Pharmacokinetic parameters for single- and multi-dose regimens for subcutaneous administration of a high-dose ceftiofur crystalline-free acid to neonatal foals.

The objective of this study was to determine the pharmacokinetics of single- and multi-dose ceftiofur crystalline-free acid (CCFA) administered subcutaneously at a dose of 13.2 mg/kg to 12 neonatal foals 1-3 days of age. Six foals received a single subcutaneous dose, while 6 additional foals received 4 doses of CCFA at 48-h intervals. Blood samples were collected at pre-determined times following drug administration, and plasma concentrations of ceftiofur free acid equivalents (CFAE) were measured using high-performance liquid chromatography. Following single-dose administration of CCFA, the mean ± standard deviation maximum observed plasma concentration was 3.1 ± 0.6 µg/mL and observed time to maximal plasma concentration was 14.0 ± 4.9 h. Following multi-dose administration of CCFA, the mean ±standard deviation times above CFAE concentrations of ≥0.5 µg/mL and ≥2.0 µg/mL were 192.95 ± 15.86 h and 78.80 ± 15.31 h, respectively. The mean ± standard deviation area under the concentration vs time curve (AUC0→∝ ) was 246.2 ± 30.7 h × µg/mL and 172.7 ± 27.14 h × µg/mL following single- and multi-dose CCFA administrations, respectively. Subcutaneous administration of CCFA at 13.2 mg/kg in neonatal foals was clinically well- tolerated and resulted in plasma concentrations sufficient for the treatment of most bacterial pathogens associated with neonatal foal septicemia. Multi-dose administration of four doses at dosing interval of 48 h between treatments maintains appropriate therapeutic concentrations in neonatal foals.

Pharmacokinetics of ceftiofur sodium and ceftiofur crystalline free acid in neonatal foals.

Ceftiofur, a third generation cephalosporin, demonstrates in vitro efficacy against microorganisms isolated from septicemic neonatal foals. This pharmacokinetic study evaluated the intravenous and subcutaneous administration of ceftiofur sodium (5 mg/kg body weight; n = 6 per group) and subcutaneous administration of ceftiofur crystalline free acid (6.6 mg/kg body weight; n = 6) in healthy foals. Plasma ceftiofur- and desfuroylceftiofur-related metabolite concentrations were measured using high performance liquid chromatography following drug administration. Mean (±SD) noncompartmental pharmacokinetic parameters for i.v. and s.c. ceftiofur sodium were: AUC(0→∝) (86.4 ± 8.5 and 91 ± 22 h·µg/mL for i.v. and s.c., respectively), terminal elimination half-life (5.82 ± 1.00 and 5.55 ± 0.81 h for i.v. and s.c., respectively), C(max(obs)) (13 ± 1.9 µg/mL s.c.), T(max(obs)) (0.75 ± 0.4 h for s.c.). Mean (± SD) noncompartmental pharmacokinetic parameters for s.c. ceftiofur crystalline free acid were: AUC(0→∝) (139.53 ± 22.63 h·µg/mL), terminal elimination half-life (39.7 ± 14.7), C(max(obs)) (2.52 ± 0.35 µg/mL) and t(max(obs)) (11.33 ± 1.63 h). No adverse effects attributed to drug administration were observed in any foal. Ceftiofur- and desfuroylceftiofur-related metabolites reached sufficient plasma concentrations to effectively treat common bacterial pathogens isolated from septicemic foals.

Congenital cardiac defects in neonatal foals: 18 cases (1992-2007).

BACKGROUND: Literature available regarding congenital cardiac defects in foals is limited to reports of individual cases or small case series. OBJECTIVE: To describe the clinical, echocardiographic, and necropsy findings and breed predilection of congenital cardiac defects in neonatal foals. ANIMALS: Eighteen foals < 15 days of age with 1 or more congenital cardiac defects. METHODS: Medical records of foals diagnosed with congenital cardiac defects at the William R. Pritchard Veterinary Medical Teaching Hospital were reviewed. Data collected included history, signalment, clinical signs, laboratory data, diagnostic and necropsy results, and outcome. RESULTS: Arabian foals represented 39% of cases with congenital cardiac defects and were significantly (P = .004) overrepresented (OR = 4.7 [CI: 1.8-12.4]) compared with the general hospital population. Ventricular septal defect (VSD) (14/18), tetralogy of Fallot (5/18), and tricuspid valve atresia (4/18) were the most common defects identified. A > or = 3/6 heart murmur (14/ 14) accompanied by tachycardia (14/17), tachypnea (17/17), and cyanosis of mucous membranes (7/16) were the most common clinical signs. Concurrent congenital defects were common (9/18). Two foals, both with VSD, survived for > or = 8 years after diagnosis and 1 was a successful performance horse. CONCLUSIONS AND CLINICAL RELEVANCE: Arabian horses appear to have a predisposition for cardiac defects. The presence of a loud murmur (> or = 3/6), cyanotic membranes, and tachycardia or tachypnea in a neonatal foal should warrant thorough evaluation of the heart for congenital defects. Foals with cardiac defects should be closely evaluated for concurrent congenital defects in other body systems.

Evolution of bubble clouds induced by pulsed cavitational ultrasound therapy - histotripsy.

Mechanical tissue fractionation can be achieved using successive, high-intensity ultrasound pulses in a process termed histotripsy. Histotripsy has many potential clinical applications where noninvasive tissue removal is desired. The primary mechanism for histotripsy is believed to be cavitation. Using fast-gated imaging, this paper studies the evolution of a cavitating bubble cloud induced by a histotripsy pulse (10 and 14 cycles) at peak negative pressures exceeding 21MPa. Bubble clouds are generated inside a gelatin phantom and at a tissue-water interface, representing two situations encountered clinically. In both environments, the imaging results show that the bubble clouds share the same evolutionary trend. The bubble cloud and individual bubbles in the cloud were generated by the first cycle of the pulse, grew with each cycle during the pulse, and continued to grow and collapsed several hundred microseconds after the pulse. For example, the bubbles started under 10 microm, grew to 50 microm during the pulse, and continued to grow 100 microm after the pulse. The results also suggest that the bubble clouds generated in the two environments differ in growth and collapse duration, void fraction, shape, and size. This study furthers our understanding of the dynamics of bubble clouds induced by histotripsy.

Using the cavitation collapse time to indicate the extent of histotripsy-induced tissue fractionation.

Histotripsy is an ultrasonic tissue ablation method based on acoustic cavitation. It has been shown that cavitation dynamics change depending on the mechanical properties of the host medium. During histotripsy treatment, the target-tissue is gradually fractionated and eventually liquefied to acellular homogenate. In this study, the change in the collapse time (t col) of the cavitation bubble cloud over the course of histotripsy treatment is investigated as an indicator for progression of the tissue fractionation process throughout treatment. A 500 kHz histotripsy transducer is used to generate single-location lesions within tissue-mimicking agar phantoms of varying stiffness levels as well as ex vivo bovine liver samples. Cavitation collapse signals are acquired with broadband hydrophones, and cavitation is imaged optically using a high-speed camera in transparent tissue-mimicking phantoms. The high-speed-camera-acquired measurements of t col validate the acoustic hydrophone measurements. Increases in t col are observed both with decreasing phantom stiffness and throughout histotripsy treatment with increasing number of pulses applied. The increasing trend of t col throughout the histotripsy treatment correlates well with the progression of lesion formation generated in tissue-mimicking phantoms (R 2 = 0.87). Finally, the increasing trend of t col over the histotripsy treatment is validated in ex vivo bovine liver.

The role of cysteine residues in S100B dimerization and regulation of target protein activity.

Previous studies have demonstrated that the two cysteine residues in the calcium-binding protein S100B are required for its extracellular functions. In the present study, a recombinant S100B protein and mutant S100Bs containing one or no cysteine residue(s) have been used to determine the contribution of cysteine residues to S100B dimerization and interaction with the intracellular target proteins aldolase, phosphoglucomutase, and the microtubule associated tau protein. Mutation of C68 to a valine or C84 to a serine, C68 to valine and C84 to serine, or C68 to valine and C84 to alanine did not significantly alter S100B activation of aldolase. However, mutation of C84 to serine resulted in calcium-independent S100B activation of phosphoglucomutase and a loss of S100B inhibition of tau phosphorylation by Ca2+/calmodulin-dependent protein kinase II. The altered functionality of the C84S mutant with phosphoglucomutase and tau was not due to altered physical properties or dimerization state. All of the mutants exhibited heat stability and calcium dependent conformational changes which were identical to recombinant S100B. In addition, S100B proteins containing two, one or no cysteine residues behaved as dimers in size exclusion chromatography experiments in the presence or absence of calcium as well as in the presence or absence of reducing agent. Dynamic light scattering and analytical ultracentrifugation experiments confirmed that dimerization was not affected by calcium or reducing agent. Altogether these results demonstrate that S100B dimerization is not calcium- or sulfhydryl-dependent. In summary, cysteine residues are not necessary for the noncovalent dimerization of S100B, but are important in certain S100B target protein-interactions.

AIDS education for hospital workers in Manila: effects on knowledge, attitudes, and infection control practices.

OBJECTIVE: To evaluate an AIDS education intervention for health workers in Metro Manila hospitals. METHODS: A randomized controlled education program consisting of lectures, role-plays, posters and pamphlets was delivered to physicians, nurses, laboratory technologists and orderlies in Manila hospitals. Knowledge, attitudes and infection control practices were measured before, immediately after, and 2 months after the intervention. RESULTS: Baseline survey among 641 hospital workers revealed poor knowledge, negative attitudes towards AIDS patients, and inappropriate infection control practices. Immediately after the intervention, there was significant improvement in (1) knowledge scores (8.7-11.2 in the intervention group versus 8.5-9.5 in the control group; range, 0-14), (2) attitude scores (54.4-60.6 versus 54.6-56.8; range, 22-88), and (3) needle-recapping practices (14-43% versus 39-43%) (all P values < 0.001). After 2 months, attitude scores in the experimental group fell to the same level as those of the control group, while improvements in knowledge and needle recapping were largely maintained. Role-playing was considered by the participants to be the most effective component of the intervention. CONCLUSIONS: These results suggest that AIDS training for hospital workers in the Philippines and in similar countries is necessary and can be effective. Ideally, such training should include role-playing and should be ongoing in order to sustain the effect.

Adolescent sexuality in Saint Petersburg, Russia.

OBJECTIVES: To describe adolescent knowledge, attitudes and behavior relevant to sexuality and the prevention of AIDS in Saint Petersburg, Russia. SUBJECTS AND METHODS: A cross-sectional descriptive study was designed, taking a random sample of 10th grade students at 14 Saint Petersburg grade schools, which were stratified by socio-economic district. A total of 185 female and 185 male students completed a self-administered 46-item questionnaire, with a response rate of 94%. RESULTS: From the questionnaires, 20% of females and 31% of males reported having had sexual intercourse and 25% of females and 12% of males reported being sexually abused. These adolescents displayed much misinformation about sexual matters and AIDS prevention. Only 25% of the females and 34% of the males believed that condoms should be used just once, and 38% of each sex believed that if washed, they could be used multiple times. Many respondents, especially males, rated their knowledge about sexual matters as high or adequate. Support for sex education was strong, especially among females, and respondents generally saw sex education as improving sexual pleasure. Most information sources about sexual activity were either not considered very credible, or not adequately accessible. CONCLUSIONS: Substantial reported rates of sexual abuse, sexual experience and much misinformation and unwarranted attitudes toward condoms, safer sexual practices and HIV/AIDS suggest the need for vigorous sex education programs for Russian youth. The early and sustained education of girls is especially important. Sex education should be introduced at an early age so that children can be taught how to reduce the risks of sexual abuse, HIV infection and other sexually transmitted diseases, and to improve their sexual experiences as responsible adults.

HIV/AIDS-related attitudes and practices of hospital-based health workers in Kampala, Uganda.

OBJECTIVE: To assess HIV/AIDS-related attitudes and practices of hospital-based health workers in Kampala, Uganda. METHODS: A cross-sectional study was conducted in Mulago Hospital, the main national referral hospital in Uganda. A total of 155 physicians and nurses completed a brief questionnaire on HIV risk perception, attitudes and practices regarding AIDS prevention education, HIV counseling and testing and care of patients with HIV disease. RESULTS: Twenty-nine per cent of health workers reported never having discussed AIDS prevention with patients, 26% had never referred patients for HIV counseling and 31% had never advised patients suspected of HIV infection to be tested. Frequent explanations for not providing AIDS prevention education included time constraints and/or lack of related knowledge or skills. While 29% perceived recapping needles as involving no risk, activities involving casual contact with patients and condom use for protection against HIV infection were associated with a high perceived risk of HIV transmission, particularly among nurses. Physicians and nurses differed in their HIV/AIDS-related attitudes and practices. The physicians had a more positive attitude towards the care of patients with HIV disease. In addition, 80% of physicians compared to 59% of nurses referred patients for HIV counseling. A similar trend was found for advising patients to obtain HIV testing. CONCLUSIONS: Hospital-based health workers are missing important opportunities for AIDS prevention education with their patients. There are gaps in their knowledge about HIV and related infection control practices. Interventions should address their concerns and barriers to HIV prevention practices.

Extremely low awareness of AIDS, sexually transmitted diseases and condoms among Dai ethnic villagers in Yunnan province, China.

OBJECTIVE: To assess the awareness of AIDS, other sexually transmitted diseases (STDs), condoms, sources of health information and HIV-related societal risks among Dai villagers in southern Yunnan Province, China. SUBJECTS AND METHODS: In November-December 1994, a cross-sectional descriptive study, comprising a questionnaire-based survey and focus group discussions, was conducted in three Dai villages in Mengla county; a total of 177 Dai villagers were interviewed in the survey and eight focus group discussions were held. Ethnographic observations provided a composite picture of HIV risks in the area. RESULTS: Only 18% of respondents had heard of AIDS, and only 25 and 28%, respectively, had heard of STDs or condoms. Furthermore, among these more aware groups, the level of knowledge was low and misconceptions were common. An ability to understand the official language (Mandarin) was the most important predictor of awareness of AIDS, other STDs or condoms. The sources of information in the three Dai villages sampled included TV, videos, radio and magazines, but only TV and videos had a large audience. Even so, these media were mostly in Mandarin and were not used in AIDS education. Travel outside of China was frequent; most villagers (77%) had traveled to Laos and 9% had traveled to Thailand. Societal risks of HIV transmission, such as an increasing incidence of STDs and an active sex industry, were observed in this area. CONCLUSIONS: Dai villagers in southern Yunnan Province had an extremely low awareness and knowledge of AIDS, other STDs and condoms. Given the high mobility of ethnic villagers to neighboring countries in Southeast Asia and the societal risks of HIV transmission in this area, there is an urgent need to provide accessible education about AIDS and other STDs. Suggestions regarding such health education and the implications of HIV policy-making are discussed.

Effect of antacids on the bioavailability of diflunisal in the fasting and postprandial states.

Diflunisal is long-acting salicylate derivative. We examined the effect of single concomitant doses of three antacids on diflunisal bioavailability under fasting or fed conditions (30 min after finishing a standard meal). With the use of an open, randomized, and balanced design, one 250-mg diflunisal tablet was given to each of 12 healthy men under six conditions: fasted, no antacid; fed, no antacid; fasted, 15 ml of aluminum hydroxide gel; fed, 15 ml of aluminum hydroxide gel; fasted, 10 ml magnesium hydroxide suspension; and fed, 15 ml of an aluminum hydroxide/magnesium hydroxide mixture. Diflunisal plasma 0- to 48-hr area uiven to each of 12 healthy men under six conditions: fasted, no antacid; fed, no antacid; fasted, 15 ml of aluminum hydroxide gel; fed, 15 ml of aluminum hydroxide gel; fasted, 10 ml magnesium hydroxide suspension; and fed, 15 ml of an aluminum hydroxide/magnesium hydroxide mixture. Diflunisal plasma 0- to 48-hr area uiven to each of 12 healthy men under six conditions: fasted, no antacid; fed, no antacid; fasted, 15 ml of aluminum hydroxide gel; fed, 15 ml of aluminum hydroxide gel; fasted, 10 ml magnesium hydroxide suspension; and fed, 15 ml of an aluminum hydroxide/magnesium hydroxide mixture. Diflunisal plasma 0- to 48-hr area under the time curve (AUC), peak plasma concentrations, and 0-to 96-hr urinary excretion were determined. Food (alone) decreased peak plasma concentrations by 16% (P less than 0.05) but did not affect AUC or urinary excretion. Under fasting conditions, aluminum hydroxide reduced AUC by 26% (P less than 0.01), peak plasma concentrations by 46% (P less than 0.01), and urinary excretion by 14% (P less than 0.05). Magenisuum hydroxide suspension (in the fasting state) increased the early plasma concentrations (by 130% at 0.5 hr and 64% at 1 hr, P less than 0.05) and increased AUC by 10% (P less than 0.05) but had no effect on urinary excretion. In the fed state neither aluminum hydroxide nor the aluminum hydroxide/magnesium hydroxide mixture had any detectable effect.

Altered cytoskeletal protein synthesis in rat cardiac isografts.

Adult rats underwent surgical placement of heterotopic cardiac isografts. From 14 to 60 days postoperatively, native heart and transplanted heart protein synthesis was determined. Right ventricle and left ventricle free walls from native and transplanted hearts were dissected, minced into cubes, and incubated in medium containing sulfur-35 methionine. Tissue was harvested, washed, and homogenized in buffer and fractionated centrifugally. Specific radioactivity of polypeptides from transplant isograft right and left ventricle fractions were 6.36 +/- 5.1 and 4.93 +/- 3.6 (mean +/- SD, x 10(-6) cpm/mg protein), respectively. In contrast, native isograft right and left ventricle specific radioactivity was 1.71 +/- 1.49 and 1.07 +/- 0.88 (mean +/- SD, x 10(-6) cpm/mg protein), respectively. Autoradiograms of two-dimensional electrophoretograms revealed increased radiodensity of resolved polypeptides from transplanted and native hearts, which comigrated with nonsarcomeric (beta, gamma) actins. Skeletin and tubulin were prominent on one-and two-dimensional autoradiograms from 14 to 60 days. Radiolabeling of alpha actin polypeptide maximized at 14 days and was found to decrease at 30 and 60 days in comparison with nonsarcomeric actin isoforms. Correlative myocardial microscopic sections showed no fiber hypertrophy, but fiber atrophy was found. Results suggest a relative increase in polypeptide synthesis in the heterotopic transplanted heart samples.

Nuclear deoxyribonucleic acid heterogeneity of ovarian borderline malignant serous tumors.

Sixteen borderline malignant serous ovarian tumors and seven well-differentiated invasive serous ovarian carcinomas were examined with the technique of Feulgen microspectrophotometry for the determination of nuclear deoxyribonucleic acid (DNA) ploidy patterns (diploid versus aneuploid) and ploidy levels of the stem cell lines. Of the nine stage I-II borderline malignant tumors, only one (11%) was aneuploid. In contrast, four of seven (57%) stage III borderline malignant neoplasms and all stage III carcinomas were aneuploid. The stem cell modal values in all borderline serous tumors were less than triploid (3N) while in five of seven carcinomas stem cell modal values were greater than triploidy. This contrast in ploidy patterns and ploidy levels may explain the differences in biologic behavior between borderline malignant serous tumors and invasive serous carcinomas of the ovary.

Quadriceps femoris muscle angle: normal values and relationships with gender and selected skeletal measures.

The quadriceps femoris angle ("Q angle") has been implicated as a source of several knee disorders, but values for normal knees have not been adequately documented in the literature. This study was designed to provide clinicians with normal values and information regarding the relationships between Q angle, gender, and selected anatomical measurements. The Q angles of 100 individuals (50 men, 50 women), who had no history of knee disorders, were measured goniometrically. The hip widths and femur lengths of all subjects were measured with calipers. The mean Q angle for women was 15.8 +/- 4.5 degrees and for men was 11.2 +/- 3.0 degrees. Using a point biserial correlation, we found a relationship between gender and Q angle (r = -.517) that remained significant (p less than .01) when the effects of femur length and hip width were controlled. The relationships identified between Q angle and the anatomical measurements were no longer significant when the effect of gender was eliminated. The results substantiate the belief that women have larger Q angles than men, but they fail to provide clinicians with an anatomical explanation or new predictor of Q angle.

The applicability of inescapable shock as a source of animal depression.

Male rats (N = 27) were given initial experience with escapable shock, equivalent amounts of inescapable shock, or no shock. Measures were then obtained in the ensuing 15 hours on food intake, water intake, number of cage crossings, and weight change for all groups. Following this, animals were tested on an escape task. Inescapably shocked animals showed significant decreases in food and water consumption in comparison to both nonshocked and escapably shocked control rats. Weight gains were significantly decreased by exposure to shock irrespective of the availability of a coping response. Consistency of these findings with proposals suggesting that exposure to inescapable shock leads to a state of animal depression (learned helplessness) is discussed and compared to alternative stress explanations.

The effect of opioid and acepromazine premedication on the anesthetic induction dose of propofol in cats.

The median effective dosage (ED50) for induction of anesthesia with propofol was determined by using the up-and-down method in 31 unpremedicated cats, in 30 cats premedicated with butorphanol, 0.4 mg/kg body weight (BW), and acepromazine, 0.1 mg/kg BW, intramuscularly, and in 30 cats premedicated with morphine, 0.2 mg/kg BW, and acepromazine, 0.1 mg/kg BW, intramuscularly. The dose required for a satisfactory anesthetic induction in 50% of unpremedicated cats (ED50) was 7.22 mg/kg BW and of premedicated cats was 5.00 mg/kg BW. The reduction in dose was statistically significant in both premedicated groups compared with no premedication. There was no significant difference in ED50 between premedication regimes. Cyanosis was the most common adverse effect observed in all groups following anesthetic induction with propofol.

Osteochondritis dissecans of the elbow: diagnosis, treatment, and prevention.

Osteochondritis dissecans (OCD) is an inflammation of the bone and cartilage that usually affects adolescents and young adults. A 16-year-old baseball player who had chronic elbow pain illustrates the typical course of OCD of the elbow. Radiographs may be diagnostic, but bone scan is a more sensitive diagnostic tool, and magnetic resonance imaging offers information for staging and characterization of lesions. If symptoms do not resolve with rest, surgery is recommended, including loose-body removal with curettage or drilling. The prognosis is good with early diagnosis and treatment. Left untreated, OCD may progress to degenerative joint disease. Prevention includes strengthening and stretching exercises and limits on throwing activities.