Search PubMed⌕ Search

Biomedical subjects

E Hunt

Publications and source records attributed to E Hunt.

At least 19 recordsLinked to original sources

Pleuromutilins. Part 1. The identification of novel mutilin 14-carbamates.

A novel series of mutilin 14-carbamates has been discovered as a result of structure-activity studies on the naturally occurring antibiotic pleuromutilin (1). In particular, the 4-methoxybenzoylcarbamate, SB-222734 (15o) displays potent antibacterial activity against a number of bacterial pathogens which are resistant to currently used agents and shows enhanced metabolic stability when compared to earlier pleuromutilin derivatives. Such derivatives therefore have the potential to provide a new class of antibacterial agents for human therapy which address the threat of bacterial resistance.

Anti-Bacterial Agents↗

Glutamine transporter in crypts compensates for loss of villus absorption in bovine cryptosporidiosis.

Cryptosporidium parvum infection represents a significant cause of diarrhea in humans and animals. We studied the effect of luminally applied glutamine and the PG synthesis inhibitor indomethacin on NaCl absorption from infected calf ileum in Ussing chambers. Infected ileum displayed a decrease in both mucosal surface area and NaCl absorption. Indomethacin and glutamine or its stable derivative alanyl-glutamine increased the net absorption of Na(+) in infected tissue in an additive manner and to a greater degree than in controls. Immunohistochemical and Western blot studies showed that in control animals neutral amino acid transport system ASC was present in villus and crypts, whereas in infected animals, ASC was strongly present only on the apical border of crypts. These results are consistent with PGs mediating the altered NaCl and water absorption in this infection. Our findings further illustrate that the combined use of a PG synthesis inhibitor and glutamine can fully stimulate Na(+) and Cl(-) absorption despite the severe villous atrophy, an effect associated with increased expression of a Na(+)-dependent amino acid transporter in infected crypts.

Amino Acid Transport Systems↗

Spatial representations of virtual mazes: the role of visual fidelity and individual differences.

Twenty-four people learned three versions of a room-sized maze: a wire-frame desktop virtual environment (VE), a normal surface-rendered desktop VE, and a real-world maze. Differences among the mental representations formed from each environment were measured with pointing and distance estimation tasks in a real-world version of each maze. People were more accurate at pointing after having learned the real and wire-frame VE maze than the surface-rendered VE maze; however, this effect was small compared with the effect of individual differences. Differences in gender, spatial ability, and prior computer experience were significantly related to the ability to acquire spatial information from the desktop VE. There was a high correlation between spatial knowledge when it was measured in the VE and spatial knowledge measured in the real world. Actual or potential applications include the design of effective VE training systems.

Adolescent↗

Subcortical hypoperfusion following surgery for aneurysmal subarachnoid haemorrhage: implications for cognitive performance?

The incidence and severity of cognitive deficits after surgery for aneurysmal subarachnoid haemorrhage and their relationship to aneurysm site remains controversial. The aim of this study was to investigate the pattern of regional cerebral blood flow which exists in patients one year post-surgery and to identify whether different patterns exist which may be related to the type of cognitive deficit or the location of the aneurysm. 62 patients underwent cognitive assessment and HMPAO SPECT imaging at a mean time of 12 months following surgery. Results were compared to those from healthy control subjects (n = 55 for neuropsychological testing; n = 14 for SPECT imaging). In the patient group, significant stable cognitive deficits occurred in all cognitive domains but no cognitive measure differentiated aneurysm site. On SPECT images, statistical parametric mapping identified a large common area of subcortical hypoperfusion in the patient group as a whole. The findings of this study suggest a possible link between reduced subcortical function and the extent and severity of cognitive deficits.

Journal Article↗

Use of blood and blood products.

It is sometimes necessary for the practitioner to transfuse the ruminant with whole blood or plasma. These techniques are often difficult to perform in practice, are time-consuming, expensive, and stressful to the animal. Acute loss of 20% to 25% of the blood volume will result in marked clinical signs of anemia, including tachycardia and maniacal behavior. The PCV is only a useful tool with which to monitor acute blood loss after intravascular equilibration with other fluid compartments has occurred. An acutely developing PCV of 15% or less may require transfusion. Chronic anemia with PCV of 7% to 12% can be tolerated without transfusion if the animal is not stressed and no further decline in erythrocyte mass occurs. Seventy-five percent of transfused bovine erythrocytes are destroyed within 48 hours of transfusion. A transfusion rate of 10 to 20 mL/kg recipient weight is necessary to result in any appreciable increase in PCV. A nonpregnant donor can contribute 10 to 15 mL of blood/kg body weight at 2- to 4-week intervals. Sodium citrate is an effective anticoagulant, but acid citrate dextrose should be used if blood is to be stored for more than a few hours. Blood should not be stored more than 2 weeks prior to administration. Heparin is an unsuitable anticoagulant because the quantity of heparin required for clot-free blood collection will lead to coagulation defects in the recipient. Blood cross-matching is only rarely performed in the ruminant. In field situations, it is advisable to inject 200 mL of donor blood into the adult recipient and wait 10 minutes. If no reaction occurs, the rest of the blood can probably be safely administered as long as volume overload problems do not develop. Adverse reactions are most commonly seen in very young animals or pregnant cattle. Signs of blood or plasma transfusion reaction include hiccoughing, tachycardia, tachypnea, sweating, muscle tremors, pruritus, salivation, cough, dyspnea, fever, lacrimation, hematuria, hemoglobinuria, collapse, apnea, and opisthotonos. Intravenous epinephrine HCl 1:1000 can be administered (0.2 to 0.5 mL) intravenously or (4 to 5 mL) intramuscularly (preferable) if clinical signs are severe. Pretreatment with antipyretics and slowing the administration rate may decrease the febrile response. Blood or plasma administered too rapidly will also result in signs of cardiovascular overload, acute heart failure, and pulmonary hypertension and edema. Furosemide and slower administration of blood or plasma should alleviate this problem. Administration rates have been suggested starting from 10 mL/kg/hr; faster rates may be necessary in peracute hemorrhage. Plasma should be administered when failure of absorption of passive maternal antibody has occurred or when protein-loosing enteropathy or nephropathy results in a total protein of less than 3 g/dL or less than 1.5 g albumin/dL. Plasma can be stored at household freezer temperatures (-15 to -20 degrees C) for a year; coagulation factors will be destroyed after 2 to 4 months when stored in this manner. To maintain viability of coagulation factors, plasma must be stored at -80 degrees C for less than 12 months. When administering plasma, a blood donor set with a built-in filter should always be used. When bovine plasma is thawed, precipitants form in the plasma and infusion of these microaggregates may result in fatal reactions in the recipient.

Anemia↗

Relationships among assisted suicide and religiousness, resources available, denial of dying, and autonomy.

A nonrandom sample of eligible voters in Michigan (N = 218; mean age 35.7 yr.) anonymously completed a questionnaire during the two weeks prior to voting on a ballot proposal endorsing physician-assisted suicide. Favoring assisted suicide correlated negatively with scores on religiousness, believing that only a troubled mind would favor assisted suicide and that vulnerable individuals would suffer were assisted suicide legal, with denial of dying, and with resources available during one's final years. Favoring assisted suicide correlated positively with indicating this to be a medical rather than moral issue, making one's own decisions on moral issues, and believing that people may have different opinions on assisted suicide. The role of experience with dying needs further study.

Adult↗

Novel C-2 substituted carbapenem derivatives. Part IV. Synthesis and biological activity of five membered heteroaromatic derivatives.

The synthesis, antibacterial activity, and stability to human dehydropeptidase-1 (DHP-1) of a novel series of (5R,6S)-6-[(1R)-1-hydroxyethyl]-2-heterocyclylcarbapen-2-em-3-carb oxylates are described. Of the compounds investigated 1,5-disubstituted pyrazol-3-yl and 3-substituted isoxazol-5-yl derivatives have the best combination of antibacterial activity and stability to DHP-1. They are particularly active against community-acquired respiratory tract pathogens and have stabilities to DHP-1 superior to that of meropenem.

Carbapenems↗

Novel C-2 substituted carbapenem derivatives. Part III. Synthesis and biological activity of 2-(functionalised ethenyl, oxyiminomethyl and alpha-[hydroxy]benzyl)-carbapenems.

The synthesis, antibacterial activity and stability to human dehydropeptidase-1 (DHP-1) of three small series of carbapenems carrying carbon-linked substituents at C-2 are described. C-2 Ethenyl carbapenems showed moderate antibacterial activity but poor stability to DHP-1, C-2 Oxyiminomethyl carbapenems demonstrated variable activity and stability C-2 alpha-(Hydroxy)benzyl carbapenems were the most promising and showed good potency and DHP-1 stability.

Carbapenems↗

Novel C-2 substituted carbapenem derivatives. Part III. Synthesis and biological activity of 2-(functionalised ethenyl, oxyiminomethyl and alpha-

The synthesis, antibacterial activity and stability to human dehydropeptidase-1 (DHP-1) of three small series of carbapenems carrying carbon-linked substituents at C-2 are described. C-2 Ethenyl carbapenems showed moderate antibacterial activity but poor stability to DHP-1. C-2 Oxyiminomethyl carbapenems demonstrated variable activity and stability. C-2 alpha-(Hydroxy)benzyl carbapenems were the most promising and showed good potency and DHP-1 stability.

Journal Article↗

Recent advances in the chemistry and biology of carbapenem antibiotics.

The discovery of the olivanic acids and thienamycin aroused considerable interest amongst medicinal chemists and microbiologists around the world. The susceptibility of these agents to metabolic degradation has, however, been a major obstacle in their development. For many years the only notable success from such intensive research was the combination of imipenem with cilastatin, an inhibitor of the renal dipeptidase enzyme DHP-1. The enormous success of Primaxin for the treatment of a range of life-threatening bacterial infections provided the impetus for the discovery of totally synthetic, non-natural carbapenem derivatives that combine the broad spectrum of antimicrobial activity with stability to enzymatic degradation. This has indeed been realised in the development of meropenem; it possesses the broad spectrum of activity and resistance to beta-lactamases that are embodied in imipenem as well as displaying increased stability to human dehydropeptidases. Most recent research has focused upon the development of carbapenem antibiotics which combine broad spectrum antimicrobial activity and metabolic stability with oral absorption, for the treatment of community-acquired infections. Indeed, the pro-drug esters of the tricyclic carbapenems represent the first significant advance in this respect. However, the increased use of carbapenem antibiotics would undoubtedly accelerate the emergence of carbapenem-hydrolysing enzymes. The ultimate challenge could therefore be the design and synthesis of carbapenem derivatives that are resistant to these metallo-beta-lactamases. Due to the enormous problems encountered in the development of the carbapenem antibiotics, this area of research has, in the past, been described as a battlefield that did not bode well for the future [181]. Primaxin and meropenem proved however that these problems were not insurmountable, and are therefore a testimony to the persistence and dedication of those scientists in their war against bacterial infection.

Bacterial Infections↗

Supplies and technical considerations for ruminant and swine anesthesia.

These authors hope that this article will augment the ability of the practitioner to procure and successfully use the appropriate catheter and ancillary supplies for any aspect of ruminant and swine anesthesia. Although we recognize that the cost of these supplies may be a limiting factor in their use, we hope that options discussed in this article will facilitate the preparation of direct intravenous lines in increasing numbers of anesthetic procedures in the future. The driving force for this article is to facilitate the anesthetic experience for animal and veterinarian alike and--as always--to preserve life by practicing the best possible and affordable medicine under every situation.

Anesthesia↗

Water and turf: fluoridation and the 20th-century fate of waterworks engineers.

Once central figures in American public health, waterworks engineers are no longer involved in many decisions made about the public water supplies. This paper argues that the profession's response to the early fluoridation movement of the 1940s and 1950s marked a change in the relationship between waterworks engineers and the other constitutive groups in public health and contributed to the disenfranchisement of the waterworks profession. Sensing a potentially divisive issue, two leaders of the profession, Abel Wolman and Linn Enslow, took steps they hoped would prevent a rift within the profession and allow waterworks engineering to continue its association with the wider public health community. Although the leaders saw the fluoridation issue differently, neither encouraged the profession to consider it openly or to take up the broader question of what limits, if any, should be placed on treating water supplies to meet human needs. Instead, they opted to locate authority for fluoridation outside the waterworks profession with dentists, doctors, and public health administrators. As a result, waterworks engineers conceded a great deal of the status and prestige associated with decision-making roles in community health issues and have largely faded from view.

Canada↗

Novel C-2 substituted carbapenem derivatives. Part I. Synthesis and biological activity of non-aromatic heterocyclic derivatives.

A new series of carbapenems, having a saturated or partially unsaturated heterocycle at C-2, has been synthesised. The in vitro antibacterial activity of these compounds and their stability to human dehydropeptidase-1 (DHP-1) are described. The stereochemistry of the C-2 side-chain and the presence of a double bond in the heterocycle were shown to have significant effects on the stabilities of the compounds to DHP-1.

Bacteria↗

Novel C-2 substituted carbapenem derivatives. Part II. Synthesis and structure-activity relationships of isoxazolin-2-yl, isoxazolidin-2-yl and 2-pyrazolin-2-yl carbapenems generated using 1,3-dipolar cycloaddition chemistry.

A series of carbapenems containing novel C-2 semisaturated heterocyclic substituents were synthesised by 1,3 dipolar cycloaddition reactions of nitrile oxides, nitrile imines and a nitrone to 2-vinylcarbapenem. The isoxazoline and isoxazolidine compounds showed potent antibacterial activity but moderate stability to human dehydropeptidase 1 (DHP-1). Stability to DHP-1 was improved by methyl substitution in the isoxazoline ring, but at the expense of antibacterial activity. The pyrazolines exhibited excellent stability to DHP-1, but reduced potency against Gram-negative organisms.

Carbapenems↗

Drug combinations in syringe drivers.

AIMS: Because of widely differing views on the drugs that can be administered in combination, this study was undertaken to record the combination of drugs in syringe drivers that we had found to be compatible. METHODS: The content of syringe drivers in 100 consecutive patients in whom continuous subcutaneous infusion was used, was recorded. The incidence of skin reactions with the different drugs was noted. The efficacy of combinations used was assessed clinically. RESULTS: A wide variety of drugs were used in many different combinations, with no clinical evidence of loss of efficacy. Some drug combinations are incompatible. Drugs known to cause skin reactions were not administered. In this study skin reactions depended on the number of drugs used in combination. CONCLUSIONS: The array of medications that can be used together in syringe drivers enable this method of drug administration to be used successfully in the control of the diverse symptoms that may arise in terminal illness. Further study is needed for quantitative measurement of drug stability.

Anti-Anxiety Agents↗

Automatic registration of SPECT images as an alternative to immobilization in neuroactivation studies.

Subtraction of the two components (baseline and stimulation) of a neuroactivation study using 99Tcm HMPAO SPECT requires accurate registration of the two images. Immobilization of the subject during and between the two components of the study can prove difficult and degrades signal to noise ratio. The use of an automated image registration technique for registering the two components of the test can, even in the case where the subject is removed from the scanner, produce significantly better registration than immobilization.

Algorithms↗