidase-conjugated monospecific antisera to human IgG and IgM in the micro-ELISA 'sandwich' technique using microplates coated with appropriately diluted antisera to human IgG and IgM. Representation of optical density as a linear function of log serum dilution was shown to be inappropriate and potentially misleading. Weighted non-linear least squares analysis of a 4-parameter logit was demonstrated to be inappropriate because it required the specification of a somewhat arbitrary variance function and weight estimates varied substantially depending on the function used. Representation of optical density as a 4-parameter logistic function with estimation carried out on the log scale was shown to be the most appropriate procedure for determining the concentration of antigens or antibodies by the ELISA method.

Short-term effects of butylated hydroxytoluene on the Wistar rat liver, urinary bladder and thyroid gland.

Long-term feeding of butylated hydroxytoluene (BHT) to rats and mice has been linked to the enhancement of the incidence of liver tumors. It is shown in this paper that in the liver, urinary bladder and thyroid of the male Wistar rat, feeding the highest tolerated doses of BHT for 30 days does not lead to detectable increases in [3H]thymidine labeling. On the other hand, treatment of rats with 0.5% dietary BHT leads to a time-limited increase in liver cell [3H]thymidine labeling that subsided to control values within 8 days. This increase in [3H]thymidine labeling in the liver is accompanied by an unexpectedly large increase in the mitotic index. These results are discussed in the light of the behavior of certain rodent liver tumorigens.

Effect of fenoldopam in dogs with spontaneous renal insufficiency.

Fenoldopam administration orally or i.v. resulted in significant increases in paraaminohippuric acid (PAH) clearance in both four control dogs and four dogs with chronic renal failure. Oral fenoldopam resulted in significant plasma levels of fenoldopam sulfate metabolites. One metabolite, fenoldopam-8-sulfate, a potential inhibitor of organic anion transport, did not depress renal cortical slice accumulation of PAH. The data therefore indicate that in dogs with chronic renal failure, PAH clearance after fenoldopam administration is a reliable measure of renal plasma flow, and fenoldopam can result in an increase in renal plasma flow.

A 13-week feeding study of butylated hydroxyanisole: the subsequent regression of the induced lesions in male Fischer 344 rat forestomach epithelium.

Feeding butylated hydroxyanisole (BHA) to male Fischer 344 rats at concentrations of 2, 0.5, 0.25, 0.1 and 0% for 13 weeks led to proliferative lesions developing in the forestomach epithelium of the 2%-treated rats but not in other groups. The [methyl-3H]thymidine labelling index was raised in the 2%- and 0.5%-treated groups and showed an apparent no observable effect level at 0.25%. Within 1 week after withdrawal of BHA the labelling indexes in all treated groups returned to near the values in the controls. The induced mucosal lesions, however, reverted more slowly and even after 9 weeks on the basal diet, the stratified squamous epithelium along the lesser curvature, was still slightly thicker than the control. There were multilayered basal cell processes in the lamina propria with connections to the basal cell layer. The possible significance of these results to the ultimate development of cancer is discussed.

A carcinogenesis reversibility study of the effects of butylated hydroxyanisole on the forestomach and urinary bladder in male Fischer 344 rats.

A reversibility study was initiated to determine if the length of feeding with 2% butylated hydroxyanisole (BHA) altered the incidence of forestomach lesions observed after a 24-month observation period. Groups of male Fischer 344 rats were fed 2% BHA for 0, 3, 6, 12, and 24 months and then the basal diet for the completion of the 24-month experimental period. Subgroups were serially sacrificed for histopathological examination and [methyl-3H]thymidine radioautography at the time when each group of animals was transferred to the basal diet and also at 15 months. The results showed that except for carcinomas and some epithelial downgrowths, cellular proliferation, measured by radioautography in the epithelium lining the greater and the lesser curvature of the forestomach, remained dependent on the continuous presence of 2% BHA for, at least, 12 months. Superficial hyperplasias, inflammatory lesions and many of the papillomas regressed after cessation of treatment at 12 months. The epithelial downgrowths did not appear to enlarge after the BHA was withdrawn. The squamous cell carcinomas occurred in almost identical yields whether the rats were fed 2% BHA for 12 months and then returned to the basal diet for 12 months or received 2% BHA continuously for 24 months. It is shown here that at several times, 2% BHA stimulated the [methyl-3H]thymidine labelling index of the transitional epithelium of the urinary bladder and that at 3 months the no observed effect level was greater than 0.5% BHA. The significance of the studies on the forestomach and bladder epithelia are discussed. It is concluded that the lesions induced by BHA are most unlikely to be relevant to humans exposed to much lower levels of BHA.

Short-term pathological and proliferative effects of butylated hydroxyanisole and other phenolic antioxidants in the forestomach of Fischer 344 rats.

Food grade butylated hydroxyanisole (BHA) when incorporated in the diet and fed to male Fischer 344 rats for 9 or 27 days induced proliferative squamous epithelial changes in the lesser curvature of the forestomach proximate to the glandular stomach. These changes were assessed histopathologically and by [methyl-3H]thymidine radioautography. It was shown that BHA mixed dry into powdered diet, incorporated into the diet in corn oil, or in a pelleted diet, induced similar effects. When levels of 2%, 1%, 0.5%, 0.25%, 0.1% and 0% BHA were incorporated in rat diet for 9 days, the proliferative effect appeared to show a no effect level at 0.25% based on the [methyl-3H]thymidine-labelling index. Other food use antioxidants, namely butylated hydroxytoluene or tertiary butylhydroquinone, induced a lesser response than BHA at the maximum dose employed in the study. Propyl gallate was without effect. Propyl-4-hydroxybenzoate, a food use phenol, on the other hand, induced a less pronounced response than BHA but was more effective than the other antioxidants. Because increased cellular proliferation often provides an optimal milieu for tumor formation, it is suggested that these observations may be relevant to rat forestomach tumors induced by BHA.

Short-term effects of various phenols and acids on the Fischer 344 male rat forestomach epithelium.

A series of phenols and acids was fed to rats for 9 days to determine effects on the [methyl-3H]thymidine labelling index and the histological appearance of the forestomach. A variety of proliferative effects in the rat forestomach were observed which paralleled changes in the [methyl-3H] thymidine labelling index. The 3-tert-butyl isomer of butylated hydroxyanisole (BHA) was as effective as the food grade mixture. In the 4-hydroxybenzoic acid ester series, activity was not found either with the free acid or the methyl ester. With the ethyl, n-propyl and n-butyl esters activity in the perfundic region of the forestomach increased with alkyl chain length, the n-butyl ester being nearly as effective as BHA. In contrast, 4-methoxyyphenol and propionic acid demonstrated their greatest effects in the midregion of the forestomach, the action of propionic acid not being apparent until 21 or 27 days of treatment. It was also found that after a 9-day treatment involving coadministration of BHA and acetylsalicyclic acid, the overall effect of the antioxidant on the forestomach was greatly reduced.

Effect of deoxynivalenol (vomitoxin) on the humoral immunity of mice.

The effects of vomitoxin (deoxynivalenol; DON) on the immune system were studied in groups of weanling male Swiss Webster mice administered by gavage 0.75, 2.5, and 7.5 mg of vomitoxin per kg body weight. Untreated controls and solvent controls (propylene glycol, ethanol, and distilled water in a ratio of 4:1:5) were also included in this study. Serum antibody (IgM) levels to sheep red blood cells (SRBC) were significantly reduced in the treatment groups compared to the control groups. Plaque-forming cell (PFC) numbers were also lower in the treated groups compared to the control groups. Furthermore, vomitoxin at a dose of 0.75 mg/kg resulted in a significant increase in the albumin, albumin/globulin ratio and a decrease in the alpha-2 globulin fraction compared to the control groups. Administration of 7.5 mg/kg of vomitoxin resulted in deaths, due to toxicity, in all animals of this group within 3 weeks. These preliminary findings are indicative of a potential effect of vomitoxin on the immune system which could have serious implications to man.

Toxicodynamics and toxicokinetics of amikacin in the guinea pig cochlea.

An extensive overview of the relationship between cochlear toxicity and amikacin blood concentrations in the guinea pig is provided which should assist in the clinical application of this class of antibiotic. A data set previously used to relate the incidence of amikacin ototoxicity to dosing rates and blood concentrations was re-examined to assess the toxicodynamics of amikacin in terms of decibels of hearing loss across dosing rate, hearing frequency and time following drug exposure. Animals in this data set had received continuously i.v. infused amikacin over an 8-fold range of dosing rates. Preliminary analysis indicated that the data were consistent with a sigmoid relationship between hearing loss (decibels) and area under the amikacin plasma concentration vs time curve cumulated over the entire course of drug administration (cAUC). The sigmoid model was therefore used as the backbone of a far more comprehensive toxicodynamic model which described all the data with a single equation. Testing with this model showed that the cAUC required to produce half-maximum hearing loss (cAUC-1/2) was related to dosing rate (P < 0.01), to hearing frequency (P < 0.00001), and to post-drug interval (P < 0.00001). Maximum hearing loss (difference between upper and lower sigmoid asymptotes) was less than total and was significantly related to frequency (P < 0.00001). No effects could be detected on the sigmoid slope. Further modelling of the significant effects detected by the comprehensive toxicodynamic model was done to determine if they could be described by simple relationships or by biologically relevant sub-models. Modelling of maximum hearing loss (postulated to represent loss of mainly outer hair cell function) indicated that this parameter was constant at about 61 decibels for 2-12 kHz and linearly decreased with log frequency for frequencies > 12 kHz. Modelling of cAUC-1/2 on frequency indicated that there was a strong inverse linear relationship to log frequency. Modelling of cAUC-1/2 on post-drug interval indicated that delayed ototoxicity continued at progressively slower rates for at least 56 days after drug administration had ceased. Modelling of cAUC-1/2 on dosing rate showed an increased requirement for drug as the dosing rate decreased. However, cAUC-1/2 changed no more than 20% across the range of dosing rates compared to the 8-fold difference in mean steady-state plasma concentrations, suggesting that plasma concentration is not a primary determinant of ototoxicity. A toxicokinetic model was developed which explained the dosing rate effect on cAUC-1/2 very successfully.(ABSTRACT TRUNCATED AT 400 WORDS)

Lifetime low-level lead exposure produces deficits in delayed alternation in adult monkeys.

Cynomolgus monkeys (Macaca fascicularis) were dosed continuously from birth onward with 100, 50, or 0 micrograms/kg/day of lead. This resulted in blood lead concentrations of 25, 15, or 3 micrograms/dl respectively before withdrawal of infant formula at 200 days of age. Blood lead concentrations declined thereafter over the next 100-150 days to steady-state concentrations of 13, 11, or 3 micrograms/dl. At seven to eight years of age, monkeys were tested on a delayed alternation task. The task required the monkey to alternate responses between two pushbuttons; each alternation was rewarded with a small amount of apple juice. After each monkey learned the task, a delay was instituted between trials. The initial delay was 100 msec, and was increased in steps to 15 sec by the end of the experiment. Treated monkeys were impaired in their ability to learn the alternation task, but were not different from controls at short delay values (1 and 3 sec). At longer delay values (5 and 15 sec), treated monkeys again exhibited impairment. At the 15 sec delay value, some individuals in both treated groups exhibited marked perseveration, responding on the same button in some instances for hours at a time. Treated monkeys were also more variable in their performance across sessions than were controls. The data are interpreted as indicative of spatial learning and short-term memory deficits in the lead-exposed monkeys.

Survey of lead, cadmium and fluoride in human milk and correlation of levels with environmental and food factors.

Lead, cadmium and fluoride were determined in 210 samples of human milk and the mean and median levels and ranges found were 1.04 and 0.55 ng/g (range less than 0.05-15.8 ng/g) for lead, 0.08 and 0.06 ng/g (range less than 0.002-4.05 ng/g) for cadmium, and 7.08 and less than 4 ng/g (range less than 2-97 ng/g) for fluoride. For mothers taking no fluoride supplements and living in communities with fluoride (1 microgram/g) in the drinking-water, the mean fluoride level was 9.8 ng/g. Where no fluoride was present in the drinking-water, the mean level was 4.4 ng/g. Geometric means for all non-zero lead, cadmium and fluoride concentrations were 0.566, 0.063 and 12 ng/g, respectively. Statistical correlation of levels with some dietary and environmental factors showed that lead levels were most strongly correlated with the age of the house (P less than 0.001), with maternal exposure to heavy traffic for more than 5 yr (P = 0.011), and with coffee consumption (P = 0.034). Fluoride levels correlated strongly (P = 0.007) with the presence of fluoride in the drinking-water. Cadmium levels correlated strongly with exposure to cigarette smoke (P = 0.005 if the mother smoked and P = 0.003 if the father smoked and the mother did not smoke).

Variability in caffeine consumption from coffee and tea: possible significance for epidemiological studies.

Five surveys, using a previously developed high-performance liquid chromatography procedure to measure caffeine concentrations, indicated great variations in the concentrations of caffeine in tea and coffee. In the study of beverages prepared at home, data on caffeine concentrations in 58 samples of tea and coffee, volumes of cups, and numbers of cups consumed/day, indicated that the range of caffeine intakes for the women participating was 49-1022 mg/day. There were considerable day-to-day variations in caffeine contents in coffee samples from some commercial coffee shops. When 17 samples of five national brands of instant coffee were made into beverages in the laboratory, variations in caffeine concentrations between lots were small but between brands were significant. A considerable range of caffeine concentrations was also found when 12 samples of coffee prepared at work by different individuals using the same jar of instant coffee were analysed. Analysis of tea samples prepared in the laboratory indicated that steeping time had an important influence on resulting caffeine and theobromine concentrations. People preparing their own beverages were found to drink more liquid than the volume offered commerically. The mean caffeine 'contents' of home-made coffee and of coffee prepared by individuals at work were 79.4 and 81.7 mg/cup respectively, indicating a mean intake of approximately 80 mg caffeine/cup. When this amount (80 mg/cup) was used to estimate daily intakes of caffeine from coffee, on the basis of the number of reported cups/day, and the values obtained were compared with the amounts actually consumed by individuals, the potential for misrepresentation of individual consumption became obvious. For example, for subjects consuming three cups of coffee, only 25% would have been correctly categorized in the expected range for the daily intake of caffeine, 39% would have been overestimated and 36% underestimated for the amount of caffeine consumed. These variations in caffeine concentrations and in the volume of coffee consumed have frequently been ignored in examinations of the possible relationship between coffee consumption and various health problems, and this could perhaps partly explain some conflicting results seen in epidemiological studies.

The toxicity of orally administered deoxynivalenol (vomitoxin) in rats and mice.

Two studies were conducted with weanling male rodents in an attempt to ascertain more precisely the toxic effects of deoxynivalenol (DON). In a feeding study of approximately 18-wk duration, groups of 90 Swiss-Webster derived mice and 50 Sprague-Dawley rats were fed a commercial chow (118 ppb DON), and groups of 80 mice and 50 rats were fed either an 'uncontaminated' diet (53 ppb DON) or a contaminated diet (6250 ppb DON), both based on wheat. A 5-wk gavage study was also performed, in which 24 litters of 5 Swiss-Webster-derived mice were divided among the following groups: an untreated control group, a solvent control group, and three treated groups receiving 0.75, 2.5 or 7.5 mg DON/kg body weight. While there were interim kills in the feeding study, most of the animals given 7.5 or 2.5 mg/kg in the gavage study died during the test period. Effects on body weight and haematological parameters in both studies indicate that DON elicited some degree of toxicity at all levels tested. The histopathological findings from the gavage study suggest that DON had effects on the immune system as well as being a gastro-intestinal irritant.

Histopathological and radioautographical studies on the forestomach of F344 rats treated with butylated hydroxyanisole and related chemicals.

Butylated hydroxyanisole, when fed to male Fischer 344 rats for periods of 9 days or more, led to forestomach epithelial cell necrosis and regeneration. Both the induced proliferation and the histopathological changes were considerably more prevalent in the prefundic region of the forestomach than in the mid-region. Using [Me-3H]thymidine, a specific DNA precursor, and radioautography it was shown that the effect of the antioxidant was apparently threshold at 0.25% in the diet after both 9 days and 3 months of treatment and that the proliferation was dependent on the continuous presence of the antioxidant in the diet at 3 and 6 months. Some other phenols and acids were investigated after 9-27 days' feeding; most induced some degree of epithelial cell proliferation in the rat forestomach, although some had a greater effect on the mid-region than on the prefundic region. These observations are discussed in terms of the likely relevance of butylated hydroxyanisole-induced forestomach tumours to the possibility that the antioxidant may lead to cancer in humans exposed to lower levels in their diet.

Toxicological consequences of Aroclor 1254 ingestion by female rhesus (Macaca mulatta) monkeys. Part 1A. Prebreeding phase: clinical health findings.

A group of 80 menstruating rhesus (Macaca mulatta) monkeys, with an average estimated age of 11.1 +/- 4.1 yr SD, were first randomly allocated to four similar test rooms (20 monkeys/room) and then randomly allocated to one of the five dose groups (four females/dose group/room). Each day, the females self-ingested capsules containing doses of 0, 5, 20, 40 or 80 micrograms Aroclor 1254/kg body weight. After 25 months of daily dosing, approximately 90% of the treated females attained a qualitative pharmacokinetic steady state with respect to the concentration of polychlorinated biphenyl in their adipose tissue. The test monkeys were monitored daily for health and menstrual status, as well as feed and water consumption. On a weekly basis, each female's body weight was determined and a detailed clinical examination was conducted. Minor treatment effects included a slight, but not statistically significant, decrease in feed and water consumption as well as a decreased feed conversion ratio and a slight increase in the duration of menses. Statistically significant, dose-related treatment effects included inflammation and/or prominence of the tarsal (Meibomian) glands, eye exudate, and various finger and toe nail changes. These results were found at doses lower than those previously reported for non-human primates.

Toxicological consequences of Aroclor 1254 ingestion by female rhesus (Macaca mulatta) monkeys. Part 1B. Prebreeding phase: clinical and analytical laboratory findings.

A group of 80 menstruating rhesus (Macaca mulatta) monkeys, with an average estimated age of 11.1 +/- 4.1 yr SD were first randomly allocated to four similar test rooms (20 monkeys/room), and then randomly allocated to one of five dose groups (four females/dose group/room). Each day, the monkeys self-ingested capsules containing doses of 0, 5, 20, 40 or 80 micrograms Aroclor 1254/kg body weight. After 25 months of daily dosing, approximately 90% of the treated females attained a qualitative pharmacokinetic steady state with respect to the concentration of polychlorinated biphenyl (PCB) in their adipose tissue. Subsequently, oestrogen and progesterone concentrations in serum were determined for one complete oestrous cycle and various immunological tests were conducted, while the monkeys continued to receive their daily dose of PCB. During the prebreeding phase of the study, blood for clinical and analytical monitoring including haematology, serum biochemistry, serum hydrocortisone, serum proteins (alpha 1, alpha 2, beta and gamma-globulins), serum immunoglobulins (A, G and M) and thyroid variables (thyroxine/triiodothyronine (T3) uptake ratio, percentage T3 uptake and free thyroxine index), were obtained monthly, as were specimens to ascertain the concentration of PCB in the blood, adipose tissue and faeces. Major findings among treated monkeys included the following: changes in haematology (decreased erythrocyte count, haematocrit, reticulocyte count, and mean platelet volume), serum biochemistry (decreased cholesterol and total bilirubin), immunotoxicity (decreased antibody production to sheep red blood cells and alterations in the percentage of T helper and T suppressor cells) and pathology (the number of regions of sebaceous gland lobules per unit of histological length was significantly reduced). These effects were observed at PCB doses lower than those previously reported for non-human primates.

A pilot study on the effects of Aroclor 1254 ingestion by rhesus and cynomolgus monkeys as a model for human ingestion of PCBs.

A pilot study using female cynomolgus (Macaca fascicularis) and female rhesus (Macaca mulatta) monkeys was conducted to study the effects of chronic ingestion of polychlorinated biphenyls (PCBs). Four control and four treated monkeys of each species received an apple juice-gelatin mixture containing 0 and 280 micrograms Aroclor 1254/kg body weight/day, respectively, 5 days/wk. The cynomolgus monkeys, which were mature monkeys with a poor breeding history, were treated for approximately 55 wk, while the rhesus monkeys, which were just attaining sexual maturity, were treated for approximately 120 wk. After 38 wk on test, the treated and control rhesus monkeys were mated with untreated males. The clinical signs resulting from the Aroclor 1254 ingestion were similar for both species, and the time of onset after initiation of treatment was not appreciably different between the two species. Several treatment and interspecies differences were found with regard to the haematological and serum biochemistry parameters monitored, but age differences between the two species may have contributed to these findings. Periodic analysis of adipose tissue, blood and faecal specimens for PCBs suggested that the rhesus monkey retained more of the ingested PCB than did the cynomolgus monkey. Following mating, all of the treated rhesus monkeys aborted within 30-60 days after becoming pregnant, while all of the control monkeys had viable offspring.

Providing vitamin D to confined sheep by oral supplementation vs ultraviolet irradiation.

Serial vitamin D3 (D3) and 25-hydroxyvitamin D3 (25 OH D3) concentrations of plasma were measured in confined, shorn sheep that had either been supplemented with vitamin D3 (50 micrograms/d) or exposed daily to ultraviolet irradiation (UVI). In the sheep administered D3 orally, plasma D3 increased continuously until d 35. This was followed by small fluctuations of the plasma D3 concentrations until a plateau was reached after 56 d of supplementation (.94 ng/ml plasma). Plasma 25 OH D3 concentrations increased continuously and plateaued between d 65 to 75 at about 21 ng/ml plasma. In the UVI sheep, plasma D3 and 25 OH D3 concentrations increased continuously for the first 49 d, then plateaued at 2.03 ng D3 and 29.6 ng 25 OH D3/ml. When a plateau was reached in plasma 25 OH D3 concentrations in both treatment groups, a 3H-labeled tracer dose of 25 OH D3 was given i.v., and disappearance of the 3H-labeled 25 OH D3 was followed. The UVI group had a faster decline in specific activities during the first exponential phase but a slower decline during the prolonged terminal elimination phase. These differences are reflected in the intercompartmental transfer rates. Our data indicate that UVI is as effective as oral vitamin D3 supplementation for improving vitamin D status of confined sheep.