Pharmacokinetics and preliminary safety evaluation of azithromycin in adult horses.

Azithromycin is widely used in foals but has not been studied in adult horses. The goals of this study were to determine the pharmacokinetic profile and to make a preliminary assessment of the safety of azithromycin in adult horses. Azithromycin was administered intravenously (5 mg/kg) and intragastrically (10 mg/kg) to six healthy mares in a crossover design. Serial plasma samples, blood neutrophils, and pulmonary macrophages were collected for the measurement of azithromycin concentrations. Azithromycin was also administered orally (10 mg/kg) once a day for 5 days to five healthy mares for preliminary evaluation of safety in adult horses. The bioavailability of azithromycin following intragastric administration was 45 ± 12%. Concentrations within peripheral neutrophils and bronchoalveolar macrophages were several fold higher than that of plasma. Mild decreases in appetite (n = 3) and alterations in fecal consistency (n = 3) were noted following repeated oral administration. The pharmacokinetic profiles of azithromycin in adult horses, especially the slow elimination rate and intraneutrophil and intrapulmonary macrophage accumulation, demonstrate that it is conducive to use in this age group. Because of the gastrointestinal alterations noted, further studies are warranted before azithromycin can be recommended for use in adult horses.

Poor decision making among older adults is related to elevated levels of neuroticism.

BACKGROUND: A well-studied index of reasoning and decision making is the Iowa Gambling Task (IGT). The IGT possesses many features important to medical decision making, such as weighing risks and benefits, dealing with unknown outcomes, and making decisions under uncertainty. PURPOSE: There exists a great deal of individual variability on the IGT, particularly among older adults, and the present study examines the role of personality in IGT performance. We explored which of the five-factor model of personality traits were predictive of decision-making performance, after controlling for relevant demographic variables. METHODS: One hundred and fifty-two healthy cognitively intact adults (aged 26-85) were individually administered the IGT and the NEO Five-Factory Inventory. RESULTS: In the older adults, but not the younger, higher NEO neuroticism was associated with poorer IGT performance. CONCLUSIONS: Our findings are discussed in the context of how stress may impact cognitive performance and cause dysfunction of neural systems in the brain important for decision making.

Comparison of function of created wetlands of two age classes in central Pennsylvania.

Hydrogeomorphic (HGM) functional assessment models were used to assess whether function in created wetlands of two ages (1 year old and >12 years old) was equivalent to that of natural (reference) mainstem floodplain wetlands. Reference wetlands scored higher than both created age classes for providing energy dissipation and short-term surface water storage. Reference wetlands scored higher in maintaining native plant community and structure than 1-year-old sites, and 12-year-old wetlands scored higher than reference sites for providing vertebrate habitat structure. Analysis of individual model variables showed that reference wetlands had greater vegetative biomass and higher soil organic matter content than both created wetland age classes. Created wetlands were farther from natural wetlands and had smaller mean forest patch sizes within a 1-km-radius circle around the site than did the reference sites, indicating less hydrologic connectivity. Created wetlands also had less microtopographic variation than reference wetlands. The 1-year-old created sites were placed in landscape settings with greater land use diversity and road density than reference sites. The 12-year-old sites had a higher gradient and a higher percentage of their surrounding area in urban land use. These results show that the created wetlands were significantly structurally different (if not functionally so) from reference wetlands even after 12 years. The most profound differences were in hydrology and the characteristics of the surrounding landscape. More attention needs to be focused on placing created wetlands in appropriate settings to encourage proper hydrodynamics, eliminate habitat fragmentation, and minimize the effects of stressors to the site.

Length of incubation and hatchling body weight in quail selected for reduced or exaggerated adrenocortical responsiveness to brief restraint.

1. While changes in corticosterone (B) during late embryogenesis are thought to play a role in the hatching process, only a scant and controversial literature exists concerning the effects of in ovo B on the length of incubation and chick body weight at hatching. Because female Japanese quail selected for exaggerated (high stress, HS) rather than reduced (low stress, LS) plasma B response to brief mechanical restraint deposit more B into their eggs, these stress lines provide an excellent model to study the relationship between embryonic B and incubation length and hatchling body weight. 2. Differences in the duration of incubation and chick body weight at emergence were assessed using eggs laid by LS and HS quail. 3. On average, eggs from HS hens hatched 3.7 h sooner than did eggs from LS hens while mean body weight at emergence was similar in hatchlings of both lines. Thus, selection for exaggerated adrenocortical responsiveness is associated with a reduction in the length of egg incubation without altering hatchling body weight. 4. This finding is important to the poultry industry because it warns layer, breeder farm and hatchery managers that unless stress in hens during egg formation is avoided, an abbreviated incubation period may result.

Maternal corticosterone further reduces the reproductive function of male offspring hatched from eggs laid by quail hens selected for exaggerated adrenocortical stress responsiveness.

Activation of the hypothalamic-pituitary-adrenal (HPA) axis can depress the hypothalamic-pituitary-testicular axis. Male quail cloacal gland (CG) size and foam production shows androgen dependency, and males selected for exaggerated [high stress (HS)] rather than reduced [low stress (LS)] plasma corticosterone (B) stress response exhibit reduced CG and testes development. High stress hens also deposit more B into egg yolks than LS ones, and quail hens given B produce chicks that have a reduced growth rate and adults with heightened HPA responsiveness. Herein, we gave LS and HS hens no B [empty implants, control (CON)] or B-filled implants and assessed the reproductive performances of these hens and their male offspring. Mortality was similarly elevated in LS and HS B-treated hens, but only HS B-implanted hens showed reduced egg production. In male offspring, CG volume (CVOL), intensity of CG foam production (CFP), and the proportion of individuals that produced CG foam were measured from 4 to 11 wk of age. At 6 wk, BW, and at 15 wk, BW, testes weight (TWT), and TWT relative to BW were also determined. Hen treatments did not affect male chick CVOL at 4 wk, but CVOL differed thereafter as follows: LS CON > LS B = HS CON = HS B at 5 and 6 wk and LS CON > LS B > HS CON = HS B from 7 to 11 wk. By 8 wk, and thereafter, CFP differed as follows: LS CON > LS B > HS CON > HS B. Group differences in the proportion of individuals that produced CG foam generally supported CFP findings from 4 to 8 wk of age. Body weight did not differ by treatment at 6 wk of age. By 15 wk, TWT were similarly depressed in both HS groups. However, similarly higher 15-wk BW in the LS-CON and HS-B groups contributed to TWT relative to BW differences as follows: LS-B > LS-CON > HS-B; LS-CON = HS-CON; LS-B > HS-CON; and, HS-CON = HS-B. Both selection for exaggerated HPA responsiveness and maternal B treatment negatively affected the reproductive function of HS male offspring.

Cloacal gland and gonadal photoresponsiveness in male Japanese quail selected for divergent plasma corticosterone response to brief restraint.

Corticosterone is linked to testicular depression, and in Coturnix, a relatively photorefractory species, day length and androgen dependency in cloacal gland development and foam production are evident. Furthermore, male quail selected for reduced (low stress, LS) rather than exaggerated (high stress, HS) plasma corticosterone stress response show more photo-induced reproductive development, greater resistance to reproductive declines induced by exposure to very short days, and a quicker recovery to a higher reproductive level upon return to long days. To determine whether a milder reduction in day length would also influence stress line reproductive photoresponsiveness, and perhaps photorefractoriness, males grown on 16 h of light were given 13 h of light for 4 wk followed by a return to long days for 12 wk. Cloacal gland measurements were made following the initial stimulatory photoperiod and weekly thereafter during the 2 light treatments. Plasma testosterone was determined initially, after 4 wk of light reduction, and at the end of the study, along with BW, testes weight (TWT), and TWT relative to BW. Cloacal gland volume (CVOL) was greater in LS than HS males grown on long days. Whereas exposure to 13 h of light reduced CVOL in both lines, line differences (LS > HS) persisted during the first 3 wk of light reduction. Moreover, by 2 wk of rephotostimulation, and weekly thereafter, line differences (LS > HS) in CVOL reemerged. Cloacal gland foam production and the proportion of individuals that produced cloacal gland foam responses reflected changes in CVOL. The BW did not differ by line, yet LS males had a higher TWT and TWT relative to BW than HS ones. All individuals, however, exhibited relative photorefractory responses. Whereas none of the LS males completely resisted reproductive regression induced by a 3 h light reduction, LS males showed other reproductive benefits upon mild photocastration and subsequent rephotostimulation (e.g., greater resistance to CVOL and cloacal gland foam production losses during a mild light crash and quicker restoration to full reproductive potential upon relighting).

New 9-stubstituted 3-N,O-diacetylhydroxylaminofluorenes: enhanced electrophilicity and mutagenicity. Derivatives of fluorene. 38.

The compound 2-acetamidofluorene is a potent hepatocarcinogen; its N-acetoxy derivative (2-NOAc-AAF), a model ultimate form of the carcinogen, is strongly mutagenic and is chemically reactive with nucleophiles. The isomeric 3-acetamidofluorene is a mammary carcinogen, but is not hepatocarinogenic; its N-acetoxy derivative (3-NOAc-AAF) is not reactive with nucleophiles. Derivatives of 3-NOAc-AAF containing electron-donating groups in positions conjugated with the 3-position have been synthesized. These show increased electrophilicity and mutagenicity. Thus, by electronic manipulation of the leaving-group capacity of the -OAc group of 3-NOAc-AAF, we have obtained compounds with increased biological activity, as well as increased chemical reactivity. Future experiments could show whether in vivo effects of these derivatives of 3-NOAc-AAF are more like the effects of 2-NOAc-AAF or of 3-NOAc-AAF.

New compounds: derivatives of fluorene XXXVII: 9-substituted 3-nitrofluorenes.

New 9-substituted 3-nitrofluorenes were prepared as potential intermediates in a study of modified electrophilicity and mutagenicity of the carcinogen 3-N,O-diacetylhydroxylaminofluorene. The reported derivatives, together with some already known 9-substituted 3-nitrofluorenes, were too unstable to survive the reducing conditions required to transform the nitro group to the corresponding hydroxylamine.

Losing function through wetland mitigation in central Pennsylvania, USA.

In the United States, the Clean Water Act requires mitigation for wetlands that are negatively impacted by dredging and filling activities. During the mitigation process, there generally is little effort to assess function for mitigation sites and function is usually inferred based on vegetative cover and acreage. In our study, hydrogeomorphic (HGM) functional assessment models were used to compare predicted and potential levels of functional capacity in created and natural reference wetlands. HGM models assess potential function by measurement of a suite of structural variables and these modeled functions can then be compared to those in natural, reference wetlands. The created wetlands were built in a floodplain setting of a valley in central Pennsylvania to replace natural ridge-side slope wetlands. Functional assessment models indicated that the created sites differed significantly from natural wetlands that represented the impacted sites for seven of the ten functions assessed. This was expected because the created wetlands were located in a different geomorphic setting than the impacted sites, which would affect the type and degree of functions that occur. However, functional differences were still observed when the created sites were compared with a second set of reference wetlands that were located in a similar geomorphic setting (floodplain). Most of the differences observed in both comparisons were related to unnatural hydrologic regimes and to the characteristics of the surrounding landscape. As a result, the created wetlands are not fulfilling the criteria for successful wetland mitigation.

Health care litigation: new views on litigation management.

This is the first in a series of articles on health care litigation. The first article describes a new perspective on litigation management and suggests techniques to achieve better results at more reasonable cost.

Health care litigation: understanding and explaining causation.

This is the fourth in a series of articles on health care litigation. This article focuses on the substantive aspects of causation, one of the most difficult and controversial issues in health care litigation. The article identifies the differing perspectives of the medical and legal professions on the concept of cause and proposes an approach to clarify the concept for juries, judges, and arbitrators. An analysis of the procedural aspects of causation will appear in the next issue of The Medical Staff Counselor.

Health care litigation: proving--and disproving--causation.

This article, the fifth in a series, focuses on procedural issues concerning the causation element in health care litigation. The fourth article in the series identified the different perspectives of the medical and legal professions on the concept of cause and proposed an approach to clarify the concept for juries, judges, and arbitrators. This article analyzes the procedural aspects of proving causation or--as most health care providers in litigation often find it necessary to do--disproving causation.

Health care litigation: managing an appeal.

This is the third in a series of articles on health care litigation. This article illustrates how unfavorable appellate precedent can occur and proposes techniques for preventing such adverse results.

Health care litigation: the arbitration alternative for dispute resolution.

This is the second in a series of articles on health care litigation. This article focuses on the benefits of arbitration as an alternative dispute mechanism for health care providers. The use of arbitration offers speed and economy to the parties. For the health care provider, arbitration can reduce litigation expense and the likelihood of "runaway" jury verdicts.