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Biomedical subjects

M S Christian

Publications and source records attributed to M S Christian.

52 records · Page 3Linked to original sources
PubMed1976

Non-fatal injuries sustained by seatbelt wearers: a comparative study.

The injuries sustained by 969 drivers and front-seat passengers in road-traffic accidents were studied. Altogether 196 (20-2%) of the drivers and passengers were wearing seat belts and 773 (79-8%) were not. The injuries among the two groups differed greatly in both severity and distribution. A total of 54 (27-6%) of the seatbelt wearers sustained one or more fractures compared with 300 (38-8%) of the non-wearers, and 18 (9-2%) of the seatbelt wearers were severely injured compared with 300 (38-8%) of the non-wearers. Soft-tissue injuries to the face were sustained by only 29 (14-8%) of the seatbelt wearers compared with 425 (55%) of the non-wearers. Since wearing seatbelts may become compulsory, the type and pattern of injuries to be expected in wearers should be appreciated.

Abdominal Injuries↗
PubMed1975

Non-fatal injuries sustained by back seat passengers.

Of 2,275 cases of non-fatal injuries sustained by all categories of road users 185 were inflicted on back seat passengers. Twenty-six such passengers sustained severe and 66 moderately severe injuries. Only two patients (aged 18 months and 3 years) wore any form of restraint. Back seat passengers may be injured by impact with the rear of the front seat or other objects in the rear compartment; by objects in the front compartment; or by being thrown out of the car completely. An adequate restraint system, such as the lap-and-diagnoal type of seat belt, would reduce the incidence and severity of injuries.

Abdominal Injuries↗
PubMedDate not supplied

Reproductive effects of chronic administration of murine interferon-gamma.

Daily subcutaneous doses of 0.02, 0.2, or 2 mg/kg/d of recombinant murine interferon-gamma (rmuIFN-gamma) were given to mice on postnatal days 8 through 60 to determine effects on maturation, behavioral/ functional development, and reproductive capacity. Male mice receiving 2 mg/kg/d rmuIFN-gamma had delayed sexual maturation, reduced epididymal and testes weights, reduced sperm count and concentration, and sperm abnormalities (crimped flagellum). Mating performance and fertility were also reduced in the absence of altered histopathology of the testes. Males given 0.2 and 2 mg/kg/d had swelling and ulcerative dermatitis around the urogenital area, which were observed after sexual contact and attributed to a bacterial infection. Motor activity (time spent in movement) was decreased in all mice receiving 2 mg/kg/d. No microscopic changes observed in any organs were attributed to rmuIFN-gamma administration.

Analysis of Variance↗
PubMedDate not supplied

Introduction/overview: gender-based differences in pharmacologic and toxicologic responses.

Gender may be the most important factor in mammalian development and response to exogenous agents. From believing sex-related differences required sheltering women to protect their reproductive capacity (Victorians thought exercise, education, train travel, and certain music neuro- and reprotoxic to females) to legislating a status of essential equality of the sexes may have increased women's health issues. Men and women often respond differently to drugs. Inclusion of women in phase I/II clinical trials is insufficient to identify gender-based differences in response; rather, animal models should be the basis for predicting gender-based differences in pharmacologic and toxicologic effects. Unfortunately, current animal models do not consistently demonstrate such differences. Use of commonly used species (e.g., rats and dogs) does not necessarily result in relevant evaluation of an agent in a species at appropriate development (age), physiological state, anatomy, metabolism, or kinetics for estimation of human risks. The need to test agents in relevant animal models and advances in metabolic, pharmacokinetic, and pharmacodynamic capabilities challenge us to improve methods by using the most relevant models for estimating human risk. We need to be concerned about gender-related differences and the dynamics of gender-based growth and development over the entire life cycle. We must also consider potential interactions of dietary supplements and other exogenous agents that can act as drugs or modulate the potential effects of drugs differently in men, women, and developing children of both sexes. To this end, the health benefits of genistein and the effects of this dietary agent in a multigeneration study in rats will be described. It is envisioned that this symposium will assist in re-recognition of the importance of gender-related differences in use and response to pharmaceuticals and result in optimization of nonclinical testing procedures to identify benefits and risks for human use of these agents.

Adult↗
PubMedDate not supplied

Rat and rabbit oral developmental toxicology studies with two perfluorinated compounds.

Developmental toxicology (teratology) studies were done on two perfluorinated compounds-perfluorooctanesulfonate (PFOS) and 2-(N-ethylperfluorooctanesulfonamido)ethyl alcohol (N-EtFOSE) in rats and rabbits. Dose selection for these oral developmental toxicity studies were based upon dose-range study results. Dose levels of 0, 1, 5, 10, and 20 mg/kg/day were used for the rat N-EtFOSE study, and dose levels of 0, 0.1, 1.0, 2.5, and 3.75 mg/kg/day were used for both the PFOS and the N-EtFOSE rabbit studies. Although no compound-related deaths occurred in the dosed pregnant females on the developmental toxicity studies, maternal toxicity (reduced body weight gain and feed consumption) was present at higher dose levels in all three studies. At high maternally toxic doses, associated effects occurred in the conceptuses--increased abortions in PFOS and N-EtFOSE rabbits, reduced fetal weights in N-EtFOSE rats and PFOS rabbits, and increased late resorptions in N-EtFOSE rabbits. Detailed external gross, soft tissue, and skeletal fetal examinations failed to reveal any compound-related malformations in either species. Similar results, that is, only effects associated with maternal toxicity, had been found in previously conducted PFOS rat developmental toxicity studies. It was concluded that these perfluorinated compounds were not selective developmental toxicants in either rats or rabbits.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

Oral (drinking water) developmental toxicity studies of bromodichloromethane (BDCM) in rats and rabbits.

Crl:CD(SD)IGS BR VAF/Plus (Crl SD) rats and Hra(NZW) SPF rabbits were tested for potential developmental toxicity from bromodichloromethane (BDCM) provided continuously in the drinking water during gestation (gestation days [GDs] 6 to 21 in rats and GDs 6 to 29 in rabbits). Concentrations of 0, 50, 150, 450, or 900 ppm of BDCM were used for rats; 0, 15, 150, 450, or 900 ppm were used for rabbits (in dose range-finding studies, 1350 ppm was excessively maternotoxic to both species). Investigated maternal parameters included viability, clinical signs, water and feed consumption, and body weights. Maternal gross lesions, gravid uterine weights, abnormal placentas, and numbers of corpora lutea, implantation sites, live and dead fetuses, and early and late resorptions were observed at time of Caesarean sectioning (GD 21 in rats; GD 29 in rabbits). Body weights, sex ratios, and morphological abnormalities (external, soft tissue, and skeletal) were noted in the fetuses. Mean consumed doses of BDCM were calculated to be 0, 2.2, 18.4, 45.0, or 82.0 mg/kg/day for the rats, and 0, 1.4, 13.4, 35.6, or 55.3 mg/kg/day for the rabbits (approximate human intake is 0.8 microg/kg/day [0.0008 mg/kg/day] in adults). In pregnant rats, toxicologically important, statistically significant effects included reduced absolute (g/day) and relative (g/kg/day) water consumption values at > or =50 ppm (2.2 mg/kg/day) and reduced body weight gains (also when corrected for gravid uterine weight) and absolute (g/day) and relative (g/kg/day) feed consumption values at >450 ppm (45.0 mg/kg/day). These parameters were also significantly reduced at > or =450 ppm (35.6 mg/kg/day) in pregnant rabbits (significant weight loss occurred in the rabbits at 900 ppm, i.e., 55.3 mg/kg/day). Thus, the maternal no-observable-adverse-effect level (NOAEL) for BDCM was 150 ppm, i.e., 18.4 and 13.4 mg/kg/day in rats and rabbits, respectively. No adverse effects on embryofetal viability, growth, sex ratio, gross external, soft tissue, or skeletal morphology occurred at 900 ppm in rats or rabbits. Minimal delays in the ossification of forepaw phalanges and hindpaw metatarsals and phalanges occurred in rat fetuses at 900 ppm; delays were considered marginal, reversible, and associated with severely reduced maternal weight gain. Therefore, the developmental NOAEL for rats was 450 ppm (45.0 mg/kg/day), whereas in rabbits it was 900 ppm (55.3 mg/kg/day). These NOAELs are 56,250 and 69,120 times the human adult exposure level of 0.0008 mg/kg/day, respectively. Based on the results of these studies, BDCM should not be identified as a risk to development of human conceptuses.

Administration, Oral↗
PubMedDate not supplied

Biodisposition of dibromoacetic acid (DBA) and bromodichloromethane (BDCM) administered to rats and rabbits in drinking water during range-finding reproduction and developmental toxicity studies.

Dibromoacetic acid (DBA) and bromodichloromethane (BDCM), by-products of chlorine disinfection of water, were provided in drinking water in range-finding reproductive/developmental toxicity studies (rats) and a developmental toxicity study (BDCM) in rabbits. Studies included absorption and biodisposition of DBA and BDCM, including passage into placentas, amniotic fluid, fetuses (rats and rabbits), or milk (rats). The DBA and BDCM range-finding reproductive/developmental toxicity studies each included 50 Sprague-Dawley rats/sex/group. DBA (0, 125, 250, 500, or 1000 ppm) or BDCM (0, 50, 150, 450, or 1350 ppm) was provided in drinking water 14 days premating through gestation and lactation (63 to 70 days). The developmental toxicity range-finding study included 25 time-mated New Zealand white rabbits/group given 0, 50, 150, 450, or 1350 ppm BDCM in drinking water on gestation days (GDs) 6 through 29. Satellite groups (6 male, 17 female rats/group/study and 4 rabbits/group) were used for bioanalytical sampling. Rats and rabbits had exposure-related reduced water consumption caused by apparent taste aversion to DBA or BDCM, especially in the parental animals at the two highest exposure levels (500 and 1000 ppm DBA; 450 and 1350 ppm BDCM). Female rats consumed slightly higher mg/kg/day doses of DBA than male rats, especially during gestation and lactation; weanling rats consumed the highest mg/kg/day doses. DBA produced detectable and quantifiable concentrations in plasma, placentas, amniotic fluid, and milk. Plasma samples confirmed that rats drink predominately during the dark; this drinking pattern, not accumulation, produced detectable plasma concentrations for 18 to 24 hours/day. No quantifiable concentrations of BDCM occurred in plasma, placentas, amniotic fluid, or milk, suggesting that BDCM is rapidly degraded or metabolized in vivo. DBA (500 and 1000 ppm, rats) and BDCM (450 and 1350 ppm, rats and rabbits) produced secondary toxicity in the parental generation by reducing water consumption, which caused severe exposure-related apparent dehydration, reduced feed intake and weight gain. Reproductive and developmental parameters were essentially unaffected (mating possibly reduced [DBA at 1000 ppm]; exposure-related decreases in body weights of pups secondary to reduced water and feed consumption [DBA at 250, 500, and 1000 ppm; BDCM at 150, 450, and 1350 ppm]). No effects on development of rabbit fetuses occurred at BDCM concentrations as high as 1350 ppm. Results from these preliminary studies, in which DBA and BDCM were provided in the drinking water at concentrations thousands of times higher than those to which humans are exposed, suggest that neither DBA nor BDCM are reproductive/developmental risks for humans.

Acetates↗
PubMedDate not supplied

Oral (drinking water) two-generation reproductive toxicity study of bromodichloromethane (BDCM) in rats.

Bromodichloromethane (BDCM) was tested for reproductive toxicity in a two-generation study in CRL SD rats. Thirty rats/sex/ group/generation were continuously provided BDCM in drinking water at 0 (control carrier, reverse osmosis membrane-processed water), 50,150, and 450 ppm (0, 4.1 to 12.6, 11.6 to 40.2, and 29.5 to 109.0 mg/kg/day, respectively). Adult human intake approximates 0.8 microg/kg/day (0.0008 mg/kg/day). P and F1 rats were observed for general toxicity (viability, clinical signs, water and feed consumption, body weights, organ weights [also three weanling Fl and F2 pups/sex/litter], histopathology [10/sex, 0- and 450-ppm exposure groups]) and reproduction (mating, fertility, abortions, premature deliveries, durations of gestation, litter sizes, sex ratios, viabilities, maternal behaviors, reproductive organ weights [also three weanling Fl and F2 pups/sex/ litter], sperm parameters, and implantations. F1 rats were evaluated for age at vaginal patency or preputial separation. Ten P and F1 rats/sex from the 0- and 450-ppm exposure groups and rats at 50 and 150 ppm with reduced fertility were evaluated for histopathology (gross lesions, testes, intact epididymis, all F1 dams for number of primordial follicles). Developmental parameters in offspring included implantation and pup numbers, sexes, viabilities, body weights, gross external alterations, and reproductive parameters (Fl adults). Toxicologically important, statistically significant effects at 150 and/or 450 ppm included mortality and clinical signs associated with reduced absolute and relative water consumption, reduced body weights and weight gains, and reduced absolute and relative feed consumption (P and F1 rats). Significantly reduced body weights at 150 and 450 ppm were associated with reduced organ weights and increased organ weight ratios (% body and/or brain weight). Histopathology did not identify abnormalities. Small delays in sexual maturation (preputial separation, vaginal patency) and more Fl rats with prolonged diestrus were also attributable to severely reduced pup body weights. Mating, fertility, sperm parameters, and primordial ovarian follicular counts were unaffected. The no-observable-adverse-effect level (NOAEL) and the reproductive and developmental NOAELs for BDCM were at least 50 ppm (4.1 to 12.6 mg/kg/day), 5125 to 15,750 times the human adult exposure level, if delayed sexual maturational associated with severely reduced body weights is considered reproductive toxicity. If considered general toxicity, reproductive and developmental NOAELs for BDCM are greater than 450 ppm (29.5 to 109.0 mg/kg/day), or 36,875 to 136,250 times the human adult exposure level. Regardless, these data indicate that BDCM should not be identified as a risk to human reproductive performance or development of human conceptuses.

Administration, Oral↗
PubMedDate not supplied

Oral (drinking water) two-generation reproductive toxicity study of dibromoacetic acid (DBA) in rats.

In a two-generation study of dibromoacetic acid (DBA), Crl SD rats (30 rats/sex/group/generation) were provided DBA in drinking water at 0 (reverse osmosis-deionized water), 50, 250, and 650 ppm (0, 4.4 to 11.6, 22.4 to 55.6, and 52.4 to 132.0 mg/kg/day, respectively; human intake approximates 0.1 microg/kg/day [0.0001 mg/kg/day]). Observations included viability, clinical signs, water and feed consumption, body and organ weights, histopathology, and reproductive parameters (mating, fertility, abortions, premature deliveries, durations of gestation, litter sizes, sex ratios and viabilities, maternal behaviors, reproductive organ weights, sperm parameters and implantation sites, sexual maturation). Histopathological evaluations were performed on at least 10 P and F1 rats/sex at 0 and 650 ppm (gross lesions, testes, intact epididymis; 10 F1 dams at 0, 250, and 650 ppm for primordial follicles). Developmental observations included implantations, pup numbers, sexes, viabilities, body weights, morphology, and reproductive performance. At 50 ppm and higher, both sexes and generations had increased absolute and relative liver and kidneys weights, and female rats in both generations had reduced absolute and relative adrenal weights; adrenal changes were probably associated with physiological changes in water balance. The livers and kidneys (10/sex/group/generation) had no histopathological changes. Other minimal effects at 50 ppm were reduced water consumption and a transient reduction in body weight. At 250 and 650 ppm, DBA reduced parental water consumption, body weight gains, body weights, feed consumption, and pup body weights. P and F1 generation male rats at 250 and 650 ppm had altered sperm production (retained step 19 spermatids in stages IX and X tubules sometimes associated with residual bodies) and some epididymal tubule changes (increased amounts of exfoliated spermatogenic cells/residual bodies in epididymal tubules, atrophy, and hypospermia), although inconsistently and at much lower incidences. Unilateral abnormalities of the epididymis (small or absent epididymis) at 650 ppm in four F1 generation male rats were considered reproductive tract malformations. The no-observable-adverse-effect level (NOAEL) and reproductive and developmental NOAELs for DBA were at least 50 ppm (4.5 to 11.6 mg/kg/day), 45,000 to 116,000 times the human adult exposure level. Reproductive and developmental effects did not occur in female rats exposed to DBA concentrations as high as 650 ppm. Based on the high multiples of human exposure required to produce effects in male rats, DBA should not be identified as a human reproductive or developmental risk.

Acetates↗
PubMedDate not supplied

Detection of prenatal effects on learning as a function of differential criteria.

The role of appropriate criteria for detecting prenatal effects on learning was evaluated in Crl:COBS CD (SD)BR rats using a two-choice spatial discrimination escape paradigm. Alcohol was the prenatal treatment, as it has been reported to produce learning deficits in rats. The offspring of dams which consumed either a lab chow diet or isocaloric liquid diets containing 0%, 17.5% or 35% ethanol-derived calories during pregnancy were reared by surrogate control dams and tested for watermaze learning at 20 days postparturition. Learning performance and the required number of trials to the selected criterion were interrelated: (1) four or five consecutive errorless trials were too difficult, as high error rates occurred in all groups, including the control; (2) two consecutive errorless trials, or the number of trials before the first errorless trial, were too simple, as low error rates occurred in all groups, including the high dosage group; and (3) three consecutive errorless trials revealed significant dosage-dependent learning decrements in the alcohol-exposed groups. The results indicate that selection of the appropriate criterion in learning paradigms is critical for valid testing of prenatal effects.

Animals↗
PubMedDate not supplied

Traumatic rupture of the spleen.

Sixty-three cases of traumatic rupture of the spleen were analyzed. The patients were admitted to our hospitals during the last 24 years and there has been a steady increase in the numbers seen. The great majority of these cases resulted from road traffic accidents, and 33% of the patients had multiple injuries. Most were in the second and fourth decades; males outnumbered females by nearly four to one. Associated injuries, which occurred in 33% of cases, significantly raised the mortality. The mortality was also higher in the older age group and in those patients who had multiple injuries and were severely shocked on admission. Difficulty and delay in diagnosis occurred particularly in the unconscious patients and also in those in whom shock was not apparent, particularly when abdominal signs were late in developing. Treatment by resuscitation and splenectomy was used routinely and our overall mortality was 17.5%. Complications were frequent, the most serious being gastrointestinal and respiratory. A long-term follow-up showed that the great majority of patients have done well. There has been no evidence of an increased infection risk following splenectomy, and all but a few patients were able to return to their former sporting activities.

Accidents, Traffic↗