Revisiting the concept of behavior patterns in animal behavior with an example from food-caching sequences in wolves (Canis lupus), coyotes (Canis latrans), and red foxes (Vulpes vulpes).

We discuss the history, conceptualization, and relevance of behavior patterns in modern ethology by explaining the evolution of the concepts of fixed action patterns and modal action patterns. We present the movement toward a more flexible concept of natural action sequences with significant degrees of (production and expressive) freedom. An example is presented with the food caching behavior of three Canidae species: red fox (Vulpes vulpes), coyote (Canis latrans) and gray wolf (Canis lupus). Evolutionary, ecological, and neuroecological/neuroethological arguments are presented to explain the difference in levels of complexity and stereotypy between Canis and Vulpes. This article is part of a Special Issue entitled: Canine Behavior.

Candesartan and cognitive decline in older patients with hypertension: a substudy of the SCOPE trial.

BACKGROUND: Hypertension is associated with impaired cognitive function but the effect of antihypertensive treatment on cognitive function is unclear. METHODS: We investigated the effect of treatment of hypertension on cognition with the angiotensin-receptor-blocker, candesartan, in a placebo-controlled, double-blind, randomized controlled trial at one center participating in the Study on Cognition and Prognosis in the Elderly. A total of 257 older adults with hypertension (mean age 76 years, blood pressure 165 +/- 8/88 +/- 7 mm Hg) were recruited from general practice and treated with 8-16 mg candesartan or placebo once daily, for a mean follow-up period of 44 months. Additional antihypertensive therapy was permitted in both groups to achieve treatment targets. Cognitive function was measured using the Cognitive Drug Research computerized assessment battery, trail-making tests, and verbal fluency. Data from annual assessments were used to calculate individual coefficients of decline by regressing composite test scores over time for five cognitive domains. RESULTS: The blood pressure difference between groups at study close was 8/3 mm Hg. The candesartan group showed less decline in attention (0.004 vs -0.036, p = 0.04) and episodic memory (0.14 vs -0.22, p = 0.04) compared to placebo, a similar trend for speed of cognition (-2.3 vs -17.4, p = 0.15), but no differences in working memory (0.0014 vs 0.0010, p = 0.90) or executive function (-0.0031 vs -0.0023, p = 0.95). Effect sizes were in the small-to-moderate range. CONCLUSIONS: The potential for blood pressure-lowering with angiotensin-receptor-blockers to reduce the rate of decline of specific areas of cognitive function in older patients with hypertension warrants further investigation to determine clinical efficacy.

Dynamic equilibria in the products of intramolecular Buchner additions of diazoketones to aryl rings bearing methoxy substituents.

Rhodium carboxylate catalyzed aromatic addition reactions of a range of diazoketones bearing methoxy-substituted aryl rings have been explored. While the existence of norcaradiene-cycloheptatriene equilibria in related compounds is well established, the aromatic addition products in this study display more complex dynamic equilibria due to conjugation with the methoxy group; the experimental evidence for this is discussed in detail. In the azulenone products 21-26 derived from p-methoxy-substituted diazoketones 14-16, the diastereomers interconvert via a spiro intermediate 39. A related mechanistic process in the azulenones 43-46 derived from the o-methoxy-substituted diazoketones 17, 18 interconverts regioisomers, explaining the conflicting reports for the regioselectivity of the cyclization of diazoketone 1. With the m-methoxy-substituted diazoketone 19, involvement of the methoxy group through a different pathway results in fragmentation of the azulenone to form the tetralone 47. With the azulenones 21-26 exclusive trapping of the norcaradiene associated with the less thermodynamically stable diastereomers in a cycloadduct with N-phenylmaleimide is observed. Due to the presence of the activating methoxy substituent on the aromatic ring, the aromatic addition reactions of the diazoketones studied were not very sensitive to the nature of the rhodium catalyst.

An articulating retractor holder to facilitate laparoscopic adrenalectomy and nephrectomy.

PURPOSE: Minimally invasive surgical approaches to renal and adrenal tumors have gained increasing use. The addition of robotic assistance and mechanical devices has decreased the number of assistants required for these often long cases. We describe an articulating arm retractor holder to aid in liver and spleen retraction during laparoscopic surgery. MATERIALS AND METHODS: The articulating retractor holder consists of 4 components, including a base rod, flexible extension arm, stainless steel precision clamp and table attachment. During laparoscopy the abdomen is visualized using standard approaches. The articulating retractor holder is clamped to the table via the base rod and brought into the surgical field using sterile technique. A retractor is placed intracorporeally to elevate the liver or spleen and the handle is secured in place using the precision clamp. RESULTS: The articulating retractor holder was used in all right and approximately 50% of left laparoscopic cases. Adequate visualization was obtained in all patients. There were no device failures or retractor related complications. CONCLUSIONS: The articulating retractor holder is a useful tool to aid in laparoscopic retraction that should be added to the urologist armamentarium.

Relationship of baroreflex sensitivity and blood pressure in an older population.

OBJECTIVES: Ageing and hypertension are associated with reduced baroreflex sensitivity (BRS) in young and middle-aged populations. The effects of blood pressure level on BRS in the older population are unclear. We examined the association between blood pressure and BRS in older persons with blood pressure below 180 mmHg. METHODS: BRS, high (alphaHF 0.15-0.4 Hz) and low (alphaLF 0.04-0.15 Hz) frequency alpha-index, was determined in 75 normotensive subjects (aged 75 +/- 4 years, 41% female, 131 +/- 10/74 +/- 7 mmHg) and 64 untreated hypertensive subjects (aged 76 +/- 5 years, 48% female, 165 +/- 7/ 88 +/- 7 mmHg) by spectral analysis of 20 min continuous blood pressure and heart rate recordings using finger plethysmography. Subjects were recruited from 10 general practices and were taking no cardiovascular medications. RESULTS: High but not low frequency alpha-index was significantly blunted in hypertensive subjects (alphaHF 5.1 +/- 3.1 versus 8.4 +/- 7.4 ms/mmHg, P< 0.001 and alphaLF 4.7 +/- 3.0 versus 5.8 +/- 3.9 ms/mmHg, P= 0.07). Multivariate analysis of the relationship between age and blood pressure demonstrated systolic and to a lesser extent diastolic blood pressure were significant predictors of variance in BRS for alphaHF [systolic blood pressure (SBP) P< 0.0001, diastolic blood pressure (DBP) P< 0.05, r2 = 0.1] and alphaLF (SBP P=0.01, DBP P<0.05, r2 = 0.04). Age was not a significant predictor for either measure, in the 20 year range studied. CONCLUSIONS: In an older population blood pressure is associated with reduced BRS, particularly for the high frequency component. Such a change may place older subjects with hypertension at increased risk of orthostatic hypotension, vasovagal syncope and sudden cardiac death.

Cognitive performance in hypertensive and normotensive older subjects.

Longitudinal studies suggest that hypertension in midlife is associated with cognitive impairment in later life. Cross-sectional studies are difficult to interpret because blood pressure can change with onset of dementia and the inclusion of subjects on treatment and with hypertensive end-organ damage can make analysis difficult. We examined cognitive performance in hypertensive and normotensive subjects without dementia or stroke >/=70 years of age. Cognitive performance was determined with the use of a computerized assessment battery in 107 untreated hypertensives (55 women, age 76+/-4 years, blood pressure, 164+/-9/89+/-7; range, 138 to 179/68 to 99 mm Hg) and 116 normotensives (51 female, age 76+/-4 years, 131+/-10/74+/-7; 108 to 149/60 to 89 mm Hg). Older subjects with hypertension were significantly slower in all tests (reaction time, milliseconds; simple, 346+/-100 versus 318+/-56, P<0.05; memory scanning, 867+/-243 versus 789+/-159, P<0.01; immediate word recognition, 947+/-261 versus 886+/-192, P<0.05; and delayed word recognition, 937+/-230 versus 856+/-184, P<0.05; picture recognition, 952+/-184 versus 894+/-137, P<0.01; spatial memory, 1390+/-439 versus 1258+/-394, P<0.01; excepting choice reaction time, 510+/-75 versus 498+/-72, P=0.08). Accuracy was also impaired in tests of number vigilance, 99.2+/-2.5% versus 99.9+/-0.9, P<0.01; delayed word recognition, 83.5+/-16 versus 87.9+/-9.8, P<0.01; and spatial memory 64+/-32 versus 79+/-20, P<0.001. Hypertension in older subjects is associated with impaired cognition in a broad range of areas in the absence of clinically evident target organ damage.

Head and neck compensation for total body irradiation using opposed laterals.

Using shaped brass compensators that follow the coronal profile of a patient's head and neck, we confirm that adequate compensation can be made to prevent overdosing in these regions when delivering total body irradiation using opposed lateral fields. Initially, these compensators were custom made for each patient, but we have shown that the variation from patient to patient is sufficiently small that individual compensators can be used for a number of different patients without compromising the dose distribution. In a subgroup of 35 patients on whom diode measurements were made, 20 used compensators from the library of approximately 40 compensators made for previous patients and 15 required new compensators to be fabricated. No significant difference (3.4% on average) was observed in the dose distribution. By examining the profiles accumulated from 81 patients, we have shown that the primary difference between patients is not in the shape of the head and neck, but in the distance from the top of the head to the suprasternal notch and in the slope of the shoulders; thus, shaped compensators are not necessary and the same quality of dose homogeneity can be achieved using simple flat brass plates. Further, if the arms are supported so that the slope of the shoulders is constant, a relatively small number (15) of square-ended plates of thickness ranging from 4.0 to 11.0 mm would be sufficient to treat all 81 patients in our sample.

Vitamin D receptor gene polymorphism in men and its effect on bone density and calcium absorption.

OBJECTIVE: Previous studies have suggested that polymorphism of the alleles of the vitamin D receptor (VDR) gene may account for the major part of the heritable component of bone density in women, possibly mediated in part by impaired calcium absorption from the bowel. In view of the increasing importance of osteoporosis in men, we have now investigated the association between common allelic variations in the vitamin D receptor gene, calcium absorption and bone density in men. SUBJECTS: Forty-eight men (median age 64, range 27-77) with a wide range of bone density measurements, comprising 20 men with vertebral crush fractures and 28 male control subjects. MEASUREMENTS: Analysis of the VDR gene polymorphism and measurement of fractional radiocalcium absorption and bone mineral density was performed in all subjects. RESULTS: The distribution of the three genotypes (TT, tt, Tt) was comparable to that reported previously. There was no significant difference in femoral neck bone density Z-scores between the three genotypes (mean +/- SD TT -0.31 +/- 1.19, tt -0.08 +/- 1.28 and Tt -0.37 +/- 1.17). There were also no significant differences in mean femoral neck bone density T-scores or lumbar spine bone density Z or T-scores between the three genotypes. Fractional radiocalcium absorption was 0.59 +/- 0.27 for TT, 0.69 +/- 0.30 for tt and 0.60 +/- 0.30 for Tt, showing no significant difference between the genotypes. CONCLUSIONS: This study shows no association between vitamin D receptor gene polymorphism and bone density or fractional calcium absorption in a group of men with a range of bone density values. We conclude that the vitamin D receptor gene alleles probably account at most for only a small part of the genetic component of bone density in men.

Structure-activity relationships within a series of C(7)-substitutedoxyiminocephalosporins containing the C(3)-methylaminopyridiniumthiomethyl substituent. Synthesis and biological properties of BRL 57342 and some close analogues.

(6R,7R)-7-[2-(2-Amino-4-thiazolyl)-2-[(Z)-[(S)-carboxy(3,4- dihydroxyphenyl)methyl]oxyimino]acetamido]-3-(1-methylaminopyri dinium-4-thiomethyl)ceph-3-em-4-carboxylate sodium salt (BRL 57342, 1f) combines excellent in vitro antibacterial potency against Gram-positive and Gram-negative bacteria, including P. aeruginosa and Acinetobacter spp., with excellent stability to extended spectrum beta-lactamases. This potency is reflected in in vivo efficacy studies.

Healing impairment of open wounds by skin irradiation.

BACKGROUND: Ionizing radiation is frequently used for the treatment of malignancy. Sequelae of therapeutic radiation frequently present clinical problems in the form of poor wound healing and easy injury of treated tissue in response to mild trauma. OBJECTIVE: We describe a radiation-impaired wound healing model in guinea pigs, developed to determine the effect of cutaneous irradiation on wound contraction. METHODS: Guinea pigs were anesthetized and a flap of skin was isolated and treated with x-rays to 18 Gy. Circular wounds of identical size were made in irradiated and control skin, and average wound size was recorded. RESULTS: Our results demonstrate that a statistically significant wound healing deficit is produced in open wounds by surface irradiation of skin. CONCLUSION: Radiation of skin results in slower healing of open wounds, and provides an in vivo system for evaluation of topical dressings and growth factors in radiation-impaired wounds.

Intrathoracic photodynamic therapy: a canine normal tissue tolerance study and early clinical experience.

Surgery with intraoperative photodynamic therapy (PDT) has the potential to improve the treatment of pleural malignancies. Before embarking on such treatment in humans, however, thoracic tissue tolerance to PDT was studied. For each of three (1 week, 1 month, and 6 month) study end-points, one control (no Photofrin II [PII]) and four treated animals underwent thoracotomy 72 hours after I.V. injection (6 mg/kg) PII. Red light (630 nm) was delivered (5-40 J/cm2) to the pleural surface (1 cm diameter) of selected thoracic organs. No clinical differences were observed between PDT and control dogs. The control showed no histological changes; however, in the treated animals focal areas of coagulation necrosis were found at 1 week which progressed to fibrosis at 1 month. The extent and depth of injury was proportional to light dose. The lung was the most sensitive; the chest wall was the most resistant. Myocardium had superficial damage, whereas coronary arteries appeared normal. The results provide the basis for proceeding to phase I human trials in the evaluation of PDT as an intraoperative adjuvant treatment in the management of pleural malignancies.

Synthesis and biological activity of 3-(N-substituted pyridinium-4-thiomethyl)-7 alpha-formamido cephalosporins.

The synthesis and antibacterial activity of a series of 3-(1-substituted pyridinium-4-thiomethyl)-7 alpha-formamido cephalosporins is described. All the derivatives showed good potency and stability to bacterial beta-lactamases. The antibacterial efficacy seen with the N-alkyl pyridinium substituents was enhanced by the introduction of a catecholic side chain at C-7 and by preparation of N-(substituted amino)pyridinium derivatives.

Synthesis and biological properties of some 3-[(N-substituted-amino)pyridinium-4-thiomethyl]-7-[2-(2-amino-thiazol- 4-yl)-2-(Z)-(methoxyimino)acetamido]ceph-3-em-4-carboxylates.

The synthesis and antibacterial activity of a series of beta-lactamase stable, broad spectrum 7-[2-(2-amino-thiazol-4-yl)-2-(Z)-(methoxyimino)acetamido]-cephalo sporins, characterised by a C-3-[N-(substituted-amino)pyridinium-4-thiomethyl] group, is described. Gram-positive and Gram-negative bacteria including extended spectrum beta-lactamase-producing strains were most susceptible to the N-amino- and N-methylamino derivatives (3a) and (3b); with the exception of Pseudomonas aeruginosa, (3b) was more active in vitro and in vivo than cefpirome or ceftazidime.

Collagen gene expression and wound strength in normal and radiation-impaired wounds. A model of radiation-impaired wound healing.

BACKGROUND: Poorly healing wounds result in significant morbidity postoperatively. Numerous attempts have been made to study wound healing in vivo to understand better the normal healing process and factors that impair healing. Animal models of wound healing have been developed to evaluate wound healing in a systematic and controlled setting. Incisional wounds are created in animals to mimic the surgical patient. They may then be evaluated by a variety of methods for degree of healing. OBJECTIVE: To give insight into the mechanisms of wound healing impairment, we developed a model of impaired wound healing in guinea pigs using radiation applied to the skin surfaces only. METHODS: Wound bursting strength, a direct measure of the force required to burst apart healing linear incisions, was measured. Collagen content, measured indirectly as collagen gene expression, was measured. RESULTS: Significant reductions in wound bursting strength were noted after radiation administration. Collagen gene expression was decreased in wounds 7 days after radiation, but recovered to control levels 14 days after irradiation. Our model enables the inclusion of irradiated and unirradiated skin flaps within the same animal, thus eliminating intra-animal variation when comparing impaired and normal wounds. CONCLUSION: Wound bursting strength analysis, combined with techniques aimed at elucidating changes at the molecular level, provides a useful tool for the study of factors that impair healing and potential treatments for resulting healing deficits.

Neurobiology of motivation: double dissociation of two motivational mechanisms mediating opiate reward in drug-naive versus drug-dependent animals.

Separate brain manipulations double dissociate two motivational mechanisms underlying the rewarding effects of opiates. Lesions of the brain stem tegmental pedunculopontine nucleus block the rewarding properties of morphine in drug-naive, but not in drug-dependent, rats. Neuroleptics (which block the action of the neurotransmitter dopamine) abolished opiate motivational effects in drug-dependent, but not in drug-naive, rats in place conditioning paradigms. This second dopaminergic opiate reward mechanism mediates morphine's alleviation of the withdrawal distress associated with abstinence in opiate-dependent animals. Furthermore, neuroleptic-induced blockade of food-related motivational effects in food-deprived, but not in food-sated (non-food-deprived), animals suggests that the neural substrates of motivational events do not dissociate along the line between different rewarding stimuli but along the line between deprivation and nondeprivation.

Metabolism of phosphonoacetate as the sole carbon and phosphorus source by an environmental bacterial isolate.

A gram-negative bacterium isolated from activated sludge was able to utilize up to 25 mM phosphonoacetate as the sole carbon and phosphorus source, with simultaneous excretion of virtually equimolar levels of phosphate. 2-Aminoethylphosphonate was similarly utilized with equivalent growth rates and cellular yields, while 3-aminopropyl-, 4-aminobutyl-, methyl-, ethyl-, and phenylphosphonates served only as phosphorus sources.

A simple CT aperture emulator for use with a radiotherapy simulator.

Tumor localization in radiation treatment planning often involves the generation of quantitative anatomical data from multiple imaging modalities. It is desirable to take all of the images in the selected treatment position, which is usually decided upon during the initial simulator session. The different scanning modalities are often operated by different staff, at different times and in different locations; thus, it is difficult to ensure consistency in the position of the patient's body, and its documentation, at various times and places. Also, devices such as CT and MR scanners frequently pose restrictions due to their limited apertures. Failure to consider the physical limitations of such scanning equipment at the time of simulation or localization may result in placing the patient in a treatment position which will not fit through the aperture of the CT (or MRI) scanner, or which will result in a clinically important portion of the anatomy being "cut off" in the resulting scans. This can lead to re-simulation of the patient or result in a lack of accurate coordination of simulator and CT scan data. To minimize problems such as these, we have developed a CT Aperture Emulator which can be used at the time of the initial simulation. This is a lightweight "halo" easily attached to the simulator, which mimics the size and shape of the CT aperture. It permits reproducible adjustment of the patient's position, while allowing technologists and physicians to set up the patient with respect to potential CT constraints, in particular with regard to the use of immobilization and support devices. The emulator device also facilitates reproducing a patient's treatment position on the CT scanner. The concept has been found to have additional clinical uses and can be extended to a variety of imaging equipment.

A light-diffusing device for intraoperative photodynamic therapy in the peritoneal or pleural cavity.

Light delivery to anatomic areas involved by tumor is critical for effective photodynamic therapy. The authors provide a detailed overview of a light-diffusing device which they have used for intraoperative illumination of the peritoneal and pleural cavities in patients with tumors involving the surfaces of these cavities. Their device represents an inexpensive modification of widely available endotracheal tubes. It has been used to deliver intraoperative photodynamic therapy in over 50 patients without episodes of device failure. When combined with a lipid-based, light-diffusing medium and on-line power/energy density monitoring, it allows homogeneous illumination of these complex surfaces.

An isocentric chair for the simulation and treatment of radiation therapy patients.

There are a variety of clinical situations in which patients undergoing radiation therapy can benefit from being treated in an upright position. The authors describe a new design for a treatment chair to assist in accomplishing this task. The present chair differs from previous designs in that it can be used with existing radiotherapy simulators as well as treatment units and that it permits isocentric setup and treatment of tumors either at the nominal source-to-axis distance (SAD) of a machine or at extended distance. This design permits treatment of mediastinal tumors as well as those of the head and neck using a variety of field arrangements including AP-PA, opposed laterals, and multiple obliques. The seat is designed on the "tool platform" principle. A wide variety of devices can be attached onto it to ensure accurate and reproducible, yet comfortable, patient positioning.