NLFM waveform generation using tunable integrated optical ring resonators: simulation and proof of concept experiment.

The NLFM waveform resulting from a tunable integrated optical ring resonator is simulated. The metrics of interest are the first sidelobe levels and FWHM times of the autocorrelation, as these directly relate to the long-range performance and fine range resolution of a LADAR system, and should ideally be as small as possible. Through simulation, the maximum sidelobe level of the autocorrelation of an NLFM waveform generated by a series of tunable integrated optical ring resonators is shown to be -20 to -30 dB or lower. A proof of concept experiment employing an off-the-shelf thermally tunable silicon-nitride optical ring resonator is shown to generate NLFM chirped waveforms with a bandwidth of 28 kHz.

The cheetah: native american.

Two North American fossil species of large felids, hitherto regarded as Late Cenozoic pumas (mountain lion), are in fact closely related to the living cheetah, Acinonyx, of Africa and Eurasia. A new subgenus (Miracinonyx) is proposed for the American species. Cheetahs and pumas may have had a common ancestor in the Miocene of North America.

Cells related to fighting behavior recorded from midbrain central gray neuropil of cat.

Cells were recorded in the midbrain central gray neuropil of the cat that responded with action potentials only during fighting behavior and not while the cat was resting or while control manipulations were performed. Some other cells in the same region responded maximally during fighting, and all cells responded to at least one manipulation. Brain stimulation at sites of cells related to fighting caused the animals to hiss.

A cheetah-like cat in the north american pleistocene.

The discovery of abundant skeletal remains of Felis trumani from a late Pleistocene deposit in Wyoming shows that it was as highly modified for cursorial locomotion as the cheetah (Acinonyx). Several other Pleistocene felids that have been regarded as pumas seem to be related forms. The late Pleistocene fauna of the Big Horn Basin in Wyoming is dominated by cursorial taxa.

Phase I and pharmacokinetic study of brequinar sodium (NSC 368390).

Brequinar sodium is a quinoline carboxylic acid derivative that has shown antitumor activity in a number of in vivo murine and human tumor xenograft models. Its mechanism of action is blockade of de novo pyrimidine biosynthesis by inhibition of dihydroorotic acid dehydrogenase. In vitro and in vivo studies demonstrate the superiority of prolonged drug exposure in achieving tumor growth inhibition. This phase I study evaluated the administration of brequinar sodium by short, daily i.v. infusion for 5 days repeated every 4 weeks. Fifty-four subjects were enrolled in the study and received drug in doses ranging from 36-300 mg/m2. The dose-limiting toxicities were mucositis and diffuse skin rash. Other toxicities included myelosuppression, nausea, vomiting, malaise, and burning at the infusion site. The maximum tolerated dose on the "daily times 5" schedule was 300 mg/m2. The recommended phase II dose is 250 mg/m2. Pharmacokinetic analysis of the day 1 drug clearance curves in 51 subjects showed slight nonlinearity in the relationship between dose and area under the clearance curve (AUC). The dose versus AUC relationship was well described using a Michaelis-Menten model of brequinar elimination kinetics with Vmax = 45 (micrograms/ml)/h and Km = 123 micrograms. Analysis of the day 5 drug clearance curves revealed a diminution in Vmax to 30 (micrograms/ml)/h. As a consequence of the reduction in Vmax brequinar plasma concentrations on day 5 were higher than predicted from day 1 drug kinetics. Pharmacodynamic analysis of the day 1 kinetic parameters and the toxicities occurring during the first cycle of drug therapy revealed significant correlations between mucositis and dose, AUC, and peak brequinar concentration; between leukopenia and AUC and peak drug concentration; and between thrombocytopenia and beta elimination rate.

Prenatal transmission of scrapie in sheep and goats: A case study for veterinary public health.

Unsettled knowledge as to whether scrapie transmits prenatally in sheep and goats and transmits by semen and preimplantation embryos has a potential to compromise measures for controlling, preventing and eliminating the disease. The remedy may be analysis according to a systematic review, allowing comprehensive and accessible treatment of evidence and reasoning, clarifying the issue and specifying the uncertainties. Systematic reviews have clearly formulated questions, can identify relevant studies and appraise their quality and can summarise evidence and reasoning with an explicit methodology. The present venture lays a foundation for a possible systematic review and applies three lines of evidence and reasoning to two questions. The first question is whether scrapie transmits prenatally in sheep and goats. It leads to the second question, which concerns the sanitary safety of artificial breeding technologies, and is whether scrapie transmits in sheep and goats by means of semen and washed or unwashed in vivo derived embryos. The three lines of evidence derive from epidemiological, field and clinical studies, experimentation, and causal reasoning, where inferences are made from the body of scientific knowledge and an understanding of animal structure and function. Evidence from epidemiological studies allow a conclusion that scrapie transmits prenatally and that semen and embryos are presumptive hazards for the transmission of scrapie. Evidence from experimentation confirms that semen and washed or unwashed in vivo derived embryos are hazards for the transmission of scrapie. Evidence from causal reasoning, including experience from other prion diseases, shows that mechanisms exist for prenatal transmission and transmission by semen and embryos in both sheep and goats.

Echo-Doppler in the diagnosis and management of congenital heart disease.

Advancements in echo-Doppler technology now provide the capability for both high-quality anatomic imaging as well as the assessment of cardiac flows and hemodynamics. Given these capabilities, and the potentially complex nature of all congenital heart lesions, echo-Doppler is well suited for the diagnostic assessment of congenital heart disease. As a noninvasive, reliable, and relatively inexpensive tool, it is well suited for the longitudinal follow-up of patients with treated and untreated congenital heart lesions. Recent experience with intraoperative imaging has indicated that direct epicardial echo-Doppler examination provides clinically useful information for the surgeon treating congenital heart lesions. Echo-Doppler examination continues to evolve into a primary modality for the recognition, evaluation, and treatment of congenital heart disease.

A preliminary evaluation of factors affecting an experimental system for vaccination-and-challenge with Haemonchus contortus in sheep.

A preliminary evaluation of factors affecting an experimental system for vaccination-and-challenge with Haemonchus contortus in sheep. International Journal for Parasitology 19: 169-175. Studies were made with Haemonchus contortus in sheep to ascertain the influence of a range of factors in the domain of the host, the parasite or the vaccine on the formulation of protocols for vaccination-and-challenge to be used in identifying protective immunogens. The results corroborate earlier findings that protective immunity can follow vaccination with homogenates of parasites and show that initial processing of parasites for a vaccine leaves protective immunogen in a functional state. Sonicates of adult worms produced protective immunity and were identified as raw stock in which to prospect for candidate immunogens. By contrast, sonicates of infective larvae and exsheathing fluid invoked no significant protection and were not accredited for the same purpose. In an experiment unaccompanied by protective immunity, ewes contained lower worm burdens than castrate males indicating that vaccination experiments should be made with hosts of one sex only. Again in an experiment unaccompanied by protective immunity, Freund's complete adjuvant increased susceptibility to infection compared with Freund's incomplete adjuvant or no adjuvant implying a profound and persistent interference from killed mycobacteria on resistance against H. contortus.

Infection of immunosuppressed mice with the abomasal nematode parasite of ruminants, Haemonchus contortus.

Infective larvae of Haemonchus contortus established in mice either immunosuppressed with the corticosteroid, dexamethasone, or the cytotoxic drug, cyclophosphamide, or treated with the histamine H2 inhibitor, cimetidine. Infections persisted for as long as the immunosuppressive treatment (7 days) and growth of larvae was similar to that seen in sheep. Virtually no larvae survived in untreated mice. Accordingly, it would appear that adaptive immunity is an important barrier against primary infection by H. contortus in mice and is a determinant of host-range for this parasite. Antibody raised in either sheep or mice against soluble extracts of adult H. contortus precipitated with different but overlapping sets of worm antigens. This suggests that the unique antigens recognized by the mouse compared with the sheep are crucial for the rapid protective responses which prevent primary infection.

The effect of infection with the abomasal nematode, Haemonchus contortus, on the avoidance behaviour of sheep in a motivational-choice test.

The behaviour of immune and non-immune sheep infected with H. contortus and undergoing a variety of experimental treatments was investigated in a motivational-choice test, the arena test. This test evaluates motivational state in sheep by pitting the motivation of test animals to approach a small flock of sheep against the motivation to avoid a human decoy located directly in front of the small flock. Approach distance is decreased by infection in immune ewes but was unaffected by infection in non-immune weaner lambs in the present study. Experimental drug-treatments with the opiate-antagonist nalorphine, the antihistamine chlorpheniramine, and the immunosuppressive glucocorticoid dexamethasone, affected avoidance behaviour but did not shed light on possible mechanisms involved in the changes observed when immune sheep are infected with the parasite. These substances may affect motivational state directly and not through a pharmacological action on processes triggered by infection in immune sheep. Arena tests conducted in immune ewes at 4, 7 and 11 days after challenge infection showed a fluctuating locomotor behaviour, which may arise from either the dynamics of a standard secondary immune response or particular antigens released during larval development. The immune-mediated changes in behaviour in the arena test will have entailed information-processing or cognitive pathways, but it is not known whether they also involved the physiological manifestations of emotion.

Immunity to Haemonchus contortus and the cellular response to helminth antigens in the mammary gland of non-lactating sheep.

Cellular exudates induced by infusion with helminth antigens were examined in non-lactating mammary glands of ewes immune to infection with the abomasal nematode, Haemonchus contortus. Secondary immunological responsiveness was expressed in two ways. Firstly, antigens from adult H. contortus elicited larger eosinophil-rich cellular exudates in immune compared to non-immune ewes. In this situation, secondary responsiveness in the mammary gland must have been generated through abomasal infection with the parasite. Secondly, repeated infusion with the antigens from adult H. contortus increased the size of cellular exudates in both immune and non-immune ewes. Eosinophils predominated but numbers of macrophages and lymphocytes were also increased. In this second situation, secondary responsiveness must have been either supplemented in immune ewes or derived completely in non-immune ewes by contact with helminth antigens through the mammary gland. The helminth antigens which induce eosinophil exudates in the mammary gland may not be potently protective against H. contortus. Furthermore, eosinophil exudation may not be an in vivo correlate of immunity which is directly useful for discriminating protective antigens and applicable to vaccine development. Infusion with antigens from adult forms of either H. contortus or Trichostrongylus colubriformis elicited cellular exudates equally well in immune ewes primed by infusion with H. contortus adult antigens 7 days beforehand. In addition, antigens from infective larvae of H. contortus elicited cellular exudates more potently than antigens from adult worms. However, vaccination with irradiated larvae has shown that species-specific protective immunity for H. contortus is stronger than cross-protective immunity conferred by T. colubriformis.(ABSTRACT TRUNCATED AT 250 WORDS)

Cross-immunity between Haemonchus contortus and Trichostrongylus colubriformis in sheep.

Cross-protective immunity between the nematode parasites, Haemonchus contortus and Trichostrongylus colubriformis, was examined in sheep vaccinated with irradiated larvae of either species. Secondary immunological responsiveness stimulated in this manner protected only against challenge infection with the species used for vaccination. Significant cross-protective immunity was not observed. Titres of serum antibody to an extract of adult but not infective larval T. colubriformis reflected the specificity for protective immunity. Immediate hypersensitivity skin reactions to nematode extracts did not reflect the antigen-specificity for protective immunity.

A pilot study evaluating the efficacy of a fully acetylated poly-N-acetyl glucosamine membrane formulation as a topical hemostatic agent.

BACKGROUND: Topical hemostatic agents are frequently needed for control of intraoperative bleeding. Currently available topical products each have potential drawbacks, making a more effective topical hemostatic agent desirable. This study was performed to evaluate the effectiveness of a particular formulation of a newly available polysaccharide polymer, poly-N-acetyl glucosamine (p-GlcNAc), as a topical hemostatic agent for use in the operating room. Swine splenic incision and splenic capsular stripping hemorrhage models were initially used, with a subsequent pilot human study then performed. METHODS: For the swine splenic incision model, anesthetized immature female Yorkshire white swine had a 3 x 8 mm incision created on the spleen. One of 3 agents (p-GlcNAc membrane, oxidized cellulose, or absorbable collagen) was sequentially applied to individual wounds and digitally compressed for 20 seconds. The wound was observed without pressure for 2 minutes. Up to 8 wounds per animal were created in 7 animals. For the swine splenic capsular stripping model a 2 x 2 cm area of capsular stripping on the surface of the spleen to a depth of 3 mm was created. Either p-GlcNAc membrane or oxidized cellulose was applied and digitally compressed for 60 seconds, followed by observation without pressure for 2 minutes. Six wounds per animal were created in 2 animals. If bleeding persisted in either model, a new cycle of compression was applied. These steps were repeated until hemostasis was achieved. No change in hemodynamics or coagulation factors was observed in either model. Subsequently, 10 consecutive patients undergoing elective small-bowel surgery were enrolled on pilot study. A 5 x 3 x 3 mm cruciate incision was created midway between the mesenteric and antimesenteric borders of the small bowel. Either p-GlcNAc membrane formulation or oxidized cellulose was applied (the sequence alternated per patient) with a 400-mg weight used for even, direct pressure. A second cruciate incision was then created on the contralateral side of the bowel to evaluate the second material. The number of applications required for hemostasis was assessed. Hemodynamics, small-bowel pathologic condition, and hematologic parameters were evaluated. RESULTS: The p-GlcNAc membrane required fewer cycles of compression in the swine splenic incision model to achieve hemostasis than either absorbable collagen or oxidized cellulose (1.25 vs 2.58 and 3.41, respectively; P < .01) and caused more effective immediate cessation of bleeding (79% for p-GlcNAc vs 17% for both absorbable collagen and oxidized cellulose). With the more traumatic splenic capsular stripping model, p-GlcNAc required fewer cycles of compression to achieve hemostasis than oxidized cellulose (average, 2.5 versus 6.8 respectively; P < .01) and was able to achieve hemostasis with greater efficacy (50%) in 2 applications than did oxidized cellulose (0%; P < .01). When used in the human pilot study, p-GlcNAc membranes required fewer cycles of compression than oxidized cellulose (2.5 vs 5.4, respectively; P < .002), was able to stop bleeding with greater efficacy in 1 cycle of compression (50% vs 0%, respectively; P < .01), and ultimately accomplished hemostasis in 80% of the cases as opposed to 20%. CONCLUSIONS: On the basis of its greater hemostatic efficacy as compared with collagen or oxidized cellulose-based products, p-GlcNAc holds promise as an effective topical hemostatic agent and deserves further evaluation.

Percutaneous catheter drainage of infected pancreatic and peripancreatic fluid collections.

Operative drainage is the cornerstone of therapy for pancreatic abscess. Recently it has been suggested that successful percutaneous catheter drainage of infected pancreatic and peripancreatic fluid collections may serve as definitive therapy. We undertook therapeutic, computed tomography-directed percutaneous drainage in a selected group of 29 patients with infected pancreatic and peripancreatic fluid collections. Twenty-three patients (79%) were successfully treated with percutaneous drainage. Of six patients (21%) representing failures of percutaneous drainage, four died and two recovered after operative drainage. The four patients who died had a mean APACHE (acute physiology and chronic health evaluation) II score of 23 and five of Ranson's prognostic signs. Ranson's signs and APACHE II scores were predictive of success and mortality. We conclude that in selected patients, infected pancreatic and peripancreatic fluid collections can be treated definitively with therapeutic percutaneous catheter drainage. Based on this experience, recommendations regarding patient selection are included.

Activity of basal forebrain neurons in the rat during motivated behaviors.

The activity of single neurons in the basal forebrain was recorded in the freely-moving rat with moveable fine-wire electrodes. Neural activity was observed while the water-deprived male rat was exposed to three different types of motivating stimuli that elicit locomotion in a running wheel: an estrous female rat; a drinking tube containing water; and grasping and lifting by the experimenter. The neural activity was also observed when the subject was presented with standardized sensory tests and during single pulse stimulation of other brain structures. A majority of the 76 neurons recorded in the forebrain changed their firing rate during orienting and/or locomotion in general (23 neurons) or during behavior related to only one of the specific motivational contexts: the conspecific female (4 neurons); water (7 neurons); or grasp by the experimenter (8 neurons). Whereas the neurons related to orienting and/or locomotion in general were scattered through various brain structures, those neurons related to specific motivational contexts were concentrated in specific areas: the sexually dimorphic nucleus of the medial preoptic area (conspecific female); lateral septum (water); and lateral preoptic area (water and grasp). The present results, although based on relatively few neurons, are consonant with results of research using other techniques. This indicates that analyses at the level of the single neuron promise to be useful for understanding the role of the basal forebrain in motivational systems.

Extent of bladder and ureteric involvement and urologic management in patients with enterovesical fistulas.

A retrospective review of hospital charts from 1978-1989 identified 21 patients with acquired enterovesical fistulas. Nine patients with fistulas secondary to benign inflammatory processes required extensive bladder resection; 2 of these had ureteric involvement. Of the 9 patients requiring extensive bladder resection, necrotic and severely inflamed bladder was excised and the bladder was closed in a multilayered fashion with absorbable sutures. An omental flap was used when possible. Postoperative bladder drainage was maintained for seven to fourteen days. Ureteral involvement was managed by stenting in 1 case and ureteroureterostomy in another. No postoperative bladder leaks or recurrent fistulas were reported. Extensive inflammatory involvement of the bladder wall may necessitate a large vesical resection. Excision of diseased bladder tissue, multilayered closure, and the use of omental interposition may help reduce postoperative complications and the risk of recurrence. Associated ureteral involvement may be present in these patients and requires urologic management.

Protein binding of brequinar in the plasma of healthy donors and cancer patients and analysis of the relationship between protein binding and pharmacokinetics in cancer patients.

The protein binding of weakly acidic and basic drugs has been shown to be altered in cancer patients. Brequinar is a weakly acidic, low-clearance, and highly protein-bound (> 98% bound) antitumor agent. The pharmacokinetic parameters of brequinar are subject to large interpatient variability. This large interpatient variability may be related to brequinar's plasma protein-binding capacity (assuming no change in the intrinsic clearance of the unbound drug). The objectives of this study, therefore, were (a) to characterize brequinar's protein binding in the plasma of healthy donors and cancer patients and (b) to examine the relationships between brequinar's plasma protein binding and its pharmacokinetics in patients. Brequinar protein binding was determined in human serum albumin (HSA) solution, drug-free donor plasma, and brequinar-free, predose plasma samples obtained from a phase I cancer trial. Pharmacokinetic results from this study were used to examine relationships between plasma protein binding and drug disposition. In HSA solution and healthy donor plasma, brequinar's protein binding as determined using spiked samples was concentration-dependent. The unbound brequinar fraction increased by a factor of 3 (from 0.3% to 0.9% free) in 4% HSA solution and by a factor of 4 (from 0.4% to 1.6% free) in donor plasma as the brequinar concentrations increased from 0.1 to 2.3 mM in the HSA solution and from 0.076 to 1.5 mM in the donor plasma. Analysis of brequinar binding characteristics using the binding ratio and Rosenthal binding plots showed that albumin was the primary protein for brequinar binding in human plasma. The addition of various concentrations of alpha 1-acid glycoprotein to 4% HSA solution did not affect the protein binding of brequinar to HSA. The protein binding determined in the plasma of cancer patients was not quantitatively different, except for variability, from that observed in the plasma of healthy donors. Examination of relationships between the unbound brequinar fraction and pharmacokinetics suggested that plasma protein binding was not a major determinant of brequinar disposition in cancer patients.

Single unit recording in the midbrain of rats during shock-elicited fighting behavior.

Single unit activity was recorded extracellularly from the midbrain of rats during fighting behavior and during non-fighting control manipulations. Fighting behavior was elicited by footshock or startle stimuli or occurred spontaneously as a result of prior footshock presentations. Seven cells were found in the midbrain reticular formation and central gray which displayed maximum firing rates during fighting behavior. These cells also fired to a limited extent to some of the control manipulations, particularly contralateral vibrissae stimulation. These cells fired phasically during fighting behavior and their firing was correlated with either the approach or paw-strike of the opponent animal or to the response of the recording animal to a tactic of the opponent animal. However, no specific movement or sensory event reliably predicted the firing of these cells during fight sequences. Cells located in other midbrain areas, such as the deep tectum or the area of the red nucleus, also responded during fighting behavior. However, the discharge of these cells was correlated with specific body movements or sensory events. The activity during fighting was similar in rate and pattern to activity during control manipulations whenever similar movements or sensory stimulation were produced. Cells were also found which did not discharge during fighting behavior although they fired under a variety of other conditions.

Nonfunctioning pancreatic neuroendocrine tumors presenting as pancreatitis: report of four cases.

The presentation of pancreatic adenocarcinoma as acute or chronic pancreatitis has been well documented; however, there has been only one previous report of either functioning or nonfunctioning pancreatic neuroendocrine tumors associated with pancreatitis. At the Medical University of South Carolina in Charleston, from March 1982 through September 1987, we have managed four patients with nonfunctioning pancreatic islet cell tumors or carcinoids, which presented with attacks of pancreatitis. Three of the patients had recurrent bouts of upper abdominal and lower dorsal back pain with elevation of the serum amylase. One patient presented initially with acute upper abdominal pain and elevation of the serum amylase. Each patient had an endoscopic retrograde cholangeography pancreatography (ERCP) pattern involving the pancreatic duct which was characterized by diffuse dilatation proximal to the site of obstruction. One of the four had a tumor blush on splanchnic angiography. Each patient had CT evidence of a mass in the head of the pancreas; however, one of the four was found to have diffuse involvement of the entire gland at operation. Surgical therapy varied: (a) local excision of the ampullary area with re-anastomosis of the pancreatic duct to the duodenum and choledochoduodenostomy; (b) bypass with cholecystoduodenostomy and caudal pancreaticojejunostomy; (e) total pancreatectomy; or (d) bypass with a Roux-en-Y cholecystojejunostomy and gastrojejunostomy. The choice of the procedure was based on the patient's condition and operative findings.

Reporting of preliminary data: time to take our sonographers "off the hook".

The article by McDonald et al. points out the widespread demand for preliminary reporting of echocardiographic data by sonographers, at least in the setting of physicians in training. Such preliminary reporting is illegal in most states because it constitutes the unauthorized practice of medicine. In most states it is also illegal for physicians to authorize sonographers to do such preliminary reporting because it aids and abets the unauthorized practice of medicine. Such practices also likely violate federal Medicare statutes. Lastly, the practice is simply not fair to patients who are deserving of final diagnostic information. Now that we know the practice is widespread among physicians in training, we can conjecture that the demand for improper reporting of diagnostic data by sonographers is likely widespread among physicians in practice also. Now is the time to check your local statutes, change the way your practice works, and adopt a clear policy for reporting of diagnostic echocardiographic and Doppler data.